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A Study Assessing Pamiparib With Radiation and/or Temozolomide (TMZ) in Participants With Newly Diagnosed or Recurrent Glioblastoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03150862
Recruitment Status : Completed
First Posted : May 12, 2017
Results First Posted : May 31, 2022
Last Update Posted : May 31, 2022
Sponsor:
Information provided by (Responsible Party):
BeiGene ( BeiGene USA, Inc. )

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Brain and Central Nervous System Tumors
Interventions Drug: Pamiparib
Drug: TMZ
Radiation: Radiation
Enrollment 116
Recruitment Details This study consisted of a dose escalation phase and a dose expansion phase. A total of 116 participants were recruited in Netherlands, Switzerland and United States.
Pre-assignment Details  
Arm/Group Title Arm A: Dose Escalation (DE) - Pamiparib 2 Weeks (Wks) + Radiation Therapy (RT) 6 Wks Arm A: DE-Pamiparib 4 Wks + RT 6 Wks Arm A: DE- Pamiparib 6Wks + RT 6 Wks Arm A: Dose Expansion (E) - Pamiparib 6 Wks + RT 6 Wks Arm B: DE-Pamiparib 6 Wks + RT 6 Wks + Temozolomide Arm C: DE - Pamiparib + Temozolomide 20 mg Arm C: DE - Pamiparib + Temozolomide 40 mg Arm C: E- Pamiparib + Temozolomide 60 mg
Hide Arm/Group Description Participants with newly diagnosed unmethylated glioblastoma (GBM) received 60 milligrams (mg) pamiparib orally twice daily (BID) for 2 weeks in combination with up to 60 Gy radiation for 6 weeks Participants with newly diagnosed unmethylated GBM received 60 mg pamiparib orally for 4 weeks in combination with up to 60 Gy radiation for 6 weeks Participants with newly diagnosed unmethylated GBM received 60 mg pamiparib orally for 6 weeks in combination with up to 60 Gy radiation for 6 weeks Participants with newly diagnosed unmethylated GBM received 60 mg pamiparib orally for 6 weeks in combination with up to 60 Gy radiation for 6 weeks Participants with newly diagnosed unmethylated GBM received 60 mg pamiparib orally for 6 weeks in combination with up to 60 Gy radiation for 6 weeks and 60 mg temozolomide Wks 1 and 5 Participants with both methylated and unmethylated recurrent/refractory GBM received 60 mg pamiparib BID and 20 mg temozolomide once daily orally from Day 1 to Day 21 Participants with both methylated and unmethylated recurrent/refractory GBM received 60 mg pamiparib BID and 40 mg temozolomide once daily orally from Day 1 to Day 21 Participants with both methylated and unmethylated recurrent/refractory GBM received 60 mg pamiparib BID and 60 mg temozolomide once daily orally from Day 1 to Day 7
Period Title: Overall Study
Started 3 8 9 40 9 9 8 30
Completed 0 0 0 0 0 0 0 0
Not Completed 3 8 9 40 9 9 8 30
Reason Not Completed
Death             2             7             8             27             4             8             6             21
Withdrawal by Subject             1             1             0             3             1             1             1             3
Lost to Follow-up             0             0             1             0             0             0             0             2
Sponsor's decision             0             0             0             10             3             0             1             1
Change in Methylation status             0             0             0             0             1             0             0             0
Roll over in to Long Term Extension             0             0             0             0             0             0             0             1
Progressive Disease             0             0             0             0             0             0             0             2
Arm/Group Title Arm A: DE - Pamiparib 2 Wks + Radiation Therapy (RT) 6 Wks Arm A: DE-Pamiparib 4 Wks + RT 6 Wks Arm A: DE- Pamiparib 6Wks + RT 6 Wks Arm A: Dose Expansion (E) - Pamiparib 6 Wks + RT 6 Wks Arm B: DE-Pamiparib 6 Wks + RT 6 Wks + Temozolomide Arm C: DE - Pamiparib + Temozolomide 20 mg Arm C: DE - Pamiparib + Temozolomide 40 mg Arm C: E- Pamiparib + Temozolomide 60 mg Total
Hide Arm/Group Description Participants with newly diagnosed unmethylated glioblastoma (GBM) received 60 mg pamiparib orally BID for 2 weeks in combination with up to 60 Gy radiation for 6 weeks Participants with newly diagnosed unmethylated GBM received 60 mg pamiparib orally for 4 weeks in combination with up to 60 Gy radiation for 6 weeks Participants with newly diagnosed unmethylated GBM received 60 mg pamiparib orally for 6 weeks in combination with up to 60 Gy radiation for 6 weeks Participants with newly diagnosed unmethylated GBM received 60 mg pamiparib orally for 6 weeks in combination with up to 60 Gy radiation for 6 weeks Participants with newly diagnosed unmethylated GBM received 60 mg pamiparib orally for 6 weeks in combination with up to 60 Gy radiation for 6 weeks and 60 mg temozolomide Wks 1 and 5 Participants with both methylated and unmethylated recurrent/refractory GBM received 60 mg pamiparib BID and 20 mg temozolomide once daily orally from Day 1 to Day 21 Participants with both methylated and unmethylated recurrent/refractory GBM received 60 mg pamiparib BID and 40 mg temozolomide once daily orally from Day 1 to Day 21 Participants with both methylated and unmethylated recurrent/refractory GBM received 60 mg pamiparib BID and 60 mg temozolomide once daily orally from Day 1 to Day 7 Total of all reporting groups
Overall Number of Baseline Participants 3 8 9 40 9 9 8 30 116
Hide Baseline Analysis Population Description
The Safety Analysis Set includes all participants who received any study treatment (pamiparib, RT, and/or TMZ). The Safety Analysis Set was used for all efficacy and safety analyses.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 3 participants 8 participants 9 participants 40 participants 9 participants 9 participants 8 participants 30 participants 116 participants
59.7  (8.39) 63.4  (8.80) 58.8  (7.66) 56.7  (13.48) 60.9  (9.94) 49.2  (12.63) 49.1  (15.51) 58.6  (10.54) 57.10  (12.10)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 8 participants 9 participants 40 participants 9 participants 9 participants 8 participants 30 participants 116 participants
Female
0
   0.0%
1
  12.5%
2
  22.2%
17
  42.5%
4
  44.4%
1
  11.1%
4
  50.0%
10
  33.3%
39
  33.6%
Male
3
 100.0%
7
  87.5%
7
  77.8%
23
  57.5%
5
  55.6%
8
  88.9%
4
  50.0%
20
  66.7%
77
  66.4%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
 Number Analyzed 3 participants 8 participants 9 participants 40 participants 9 participants 9 participants 8 participants 30 participants 116 participants
Asian
0
   0.0%
0
   0.0%
1
  11.1%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   3.3%
2
   1.7%
Black or African American
0
   0.0%
1
  12.5%
1
  11.1%
0
   0.0%
0
   0.0%
1
  11.1%
0
   0.0%
0
   0.0%
3
   2.6%
White
3
 100.0%
7
  87.5%
7
  77.8%
38
  95.0%
9
 100.0%
7
  77.8%
8
 100.0%
27
  90.0%
106
  91.4%
Unknown/Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
2
   5.0%
0
   0.0%
1
  11.1%
0
   0.0%
2
   6.7%
5
   4.3%
1.Primary Outcome
Title Phase 1b Escalation Phase: Number of Participants With Dose-Limiting Toxicities (DLTs) as Assessed by CTCAE
Hide Description

A DLT is defined as one of the following toxicities occurring during the DLT assessment window:

Grade ≥3 non-hematologic, non-hepatic major organ adverse event (AE) Grade 4 neutropenia lasting >7 days Grade ≥3 febrile neutropenia Grade 3 thrombocytopenia with clinically significant bleeding Grade 4 thrombocytopenia lasting > 3 days and requiring transfusion, or any decreased platelet count <15,000/mm3/ <15.0 x 109/L Grade ≥4 anemia Grade ≥3 total bilirubin or hepatic transaminases (ALT or AST)
Time Frame Arm A:Day 1 Pamiparib dose until 4 weeks after the last RT; Arm B: Day 1 of Pamiparib and Temozolomide until 4 weeks after the last RT; Arm C: 1st cycle of 28 days
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Analysis Set
Arm/Group Title Arm A: DE - Pamiparib 2 Wks + Radiation Therapy (RT) 6 Wks Arm A: DE-Pamiparib 4 Wks + RT 6 Wks Arm A: DE- Pamiparib 6Wks + RT 6 Wks Arm B: DE-Pamiparib 6 Wks + RT 6 Wks + Temozolomide Arm C: DE - Pamiparib + Temozolomide 20 mg Arm C: DE - Pamiparib + Temozolomide 40 mg
Hide Arm/Group Description:
Participants with newly diagnosed unmethylated glioblastoma (GBM) received 60 mg pamiparib orally BID for 2 weeks in combination with up to 60 Gy radiation for 6 weeks
Participants with newly diagnosed unmethylated GBM received 60 mg pamiparib orally for 4 weeks in combination with up to 60 Gy radiation for 6 weeks
Participants with newly diagnosed unmethylated GBM received 60 mg pamiparib orally for 6 weeks in combination with up to 60 Gy radiation for 6 weeks
Participants with newly diagnosed unmethylated GBM received 60 mg pamiparib orally for 6 weeks in combination with up to 60 Gy radiation for 6 weeks and 60 mg temozolomide Wks 1 and 5
Participants with both methylated and unmethylated recurrent/refractory GBM received 60 mg pamiparib BID and 20 mg temozolomide once daily orally from Day 1 to Day 21
Participants with both methylated and unmethylated recurrent/refractory GBM received 60 mg pamiparib BID and 40 mg temozolomide once daily orally from Day 1 to Day 21
Overall Number of Participants Analyzed 3 8 9 9 9 8
Measure Type: Number
Unit of Measure: participants
0 0 2 1 0 3
2.Primary Outcome
Title Phase 1b Escalation Phase: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) as Assessed by CTCAE
Hide Description

A treatment-emergent adverse event (TEAE) is defined as an AE that had an onset date on or after first dose of study treatment or was worsening in severity from baseline (pretreatment) up to 30 days following permanent study treatment discontinuation or initiation of new anti-cancer therapy, whichever occurs first.

An SAE is any untoward medical occurrence that, at any dose meets at least one of the following criteria: results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, is considered a significant medical AE based on medical judgment.
