A study assessing Saxagliptin treatment in subjects with type 2 diabetes who are not controlled with diet and exercise

Study identifier:CV181-041

ClinicalTrials.gov identifier:N/A

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

Mechanism of Action and Efficacy of Saxagliptin (BMS-477118) in the Treatment of Type 2 Diabetic Patients

Medical condition

Type 2 Diabetes

Phase

Phase 3

Healthy volunteers

Study drug

Saxagliptin, Placebo, Metformin (blinded), Metformin (open-label)

Sex

All

Actual Enrollment

156

Study type

Interventional

Age

18 Years - 70 Years

Date

Study Start Date: 01 Sept 2006

Primary Completion Date: 01 Jan 2008

Study Completion Date: 01 Dec 2009

Study design

Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind
Primary Purpose: Treatment

Verification:

Verified 01 Mar 2015 by AstraZeneca Pharmaceuticals

Collaborators

Inclusion and exclusion criteria

Location

Va San Diego Healthcare System

San Diego, CA, United States, 92161

Location

Diabetes & Glandular Disease Research Assoc,, Inc.

San Antonio, TX, United States, 78229

Location

Pennington Biomedical Research Center

Baton Rouge, LA, United States, 70808

Arms	Assigned Interventions
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 Name: 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)

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
156 participants were enrolled in the study; 110 participants failed screening; 10 subjects entered lead-in and discontinued prior to randomization.

Reporting Groups

	Description
Saxagliptin 5 mg	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 / Metformin	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).

Participant Flow for 2 periods

Period 1: 12-Week Short-term Period

	Saxagliptin 5 mg	Placebo / Metformin
STARTED	20	16
COMPLETED	17	15
NOT COMPLETED	3	1
Subject Withdrew Consent	3	1

Period 2: 116-Week Short-term + Long-term Period

	Saxagliptin 5 mg	Placebo / Metformin
STARTED	20	16
Completed 12-week short term period	17	15
COMPLETED	7	2
NOT COMPLETED	13	14
Subject Withdrew Consent	8	9
Lack of Efficacy	4	2
Adverse Event	0	2
Lost to Follow-up	1	1

Baseline Characteristics

Analysis Population Description -- Explanation of how the number of participants for analysis was determined.

Reporting Groups

	Description
Saxagliptin 5 mg	Tablet, Oral, 5 mg, once daily, up to 12 weeks (short-term) and up to 104 weeks (long-term)
Placebo / Metformin	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

Baseline Measures

	Saxagliptin 5 mg	Placebo / Metformin	Total
Number of Participants [units: Participants]	20	16	36
Age Continuous [units: years] Median ( Full Range )	58 (43 to 69)	55 (45 to 69)	55.5 (43 to 69)
Gender, Male/Female [units: participants]
Female	12	10	22
Male	8	6	14
Race/Ethnicity, Customized [units: participants]
White	16	12	28
Black/African American	3	4	7
Other	1	0	1
Region of Enrollment [units: participants] North America	20	16	36
Body Mass Index (BMI) [units: kg/m^2] Median ( Full Range )	33.36 (24.67 to 39.35)	32.31 (25.56 to 38.55)	33.01 (24.67 to 39.35)

Outcome Measures

1. Primary Outcome Measure: Insulin Secretion Rate Area Under the Curve (AUC) During intravenous (IV)-oral Hyperglycemic Clamp - Percent Change From Baseline at Week 12 [ Time Frame: Baseline, Week 12 ]

Measure Type	Primary
Measure Name	Insulin Secretion Rate Area Under the Curve (AUC) During intravenous (IV)-oral Hyperglycemic Clamp - Percent Change From Baseline at Week 12
Measure 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
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Randomized participants with both a baseline and post-baseline value (up to Week 12).

