A Study Assessing Saxagliptin Treatment in Subjects With Type 2 Diabetes Who Are Not Controlled With Diet and Exercise

• Sponsor: AstraZeneca (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00374907
• Collaborator: (none)
• Enrollment: 156
• Locations: 3
• Arms: 2
• Duration (Months): 39
• Patients Per Site: 52
• Patients Per Site Per Month: 1.3

Study Details

Study Description

Brief Summary

The purpose of this clinical research study is to learn whether Saxagliptin can improve the body's ability to make its own insulin and lower blood sugar in people with type 2 diabetes

Condition or Disease	Intervention/Treatment	Phase
Type 2 Diabetes	Drug: Saxagliptin; Drug: Placebo; Drug: Metformin (blinded); Drug: Metformin (open-label)	Phase 3

Detailed Description

All subjects will participate in a lead-in period, and qualifying subjects will continue into a short-term randomized treatment period. Subjects who complete the short-term period will be eligible to enter the long term extension period. Also, subjects who have an elevated blood sugar that requires additional medication for blood sugar control will be eligible to receive open-label metformin added onto their blinded study medication

Study Design

• Study Type: Interventional
• Actual Enrollment: 156 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Mechanism of Action and Efficacy of Saxagliptin (BMS-477118) in the Treatment of Type 2 Diabetic Patients
• Study Start Date: Sep 1, 2006
• Actual Primary Completion Date: Jan 1, 2008
• Actual Study Completion Date: Dec 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Saxagliptin (A) Metformin 500-1500 mg (open-label, as needed for rescue in LT)	Drug: Saxagliptin; Tablet, Oral, 5 mg, Once daily, (up to 12 weeks ST, up to 104 weeks LT); Other Names: BMS-477118
Placebo Comparator: Placebo (ST) / Metformin (LT) (B) Metformin 500-1500 mg (open-label, as needed for rescue in LT)	Drug: Placebo; Tablet, Oral, 0 mg, Once daily (up to 12 weeks ST); Drug: Metformin (blinded); Tablet, Oral, 500 mg titrated to 1000 mg, Once daily (up to 104 weeks LT, starting at Week 12); Drug: Metformin (open-label); Tablets, Oral, 500-1500 mg, as needed (starting in LT)

Outcome Measures

Primary Outcome Measures

1. Insulin Secretion Rate Area Under the Curve (AUC) During Intravenous (IV)-Oral Hyperglycemic Clamp - Percent Change From Baseline at Week 12 [Baseline, Week 12]

   Adjusted percent change in the insulin secretion rate AUC during a hyperglycemic clamp with an enteral glucose load [intravenous-oral hyperglycemic clamp (180-480 minutes)] at Week 12. The method used for calculating the insulin secretion rate was C-peptide deconvolution.

Secondary Outcome Measures

1. Insulin Secretion Rate AUC During IV Hyperglycemic Clamp - Percent Change From Baseline at Week 12 [Baseline, Week 12]

   Adjusted percent change in the insulin secretion rate AUC during an intravenous hyperglycemic clamp (120-180 minutes) at Week 12. The method used for calculating the insulin secretion rate was C-peptide deconvolution.

Other Outcome Measures

1. Overall Summary of Adverse Events (AEs) Serious AEs (SAEs), Discontinuations, and Deaths During the ST + LT Treatment Period [116 weeks]

   AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. SAE=any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in development of drug dependency or drug abuse, is an important medical event. Related events=relationship of certain, probable, possible, or missing.