Time Frame From initiation of study treatment (for TEAE) or from the date informed consent has been signed (for SAE), until 30 days after last study treatment or initiation of new anticancer therapy, whichever occurs first (up to 3 years and 7.5 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Analysis Set
Arm/Group Title Arm A: DE - Pamiparib 2 Wks + Radiation Therapy (RT) 6 Wks Arm A: DE-Pamiparib 4 Wks + RT 6 Wks Arm A: DE- Pamiparib 6Wks + RT 6 Wks Arm B: DE-Pamiparib 6 Wks + RT 6 Wks + Temozolomide Arm C: DE - Pamiparib + Temozolomide 20 mg Arm C: DE - Pamiparib + Temozolomide 40 mg
Hide Arm/Group Description:
Participants with newly diagnosed unmethylated glioblastoma (GBM) received 60 mg pamiparib orally BID for 2 weeks in combination with up to 60 Gy radiation for 6 weeks
Participants with newly diagnosed unmethylated GBM received 60 mg pamiparib orally for 4 weeks in combination with up to 60 Gy radiation for 6 weeks
Participants with newly diagnosed unmethylated GBM received 60 mg pamiparib orally for 6 weeks in combination with up to 60 Gy radiation for 6 weeks
Participants with newly diagnosed unmethylated GBM received 60 mg pamiparib orally for 6 weeks in combination with up to 60 Gy radiation for 6 weeks and 60 mg temozolomide Wks 1 and 5
Participants with both methylated and unmethylated recurrent/refractory GBM received 60 mg pamiparib BID and 20 mg temozolomide once daily orally from Day 1 to Day 21
Participants with both methylated and unmethylated recurrent/refractory GBM received 60 mg pamiparib BID and 40 mg temozolomide once daily orally from Day 1 to Day 21
Overall Number of Participants Analyzed 3 8 9 9 9 8
Measure Type: Number
Unit of Measure: participants
Participants with At Least 1 TEAE 3 8 9 9 9 8
TEAE with Grade 3 or Higher 1 3 4 4 5 7
Treatment Emergent SAEs 0 2 2 2 4 3
TEAE Leading to Death 0 0 0 0 0 0
3.Primary Outcome
Title Phase 1b Escalation Phase Arm C: Number of Participants With Clinically Relevant Changes in Vital Signs and Clinical Laboratory Measurements
Hide Description [Not Specified]
Time Frame From the date of first dose up to end of study (EOS) visit (up to 3 years and 7.5 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Analysis Set
Arm/Group Title Arm C: DE - Pamiparib + Temozolomide 20 mg Arm C: DE - Pamiparib + Temozolomide 40 mg
Hide Arm/Group Description:
Participants with both methylated and unmethylated recurrent/refractory GBM received 60 mg pamiparib BID and 20 mg temozolomide once daily orally from Day 1 to Day 21
Participants with both methylated and unmethylated recurrent/refractory GBM received 60 mg pamiparib BID and 40 mg temozolomide once daily orally from Day 1 to Day 21
Overall Number of Participants Analyzed 9 8
Measure Type: Number
Unit of Measure: Number of participants
0 0
4.Primary Outcome
Title Phase 2 Arm A: Modified Disease Control Rate (DCR) as Assessed by Response Assessment in Neuro-Oncology (RANO) Criteria
Hide Description Modified DCR is defined as the percentage of participants with complete response (CR), partial response (PR) or stable disease (SD) per RANO criteria as the response assessment at the end-of-treatment (EOT) visit.
Time Frame From the date of first dose up to first documentation of disease progression while participant is alive ( up to 3 years and 7.5 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The Efficacy Analysis Set (Arm A) includes participants in the Safety Analysis Set who had a tumor assessment at baseline and at End of Treatment unless discontinued treatment or study early due to disease progression or death prior to tumor assessment. Participants with available data were included in the analysis.
Arm/Group Title Arm A: Dose Expansion (E) - Pamiparib 6 Wks + RT 6 Wks
Hide Arm/Group Description:
Participants with newly diagnosed unmethylated GBM received 60 mg pamiparib orally for 6 weeks in combination with up to 60 Gy radiation for 6 weeks
Overall Number of Participants Analyzed 32
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
65.6
(46.8 to 81.4)
5.Primary Outcome
Title Phase 2 Arm C: Objective Response Rate (ORR) as Assessed Using RANO Criteria
Hide Description ORR (objective response rate) is defined as percentage of participants with best overall response of CR or PR per RANO criteria (confirmed by a subsequent tumor assessment at least four weeks apart).
Time Frame From the date of first dose up to first documentation of disease progression while participant is alive (up to 3 years and 7.5 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The Efficacy Analysis Set (Arm C) includes participants in the Safety Analysis Set who had measurable disease at baseline and at least one postbaseline tumor assessment unless discontinued treatment or study early due to disease progression or death prior to tumor assessment. Participants with available data were included in the analysis.
Arm/Group Title Arm C: E- Pamiparib + Temozolomide 60 mg
Hide Arm/Group Description:
Participants with both methylated and unmethylated recurrent/refractory GBM received 60 mg pamiparib BID and 60 mg temozolomide once daily orally from Day 1 to Day 7
Overall Number of Participants Analyzed 28
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
10.7
(2.3 to 28.2)
6.Primary Outcome
Title Phase 1b Arm C: Number of Cycles of Treatment Received by Participants
Hide Description Data shows the number of participants who received treatment for the given number of cycles.
Time Frame From the date of first dose up to EOS visit ( up to 3 years and 7.5 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Analysis Set
Arm/Group Title Arm C: DE - Pamiparib + Temozolomide 20 mg Arm C: DE - Pamiparib + Temozolomide 40 mg
Hide Arm/Group Description:
Participants with both methylated and unmethylated recurrent/refractory GBM received 60 mg pamiparib BID and 20 mg temozolomide once daily orally from Day 1 to Day 21
Participants with both methylated and unmethylated recurrent/refractory GBM received 60 mg pamiparib BID and 40 mg temozolomide once daily orally from Day 1 to Day 21
Overall Number of Participants Analyzed 9 8
Measure Type: Number
Unit of Measure: participants
<1 cycle 2 3
1 cycle 4 0
2 cycles 1 2
3 cycles 0 1
4 cycles 1 0
5 cycles 1 0
6 cycles 0 0
7 cycles 0 0
>7 cycles 0 2
7.Primary Outcome
Title Phase 1b Arm C: Average Dose Intensity of Pamiparib And TMZ Received Per Participant
Hide Description The average dose intensity per participant = total dose (mg) per participant / duration of treatment (days).
Time Frame From the date of first dose until EOS visit (up to 3 years and 7.5 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Analysis Set
Arm/Group Title Arm C: DE - Pamiparib + Temozolomide 20 mg Arm C: DE - Pamiparib + Temozolomide 40 mg
Hide Arm/Group Description:
Participants with both methylated and unmethylated recurrent/refractory GBM received 60 mg pamiparib BID and 20 mg temozolomide once daily orally from Day 1 to Day 21
Participants with both methylated and unmethylated recurrent/refractory GBM received 60 mg pamiparib BID and 40 mg temozolomide once daily orally from Day 1 to Day 21
Overall Number of Participants Analyzed 9 8
Mean (Standard Deviation)
Unit of Measure: milligrams/Day
Pamiparib 97.5  (25.41) 107.6  (14.65)
TMZ 13.6  (1.88) 28.2  (10.80)
8.Secondary Outcome
Title Phase 1B and Phase 2: Pharmacokinetics: Ctrough of Pamiparib
Hide Description [Not Specified]
Time Frame Pre-dose, 2 hours post dose on Days 1 and 15 of radiation Therapy
Hide Outcome Measure Data
Hide Analysis Population Description
The Pharmacokinetic (PK) Analysis Set includes all participants for whom valid pamiparib PK parameters can be estimated. Participants with available data were included in the analysis.
Arm/Group Title Arm A: DE - Pamiparib 2 Wks + Radiation Therapy (RT) 6 Wks Arm A: DE-Pamiparib 4 Wks + RT 6 Wks Arm A: DE- Pamiparib 6Wks + RT 6 Wks Arm A: Dose Expansion (E) - Pamiparib 6 Wks + RT 6 Wks Arm B: DE-Pamiparib 6 Wks + RT 6 Wks + Temozolomide Arm C: DE - Pamiparib + Temozolomide 20 mg Arm C: DE - Pamiparib + Temozolomide 40 mg Arm C: E- Pamiparib + Temozolomide 60 mg
Hide Arm/Group Description:
Participants with newly diagnosed unmethylated glioblastoma (GBM) received 60 mg pamiparib orally BID for 2 weeks in combination with up to 60 Gy radiation for 6 weeks
Participants with newly diagnosed unmethylated GBM received 60 mg pamiparib orally for 4 weeks in combination with up to 60 Gy radiation for 6 weeks
Participants with newly diagnosed unmethylated GBM received 60 mg pamiparib orally for 6 weeks in combination with up to 60 Gy radiation for 6 weeks
Participants with newly diagnosed unmethylated GBM received 60 mg pamiparib orally for 6 weeks in combination with up to 60 Gy radiation for 6 weeks
Participants with newly diagnosed unmethylated GBM received 60 mg pamiparib orally for 6 weeks in combination with up to 60 Gy radiation for 6 weeks and 60 mg temozolomide Wks 1 and 5
Participants with both methylated and unmethylated recurrent/refractory GBM received 60 mg pamiparib BID and 20 mg temozolomide once daily orally from Day 1 to Day 21
Participants with both methylated and unmethylated recurrent/refractory GBM received 60 mg pamiparib BID and 40 mg temozolomide once daily orally from Day 1 to Day 21
Participants with both methylated and unmethylated recurrent/refractory GBM received 60 mg pamiparib BID and 60 mg temozolomide once daily orally from Day 1 to Day 7
Overall Number of Participants Analyzed 3 5 6 35 7 6 6 25
Mean (Standard Deviation)
Unit of Measure: ng/mL
891.3  (444.51) 1817.0  (1226.53) 1848.3  (784.38) 2239.9  (1011.07) 2134.3  (953.06) 1893.3  (718.46) 1550.8  (1422.55) 1500.2  (943.35)
9.Secondary Outcome
Title Phase 1b Arm A and Arm B Escalation Phase: Modified Disease Control Rate as Assessed by RANO Criteria
Hide Description Modified DCR is defined as the percentage of participants with complete response (CR), partial response (PR) or stable disease (SD) per RANO criteria as the response assessment at the end-of-treatment (EOT) visit.
Time Frame From the date of first dose up to first documentation of disease progression while participant is alive (approximately 3 years and 7.5 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Analysis Set; Participants with available data were included in the analysis
Arm/Group Title Arm A: DE - Pamiparib 2 Wks + Radiation Therapy (RT) 6 Wks Arm A: DE-Pamiparib 4 Wks + RT 6 Wks Arm A: DE- Pamiparib 6Wks + RT 6 Wks Arm B: DE-Pamiparib 6 Wks + RT 6 Wks + Temozolomide
Hide Arm/Group Description:
Participants with newly diagnosed unmethylated glioblastoma (GBM) received 60 mg pamiparib orally BID for 2 weeks in combination with up to 60 Gy radiation for 6 weeks
Participants with newly diagnosed unmethylated GBM received 60 mg pamiparib orally for 4 weeks in combination with up to 60 Gy radiation for 6 weeks
Participants with newly diagnosed unmethylated GBM received 60 mg pamiparib orally for 6 weeks in combination with up to 60 Gy radiation for 6 weeks
Participants with newly diagnosed unmethylated GBM received 60 mg pamiparib orally for 6 weeks in combination with up to 60 Gy radiation for 6 weeks and 60 mg temozolomide Wks 1 and 5
Overall Number of Participants Analyzed 3 6 7 5
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
66.7
(9.4 to 99.2)
100.0
(54.1 to 100.0)
42.9
(9.9 to 81.6)
80.0
(28.4 to 99.5)
10.Secondary Outcome
Title Phase 1b Escalation Phase Arm C: Disease Control Rate as Assessed by RANO Criteria
Hide Description DCR is defined as the percentage of participants with best overall response of CR, PR or SD per RANO criteria. CR or PR will be confirmed by a subsequent tumor assessment at least four weeks apart
Time Frame From the date of first dose up to first documentation of disease progression while participant is alive (up to 3 years and 7.5 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Analysis Set; Participants with available data were included in the analysis.
