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Study of DS-8201a for Participants With Advanced Solid Malignant Tumors

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: NCT03383692
Recruitment Status : Completed
First Posted : December 26, 2017
Results First Posted : June 14, 2021
Last Update Posted : December 11, 2023
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
Daiichi Sankyo ( Daiichi Sankyo Co., Ltd. )

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Sequential Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Neoplasm Metastasis
Interventions Drug: DS-8201a
Drug: Ritonavir
Drug: Itraconazole
Enrollment 40
Recruitment Details A total of 40 participants who met all inclusion criteria and no exclusion criteria were enrolled and received treatment at 10 study centers in Japan, South Korea, and Taiwan.
Pre-assignment Details Based on the pharmacokinetic parameters of DS-8201a assessed in an earlier Phase 1 trial, 5.4 mg/kg DS-8201a was chosen to assess drug interactions.
Arm/Group Title Cohort 1: DS-8201a + Ritonavir Cohort 2: DS-8201a + Itraconazole
Hide Arm/Group Description Participants who received 5.4 mg/kg DS-8201a as an intravenous infusion once every 3 weeks and 200 mg ritonavir twice daily (BID) on Day 17 of Cycle 2 until Day 21 of Cycle 3. Participants who received 5.4 mg/kg DS-8201a as an intravenous infusion once every 3 weeks and 200 mg itraconazole twice daily (BID) on Day 17 of Cycle 2 followed by 200 mg daily (QD) until Day 21 of Cycle 3.
Period Title: Overall Study
Started 17 23
Completed [1] 11 19
Not Completed 6 4
Reason Not Completed
Progressive disease as per RECIST             3             3
Clinical progression             0             1
Adverse Event             3             0
[1]
Ongoing on study drug as of 26 Sep 2018
Arm/Group Title Cohort 1: DS-8201a + Ritonavir Cohort 2: DS-8201a + Itraconazole Total
Hide Arm/Group Description Participants who received 5.4 mg/kg DS-8201a as an intravenous infusion once every 3 weeks and 200 mg ritonavir twice daily on Day 17 of Cycle 2 until Day 21 of Cycle 3. Participants who received 5.4 mg/kg DS-8201a as an intravenous infusion once every 3 weeks and 200 mg itraconazole BID on Day 17 of Cycle 2 followed by 200 mg QD until Day 21 of Cycle 3. Total of all reporting groups
Overall Number of Baseline Participants 17 23 40
Hide Baseline Analysis Population Description
Demographics were assessed in the Safety Analysis Set.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 17 participants 23 participants 40 participants
60.5  (9.45) 53.5  (12.91) 56.5  (11.96)
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
 Number Analyzed 17 participants 23 participants 40 participants
<65 years
10
  58.8%
18
  78.3%
28
  70.0%
≥65 years
7
  41.2%
5
  21.7%
12
  30.0%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 17 participants 23 participants 40 participants
Female
12
  70.6%
10
  43.5%
22
  55.0%
Male
5
  29.4%
13
  56.5%
18
  45.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 17 participants 23 participants 40 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
17
 100.0%
23
 100.0%
40
 100.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
White
0
   0.0%
0
   0.0%
0
   0.0%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
1.Primary Outcome
Title Pharmacokinetic Parameter of Maximum (Peak) Observed Serum Concentration (Cmax) Following Treatment With DS-8201a and Ritonavir - Cohort 1
Hide Description Maximum concentration (Cmax) was assessed for DS-8201a and total Anti-HER2 antibody.
Time Frame Cycle 1: Day 1, pre-dose and end of infusion (EOI); Cycles 2 and 3: Day 1, pre-dose, EOI, 2 hours, 4 hours, 7 hours; Day 2, 4, 8, 12, 17, and 22; Cycles 4, 6 and 8: Day 1, pre-dose and EOI (each cycle is 22 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set.
