A Comparative Study in Chinese Subjects With Chemotherapy Naïve Stage IV Melanoma Receiving Ipilimumab (3 mg/kg) vs. Dacarbazine

• Sponsor: Bristol-Myers Squibb (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02545075
• Collaborator: (none)
• Enrollment: 182
• Locations: 8
• Arms: 2
• Actual Duration (Months): 41.6
• Patients Per Site: 22.8
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether Ipilimumab will extend the life of chinese patients with Chemotherapy Naive Stage IV Melanoma more than Dacarbazine as well as to examine safety in this patient population.

Condition or Disease	Intervention/Treatment	Phase
Melanoma	Drug: Ipilimumab; Drug: Dacarbazine	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 182 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized, Open-Label, Two-arm, Comparative Study in Chinese Subjects With Chemotherapy Naïve Stage IV Melanoma Receiving Ipilimumab (3 mg/kg) vs. Dacarbazine
• Actual Study Start Date: Oct 31, 2015
• Actual Primary Completion Date: Apr 19, 2019
• Actual Study Completion Date: Apr 19, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ipilimumab Intravenously (IV) 3 mg/kg every 3 weeks (at week 1,4,7,10) and thereafter (q3w/4 doses) at the time of progression	Drug: Ipilimumab; Other Names: MDX-010
Experimental: Dacarbazine IV solution 250 mg/m2 (Day 1-5, every 3weeks/at week 1, 4, 7, 10,13,16,19,22)	Drug: Dacarbazine; Other Names: DTIC

Outcome Measures

Primary Outcome Measures

1. Two-Years Survival Rate [24 months]

   Two-year survival rate is defined as the probability that a subject is alive at 2 years following the randomization date and will be estimated via the Kaplan-Meier (KM) method.

Secondary Outcome Measures

1. One-Year Survival Rate [Approximately 43 months]

   Survival rate at 1 year is defined as the probability that a subject is alive at 1 year following the randomization date and will be estimated via the Kaplan-Meier (KM) method.

2. Overall Survival (OS) [Approximately 43 months]

   OS is defined for each subject as the time between randomization date and the date of death (of any cause).

3. Progression Free Survival ( PFS) [Approximately 43 months]

   PFS is defined for each subject as the time between randomization date and the date of progression or death, whichever occurs first.

4. Disease Control Rate ( DCR ) [Approximately 43 months]

   Primary DCR is defined as the number of subjects in the arm with Best Overall Response (BOR) of complete response (CR), partial response (PR), or stable disease (SD), divided by the total number of randomized subjects in the arm.

5. Best Overall Response Rate ( BORR ) [Approximately 43 months]

   BORR definition is defined as the number of subjects in the arm with a BOR of CR or PR, divided by the total number of randomized subjects in the arm.

6. Duration of Response ( DoR) [Approximately 43 months]

   DoR definition for the response evaluable subjects whose BOR is CR or PR is defined as the time between the date of response of CR or PR (whichever occurs first) and the first date of progressive disease (PD) or the date of death (whichever occurs first).

7. Duration of Stable Disease ( DoSD ) [Approximately 43 months]

   Primary duration of stable disease (DoSD) definition for the randomized subjects whose BOR is SD is defined as the time between the randomization date and the first date of PD or the date of death (whichever occurs first)."

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

• Chinese males and females ≥ 18 years of age

• Histologic diagnosis of malignant melanoma

• Chemotherapy naive Stage IV melanoma (AJCC 2010)

• Life expectancy of ≥ 16 weeks

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

Exclusion Criteria:

• Evidence of brain metastases on brain imaging

• Primary ocular or mucosal melanoma

• Any other malignancy from which the patient has been disease-free for less than 5 years

• BRAF status cannot be determined by Screening test

• Human Immunodeficiency Virus (HIV) positive or hepatitis B surface antigen (HBsAg) positive, or active Hepatitis C infection

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Local Institution	Nanjing	Jiangsu	China	210000
2	Local Institution	Changchun	Jilin	China	130021
3	Local Institution	Xi'an	Shanxi	China	710038
4	Local Institution	Tianjing	Tianjin	China	300060
5	Local Institution	Hanghzou	Zhejiang	China
6	Local Institution	Beijing		China	100142
7	Local Institution	Kunming		China
8	Local Institution	Shanghai		China	200032

Sponsors and Collaborators

• Bristol-Myers Squibb

Investigators

• Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Study Documents (Full-Text)

• Statistical Analysis Plan - Jan 17, 2019
• Study Protocol - Jun 28, 2019

More Information

Additional Information:

• BMS clinical trial educational resource

Publications

None provided.

