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Cediranib Maleate and Olaparib in Treating Patients With Recurrent Ovarian, Fallopian Tube, or Peritoneal Cancer or Recurrent Triple-Negative Breast Cancer

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: NCT01116648
Recruitment Status : Active, not recruiting
First Posted : May 5, 2010
Results First Posted : July 22, 2020
Last Update Posted : April 8, 2024
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Fallopian Tube Carcinoma
Ovarian Endometrioid Adenocarcinoma
Ovarian High Grade Serous Adenocarcinoma
Ovarian Serous Adenocarcinoma
Ovarian Serous Surface Papillary Adenocarcinoma
Primary Peritoneal Serous Adenocarcinoma
Triple-Negative Breast Carcinoma
Interventions Procedure: Biopsy
Procedure: Biospecimen Collection
Drug: Cediranib Maleate
Procedure: Computed Tomography
Procedure: Echocardiography
Procedure: Magnetic Resonance Imaging
Procedure: Multigated Acquisition Scan
Drug: Olaparib
Enrollment 155
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Dose Level 0 (20mg Ced+100mg Olap) Dose Level 1 (20mg Ced + 200mg Olap) Dose Level 2 (30mg Ced + 200mg Olap) Dose Level 3 (30mg Ced + 400mg Olap) Expansion Cohort at MTD Phase 2 - Olaparib Alone Phase 2 - Cediranib/Olaparib Phase 1-T Dose Level 0-TA Phase 1-T Dose Level 1-TA Phase 1-T Dose Level 2-TA Phase 1-T Dose Level 0-TB Phase 1-T Dose Level 1-TB Phase 1-T Dose Level 2-TB Phase 1-T PKOlap Expansion Phase 1-T PKCed Expansion
Hide Arm/Group Description Assess the maximum tolerated dose (MTD) of cediranib in combination with olaparib in the treatment of recurrent ovarian, fallopian tube, or peritoneal cancer or metastatic triple-negative breast cancer. Assess the maximum tolerated dose (MTD) of cediranib in combination with olaparib in the treatment of recurrent ovarian, fallopian tube, or peritoneal cancer or metastatic triple-negative breast cancer. Assess the maximum tolerated dose (MTD) of cediranib in combination with olaparib in the treatment of recurrent ovarian, fallopian tube, or peritoneal cancer or metastatic triple-negative breast cancer. Assess the maximum tolerated dose (MTD) of cediranib in combination with olaparib in the treatment of recurrent ovarian, fallopian tube, or peritoneal cancer or metastatic triple-negative breast cancer. Assess the maximum tolerated dose (MTD) of cediranib in combination with olaparib in the treatment of recurrent ovarian, fallopian tube, or peritoneal cancer or metastatic triple-negative breast cancer. Phase 2 - a total of 46 patients were randomized to receive olaparib alone. Phase 2 - a total of 44 patients were randomized to receive cediranib and olaparib. Cediranib 30mg PO daily; Olaparib (tablet) 150mg PO BID Cediranib 30mg PO daily; Olaparib (tablet) 200mg PO BID Cediranib 30mg PO daily; Olaparib (tablet) 250mg PO BID Cediranib 20mg PO daily; Olaparib (tablet) 200mg PO BID Cediranib 20mg PO daily; Olaparib (tablet) 250 mg PO BID Cediranib 20mg PO daily; Olaparib (tablet) 300mg PO BID Cediranib 30mg PO daily; Olaparib (tablet) 200mg BID; 7-day lead-in of single-agent olaparib Cediranib 30mg PO daily; Olaparib (tablet) 200mg BID; 7-day lead-in of single agent cediranib
Period Title: Phase 1 Dose Level 0
Started 3 0 0 0 0 0 0 0 0 0 0 0 0 0 0
Completed 3 0 0 0 0 0 0 0 0 0 0 0 0 0 0
Not Completed 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
Period Title: Phase 1 Dose Level 1
Started 0 3 0 0 0 0 0 0 0 0 0 0 0 0 0
Completed 0 3 0 0 0 0 0 0 0 0 0 0 0 0 0
Not Completed 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
Period Title: Phase 1 Dose Level 2
Started 0 0 7 0 0 0 0 0 0 0 0 0 0 0 0
Completed 0 0 7 0 0 0 0 0 0 0 0 0 0 0 0
Not Completed 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
Period Title: Phase 1 Dose Level 3
Started 0 0 0 6 0 0 0 0 0 0 0 0 0 0 0
Completed 0 0 0 4 0 0 0 0 0 0 0 0 0 0 0
Not Completed 0 0 0 2 0 0 0 0 0 0 0 0 0 0 0
Reason Not Completed
Adverse Event             0             0             0             2             0             0             0             0             0             0             0             0             0             0             0
Period Title: Expansion at Maximum Tolerated Dose
Started 0 0 0 0 9 0 0 0 0 0 0 0 0 0 0
Completed 0 0 0 0 9 0 0 0 0 0 0 0 0 0 0
Not Completed 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
Period Title: Phase 2
Started 0 0 0 0 0 46 44 0 0 0 0 0 0 0 0
Completed 0 0 0 0 0 46 44 0 0 0 0 0 0 0 0
Not Completed 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
Period Title: Phase 1-T Dose Level 0-TA
Started 0 0 0 0 0 0 0 3 0 0 0 0 0 0 0
Completed 0 0 0 0 0 0 0 3 0 0 0 0 0 0 0
Not Completed 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
Period Title: Phase 1-T Dose Level 1-TA
Started 0 0 0 0 0 0 0 0 6 0 0 0 0 0 0
Completed 0 0 0 0 0 0 0 0 6 0 0 0 0 0 0
Not Completed 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
Period Title: Phase 1-T Dose Level 2-TA
Started 0 0 0 0 0 0 0 0 0 3 0 0 0 0 0
Completed 0 0 0 0 0 0 0 0 0 3 0 0 0 0 0
Not Completed 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
Period Title: Phase 1-T Dose Level 0-TB
Started 0 0 0 0 0 0 0 0 0 0 3 0 0 0 0
Completed 0 0 0 0 0 0 0 0 0 0 3 0 0 0 0
Not Completed 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
Period Title: Phase 1-T Dose Level 1-TB
Started 0 0 0 0 0 0 0 0 0 0 0 3 0 0 0
Completed 0 0 0 0 0 0 0 0 0 0 0 3 0 0 0
Not Completed 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
Period Title: Phase 1-T Dose Level 2-TB
Started 0 0 0 0 0 0 0 0 0 0 0 0 6 0 0
Completed 0 0 0 0 0 0 0 0 0 0 0 0 6 0 0
Not Completed 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
Period Title: Phase 1-T PKOlap Expansion
Started 0 0 0 0 0 0 0 0 0 0 0 0 0 6 0
Completed 0 0 0 0 0 0 0 0 0 0 0 0 0 6 0
Not Completed 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
Period Title: Phase 1-T PKCed Expansion
Started 0 0 0 0 0 0 0 0 0 0 0 0 0 0 7
Completed 0 0 0 0 0 0 0 0 0 0 0 0 0 0 7
Not Completed 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
Arm/Group Title Phase 1 Dose Level 0 (3 Participants) Phase 1 Dose Level 1 (3 Participants) Phase 1 Dose Level 2 (7 Participants) Phase 1 Dose Level 3 (6 Participants) Phase 1 Expansion at MTD (9 Participants) Phase 2 - Olaparib Alone Phase 2 - Cediranib/Olaparib Phase 1-T Dose Level 0-TA Phase 1-T Dose Level 1-TA Phase 1-T Dose Level 2-TA Phase 1-T Dose Level 0-TB Phase 1-T Dose Level 1-TB Phase 1-T Dose Level 2-TB Phase 1-T PKOlap Expansion Phase 1-T PKCed Expansion Total
Hide Arm/Group Description

Assess the maximum tolerated dose (MTD) of cediranib in combination with olaparib in the treatment of recurrent ovarian, fallopian tube, or peritoneal cancer or metastatic triple-negative breast cancer.

This was an open-label, phase 1, dose-escalation trial performed at two participating institutions evaluating increasing doses of once daily cediranib and twice daily olaparib administered continuously in 28-day cycles. Cediranib was administered as 10 and 15 mg tablets and olaparib as 50 mg capsules. The primary objectives were to determine the dose limiting toxicities (DLT) and maximum tolerated dose (MTD) of this combination. Secondary objectives included assessment of treatment-related toxicities and preliminary assessment of clinical activity as measured by response rate, clinical benefit rate (CBR) and progression-free survival (PFS), defined as time from initiation of therapy to disease progression or death from any cause.

Assess the maximum tolerated dose (MTD) of cediranib in combination with olaparib in the treatment of recurrent ovarian, fallopian tube, or peritoneal cancer or metastatic triple-negative breast cancer.