Arm/Group Title Cohort 1: DS-8201a + Ritonavir
Hide Arm/Group Description:
Participants who received 5.4 mg/kg DS-8201a as an intravenous infusion once every 3 weeks and 200 mg ritonavir twice daily (BID) on Day 17 of Cycle 2 until Day 21 of Cycle 3.
Overall Number of Participants Analyzed 12
Mean (Standard Deviation)
Unit of Measure: ug/mL
DS-8201a, Cycle 2: DS-8201a only 133  (25.5)
DS-8201a, Cycle 3: DS-8201a + ritonavir 140  (23.0)
Total Anti-HER2 antibody, Cycle 2: DS-8201a only 121  (22.2)
Total Anti-HER2 antibody, Cycle 3: DS-8201a + ritonavir 126  (23.1)
2.Primary Outcome
Title Pharmacokinetic Parameter of Maximum (Peak) Observed Serum Concentration (Cmax) For MAAA-1181a Following Treatment With DS-8201a and Ritonavir - Cohort 1
Hide Description Maximum concentration (Cmax) was assessed for MAAA-1181a.
Time Frame Cycle 1: Day 1, pre-dose and end of infusion (EOI); Cycles 2 and 3: Day 1, pre-dose, EOI, 2 hours, 4 hours, 7 hours; Day 2, 4, 8, 12, 17, and 22; Cycles 4, 6 and 8: Day 1, pre-dose and EOI (each cycle is 22 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set.
Arm/Group Title Cohort 1: DS-8201a + Ritonavir
Hide Arm/Group Description:
Participants who received 5.4 mg/kg DS-8201a as an intravenous infusion once every 3 weeks and 200 mg ritonavir twice daily (BID) on Day 17 of Cycle 2 until Day 21 of Cycle 3.
Overall Number of Participants Analyzed 12
Mean (Standard Deviation)
Unit of Measure: ng/mL
MAAA-1181a, Cycle 2: DS-8201a only 8.98  (2.83)
MAAA-1181a, Cycle 3: DS-8201a + ritonavir 8.95  (3.68)
3.Primary Outcome
Title Pharmacokinetic Parameter of Area Under the Serum Concentration-time Curve Following Treatment With DS-8201a and Ritonavir - Cohort 1
Hide Description Area under the serum concentration-time curve from time zero to 17 days (AUC17d) and during the dosing interval (AUCtau) for DS-8201a and total anti-HER2 antibody were assessed.
Time Frame Cycle 1: Day 1, pre-dose and end of infusion (EOI); Cycles 2 and 3: Day 1, pre-dose, EOI, 2 hours, 4 hours, 7 hours; Day 2, 4, 8, 12, 17, and 22; Cycles 4, 6 and 8: Day 1, pre-dose and EOI (each cycle is 22 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set.
Arm/Group Title Cohort 1: DS-8201a + Ritonavir
Hide Arm/Group Description:
Participants who received 5.4 mg/kg DS-8201a as an intravenous infusion once every 3 weeks and 200 mg ritonavir twice daily (BID) on Day 17 of Cycle 2 until Day 21 of Cycle 3.
Overall Number of Participants Analyzed 12
Mean (Standard Deviation)
Unit of Measure: ug*d/mL
DS-8201a, Cycle 2 (DS-8201a only): AUC17d Number Analyzed 12 participants
650  (168.0)
DS-8201a, Cycle 2 (DS-8201a only): AUCtau Number Analyzed 12 participants
701  (185)
DS-8201a, Cycle 3 (DS-8201a + ritonavir): AUC17d Number Analyzed 8 participants
754  (137.0)
DS-8201a, Cycle 3 (DS-8201a + ritonavir): AUCtau Number Analyzed 7 participants
810  (153.0)
Total Anti-HER2 antibody, Cycle 2 (DS-8201a only): AUC17d Number Analyzed 12 participants
723  (191)
Total Anti-HER2 antibody, Cycle 2 (DS-8201a only): AUCtau Number Analyzed 12 participants
791  (217)
Total Anti-HER2 antibody, Cycle 3 (DS-8201a + ritonavir): AUC17d Number Analyzed 8 participants
796  (155)
Total Anti-HER2 antibody, Cycle 3 (DS-8201a + ritonavir): AUCtau Number Analyzed 7 participants
860  (170)
4.Primary Outcome
Title Pharmacokinetic Parameter of Area Under the Serum Concentration-time Curve of MAAA-1181a Following Treatment With DS-8201a and Ritonavir - Cohort 1
Hide Description Area under the serum concentration-time curve from time zero to 17 days (AUC17d) and during the dosing interval (AUCtau) were assessed for MAAA-1181a.
