DS-8201a in Patients With Cancer That Tests Positive for Human Epidermal Growth Factor Receptor 2 (HER2) Protein

• Sponsor: Daiichi Sankyo Taiwan Ltd., a Daiichi Sankyo Company (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT03368196
• Collaborator: AstraZeneca (Industry)
• Enrollment: 12
• Locations: 2
• Arm: 1
• Anticipated Duration (Months): 53.9
• Patients Per Site: 6
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

HER2-positive cancer is a cancer that tests positive for a protein called human epidermal growth factor receptor 2 (HER2). HER2 promotes the growth of certain cancer cells. This study will test DS-8201a (trastuzumab deruxtecan), a HER2-targeted antibody and topoisomerase I inhibitor conjugate.

The safety and tolerability profile of DS-8201a will be assessed in Chinese patients with certain types of stomach and breast cancer that test positive for HER2. It also will test how DS-8201a moves within the body (pharmacokinetics).

Condition or Disease	Intervention/Treatment	Phase
Adenocarcinoma, Gastric; Neoplasm, Breast	Drug: DS-8201a	Phase 1

Detailed Description

The expected time from the first subject's enrollment until the last subject's enrollment is approximately 8 months. The screening period is 28 days and each cycle of treatment is 21 days.

The number of treatment cycles is not fixed in this study. Subjects who continue to derive clinical benefit from the study drug in the absence of withdrawal of consent, progressive disease (PD), or unacceptable toxicity may continue the study drug.

Study Design

• Study Type: Interventional
• Actual Enrollment: 12 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase 1, Multicenter, Open-label Study of DS-8201a to Assess Safety and Pharmacokinetics in Subjects With HER2-Positive Advanced and/or Refractory Gastric, Gastroesophageal Junction Adenocarcinoma, or Breast Cancer
• Actual Study Start Date: Apr 2, 2018
• Actual Primary Completion Date: Sep 14, 2018
• Anticipated Study Completion Date: Sep 30, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: DS-8201a DS-8201a administered by intravenous infusion on Day 1 of each cycle, once every 3 weeks (Q3W)	Drug: DS-8201a; An antibody drug conjugate

Outcome Measures

Primary Outcome Measures

1. Treatment-emergent Adverse Events Following Treatment With DS-8201a (Trastuzumab Deruxtecan) [Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever came first), up to approximately 5 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.

Secondary Outcome Measures

1. Pharmacokinetic Parameter of Maximum (Peak) Observed Serum Concentration (Cmax) Following Cycle 1 and Cycle 3 Treatment With DS-8201a (Trastuzumab Deruxtecan) [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; Cycles 2, 4, 6 and 8, Day 1: BI and EOI]

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

2. Pharmacokinetic Parameter of Maximum (Peak) Observed Serum Concentration (Cmax) of MAAA-1181a Following Cycle 1 and Cycle 3 Treatment With DS-8201a (Trastuzumab Deruxtecan) [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; Cycles 2, 4, 6 and 8, Day 1: BI and EOI]

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

3. Pharmacokinetic Parameter of Area Under the Serum Concentration-time Curve During Dosing Interval (AUCtau) Following Cycle 1 and Cycle 3 Treatment With DS-8201a (Trastuzumab Deruxtecan) [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; Cycles 2, 4, 6 and 8, Day 1: BI and EOI]

   Area under the serum concentration-time curve during dosing interval (AUCtau) of DS-8201a and total anti-HER2 antibody was assessed.

4. Pharmacokinetic Parameter of Area Under the Serum Concentration-time Curve During Dosing Interval (AUCtau) of MAAA-1181a Following Cycle 1 and Cycle 3 Treatment With DS-8201a (Trastuzumab Deruxtecan) [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; Cycles 2, 4, 6 and 8, Day 1: BI and EOI]

   Area under the serum concentration-time curve during dosing interval (AUCtau) of MAAA-1181a was assessed.

5. Best Overall Response By The Investigator's Assessment (Unconfirmed) in Participants With HER2-Positive Advanced and/or Refractory Gastric, Gastroesophageal Junction Adenocarcinoma, or Breast Cancer [Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever came first), up to approximately 5 months post-dose]

   Best overall response (BOR) was assessed by the investigator based on Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. Complete 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.

6. Objective Response Rate (Unconfirmed) As Assessed in Participants With HER2-Positive Advanced and/or Refractory Gastric, Gastroesophageal Junction Adenocarcinoma, or Breast Cancer [Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever came first), up to approximately 5 months post-dose]

   Objective response rate (ORR; 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.