Reporting Groups

	Description
Short Term Period: Saxagliptin 5 mg	Tablet, Oral, 5 mg, once daily, up to 12 weeks
Short Term Period: Placebo	Tablet, Oral, 0 mg, once daily, up to 12 weeks

Measured Values

	Short Term Period: Saxagliptin 5 mg	Short Term Period: Placebo
Number of Participants Analyzed [units:participants]	16	15
Insulin Secretion Rate Area Under the Curve (AUC) During intravenous (IV)-oral Hyperglycemic Clamp - Percent Change From Baseline at Week 12 [units: Percent Change (Percentage of Baseline)] Geometric Mean (95% Confidence Interval)	15.9 (4.2 to 29.0)	-2.2 (-12.4 to 9.3)

Statistical Analysis 1 for Insulin Secretion Rate Area Under the Curve (AUC) During intravenous (IV)-oral Hyperglycemic Clamp - Percent Change From Baseline at Week 12

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	ANCOVA
P-Value^[4]	0.0350
Other^[5]	18.5
95% Confidence Interval	( 1.3 to 38.7 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Adjusted percent difference for saxagliptin 5 mg vs placebo in Week 12 (LOCF) to baseline ratio. Adjusted for baseline.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Between-group comparisons significant at alpha = 0.05, significance testing based on hierarchical testing. Primary and secondary endpoints are presented in order of testing.
[5]	Other relevant estimation information:
	ANCOVA model: logarithm(post/pre) = logarithm(pre) treatment

2. Secondary Outcome Measure: Insulin Secretion Rate AUC During IV Hyperglycemic Clamp - Percent Change from Baseline at Week 12 [ Time Frame: Baseline, Week 12 ]

Measure Type	Secondary
Measure Name	Insulin Secretion Rate AUC During IV Hyperglycemic Clamp - Percent Change from Baseline at Week 12
Measure 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
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Randomized Participants with both a baseline and post-baseline value (up to Week 12).

Reporting Groups

	Description
Short Term Period: Saxagliptin 5 mg	Tablet, Oral, 5 mg, once daily, up to 12 weeks
Short Term Period: Placebo	Tablet, Oral, 0 mg, once daily, up to 12 weeks

Measured Values

	Short Term Period: Saxagliptin 5 mg	Short Term Period: Placebo
Number of Participants Analyzed [units:participants]	18	16
Insulin Secretion Rate AUC During IV Hyperglycemic Clamp - Percent Change from Baseline at Week 12 [units: Percent Change (Percentage of Baseline)] Geometric Mean (95% Confidence Interval)	22.6 (7.2 to 40.4)	-4.1 (-17.4 to 11.2)

Statistical Analysis 1 for Insulin Secretion Rate AUC During IV Hyperglycemic Clamp - Percent Change from Baseline at Week 12

Groups^[1]	All groups
Non-Inferiority/Equivalence Test^[2]	No
Method^[3]	ANCOVA
P-Value^[4]	0.0204
Other^[5]	27.9
95% Confidence Interval	( 4.2 to 57.1 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Additional details about a non-inferiority or equivalence analysis:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Adjusted percent difference for saxagliptin 5 mg vs placebo in Week 12 (LOCF) to baseline ratio. Adjusted for baseline.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Between-group comparisons significant at alpha = 0.05, significance testing based on hierarchical testing. Primary and secondary endpoints are presented in order of testing.
[5]	Other relevant estimation information:
	ANCOVA model: logarithm(post/pre) = logarithm(pre) treatment

3. Other Pre-specified Outcome Measure: Overall Summary of Adverse Events (AEs) Serious AEs (SAEs), Discontinuations, and Deaths During the ST + LT Treatment Period [ Time Frame: 116 weeks ]

Measure Type	Other Pre-specified
Measure Name	Overall Summary of Adverse Events (AEs) Serious AEs (SAEs), Discontinuations, and Deaths During the ST + LT Treatment Period
Measure 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
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Treated participants