Time Frame Cycle 1: Day 1, pre-dose and end of infusion (EOI); Cycles 2 and 3: Day 1, pre-dose, EOI, 2 hours, 4 hours, 7 hours; Day 2, 4, 8, 12, 17, and 22; Cycles 4, 6 and 8: Day 1, pre-dose and EOI (each cycle is 22 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set.
Arm/Group Title Cohort 1: DS-8201a + Ritonavir
Hide Arm/Group Description:
Participants who received 5.4 mg/kg DS-8201a as an intravenous infusion once every 3 weeks and 200 mg ritonavir twice daily (BID) on Day 17 of Cycle 2 until Day 21 of Cycle 3.
Overall Number of Participants Analyzed 12
Mean (Standard Deviation)
Unit of Measure: ng*d/mL
MAAA-1181a, Cycle 2 (DS-8201a only): AUC17d Number Analyzed 12 participants
32.7  (7.45)
MAAA-1181a, Cycle 2 (DS-8201a only): AUCtau Number Analyzed 12 participants
35.0  (8.10)
MAAA-1181a, Cycle 3 (DS-8201a + ritonavir): AUC17d Number Analyzed 8 participants
37.2  (6.93)
MAAA-1181a, Cycle 3 (DS-8201a + ritonavir): AUCtau Number Analyzed 7 participants
39.2  (7.98)
5.Primary Outcome
Title Pharmacokinetic Parameter of Maximum (Peak) Observed Serum Concentration (Cmax) Following Treatment With DS-8201a and Itraconazole - Cohort 2
Hide Description Maximum concentration (Cmax) was assessed for DS-8201a and total Anti-HER2 antibody.
Time Frame Cycle 1: Day 1, pre-dose and end of infusion (EOI); Cycles 2 and 3: Day 1, pre-dose, EOI, 2 hours, 4 hours, 7 hours; Day 2, 4, 8, 12, 17, and 22; Cycles 4, 6 and 8: Day 1, pre-dose and EOI (each cycle is 22 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set.
Arm/Group Title Cohort 1: DS-8201a + Itraconazole
Hide Arm/Group Description:
Participants who received 5.4 mg/kg DS-8201a as an intravenous infusion once every 3 weeks and 200 mg itraconazole twice daily (BID) on Day 17 of Cycle 2 followed by 200 mg daily (QD) until Day 21 of Cycle 3.
Overall Number of Participants Analyzed 14
Mean (Standard Deviation)
Unit of Measure: ug/mL
DS-8201a, Cycle 2: DS-8201a only 139  (23.6)
DS-8201a, Cycle 3: DS-8201a + ritonavir 142  (23.9)
Total Anti-HER2 antibody, Cycle 2: DS-8201a only 119  (19.1)
Total Anti-HER2 antibody, Cycle 3: DS-8201a + ritonavir 130  (18.2)
6.Primary Outcome
Title Pharmacokinetic Parameter of Maximum (Peak) Observed Serum Concentration (Cmax) of MAAA-1181a Following Treatment With DS-8201a and Itraconazole - Cohort 2
Hide Description Maximum concentration (Cmax) was assessed for MAAA-1181a.
Time Frame Cycle 1: Day 1, pre-dose and end of infusion (EOI); Cycles 2 and 3: Day 1, pre-dose, EOI, 2 hours, 4 hours, 7 hours; Day 2, 4, 8, 12, 17, and 22; Cycles 4, 6 and 8: Day 1, pre-dose and EOI (each cycle is 22 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set.
