Phase 1 Study to Evaluate the Effect of DS-8201a on the QT/QTc Interval and Pharmacokinetics in HER2-Expressing Breast Cancer

• Sponsor: Daiichi Sankyo Co., Ltd. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03366428
• Collaborator: AstraZeneca (Industry)
• Enrollment: 51
• Locations: 7
• Arm: 1
• Actual Duration (Months): 37.8
• Patients Per Site: 7.3
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This study will look at the effect on the QTc interval and pharmacokinetics after multiple dosing in subjects with HER2-expressing metastatic and/or unresectable breast cancer.

Condition or Disease	Intervention/Treatment	Phase
Malignant Neoplasm of Breast	Drug: DS-8201a	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 51 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase 1, Multicenter, Open-label, Multiple-dose Study of DS-8201a to Assess the Effect on the QT Interval and Pharmacokinetics in Subjects With HER2-expressing Metastatic and/or Unresectable Breast Cancer
• Actual Study Start Date: Dec 26, 2017
• Actual Primary Completion Date: Dec 5, 2018
• Actual Study Completion Date: Feb 19, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: All Participants All participants will receive DS-8201a by intravenous infusion	Drug: DS-8201a; DS-8201a is supplied as a lyophilized powder which is reconstituted for infusion; Other Names: Experimental product

Outcome Measures

Primary Outcome Measures

1. Changes in QTcF After Treatment With DS-8201a in Participants With HER2-expressing Metastatic and/or Unresectable Breast Cancer [Screening (within 7 days before enrollment) up to Cycle 3 Day 15 (each cycle is 21 days)]

   The number of participants with notable electrocardiogram changes meeting predefined criteria is being reported.

2. Pharmacokinetic Parameters of Maximum Serum Concentration (Cmax) After Cycle 1 and Cycle 3 Treatments With DS-8201a in Participants With HER2-expressing Metastatic and/or Unresectable Breast Cancer [Cycles 1 and 3: Day 1: before infusion (BI), end of infusion (EOI), 2 hours, 4 hours, 7 hours; Days 2 and 4: 24 hours, 72 hours; Days 8 and 15; Cycle 2: Day 1 BI, EOI; Cycles 4, 6, and 8: Day 1 BI and EOI (each cycle is 21 days)]

   Maximum serum concentration (Cmax) of DS-8201a and total anti-HER2 antibody was assessed.

3. Pharmacokinetic Parameters of Maximum Serum Concentration (Cmax) of MAAA-1181 After Cycle 1 and Cycle 3 Treatments With DS-8201a in Participants With HER2-expressing Metastatic and/or Unresectable Breast Cancer [Cycles 1 and 3: Day 1: before infusion (BI), end of infusion (EOI), 2 hours, 4 hours, 7 hours; Days 2 and 4: 24 hours, 72 hours; Days 8 and 15; Cycle 2: Day 1 BI, EOI; Cycles 4, 6, and 8: Day 1 BI and EOI (each cycle is 21 days)]

   Maximum serum concentration (Cmax) of MAAA-1181 was assessed.

4. Pharmacokinetic Parameters Area Under the Concentration-Time Curve After Cycle 1 and Cycle 3 Treatments With DS-8201a in Participants With HER2-expressing Metastatic and/or Unresectable Breast Cancer [Cycles 1 and 3: Day 1: before infusion (BI), end of infusion (EOI), 2 hours, 4 hours, 7 hours; Days 2 and 4: 24 hours, 72 hours; Days 8 and 15; Cycle 2: Day 1 BI, EOI; Cycles 4, 6, and 8: Day 1 BI and EOI (each cycle is 21 days)]

   Area under the concentration versus-time curve from time 0 to the last quantifiable concentration (AUClast) and during the dosing interval (AUCtau) of DS-8201a and total anti-HER2 antibody were assessed.