Reporting Groups

	Description
Saxagliptin 5 mg	Tablet, Oral, 5 mg, once daily, up to 12 weeks (short-term) and up to 104 weeks (long-term)
Placebo / Metformin	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

Measured Values

	Saxagliptin 5 mg	Placebo / Metformin
Number of Participants Analyzed [units:participants]	20	16
Overall Summary of Adverse Events (AEs) Serious AEs (SAEs), Discontinuations, and Deaths During the ST + LT Treatment Period [units: participants]
At Least 1 AE	17	14
At Least 1 Related AE	7	6
Deaths	0	0
At Least 1 SAE	1	2
At Least 1 Related SAE	0	0
Discontinuations Due to SAEs	0	1
Discontinuations Due to AEs	0	2

No statistical analysis provided for Overall Summary of Adverse Events (AEs) Serious AEs (SAEs), Discontinuations, and Deaths During the ST + LT Treatment Period

4. Other Pre-specified Outcome Measure: Marked Laboratory Abnormalities - During ST + LT Treatment Period [ Time Frame: 116 weeks ]

Measure Type	Other Pre-specified
Measure Name	Marked Laboratory Abnormalities - During ST + LT Treatment Period
Measure 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
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups

	Description
Saxagliptin 5 mg	Tablet, Oral, 5 mg, once daily, up to 12 weeks (short-term) and up to 104 weeks (long-term)
Placebo / Metformin	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

Measured Values

	Saxagliptin 5 mg	Placebo / Metformin
Number of Participants Analyzed [units:participants]	20	16
Marked Laboratory Abnormalities - During ST + LT Treatment Period [units: participants]
Hemoglobin < 8 g/dL (n=0, 0)	0	0
Hematocrit < 0.75 x pre-Rx (n=0, 0)	0	0
Platelets < 50 x 10^9 c/L (n=0, 0)	0	0
Platelets > 1.5 x ULN (n=0, 0)	0	0
Leukocytes < 2 x 1000 c/uL (n=0, 0)	0	0
Neutrophils+Bands <1x1000 c/uL (n=18, 0)	1	0
Eosinophils >0.9x1000 c/uL (n=18, 0)	1	0
Lymphocytes <=0.75x1000 c/uL (n=18, 0)	2	0
ALP >3 x pre-Rx and >ULN (n=0, 0)	0	0
AST >3 x ULN (n=0, 0)	0	0
AST >5 x ULN (n=0, 0)	0	0
ALT >3 x ULN (n=0, 0)	0	0
ALT >5 x ULN (n=0, 0)	0	0
Bilirubin Total >2mg/dL (n=0, 0)	0	0
BUN >2 x pre-Rx and >ULN (n=0, 0)	0	0
Creatinine >2.5 mg/dL (n=0, 0)	0	0
Glucose, Serum Fasting < 50 mg/dL (n=0, 0)	0	0
Glucose, Serum Fasting > 500 mg/dL (n=0, 0)	0	0
Glucose, Serum Unspec. < 50 mg/dL (n=0, 0)	0	0
Glucose, Serum Unspec. > 500 mg/dL (n=0, 0)	0	0
Glucose, Plasma Fasting <50 mg/dL (n=0, 0)	0	0
Glucose,Plasma Fasting >500 mg/dL (n=0, 0)	0	0
Glucose, Plasma Unspec. <50 mg/dL (n=0, 0)	0	0
Glucose, Plasma Unspec. >500 mg/dL (n=18, 16)	8	9
Sodium, Serum Low (see description) (n=0, 0)	0	0
Sodium, Serum High (see description) (n=0, 0)	0	0
Potassium, Serum Low (see description) (n=0, 0)	0	0
Potassium, Serum High (see description) (n=0, 0)	0	0
Chloride < 90 mEq/L (n=0, 0)	0	0
Chloride > 120 mEq/L (n=0, 0)	0	0
Albumin < 0.9 LLN (n=0, 0)	0	0
Creatine Kinase > 5 x ULN (n=18, 16)	1	1
Uric Acid > 1.5 x ULN (n=0, 0)	0	0
Protein Urine, >=2-4 (n=0, 0)	0	0
Blood Urine >=2-4 (n=18, 0)	1	0
Red Blood Cells Urine >=2-4 (n=0, 0)	0	0
White Blood Cells Urine >=2-4 (n=0, 0)	2	1