Arm/Group Title Cohort 2: DS-8201a + Itraconazole
Hide Arm/Group Description:
Participants who received 5.4 mg/kg DS-8201a as an intravenous infusion once every 3 weeks and 200 mg itraconazole twice daily (BID) on Day 17 of Cycle 2 followed by 200 mg daily (QD) until Day 21 of Cycle 3.
Overall Number of Participants Analyzed 14
Mean (Standard Deviation)
Unit of Measure: ng/mL
MAAA-1181a, Cycle 2: DS-8201a only 8.65  (2.03)
MAAA-1181a, Cycle 3: DS-8201a + ritonavir 8.93  (1.77)
7.Primary Outcome
Title Pharmacokinetic Parameter of Area Under the Serum Concentration-time Curve Following Treatment With DS-8201a and Itraconazole - Cohort 2
Hide Description Area under the serum concentration-time curve from time zero to 17 days (AUC17d) and during the dosing interval (AUCtau) were assessed for DS-8201a and total anti-HER2 antibody.
Time Frame Cycle 1: Day 1, pre-dose and end of infusion (EOI); Cycles 2 and 3: Day 1, pre-dose, EOI, 2 hours, 4 hours, 7 hours; Day 2, 4, 8, 12, 17, and 22; Cycles 4, 6 and 8: Day 1, pre-dose and EOI (each cycle is 22 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set.
Arm/Group Title Cohort 2: DS-8201a + Itraconazole
Hide Arm/Group Description:
Participants who received 5.4 mg/kg DS-8201a as an intravenous infusion once every 3 weeks and 200 mg itraconazole twice daily (BID) on Day 17 of Cycle 2 followed by 200 mg daily (QD) until Day 21 of Cycle 3.
Overall Number of Participants Analyzed 14
Mean (Standard Deviation)
Unit of Measure: ug*d/mL
DS-8201a, Cycle 2 (DS-8201a only): AUC17d 644  (188)
DS-8201a, Cycle 2 (DS-8201a only): AUCtau 706  (211)
DS-8201a, Cycle 3 (DS-8201a + ritonavir): AUC17d 710  (187)
DS-8201a, Cycle 3 (DS-8201a + ritonavir): AUCtau 789  (217)
Total Anti-HER2 antibody, Cycle 2 (DS-8201a only): AUC17d 707  (194)
Total Anti-HER2 antibody, Cycle 2 (DS-8201a only): AUCtau 790  (224)
Total Anti-HER2 antibody, Cycle 3 (DS-8201a + ritonavir): AUC17d 781  (196)
Total Anti-HER2 antibody, Cycle 3 (DS-8201a + ritonavir): AUCtau 883  (238)
8.Primary Outcome
Title Pharmacokinetic Parameter of Area Under the Serum Concentration-time Curve of MAAA-1181a Following Treatment With DS-8201a and Itraconazole - Cohort 2
Hide Description Area under the serum concentration-time curve from time zero to 17 days (AUC17d) and during the dosing interval (AUCtau) were assessed for MAAA-1181a.
Time Frame Cycle 1: Day 1, pre-dose and end of infusion (EOI); Cycles 2 and 3: Day 1, pre-dose, EOI, 2 hours, 4 hours, 7 hours; Day 2, 4, 8, 12, 17, and 22; Cycles 4, 6 and 8: Day 1, pre-dose and EOI (each cycle is 22 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set.
Arm/Group Title Cohort 2: DS-8201a + Itraconazole
Hide Arm/Group Description:
Participants who received 5.4 mg/kg DS-8201a as an intravenous infusion once every 3 weeks and 200 mg itraconazole twice daily (BID) on Day 17 of Cycle 2 followed by 200 mg daily (QD) until Day 21 of Cycle 3.