7. Disease Control Rate (Unconfirmed) As Assessed in Participants With HER2-Positive Advanced and/or Refractory Gastric, Gastroesophageal Junction Adenocarcinoma, or Breast Cancer [Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever came first), up to approximately 5 months post-dose]

   Disease control rate (DCR; defined as participants who achieved CR, PR, and SD) 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, PR was defined as at least a 30% decrease in the sum of diameters of target lesions, and SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD defined as at least a 20% increase in the sum of diameters of target lesions.

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 gastric or GEJ adenocarcinoma, or breast cancer, with HER2 expression [immunohistochemistry (IHC) 3+, 2+, or 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

• Has any other history or condition that might compromise:

1. Safety of the participant or offspring

2. Safety of study staff

3. Analysis of Results

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	National Taiwan University Hospital	Taipei		Taiwan	100
2	Taipei Veterans General Hospital	Taipei		Taiwan	112

Sponsors and Collaborators

• Daiichi Sankyo Taiwan Ltd., a Daiichi Sankyo Company
• 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 Taiwan Ltd., a Daiichi Sankyo Company
• ClinicalTrials.gov Identifier: NCT03368196
• Other Study ID Numbers: DS8201-A-A103
• First Posted: Dec 11, 2017
• Last Update Posted: Aug 3, 2022
• Last Verified: Aug 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 Taiwan Ltd., a Daiichi Sankyo Company: Stomach cancer; Cancer where the esophagus meets the stomach; Human epidermal growth factor 2; HER2; Breast Cancer; Adenocarcinoma, Gastroesophageal Junction (GEJ); Gastric Cancer; Antibody drug conjugate (ADC); Oncology
• Additional relevant MeSH terms: Adenocarcinoma; Breast Neoplasms

Study Results

Participant Flow

Recruitment Details	A total of 12 participants who met all inclusion criteria and no exclusion criteria were enrolled and received treatment in Taiwan.
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 DS-8201a administered by intravenous infusion on Day 1 of each cycle, once every 3 weeks.
Period Title: Overall Study
STARTED	12
COMPLETED	12
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	DS-8201a
Arm/Group Description	Participants who received 6.4 mg/kg DS-8201a administered by intravenous infusion on Day 1 of each cycle, once every 3 weeks.
Overall Participants	12
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	11 91.7%
>=65 years	1 8.3%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	54.8 (8.73)
Sex: Female, Male (Count of Participants)
Female	12 100%
Male	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	12 100%
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]
Taiwan	12 100%

Outcome Measures

1. Primary Outcome

Title	Treatment-emergent Adverse Events Following Treatment With DS-8201a (Trastuzumab Deruxtecan)
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 came first), up to approximately 5 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 DS-8201a administered by intravenous infusion on Day 1 of each cycle, once every 3 weeks.
Measure Participants	12
Any TEAE	12 100%
Any drug-related TEAE	12 100%
Any TEAE of CTCAE Grade ≥3	7 58.3%
Any drug-related TEAE of CTCAE Grade ≥3	6 50%
Any serious TEAE	2 16.7%
Any drug-related serious TEAE	1 8.3%
Any serious TEAE of CTCAE Grade ≥3	2 16.7%
Any drug-related serious TEAE of CTCAE Grade ≥3	1 8.3%
Any TEAE leading to drug withdrawal	0 0%
Any TEAE leading to dose reduction	2 16.7%
Any drug-related TEAE leading to dose reduction	2 16.7%
Any TEAE leading to dose interruption	5 41.7%
Any drug-related TEAE leading to dose interruption	5 41.7%
Any TEAE leading to death	0 0%

2. Secondary Outcome

Title	Pharmacokinetic Parameter of Maximum (Peak) Observed Serum Concentration (Cmax) Following Cycle 1 and Cycle 3 Treatment With DS-8201a (Trastuzumab Deruxtecan)
Description	Maximum 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; Cycles 2, 4, 6 and 8, Day 1: BI and EOI

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 DS-8201a administered by intravenous infusion on Day 1 of each cycle, once every 3 weeks.
Measure Participants	12
DS-8201a, Cycle 1	157 (19.1)
DS-8201a, Cycle 3	163 (19.5)
Total Anti-HER2 antibody, Cycle 1	150 (22.6)
Total Anti-HER2 antibody, Cycle 3	154 (16.6)