5. Pharmacokinetic Parameters Area Under the Concentration-Time Curve of MAAA-1181 After Cycle 1 and Cycle 3 Treatments With DS-8201a in Participants With HER2-expressing Metastatic and/or Unresectable Breast Cancer [Cycles 1 and 3: Day 1: before infusion (BI), end of infusion (EOI), 2 hours, 4 hours, 7 hours; Days 2 and 4: 24 hours, 72 hours; Days 8 and 15; Cycle 2: Day 1 BI, EOI; Cycles 4, 6, and 8: Day 1 BI and EOI (each cycle is 21 days)]

   Area under the concentration versus-time curve from time 0 to the last quantifiable concentration (AUClast) and during the dosing interval (AUCtau) were assessed.

Secondary Outcome Measures

1. Objective Response Rate Based on The Investigator's Assessment (Unconfirmed) Following DS-8201a Treatment in Participants With HER2-expressing Metastatic and/or Unresectable Breast Cancer [Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 12 months post-dose]

   Objective response rate (ORR) was defined as unconfirmed complete response (CR) and partial response (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.

2. Objective Response Rate Based on The Investigator's Assessment (Unconfirmed) Following DS-8201a Treatment in Participants With HER2-expressing Metastatic and/or Unresectable Breast Cancer [Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 38 months post-dose]

   Objective response rate (ORR) was defined as unconfirmed complete response (CR) and partial response (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.

3. Treatment-Emergent Adverse Events of Any Grade by System Organ Classes and Preferred Term Following DS-8201a Treatment in Participants With HER2-expressing Metastatic and/or Unresectable Breast Cancer [Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to approximately 12 months post-dose]

   Adverse events (AEs) were to be coded using MedDRA Version 20.1 and assigned severity grades based on Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03. A treatment-emergent adverse event (TEAE) was defined as an AE that occurred, having been absent before the first dose of study drug, or had worsened in severity or seriousness after initiating the study drug until 47 days after last dose of study drug.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Has a pathologically documented unresectable or metastatic breast cancer with HER2 expression (immunohistochemistry [IHC] 3+, IHC 2+, IHC 1+ and/or in situ hybridization [ISH] +) that is refractory to or intolerable with standard treatment, or for which no standard treatment is available

• Has a left ventricular ejection fraction (LVEF) ≥ 50%

• Has an Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0 or 1

Exclusion Criteria:

• Has a medical history of myocardial infarction within 6 months before enrollment

• Has a medical history of ventricular arrhythmias, other than rare occasional premature ventricular contractions

• Has uncontrolled or significant cardiovascular disease

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Kanagawa Cancer Center	Yokohama	Kanagawa	Japan	241-8515
2	National Cancer Center Hospital	Chuo Ku	Tokyo	Japan	104-0045
3	The Cancer Institute Hospital of Japanese Foundation For Cancer Research	Koto-Ku	Tokyo	Japan	135-8550
4	Toranomon Hospital	Minato-Ku	Tokyo	Japan	105-8470
5	National Hospital Organization Kyushu Cancer Center	Fukuoka		Japan	811-1395
6	Social Medical Corporation Hakuaikai Sagara Hospital	Kagoshima		Japan	892-0833
7	Shizuoka Cancer Center	Shizuoka		Japan	411-8777

Sponsors and Collaborators

• Daiichi Sankyo Co., Ltd.
• AstraZeneca

Investigators

• Study Director: Global Clinical Leader, Daiichi Sankyo, Inc.

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jul 3, 2020

More Information

Publications

None provided.

• Responsible Party: Daiichi Sankyo Co., Ltd.
• ClinicalTrials.gov Identifier: NCT03366428
• Other Study ID Numbers: DS8201-A-J102; 173791
• First Posted: Dec 8, 2017
• Last Update Posted: Apr 12, 2022
• Last Verified: Mar 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Daiichi Sankyo Co., Ltd.: HER2; Breast cancer; Oncology; Antibody drug conjugate; ADC
• Additional relevant MeSH terms: Breast Neoplasms; Neoplasms

Study Results

Participant Flow

Recruitment Details	A total of 51 participants who met all inclusion criteria and no exclusion criteria were enrolled and treated at 7 sites in Japan.
Pre-assignment Detail	The 6.4 mg/kg DS-8201a dose was chosen for this study based on the efficacy, safety, and pharmacokinetic profiles established in an earlier Phase 1 trial.