Overall Number of Participants Analyzed 14
Mean (Standard Deviation)
Unit of Measure: ng*d/mL
MAAA-1181a, Cycle 2 (DS-8201a only): AUC17d 29.9  (8.31)
MAAA-1181a, Cycle 2 (DS-8201a only): AUCtau 32.4  (9.21)
MAAA-1181a, Cycle 3 (DS-8201a + ritonavir): AUC17d 34.8  (8.04)
MAAA-1181a, Cycle 3 (DS-8201a + ritonavir): AUCtau 37.7  (8.87)
9.Secondary Outcome
Title Best Objective Response as Confirmed By The Investigator's Assessment in Participants With HER2-Expressing Advanced Solid Malignant Tumors
Hide Description Best objective response (BOR) was assessed by the investigator based on Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. Completed response (CR) was defined as a disappearance of all target lesions, PR was defined as at least a 30% decrease in the sum of diameters of target lesions, and stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD; at least a 20% increase in the sum of diameters of target lesions.
Time Frame Baseline up to disease progression, death, lost to follow up, or study discontinuation (whichever comes first), up to approximately 9 months post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Response was assessed in the Efficacy Analysis Set.
Arm/Group Title Cohort 1: DS-8201a + Ritonavir Cohort 2: DS-8201a + Itraconazole
Hide Arm/Group Description:
Participants who received 5.4 mg/kg DS-8201a as an intravenous infusion once every 3 weeks and 200 mg ritonavir twice daily (BID) on Day 17 of Cycle 2 until Day 21 of Cycle 3.
Participants who received 5.4 mg/kg DS-8201a as an intravenous infusion once every 3 weeks and 200 mg itraconazole twice daily (BID) on Day 17 of Cycle 2 followed by 200 mg daily (QD) until Day 21 of Cycle 3.
Overall Number of Participants Analyzed 17 19
Measure Type: Count of Participants
Unit of Measure: Participants
Complete response (CR)
0
   0.0%
0
   0.0%
Partial response (PR)
9
  52.9%
10
  52.6%
Stable disease (SD)
8
  47.1%
8
  42.1%
Non-CR/Non-PR
0
   0.0%
0
   0.0%
Progressive disease (PD)
0
   0.0%
1
   5.3%
Non evaluable
0
   0.0%
0
   0.0%
10.Secondary Outcome
Title Objective Response Ratio (ORR) as Confirmed By The Investigator's Assessment in Participants With HER2-Expressing Advanced Solid Malignant Tumors
Hide Description Objective response ratio (ORR) was defined as the proportion of participants who achieved CR and PR as assessed by the investigator based on Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. CR was defined as a disappearance of all target lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesions.
Time Frame Baseline up to disease progression, death, lost to follow up, or study discontinuation (whichever comes first), up to approximately 9 months post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Response was assessed in the Efficacy Analysis Set.
Arm/Group Title Cohort 1: DS-8201a + Ritonavir Cohort 2: DS-8201a + Itraconazole
Hide Arm/Group Description:
Participants who received 5.4 mg/kg DS-8201a as an intravenous infusion once every 3 weeks and 200 mg ritonavir twice daily (BID) on Day 17 of Cycle 2 until Day 21 of Cycle 3.
Participants who received 5.4 mg/kg DS-8201a as an intravenous infusion once every 3 weeks and 200 mg itraconazole twice daily (BID) on Day 17 of Cycle 2 followed by 200 mg daily (QD) until Day 21 of Cycle 3.
Overall Number of Participants Analyzed 17 19
Measure Type: Count of Participants
Unit of Measure: Participants
9
  52.9%
10
  52.6%
11.Secondary Outcome
Title Objective Response Rate as Confirmed By The Investigator's Assessment in Participants With HER2-Expressing Advanced Solid Malignant Tumors
Hide Description Objective response rate (defined as participants who achieved CR and PR) was assessed by the investigator based on Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. CR was defined as a disappearance of all target lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesions. ORR with confirmation is Objective Response Rate applying a confirmed response of CR/PR in RECIST version 1.1.