No statistical analysis provided for Marked Laboratory Abnormalities - During ST + LT Treatment Period

Serious Adverse Events

Time Frame	Short term period (up to 12 weeks) + long term period (up to 104 weeks)
Additional Description	No text entered.

Reporting Groups

	Description
PLACEBO/METFORMIN	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)
SAXAGLIPTIN 5 MG	Tablet, Oral, 5 mg, once daily, up to 12 weeks (short term); Tablet, Oral, 5 mg, once daily, up to 104 weeks (long term)

Serious Adverse Events

PLACEBO/METFORMIN

SAXAGLIPTIN 5 MG

Total, serious adverse events

# participants affected / at risk

2/16 (12.50%)

1/20 (5.00%)

CARDIAC DISORDERS

ANGINA UNSTABLE¹,^†

# participants affected / at risk

1/16 (6.25%)

0/20 (0.00%)

HEPATOBILIARY DISORDERS

CHOLECYSTITIS¹,^†

# participants affected / at risk

1/16 (6.25%)

0/20 (0.00%)

GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS

CHEST DISCOMFORT¹,^†

# participants affected / at risk

0/16 (0.00%)

1/20 (5.00%)

NEOPLASMS BENIGN, MALIGNANT AND UNSPECIFIED (INCL CYSTS AND POLYPS)

COLON CANCER¹,^†

# participants affected / at risk

1/16 (6.25%)

0/20 (0.00%)

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 12.1
2	Term from vocabulary,

Other Adverse Events

Time Frame	Short term period (up to 12 weeks) + long term period (up to 104 weeks)
Additional Description	No text entered.

Frequency Threshold

Threshold above which other adverse events are reported	5%

Reporting Groups

	Description
PLACEBO/METFORMIN	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)
SAXAGLIPTIN 5 MG	Tablet, Oral, 5 mg, once daily, up to 12 weeks (short term); Tablet, Oral, 5 mg, once daily, up to 104 weeks (long term)

Other Adverse Events

PLACEBO/METFORMIN

SAXAGLIPTIN 5 MG

Total, other (not including serious) adverse events

# participants affected / at risk

14/16 (87.50%)

17/20 (85.00%)

EYE DISORDERS

EYE IRRITATION¹,^†

# participants affected / at risk

1/16 (6.25%)

0/20 (0.00%)

EYE DISORDERS

LACRIMATION INCREASED¹,^†

# participants affected / at risk

0/16 (0.00%)

1/20 (5.00%)

INVESTIGATIONS

CARDIAC MURMUR¹,^†

# participants affected / at risk

0/16 (0.00%)

1/20 (5.00%)

INVESTIGATIONS

URINE OUTPUT DECREASED¹,^†

# participants affected / at risk

0/16 (0.00%)

1/20 (5.00%)

INVESTIGATIONS

BLOOD PRESSURE INCREASED¹,^†

# participants affected / at risk

1/16 (6.25%)

0/20 (0.00%)

INVESTIGATIONS

EOSINOPHIL COUNT INCREASED¹,^†

# participants affected / at risk

0/16 (0.00%)

1/20 (5.00%)

INVESTIGATIONS

LYMPHOCYTE COUNT DECREASED¹,^†

# participants affected / at risk

0/16 (0.00%)

1/20 (5.00%)

INVESTIGATIONS

NEUTROPHIL COUNT DECREASED¹,^†

# participants affected / at risk

0/16 (0.00%)

1/20 (5.00%)