Arm/Group Title	DS-8201a
Arm/Group Description	Participants who received 6.4 mg/kg of DS-8201a as an intravenous (IV) infusion once every 3 weeks (Q3W) on Day 1 of each 21-day cycle.
Period Title: Overall Study
STARTED	51
COMPLETED	0
NOT COMPLETED	51

Baseline Characteristics

Arm/Group Title	DS-8201a
Arm/Group Description	Participants who received 6.4 mg/kg of DS-8201a as an intravenous (IV) infusion once every 3 weeks on Day 1 of each 21-day cycle.
Overall Participants	51
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	55.9 (10.48)
Age, Customized (Count of Participants)
<65	38 74.5%
≥65	13 25.5%
>75	1 2%
Sex: Female, Male (Count of Participants)
Female	51 100%
Male	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	51 100%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	0 0%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
Japan	51 100%

Outcome Measures

1. Primary Outcome

Title	Changes in QTcF After Treatment With DS-8201a in Participants With HER2-expressing Metastatic and/or Unresectable Breast Cancer
Description	The number of participants with notable electrocardiogram changes meeting predefined criteria is being reported.
Time Frame	Screening (within 7 days before enrollment) up to Cycle 3 Day 15 (each cycle is 21 days)

Outcome Measure Data

Analysis Population Description

QTc and QTcF were assessed in the Cardiac Analysis Set.

Arm/Group Title	DS-8201a
Arm/Group Description	Participants who received 6.4 mg/kg of DS-8201a as an intravenous (IV) infusion once every 3 weeks on Day 1 of each 21-day cycle.
Measure Participants	49
Maximum change from baseline in QTcF: >30 ms	3 5.9%
Maximum change from baseline in QTcF: >60 ms	0 0%

2. Primary Outcome

Title	Pharmacokinetic Parameters of Maximum Serum Concentration (Cmax) After Cycle 1 and Cycle 3 Treatments With DS-8201a in Participants With HER2-expressing Metastatic and/or Unresectable Breast Cancer
Description	Maximum serum concentration (Cmax) of DS-8201a and total anti-HER2 antibody was assessed.
Time Frame	Cycles 1 and 3: Day 1: before infusion (BI), end of infusion (EOI), 2 hours, 4 hours, 7 hours; Days 2 and 4: 24 hours, 72 hours; Days 8 and 15; Cycle 2: Day 1 BI, EOI; Cycles 4, 6, and 8: Day 1 BI and EOI (each cycle is 21 days)

Outcome Measure Data

Analysis Population Description

Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set.

Arm/Group Title	DS-8201a
Arm/Group Description	Participants who received 6.4 mg/kg of DS-8201a as an intravenous (IV) infusion once every 3 weeks on Day 1 of each 21-day cycle.
Measure Participants	51
DS-8201: Cycle 1	179 (112)
DS-8201: Cycle 3	154 (23.3)
Total Anti-HER2 antibody: Cycle 1	165 (110)
Total Anti-HER2 antibody: Cycle 3	142 (27.0)

3. Primary Outcome

Title	Pharmacokinetic Parameters of Maximum Serum Concentration (Cmax) of MAAA-1181 After Cycle 1 and Cycle 3 Treatments With DS-8201a in Participants With HER2-expressing Metastatic and/or Unresectable Breast Cancer
Description	Maximum serum concentration (Cmax) of MAAA-1181 was assessed.
Time Frame	Cycles 1 and 3: Day 1: before infusion (BI), end of infusion (EOI), 2 hours, 4 hours, 7 hours; Days 2 and 4: 24 hours, 72 hours; Days 8 and 15; Cycle 2: Day 1 BI, EOI; Cycles 4, 6, and 8: Day 1 BI and EOI (each cycle is 21 days)

Outcome Measure Data

Analysis Population Description

Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set.