2. Marked Laboratory Abnormalities - During ST + LT Treatment Period [116 weeks]

   A laboratory value was considered a marked abnormality if it is outside the pre-defined criteria for marked abnormality and the on-treatment value was more extreme (farther from the limit) than the baseline value. Pre-Rx=pretreatment; ULN=upper limit of normal; ALP=alkaline phosphatase; AST=aspartate aminotransferase; ALT=alanine aminotransferase; BUN=blood urea nitrogen; unspec.=unspecified; sodium serum low: <0.9 x Pre-Rx & <=130mEq/L / high: >1.1 x Pre-Rx & >=150mEq/L; potassium, serum low: <=0.8 x Pre-Rx & >=6.0mEq/L / high: 1.2 x Pre-Rx & >=6.0mEq/L; LLN=lower limit of normal.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Type 2 diabetes mellitus

• Drug naive

• Hemoglobin A1c (HbA1c) ≥6.0% and ≤8.0%

• Fasting C-peptide ≥1.0 ng/mL

• Body mass index ≤40 kg/m²

Exclusion Criteria:

• Recent cardiac or cerebrovascular event

• Elevated serum creatinine

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Va San Diego Healthcare System	San Diego	California	United States	92161
2	Pennington Biomedical Research Center	Baton Rouge	Louisiana	United States	70808
3	Diabetes & Glandular Disease Research Assoc,, Inc.	San Antonio	Texas	United States	78229

Sponsors and Collaborators

• AstraZeneca

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT00374907
• Other Study ID Numbers: CV181-041
• First Posted: Sep 12, 2006
• Last Update Posted: May 7, 2015
• Last Verified: Mar 1, 2015

• Additional relevant MeSH terms: Diabetes Mellitus, Type 2; Metformin; Saxagliptin

Study Results

Participant Flow

Pre-assignment Detail	156 participants were enrolled in the study; 110 participants failed screening; 10 subjects entered lead-in and discontinued prior to randomization.

Arm/Group Title	Saxagliptin 5 mg	Placebo / Metformin
Arm/Group Description	Tablet, Oral, 5 mg, once daily, up to 12 weeks (short-term) and up to 104 weeks (long-term). Metformin 500-1500 mg (open-label, as needed for rescue in LT).	Placebo Tablet, Oral, 0 mg, once daily, up to 12 weeks; Metformin Tablet, Oral, 500 mg/1000 mg, once daily, up to 104 weeks starting at Week 12 (end of ST period). Metformin 500-1500 mg (open-label, as needed for rescue in LT).
Period Title: 12-Week Short-term Period
STARTED	20	16
COMPLETED	17	15
NOT COMPLETED	3	1
Period Title: 12-Week Short-term Period
STARTED	20	16
Completed 12-week Short Term Period	17	15
COMPLETED	7	2
NOT COMPLETED	13	14

Baseline Characteristics

Arm/Group Title	Saxagliptin 5 mg	Placebo / Metformin	Total
Arm/Group Description	Tablet, Oral, 5 mg, once daily, up to 12 weeks (short-term) and up to 104 weeks (long-term)	Placebo Tablet, Oral, 0 mg, once daily, up to 12 weeks; Metformin Tablet, Oral, 500 mg/1000 mg, once daily, starting at Week 12 and up to 104 weeks	Total of all reporting groups
Overall Participants	20	16	36
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	58	55	55.5
Sex: Female, Male (Count of Participants)
Female	12 60%	10 62.5%	22 61.1%
Male	8 40%	6 37.5%	14 38.9%
Race/Ethnicity, Customized (participants) [Number]
White	16 80%	12 75%	28 77.8%
Black/African American	3 15%	4 25%	7 19.4%
Other	1 5%	0 0%	1 2.8%
Region of Enrollment (participants) [Number]
North America	20 100%	16 100%	36 100%
Body Mass Index (BMI) (kg/m^2) [Median (Full Range) ]
Median (Full Range) [kg/m^2]	33.36	32.31	33.01

Outcome Measures

1. Primary Outcome

Title	Insulin Secretion Rate Area Under the Curve (AUC) During Intravenous (IV)-Oral Hyperglycemic Clamp - Percent Change From Baseline at Week 12
Description	Adjusted percent change in the insulin secretion rate AUC during a hyperglycemic clamp with an enteral glucose load [intravenous-oral hyperglycemic clamp (180-480 minutes)] at Week 12. The method used for calculating the insulin secretion rate was C-peptide deconvolution.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Randomized participants with both a baseline and post-baseline value (up to Week 12).