3. Secondary Outcome

Title	Pharmacokinetic Parameter of Maximum (Peak) Observed Serum Concentration (Cmax) of MAAA-1181a Following Cycle 1 and Cycle 3 Treatment With DS-8201a (Trastuzumab Deruxtecan)
Description	Maximum concentration (Cmax) of MAAA-1181a 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; Cycles 2, 4, 6 and 8, Day 1: BI and EOI

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 DS-8201a administered by intravenous infusion on Day 1 of each cycle, once every 3 weeks.
Measure Participants	12
MAAA-1181a, Cycle 1	11.9 (3.79)
MAAA-1181a, Cycle 3	9.01 (1.36)

4. Secondary Outcome

Title	Pharmacokinetic Parameter of Area Under the Serum Concentration-time Curve During Dosing Interval (AUCtau) Following Cycle 1 and Cycle 3 Treatment With DS-8201a (Trastuzumab Deruxtecan)
Description	Area under the serum concentration-time curve during dosing interval (AUCtau) 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; Cycles 2, 4, 6 and 8, Day 1: BI and EOI

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 DS-8201a administered by intravenous infusion on Day 1 of each cycle, once every 3 weeks.
Measure Participants	12
DS-8201a, Cycle 1	631 (173)
DS-8201a, Cycle 3	991 (109)
Total Anti-HER2 antibody, Cycle 1	821 (312)
Total Anti-HER2 antibody, Cycle 3	1180 (208)

5. Secondary Outcome

Title	Pharmacokinetic Parameter of Area Under the Serum Concentration-time Curve During Dosing Interval (AUCtau) of MAAA-1181a Following Cycle 1 and Cycle 3 Treatment With DS-8201a (Trastuzumab Deruxtecan)
Description	Area under the serum concentration-time curve during dosing interval (AUCtau) of MAAA-1181a 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; Cycles 2, 4, 6 and 8, Day 1: BI and EOI

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 DS-8201a administered by intravenous infusion on Day 1 of each cycle, once every 3 weeks.
Measure Participants	12
MAAA-1181a, Cycle 1	36.1 (9.71)
MAAA-1181a, Cycle 3	41.3 (5.06)

6. Secondary Outcome

Title	Best Overall Response By The Investigator's Assessment (Unconfirmed) in Participants With HER2-Positive Advanced and/or Refractory Gastric, Gastroesophageal Junction Adenocarcinoma, or Breast Cancer
Description	Best overall response (BOR) was assessed by the investigator based on Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. Complete 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 withdrawal of consent, progressive disease, or unacceptable toxicity (whichever came first), up to approximately 5 months post-dose

Outcome Measure Data

Analysis Population Description

Response was assessed in the Response Evaluable Set.

Arm/Group Title	DS-8201a
Arm/Group Description	Participants who received 6.4 mg/kg DS-8201a administered by intravenous infusion on Day 1 of each cycle, once every 3 weeks.
Measure Participants	11
Complete response (CR)	0 0%
Partial response (PR)	4 33.3%
Stable disease (SD)	7 58.3%
Non-Complete Response (CR)/Non-Progressive Disease (PD)	0 0%
Progressive Disease (PD)	0 0%
Non-evaluable (NE)	0 0%

7. Secondary Outcome

Title	Objective Response Rate (Unconfirmed) As Assessed in Participants With HER2-Positive Advanced and/or Refractory Gastric, Gastroesophageal Junction Adenocarcinoma, or Breast Cancer
Description	Objective response rate (ORR; 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.
Time Frame	Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever came first), up to approximately 5 months post-dose

Outcome Measure Data

Analysis Population Description

Response was evaluated in the Response Evaluable Set.

Arm/Group Title	DS-8201a
Arm/Group Description	Participants who received 6.4 mg/kg DS-8201a administered by intravenous infusion on Day 1 of each cycle, once every 3 weeks.
Measure Participants	11
Count of Participants [Participants]	4 33.3%

8. Secondary Outcome

Title	Disease Control Rate (Unconfirmed) As Assessed in Participants With HER2-Positive Advanced and/or Refractory Gastric, Gastroesophageal Junction Adenocarcinoma, or Breast Cancer
Description	Disease control rate (DCR; defined as participants who achieved CR, PR, and SD) 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, PR was defined as at least a 30% decrease in the sum of diameters of target lesions, and SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD defined as at least a 20% increase in the sum of diameters of target lesions.
Time Frame	Baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever came first), up to approximately 5 months post-dose

Outcome Measure Data

Analysis Population Description

Response was evaluated in the Response Evaluable Set.