Arm/Group Title	DS-8201a
Arm/Group Description	Participants who received 6.4 mg/kg of DS-8201a as an intravenous (IV) infusion once every 3 weeks on Day 1 of each 21-day cycle.
Measure Participants	51
MAAA-1181a: Cycle 1	12.6 (4.49)
MAAA-1181a: Cycle 3	9.60 (3.89)

4. Primary Outcome

Title	Pharmacokinetic Parameters Area Under the Concentration-Time Curve After Cycle 1 and Cycle 3 Treatments With DS-8201a in Participants With HER2-expressing Metastatic and/or Unresectable Breast Cancer
Description	Area under the concentration versus-time curve from time 0 to the last quantifiable concentration (AUClast) and during the dosing interval (AUCtau) of DS-8201a and total anti-HER2 antibody were assessed.
Time Frame	Cycles 1 and 3: Day 1: before infusion (BI), end of infusion (EOI), 2 hours, 4 hours, 7 hours; Days 2 and 4: 24 hours, 72 hours; Days 8 and 15; Cycle 2: Day 1 BI, EOI; Cycles 4, 6, and 8: Day 1 BI and EOI (each cycle is 21 days)

Outcome Measure Data

Analysis Population Description

Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set.

Arm/Group Title	DS-8201a
Arm/Group Description	Participants who received 6.4 mg/kg of DS-8201a as an intravenous (IV) infusion once every 3 weeks on Day 1 of each 21-day cycle.
Measure Participants	51
AUClast, DS-8201: Cycle 1	677 (143)
AUClast, Total Anti-HER2 antibody: Cycle 1	753 (190)
AUCtau, DS-8201: Cycle 1	677 (141)
AUCtau, DS-8201: Cycle 3	905 (189)
AUCtau, Total Anti-HER2 antibody: Cycle 1	752 (185)
AUCtau, Total Anti-HER2 antibody: Cycle 3	1030 (256)

5. Primary Outcome

Title	Pharmacokinetic Parameters Area Under the Concentration-Time Curve of MAAA-1181 After Cycle 1 and Cycle 3 Treatments With DS-8201a in Participants With HER2-expressing Metastatic and/or Unresectable Breast Cancer
Description	Area under the concentration versus-time curve from time 0 to the last quantifiable concentration (AUClast) and during the dosing interval (AUCtau) were assessed.
Time Frame	Cycles 1 and 3: Day 1: before infusion (BI), end of infusion (EOI), 2 hours, 4 hours, 7 hours; Days 2 and 4: 24 hours, 72 hours; Days 8 and 15; Cycle 2: Day 1 BI, EOI; Cycles 4, 6, and 8: Day 1 BI and EOI (each cycle is 21 days)

Outcome Measure Data

Analysis Population Description

Pharmacokinetic parameters were assessed in the Pharmacokinetic Analysis Set.

Arm/Group Title	DS-8201a
Arm/Group Description	Participants who received 6.4 mg/kg of DS-8201a as an intravenous (IV) infusion once every 3 weeks on Day 1 of each 21-day cycle.
Measure Participants	51
AUClast, MAAA-1181a: Cycle 1	39.3 (11.3)
AUCtau, MAAA-1181a: Cycle 1	39.0 (11.2)
AUCtau, MAAA-1181a: Cycle 3	41.5 (13.8)

6. Secondary Outcome

Title	Objective Response Rate Based on The Investigator's Assessment (Unconfirmed) Following DS-8201a Treatment in Participants With HER2-expressing Metastatic and/or Unresectable Breast Cancer
Description	Objective response rate (ORR) was defined as unconfirmed complete response (CR) and partial response (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 withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 12 months post-dose

Outcome Measure Data

Analysis Population Description

Response was assessed in the Efficacy Analysis Set.