• Responsible Party: Bristol-Myers Squibb
• ClinicalTrials.gov Identifier: NCT02545075
• Other Study ID Numbers: CA184-248
• First Posted: Sep 9, 2015
• Last Update Posted: May 19, 2020
• Last Verified: May 1, 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Additional relevant MeSH terms: Melanoma; Ipilimumab; Dacarbazine

Study Results

Participant Flow

Pre-assignment Detail	182 participants were enrolled, 68 were not randomized, reasons for not being randomized:3 participants withdrew consent and 65 no longer meet study criteria.

Arm/Group Title	Ipilimumab (3 mg/kg)	Dacarbazine (250 mg/m2)
Arm/Group Description	Ipilimumab 3 mg/kg to be administered via intravenous infusion over 90 minutes at Weeks 1, 4, 7 and 10, for a total of four doses in Induction (and Re-Induction for those randomized to the ipilimumab arm who qualify)	DTIC 250 mg/m2 - Day 1 - 5, to be administered via intravenous infusion at Weeks 1, 4, 7, 10, 13, 16,19, and 22.
Period Title: Randomization
STARTED	122	60
COMPLETED	122	53
NOT COMPLETED	0	7
Period Title: Randomization
STARTED	122	53
COMPLETED	0	0
NOT COMPLETED	122	53

Baseline Characteristics

Arm/Group Title	Ipilimumab (3 mg/kg)	Dacarbazine (250 mg/m2)	Total
Arm/Group Description	Ipilimumab 3 mg/kg to be administered via intravenous infusion over 90 minutes at Weeks 1, 4, 7 and 10, for a total of four doses in Induction (and Re-Induction for those randomized to the ipilimumab arm who qualify)	DTIC 250 mg/m2 - Day 1 - 5, to be administered via intravenous infusion at Weeks 1, 4, 7, 10, 13, 16,19, and 22.	Total of all reporting groups
Overall Participants	122	60	182
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	53.6 (13.69)	54.3 (13.39)	53.8 (13.56)
Sex: Female, Male (Count of Participants)
Female	53 43.4%	26 43.3%	79 43.4%
Male	69 56.6%	34 56.7%	103 56.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	0 0%	0 0%	0 0%
Unknown or Not Reported	122 100%	60 100%	182 100%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	122 100%	60 100%	182 100%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	0 0%	0 0%	0 0%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Two-Years Survival Rate
Description	Two-year survival rate is defined as the probability that a subject is alive at 2 years following the randomization date and will be estimated via the Kaplan-Meier (KM) method.
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

All randomized participants

Arm/Group Title	Ipilimumab (3 mg/kg)	Dacarbazine (250 mg/m2)
Arm/Group Description	Ipilimumab 3 mg/kg to be administered via intravenous infusion over 90 minutes at Weeks 1, 4, 7 and 10, for a total of four doses in Induction (and Re-Induction for those randomized to the ipilimumab arm who qualify)	DTIC 250 mg/m2 - Day 1 - 5, to be administered via intravenous infusion at Weeks 1, 4, 7, 10, 13, 16,19, and 22.
Measure Participants	122	60
Number (80% Confidence Interval) [Percentage of Participants]	33.98 27.9%	34.09 56.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ipilimumab (3 mg/kg), Dacarbazine (250 mg/m2)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5059
	Comments
	Method	Chi-squared
	Comments	One-sided p-value based on unstratified chi-square test

2. Secondary Outcome

Title	One-Year Survival Rate
Description	Survival rate at 1 year is defined as the probability that a subject is alive at 1 year following the randomization date and will be estimated via the Kaplan-Meier (KM) method.
Time Frame	Approximately 43 months