Arm/Group Title	DS-8201a
Arm/Group Description	Participants who received 6.4 mg/kg DS-8201a administered by intravenous infusion on Day 1 of each cycle, once every 3 weeks.
Measure Participants	11
Count of Participants [Participants]	11 91.7%

Adverse Events

Time Frame	Adverse events were assessed from baseline up to withdrawal of consent, progressive disease, or unacceptable toxicity (whichever came first), up to approximately 5 months.
Arm/Group Title	DS-8201a
Arm/Group Description	Participants who received 6.4 mg/kg DS-8201a administered by intravenous infusion on Day 1 of each cycle, once every 3 weeks.
All Cause Mortality
	DS-8201a
	Affected / at Risk (%)	# Events
Total	0/12 (0%)
Serious Adverse Events
	DS-8201a
	Affected / at Risk (%)	# Events
Total	2/12 (16.7%)
Blood and lymphatic system disorders
Febrile neutropenia	1/12 (8.3%)
Infections and infestations
Urinary tract infection	1/12 (8.3%)
Other (Not Including Serious) Adverse Events
	DS-8201a
	Affected / at Risk (%)	# Events
Total	12/12 (100%)
Blood and lymphatic system disorders
Febrile neutropenia	1/12 (8.3%)
Anaemia	4/12 (33.3%)
Eye disorders
Conjunctival haemorrhage	1/12 (8.3%)
Dry eye	1/12 (8.3%)
Punctate keratitis	1/12 (8.3%)
Vision blurred	1/12 (8.3%)
Gastrointestinal disorders
Nausea	7/12 (58.3%)
Stomatitis	3/12 (25%)
Abdominal distension	2/12 (16.7%)
Constipation	2/12 (16.7%)
Diarrhoea	2/12 (16.7%)
Abdominal pain	1/12 (8.3%)
Dental caries	1/12 (8.3%)
Gastritis	1/12 (8.3%)
Gastrooesophageal reflux disease	1/12 (8.3%)
Haemorrhoids	1/12 (8.3%)
Vomiting	1/12 (8.3%)
General disorders
Fatigue	3/12 (25%)
Influenza like illness	1/12 (8.3%)
Oedema peripheral	1/12 (8.3%)
Pyrexia	1/12 (8.3%)
Infections and infestations
Cellulitis	2/12 (16.7%)
Gastroenteritis	1/12 (8.3%)
Tinea pedis	1/12 (8.3%)
Upper respiratory tract infection	1/12 (8.3%)
Urinary tract infection	1/12 (8.3%)
Investigations
Platelet count decreased	7/12 (58.3%)
Aspartate aminotransferase increased	6/12 (50%)
White blood cell count decreased	5/12 (41.7%)
Alanine aminotransferase increased	4/12 (33.3%)
Blood bilirubin increased	3/12 (25%)
Weight decreased	3/12 (25%)
Blood alkaline phosphatase increased	2/12 (16.7%)
Neutrophil count decreased	2/12 (16.7%)
Ejection fraction decreased	1/12 (8.3%)
Liver function test increased	1/12 (8.3%)
Lymphocyte count decreased	1/12 (8.3%)
Metabolism and nutrition disorders
Decreased appetite	4/12 (33.3%)
Hypoalbuminaemia	1/12 (8.3%)
Hypokalaemia	1/12 (8.3%)
Hypomagnesaemia	1/12 (8.3%)
Musculoskeletal and connective tissue disorders
Back pain	2/12 (16.7%)
Gouty arthritis	1/12 (8.3%)
Intervertebral disc protusion	1/12 (8.3%)
Pain in extremity	1/12 (8.3%)
Nervous system disorders
Dizziness	1/12 (8.3%)
Hypoaesthesia	1/12 (8.3%)
Psychiatric disorders
Insomnia	1/12 (8.3%)
Renal and urinary disorders
Hydronephrosis	1/12 (8.3%)
Respiratory, thoracic and mediastinal disorders
Cough	1/12 (8.3%)
Oropharyngeal pain	1/12 (8.3%)
Skin and subcutaneous tissue disorders
Alopecia	2/12 (16.7%)
Skin hyperpigmentation	2/12 (16.7%)
Rash	1/12 (8.3%)
Skin hypopigmentation	1/12 (8.3%)

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.