Arm/Group Title	Short Term Period: Saxagliptin 5 mg	Short Term Period: Placebo
Arm/Group Description	Tablet, Oral, 5 mg, once daily, up to 12 weeks	Tablet, Oral, 0 mg, once daily, up to 12 weeks
Measure Participants	16	15
Geometric Mean (95% Confidence Interval) [Percent Change (Percentage of Baseline)]	15.9	-2.2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Short Term Period: Saxagliptin 5 mg, Short Term Period: Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0350
	Comments	Between-group comparisons significant at alpha = 0.05, significance testing based on hierarchical testing. Primary and secondary endpoints are presented in order of testing.
	Method	ANCOVA
	Comments	Adjusted percent difference for saxagliptin 5 mg vs placebo in Week 12 (LOCF) to baseline ratio. Adjusted for baseline.
Method of Estimation	Estimation Parameter	Adjusted Percent Difference
	Estimated Value	18.5
	Confidence Interval	(2-Sided) 95%; 1.3 to 38.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	ANCOVA model: logarithm(post/pre) = logarithm(pre) treatment

2. Secondary Outcome

Title	Insulin Secretion Rate AUC During IV Hyperglycemic Clamp - Percent Change From Baseline at Week 12
Description	Adjusted percent change in the insulin secretion rate AUC during an intravenous hyperglycemic clamp (120-180 minutes) at Week 12. The method used for calculating the insulin secretion rate was C-peptide deconvolution.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Randomized Participants with both a baseline and post-baseline value (up to Week 12).

Arm/Group Title	Short Term Period: Saxagliptin 5 mg	Short Term Period: Placebo
Arm/Group Description	Tablet, Oral, 5 mg, once daily, up to 12 weeks	Tablet, Oral, 0 mg, once daily, up to 12 weeks
Measure Participants	18	16
Geometric Mean (95% Confidence Interval) [Percent Change (Percentage of Baseline)]	22.6	-4.1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Short Term Period: Saxagliptin 5 mg, Short Term Period: Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0204
	Comments	Between-group comparisons significant at alpha = 0.05, significance testing based on hierarchical testing. Primary and secondary endpoints are presented in order of testing.
	Method	ANCOVA
	Comments	Adjusted percent difference for saxagliptin 5 mg vs placebo in Week 12 (LOCF) to baseline ratio. Adjusted for baseline.
Method of Estimation	Estimation Parameter	Adjusted Percent Difference
	Estimated Value	27.9
	Confidence Interval	(2-Sided) 95%; 4.2 to 57.1
	Parameter Dispersion	Type: Value:
	Estimation Comments	ANCOVA model: logarithm(post/pre) = logarithm(pre) treatment

3. Other Pre-specified Outcome

Title	Overall Summary of Adverse Events (AEs) Serious AEs (SAEs), Discontinuations, and Deaths During the ST + LT Treatment Period
Description	AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. SAE=any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in development of drug dependency or drug abuse, is an important medical event. Related events=relationship of certain, probable, possible, or missing.
Time Frame	116 weeks

Outcome Measure Data

Analysis Population Description

Treated participants

Arm/Group Title	Saxagliptin 5 mg	Placebo / Metformin
Arm/Group Description	Tablet, Oral, 5 mg, once daily, up to 12 weeks (short-term) and up to 104 weeks (long-term)	Placebo Tablet, Oral, 0 mg, once daily, up to 12 weeks; Metformin Tablet, Oral, 500 mg/1000 mg, once daily, starting at Week 12 and up to 104 weeks
Measure Participants	20	16
At Least 1 AE	17 85%	14 87.5%
At Least 1 Related AE	7 35%	6 37.5%
Deaths	0 0%	0 0%
At Least 1 SAE	1 5%	2 12.5%
At Least 1 Related SAE	0 0%	0 0%
Discontinuations Due to SAEs	0 0%	1 6.3%
Discontinuations Due to AEs	0 0%	2 12.5%