Arm/Group Title Arm C: DE- Pamiparib + Temozolomide 20 mg Arm C: DE - Pamiparib + Temozolomide 40 mg
Hide Arm/Group Description:
Participants with both methylated and unmethylated recurrent/refractory GBM received 60 mg pamiparib BID and 20 mg temozolomide once daily orally from Day 1 to Day 21
Participants with both methylated and unmethylated recurrent/refractory GBM received 60 mg pamiparib BID and 40 mg temozolomide once daily orally from Day 1 to Day 21
Overall Number of Participants Analyzed 9 7
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
55.6
(21.2 to 86.3)
71.4
(29.0 to 96.3)
11.Secondary Outcome
Title Phase 1b and Phase 2 Arms A and B: ORR as Assessed Using RANO Criteria
Hide Description ORR is defined as percentage of participants with best overall response of CR or PR per RANO criteria (confirmed by a subsequent tumor assessment at least four weeks apart).
Time Frame From the date of first dose up to first documentation of disease progression while participant is alive ( up to 3 years and 7.5 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Evaluable Analysis Set; Participants with available data were included in the analysis.
Arm/Group Title Arm A: DE - Pamiparib 2 Wks + Radiation Therapy (RT) 6 Wks Arm A: DE-Pamiparib 4 Wks + RT 6 Wks Arm A: DE- Pamiparib 6Wks + RT 6 Wks Arm A: Dose Expansion (E) - Pamiparib 6 Wks + RT 6 Wks Arm B: DE-Pamiparib 6 Wks + RT 6 Wks + Temozolomide
Hide Arm/Group Description:
Participants with newly diagnosed unmethylated glioblastoma (GBM) received 60 mg pamiparib orally BID for 2 weeks in combination with up to 60 Gy radiation for 6 weeks
Participants with newly diagnosed unmethylated GBM received 60 mg pamiparib orally for 4 weeks in combination with up to 60 Gy radiation for 6 weeks
Participants with newly diagnosed unmethylated GBM received 60 mg pamiparib orally for 6 weeks in combination with up to 60 Gy radiation for 6 weeks
Participants with newly diagnosed unmethylated GBM received 60 mg pamiparib orally for 6 weeks in combination with up to 60 Gy radiation for 6 weeks
Participants with newly diagnosed unmethylated GBM received 60 mg pamiparib orally for 6 weeks in combination with up to 60 Gy radiation for 6 weeks and 60 mg temozolomide Wks 1 and 5
Overall Number of Participants Analyzed 3 6 7 32 5
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
0
(0.0 to 70.8)
16.7
(0.4 to 64.1)
0
(0.0 to 41.0)
3.1
(0.1 to 16.2)
0
(0.0 to 52.2)
12.Secondary Outcome
Title Phase 1b and Phase 2 Arms A, B and C: Clinical Benefit Rate as Assessed Using RANO Criteria
Hide Description Clinical benefit rate (CBR) is defined as the percentage of participants with best overall response of CR, PR or SD ≥ 24 weeks per RANO criteria (confirmed by a subsequent tumor assessment at least four weeks apart).
Time Frame From the date of first dose up to first documentation of disease progression while participant is alive (up to 3 years and 7.5 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Analysis Set; participants with available data were included in the analysis
Arm/Group Title Arm A: DE - Pamiparib 2 Wks + Radiation Therapy (RT) 6 Wks Arm A: DE-Pamiparib 4 Wks + RT 6 Wks Arm A: DE- Pamiparib 6Wks + RT 6 Wks Arm A: Dose Expansion (E) - Pamiparib 6 Wks + RT 6 Wks Arm B: DE-Pamiparib 6 Wks + RT 6 Wks + Temozolomide Arm C: DE - Pamiparib + Temozolomide 20 mg Arm C: DE - Pamiparib + Temozolomide 40 mg Arm C: E- Pamiparib + Temozolomide 60 mg
Hide Arm/Group Description:
Participants with newly diagnosed unmethylated glioblastoma (GBM) received 60 mg pamiparib orally BID for 2 weeks in combination with up to 60 Gy radiation for 6 weeks
Participants with newly diagnosed unmethylated GBM received 60 mg pamiparib orally for 4 weeks in combination with up to 60 Gy radiation for 6 weeks
Participants with newly diagnosed unmethylated GBM received 60 mg pamiparib orally for 6 weeks in combination with up to 60 Gy radiation for 6 weeks
Participants with newly diagnosed unmethylated GBM received 60 mg pamiparib orally for 6 weeks in combination with up to 60 Gy radiation for 6 weeks
Participants with newly diagnosed unmethylated GBM received 60 mg pamiparib orally for 6 weeks in combination with up to 60 Gy radiation for 6 weeks and 60 mg temozolomide Wks 1 and 5
Participants with both methylated and unmethylated recurrent/refractory GBM received 60 mg pamiparib BID and 20 mg temozolomide once daily orally from Day 1 to Day 21
Participants with both methylated and unmethylated recurrent/refractory GBM received 60 mg pamiparib BID and 40 mg temozolomide once daily orally from Day 1 to Day 21
Participants with both methylated and unmethylated recurrent/refractory GBM received 60 mg pamiparib BID and 60 mg temozolomide once daily orally from Day 1 to Day 7
Overall Number of Participants Analyzed 3 6 7 32 5 9 7 28
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
0
(0.0 to 70.8)
33.3
(4.3 to 77.7)
0
(0.0 to 41.0)
37.6
(21.1 to 56.3)
40.0
(5.3 to 85.3)
0
(0.0 to 33.6)
28.6
(3.7 to 71.0)
17.9
(6.1 to 36.9)
13.Secondary Outcome
Title Phase 1b and Phase 2 Arms A, B and C: Duration of Response (DOR) as Assessed Using RANO Criteria
Hide Description DOR is defined as the time from the date of the earliest documented response to disease progression or death for any cause whichever occurs earlier (confirmed by a subsequent tumor assessment at least four weeks apart).
Time Frame From first documentation of CR or PR to first documentation of disease progression or death (up to 3 years and 7.5 months)
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Hide Analysis Population Description
Efficacy Analysis Set; Only the participants with objective responses were included in DOR analysis.
Arm/Group Title Arm A: DE - Pamiparib 2 Wks + Radiation Therapy (RT) 6 Wks Arm A: DE-Pamiparib 4 Wks + RT 6 Wks Arm A: DE- Pamiparib 6Wks + RT 6 Wks Arm A: Dose Expansion (E) - Pamiparib 6 Wks + RT 6 Wks Arm B: DE-Pamiparib 6 Wks + RT 6 Wks + Temozolomide Arm C: DE - Pamiparib + Temozolomide 20 mg Arm C: DE - Pamiparib + Temozolomide 40 mg Arm C: E- Pamiparib + Temozolomide 60 mg
Hide Arm/Group Description:
Participants with newly diagnosed unmethylated glioblastoma (GBM) received 60 mg pamiparib orally BID for 2 weeks in combination with up to 60 Gy radiation for 6 weeks
Participants with newly diagnosed unmethylated GBM received 60 mg pamiparib orally for 4 weeks in combination with up to 60 Gy radiation for 6 weeks
Participants with newly diagnosed unmethylated GBM received 60 mg pamiparib orally for 6 weeks in combination with up to 60 Gy radiation for 6 weeks
Participants with newly diagnosed unmethylated GBM received 60 mg pamiparib orally for 6 weeks in combination with up to 60 Gy radiation for 6 weeks
Participants with newly diagnosed unmethylated GBM received 60 mg pamiparib orally for 6 weeks in combination with up to 60 Gy radiation for 6 weeks and 60 mg temozolomide Wks 1 and 5
Participants with both methylated and unmethylated recurrent/refractory GBM received 60 mg pamiparib BID and 20 mg temozolomide once daily orally from Day 1 to Day 21
Participants with both methylated and unmethylated recurrent/refractory GBM received 60 mg pamiparib BID and 40 mg temozolomide once daily orally from Day 1 to Day 21
Participants with both methylated and unmethylated recurrent/refractory GBM received 60 mg pamiparib BID and 60 mg temozolomide once daily orally from Day 1 to Day 7
Overall Number of Participants Analyzed 0 1 0 1 0 0 1 3
Median (95% Confidence Interval)
Unit of Measure: Months
6.44 [1] 
(NA to NA)
10.32 [1] 
(NA to NA)
11.7 [1] 
(NA to NA)
NA [1] 
(12.68 to NA)
[1]
NA = NE; Not estimable due to insufficient number of events
14.Secondary Outcome
Title Phase 1b and Phase 2 Arms A, B and C: Progression Free Survival (PFS) as Assessed Using RANO Criteria
Hide Description PFS is defined as the time from the first dose date to disease progression per RANO criteria or death, whichever occurs first.
Time Frame From the date of first dose up to first documentation of disease progression or death (up to 3 years and 7.5 months)
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Hide Analysis Population Description
Safety Analysis Set
Arm/Group Title Arm A: DE - Pamiparib 2 Wks + Radiation Therapy (RT) 6 Wks Arm A: DE-Pamiparib 4 Wks + RT 6 Wks Arm A: DE- Pamiparib 6Wks + RT 6 Wks Arm A: Dose Expansion (E) - Pamiparib 6 Wks + RT 6 Wks Arm B: DE-Pamiparib 6 Wks + RT 6 Wks + Temozolomide Arm C: DE - Pamiparib + Temozolomide 20 mg Arm C: DE - Pamiparib + Temozolomide 40 mg Arm C: E- Pamiparib + Temozolomide 60 mg
Hide Arm/Group Description:
Participants with newly diagnosed unmethylated glioblastoma (GBM) received 60 mg pamiparib orally BID for 2 weeks in combination with up to 60 Gy radiation for 6 weeks
Participants with newly diagnosed unmethylated GBM received 60 mg pamiparib orally for 4 weeks in combination with up to 60 Gy radiation for 6 weeks
Participants with newly diagnosed unmethylated GBM received 60 mg pamiparib orally for 6 weeks in combination with up to 60 Gy radiation for 6 weeks
Participants with newly diagnosed unmethylated GBM received 60 mg pamiparib orally for 6 weeks in combination with up to 60 Gy radiation for 6 weeks
Participants with newly diagnosed unmethylated GBM received 60 mg pamiparib orally for 6 weeks in combination with up to 60 Gy radiation for 6 weeks and 60 mg temozolomide Wks 1 and 5
Participants with both methylated and unmethylated recurrent/refractory GBM received 60 mg pamiparib BID and 20 mg temozolomide once daily orally from Day 1 to Day 21
Participants with both methylated and unmethylated recurrent/refractory GBM received 60 mg pamiparib BID and 40 mg temozolomide once daily orally from Day 1 to Day 21
Participants with both methylated and unmethylated recurrent/refractory GBM received 60 mg pamiparib BID and 60 mg temozolomide once daily orally from Day 1 to Day 7
Overall Number of Participants Analyzed 3 8 9 40 8 9 8 30
Median (95% Confidence Interval)
Unit of Measure: Months
3.12
(2.79 to 3.29)
8.94
(3.78 to 11.56)
2.56 [1] 
(2.14 to NA)
4.44
(3.29 to 6.24)
5.75
(2.37 to 6.47)
1.81
(0.82 to 3.48)
2.66
(0.66 to 7.39)
1.87
(1.48 to 1.91)
[1]
NA = NE; Not estimable to due to insufficient number of events
15.Secondary Outcome
Title Phase 1b and Phase 2 Arms A, B and C: Overall Survival (OS)
Hide Description OS is defined as the time from the first dose date to date of death for any cause.