This was an open-label, phase 1, dose-escalation trial performed at two participating institutions evaluating increasing doses of once daily cediranib and twice daily olaparib administered continuously in 28-day cycles. Cediranib was administered as 10 and 15 mg tablets and olaparib as 50 mg capsules. The primary objectives were to determine the dose limiting toxicities (DLT) and maximum tolerated dose (MTD) of this combination. Secondary objectives included assessment of treatment-related toxicities and preliminary assessment of clinical activity as measured by response rate, clinical benefit rate (CBR) and progression-free survival (PFS), defined as time from initiation of therapy to disease progression or death from any cause.

Assess the maximum tolerated dose (MTD) of cediranib in combination with olaparib in the treatment of recurrent ovarian, fallopian tube, or peritoneal cancer or metastatic triple-negative breast cancer.

This was an open-label, phase 1, dose-escalation trial performed at two participating institutions evaluating increasing doses of once daily cediranib and twice daily olaparib administered continuously in 28-day cycles. Cediranib was administered as 10 and 15 mg tablets and olaparib as 50 mg capsules. The primary objectives were to determine the dose limiting toxicities (DLT) and maximum tolerated dose (MTD) of this combination. Secondary objectives included assessment of treatment-related toxicities and preliminary assessment of clinical activity as measured by response rate, clinical benefit rate (CBR) and progression-free survival (PFS), defined as time from initiation of therapy to disease progression or death from any cause.

Assess the maximum tolerated dose (MTD) of cediranib in combination with olaparib in the treatment of recurrent ovarian, fallopian tube, or peritoneal cancer or metastatic triple-negative breast cancer.

This was an open-label, phase 1, dose-escalation trial performed at two participating institutions evaluating increasing doses of once daily cediranib and twice daily olaparib administered continuously in 28-day cycles. Cediranib was administered as 10 and 15 mg tablets and olaparib as 50 mg capsules. The primary objectives were to determine the dose limiting toxicities (DLT) and maximum tolerated dose (MTD) of this combination. Secondary objectives included assessment of treatment-related toxicities and preliminary assessment of clinical activity as measured by response rate, clinical benefit rate (CBR) and progression-free survival (PFS), defined as time from initiation of therapy to disease progression or death from any cause.

Assess the maximum tolerated dose (MTD) of cediranib in combination with olaparib in the treatment of recurrent ovarian, fallopian tube, or peritoneal cancer or metastatic triple-negative breast cancer.

This was an open-label, phase 1, dose-escalation trial performed at two participating institutions evaluating increasing doses of once daily cediranib and twice daily olaparib administered continuously in 28-day cycles. Cediranib was administered as 10 and 15 mg tablets and olaparib as 50 mg capsules. The primary objectives were to determine the dose limiting toxicities (DLT) and maximum tolerated dose (MTD) of this combination. Secondary objectives included assessment of treatment-related toxicities and preliminary assessment of clinical activity as measured by response rate, clinical benefit rate (CBR) and progression-free survival (PFS), defined as time from initiation of therapy to disease progression or death from any cause.

 Assess the efficacy (as measured by progression-free survival (PFS) ) of olaparib alone in recurrent grade 2 or 3 platinum-sensitive papillary-serous or endometrioid ovarian, fallopian tube, or peritoneal cancer. Assess the efficacy (as measured by progression-free survival (PFS) ) of the combination of cediranib and olaparib in recurrent grade 2 or 3 platinum-sensitive papillary-serous or endometrioid ovarian, fallopian tube, or peritoneal cancer. Cediranib 30mg PO daily; Olaparib (tablet) 150mg PO BID Cediranib 30mg PO daily; Olaparib (tablet) 200mg PO BID Cediranib 30mg PO daily; Olaparib (tablet) 250mgPO BID Cediranib 20mg PO daily; Olaparib (tablet) 200mg PO BID Cediranib 20mg PO daily; Olaparib (tablet) 250mg PO BID Cediranib 20mg PO daily; Olaparib (tablet) 300mg PO BID Cediranib 30mg PO daily; Olaparib (tablet) 200mg PO BID; 7-day lead-in of single-agent olaparib Cediranib 30mg PO daily; Olaparib (tablet) 200mg PO BID; 7-day lead-in of single-agent cediranib Total of all reporting groups
Overall Number of Baseline Participants 3 3 7 6 9 46 44 3 6 3 3 3 6 6 7 155
Hide Baseline Analysis Population Description
Phase 1 was composed of 20 ovarian patients & 8 breast patients Phase 2 was composed of 90 ovarian patients Phase 1-T was composed of 37 ovarian patients
Age, Continuous  
Mean (Full Range)
Unit of measure:  Years
Number Analyzed 3 participants 3 participants 7 participants 6 participants 9 participants 46 participants 44 participants 3 participants 6 participants 3 participants 3 participants 3 participants 6 participants 6 participants 7 participants 155 participants
49
(39 to 69)
59
(53 to 63)
57
(36 to 71)
56
(46 to 68)
57
(45 to 69)
58.1
(32.7 to 81.9)
57.8
(41.9 to 85.6)
55.6
(45.5 to 63.3)
61.5
(38.3 to 71.7)
58.7
(47.7 to 79.9)
57.8
(48.6 to 70.1)
59.0
(54.9 to 63.8)
59.8
(40.3 to 76.6)
58.7
(47.0 to 69.6)
54.5
(41.5 to 66.9)
57.7
(32.7 to 85.6)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 3 participants 7 participants 6 participants 9 participants 46 participants 44 participants 3 participants 6 participants 3 participants 3 participants 3 participants 6 participants 6 participants 7 participants 155 participants
Female
3
 100.0%
3
 100.0%
7
 100.0%
6
 100.0%
9
 100.0%
46
 100.0%
44
 100.0%
3
 100.0%
6
 100.0%
3
 100.0%
3
 100.0%
3
 100.0%
6
 100.0%
6
 100.0%
7
 100.0%
155
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 3 participants 7 participants 6 participants 9 participants 46 participants 44 participants 3 participants 6 participants 3 participants 3 participants 3 participants 6 participants 6 participants 7 participants 155 participants
Hispanic or Latino
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   2.2%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   0.6%
Not Hispanic or Latino
3
 100.0%
3
 100.0%
7
 100.0%
5
  83.3%
9
 100.0%
44
  95.7%
43
  97.7%
3
 100.0%
5
  83.3%
3
 100.0%
3
 100.0%
3
 100.0%
6
 100.0%
5
  83.3%
7
 100.0%
149
  96.1%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
1
  16.7%
0
   0.0%
1
   2.2%
1
   2.3%
0
   0.0%
1
  16.7%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  16.7%
0
   0.0%
5
   3.2%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 3 participants 7 participants 6 participants 9 participants 46 participants 44 participants 3 participants 6 participants 3 participants 3 participants 3 participants 6 participants 6 participants 7 participants 155 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   2.2%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  33.3%
0
   0.0%
0
   0.0%
0
   0.0%
1
  14.3%
3
   1.9%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
1
  14.3%
1
  16.7%
0
   0.0%
1
   2.2%
1
   2.3%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  16.7%
0
   0.0%
0
   0.0%
5
   3.2%
White
3
 100.0%
3
 100.0%
6
  85.7%
4
  66.7%
9
 100.0%
42
  91.3%
43
  97.7%
3
 100.0%
5
  83.3%
2
  66.7%
2
  66.7%
3
 100.0%
4
  66.7%
6
 100.0%
6
  85.7%
141
  91.0%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  16.7%
0
   0.0%
0
   0.0%
1
   0.6%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
1
  16.7%
0
   0.0%
2
   4.3%
0
   0.0%
0
   0.0%
1
  16.7%
1
  33.3%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
5
   3.2%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 3 participants 3 participants 7 participants 6 participants 9 participants 46 participants 44 participants 3 participants 6 participants 3 participants 3 participants 3 participants 6 participants 6 participants 7 participants 155 participants
3 3 7 6 9 46 44 3 6 3 3 3 6 6 7 155
Eastern Cooperative Oncology Group (ECOG) Performance Status   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 3 participants 7 participants 6 participants 9 participants 46 participants 44 participants 3 participants 6 participants 3 participants 3 participants 3 participants 6 participants 6 participants 7 participants 155 participants
0
2
  66.7%
0
   0.0%
2
  28.6%
1
  16.7%
4
  44.4%
34
  73.9%
31
  70.5%
2
  66.7%
6
 100.0%
2
  66.7%
3
 100.0%
2
  66.7%
4
  66.7%
5
  83.3%
7
 100.0%
105
  67.7%
1
1
  33.3%
3
 100.0%
5
  71.4%
5
  83.3%
5
  55.6%
12
  26.1%
13
  29.5%
1
  33.3%
0
   0.0%
1
  33.3%
0
   0.0%
1
  33.3%
2
  33.3%
1
  16.7%
0
   0.0%
50
  32.3%
[1]
Measure Description:

ECOG Performance Status

0. Fully active, able to carry on all pre-disease performance without restriction

  1. Restricted in physically strenuous activity but able to carry out work of a light or sedentary nature, e.g., light house work, office work
  2. Ambulatory and capable of all selfcare but unable to carry out any work activities; up and about more than 50% of waking hours
  3. Capable of only limited selfcare; confined to bed or chair more than 50% of waking hours
  4. Completely disabled; cannot carry on any selfcare; totally confined to bed or chair
  5. Dead
Diagnosis  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 3 participants 7 participants 6 participants 9 participants 46 participants 44 participants 3 participants 6 participants 3 participants 3 participants 3 participants 6 participants 6 participants 7 participants 155 participants
Ovarian
2
  66.7%
2
  66.7%
5
  71.4%
4
  66.7%
7
  77.8%
46
 100.0%
44
 100.0%
3
 100.0%
6
 100.0%
3
 100.0%
3
 100.0%
3
 100.0%
6
 100.0%
6
 100.0%
7
 100.0%
147
  94.8%
Breast
1
  33.3%
1
  33.3%
2
  28.6%
2
  33.3%
2
  22.2%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
8
   5.2%
BRCA Status  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 3 participants 7 participants 6 participants 9 participants 46 participants 44 participants 3 participants 6 participants 3 participants 3 participants 3 participants 6 participants 6 participants 7 participants 155 participants
Mutation carrier
1
  33.3%
2
  66.7%
5
  71.4%
3
  50.0%
4
  44.4%
24
  52.2%
23
  52.3%
2
  66.7%
2
  33.3%
2
  66.7%
0
   0.0%
1
  33.3%
3
  50.0%
2
  33.3%
1
  14.3%
75
  48.4%
Wild-type
2
  66.7%
0
   0.0%
0
   0.0%
0
   0.0%
2
  22.2%
11
  23.9%
12
  27.3%
1
  33.3%
4
  66.7%
1
  33.3%
3
 100.0%
2
  66.7%
2
  33.3%
3
  50.0%
5
  71.4%
48
  31.0%
Unknown
0
   0.0%
1
  33.3%
2
  28.6%
3
  50.0%
3
  33.3%
11
  23.9%
9
  20.5%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  16.7%
1
  16.7%
1
  14.3%
32
  20.6%
Number of prior regimens (median; Phase 1)   [1] 
Median (Full Range)
Unit of measure:  Number of prior regimens
Ovarian Number Analyzed 2 participants 2 participants 5 participants 4 participants 7 participants 0 participants 0 participants 0 participants 0 participants 0 participants 0 participants 0 participants 0 participants 0 participants 0 participants 20 participants
3.5
(2 to 5)
6.5
(1 to 12)
2
(1 to 5)
2
(1 to 4)
1
(1 to 5)
2
(1 to 12)
Breast Number Analyzed 1 participants 1 participants 2 participants 2 participants 2 participants 0 participants 0 participants 0 participants 0 participants 0 participants 0 participants 0 participants 0 participants 0 participants 0 participants 8 participants
3
(3 to 3)
3
(3 to 3)
5
(4 to 6)
2
(2 to 2)
2.5
(2 to 3)
3
(2 to 6)
[1]
Measure Analysis Population Description: Participants were assessed according to diagnosis.
Number of Prior Lines (Phase 2 and 1-T)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 0 participants 0 participants 0 participants 0 participants 0 participants 46 participants 44 participants 3 participants 6 participants 3 participants 3 participants 3 participants 6 participants 6 participants 7 participants 127 participants
1
17
  37.0%
26
  59.1%
1
  33.3%
3
  50.0%
1
  33.3%
1
  33.3%
0
   0.0%
2
  33.3%
2
  33.3%
2
  28.6%
55
  43.3%
2
18
  39.1%
10
  22.7%
1
  33.3%
1
  16.7%
1
  33.3%
0
   0.0%
0
   0.0%
3
  50.0%
1
  16.7%
5
  71.4%
40
  31.5%
3 or More
11
  23.9%
8
  18.2%
1
  33.3%
2
  33.3%
1
  33.3%
2
  66.7%
3
 100.0%
1
  16.7%
3
  50.0%
0
   0.0%
32
  25.2%
[1]
Measure Analysis Population Description: Number of Prior Lines was captured as displayed for Phase 2 and Phase 1-T cohorts.
Platinum-sensitivity (ovarian patients only)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2 participants 2 participants 5 participants 4 participants 7 participants 46 participants 44 participants 3 participants 6 participants 3 participants 3 participants 3 participants 6 participants 6 participants 7 participants 147 participants
Platinum-sensitive
0
   0.0%
2
 100.0%
4
  80.0%
4
 100.0%
4
  57.1%
46
 100.0%
44
 100.0%
0
   0.0%
3
  50.0%
2
  66.7%
1
  33.3%
1
  33.3%
2
  33.3%
2
  33.3%
4
  57.1%
119
  81.0%
Platinum-resistant
2
 100.0%
0
   0.0%
1
  20.0%
0
   0.0%
3
  42.9%
0
   0.0%
0
   0.0%
3
 100.0%
3
  50.0%
1
  33.3%
2
  66.7%
2
  66.7%
4
  66.7%
4
  66.7%
3
  42.9%
28
  19.0%
[1]
Measure Analysis Population Description: Platinum-sensitivity is reported only for the Ovarian cohort
Histology (ovarian patients only; Phase 1 and Phase 2)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2 participants 2 participants 5 participants 4 participants 7 participants 46 participants 44 participants 3 participants 0 participants 0 participants 0 participants 0 participants 0 participants 0 participants 0 participants 113 participants
Papillary-serous
2
 100.0%
2
 100.0%
3
  60.0%
3
  75.0%
6
  85.7%
40
  87.0%
41
  93.2%
2
  66.7%
99
  87.6%
Endometrioid
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  14.3%
5
  10.9%
0
   0.0%
0
   0.0%
6
   5.3%
Mixed
0
   0.0%
0
   0.0%
1
  20.0%
1
  25.0%
0
   0.0%
0
   0.0%
2
   4.5%
0
   0.0%
4
   3.5%
Other
0
   0.0%
0
   0.0%
1
  20.0%
0
   0.0%
0
   0.0%
1
   2.2%
1
   2.3%
1
  33.3%
4
   3.5%
[1]
Measure Analysis Population Description: Histologic subtype only applies to the Ovarian cohort
Histology (Phase 1-T)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 0 participants 0 participants 0 participants 0 participants 0 participants 0 participants 0 participants 3 participants 6 participants 3 participants 3 participants 3 participants 6 participants 6 participants 7 participants 37 participants
Serous
2
  66.7%
5
  83.3%
2
  66.7%
3
 100.0%
2
  66.7%
4
  66.7%
4
  66.7%
6
  85.7%
28
  75.7%
Endometrioid
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  33.3%
0
   0.0%
1
  16.7%
0
   0.0%
2
   5.4%
Clear Cell
0
   0.0%
1
  16.7%
1
  33.3%
0
   0.0%
0
   0.0%
1
  16.7%
0
   0.0%
0
   0.0%
3
   8.1%
Other/Unknown
1
  33.3%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  16.7%
1
  16.7%
1
  14.3%
4
  10.8%
[1]
Measure Analysis Population Description: Histologic sub-types were captured/displayed differently between phases in this trial. The histologic subtypes in this table refer to those captured/displayed for Phase 1-T participants.
1.Primary Outcome
Title Number of Participants With Dose Limiting Toxicities of Cediranib Maleate in Combination With Olaparib (Phase I)
Hide Description Was determined using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
Time Frame At 28 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Level 0 Level 1 Level 2 Level 3
Hide Arm/Group Description:
Assess the maximum tolerated dose (MTD) of cediranib in combination with olaparib in the treatment of recurrent ovarian, fallopian tube, or peritoneal cancer or metastatic triple-negative breast cancer.
Assess the maximum tolerated dose (MTD) of cediranib in combination with olaparib in the treatment of recurrent ovarian, fallopian tube, or peritoneal cancer or metastatic triple-negative breast cancer.
Assess the maximum tolerated dose (MTD) of cediranib in combination with olaparib in the treatment of recurrent ovarian, fallopian tube, or peritoneal cancer or metastatic triple-negative breast cancer.
Assess the maximum tolerated dose (MTD) of cediranib in combination with olaparib in the treatment of recurrent ovarian, fallopian tube, or peritoneal cancer or metastatic triple-negative breast cancer.
Overall Number of Participants Analyzed 3 3 7 6
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
0
   0.0%
2
  33.3%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Level 0, Level 1, Level 2, Level 3
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Maximum Tolerated Dose (mg)
Estimated Value 30
Estimation Comments Cediranib
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Level 0, Level 1, Level 2, Level 3
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Maximum Tolerated Dose (mg BID)
Estimated Value 200
Estimation Comments Olaparib
2.Primary Outcome
Title The Maximum Tolerated Dose (MTD) of Cediranib in Combination With Olaparib in the Treatment of Recurrent Ovarian, Fallopian Tube, or Peritoneal Cancer or Metastatic Triple-negative Breast Cancer (Phase I)
Hide Description This trial employed a 3+3 design, escalating on 0/3 or 1/6 DLT, and de-escalating if 2 DLTs were encountered. The MTD (maximum tolerated dose) was the dose at which no more than 1 patient developed a dose-limiting toxicity (DLT) when at least 6 patients had been treated.
Time Frame At 28 Days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title All Phase 1 Participants (28 Participants)
Hide Arm/Group Description:
All Phase 1 participants who received at least 1 dose of olaparib and cediranib.
Overall Number of Participants Analyzed 28
Measure Type: Number
Unit of Measure: mg
Cediranib PO daily 30
Olaparib PO BID 200
3.Primary Outcome
Title Progression-free Survival (PFS) at the Maximum Tolerated Dose/Recommended Phase 2 Dose of Cediranib Maleate With Olaparib Compared to That of Olaparib Alone (Phase II)
Hide Description