Time Frame Baseline up to disease progression, death, lost to follow up, or study discontinuation (whichever comes first), up to approximately 9 months post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Response was assessed in the Efficacy Analysis Set.
Arm/Group Title Cohort 1: DS-8201a + Ritonavir Cohort 2: DS-8201a + Itraconazole
Hide Arm/Group Description:
Participants who received 5.4 mg/kg DS-8201a as an intravenous infusion once every 3 weeks and 200 mg ritonavir twice daily (BID) on Day 17 of Cycle 2 until Day 21 of Cycle 3.
Participants who received 5.4 mg/kg DS-8201a as an intravenous infusion once every 3 weeks and 200 mg itraconazole twice daily (BID) on Day 17 of Cycle 2 followed by 200 mg daily (QD) until Day 21 of Cycle 3.
Overall Number of Participants Analyzed 17 19
Measure Type: Count of Participants
Unit of Measure: Participants
8
  47.1%
7
  36.8%
Time Frame Adverse event data were collected from baseline up to approximately 9 months post-dose.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Cohort 1: DS-8201a + Ritonavir Cohort 2: DS-8201a + Itraconazole
Hide Arm/Group Description Participants who received 5.4 mg/kg DS-8201a as an intravenous infusion once every 3 weeks and 200 mg ritonavir twice daily on Day 17 of Cycle 2 until Day 21 of Cycle 3. Participants who received 5.4 mg/kg DS-8201a as an intravenous infusion once every 3 weeks and 200 mg itraconazole BID on Day 17 of Cycle 2 followed by 200 mg QD until Day 21 of Cycle 3.
All-Cause Mortality
Cohort 1: DS-8201a + Ritonavir Cohort 2: DS-8201a + Itraconazole
Affected / at Risk (%) Affected / at Risk (%)
Total   1/17 (5.88%)   0/23 (0.00%) 
Hide Serious Adverse Events
Cohort 1: DS-8201a + Ritonavir Cohort 2: DS-8201a + Itraconazole
Affected / at Risk (%) Affected / at Risk (%)
Total   2/17 (11.76%)   3/23 (13.04%) 
Gastrointestinal disorders     
Diarrhoea † 1  0/17 (0.00%)  1/23 (4.35%) 
Ileus † 1  0/17 (0.00%)  1/23 (4.35%) 
Nausea † 1  0/17 (0.00%)  1/23 (4.35%) 
Vomiting † 1  0/17 (0.00%)  1/23 (4.35%) 
General disorders     
Disease progression † 1  1/17 (5.88%)  0/23 (0.00%) 
Pyrexia † 1  0/17 (0.00%)  1/23 (4.35%) 
Infections and infestations     
Sepsis † 1  0/17 (0.00%)  1/23 (4.35%) 
Respiratory, thoracic and mediastinal disorders     
Pneumonitis † 1  1/17 (5.88%)  0/23 (0.00%) 
1
Term from vocabulary, MedDRA 20.1
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Cohort 1: DS-8201a + Ritonavir Cohort 2: DS-8201a + Itraconazole
Affected / at Risk (%) Affected / at Risk (%)
Total   17/17 (100.00%)   22/23 (95.65%) 
Blood and lymphatic system disorders     
Anaemia † 1  6/17 (35.29%)  5/23 (21.74%) 
Neutropenia † 1  5/17 (29.41%)  1/23 (4.35%) 
Thrombocytopenia † 1  4/17 (23.53%)  1/23 (4.35%) 