Time Frame From the date of first dose up to the date of death (up to 3 years and 7.5 months)
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Hide Analysis Population Description
Safety Analysis Set
Arm/Group Title Arm A: DE - Pamiparib 2 Wks + Radiation Therapy (RT) 6 Wks Arm A: DE-Pamiparib 4 Wks + RT 6 Wks Arm A: DE- Pamiparib 6Wks + RT 6 Wks Arm A: Dose Expansion (E) - Pamiparib 6 Wks + RT 6 Wks Arm B: DE-Pamiparib 6 Wks + RT 6 Wks + Temozolomide Arm C: DE - Pamiparib + Temozolomide 20 mg Arm C: DE - Pamiparib + Temozolomide 40 mg Arm C: E- Pamiparib + Temozolomide 60 mg
Hide Arm/Group Description:
Participants with newly diagnosed unmethylated glioblastoma (GBM) received 60 mg pamiparib orally BID for 2 weeks in combination with up to 60 Gy radiation for 6 weeks
Participants with newly diagnosed unmethylated GBM received 60 mg pamiparib orally for 4 weeks in combination with up to 60 Gy radiation for 6 weeks
Participants with newly diagnosed unmethylated GBM received 60 mg pamiparib orally for 6 weeks in combination with up to 60 Gy radiation for 6 weeks
Participants with newly diagnosed unmethylated GBM received 60 mg pamiparib orally for 6 weeks in combination with up to 60 Gy radiation for 6 weeks
Participants with newly diagnosed unmethylated GBM received 60 mg pamiparib orally for 6 weeks in combination with up to 60 Gy radiation for 6 weeks and 60 mg temozolomide Wks 1 and 5
Participants with both methylated and unmethylated recurrent/refractory GBM received 60 mg pamiparib BID and 20 mg temozolomide once daily orally from Day 1 to Day 21
Participants with both methylated and unmethylated recurrent/refractory GBM received 60 mg pamiparib BID and 40 mg temozolomide once daily orally from Day 1 to Day 21
Participants with both methylated and unmethylated recurrent/refractory GBM received 60 mg pamiparib BID and 60 mg temozolomide once daily orally from Day 1 to Day 7
Overall Number of Participants Analyzed 3 8 9 40 8 9 8 30
Median (95% Confidence Interval)
Unit of Measure: Months
14.46
(13.93 to 14.98)
13.44
(4.14 to 20.24)
10.25
(4.44 to 19.84)
12.71
(9.79 to 14.46)
14.23 [1] 
(7.98 to NA)
6.00
(2.60 to 9.79)
8.62 [1] 
(2.96 to NA)
7.79
(6.21 to 10.68)
[1]
NA = NE; Not estimable due to insufficient number of events
16.Secondary Outcome
Title Phase 2 Arms A and C Expansion Phase: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Hide Description A treatment-emergent adverse event (TEAE) is defined as an AE that had an onset date on or after first dose of study treatment or was worsening in severity from baseline (pretreatment) up to 30 days following permanent study treatment discontinuation or initiation of new anti-cancer therapy, whichever occurs first. An SAE is any untoward medical occurrence that, at any dose meets at least one of the following criteria: results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, is considered a significant medical AE based on medical judgment.
Time Frame From initiation of study treatment (for TEAE) or from the date informed consent has been signed (for SAE), until 30 days after last study treatment or initiation of new anticancer therapy, whichever occurs first (up to 3 years and 7.5 months)
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Hide Analysis Population Description
Safety Analysis Set
Arm/Group Title Arm A: Dose Expansion (E) - Pamiparib 6 Wks + RT 6 Wks Arm C: E- Pamiparib + Temozolomide 60 mg
Hide Arm/Group Description:
Participants with newly diagnosed unmethylated GBM received 60 mg pamiparib orally for 6 weeks in combination with up to 60 Gy radiation for 6 weeks
Participants with both methylated and unmethylated recurrent/refractory GBM received 60 mg pamiparib BID and 60 mg temozolomide once daily orally from Day 1 to Day 7
Overall Number of Participants Analyzed 40 30
Measure Type: Number
Unit of Measure: Number of participants
Participants with at Lease 1 TEAE 40 29
TEAE with Grade 3 or Higher 25 19
Treatment Emergent SAEs 18 11
TEAE Leading to Death 3 1
17.Secondary Outcome
Title Phase 2 Expansion Phase Arm A and C: Number of Participants With Clinically Relevant Changes in Vital Signs and Clinical Laboratory Measurements
Hide Description [Not Specified]
Time Frame From the date of first dose up to EOS visit (up to 3 years and 7.5 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Analysis Set
Arm/Group Title Arm A: Dose Expansion (E) - Pamiparib 6 Wks + RT 6 Wks Arm C: E- Pamiparib + Temozolomide 60 mg
Hide Arm/Group Description:
Participants with newly diagnosed unmethylated GBM received 60 mg pamiparib orally for 6 weeks in combination with up to 60 Gy radiation for 6 weeks
Participants with both methylated and unmethylated recurrent/refractory GBM received 60 mg pamiparib BID and 60 mg temozolomide once daily orally from Day 1 to Day 7
Overall Number of Participants Analyzed 40 30
Measure Type: Number
Unit of Measure: Number of participants
0 0
18.Secondary Outcome
Title Phase 2 Arms A and C Expansion Phase: Number of Cycles of Treatment Received by Participants
Hide Description Data shows the number of participants who received treatment for the given number of cycles.
Time Frame From date of first dose up to EOS Visit (up to 3 years and 7.5 months)
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Hide Analysis Population Description
Safety Analysis Set; For Arm A Only participants who entered the maintenance phase were included in the analysis as per protocol.
Arm/Group Title Arm A: Dose Expansion (E) - Pamiparib 6 Wks + RT 6 Wks Arm C: E- Pamiparib + Temozolomide 60 mg
Hide Arm/Group Description:
Participants with newly diagnosed unmethylated GBM received 60 mg pamiparib orally for 6 weeks in combination with up to 60 Gy radiation for 6 weeks
Participants with both methylated and unmethylated recurrent/refractory GBM received 60 mg pamiparib BID and 60 mg temozolomide once daily orally from Day 1 to Day 7
Overall Number of Participants Analyzed 29 30
Measure Type: Number
Unit of Measure: participants
<1 cycle 3 8
1 cycle 9 8
2 cycles 2 7
3 cycles 2 1
4 cycles 3 1
5 cycles 3 0
6 cycles 3 0
7 cycles 0.0 0
>7 cycles 4 5
19.Secondary Outcome
Title Phase 2 Arms A and C Expansion Phase: Average Dose Intensity of Pamiparib and TMZ Received Per Participant
Hide Description The average dose intensity per participant = total dose (mg) per participant / duration of treatment (days).
Time Frame From date of first dose up to EOS Visit (up to 3 years and 7.5 months)
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Hide Analysis Population Description
Safety Analysis Set
Arm/Group Title Arm A: Dose Expansion (E) - Pamiparib 6 Wks + RT 6 Wks Arm C: E- Pamiparib + Temozolomide 60 mg
Hide Arm/Group Description:
Participants with newly diagnosed unmethylated GBM received 60 mg pamiparib orally for 6 weeks in combination with up to 60 Gy radiation for 6 weeks
Participants with both methylated and unmethylated recurrent/refractory GBM received 60 mg pamiparib BID and 60 mg temozolomide once daily orally from Day 1 to Day 7
Overall Number of Participants Analyzed 40 30
Mean (Standard Deviation)
Unit of Measure: Milligrams/Day
Pamiparib 109.0  (22.07) 109.5  (15.22)
TMZ NA [1]   (NA) 19.6  (11.60)
[1]
NA = Not applicable since no TMZ was administered in this arm
Time Frame From initiation of study treatment (for TEAE) or from the date informed consent has been signed (for SAE), until 30 days after last study treatment or initiation of new anticancer therapy, whichever occurs first (up to 3 years and 7.5 months)
Adverse Event Reporting Description A treatment-emergent adverse event (TEAE) is defined as an AE that had an onset date on or after first dose of study treatment or was worsening in severity from baseline (pretreatment) up to 30 days following permanent study treatment discontinuation or initiation of new anti-cancer therapy, whichever occurs first.