Evaluated by Kaplan-Meier analysis and log-rank test for between group comparison, and median survival times reported.

PFS is defined as time from randomization to investigator-assessed radiographic progression by RECIST 1.1 criteria or death.

Patients alive without evidence of progression were censored at the last disease assessment.
Time Frame Time from start of treatment to time of objective disease progression, assessed up to 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Platinum-sensitive recurrent grade 2 or 3 platinum-sensitive papillary-serous or endometrioid ovarian, fallopian tube, or peritoneal cancer.
Arm/Group Title Phase 2 - Olaparib Alone (46 Participants) Phase 2 - Cediranib/Olaparib (44 Participants)
Hide Arm/Group Description:
Assess the efficacy (as measured by progression-free survival (PFS) ) of olaparib alone in recurrent grade 2 or 3 platinum-sensitive papillary-serous or endometrioid ovarian, fallopian tube, or peritoneal cancer.
Assess the efficacy (as measured by progression-free survival (PFS) ) of the combination of cediranib and olaparib in recurrent grade 2 or 3 platinum-sensitive papillary-serous or endometrioid ovarian, fallopian tube, or peritoneal cancer.
Overall Number of Participants Analyzed 46 44
Median (Full Range)
Unit of Measure: months
8.2
(1 to 49)
16.5
(4 to 60)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Phase 2 - Olaparib Alone (46 Participants), Phase 2 - Cediranib/Olaparib (44 Participants)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.006
Comments [Not Specified]
Method Kaplan-Meier Plot
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.50
Confidence Interval (2-Sided) 95%
0.30 to 0.83
Estimation Comments [Not Specified]
4.Primary Outcome
Title The Maximum Tolerated Dose (MTD) of Cediranib in Combination With Olaparib Tablet Formulation in the Treatment of Recurrent Ovarian, Fallopian Tube, or Peritoneal Cancer (Phase I-T).
Hide Description The Phase 1-T component of this trial employed a 3+3 design, escalating on 0/3 or 1/6 DLT, and de-escalating if 2 DLTs were encountered. The MTD (maximum tolerated dose) was the dose at which no more than 1 patient developed a DLT when at least 6 patients had been treated.
Time Frame At 28 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title All Phase 1-T Participants
Hide Arm/Group Description:
All Phase 1-T participants who received protocol treatment.
Overall Number of Participants Analyzed 37
Measure Type: Number
Unit of Measure: mg
Cediranib PO daily 30
Olaparib (tablet) PO BID 200
5.Secondary Outcome
Title Number of Participants With Treatment-related Toxicities of the Combination of Cediranib Maleate and Olaparib (Phase I)
Hide Description Will be determined using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0, study-related adverse events observed in >10% of participants (n=28).
Time Frame Adverse Events monitored for 3 years, mortality assessed up to 5 years
Outcome Measure Data Not Reported
6.Secondary Outcome
Title Tumor Response Rate (Objective Response Rate) Defined by Response Evaluation Criteria in Solid Tumors Criteria (Phase II)
Hide Description

The response rates are compared by an exact test and 95% confidence intervals will also be reported.

Objective response rate (ORR) is defined as the best confirmed RECIST response, ORR is defined as the number of participants with CR, PR or SD.
Time Frame Up to 5 years
Outcome Measure Data Not Reported
7.Secondary Outcome
Title Overall Survival (Phase II)
Hide Description Will be evaluated by Kaplan-Meier analysis and log-rank test for between-group comparison, and median survival time will be reported.
Time Frame Up to 5 years
Outcome Measure Data Not Reported
8.Secondary Outcome
Title Number of Participants With Treatment-related Toxicities of the Combination of Cediranib and Olaparib (Tablet Formulation) in the Treatment of Recurrent Ovarian, Fallopian Tube, or Peritoneal Cancer (Phase I-T).
Hide Description Will be determined using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. This outcome reports treatment-related adverse events that occurred in at least 10% of participants.
Time Frame Up to 3 years
Outcome Measure Data Not Reported
Time Frame Adverse Events monitored for 3 years, mortality assessed up to 5 years
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Phase I Dose Level 0 Phase I Dose Level 1 Phase I Dose Level 2 Phase I Dose Level 3 Phase I Expansion Cohort at MTD Phase II Olaparib Alone Phase II Cediranib/Olaparib Phase I-T Dose Level 0-TA Phase I-T Dose Level 1-TA Phase I-T Dose Level 1-TPKCed Phase I-T Dose Level 1-TPKOlap Phase I-T Dose Level 2-TA Phase I-T Dose Level 0-TB Phase I-T Dose Level 1-TB Phase I-T Dose Level 2-TB
Hide Arm/Group Description

Participants received cediranib 20 mg daily and olaparib 100 mg twice daily.

Cediranib was administered as 10 and 15 mg tablets and olaparib as 50 mg capsules.

Participants received cediranib 20 mg daily and olaparib 200 mg twice daily.

Cediranib was administered as 10 and 15 mg tablets and olaparib as 50 mg capsules.

Participants received cediranib 30 mg daily and olaparib 200 mg twice daily.

Cediranib was administered as 10 and 15 mg tablets and olaparib as 50 mg capsules.

Participants received cediranib 30 mg daily and olaparib 400 mg twice daily.

Cediranib was administered as 10 and 15 mg tablets and olaparib as 50 mg capsules.

Participants received cediranib 30 mg daily and olaparib 200 mg twice daily.

Cediranib was administered as 10 and 15 mg tablets and olaparib as 50 mg capsules.