4. Other Pre-specified Outcome

Title	Marked Laboratory Abnormalities - During ST + LT Treatment Period
Description	A laboratory value was considered a marked abnormality if it is outside the pre-defined criteria for marked abnormality and the on-treatment value was more extreme (farther from the limit) than the baseline value. Pre-Rx=pretreatment; ULN=upper limit of normal; ALP=alkaline phosphatase; AST=aspartate aminotransferase; ALT=alanine aminotransferase; BUN=blood urea nitrogen; unspec.=unspecified; sodium serum low: <0.9 x Pre-Rx & <=130mEq/L / high: >1.1 x Pre-Rx & >=150mEq/L; potassium, serum low: <=0.8 x Pre-Rx & >=6.0mEq/L / high: 1.2 x Pre-Rx & >=6.0mEq/L; LLN=lower limit of normal.
Time Frame	116 weeks

Outcome Measure Data

Analysis Population Description

Number of Participants Analyzed=Treated participants; n=number of treated subjects with baseline value and at least one value during the ST + LT treatment period.

Arm/Group Title	Saxagliptin 5 mg	Placebo / Metformin
Arm/Group Description	Tablet, Oral, 5 mg, once daily, up to 12 weeks (short-term) and up to 104 weeks (long-term)	Placebo Tablet, Oral, 0 mg, once daily, up to 12 weeks; Metformin Tablet, Oral, 500 mg/1000 mg, once daily, starting at Week 12 and up to 104 weeks
Measure Participants	20	16
Hemoglobin < 8 g/dL (n=0, 0)	0 0%	0 0%
Hematocrit < 0.75 x pre-Rx (n=0, 0)	0 0%	0 0%
Platelets < 50 x 10^9 c/L (n=0, 0)	0 0%	0 0%
Platelets > 1.5 x ULN (n=0, 0)	0 0%	0 0%
Leukocytes < 2 x 1000 c/uL (n=0, 0)	0 0%	0 0%
Neutrophils+Bands <1x1000 c/uL (n=18, 0)	1 5%	0 0%
Eosinophils >0.9x1000 c/uL (n=18, 0)	1 5%	0 0%
Lymphocytes <=0.75x1000 c/uL (n=18, 0)	2 10%	0 0%
ALP >3 x pre-Rx and >ULN (n=0, 0)	0 0%	0 0%
AST >3 x ULN (n=0, 0)	0 0%	0 0%
AST >5 x ULN (n=0, 0)	0 0%	0 0%
ALT >3 x ULN (n=0, 0)	0 0%	0 0%
ALT >5 x ULN (n=0, 0)	0 0%	0 0%
Bilirubin Total >2mg/dL (n=0, 0)	0 0%	0 0%
BUN >2 x pre-Rx and >ULN (n=0, 0)	0 0%	0 0%
Creatinine >2.5 mg/dL (n=0, 0)	0 0%	0 0%
Glucose, Serum Fasting < 50 mg/dL (n=0, 0)	0 0%	0 0%
Glucose, Serum Fasting > 500 mg/dL (n=0, 0)	0 0%	0 0%
Glucose, Serum Unspec. < 50 mg/dL (n=0, 0)	0 0%	0 0%
Glucose, Serum Unspec. > 500 mg/dL (n=0, 0)	0 0%	0 0%
Glucose, Plasma Fasting <50 mg/dL (n=0, 0)	0 0%	0 0%
Glucose,Plasma Fasting >500 mg/dL (n=0, 0)	0 0%	0 0%
Glucose, Plasma Unspec. <50 mg/dL (n=0, 0)	0 0%	0 0%
Glucose, Plasma Unspec. >500 mg/dL (n=18, 16)	8 40%	9 56.3%
Sodium, Serum Low (see description) (n=0, 0)	0 0%	0 0%
Sodium, Serum High (see description) (n=0, 0)	0 0%	0 0%
Potassium, Serum Low (see description) (n=0, 0)	0 0%	0 0%
Potassium, Serum High (see description) (n=0, 0)	0 0%	0 0%
Chloride < 90 mEq/L (n=0, 0)	0 0%	0 0%
Chloride > 120 mEq/L (n=0, 0)	0 0%	0 0%
Albumin < 0.9 LLN (n=0, 0)	0 0%	0 0%
Creatine Kinase > 5 x ULN (n=18, 16)	1 5%	1 6.3%
Uric Acid > 1.5 x ULN (n=0, 0)	0 0%	0 0%
Protein Urine, >=2-4 (n=0, 0)	0 0%	0 0%
Blood Urine >=2-4 (n=18, 0)	1 5%	0 0%
Red Blood Cells Urine >=2-4 (n=0, 0)	0 0%	0 0%
White Blood Cells Urine >=2-4 (n=0, 0)	2 10%	1 6.3%