INVESTIGATIONS

BLOOD CREATINE PHOSPHOKINASE INCREASED¹,^†

# participants affected / at risk

1/16 (6.25%)

0/20 (0.00%)

CARDIAC DISORDERS

TACHYCARDIA¹,^†

# participants affected / at risk

1/16 (6.25%)

0/20 (0.00%)

VASCULAR DISORDERS

HAEMATOMA¹,^†

# participants affected / at risk

1/16 (6.25%)

0/20 (0.00%)

VASCULAR DISORDERS

HOT FLUSH¹,^†

# participants affected / at risk

1/16 (6.25%)

0/20 (0.00%)

VASCULAR DISORDERS

HYPERTENSION¹,^†

# participants affected / at risk

2/16 (12.50%)

0/20 (0.00%)

VASCULAR DISORDERS

PERIPHERAL COLDNESS¹,^†

# participants affected / at risk

1/16 (6.25%)

0/20 (0.00%)

PSYCHIATRIC DISORDERS

STRESS¹,^†

# participants affected / at risk

0/16 (0.00%)

1/20 (5.00%)

PSYCHIATRIC DISORDERS

INSOMNIA¹,^†

# participants affected / at risk

1/16 (6.25%)

0/20 (0.00%)

PSYCHIATRIC DISORDERS

AGITATION¹,^†

# participants affected / at risk

0/16 (0.00%)

1/20 (5.00%)

IMMUNE SYSTEM DISORDERS

HYPERSENSITIVITY¹,^†

# participants affected / at risk

1/16 (6.25%)

0/20 (0.00%)

IMMUNE SYSTEM DISORDERS

SEASONAL ALLERGY¹,^†

# participants affected / at risk

1/16 (6.25%)

0/20 (0.00%)

NERVOUS SYSTEM DISORDERS

TREMOR¹,^†

# participants affected / at risk

0/16 (0.00%)

1/20 (5.00%)

NERVOUS SYSTEM DISORDERS

AGEUSIA¹,^†

# participants affected / at risk

0/16 (0.00%)

1/20 (5.00%)

NERVOUS SYSTEM DISORDERS

HEADACHE¹,^†

# participants affected / at risk

3/16 (18.75%)

5/20 (25.00%)

NERVOUS SYSTEM DISORDERS

DIZZINESS¹,^†

# participants affected / at risk

1/16 (6.25%)

0/20 (0.00%)

NERVOUS SYSTEM DISORDERS

DYSGEUSIA¹,^†

# participants affected / at risk

0/16 (0.00%)

1/20 (5.00%)

NERVOUS SYSTEM DISORDERS

PRESYNCOPE¹,^†

# participants affected / at risk

1/16 (6.25%)

0/20 (0.00%)

NERVOUS SYSTEM DISORDERS

PARAESTHESIA¹,^†

# participants affected / at risk

0/16 (0.00%)

2/20 (10.00%)

NERVOUS SYSTEM DISORDERS

HYPOAESTHESIA¹,^†

# participants affected / at risk

1/16 (6.25%)

1/20 (5.00%)

NERVOUS SYSTEM DISORDERS

SINUS HEADACHE¹,^†

# participants affected / at risk

1/16 (6.25%)

0/20 (0.00%)

NERVOUS SYSTEM DISORDERS

NEUROPATHY PERIPHERAL¹,^†

# participants affected / at risk

0/16 (0.00%)

1/20 (5.00%)

NERVOUS SYSTEM DISORDERS

CARPAL TUNNEL SYNDROME¹,^†

# participants affected / at risk

0/16 (0.00%)

1/20 (5.00%)

GASTROINTESTINAL DISORDERS

NAUSEA¹,^†

# participants affected / at risk

3/16 (18.75%)

2/20 (10.00%)

GASTROINTESTINAL DISORDERS

VOMITING¹,^†

# participants affected / at risk

0/16 (0.00%)

1/20 (5.00%)