 Participants received olaparib capsule monotherapy 400 mg orally twice daily. Participants received a previously established recommended Phase 2 dose of cediranib 30 mg orally daily with olaparib capsules 200 mg orally twice daily. Participants received 30 mg cediranib daily with olaparib tablets at 150 mg twice daily. Participants received 30 mg cediranib daily with olaparib tablets at 200 mg twice daily. Participants received 30 mg cediranib daily with olaparib tablets at 200 mg twice daily. Participants received 30 mg cediranib daily with olaparib tablets at 200 mg twice daily. Participants received 30 mg cediranib daily with olaparib tablets at 250 mg twice daily. Participants received 20 mg cediranib daily with olaparib tablets at 200 mg twice daily. Participants received 20 mg cediranib daily with olaparib tablets at 250 mg twice daily. Participants received 20 mg cediranib daily with olaparib tablets at 300 mg twice daily.
All-Cause Mortality
Phase I Dose Level 0 Phase I Dose Level 1 Phase I Dose Level 2 Phase I Dose Level 3 Phase I Expansion Cohort at MTD Phase II Olaparib Alone Phase II Cediranib/Olaparib Phase I-T Dose Level 0-TA Phase I-T Dose Level 1-TA Phase I-T Dose Level 1-TPKCed Phase I-T Dose Level 1-TPKOlap Phase I-T Dose Level 2-TA Phase I-T Dose Level 0-TB Phase I-T Dose Level 1-TB Phase I-T Dose Level 2-TB
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) 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   3/3 (100.00%)   3/3 (100.00%)   6/7 (85.71%)   6/6 (100.00%)   7/9 (77.78%)   29/46 (63.04%)   26/44 (59.09%)   1/3 (33.33%)   2/6 (33.33%)   2/7 (28.57%)   3/6 (50.00%)   1/3 (33.33%)   1/3 (33.33%)   2/3 (66.67%)   1/6 (16.67%) 
Hide Serious Adverse Events
Phase I Dose Level 0 Phase I Dose Level 1 Phase I Dose Level 2 Phase I Dose Level 3 Phase I Expansion Cohort at MTD Phase II Olaparib Alone Phase II Cediranib/Olaparib Phase I-T Dose Level 0-TA Phase I-T Dose Level 1-TA Phase I-T Dose Level 1-TPKCed Phase I-T Dose Level 1-TPKOlap Phase I-T Dose Level 2-TA Phase I-T Dose Level 0-TB Phase I-T Dose Level 1-TB Phase I-T Dose Level 2-TB
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) 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   0/3 (0.00%)   1/3 (33.33%)   0/7 (0.00%)   2/6 (33.33%)   0/9 (0.00%)   2/46 (4.35%)   3/44 (6.82%)   0/3 (0.00%)   0/6 (0.00%)   1/7 (14.29%)   0/6 (0.00%)   1/3 (33.33%)   0/3 (0.00%)   0/3 (0.00%)   1/6 (16.67%) 
Blood and lymphatic system disorders                               
Anemia † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%) 
Investigations                               
Aspartate aminotransferase increased † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/7 (14.29%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Lipase increased † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  1/46 (2.17%)  0/44 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Neutrophil count decreased † 1  0/3 (0.00%)  1/3 (33.33%)  0/7 (0.00%)  1/6 (16.67%)  0/9 (0.00%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Platelet count decreased † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/6 (16.67%)  0/9 (0.00%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Serum amylase increased † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  1/46 (2.17%)  0/44 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)                               
Myelodysplastic syndrome † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/46 (0.00%)  1/44 (2.27%)  0/3 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Nervous system disorders                               
Stroke † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  1/46 (2.17%)  0/44 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Vascular disorders                               
Hypertension † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/46 (0.00%)  2/44 (4.55%)  0/3 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
1
Term from vocabulary, CTCAE (4.0)
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Phase I Dose Level 0 Phase I Dose Level 1 Phase I Dose Level 2 Phase I Dose Level 3 Phase I Expansion Cohort at MTD Phase II Olaparib Alone Phase II Cediranib/Olaparib Phase I-T Dose Level 0-TA Phase I-T Dose Level 1-TA Phase I-T Dose Level 1-TPKCed Phase I-T Dose Level 1-TPKOlap Phase I-T Dose Level 2-TA Phase I-T Dose Level 0-TB Phase I-T Dose Level 1-TB Phase I-T Dose Level 2-TB
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) 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   3/3 (100.00%)   3/3 (100.00%)   7/7 (100.00%)   6/6 (100.00%)   9/9 (100.00%)   45/46 (97.83%)   44/44 (100.00%)   3/3 (100.00%)   6/6 (100.00%)   7/7 (100.00%)   6/6 (100.00%)   3/3 (100.00%)   3/3 (100.00%)   3/3 (100.00%)   6/6 (100.00%) 
Blood and lymphatic system disorders                               
Blood and lymphatic system disorders - Other, NOS † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/46 (0.00%)  3/44 (6.82%)  0/3 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Febrile neutropenia † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/7 (14.29%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Leukocytosis † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Cardiac disorders                               
Cardiac disorders - Other, NOS † 1  0/3 (0.00%)  1/3 (33.33%)  0/7 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Chest pain - cardiac † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/46 (0.00%)  3/44 (6.82%)  0/3 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Sinus tachycardia † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  1/9 (11.11%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Supraventricular tachycardia † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Ventricular arrhythmia † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/6 (0.00%)  0/9 (0.00%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Ear and labyrinth disorders                               
Ear pain † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/6 (16.67%)  0/9 (0.00%)  0/46 (0.00%)  0/44 (0.00%)  1/3 (33.33%)  0/6 (0.00%)  1/7 (14.29%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Hearing impaired † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  1/9 (11.11%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Tinnitus † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  2/9 (22.22%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Vertigo † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  2/6 (33.33%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Endocrine disorders                               
Hyperthyroidism † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/6 (0.00%)  0/9 (0.00%)  0/46 (0.00%)  3/44 (6.82%)  1/3 (33.33%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%) 
Hypothyroidism † 1  0/3 (0.00%)  2/3 (66.67%)  2/7 (28.57%)  2/6 (33.33%)  3/9 (33.33%)  0/46 (0.00%)  8/44 (18.18%)  0/3 (0.00%)  3/6 (50.00%)  2/7 (28.57%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  2/6 (33.33%) 
Eye disorders                               
Blurred vision † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/46 (0.00%)  3/44 (6.82%)  0/3 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Cataract † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/7 (14.29%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Eye disorders - Other, NOS † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/6 (16.67%)  0/9 (0.00%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  2/6 (33.33%) 
Floaters † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  1/9 (11.11%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Gastrointestinal disorders                               
Abdominal distension † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  1/9 (11.11%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/7 (14.29%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Abdominal pain † 1  0/3 (0.00%)  1/3 (33.33%)  3/7 (42.86%)  1/6 (16.67%)  4/9 (44.44%)  15/46 (32.61%)  20/44 (45.45%)  2/3 (66.67%)  2/6 (33.33%)  3/7 (42.86%)  4/6 (66.67%)  2/3 (66.67%)  3/3 (100.00%)  3/3 (100.00%)  2/6 (33.33%) 
Ascites † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/46 (0.00%)  0/44 (0.00%)  1/3 (33.33%)  0/6 (0.00%)  0/7 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%) 
Bloating † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  1/9 (11.11%)  3/46 (6.52%)  8/44 (18.18%)  2/3 (66.67%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  1/6 (16.67%) 
Colitis † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/6 (0.00%)  0/9 (0.00%)  0/46 (0.00%)  5/44 (11.36%)  0/3 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  0/6 (0.00%) 
Colonic obstruction † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/7 (14.29%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Constipation † 1  0/3 (0.00%)  1/3 (33.33%)  5/7 (71.43%)  1/6 (16.67%)  2/9 (22.22%)  15/46 (32.61%)  18/44 (40.91%)  0/3 (0.00%)  3/6 (50.00%)  2/7 (28.57%)  2/6 (33.33%)  1/3 (33.33%)  2/3 (66.67%)  0/3 (0.00%)  3/6 (50.00%) 
Dental caries † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/6 (0.00%)  0/9 (0.00%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  1/3 (33.33%)  1/3 (33.33%)  0/3 (0.00%)  0/6 (0.00%) 
Diarrhea † 1  2/3 (66.67%)  3/3 (100.00%)  6/7 (85.71%)  5/6 (83.33%)  9/9 (100.00%)  14/46 (30.43%)  41/44 (93.18%)  3/3 (100.00%)  6/6 (100.00%)  5/7 (71.43%)  5/6 (83.33%)  2/3 (66.67%)  3/3 (100.00%)  2/3 (66.67%)  5/6 (83.33%) 
Dry mouth † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/6 (0.00%)  1/9 (11.11%)  0/46 (0.00%)  6/44 (13.64%)  1/3 (33.33%)  1/6 (16.67%)  0/7 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%) 