Leukopenia † 1  2/17 (11.76%)  0/23 (0.00%) 
Lymphopenia † 1  1/17 (5.88%)  0/23 (0.00%) 
Cardiac disorders     
Atrioventricular block first degree † 1  1/17 (5.88%)  0/23 (0.00%) 
Palpitations † 1  1/17 (5.88%)  0/23 (0.00%) 
Eye disorders     
Eye discharge † 1  1/17 (5.88%)  0/23 (0.00%) 
Gastrointestinal disorders     
Nausea † 1  17/17 (100.00%)  15/23 (65.22%) 
Constipation † 1  8/17 (47.06%)  7/23 (30.43%) 
Diarrhoea † 1  8/17 (47.06%)  5/23 (21.74%) 
Vomiting † 1  3/17 (17.65%)  8/23 (34.78%) 
Stomatitis † 1  4/17 (23.53%)  2/23 (8.70%) 
Haemorrhoids † 1  1/17 (5.88%)  1/23 (4.35%) 
Ileus † 1  0/17 (0.00%)  2/23 (8.70%) 
Abdominal discomfort † 1  1/17 (5.88%)  0/23 (0.00%) 
Abdominal pain † 1  1/17 (5.88%)  0/23 (0.00%) 
Abdominal pain upper † 1  1/17 (5.88%)  0/23 (0.00%) 
Mouth haemorrhage † 1  1/17 (5.88%)  0/23 (0.00%) 
General disorders     
Fatigue † 1  5/17 (29.41%)  4/23 (17.39%) 
Malaise † 1  4/17 (23.53%)  1/23 (4.35%) 
Pyrexia † 1  1/17 (5.88%)  1/23 (4.35%) 
Disease progression † 1  1/17 (5.88%)  0/23 (0.00%) 
Oedema peripheral † 1  1/17 (5.88%)  0/23 (0.00%) 
Peripheral swelling † 1  1/17 (5.88%)  0/23 (0.00%) 
Hepatobiliary disorders     
Hepatic function abnormal † 1  1/17 (5.88%)  0/23 (0.00%) 
Infections and infestations     
Nasopharyngitis † 1  3/17 (17.65%)  0/23 (0.00%) 
Paroncyhia † 1  1/17 (5.88%)  1/23 (4.35%) 
Cystitis † 1  1/17 (5.88%)  0/23 (0.00%) 
Infected dermal cyst † 1  1/17 (5.88%)  0/23 (0.00%) 
Influenza † 1  1/17 (5.88%)  0/23 (0.00%) 
Osteomyelitis † 1  1/17 (5.88%)  0/23 (0.00%) 
Upper respiratory tract infection † 1  1/17 (5.88%)  0/23 (0.00%) 
Vulvovaginal candidiasis † 1  1/17 (5.88%)  0/23 (0.00%) 
Investigations     
Neutrophil count decreased † 1  6/17 (35.29%)  8/23 (34.78%) 
White blood cell count decreased † 1  7/17 (41.18%)  7/23 (30.43%) 
Platelet count decreased † 1  9/17 (52.94%)  4/23 (17.39%) 
Aspartate aminotransferase increased † 1  6/17 (35.29%)  5/23 (21.74%) 
Alanine aminotransferase increased † 1  7/17 (41.18%)  3/23 (13.04%) 
Blood alkaline phosphatase increased † 1  4/17 (23.53%)  0/23 (0.00%) 
Weight decreased † 1  2/17 (11.76%)  2/23 (8.70%) 
Blood creatinine increased † 1  2/17 (11.76%)  1/23 (4.35%) 
Troponin I increased † 1  1/17 (5.88%)  1/23 (4.35%) 
Alanine aminotransferase decreased † 1  1/17 (5.88%)  0/23 (0.00%) 
Aspartate aminotransferase decreased † 1  1/17 (5.88%)  0/23 (0.00%) 
Blood bilirubin increased † 1  1/17 (5.88%)  0/23 (0.00%) 
Blood lactate dehydrogenase increased † 1  1/17 (5.88%)  0/23 (0.00%) 
Gamma-glutamyltransferase increased † 1  1/17 (5.88%)  0/23 (0.00%) 
Ophthalmological examination abnormal † 1  1/17 (5.88%)  0/23 (0.00%) 
Protein total decreased † 1  1/17 (5.88%)  0/23 (0.00%) 