Outcome Measure Data

Analysis Population Description

All randomized participants

Arm/Group Title	Ipilimumab (3 mg/kg)	Dacarbazine (250 mg/m2)
Arm/Group Description	Ipilimumab 3 mg/kg to be administered via intravenous infusion over 90 minutes at Weeks 1, 4, 7 and 10, for a total of four doses in Induction (and Re-Induction for those randomized to the ipilimumab arm who qualify)	DTIC 250 mg/m2 - Day 1 - 5, to be administered via intravenous infusion at Weeks 1, 4, 7, 10, 13, 16,19, and 22.
Measure Participants	122	60
Number (80% Confidence Interval) [Percentage of Participants]	61.68 50.6%	64.11 106.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ipilimumab (3 mg/kg), Dacarbazine (250 mg/m2)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6202
	Comments
	Method	Chi-squared
	Comments	One-sided unstratified chi-square

3. Secondary Outcome

Title	Overall Survival (OS)
Description	OS is defined for each subject as the time between randomization date and the date of death (of any cause).
Time Frame	Approximately 43 months

Outcome Measure Data

Analysis Population Description

All randomized participants

Arm/Group Title	Ipilimumab (3 mg/kg)	Dacarbazine (250 mg/m2)
Arm/Group Description	Ipilimumab 3 mg/kg to be administered via intravenous infusion over 90 minutes at Weeks 1, 4, 7 and 10, for a total of four doses in Induction (and Re-Induction for those randomized to the ipilimumab arm who qualify)	DTIC 250 mg/m2 - Day 1 - 5, to be administered via intravenous infusion at Weeks 1, 4, 7, 10, 13, 16,19, and 22.
Measure Participants	122	60
Median (80% Confidence Interval) [Months]	15.08	14.55

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ipilimumab (3 mg/kg), Dacarbazine (250 mg/m2)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7267
	Comments
	Method	Log Rank
	Comments	One-sided p-value from Log-rank Test stratified by M substage (M1a+M1b vs. M1c)
Method of Estimation	Estimation Parameter	Stratified cox proportional hazard model
	Estimated Value	1.13
	Confidence Interval	(2-Sided) 80%; 0.87 to 1.45
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Progression Free Survival ( PFS)
Description	PFS is defined for each subject as the time between randomization date and the date of progression or death, whichever occurs first.
Time Frame	Approximately 43 months

Outcome Measure Data

Analysis Population Description

All randomized participants

Arm/Group Title	Ipilimumab (3 mg/kg)	Dacarbazine (250 mg/m2)
Arm/Group Description	Ipilimumab 3 mg/kg to be administered via intravenous infusion over 90 minutes at Weeks 1, 4, 7 and 10, for a total of four doses in Induction (and Re-Induction for those randomized to the ipilimumab arm who qualify)	DTIC 250 mg/m2 - Day 1 - 5, to be administered via intravenous infusion at Weeks 1, 4, 7, 10, 13, 16,19, and 22.
Measure Participants	122	60
Median (80% Confidence Interval) [Months]	2.60	1.84

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ipilimumab (3 mg/kg), Dacarbazine (250 mg/m2)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2503
	Comments
	Method	Log Rank
	Comments	One-sided p-value from Log-rank Test stratified by M substage (M1a+M1b vs. M1c) and BRAF mutation status as entered into the IVRS
Method of Estimation	Estimation Parameter	Stratified Cox proportional hazard
	Estimated Value	0.90
	Confidence Interval	(2-Sided) 80%; 0.71 to 1.15
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Disease Control Rate ( DCR )
Description	Primary DCR is defined as the number of subjects in the arm with Best Overall Response (BOR) of complete response (CR), partial response (PR), or stable disease (SD), divided by the total number of randomized subjects in the arm.
Time Frame	Approximately 43 months

Outcome Measure Data

Analysis Population Description

All randomized participants

Arm/Group Title	Ipilimumab (3 mg/kg)	Dacarbazine (250 mg/m2)
Arm/Group Description	Ipilimumab 3 mg/kg to be administered via intravenous infusion over 90 minutes at Weeks 1, 4, 7 and 10, for a total of four doses in Induction (and Re-Induction for those randomized to the ipilimumab arm who qualify)	DTIC 250 mg/m2 - Day 1 - 5, to be administered via intravenous infusion at Weeks 1, 4, 7, 10, 13, 16,19, and 22.
Measure Participants	122	60
Number (80% Confidence Interval) [Percentage of participants]	32 26.2%	31.7 52.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ipilimumab (3 mg/kg), Dacarbazine (250 mg/m2)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9932
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.00
	Confidence Interval	(2-Sided) 80%; 0.64 to 1.55
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Best Overall Response Rate ( BORR )
Description	BORR definition is defined as the number of subjects in the arm with a BOR of CR or PR, divided by the total number of randomized subjects in the arm.
Time Frame	Approximately 43 months