Dyspepsia † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/6 (0.00%)  1/9 (11.11%)  10/46 (21.74%)  11/44 (25.00%)  0/3 (0.00%)  2/6 (33.33%)  0/7 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  2/3 (66.67%)  0/3 (0.00%)  0/6 (0.00%) 
Flatulence † 1  0/3 (0.00%)  1/3 (33.33%)  2/7 (28.57%)  0/6 (0.00%)  0/9 (0.00%)  0/46 (0.00%)  0/44 (0.00%)  1/3 (33.33%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%) 
Gastritis † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/7 (14.29%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%) 
Gastroesophageal reflux disease † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  2/6 (33.33%)  1/9 (11.11%)  3/46 (6.52%)  8/44 (18.18%)  0/3 (0.00%)  3/6 (50.00%)  0/7 (0.00%)  2/6 (33.33%)  1/3 (33.33%)  0/3 (0.00%)  1/3 (33.33%)  0/6 (0.00%) 
Gastrointestinal disorders - Other, NOS † 1  1/3 (33.33%)  0/3 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  2/9 (22.22%)  3/46 (6.52%)  8/44 (18.18%)  0/3 (0.00%)  2/6 (33.33%)  0/7 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%) 
Gastroparesis † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%) 
Gingival pain † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/7 (14.29%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Hemorrhoidal hemorrhage † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/46 (0.00%)  0/44 (0.00%)  1/3 (33.33%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Hemorrhoids † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/46 (0.00%)  4/44 (9.09%)  1/3 (33.33%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  0/6 (0.00%) 
Mucositis oral † 1  0/3 (0.00%)  1/3 (33.33%)  1/7 (14.29%)  1/6 (16.67%)  1/9 (11.11%)  0/46 (0.00%)  9/44 (20.45%)  2/3 (66.67%)  2/6 (33.33%)  0/7 (0.00%)  1/6 (16.67%)  1/3 (33.33%)  2/3 (66.67%)  1/3 (33.33%)  0/6 (0.00%) 
Nausea † 1  1/3 (33.33%)  1/3 (33.33%)  4/7 (57.14%)  4/6 (66.67%)  7/9 (77.78%)  36/46 (78.26%)  35/44 (79.55%)  3/3 (100.00%)  5/6 (83.33%)  4/7 (57.14%)  5/6 (83.33%)  1/3 (33.33%)  3/3 (100.00%)  3/3 (100.00%)  5/6 (83.33%) 
Oral dysesthesia † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Oral hemorrhage † 1  0/3 (0.00%)  0/3 (0.00%)  2/7 (28.57%)  0/6 (0.00%)  0/9 (0.00%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Oral pain † 1  0/3 (0.00%)  0/3 (0.00%)  3/7 (42.86%)  0/6 (0.00%)  2/9 (22.22%)  0/46 (0.00%)  4/44 (9.09%)  1/3 (33.33%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Periodontal disease † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/7 (14.29%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Proctitis † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/6 (0.00%)  0/9 (0.00%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Rectal hemorrhage † 1  0/3 (0.00%)  0/3 (0.00%)  2/7 (28.57%)  0/6 (0.00%)  0/9 (0.00%)  4/46 (8.70%)  0/44 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Small intestinal obstruction † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/6 (0.00%)  0/9 (0.00%)  0/46 (0.00%)  0/44 (0.00%)  1/3 (33.33%)  0/6 (0.00%)  0/7 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Stomach pain † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/6 (16.67%)  1/9 (11.11%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Vomiting † 1  0/3 (0.00%)  1/3 (33.33%)  2/7 (28.57%)  3/6 (50.00%)  3/9 (33.33%)  14/46 (30.43%)  11/44 (25.00%)  3/3 (100.00%)  3/6 (50.00%)  3/7 (42.86%)  2/6 (33.33%)  1/3 (33.33%)  1/3 (33.33%)  1/3 (33.33%)  4/6 (66.67%) 
General disorders                               
Chills † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  1/9 (11.11%)  0/46 (0.00%)  4/44 (9.09%)  0/3 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Edema limbs † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/6 (0.00%)  1/9 (11.11%)  6/46 (13.04%)  9/44 (20.45%)  0/3 (0.00%)  1/6 (16.67%)  1/7 (14.29%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Fatigue † 1  3/3 (100.00%)  3/3 (100.00%)  6/7 (85.71%)  6/6 (100.00%)  9/9 (100.00%)  36/46 (78.26%)  40/44 (90.91%)  3/3 (100.00%)  6/6 (100.00%)  5/7 (71.43%)  6/6 (100.00%)  3/3 (100.00%)  3/3 (100.00%)  3/3 (100.00%)  6/6 (100.00%) 
Fever † 1  0/3 (0.00%)  1/3 (33.33%)  1/7 (14.29%)  0/6 (0.00%)  1/9 (11.11%)  0/46 (0.00%)  3/44 (6.82%)  0/3 (0.00%)  2/6 (33.33%)  1/7 (14.29%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%) 
Flu like symptoms † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/6 (0.00%)  0/9 (0.00%)  0/46 (0.00%)  4/44 (9.09%)  0/3 (0.00%)  0/6 (0.00%)  2/7 (28.57%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%) 
Gait disturbance † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
General disorders and administration site conditions - Other, NOS † 1  0/3 (0.00%)  1/3 (33.33%)  0/7 (0.00%)  1/6 (16.67%)  0/9 (0.00%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Malaise † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  1/9 (11.11%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Non-cardiac chest pain † 1  0/3 (0.00%)  1/3 (33.33%)  1/7 (14.29%)  0/6 (0.00%)  0/9 (0.00%)  0/46 (0.00%)  3/44 (6.82%)  0/3 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  0/6 (0.00%) 
Pain † 1  0/3 (0.00%)  1/3 (33.33%)  1/7 (14.29%)  2/6 (33.33%)  3/9 (33.33%)  7/46 (15.22%)  8/44 (18.18%)  0/3 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  2/6 (33.33%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  3/6 (50.00%) 
Hepatobiliary disorders                               
Cholecystitis † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/6 (0.00%)  0/9 (0.00%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Gallbladder pain † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/6 (0.00%)  0/9 (0.00%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Immune system disorders                               
Allergic reaction † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/46 (0.00%)  3/44 (6.82%)  1/3 (33.33%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Infections and infestations                               
Gum infection † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/7 (14.29%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Infections and infestations - Other, NOS † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/6 (0.00%)  1/9 (11.11%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/6 (0.00%) 
Lung infection † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/6 (0.00%)  0/9 (0.00%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Mucosal infection † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/46 (0.00%)  0/44 (0.00%)  1/3 (33.33%)  0/6 (0.00%)  1/7 (14.29%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Papulopustular rash † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/6 (0.00%)  0/9 (0.00%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/7 (14.29%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Sinusitis † 1  1/3 (33.33%)  1/3 (33.33%)  1/7 (14.29%)  0/6 (0.00%)  0/9 (0.00%)  3/46 (6.52%)  3/44 (6.82%)  0/3 (0.00%)  0/6 (0.00%)  2/7 (28.57%)  0/6 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  0/6 (0.00%) 
Skin infection † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/6 (0.00%)  0/9 (0.00%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Tooth infection † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  1/6 (16.67%) 
Upper respiratory infection † 1  1/3 (33.33%)  0/3 (0.00%)  1/7 (14.29%)  1/6 (16.67%)  1/9 (11.11%)  6/46 (13.04%)  9/44 (20.45%)  0/3 (0.00%)  2/6 (33.33%)  0/7 (0.00%)  1/6 (16.67%)  1/3 (33.33%)  1/3 (33.33%)  0/3 (0.00%)  1/6 (16.67%) 
Urinary tract infection † 1  0/3 (0.00%)  0/3 (0.00%)  2/7 (28.57%)  0/6 (0.00%)  1/9 (11.11%)  5/46 (10.87%)  6/44 (13.64%)  0/3 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  4/6 (66.67%) 
Vaginal infection † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Injury, poisoning and procedural complications                               
Bruising † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  0/6 (0.00%) 
Fall † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  1/9 (11.11%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Fracture † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/6 (16.67%)  0/9 (0.00%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%) 
Injury, poisoning and procedural complications - Other, NOS † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/46 (0.00%)  3/44 (6.82%)  0/3 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Investigations                               
Activated partial thromboplastin time prolonged † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  0/6 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%) 
Alanine aminotransferase increased † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  3/6 (50.00%)  1/9 (11.11%)  4/46 (8.70%)  6/44 (13.64%)  0/3 (0.00%)  2/6 (33.33%)  1/7 (14.29%)  3/6 (50.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%) 
Alkaline phosphatase increased † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  3/6 (50.00%)  1/9 (11.11%)  0/46 (0.00%)  5/44 (11.36%)  1/3 (33.33%)  2/6 (33.33%)  0/7 (0.00%)  1/6 (16.67%)  1/3 (33.33%)  0/3 (0.00%)  0/3 (0.00%)  4/6 (66.67%) 
Blood bilirubin increased † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/6 (0.00%)  1/9 (11.11%)  0/46 (0.00%)  0/44 (0.00%)  1/3 (33.33%)  0/6 (0.00%)  1/7 (14.29%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%) 
Cardiac troponin T increased † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  1/9 (11.11%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Cholesterol high † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Creatinine increased † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/6 (16.67%)  0/9 (0.00%)  3/46 (6.52%)  6/44 (13.64%)  0/3 (0.00%)  2/6 (33.33%)  0/7 (0.00%)  1/6 (16.67%)  1/3 (33.33%)  0/3 (0.00%)  1/3 (33.33%)  2/6 (33.33%) 