Arm/Group Title	HER2 Positive	HER2 Low
Arm/Group Description	Participants with HER2 positive expression (defined as immunohistochemistry 3+ or in situ hybridization positive) who received 6.4 mg/kg of DS-8201a as an intravenous (IV) infusion once every 3 weeks on Day 1 of each 21-day cycle.	Participants with HER2 low expression (defined as immunohistochemistry 1+ or 2+/ in situ hybridization negative or missing) who received 6.4 mg/kg of DS-8201a as an intravenous (IV) infusion once every 3 weeks on Day 1 of each 21-day cycle.
Measure Participants	4	47
Count of Participants [Participants]	2 3.9%	18 NaN

7. Secondary Outcome

Title	Objective Response Rate Based on The Investigator's Assessment (Unconfirmed) Following DS-8201a Treatment in Participants With HER2-expressing Metastatic and/or Unresectable Breast Cancer
Description	Objective response rate (ORR) was defined as unconfirmed complete response (CR) and partial response (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 withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 38 months post-dose

Outcome Measure Data

Analysis Population Description

Response was assessed in the Efficacy Analysis Set.

Arm/Group Title	HER2 Positive	HER2 Low
Arm/Group Description	Participants with HER2 positive expression (defined as immunohistochemistry 3+ or in situ hybridization positive) who received 6.4 mg/kg of DS-8201a as an intravenous (IV) infusion once every 3 weeks on Day 1 of each 21-day cycle.	Participants with HER2 low expression (defined as immunohistochemistry 1+ or 2+/ in situ hybridization negative or missing) who received 6.4 mg/kg of DS-8201a as an intravenous (IV) infusion once every 3 weeks on Day 1 of each 21-day cycle.
Measure Participants	4	47
Count of Participants [Participants]	2 3.9%	23 NaN

8. Secondary Outcome

Title	Treatment-Emergent Adverse Events of Any Grade by System Organ Classes and Preferred Term Following DS-8201a Treatment in Participants With HER2-expressing Metastatic and/or Unresectable Breast Cancer
Description	Adverse events (AEs) were to be coded using MedDRA Version 20.1 and assigned severity grades based on Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03. A treatment-emergent adverse event (TEAE) was defined as an AE that occurred, having been absent before the first dose of study drug, or had worsened in severity or seriousness after initiating the study drug until 47 days after last dose of study drug.
Time Frame	Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to approximately 12 months post-dose

Outcome Measure Data

Analysis Population Description

Treatment-emergent adverse events (TEAEs) were assessed in the Safety Analysis Set.

Arm/Group Title	DS-8201a
Arm/Group Description	Participants who received 6.4 mg/kg of DS-8201a as an intravenous (IV) infusion once every 3 weeks on Day 1 of each 21-day cycle.
Measure Participants	51
Any TEAEs	51 100%
Gastrointestinal Disorders	45 88.2%
Nausea	42 82.4%
Vomiting	20 39.2%
Constipation	16 31.4%
Stomatitis	16 31.4%
Diarrhoea	14 27.5%
Investigations	45 88.2%
Neutrophil count decreased	36 70.6%
White blood cell count decreased	31 60.8%
Platelet count decreased	20 39.2%
Lymphocyte count decreased	13 25.5%
Alanine aminotransferase increased	12 23.5%
Aspartate aminotransferase increased	12 23.5%
Blood and Lymphatic System Disorders	30 58.8%
Anaemia	30 58.8%
Skin and Subcutaneous Tissue Disorders	27 52.9%
Alopecia	21 41.2%
General Disorders and Administration Site Conditions	25 49%
Fatigue	11 21.6%
Infections and Infestations	21 41.2%
Nasopharyngitis	11 21.6%
Metabolism and Nutrition Disorders	19 37.3%
Decreased appetite	16 31.4%
Nervous System Disorders	15 29.4%
Respiratory, Thoracic, and Mediastinal Disorders	12 23.5%