 
Arm/Group Title Arm 1Arm A: DE - Pamiparib 2 Wks + Radiation Therapy (RT) 6 Wks Arm A: DE-Pamiparib 4 Wks + RT 6 Wks Arm A: DE- Pamiparib 6Wks + RT 6 Wks Arm A: Dose Expansion (E) - Pamiparib 6 Wks + RT 6 Wks Arm B: DE-Pamiparib 6 Wks + RT 6 Wks + Temozolomide Arm C: DE - Pamiparib + Temozolomide 20 mg Arm C: DE - Pamiparib + Temozolomide 40 mg Arm C: E- Pamiparib + Temozolomide 60 mg
Hide Arm/Group Description Participants with newly diagnosed unmethylated glioblastoma (GBM) received 60 mg pamiparib orally BID for 2 weeks in combination with up to 60 Gy radiation for 6 weeks Participants with newly diagnosed unmethylated GBM received 60 mg pamiparib orally for 4 weeks in combination with up to 60 Gy radiation for 6 weeks Participants with newly diagnosed unmethylated GBM received 60 mg pamiparib orally for 6 weeks in combination with up to 60 Gy radiation for 6 weeks Participants with newly diagnosed unmethylated GBM received 60 mg pamiparib orally for 6 weeks in combination with up to 60 Gy radiation for 6 weeks Participants with newly diagnosed unmethylated GBM received 60 mg pamiparib orally for 6 weeks in combination with up to 60 Gy radiation for 6 weeks and 60 mg temozolomide Wks 1 and 5 Participants with both methylated and unmethylated recurrent/refractory GBM received 60 mg pamiparib BID and 20 mg temozolomide once daily orally from Day 1 to Day 21 Participants with both methylated and unmethylated recurrent/refractory GBM received 60 mg pamiparib BID and 40 mg temozolomide once daily orally from Day 1 to Day 21 Participants with both methylated and unmethylated recurrent/refractory GBM received 60 mg pamiparib BID and 60 mg temozolomide once daily orally from Day 1 to Day 7
All-Cause Mortality
Arm 1Arm A: DE - Pamiparib 2 Wks + Radiation Therapy (RT) 6 Wks Arm A: DE-Pamiparib 4 Wks + RT 6 Wks Arm A: DE- Pamiparib 6Wks + RT 6 Wks Arm A: Dose Expansion (E) - Pamiparib 6 Wks + RT 6 Wks Arm B: DE-Pamiparib 6 Wks + RT 6 Wks + Temozolomide Arm C: DE - Pamiparib + Temozolomide 20 mg Arm C: DE - Pamiparib + Temozolomide 40 mg Arm C: E- Pamiparib + Temozolomide 60 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   2/3 (66.67%)      7/8 (87.50%)      8/9 (88.89%)      27/40 (67.50%)      4/9 (44.44%)      8/9 (88.89%)      6/8 (75.00%)      21/30 (70.00%)    
Hide Serious Adverse Events
Arm 1Arm A: DE - Pamiparib 2 Wks + Radiation Therapy (RT) 6 Wks Arm A: DE-Pamiparib 4 Wks + RT 6 Wks Arm A: DE- Pamiparib 6Wks + RT 6 Wks Arm A: Dose Expansion (E) - Pamiparib 6 Wks + RT 6 Wks Arm B: DE-Pamiparib 6 Wks + RT 6 Wks + Temozolomide Arm C: DE - Pamiparib + Temozolomide 20 mg Arm C: DE - Pamiparib + Temozolomide 40 mg Arm C: E- Pamiparib + Temozolomide 60 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/3 (0.00%)      2/8 (25.00%)      2/9 (22.22%)      18/40 (45.00%)      2/9 (22.22%)      4/9 (44.44%)      3/8 (37.50%)      11/30 (36.67%)    
Blood and lymphatic system disorders                 
Anaemia † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 2/40 (5.00%)  2 1/9 (11.11%)  1 0/9 (0.00%)  0 0/8 (0.00%)  0 0/30 (0.00%)  0
Febrile neutropenia † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 0/40 (0.00%)  0 1/9 (11.11%)  1 0/9 (0.00%)  0 0/8 (0.00%)  0 0/30 (0.00%)  0
Neutropenia † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 1/40 (2.50%)  1 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/30 (0.00%)  0
Cardiac disorders                 
Atrial fibrillation † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 0/40 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 1/30 (3.33%)  1
Ear and labyrinth disorders                 
Vertigo † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 1/9 (11.11%)  1 0/40 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/30 (0.00%)  0
Gastrointestinal disorders                 
Anal incontinence † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 1/9 (11.11%)  1 0/40 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/30 (0.00%)  0
Constipation † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 1/40 (2.50%)  1 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/30 (0.00%)  0
Gastrointestinal haemorrhage † 1  0/3 (0.00%)  0 1/8 (12.50%)  1 0/9 (0.00%)  0 0/40 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/30 (0.00%)  0
Nausea † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 1/9 (11.11%)  1 1/40 (2.50%)  2 0/9 (0.00%)  0 0/9 (0.00%)  0 1/8 (12.50%)  1 0/30 (0.00%)  0
Vomiting † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 1/9 (11.11%)  1 1/40 (2.50%)  2 0/9 (0.00%)  0 0/9 (0.00%)  0 1/8 (12.50%)  1 0/30 (0.00%)  0
General disorders                 
Asthenia † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 1/9 (11.11%)  1 0/40 (0.00%)  0 0/9 (0.00%)  0 1/9 (11.11%)  1 0/8 (0.00%)  0 0/30 (0.00%)  0
Chills † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 1/9 (11.11%)  1 0/40 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/30 (0.00%)  0
Fatigue † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 2/40 (5.00%)  2 0/9 (0.00%)  0 0/9 (0.00%)  0 1/8 (12.50%)  1 0/30 (0.00%)  0
Gait disturbance † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 1/40 (2.50%)  1 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 1/30 (3.33%)  1
Impaired healing † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 0/40 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 1/30 (3.33%)  1
Pyrexia † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 1/40 (2.50%)  2 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/30 (0.00%)  0
Infections and infestations                 
Bronchitis † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 1/40 (2.50%)  1 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/30 (0.00%)  0
Pneumonia † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 0/40 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 1/30 (3.33%)  1
Sepsis † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 1/40 (2.50%)  1 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/30 (0.00%)  0
Wound infection † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 1/40 (2.50%)  1 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 1/30 (3.33%)  1
Injury, poisoning and procedural complications                 
Fall † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 0/40 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 1/30 (3.33%)  1
Subarachnoid haematoma † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 0/40 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 1/30 (3.33%)  1
Musculoskeletal and connective tissue disorders                 
Muscular weakness † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 0/40 (0.00%)  0 0/9 (0.00%)  0 1/9 (11.11%)  1 0/8 (0.00%)  0 2/30 (6.67%)  2
Neck pain † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 1/40 (2.50%)  1 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/30 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)                 
Malignant melanoma † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 0/40 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 1/30 (3.33%)  1
Tumour flare † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 0/40 (0.00%)  0 1/9 (11.11%)  1 0/9 (0.00%)  0 0/8 (0.00%)  0 1/30 (3.33%)  1
Nervous system disorders                 
Aphasia † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 1/40 (2.50%)  1 0/9 (0.00%)  0 1/9 (11.11%)  1 0/8 (0.00%)  0 1/30 (3.33%)  1
Apraxia † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 1/40 (2.50%)  1 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/30 (0.00%)  0
Brain oedema † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 1/40 (2.50%)  1 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/30 (0.00%)  0
Cerebral cyst † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 1/40 (2.50%)  1 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/30 (0.00%)  0
Cerebrovascular accident † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 0/40 (0.00%)  0 0/9 (0.00%)  0 1/9 (11.11%)  1 0/8 (0.00%)  0 0/30 (0.00%)  0
Depressed level of consciousness † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 0/40 (0.00%)  0 1/9 (11.11%)  1 0/9 (0.00%)  0 0/8 (0.00%)  0 0/30 (0.00%)  0
Dysaesthesia † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 0/40 (0.00%)  0 0/9 (0.00%)  0 1/9 (11.11%)  1 0/8 (0.00%)  0 0/30 (0.00%)  0
Dysarthria † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 1/40 (2.50%)  1 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/30 (0.00%)  0
Hemiparesis † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 1/40 (2.50%)  1 0/9 (0.00%)  0 1/9 (11.11%)  1 0/8 (0.00%)  0 0/30 (0.00%)  0
Hemiplegia † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 1/40 (2.50%)  1 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/30 (0.00%)  0
Hydrocephalus † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 1/40 (2.50%)  1 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/30 (0.00%)  0
Nervous system disorder † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 1/40 (2.50%)  1 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/30 (0.00%)  0
Partial seizures † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 1/40 (2.50%)  1 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 1/30 (3.33%)  1
Psychogenic seizure † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 1/40 (2.50%)  1 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/30 (0.00%)  0
Seizure † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 2/40 (5.00%)  2 1/9 (11.11%)  1 1/9 (11.11%)  1 0/8 (0.00%)  0 0/30 (0.00%)  0
Syncope † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 1/40 (2.50%)  1 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/30 (0.00%)  0
Vasogenic cerebral oedema † 1  0/3 (0.00%)  0 1/8 (12.50%)  1 0/9 (0.00%)  0 1/40 (2.50%)  1 0/9 (0.00%)  0 0/9 (0.00%)  0 1/8 (12.50%)  1 0/30 (0.00%)  0
Psychiatric disorders                 
Agitation † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 1/40 (2.50%)  1 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/30 (0.00%)  0
Confusional state † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 0/40 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 1/8 (12.50%)  1 1/30 (3.33%)  1
Mental status changes † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 1/40 (2.50%)  1 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/30 (0.00%)  0
Suicide attempt † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 1/40 (2.50%)  1 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/30 (0.00%)  0
Renal and urinary disorders                 
Nephrolithiasis † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 1/40 (2.50%)  1 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 1/30 (3.33%)  1
Respiratory, thoracic and mediastinal disorders                 
Laryngeal haemorrhage † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 0/40 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 1/30 (3.33%)  1
Pulmonary embolism † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 3/40 (7.50%)  3 0/9 (0.00%)  0 0/9 (0.00%)  0 1/8 (12.50%)  1 0/30 (0.00%)  0
Skin and subcutaneous tissue disorders                 
Rash † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 1/40 (2.50%)  1 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/30 (0.00%)  0
Vascular disorders                 
Deep vein thrombosis † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 0/40 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 1/8 (12.50%)  1 0/30 (0.00%)  0
Embolism † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 0/40 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 2/30 (6.67%)  2