Hemoglobin increased † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/46 (0.00%)  3/44 (6.82%)  0/3 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
INR increased † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/6 (16.67%)  0/9 (0.00%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Investigations - Other, NOS † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  3/6 (50.00%)  1/9 (11.11%)  0/46 (0.00%)  3/44 (6.82%)  0/3 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Lymphocyte count decreased † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  3/6 (50.00%)  0/9 (0.00%)  4/46 (8.70%)  5/44 (11.36%)  0/3 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Weight gain † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/6 (0.00%)  1/9 (11.11%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Weight loss † 1  0/3 (0.00%)  0/3 (0.00%)  2/7 (28.57%)  1/6 (16.67%)  1/9 (11.11%)  0/46 (0.00%)  12/44 (27.27%)  0/3 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  1/6 (16.67%) 
White blood cell decreased † 1  1/3 (33.33%)  1/3 (33.33%)  2/7 (28.57%)  2/6 (33.33%)  2/9 (22.22%)  6/46 (13.04%)  7/44 (15.91%)  0/3 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  1/3 (33.33%)  1/3 (33.33%)  1/3 (33.33%)  1/6 (16.67%) 
Metabolism and nutrition disorders                               
Anorexia † 1  0/3 (0.00%)  2/3 (66.67%)  4/7 (57.14%)  0/6 (0.00%)  3/9 (33.33%)  6/46 (13.04%)  14/44 (31.82%)  1/3 (33.33%)  1/6 (16.67%)  1/7 (14.29%)  0/6 (0.00%)  0/3 (0.00%)  3/3 (100.00%)  1/3 (33.33%)  1/6 (16.67%) 
Dehydration † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/6 (0.00%)  2/9 (22.22%)  3/46 (6.52%)  0/44 (0.00%)  1/3 (33.33%)  3/6 (50.00%)  0/7 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  1/6 (16.67%) 
Hypercalcemia † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  1/9 (11.11%)  3/46 (6.52%)  4/44 (9.09%)  0/3 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%) 
Hyperglycemia † 1  2/3 (66.67%)  1/3 (33.33%)  1/7 (14.29%)  4/6 (66.67%)  3/9 (33.33%)  3/46 (6.52%)  8/44 (18.18%)  0/3 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  1/6 (16.67%)  1/3 (33.33%)  1/3 (33.33%)  0/3 (0.00%)  1/6 (16.67%) 
Hyperkalemia † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/6 (0.00%)  0/9 (0.00%)  0/46 (0.00%)  4/44 (9.09%)  0/3 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Hypoalbuminemia † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  2/6 (33.33%)  0/9 (0.00%)  0/46 (0.00%)  5/44 (11.36%)  0/3 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%) 
Hypocalcemia † 1  1/3 (33.33%)  0/3 (0.00%)  0/7 (0.00%)  2/6 (33.33%)  0/9 (0.00%)  3/46 (6.52%)  4/44 (9.09%)  0/3 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  0/6 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Hypoglycemia † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  1/9 (11.11%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Hypokalemia † 1  0/3 (0.00%)  1/3 (33.33%)  0/7 (0.00%)  2/6 (33.33%)  0/9 (0.00%)  0/46 (0.00%)  8/44 (18.18%)  0/3 (0.00%)  2/6 (33.33%)  1/7 (14.29%)  1/6 (16.67%)  0/3 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  0/6 (0.00%) 
Hypomagnesemia † 1  2/3 (66.67%)  1/3 (33.33%)  2/7 (28.57%)  1/6 (16.67%)  1/9 (11.11%)  11/46 (23.91%)  10/44 (22.73%)  1/3 (33.33%)  2/6 (33.33%)  3/7 (42.86%)  1/6 (16.67%)  0/3 (0.00%)  1/3 (33.33%)  1/3 (33.33%)  4/6 (66.67%) 
Hyponatremia † 1  1/3 (33.33%)  2/3 (66.67%)  0/7 (0.00%)  0/6 (0.00%)  1/9 (11.11%)  3/46 (6.52%)  11/44 (25.00%)  1/3 (33.33%)  3/6 (50.00%)  4/7 (57.14%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%) 
Hypophosphatemia † 1  2/3 (66.67%)  1/3 (33.33%)  0/7 (0.00%)  1/6 (16.67%)  0/9 (0.00%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Metabolism and nutrition disorders - Other, NOS † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/6 (16.67%)  0/9 (0.00%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Musculoskeletal and connective tissue disorders                               
Arthralgia † 1  0/3 (0.00%)  1/3 (33.33%)  2/7 (28.57%)  1/6 (16.67%)  2/9 (22.22%)  0/46 (0.00%)  7/44 (15.91%)  0/3 (0.00%)  0/6 (0.00%)  1/7 (14.29%)  0/6 (0.00%)  1/3 (33.33%)  1/3 (33.33%)  1/3 (33.33%)  0/6 (0.00%) 
Arthritis † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/46 (0.00%)  7/44 (15.91%)  0/3 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Back pain † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/6 (16.67%)  2/9 (22.22%)  5/46 (10.87%)  7/44 (15.91%)  1/3 (33.33%)  1/6 (16.67%)  3/7 (42.86%)  0/6 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  1/6 (16.67%) 
Bone pain † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/46 (0.00%)  3/44 (6.82%)  0/3 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%) 
Chest wall pain † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/6 (16.67%)  1/9 (11.11%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Flank pain † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/7 (14.29%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%) 
Joint effusion † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  0/6 (0.00%) 
Joint range of motion decreased † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/7 (14.29%)  0/6 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  1/6 (16.67%) 
Joint range of motion decreased cervical spine † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Muscle weakness lower limb † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  1/9 (11.11%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Musculoskeletal and connective tissue disorder - Other, NOS † 1  0/3 (0.00%)  1/3 (33.33%)  0/7 (0.00%)  1/6 (16.67%)  0/9 (0.00%)  0/46 (0.00%)  5/44 (11.36%)  0/3 (0.00%)  2/6 (33.33%)  1/7 (14.29%)  2/6 (33.33%)  0/3 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  1/6 (16.67%) 
Myalgia † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/6 (0.00%)  3/9 (33.33%)  0/46 (0.00%)  7/44 (15.91%)  0/3 (0.00%)  3/6 (50.00%)  0/7 (0.00%)  3/6 (50.00%)  0/3 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  2/6 (33.33%) 
Neck pain † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/6 (0.00%)  0/9 (0.00%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%) 
Pain in extremity † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  1/6 (16.67%)  4/9 (44.44%)  6/46 (13.04%)  11/44 (25.00%)  2/3 (66.67%)  1/6 (16.67%)  2/7 (28.57%)  3/6 (50.00%)  0/3 (0.00%)  1/3 (33.33%)  1/3 (33.33%)  1/6 (16.67%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)                               
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, NOS † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  0/6 (0.00%) 
Tumor pain † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  1/9 (11.11%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Nervous system disorders                               
Ataxia † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  1/9 (11.11%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Cognitive disturbance † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  1/9 (11.11%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Concentration impairment † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  1/9 (11.11%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Dizziness † 1  0/3 (0.00%)  1/3 (33.33%)  0/7 (0.00%)  1/6 (16.67%)  2/9 (22.22%)  6/46 (13.04%)  10/44 (22.73%)  0/3 (0.00%)  1/6 (16.67%)  2/7 (28.57%)  1/6 (16.67%)  0/3 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  1/6 (16.67%) 
Dysesthesia † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  0/6 (0.00%) 
Dysgeusia † 1  0/3 (0.00%)  0/3 (0.00%)  2/7 (28.57%)  0/6 (0.00%)  2/9 (22.22%)  5/46 (10.87%)  6/44 (13.64%)  0/3 (0.00%)  1/6 (16.67%)  2/7 (28.57%)  0/6 (0.00%)  2/3 (66.67%)  1/3 (33.33%)  2/3 (66.67%)  1/6 (16.67%) 
Headache † 1  1/3 (33.33%)  2/3 (66.67%)  3/7 (42.86%)  2/6 (33.33%)  4/9 (44.44%)  9/46 (19.57%)  24/44 (54.55%)  1/3 (33.33%)  3/6 (50.00%)  3/7 (42.86%)  3/6 (50.00%)  1/3 (33.33%)  1/3 (33.33%)  2/3 (66.67%)  3/6 (50.00%) 
Intracranial hemorrhage † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Memory impairment † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/6 (0.00%)  0/9 (0.00%)  0/46 (0.00%)  3/44 (6.82%)  0/3 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Nervous system disorders - Other, NOS † 1  0/3 (0.00%)  1/3 (33.33%)  0/7 (0.00%)  1/6 (16.67%)  1/9 (11.11%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%) 
Peripheral motor neuropathy † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/6 (16.67%)  0/9 (0.00%)  3/46 (6.52%)  5/44 (11.36%)  0/3 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%) 
Peripheral sensory neuropathy † 1  0/3 (0.00%)  2/3 (66.67%)  0/7 (0.00%)  3/6 (50.00%)  3/9 (33.33%)  11/46 (23.91%)  16/44 (36.36%)  2/3 (66.67%)  5/6 (83.33%)  3/7 (42.86%)  3/6 (50.00%)  2/3 (66.67%)  1/3 (33.33%)  1/3 (33.33%)  3/6 (50.00%) 
Seizure † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Sinus pain † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/6 (0.00%)  0/9 (0.00%)  0/46 (0.00%)  0/44 (0.00%)  1/3 (33.33%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  0/6 (0.00%) 
Syncope † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Transient ischemic attacks † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%) 
Vasovagal reaction † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Psychiatric disorders                               
Anxiety † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/6 (16.67%)  2/9 (22.22%)  6/46 (13.04%)  11/44 (25.00%)  1/3 (33.33%)  2/6 (33.33%)  1/7 (14.29%)  0/6 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  1/3 (33.33%)  2/6 (33.33%) 