Adverse Events

Time Frame	Adverse event data were collected from baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever occurs first), up to 38 months post-dose.
Arm/Group Title	DS-8201a
Arm/Group Description	Participants who received 6.4 mg/kg of DS-8201a as an intravenous (IV) infusion once every 3 weeks on Day 1 of each 21-day cycle.
All Cause Mortality
	DS-8201a
	Affected / at Risk (%)	# Events
Total	0/51 (0%)
Serious Adverse Events
	DS-8201a
	Affected / at Risk (%)	# Events
Total	9/51 (17.6%)
Gastrointestinal disorders
Nausea	2/51 (3.9%)
Infections and infestations
Cellulitis	1/51 (2%)
Lung infection	1/51 (2%)
Injury, poisoning and procedural complications
Femur fracture	1/51 (2%)
Post procedural complication	1/51 (2%)
Fracture	1/51 (2%)
Respiratory, thoracic and mediastinal disorders
Interstitial lung disease	1/51 (2%)
Pneumonitis	1/51 (2%)
Other (Not Including Serious) Adverse Events
	DS-8201a
	Affected / at Risk (%)	# Events
Total	51/51 (100%)
Blood and lymphatic system disorders
Anaemia	32/51 (62.7%)
Cardiac disorders
Palpitations	1/51 (2%)
Ear and labyrinth disorders
Ear pain	1/51 (2%)
Eye disorders
Conjunctivitis allergic	2/51 (3.9%)
Dry eye	2/51 (3.9%)
Punctate keratitis	2/51 (3.9%)
Blepharitis	1/51 (2%)
Cataract	1/51 (2%)
Chalazion	1/51 (2%)
Corneal disorder	1/51 (2%)
Gastrointestinal disorders
Nausea	42/51 (82.4%)
Vomiting	21/51 (41.2%)
Constipation	17/51 (33.3%)
Stomatitis	21/51 (41.2%)
Diarrhoea	17/51 (33.3%)
Abdominal discomfort	5/51 (9.8%)
Abdominal pain upper	5/51 (9.8%)
Periodontal disease	3/51 (5.9%)
Proctalgia	3/51 (5.9%)
Haemorrhoids	2/51 (3.9%)
Haemorrhoidal haemorrhage	2/51 (3.9%)
Faeces soft	2/51 (3.9%)
Anal fissure	1/51 (2%)
Ascites	1/51 (2%)
Dry mouth	1/51 (2%)
Enterocolitis	1/51 (2%)
Food poisoning	1/51 (2%)
Gastritis	1/51 (2%)
Mouth haemorrhage	1/51 (2%)
Toothache	1/51 (2%)
General disorders
Fatigue	11/51 (21.6%)
Malaise	12/51 (23.5%)
Pyrexia	14/51 (27.5%)
Oedema	3/51 (5.9%)
Oedema peripheral	3/51 (5.9%)
Chest pain	2/51 (3.9%)
Withdrawal syndrome	1/51 (2%)
Non-cardiac chest pain	1/51 (2%)
Hepatobiliary disorders
Hepatic function abnormal	5/51 (9.8%)
Immune system disorders
Seasonal allergy	2/51 (3.9%)
Allergy to arthropod sting	1/51 (2%)
Contrast media allergy	1/51 (2%)
Infections and infestations
Nasopharyngitis	16/51 (31.4%)
Lung infection	4/51 (7.8%)
Upper respiratory tract infection	5/51 (9.8%)
Ginsivitis	3/51 (5.9%)
Influenza	3/51 (5.9%)
Gastroenteritis	2/51 (3.9%)
Paronychia	2/51 (3.9%)
Pharyngitis	2/51 (3.9%)
Rhinitis	2/51 (3.9%)
Angular cheilitis	1/51 (2%)
Cellulitis	1/51 (2%)
Cystitis	1/51 (2%)
Dacryocystitis	1/51 (2%)
Folliculitis	1/51 (2%)
Hordeolum	1/51 (2%)
Infection	1/51 (2%)
Laryngitis	1/51 (2%)
Oral candidiasis	1/51 (2%)
Periodontitis	1/51 (2%)
Sinusitis	1/51 (2%)
Skin infection	1/51 (2%)
Urinary tract infection	1/51 (2%)
Vaginal infection	1/51 (2%)