Outcome Measure Data

Analysis Population Description

All randomized participants

Arm/Group Title	Ipilimumab (3 mg/kg)	Dacarbazine (250 mg/m2)
Arm/Group Description	Ipilimumab 3 mg/kg to be administered via intravenous infusion over 90 minutes at Weeks 1, 4, 7 and 10, for a total of four doses in Induction (and Re-Induction for those randomized to the ipilimumab arm who qualify)	DTIC 250 mg/m2 - Day 1 - 5, to be administered via intravenous infusion at Weeks 1, 4, 7, 10, 13, 16,19, and 22.
Measure Participants	122	60
Number (80% Confidence Interval) [Percentage of participants]	8.2 6.7%	8.3 13.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ipilimumab (3 mg/kg), Dacarbazine (250 mg/m2)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9738
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.98
	Confidence Interval	(2-Sided) 80%; 0.48 to 2.03
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Duration of Response ( DoR)
Description	DoR definition for the response evaluable subjects whose BOR is CR or PR is defined as the time between the date of response of CR or PR (whichever occurs first) and the first date of progressive disease (PD) or the date of death (whichever occurs first).
Time Frame	Approximately 43 months

Outcome Measure Data

Analysis Population Description

All randomized participants with response

Arm/Group Title	Ipilimumab (3 mg/kg)	Dacarbazine (250 mg/m2)
Arm/Group Description	Ipilimumab 3 mg/kg to be administered via intravenous infusion over 90 minutes at Weeks 1, 4, 7 and 10, for a total of four doses in Induction (and Re-Induction for those randomized to the ipilimumab arm who qualify)	DTIC 250 mg/m2 - Day 1 - 5, to be administered via intravenous infusion at Weeks 1, 4, 7, 10, 13, 16,19, and 22.
Measure Participants	10	5
Median (80% Confidence Interval) [Months]	8.99	7.98

8. Secondary Outcome

Title	Duration of Stable Disease ( DoSD )
Description	Primary duration of stable disease (DoSD) definition for the randomized subjects whose BOR is SD is defined as the time between the randomization date and the first date of PD or the date of death (whichever occurs first)."
Time Frame	Approximately 43 months

Outcome Measure Data

Analysis Population Description

All randomized participants with BOR as stable disease

Arm/Group Title	Ipilimumab (3 mg/kg)	Dacarbazine (250 mg/m2)
Arm/Group Description	Ipilimumab 3 mg/kg to be administered via intravenous infusion over 90 minutes at Weeks 1, 4, 7 and 10, for a total of four doses in Induction (and Re-Induction for those randomized to the ipilimumab arm who qualify)	DTIC 250 mg/m2 - Day 1 - 5, to be administered via intravenous infusion at Weeks 1, 4, 7, 10, 13, 16,19, and 22.
Measure Participants	29	14
Median (80% Confidence Interval) [Months]	6.83	9.40