Confusion † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/6 (16.67%)  0/9 (0.00%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Depression † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  1/6 (16.67%)  0/9 (0.00%)  0/46 (0.00%)  6/44 (13.64%)  0/3 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  0/6 (0.00%)  1/3 (33.33%)  2/3 (66.67%)  1/3 (33.33%)  0/6 (0.00%) 
Insomnia † 1  1/3 (33.33%)  0/3 (0.00%)  1/7 (14.29%)  0/6 (0.00%)  2/9 (22.22%)  3/46 (6.52%)  8/44 (18.18%)  2/3 (66.67%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  1/3 (33.33%)  2/3 (66.67%)  0/3 (0.00%)  0/6 (0.00%) 
Psychiatric disorders - Other, NOS † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/46 (0.00%)  5/44 (11.36%)  0/3 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Renal and urinary disorders                               
Hematuria † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  1/9 (11.11%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  2/6 (33.33%) 
Hemoglobinuria † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  2/6 (33.33%)  0/7 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Proteinuria † 1  1/3 (33.33%)  1/3 (33.33%)  0/7 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/46 (0.00%)  5/44 (11.36%)  0/3 (0.00%)  2/6 (33.33%)  2/7 (28.57%)  1/6 (16.67%)  1/3 (33.33%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Renal and urinary disorders - Other, NOS † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%) 
Urinary frequency † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Urinary incontinence † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/6 (0.00%)  0/9 (0.00%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Urinary tract obstruction † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/6 (0.00%)  0/9 (0.00%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/7 (14.29%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Urinary urgency † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Reproductive system and breast disorders                               
Breast pain † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/6 (0.00%)  1/9 (11.11%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Dyspareunia † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Pelvic floor muscle weakness † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Pelvic pain † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/46 (0.00%)  3/44 (6.82%)  1/3 (33.33%)  1/6 (16.67%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  1/3 (33.33%)  2/6 (33.33%) 
Vaginal discharge † 1  0/3 (0.00%)  1/3 (33.33%)  0/7 (0.00%)  0/6 (0.00%)  1/9 (11.11%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Vaginal dryness † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  1/9 (11.11%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Vaginal hemorrhage † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/6 (0.00%)  0/9 (0.00%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/7 (14.29%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Respiratory, thoracic and mediastinal disorders                               
Allergic rhinitis † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/6 (0.00%)  0/9 (0.00%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  0/6 (0.00%) 
Atelectasis † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%) 
Bronchospasm † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Cough † 1  0/3 (0.00%)  1/3 (33.33%)  2/7 (28.57%)  0/6 (0.00%)  0/9 (0.00%)  3/46 (6.52%)  11/44 (25.00%)  0/3 (0.00%)  0/6 (0.00%)  2/7 (28.57%)  0/6 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  2/6 (33.33%) 
Dyspnea † 1  0/3 (0.00%)  1/3 (33.33%)  1/7 (14.29%)  3/6 (50.00%)  2/9 (22.22%)  3/46 (6.52%)  11/44 (25.00%)  0/3 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  1/6 (16.67%)  1/3 (33.33%)  1/3 (33.33%)  0/3 (0.00%)  2/6 (33.33%) 
Epistaxis † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  1/9 (11.11%)  0/46 (0.00%)  7/44 (15.91%)  0/3 (0.00%)  0/6 (0.00%)  1/7 (14.29%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Hiccups † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/7 (14.29%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Hoarseness † 1  1/3 (33.33%)  2/3 (66.67%)  2/7 (28.57%)  1/6 (16.67%)  1/9 (11.11%)  0/46 (0.00%)  12/44 (27.27%)  0/3 (0.00%)  2/6 (33.33%)  1/7 (14.29%)  2/6 (33.33%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Hypoxia † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/6 (16.67%)  0/9 (0.00%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Laryngeal inflammation † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/6 (16.67%)  0/9 (0.00%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Nasal congestion † 1  0/3 (0.00%)  1/3 (33.33%)  1/7 (14.29%)  0/6 (0.00%)  1/9 (11.11%)  0/46 (0.00%)  4/44 (9.09%)  0/3 (0.00%)  0/6 (0.00%)  1/7 (14.29%)  0/6 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  1/3 (33.33%)  0/6 (0.00%) 
Pleural effusion † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  1/9 (11.11%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  1/7 (14.29%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%) 
Pneumothorax † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  1/9 (11.11%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Postnasal drip † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/6 (0.00%)  0/9 (0.00%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%) 
Productive cough † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/6 (0.00%)  0/9 (0.00%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  2/7 (28.57%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Sore throat † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/6 (0.00%)  0/9 (0.00%)  0/46 (0.00%)  0/44 (0.00%)  1/3 (33.33%)  0/6 (0.00%)  3/7 (42.86%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Voice alteration † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/6 (0.00%)  1/9 (11.11%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%) 
Skin and subcutaneous tissue disorders                               
Alopecia † 1  1/3 (33.33%)  0/3 (0.00%)  2/7 (28.57%)  1/6 (16.67%)  0/9 (0.00%)  0/46 (0.00%)  3/44 (6.82%)  0/3 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  1/3 (33.33%)  1/3 (33.33%)  0/6 (0.00%) 
Erythroderma † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/6 (16.67%)  0/9 (0.00%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Hyperhidrosis † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  0/6 (0.00%) 
Palmar-plantar erythrodysesthesia syndrome † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/6 (0.00%)  2/9 (22.22%)  0/46 (0.00%)  8/44 (18.18%)  1/3 (33.33%)  0/6 (0.00%)  0/7 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  0/6 (0.00%) 
Rash acneiform † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/46 (0.00%)  3/44 (6.82%)  0/3 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%) 
Rash maculo-papular † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/6 (16.67%)  1/9 (11.11%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  3/7 (42.86%)  1/6 (16.67%)  1/3 (33.33%)  0/3 (0.00%)  1/3 (33.33%)  0/6 (0.00%) 
Skin and subcutaneous tissue disorders - Other, NOS † 1  0/3 (0.00%)  0/3 (0.00%)  2/7 (28.57%)  0/6 (0.00%)  0/9 (0.00%)  4/46 (8.70%)  4/44 (9.09%)  0/3 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  1/6 (16.67%)  0/3 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  2/6 (33.33%) 
Skin atrophy † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  0/6 (0.00%) 
Surgical and medical procedures                               
Surgical and medical procedures - Other, NOS † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/6 (0.00%)  0/9 (0.00%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Vascular disorders                               
Flushing † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  1/3 (33.33%)  0/6 (0.00%) 
Hot flashes † 1  1/3 (33.33%)  0/3 (0.00%)  1/7 (14.29%)  0/6 (0.00%)  2/9 (22.22%)  4/46 (8.70%)  0/44 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  0/7 (0.00%)  0/6 (0.00%)  2/3 (66.67%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Hypotension † 1  1/3 (33.33%)  1/3 (33.33%)  0/7 (0.00%)  0/6 (0.00%)  0/9 (0.00%)  0/46 (0.00%)  5/44 (11.36%)  0/3 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  1/3 (33.33%)  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%) 
Thromboembolic event † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  2/6 (33.33%)  0/9 (0.00%)  4/46 (8.70%)  4/44 (9.09%)  2/3 (66.67%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
Vascular disorders - Other, NOS † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/6 (16.67%)  0/9 (0.00%)  0/46 (0.00%)  0/44 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/7 (0.00%)  0/6 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%) 
1
Term from vocabulary, CTCAE (4.0)
†
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Joyce Liu
Organization: Dana-Farber Cancer Institute
Phone: 617-632-5269
EMail: joyce_liu@dfci.harvard.edu
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01116648    
Obsolete Identifiers: NCT01115829
Other Study ID Numbers: NCI-2012-02938
NCI-2012-02938 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
NCI-2010-01329
DFCI IRB 09-293
NCI-2013-00578
8348 ( Other Identifier: Dana-Farber Cancer Institute )
8348 ( Other Identifier: CTEP )
N01CM00071 ( U.S. NIH Grant/Contract )
P30CA006516 ( U.S. NIH Grant/Contract )
U01CA062490 ( U.S. NIH Grant/Contract )
UM1CA186709 ( U.S. NIH Grant/Contract )
First Submitted: April 29, 2010
First Posted: May 5, 2010
Results First Submitted: February 4, 2020
Results First Posted: July 22, 2020
Last Update Posted: April 8, 2024