GASTROINTESTINAL DISORDERS

DIARRHOEA¹,^†

# participants affected / at risk

1/16 (6.25%)

2/20 (10.00%)

GASTROINTESTINAL DISORDERS

DYSPEPSIA¹,^†

# participants affected / at risk

0/16 (0.00%)

1/20 (5.00%)

GASTROINTESTINAL DISORDERS

GASTRITIS¹,^†

# participants affected / at risk

0/16 (0.00%)

2/20 (10.00%)

GASTROINTESTINAL DISORDERS

FLATULENCE¹,^†

# participants affected / at risk

2/16 (12.50%)

0/20 (0.00%)

GASTROINTESTINAL DISORDERS

GASTRIC ULCER¹,^†

# participants affected / at risk

0/16 (0.00%)

1/20 (5.00%)

GASTROINTESTINAL DISORDERS

ABDOMINAL PAIN¹,^†

# participants affected / at risk

2/16 (12.50%)

0/20 (0.00%)

GASTROINTESTINAL DISORDERS

FAECES DISCOLOURED¹,^†

# participants affected / at risk

0/16 (0.00%)

1/20 (5.00%)

GASTROINTESTINAL DISORDERS

ABDOMINAL DISCOMFORT¹,^†

# participants affected / at risk

2/16 (12.50%)

2/20 (10.00%)

GASTROINTESTINAL DISORDERS

ABDOMINAL PAIN UPPER¹,^†

# participants affected / at risk

0/16 (0.00%)

1/20 (5.00%)

GASTROINTESTINAL DISORDERS

GASTROOESOPHAGEAL REFLUX DISEASE¹,^†

# participants affected / at risk

0/16 (0.00%)

1/20 (5.00%)

EAR AND LABYRINTH DISORDERS

VERTIGO¹,^†

# participants affected / at risk

0/16 (0.00%)

1/20 (5.00%)

EAR AND LABYRINTH DISORDERS

MIDDLE EAR EFFUSION¹,^†

# participants affected / at risk

0/16 (0.00%)

1/20 (5.00%)

INFECTIONS AND INFESTATIONS

CYSTITIS¹,^†

# participants affected / at risk

0/16 (0.00%)

1/20 (5.00%)

INFECTIONS AND INFESTATIONS

RHINITIS¹,^†

# participants affected / at risk

0/16 (0.00%)

1/20 (5.00%)

INFECTIONS AND INFESTATIONS

INFLUENZA¹,^†

# participants affected / at risk

5/16 (31.25%)

0/20 (0.00%)

INFECTIONS AND INFESTATIONS

SINUSITIS¹,^†

# participants affected / at risk

0/16 (0.00%)

3/20 (15.00%)

INFECTIONS AND INFESTATIONS

BRONCHITIS¹,^†

# participants affected / at risk

1/16 (6.25%)

0/20 (0.00%)

INFECTIONS AND INFESTATIONS

BACTERIURIA¹,^†

# participants affected / at risk

0/16 (0.00%)

1/20 (5.00%)

INFECTIONS AND INFESTATIONS

INFECTED CYST¹,^†

# participants affected / at risk

1/16 (6.25%)

0/20 (0.00%)

INFECTIONS AND INFESTATIONS

LABYRINTHITIS¹,^†

# participants affected / at risk

0/16 (0.00%)

1/20 (5.00%)

INFECTIONS AND INFESTATIONS

TOOTH ABSCESS¹,^†

# participants affected / at risk

1/16 (6.25%)

0/20 (0.00%)

INFECTIONS AND INFESTATIONS

OTITIS EXTERNA¹,^†

# participants affected / at risk

1/16 (6.25%)

0/20 (0.00%)

INFECTIONS AND INFESTATIONS

GASTROENTERITIS¹,^†

# participants affected / at risk

0/16 (0.00%)

2/20 (10.00%)

INFECTIONS AND INFESTATIONS

NASOPHARYNGITIS¹,^†

# participants affected / at risk

3/16 (18.75%)