Adverse Events

Time Frame	Approximately 43 months
Adverse Event Reporting Description	Adverse events are reported between first dose and 90 days after last dose of study therapy.
Arm/Group Title	Ipilimumab		Dacarbazine
Arm/Group Description	Ipilimumab 3 mg/kg to be administered via intravenous infusion over 90 minutes at Weeks 1, 4, 7 and 10, for a total of four doses in Induction (and Re-Induction for those randomized to the ipilimumab arm who qualify)		DTIC 250 mg/m2 - Day 1 - 5, to be administered via intravenous infusion at Weeks 1, 4, 7, 10, 13, 16,19, and 22.
All Cause Mortality
	Ipilimumab		Dacarbazine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	93/122 (76.2%)		39/53 (73.6%)
Serious Adverse Events
	Ipilimumab		Dacarbazine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	34/122 (27.9%)		12/53 (22.6%)
Blood and lymphatic system disorders
Anaemia	1/122 (0.8%)		1/53 (1.9%)
Bone marrow failure	0/122 (0%)		1/53 (1.9%)
Endocrine disorders
Hypophysitis	1/122 (0.8%)		0/53 (0%)
Hypopituitarism	1/122 (0.8%)		0/53 (0%)
Gastrointestinal disorders
Abdominal pain	2/122 (1.6%)		0/53 (0%)
Ascites	1/122 (0.8%)		0/53 (0%)
Diarrhoea	2/122 (1.6%)		0/53 (0%)
Gastrointestinal haemorrhage	1/122 (0.8%)		0/53 (0%)
Haematemesis	0/122 (0%)		1/53 (1.9%)
General disorders
Oedema peripheral	1/122 (0.8%)		0/53 (0%)
Pyrexia	1/122 (0.8%)		0/53 (0%)
Sudden death	1/122 (0.8%)		0/53 (0%)
Hepatobiliary disorders
Cholecystitis acute	1/122 (0.8%)		0/53 (0%)
Immune system disorders
Hypersensitivity	1/122 (0.8%)		0/53 (0%)
Infections and infestations
Cellulitis	1/122 (0.8%)		0/53 (0%)
Skin infection	0/122 (0%)		1/53 (1.9%)
Injury, poisoning and procedural complications
Overdose	0/122 (0%)		1/53 (1.9%)
Wrist fracture	1/122 (0.8%)		0/53 (0%)
Investigations
Blood bilirubin increased	1/122 (0.8%)		0/53 (0%)
Metabolism and nutrition disorders
Electrolyte imbalance	0/122 (0%)		1/53 (1.9%)
Hypoproteinaemia	0/122 (0%)		1/53 (1.9%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant neoplasm progression	16/122 (13.1%)		7/53 (13.2%)
Nervous system disorders
Cerebral infarction	1/122 (0.8%)		0/53 (0%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome	1/122 (0.8%)		0/53 (0%)
Dyspnoea	1/122 (0.8%)		0/53 (0%)
Interstitial lung disease	1/122 (0.8%)		0/53 (0%)
Pleural effusion	1/122 (0.8%)		0/53 (0%)
Pulmonary embolism	0/122 (0%)		1/53 (1.9%)
Skin and subcutaneous tissue disorders
Erythema	1/122 (0.8%)		0/53 (0%)
Rash	2/122 (1.6%)		1/53 (1.9%)
Vascular disorders
Pelvic venous thrombosis	1/122 (0.8%)		0/53 (0%)
Other (Not Including Serious) Adverse Events
	Ipilimumab		Dacarbazine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	118/122 (96.7%)		48/53 (90.6%)
Blood and lymphatic system disorders
Anaemia	8/122 (6.6%)		3/53 (5.7%)
Bone marrow failure	0/122 (0%)		4/53 (7.5%)
Leukopenia	0/122 (0%)		4/53 (7.5%)
Neutropenia	1/122 (0.8%)		3/53 (5.7%)
Cardiac disorders
Sinus bradycardia	4/122 (3.3%)		3/53 (5.7%)
Supraventricular tachycardia	8/122 (6.6%)		0/53 (0%)
Gastrointestinal disorders
Abdominal distension	5/122 (4.1%)		4/53 (7.5%)
Constipation	14/122 (11.5%)		14/53 (26.4%)
Diarrhoea	7/122 (5.7%)		4/53 (7.5%)
Gastrointestinal disorder	4/122 (3.3%)		8/53 (15.1%)
Nausea	18/122 (14.8%)		22/53 (41.5%)