Adverse Events

Time Frame	Short term period (up to 12 weeks) + long term period (up to 104 weeks)
Arm/Group Title	PLACEBO/METFORMIN		SAXAGLIPTIN 5 MG
Arm/Group Description	Placebo Tablet, Oral, 0 mg, once daily, up to 12 weeks (short term); Metformin Tablet, Oral, 500 mg titrated to 1000 mg, once daily, up to 104 weeks (long term)		Tablet, Oral, 5 mg, once daily, up to 12 weeks (short term); Tablet, Oral, 5 mg, once daily, up to 104 weeks (long term)
All Cause Mortality
	PLACEBO/METFORMIN		SAXAGLIPTIN 5 MG
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	PLACEBO/METFORMIN		SAXAGLIPTIN 5 MG
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/16 (12.5%)		1/20 (5%)
Cardiac disorders
ANGINA UNSTABLE	1/16 (6.3%)		0/20 (0%)
General disorders
CHEST DISCOMFORT	0/16 (0%)		1/20 (5%)
Hepatobiliary disorders
CHOLECYSTITIS	1/16 (6.3%)		0/20 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
COLON CANCER	1/16 (6.3%)		0/20 (0%)
Other (Not Including Serious) Adverse Events
	PLACEBO/METFORMIN		SAXAGLIPTIN 5 MG
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	14/16 (87.5%)		17/20 (85%)
Blood and lymphatic system disorders
ANAEMIA	0/16 (0%)		1/20 (5%)
LYMPHOPENIA	0/16 (0%)		1/20 (5%)
Cardiac disorders
TACHYCARDIA	1/16 (6.3%)		0/20 (0%)
Ear and labyrinth disorders
VERTIGO	0/16 (0%)		1/20 (5%)
MIDDLE EAR EFFUSION	0/16 (0%)		1/20 (5%)
Eye disorders
EYE IRRITATION	1/16 (6.3%)		0/20 (0%)
LACRIMATION INCREASED	0/16 (0%)		1/20 (5%)
Gastrointestinal disorders
NAUSEA	3/16 (18.8%)		2/20 (10%)
VOMITING	0/16 (0%)		1/20 (5%)
DIARRHOEA	1/16 (6.3%)		2/20 (10%)
DYSPEPSIA	0/16 (0%)		1/20 (5%)
GASTRITIS	0/16 (0%)		2/20 (10%)
FLATULENCE	2/16 (12.5%)		0/20 (0%)
GASTRIC ULCER	0/16 (0%)		1/20 (5%)
ABDOMINAL PAIN	2/16 (12.5%)		0/20 (0%)
FAECES DISCOLOURED	0/16 (0%)		1/20 (5%)
ABDOMINAL DISCOMFORT	2/16 (12.5%)		2/20 (10%)
ABDOMINAL PAIN UPPER	0/16 (0%)		1/20 (5%)
GASTROOESOPHAGEAL REFLUX DISEASE	0/16 (0%)		1/20 (5%)
General disorders
PAIN	1/16 (6.3%)		0/20 (0%)