Haematoma † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 0/40 (0.00%)  0 0/9 (0.00%)  0 1/9 (11.11%)  1 0/8 (0.00%)  0 0/30 (0.00%)  0
Hypotension † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 0/40 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 1/30 (3.33%)  1
1
Term from vocabulary, meddra 23.0
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 3%
Arm 1Arm A: DE - Pamiparib 2 Wks + Radiation Therapy (RT) 6 Wks Arm A: DE-Pamiparib 4 Wks + RT 6 Wks Arm A: DE- Pamiparib 6Wks + RT 6 Wks Arm A: Dose Expansion (E) - Pamiparib 6 Wks + RT 6 Wks Arm B: DE-Pamiparib 6 Wks + RT 6 Wks + Temozolomide Arm C: DE - Pamiparib + Temozolomide 20 mg Arm C: DE - Pamiparib + Temozolomide 40 mg Arm C: E- Pamiparib + Temozolomide 60 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/3 (100.00%)      8/8 (100.00%)      9/9 (100.00%)      40/40 (100.00%)      9/9 (100.00%)      9/9 (100.00%)      7/8 (87.50%)      29/30 (96.67%)    
Blood and lymphatic system disorders                 
Anaemia † 1  0/3 (0.00%)  0 1/8 (12.50%)  1 0/9 (0.00%)  0 13/40 (32.50%)  19 4/9 (44.44%)  7 3/9 (33.33%)  3 3/8 (37.50%)  6 6/30 (20.00%)  15
Increased tendency to bruise † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 0/40 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 1/30 (3.33%)  1
Leukopenia † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 0/40 (0.00%)  0 1/9 (11.11%)  1 0/9 (0.00%)  0 0/8 (0.00%)  0 2/30 (6.67%)  2
Lymphopenia † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 2/40 (5.00%)  2 1/9 (11.11%)  1 0/9 (0.00%)  0 0/8 (0.00%)  0 4/30 (13.33%)  4
Neutropenia † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 2/40 (5.00%)  3 1/9 (11.11%)  2 0/9 (0.00%)  0 1/8 (12.50%)  1 3/30 (10.00%)  3
Thrombocytopenia † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 4/40 (10.00%)  5 1/9 (11.11%)  1 0/9 (0.00%)  0 1/8 (12.50%)  2 3/30 (10.00%)  3
Cardiac disorders                 
Angina pectoris † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 0/40 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 1/30 (3.33%)  1
Bradycardia † 1  0/3 (0.00%)  0 1/8 (12.50%)  1 0/9 (0.00%)  0 0/40 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/30 (0.00%)  0
Sinus tachycardia † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 0/40 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 1/30 (3.33%)  1
Tachycardia † 1  0/3 (0.00%)  0 1/8 (12.50%)  1 0/9 (0.00%)  0 0/40 (0.00%)  0 0/9 (0.00%)  0 1/9 (11.11%)  1 0/8 (0.00%)  0 1/30 (3.33%)  1
Ventricular extrasystoles † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 0/40 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 1/30 (3.33%)  1
Ear and labyrinth disorders                 
Ear congestion † 1  0/3 (0.00%)  0 1/8 (12.50%)  1 0/9 (0.00%)  0 0/40 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/30 (0.00%)  0
Ear discomfort † 1  0/3 (0.00%)  0 1/8 (12.50%)  1 0/9 (0.00%)  0 1/40 (2.50%)  1 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/30 (0.00%)  0
Ear pain † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 2/40 (5.00%)  2 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/30 (0.00%)  0
Hypoacusis † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 1/9 (11.11%)  1 2/40 (5.00%)  2 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/30 (0.00%)  0
Tinnitus † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 3/40 (7.50%)  3 1/9 (11.11%)  1 0/9 (0.00%)  0 1/8 (12.50%)  1 1/30 (3.33%)  1
Vertigo † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 1/9 (11.11%)  2 0/40 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/30 (0.00%)  0
Eye disorders                 
Dry eye † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 1/40 (2.50%)  1 0/9 (0.00%)  0 1/9 (11.11%)  1 0/8 (0.00%)  0 0/30 (0.00%)  0
Erythema of eyelid † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 0/40 (0.00%)  0 0/9 (0.00%)  0 1/9 (11.11%)  1 0/8 (0.00%)  0 0/30 (0.00%)  0
Lacrimation increased † 1  0/3 (0.00%)  0 1/8 (12.50%)  1 1/9 (11.11%)  1 0/40 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/30 (0.00%)  0
Photophobia † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 0/40 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 1/30 (3.33%)  1
Vision blurred † 1  0/3 (0.00%)  0 1/8 (12.50%)  1 0/9 (0.00%)  0 3/40 (7.50%)  3 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/30 (0.00%)  0
Visual impairment † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 0/40 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 1/30 (3.33%)  1
Gastrointestinal disorders                 
Abdominal discomfort † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 1/9 (11.11%)  1 0/40 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/30 (0.00%)  0
Abdominal distension † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 2/40 (5.00%)  2 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/30 (0.00%)  0
Abdominal pain † 1  1/3 (33.33%)  1 1/8 (12.50%)  1 1/9 (11.11%)  1 5/40 (12.50%)  8 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 1/30 (3.33%)  1
Breath odour † 1  0/3 (0.00%)  0 1/8 (12.50%)  1 0/9 (0.00%)  0 0/40 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/30 (0.00%)  0
Colitis † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 0/40 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 1/30 (3.33%)  1
Constipation † 1  0/3 (0.00%)  0 1/8 (12.50%)  1 3/9 (33.33%)  3 14/40 (35.00%)  16 3/9 (33.33%)  3 2/9 (22.22%)  2 2/8 (25.00%)  2 12/30 (40.00%)  17
Diarrhoea † 1  0/3 (0.00%)  0 2/8 (25.00%)  2 0/9 (0.00%)  0 12/40 (30.00%)  17 2/9 (22.22%)  2 2/9 (22.22%)  2 1/8 (12.50%)  1 4/30 (13.33%)  5
Dry mouth † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 4/40 (10.00%)  4 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 1/30 (3.33%)  1
Dyspepsia † 1  0/3 (0.00%)  0 1/8 (12.50%)  1 1/9 (11.11%)  1 2/40 (5.00%)  2 1/9 (11.11%)  1 0/9 (0.00%)  0 0/8 (0.00%)  0 2/30 (6.67%)  2
Dysphagia † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 1/40 (2.50%)  1 1/9 (11.11%)  1 0/9 (0.00%)  0 0/8 (0.00%)  0 1/30 (3.33%)  1
Eructation † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 1/9 (11.11%)  1 1/40 (2.50%)  1 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/30 (0.00%)  0
Femoral hernia † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 0/40 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 1/30 (3.33%)  1
Flatulence † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 1/9 (11.11%)  1 2/40 (5.00%)  2 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 1/30 (3.33%)  1
Gastrooesophageal reflux disease † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 0/40 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 1/8 (12.50%)  1 1/30 (3.33%)  1
Haematemesis † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 0/40 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 1/30 (3.33%)  1
Hyperaesthesia teeth † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 0/40 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 1/30 (3.33%)  1
Inguinal hernia † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 0/40 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 1/30 (3.33%)  2
Melaena † 1  0/3 (0.00%)  0 1/8 (12.50%)  1 0/9 (0.00%)  0 0/40 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/30 (0.00%)  0
Nausea † 1  1/3 (33.33%)  1 3/8 (37.50%)  3 5/9 (55.56%)  5 29/40 (72.50%)  42 7/9 (77.78%)  8 4/9 (44.44%)  4 4/8 (50.00%)  5 13/30 (43.33%)  18
Oral dysaesthesia † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 0/40 (0.00%)  0 1/9 (11.11%)  1 0/9 (0.00%)  0 0/8 (0.00%)  0 0/30 (0.00%)  0
Retching † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 0/40 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 1/30 (3.33%)  1
Stomatitis † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 2/40 (5.00%)  2 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/30 (0.00%)  0
Tooth discolouration † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 0/40 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 1/30 (3.33%)  1
Umbilical hernia † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 0/40 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 1/30 (3.33%)  1
Vomiting † 1  1/3 (33.33%)  1 0/8 (0.00%)  0 2/9 (22.22%)  2 13/40 (32.50%)  20 2/9 (22.22%)  2 1/9 (11.11%)  1 4/8 (50.00%)  5 7/30 (23.33%)  15
Vomiting projectile † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 0/40 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 1/30 (3.33%)  1
General disorders                 
Asthenia † 1  0/3 (0.00%)  0 1/8 (12.50%)  1 0/9 (0.00%)  0 2/40 (5.00%)  2 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 1/30 (3.33%)  2
Chest pain † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 1/40 (2.50%)  1 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 1/30 (3.33%)  1
Chills † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 1/9 (11.11%)  1 0/40 (0.00%)  0 1/9 (11.11%)  1 0/9 (0.00%)  0 0/8 (0.00%)  0 0/30 (0.00%)  0
Early satiety † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 1/9 (11.11%)  1 0/40 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/30 (0.00%)  0
Fatigue † 1  3/3 (100.00%)  3 2/8 (25.00%)  2 6/9 (66.67%)  7 29/40 (72.50%)  34 6/9 (66.67%)  7 1/9 (11.11%)  1 4/8 (50.00%)  4 17/30 (56.67%)  20
Feeling cold † 1  0/3 (0.00%)  0 1/8 (12.50%)  1 0/9 (0.00%)  0 0/40 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 1/30 (3.33%)  1
Gait disturbance † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 2/40 (5.00%)  2 2/9 (22.22%)  2 1/9 (11.11%)  1 1/8 (12.50%)  1 2/30 (6.67%)  2
Influenza like illness † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 0/40 (0.00%)  0 0/9 (0.00%)  0 1/9 (11.11%)  1 0/8 (0.00%)  0 1/30 (3.33%)  1
Malaise † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 3/40 (7.50%)  3 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 1/30 (3.33%)  2
Non-cardiac chest pain † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 1/40 (2.50%)  1 0/9 (0.00%)  0 1/9 (11.11%)  1 0/8 (0.00%)  0 0/30 (0.00%)  0
Oedema peripheral † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 4/40 (10.00%)  4 2/9 (22.22%)  2 1/9 (11.11%)  1 0/8 (0.00%)  0 3/30 (10.00%)  4
Pyrexia † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 1/40 (2.50%)  1 0/9 (0.00%)  0 1/9 (11.11%)  1 0/8 (0.00%)  0 3/30 (10.00%)  3
Swelling face † 1  0/3 (0.00%)  0 1/8 (12.50%)  2 0/9 (0.00%)  0 0/40 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/30 (0.00%)  0
Vessel puncture site pain † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 0/40 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 1/30 (3.33%)  1
Hepatobiliary disorders                 
Hepatic lesion † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 0/40 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 1/30 (3.33%)  2
Infections and infestations                 
Cellulitis † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 0/40 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 1/30 (3.33%)  1
Eye infection † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 0/40 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 1/30 (3.33%)  1
Hordeolum † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 0/40 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 1/30 (3.33%)  1
Influenza † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 0/40 (0.00%)  0 1/9 (11.11%)  1 0/9 (0.00%)  0 0/8 (0.00%)  0 0/30 (0.00%)  0
Oral candidiasis † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 1/40 (2.50%)  1 2/9 (22.22%)  2 0/9 (0.00%)  0 0/8 (0.00%)  0 1/30 (3.33%)  2