Vomiting	14/122 (11.5%)		5/53 (9.4%)
General disorders
Asthenia	12/122 (9.8%)		8/53 (15.1%)
Fatigue	11/122 (9%)		6/53 (11.3%)
Oedema peripheral	7/122 (5.7%)		2/53 (3.8%)
Pain	15/122 (12.3%)		6/53 (11.3%)
Pyrexia	23/122 (18.9%)		10/53 (18.9%)
Hepatobiliary disorders
Liver injury	1/122 (0.8%)		5/53 (9.4%)
Investigations
Alanine aminotransferase increased	31/122 (25.4%)		19/53 (35.8%)
Aspartate aminotransferase increased	22/122 (18%)		17/53 (32.1%)
Bilirubin conjugated increased	9/122 (7.4%)		5/53 (9.4%)
Blood albumin decreased	15/122 (12.3%)		5/53 (9.4%)
Blood alkaline phosphatase increased	6/122 (4.9%)		4/53 (7.5%)
Blood bilirubin increased	14/122 (11.5%)		5/53 (9.4%)
Blood bilirubin unconjugated increased	7/122 (5.7%)		1/53 (1.9%)
Blood chloride decreased	7/122 (5.7%)		5/53 (9.4%)
Blood cholesterol increased	6/122 (4.9%)		4/53 (7.5%)
Blood glucose increased	10/122 (8.2%)		5/53 (9.4%)
Blood lactate dehydrogenase increased	28/122 (23%)		3/53 (5.7%)
Blood potassium decreased	1/122 (0.8%)		3/53 (5.7%)
Blood sodium decreased	9/122 (7.4%)		6/53 (11.3%)
Blood thyroid stimulating hormone decreased	11/122 (9%)		0/53 (0%)
Blood thyroid stimulating hormone increased	27/122 (22.1%)		4/53 (7.5%)
Blood triglycerides increased	15/122 (12.3%)		5/53 (9.4%)
Blood uric acid increased	7/122 (5.7%)		3/53 (5.7%)
Blood urine present	2/122 (1.6%)		3/53 (5.7%)
C-reactive protein increased	25/122 (20.5%)		4/53 (7.5%)
Electrocardiogram T wave abnormal	8/122 (6.6%)		3/53 (5.7%)
Gamma-glutamyltransferase increased	17/122 (13.9%)		11/53 (20.8%)
Haemoglobin decreased	22/122 (18%)		6/53 (11.3%)
Lymphocyte count decreased	2/122 (1.6%)		3/53 (5.7%)
Neutrophil count decreased	6/122 (4.9%)		8/53 (15.1%)
Neutrophil count increased	16/122 (13.1%)		2/53 (3.8%)
Neutrophil percentage decreased	7/122 (5.7%)		1/53 (1.9%)
Neutrophil percentage increased	11/122 (9%)		0/53 (0%)
Platelet count decreased	3/122 (2.5%)		5/53 (9.4%)
Platelet count increased	13/122 (10.7%)		1/53 (1.9%)
Protein urine present	4/122 (3.3%)		4/53 (7.5%)
Thyroxine free decreased	7/122 (5.7%)		1/53 (1.9%)
Thyroxine free increased	8/122 (6.6%)		0/53 (0%)
Tri-iodothyronine decreased	7/122 (5.7%)		0/53 (0%)
Tri-iodothyronine free decreased	9/122 (7.4%)		0/53 (0%)
Tri-iodothyronine free increased	7/122 (5.7%)		0/53 (0%)
Weight decreased	18/122 (14.8%)		3/53 (5.7%)
White blood cell count decreased	7/122 (5.7%)		15/53 (28.3%)
White blood cell count increased	21/122 (17.2%)		6/53 (11.3%)
White blood cells urine positive	10/122 (8.2%)		2/53 (3.8%)
Metabolism and nutrition disorders
Decreased appetite	27/122 (22.1%)		17/53 (32.1%)
Hypokalaemia	6/122 (4.9%)		5/53 (9.4%)
Hyponatraemia	6/122 (4.9%)		4/53 (7.5%)
Musculoskeletal and connective tissue disorders
Back pain	6/122 (4.9%)		3/53 (5.7%)
Pain in extremity	8/122 (6.6%)		1/53 (1.9%)
Nervous system disorders
Dizziness	4/122 (3.3%)		5/53 (9.4%)
Headache	8/122 (6.6%)		0/53 (0%)
Psychiatric disorders
Insomnia	8/122 (6.6%)		1/53 (1.9%)
Respiratory, thoracic and mediastinal disorders
Cough	13/122 (10.7%)		4/53 (7.5%)
Skin and subcutaneous tissue disorders
Pruritus	27/122 (22.1%)		2/53 (3.8%)
Rash	33/122 (27%)		3/53 (5.7%)
Vascular disorders
Hypertension	7/122 (5.7%)		0/53 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.