FATIGUE	2/16 (12.5%)		2/20 (10%)
CHEST PAIN	1/16 (6.3%)		0/20 (0%)
HERNIA PAIN	0/16 (0%)		1/20 (5%)
CHEST DISCOMFORT	1/16 (6.3%)		0/20 (0%)
OEDEMA PERIPHERAL	1/16 (6.3%)		2/20 (10%)
INFUSION SITE PAIN	2/16 (12.5%)		4/20 (20%)
INFUSION SITE DISCOMFORT	0/16 (0%)		1/20 (5%)
Immune system disorders
HYPERSENSITIVITY	1/16 (6.3%)		0/20 (0%)
SEASONAL ALLERGY	1/16 (6.3%)		0/20 (0%)
Infections and infestations
CYSTITIS	0/16 (0%)		1/20 (5%)
RHINITIS	0/16 (0%)		1/20 (5%)
INFLUENZA	5/16 (31.3%)		0/20 (0%)
SINUSITIS	0/16 (0%)		3/20 (15%)
BRONCHITIS	1/16 (6.3%)		0/20 (0%)
BACTERIURIA	0/16 (0%)		1/20 (5%)
INFECTED CYST	1/16 (6.3%)		0/20 (0%)
LABYRINTHITIS	0/16 (0%)		1/20 (5%)
TOOTH ABSCESS	1/16 (6.3%)		0/20 (0%)
OTITIS EXTERNA	1/16 (6.3%)		0/20 (0%)
GASTROENTERITIS	0/16 (0%)		2/20 (10%)
NASOPHARYNGITIS	3/16 (18.8%)		3/20 (15%)
KIDNEY INFECTION	1/16 (6.3%)		0/20 (0%)
GASTROENTERITIS VIRAL	1/16 (6.3%)		1/20 (5%)
HELICOBACTER INFECTION	0/16 (0%)		1/20 (5%)
URINARY TRACT INFECTION	1/16 (6.3%)		0/20 (0%)
RESPIRATORY TRACT INFECTION	1/16 (6.3%)		0/20 (0%)
VULVOVAGINAL MYCOTIC INFECTION	0/16 (0%)		1/20 (5%)
UPPER RESPIRATORY TRACT INFECTION	3/16 (18.8%)		3/20 (15%)
VIRAL UPPER RESPIRATORY TRACT INFECTION	0/16 (0%)		1/20 (5%)
Injury, poisoning and procedural complications
LIMB INJURY	1/16 (6.3%)		0/20 (0%)
MUSCLE STRAIN	0/16 (0%)		1/20 (5%)
ANKLE FRACTURE	0/16 (0%)		1/20 (5%)
HEAT EXHAUSTION	0/16 (0%)		1/20 (5%)
PROCEDURAL PAIN	1/16 (6.3%)		0/20 (0%)
ROAD TRAFFIC ACCIDENT	1/16 (6.3%)		1/20 (5%)
POST PROCEDURAL SWELLING	0/16 (0%)		1/20 (5%)
Investigations
CARDIAC MURMUR	0/16 (0%)		1/20 (5%)
URINE OUTPUT DECREASED	0/16 (0%)		1/20 (5%)
BLOOD PRESSURE INCREASED	1/16 (6.3%)		0/20 (0%)
EOSINOPHIL COUNT INCREASED	0/16 (0%)		1/20 (5%)
LYMPHOCYTE COUNT DECREASED	0/16 (0%)		1/20 (5%)
NEUTROPHIL COUNT DECREASED	0/16 (0%)		1/20 (5%)
BLOOD CREATINE PHOSPHOKINASE INCREASED	1/16 (6.3%)		0/20 (0%)
Metabolism and nutrition disorders
HYPERLIPIDAEMIA	1/16 (6.3%)		0/20 (0%)