Oral herpes † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 1/40 (2.50%)  1 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 2/30 (6.67%)  3
Osteomyelitis chronic † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 0/40 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 1/30 (3.33%)  1
Otitis media † 1  0/3 (0.00%)  0 1/8 (12.50%)  1 0/9 (0.00%)  0 2/40 (5.00%)  2 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/30 (0.00%)  0
Pneumonia † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 0/40 (0.00%)  0 0/9 (0.00%)  0 1/9 (11.11%)  1 0/8 (0.00%)  0 0/30 (0.00%)  0
Postoperative wound infection † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 1/40 (2.50%)  1 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 1/30 (3.33%)  1
Sinusitis † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 1/40 (2.50%)  1 1/9 (11.11%)  1 0/9 (0.00%)  0 0/8 (0.00%)  0 0/30 (0.00%)  0
Tooth infection † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 0/40 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 1/30 (3.33%)  1
Upper respiratory tract infection † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 2/40 (5.00%)  3 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 1/30 (3.33%)  1
Urinary tract infection † 1  0/3 (0.00%)  0 1/8 (12.50%)  1 0/9 (0.00%)  0 1/40 (2.50%)  2 1/9 (11.11%)  1 0/9 (0.00%)  0 0/8 (0.00%)  0 1/30 (3.33%)  1
Wound infection † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 0/40 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 2/30 (6.67%)  2
Injury, poisoning and procedural complications                 
Contusion † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 2/40 (5.00%)  3 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 3/30 (10.00%)  3
Eye contusion † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 0/40 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 1/30 (3.33%)  1
Fall † 1  0/3 (0.00%)  0 1/8 (12.50%)  2 0/9 (0.00%)  0 5/40 (12.50%)  6 1/9 (11.11%)  1 0/9 (0.00%)  0 3/8 (37.50%)  3 5/30 (16.67%)  8
Ligament sprain † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 0/40 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 1/30 (3.33%)  1
Pseudomeningocele † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 0/40 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 1/8 (12.50%)  1 0/30 (0.00%)  0
Radiation injury † 1  0/3 (0.00%)  0 1/8 (12.50%)  2 0/9 (0.00%)  0 1/40 (2.50%)  1 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/30 (0.00%)  0
Radiation skin injury † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 2/40 (5.00%)  2 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/30 (0.00%)  0
Skin laceration † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 0/40 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 2/30 (6.67%)  3
Subdural haematoma † 1  0/3 (0.00%)  0 1/8 (12.50%)  1 0/9 (0.00%)  0 0/40 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/30 (0.00%)  0
Traumatic haematoma † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 0/40 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 1/30 (3.33%)  1
Investigations                 
Alanine aminotransferase increased † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 3/40 (7.50%)  3 0/9 (0.00%)  0 1/9 (11.11%)  1 0/8 (0.00%)  0 1/30 (3.33%)  1
Aspartate aminotransferase increased † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 3/40 (7.50%)  3 0/9 (0.00%)  0 1/9 (11.11%)  1 0/8 (0.00%)  0 0/30 (0.00%)  0
Blood bilirubin increased † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 1/40 (2.50%)  4 1/9 (11.11%)  1 2/9 (22.22%)  2 1/8 (12.50%)  1 1/30 (3.33%)  1
Blood bilirubin unconjugated increased † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 0/40 (0.00%)  0 1/9 (11.11%)  1 0/9 (0.00%)  0 0/8 (0.00%)  0 0/30 (0.00%)  0
Blood creatinine increased † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 4/40 (10.00%)  5 0/9 (0.00%)  0 0/9 (0.00%)  0 1/8 (12.50%)  1 2/30 (6.67%)  3
Cortisol decreased † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 0/40 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 1/30 (3.33%)  1
Electrocardiogram QT prolonged † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 0/40 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 1/30 (3.33%)  1
Lymphocyte count decreased † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 1/9 (11.11%)  1 3/40 (7.50%)  3 2/9 (22.22%)  2 3/9 (33.33%)  3 1/8 (12.50%)  1 4/30 (13.33%)  5
Neutrophil count decreased † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 6/40 (15.00%)  9 3/9 (33.33%)  3 2/9 (22.22%)  2 2/8 (25.00%)  2 5/30 (16.67%)  10
Platelet count decreased † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 1/9 (11.11%)  1 7/40 (17.50%)  8 1/9 (11.11%)  2 3/9 (33.33%)  3 1/8 (12.50%)  1 8/30 (26.67%)  18
Weight decreased † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 1/9 (11.11%)  1 9/40 (22.50%)  10 0/9 (0.00%)  0 0/9 (0.00%)  0 1/8 (12.50%)  1 3/30 (10.00%)  3
White blood cell count decreased † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 1/9 (11.11%)  1 6/40 (15.00%)  8 4/9 (44.44%)  7 2/9 (22.22%)  2 1/8 (12.50%)  1 6/30 (20.00%)  10
Metabolism and nutrition disorders                 
Decreased appetite † 1  1/3 (33.33%)  1 1/8 (12.50%)  1 3/9 (33.33%)  3 14/40 (35.00%)  15 4/9 (44.44%)  4 2/9 (22.22%)  2 1/8 (12.50%)  1 7/30 (23.33%)  8
Dehydration † 1  0/3 (0.00%)  0 1/8 (12.50%)  1 0/9 (0.00%)  0 1/40 (2.50%)  2 0/9 (0.00%)  0 0/9 (0.00%)  0 1/8 (12.50%)  1 0/30 (0.00%)  0
Hyperglycaemia † 1  1/3 (33.33%)  1 0/8 (0.00%)  0 1/9 (11.11%)  1 2/40 (5.00%)  3 1/9 (11.11%)  1 2/9 (22.22%)  2 0/8 (0.00%)  0 1/30 (3.33%)  1
Hypernatraemia † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 1/40 (2.50%)  1 1/9 (11.11%)  1 1/9 (11.11%)  1 0/8 (0.00%)  0 0/30 (0.00%)  0
Hypoalbuminaemia † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 1/40 (2.50%)  1 0/9 (0.00%)  0 1/9 (11.11%)  1 0/8 (0.00%)  0 0/30 (0.00%)  0
Hypocalcaemia † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 0/40 (0.00%)  0 0/9 (0.00%)  0 1/9 (11.11%)  1 0/8 (0.00%)  0 0/30 (0.00%)  0
Hypokalaemia † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 1/9 (11.11%)  1 2/40 (5.00%)  2 2/9 (22.22%)  2 0/9 (0.00%)  0 0/8 (0.00%)  0 1/30 (3.33%)  1
Hyponatraemia † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 4/40 (10.00%)  7 0/9 (0.00%)  0 0/9 (0.00%)  0 1/8 (12.50%)  1 1/30 (3.33%)  1
Hypophosphataemia † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 3/40 (7.50%)  4 0/9 (0.00%)  0 1/9 (11.11%)  1 1/8 (12.50%)  1 0/30 (0.00%)  0
Musculoskeletal and connective tissue disorders                 
Arthralgia † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 1/40 (2.50%)  1 2/9 (22.22%)  2 0/9 (0.00%)  0 0/8 (0.00%)  0 2/30 (6.67%)  2
Back pain † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 3/40 (7.50%)  3 1/9 (11.11%)  1 1/9 (11.11%)  1 0/8 (0.00%)  0 0/30 (0.00%)  0
Flank pain † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 0/40 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 1/30 (3.33%)  1
Groin pain † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 1/40 (2.50%)  1 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 1/30 (3.33%)  1
Muscle spasms † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 1/40 (2.50%)  1 1/9 (11.11%)  2 0/9 (0.00%)  0 0/8 (0.00%)  0 0/30 (0.00%)  0
Muscular weakness † 1  0/3 (0.00%)  0 1/8 (12.50%)  1 1/9 (11.11%)  1 1/40 (2.50%)  1 1/9 (11.11%)  1 1/9 (11.11%)  1 1/8 (12.50%)  1 3/30 (10.00%)  3
Musculoskeletal pain † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 0/40 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 2/30 (6.67%)  3
Myalgia † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 1/40 (2.50%)  1 1/9 (11.11%)  1 0/9 (0.00%)  0 0/8 (0.00%)  0 3/30 (10.00%)  3
Neck pain † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 0/40 (0.00%)  0 1/9 (11.11%)  1 0/9 (0.00%)  0 0/8 (0.00%)  0 1/30 (3.33%)  1
Pain in extremity † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 1/40 (2.50%)  1 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 1/30 (3.33%)  1
Pain in jaw † 1  0/3 (0.00%)  0 1/8 (12.50%)  1 0/9 (0.00%)  0 0/40 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/30 (0.00%)  0
Tenosynovitis † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 0/40 (0.00%)  0 1/9 (11.11%)  1 0/9 (0.00%)  0 0/8 (0.00%)  0 0/30 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)                 
Renal hamartoma † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 0/40 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 1/30 (3.33%)  1
Nervous system disorders                 
Ageusia † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 1/9 (11.11%)  1 0/40 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/30 (0.00%)  0
Amnesia † 1  1/3 (33.33%)  1 1/8 (12.50%)  1 0/9 (0.00%)  0 0/40 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 2/30 (6.67%)  2
Aphasia † 1  0/3 (0.00%)  0 1/8 (12.50%)  1 3/9 (33.33%)  3 6/40 (15.00%)  7 1/9 (11.11%)  2 1/9 (11.11%)  1 0/8 (0.00%)  0 3/30 (10.00%)  3
Ataxia † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 1/9 (11.11%)  1 0/40 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/30 (0.00%)  0
Balance disorder † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 2/9 (22.22%)  2 0/40 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/30 (0.00%)  0
Brain oedema † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 0/40 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 1/8 (12.50%)  1 0/30 (0.00%)  0
Carpal tunnel syndrome † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 0/40 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 1/30 (3.33%)  1
Cerebrospinal fluid leakage † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 0/40 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 1/30 (3.33%)  1
Cognitive disorder † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 2/40 (5.00%)  2 0/9 (0.00%)  0 2/9 (22.22%)  2 0/8 (0.00%)  0 0/30 (0.00%)  0
Disturbance in attention † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 1/40 (2.50%)  1 0/9 (0.00%)  0 1/9 (11.11%)  1 0/8 (0.00%)  0 1/30 (3.33%)  1
Dizziness † 1  0/3 (0.00%)  0 1/8 (12.50%)  1 0/9 (0.00%)  0 11/40 (27.50%)  12 2/9 (22.22%)  2 1/9 (11.11%)  1 1/8 (12.50%)  1 8/30 (26.67%)  8
Drooling † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 0/40 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 1/30 (3.33%)  1
Dysaesthesia † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 0/40 (0.00%)  0 0/9 (0.00%)  0 1/9 (11.11%)  1 0/8 (0.00%)  0 0/30 (0.00%)  0
Dysarthria † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 0/40 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 1/30 (3.33%)  1
Dysgeusia † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 10/40 (25.00%)  11 2/9 (22.22%)  2 1/9 (11.11%)  1 0/8 (0.00%)  0 2/30 (6.67%)  3
Dyslexia † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 0/40 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 1/30 (3.33%)  1
Encephalopathy † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 0/40 (0.00%)  0 0/9 (0.00%)  0 1/9 (11.11%)  1 0/8 (0.00%)  0 0/30 (0.00%)  0
Epilepsy † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 0/40 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 1/30 (3.33%)  3
Facial paralysis † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 1/9 (11.11%)  1 0/40 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/30 (0.00%)  0
Facial paresis † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 0/40 (0.00%)  0 0/9 (0.00%)  0 1/9 (11.11%)  1 0/8 (0.00%)  0 1/30 (3.33%)  1