Skin candida	1/51 (2%)
Oral herpes	1/51 (2%)
Injury, poisoning and procedural complications
Bite	1/51 (2%)
Fall	1/51 (2%)
Femur fracture	1/51 (2%)
Foot fracture	1/51 (2%)
Fracture	1/51 (2%)
Ligament sprain	1/51 (2%)
Spinal compression fracture	1/51 (2%)
Thermal burn	1/51 (2%)
Post procedural complication	1/51 (2%)
Investigations
Neutrophil count decreased	36/51 (70.6%)
White blood cell count decreased	34/51 (66.7%)
Platelet count decreased	20/51 (39.2%)
Lymphocyte count decreased	15/51 (29.4%)
Alanine aminotransferase increased	14/51 (27.5%)
Aspartate aminotransferase increased	13/51 (25.5%)
Electrocardiogram QT prolonged	5/51 (9.8%)
Weight decreased	5/51 (9.8%)
Blood alkaline phosphatase increased	5/51 (9.8%)
Blood bilirubin increased	4/51 (7.8%)
Blood creatinine increased	2/51 (3.9%)
Blood lactate dehydrogenase increased	2/51 (3.9%)
Gamma-glutamyltransferase increased	2/51 (3.9%)
Protein total decreased	2/51 (3.9%)
Blood urea increased	1/51 (2%)
Weight increased	1/51 (2%)
Ejection fraction decreased	1/51 (2%)
Metabolism and nutrition disorders
Decreased appetite	16/51 (31.4%)
Hypoalbuminaemia	6/51 (11.8%)
Hypokalaemia	2/51 (3.9%)
Dehydration	1/51 (2%)
Hyperglycaemia	1/51 (2%)
Hypermagnesaemia	1/51 (2%)
Hypocalcaemia	1/51 (2%)
Musculoskeletal and connective tissue disorders
Arthralgia	4/51 (7.8%)
Back pain	3/51 (5.9%)
Myalgia	2/51 (3.9%)
Flank pain	1/51 (2%)
Musculoskeletal pain	1/51 (2%)
Periarthritis	1/51 (2%)
Spinal osteoarthritis	1/51 (2%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Haemangioma	1/51 (2%)
Nervous system disorders
Dysgeusia	7/51 (13.7%)
Headache	7/51 (13.7%)
Dizziness	5/51 (9.8%)
Peripheral sensory neuropathy	2/51 (3.9%)
Akathisia	1/51 (2%)
Vagus nerve disorder	1/51 (2%)
Visual perseveration	1/51 (2%)
Psychiatric disorders
Anxiety	3/51 (5.9%)
Insomnia	5/51 (9.8%)
Agitation	1/51 (2%)
Renal and urinary disorders
Hydronephrosis	1/51 (2%)
Renal impairment	1/51 (2%)
Cystitis noninfective	1/51 (2%)
Reproductive system and breast disorders
Uterine polyp	1/51 (2%)
Genital haemorrhage	1/51 (2%)
Respiratory, thoracic and mediastinal disorders
Pneumonitis	8/51 (15.7%)
Epistaxis	7/51 (13.7%)
Interstitial lung disease	5/51 (9.8%)
Oropharyngeal pain	5/51 (9.8%)
Cough	3/51 (5.9%)
Hiccups	1/51 (2%)
Pleural effusion	1/51 (2%)
Productive cough	3/51 (5.9%)
Organising pneumonia	1/51 (2%)
Skin and subcutaneous tissue disorders
Alopecia	21/51 (41.2%)
Pruritus	5/51 (9.8%)
Dry skin	5/51 (9.8%)
Rash	4/51 (7.8%)
Rash maculo-papular	3/51 (5.9%)
Eczema	1/51 (2%)
Erythema	1/51 (2%)
Haemorrhage subcutaneous	1/51 (2%)
Ingrowing nail	1/51 (2%)
Purpura	1/51 (2%)
Skin disorder	1/51 (2%)
Skin erosion	1/51 (2%)
Onychalgia	1/51 (2%)
Vascular disorders
Hypotension	1/51 (2%)
Embolism	1/51 (2%)
Venous thrombosis limb	1/51 (2%)

Limitations/Caveats

[Not Specified]

More Information

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.