Musculoskeletal and connective tissue disorders
MYALGIA	1/16 (6.3%)		1/20 (5%)
BACK PAIN	2/16 (12.5%)		2/20 (10%)
NECK PAIN	0/16 (0%)		1/20 (5%)
ARTHRALGIA	1/16 (6.3%)		1/20 (5%)
TENDONITIS	0/16 (0%)		1/20 (5%)
MUSCLE SPASMS	0/16 (0%)		5/20 (25%)
JOINT SWELLING	1/16 (6.3%)		0/20 (0%)
PAIN IN EXTREMITY	0/16 (0%)		2/20 (10%)
MUSCULOSKELETAL PAIN	2/16 (12.5%)		0/20 (0%)
Nervous system disorders
TREMOR	0/16 (0%)		1/20 (5%)
AGEUSIA	0/16 (0%)		1/20 (5%)
HEADACHE	3/16 (18.8%)		5/20 (25%)
DIZZINESS	1/16 (6.3%)		0/20 (0%)
DYSGEUSIA	0/16 (0%)		1/20 (5%)
PRESYNCOPE	1/16 (6.3%)		0/20 (0%)
PARAESTHESIA	0/16 (0%)		2/20 (10%)
HYPOAESTHESIA	1/16 (6.3%)		1/20 (5%)
SINUS HEADACHE	1/16 (6.3%)		0/20 (0%)
NEUROPATHY PERIPHERAL	0/16 (0%)		1/20 (5%)
CARPAL TUNNEL SYNDROME	0/16 (0%)		1/20 (5%)
Psychiatric disorders
STRESS	0/16 (0%)		1/20 (5%)
INSOMNIA	1/16 (6.3%)		0/20 (0%)
AGITATION	0/16 (0%)		1/20 (5%)
Renal and urinary disorders
BLADDER DILATATION	0/16 (0%)		1/20 (5%)
Reproductive system and breast disorders
PROSTATITIS	1/16 (6.3%)		0/20 (0%)
GYNAECOMASTIA	0/16 (0%)		1/20 (5%)
TESTICULAR PAIN	0/16 (0%)		1/20 (5%)
UTERINE PROLAPSE	0/16 (0%)		1/20 (5%)
ENDOMETRIAL HYPERTROPHY	1/16 (6.3%)		0/20 (0%)
PROSTATIC CALCIFICATION	0/16 (0%)		1/20 (5%)
BENIGN PROSTATIC HYPERPLASIA	0/16 (0%)		1/20 (5%)
Respiratory, thoracic and mediastinal disorders
COUGH	3/16 (18.8%)		0/20 (0%)
ASTHMA	1/16 (6.3%)		0/20 (0%)
SINUS CONGESTION	2/16 (12.5%)		0/20 (0%)
OROPHARYNGEAL PAIN	1/16 (6.3%)		1/20 (5%)
SLEEP APNOEA SYNDROME	0/16 (0%)		1/20 (5%)
Skin and subcutaneous tissue disorders
RASH	0/16 (0%)		2/20 (10%)
ERYTHEMA	1/16 (6.3%)		0/20 (0%)
URTICARIA	0/16 (0%)		1/20 (5%)
SKIN LESION	2/16 (12.5%)		0/20 (0%)
RASH GENERALISED	0/16 (0%)		1/20 (5%)
Vascular disorders
HAEMATOMA	1/16 (6.3%)		0/20 (0%)
HOT FLUSH	1/16 (6.3%)		0/20 (0%)
HYPERTENSION	2/16 (12.5%)		0/20 (0%)
PERIPHERAL COLDNESS	1/16 (6.3%)		0/20 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.