Headache † 1  1/3 (33.33%)  1 1/8 (12.50%)  1 4/9 (44.44%)  4 18/40 (45.00%)  24 2/9 (22.22%)  3 1/9 (11.11%)  1 0/8 (0.00%)  0 8/30 (26.67%)  11
Hemianopia homonymous † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 1/9 (11.11%)  1 0/40 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/30 (0.00%)  0
Hemiparesis † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 1/9 (11.11%)  1 8/40 (20.00%)  9 3/9 (33.33%)  3 3/9 (33.33%)  3 1/8 (12.50%)  1 4/30 (13.33%)  4
Hypersomnia † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 1/40 (2.50%)  1 1/9 (11.11%)  1 0/9 (0.00%)  0 0/8 (0.00%)  0 2/30 (6.67%)  2
Hypoaesthesia † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 2/40 (5.00%)  2 1/9 (11.11%)  1 0/9 (0.00%)  0 0/8 (0.00%)  0 0/30 (0.00%)  0
Memory impairment † 1  0/3 (0.00%)  0 1/8 (12.50%)  1 0/9 (0.00%)  0 6/40 (15.00%)  6 1/9 (11.11%)  1 1/9 (11.11%)  1 0/8 (0.00%)  0 0/30 (0.00%)  0
Muscle spasticity † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 0/40 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 1/30 (3.33%)  2
Myoclonus † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 1/9 (11.11%)  1 0/40 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/30 (0.00%)  0
Paraesthesia † 1  0/3 (0.00%)  0 1/8 (12.50%)  1 1/9 (11.11%)  1 1/40 (2.50%)  1 1/9 (11.11%)  1 1/9 (11.11%)  1 0/8 (0.00%)  0 2/30 (6.67%)  2
Partial seizures † 1  0/3 (0.00%)  0 1/8 (12.50%)  1 1/9 (11.11%)  1 2/40 (5.00%)  2 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/30 (0.00%)  0
Peripheral motor neuropathy † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 1/9 (11.11%)  1 0/40 (0.00%)  0 0/9 (0.00%)  0 1/9 (11.11%)  2 0/8 (0.00%)  0 0/30 (0.00%)  0
Peripheral sensory neuropathy † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 0/40 (0.00%)  0 1/9 (11.11%)  1 0/9 (0.00%)  0 0/8 (0.00%)  0 0/30 (0.00%)  0
Seizure † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 1/9 (11.11%)  1 6/40 (15.00%)  9 0/9 (0.00%)  0 1/9 (11.11%)  1 0/8 (0.00%)  0 4/30 (13.33%)  4
Somnolence † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 0/40 (0.00%)  0 0/9 (0.00%)  0 1/9 (11.11%)  1 0/8 (0.00%)  0 0/30 (0.00%)  0
Taste disorder † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 1/9 (11.11%)  1 0/40 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/30 (0.00%)  0
Tremor † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 1/9 (11.11%)  2 1/40 (2.50%)  1 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 1/30 (3.33%)  1
Visual field defect † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 3/40 (7.50%)  3 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 2/30 (6.67%)  2
Psychiatric disorders                 
Agitation † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 4/40 (10.00%)  4 1/9 (11.11%)  1 1/9 (11.11%)  1 0/8 (0.00%)  0 0/30 (0.00%)  0
Alcohol abuse † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 0/40 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 1/30 (3.33%)  1
Anxiety † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 1/9 (11.11%)  1 6/40 (15.00%)  6 2/9 (22.22%)  2 0/9 (0.00%)  0 0/8 (0.00%)  0 1/30 (3.33%)  1
Confusional state † 1  0/3 (0.00%)  0 2/8 (25.00%)  2 1/9 (11.11%)  1 4/40 (10.00%)  5 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 3/30 (10.00%)  3
Decreased interest † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 0/40 (0.00%)  0 1/9 (11.11%)  1 0/9 (0.00%)  0 0/8 (0.00%)  0 0/30 (0.00%)  0
Depression † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 1/40 (2.50%)  1 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 3/30 (10.00%)  3
Insomnia † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 6/40 (15.00%)  6 2/9 (22.22%)  2 0/9 (0.00%)  0 1/8 (12.50%)  1 4/30 (13.33%)  4
Irritability † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 2/40 (5.00%)  2 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/30 (0.00%)  0
Persistent depressive disorder † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 0/40 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 1/30 (3.33%)  1
Suicidal ideation † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 0/40 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 1/30 (3.33%)  1
Renal and urinary disorders                 
Acute kidney injury † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 0/40 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 1/30 (3.33%)  1
Haematuria † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 1/9 (11.11%)  1 2/40 (5.00%)  2 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 1/30 (3.33%)  1
Nephrolithiasis † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 0/40 (0.00%)  0 1/9 (11.11%)  1 0/9 (0.00%)  0 0/8 (0.00%)  0 0/30 (0.00%)  0
Pollakiuria † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 1/40 (2.50%)  1 0/9 (0.00%)  0 0/9 (0.00%)  0 1/8 (12.50%)  1 1/30 (3.33%)  1
Polyuria † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 0/40 (0.00%)  0 1/9 (11.11%)  1 0/9 (0.00%)  0 0/8 (0.00%)  0 0/30 (0.00%)  0
Urinary incontinence † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 6/40 (15.00%)  6 2/9 (22.22%)  2 1/9 (11.11%)  1 0/8 (0.00%)  0 0/30 (0.00%)  0
Respiratory, thoracic and mediastinal disorders                 
Chronic obstructive pulmonary disease † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 0/40 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 1/30 (3.33%)  1
Cough † 1  0/3 (0.00%)  0 1/8 (12.50%)  1 0/9 (0.00%)  0 4/40 (10.00%)  5 0/9 (0.00%)  0 1/9 (11.11%)  1 0/8 (0.00%)  0 2/30 (6.67%)  3
Dysphonia † 1  0/3 (0.00%)  0 2/8 (25.00%)  2 0/9 (0.00%)  0 0/40 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/30 (0.00%)  0
Dyspnoea † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 1/40 (2.50%)  1 1/9 (11.11%)  1 0/9 (0.00%)  0 0/8 (0.00%)  0 4/30 (13.33%)  5
Dyspnoea exertional † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 0/40 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 1/30 (3.33%)  1
Epistaxis † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 1/9 (11.11%)  1 0/40 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/30 (0.00%)  0
Hiccups † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 1/9 (11.11%)  1 1/40 (2.50%)  1 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 1/30 (3.33%)  1
Hypoxia † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 0/40 (0.00%)  0 0/9 (0.00%)  0 1/9 (11.11%)  2 0/8 (0.00%)  0 0/30 (0.00%)  0
Laryngeal inflammation † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 0/40 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 1/30 (3.33%)  1
Nasal congestion † 1  0/3 (0.00%)  0 1/8 (12.50%)  1 1/9 (11.11%)  1 3/40 (7.50%)  3 1/9 (11.11%)  1 0/9 (0.00%)  0 1/8 (12.50%)  1 3/30 (10.00%)  3
Nasal polyps † 1  0/3 (0.00%)  0 1/8 (12.50%)  1 0/9 (0.00%)  0 0/40 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/30 (0.00%)  0
Productive cough † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 0/40 (0.00%)  0 1/9 (11.11%)  1 0/9 (0.00%)  0 0/8 (0.00%)  0 0/30 (0.00%)  0
Pulmonary embolism † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 2/40 (5.00%)  2 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 1/30 (3.33%)  1
Rhinitis allergic † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 1/40 (2.50%)  1 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 1/30 (3.33%)  1
Sinus congestion † 1  0/3 (0.00%)  0 1/8 (12.50%)  1 0/9 (0.00%)  0 1/40 (2.50%)  1 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/30 (0.00%)  0
Upper-airway cough syndrome † 1  0/3 (0.00%)  0 1/8 (12.50%)  1 0/9 (0.00%)  0 0/40 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/30 (0.00%)  0
Wheezing † 1  0/3 (0.00%)  0 1/8 (12.50%)  1 0/9 (0.00%)  0 0/40 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 1/30 (3.33%)  1
Skin and subcutaneous tissue disorders                 
Acne † 1  0/3 (0.00%)  0 1/8 (12.50%)  1 0/9 (0.00%)  0 0/40 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/30 (0.00%)  0
Alopecia † 1  2/3 (66.67%)  2 2/8 (25.00%)  2 2/9 (22.22%)  2 14/40 (35.00%)  16 4/9 (44.44%)  4 0/9 (0.00%)  0 0/8 (0.00%)  0 0/30 (0.00%)  0
Dermatitis † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 1/9 (11.11%)  1 1/40 (2.50%)  1 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/30 (0.00%)  0
Dermatitis acneiform † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 2/40 (5.00%)  2 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/30 (0.00%)  0
Dermatitis contact † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 1/40 (2.50%)  1 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 1/30 (3.33%)  1
Dry skin † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 0/40 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 1/30 (3.33%)  1
Erythema † 1  0/3 (0.00%)  0 1/8 (12.50%)  1 1/9 (11.11%)  1 0/40 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 1/30 (3.33%)  1
Night sweats † 1  0/3 (0.00%)  0 1/8 (12.50%)  1 0/9 (0.00%)  0 1/40 (2.50%)  1 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/30 (0.00%)  0
Pain of skin † 1  0/3 (0.00%)  0 2/8 (25.00%)  2 0/9 (0.00%)  0 0/40 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/30 (0.00%)  0
Petechiae † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 0/40 (0.00%)  0 1/9 (11.11%)  1 0/9 (0.00%)  0 0/8 (0.00%)  0 0/30 (0.00%)  0
Pruritus † 1  1/3 (33.33%)  1 1/8 (12.50%)  1 0/9 (0.00%)  0 1/40 (2.50%)  1 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 1/30 (3.33%)  1
Purpura † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 0/40 (0.00%)  0 1/9 (11.11%)  1 0/9 (0.00%)  0 0/8 (0.00%)  0 0/30 (0.00%)  0
Rash maculo-papular † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 1/40 (2.50%)  1 3/9 (33.33%)  3 2/9 (22.22%)  2 0/8 (0.00%)  0 2/30 (6.67%)  2
Skin atrophy † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 2/40 (5.00%)  2 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 0/30 (0.00%)  0
Vascular disorders                 
Deep vein thrombosis † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 1/40 (2.50%)  1 1/9 (11.11%)  1 0/9 (0.00%)  0 0/8 (0.00%)  0 1/30 (3.33%)  1
Hypertension † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 1/9 (11.11%)  1 1/40 (2.50%)  1 2/9 (22.22%)  2 0/9 (0.00%)  0 0/8 (0.00%)  0 0/30 (0.00%)  0
Hypotension † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 0/40 (0.00%)  0 1/9 (11.11%)  1 1/9 (11.11%)  1 0/8 (0.00%)  0 1/30 (3.33%)  1
Pallor † 1  0/3 (0.00%)  0 0/8 (0.00%)  0 0/9 (0.00%)  0 0/40 (0.00%)  0 0/9 (0.00%)  0 0/9 (0.00%)  0 0/8 (0.00%)  0 1/30 (3.33%)  1
1
Term from vocabulary, meddra 23.0
†
Indicates events were collected by systematic assessment
[Not Specified]
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
BeiGene has 18 months from the end of the study at all sites to publish overall study results. After the 1st multi-site publication or the expiration of publication period, Investigators are free to publish/present the results of the study. Investigators must submit all draft publications/presentations to us for review 60 days prior to the planned publication/presentation date. BeiGene may request deletion of its confidential information & may request a further delay to protect its IP rights.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: BeiGene
Phone: +1-877-828-5568
EMail: clinicaltrials@beigene.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: BeiGene ( BeiGene USA, Inc. )
ClinicalTrials.gov Identifier: NCT03150862    
Other Study ID Numbers: BGB-290-104
2017-001554-33 ( EudraCT Number )
First Submitted: May 8, 2017
First Posted: May 12, 2017
Results First Submitted: March 3, 2022
Results First Posted: May 31, 2022
Last Update Posted: May 31, 2022