Metabolism and nutrition disorders     
Decreased appetite † 1  13/17 (76.47%)  9/23 (39.13%) 
Hypoalbuminaemia † 1  1/17 (5.88%)  1/23 (4.35%) 
Hypokalaemia † 1  1/17 (5.88%)  0/23 (0.00%) 
Musculoskeletal and connective tissue disorders     
Osteonecrosis of jaw † 1  2/17 (11.76%)  1/23 (4.35%) 
Arthralgia † 1  2/17 (11.76%)  0/23 (0.00%) 
Back pain † 1  0/17 (0.00%)  2/23 (8.70%) 
Musculoskeletal pain † 1  1/17 (5.88%)  0/23 (0.00%) 
Myalgia † 1  1/17 (5.88%)  0/23 (0.00%) 
Nervous system disorders     
Headache † 1  4/17 (23.53%)  2/23 (8.70%) 
Dysgeusia † 1  1/17 (5.88%)  1/23 (4.35%) 
Akathisia † 1  1/17 (5.88%)  0/23 (0.00%) 
Hyperaesthesia † 1  1/17 (5.88%)  0/23 (0.00%) 
Neuropathy peripheral † 1  1/17 (5.88%)  0/23 (0.00%) 
Peripheral sensory neuropathy † 1  1/17 (5.88%)  0/23 (0.00%) 
Somnolence † 1  1/17 (5.88%)  0/23 (0.00%) 
Renal and urinary disorders     
Dysuria † 1  1/17 (5.88%)  0/23 (0.00%) 
Renal impairment † 1  1/17 (5.88%)  0/23 (0.00%) 
Reproductive system and breast disorders     
Atrophic vulvovaginitis † 1  1/17 (5.88%)  0/23 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Cough † 1  2/17 (11.76%)  4/23 (17.39%) 
Oropharyngeal pain † 1  1/17 (5.88%)  1/23 (4.35%) 
Hypoxia † 1  1/17 (5.88%)  0/23 (0.00%) 
Organising pneumonia † 1  1/17 (5.88%)  0/23 (0.00%) 
Pneumonitis † 1  1/17 (5.88%)  0/23 (0.00%) 
Rhinitis allergic † 1  1/17 (5.88%)  0/23 (0.00%) 
Upper-airway cough syndrome † 1  1/17 (5.88%)  0/23 (0.00%) 
Skin and subcutaneous tissue disorders     
Alopecia † 1  6/17 (35.29%)  7/23 (30.43%) 
Rash † 1  1/17 (5.88%)  2/23 (8.70%) 
Dry skin † 1  2/17 (11.76%)  0/23 (0.00%) 
Rash maculo-papular † 1  2/17 (11.76%)  0/23 (0.00%) 
Dermatitis acneiform † 1  1/17 (5.88%)  0/23 (0.00%) 
Night sweats † 1  1/17 (5.88%)  0/23 (0.00%) 
Palmar-plantar erythrodysaesthesia syndrome † 1  1/17 (5.88%)  0/23 (0.00%) 
Rash erythematous † 1  1/17 (5.88%)  0/23 (0.00%) 
Vascular disorders     
Hot flush † 1  1/17 (5.88%)  0/23 (0.00%) 
1
Term from vocabulary, MedDRA 20.1
†
Indicates events were collected by systematic assessment
[Not Specified]
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT 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: Contact for Clinical Trial Information
Organization: Daiichi Sankyo
Phone: 908-992-6400
EMail: CTRinfo@dsi.com
Layout table for additonal information
Responsible Party: Daiichi Sankyo ( Daiichi Sankyo Co., Ltd. )
ClinicalTrials.gov Identifier: NCT03383692    
Other Study ID Numbers: DS8201-A-A104
173790 ( Registry Identifier: JAPIC CTI )
First Submitted: December 7, 2017
First Posted: December 26, 2017
Results First Submitted: May 18, 2021
Results First Posted: June 14, 2021
Last Update Posted: December 11, 2023