3/20 (15.00%)

INFECTIONS AND INFESTATIONS

KIDNEY INFECTION¹,^†

# participants affected / at risk

1/16 (6.25%)

0/20 (0.00%)

INFECTIONS AND INFESTATIONS

GASTROENTERITIS VIRAL¹,^†

# participants affected / at risk

1/16 (6.25%)

1/20 (5.00%)

INFECTIONS AND INFESTATIONS

HELICOBACTER INFECTION¹,^†

# participants affected / at risk

0/16 (0.00%)

1/20 (5.00%)

INFECTIONS AND INFESTATIONS

URINARY TRACT INFECTION¹,^†

# participants affected / at risk

1/16 (6.25%)

0/20 (0.00%)

INFECTIONS AND INFESTATIONS

RESPIRATORY TRACT INFECTION¹,^†

# participants affected / at risk

1/16 (6.25%)

0/20 (0.00%)

INFECTIONS AND INFESTATIONS

VULVOVAGINAL MYCOTIC INFECTION¹,^†

# participants affected / at risk

0/16 (0.00%)

1/20 (5.00%)

INFECTIONS AND INFESTATIONS

UPPER RESPIRATORY TRACT INFECTION¹,^†

# participants affected / at risk

3/16 (18.75%)

3/20 (15.00%)

INFECTIONS AND INFESTATIONS

VIRAL UPPER RESPIRATORY TRACT INFECTION¹,^†

# participants affected / at risk

0/16 (0.00%)

1/20 (5.00%)

RENAL AND URINARY DISORDERS

BLADDER DILATATION¹,^†

# participants affected / at risk

0/16 (0.00%)

1/20 (5.00%)

METABOLISM AND NUTRITION DISORDERS

HYPERLIPIDAEMIA¹,^†

# participants affected / at risk

1/16 (6.25%)

0/20 (0.00%)

BLOOD AND LYMPHATIC SYSTEM DISORDERS

ANAEMIA¹,^†

# participants affected / at risk

0/16 (0.00%)

1/20 (5.00%)

BLOOD AND LYMPHATIC SYSTEM DISORDERS

LYMPHOPENIA¹,^†

# participants affected / at risk

0/16 (0.00%)

1/20 (5.00%)

SKIN AND SUBCUTANEOUS TISSUE DISORDERS

RASH¹,^†

# participants affected / at risk

0/16 (0.00%)

2/20 (10.00%)

SKIN AND SUBCUTANEOUS TISSUE DISORDERS

ERYTHEMA¹,^†

# participants affected / at risk

1/16 (6.25%)

0/20 (0.00%)

SKIN AND SUBCUTANEOUS TISSUE DISORDERS

URTICARIA¹,^†

# participants affected / at risk

0/16 (0.00%)

1/20 (5.00%)

SKIN AND SUBCUTANEOUS TISSUE DISORDERS

SKIN LESION¹,^†

# participants affected / at risk

2/16 (12.50%)

0/20 (0.00%)

SKIN AND SUBCUTANEOUS TISSUE DISORDERS

RASH GENERALISED¹,^†

# participants affected / at risk

0/16 (0.00%)

1/20 (5.00%)

REPRODUCTIVE SYSTEM AND BREAST DISORDERS

PROSTATITIS¹,^†

# participants affected / at risk

1/16 (6.25%)

0/20 (0.00%)

REPRODUCTIVE SYSTEM AND BREAST DISORDERS

GYNAECOMASTIA¹,^†

# participants affected / at risk

0/16 (0.00%)

1/20 (5.00%)

REPRODUCTIVE SYSTEM AND BREAST DISORDERS

TESTICULAR PAIN¹,^†

# participants affected / at risk

0/16 (0.00%)

1/20 (5.00%)

REPRODUCTIVE SYSTEM AND BREAST DISORDERS

UTERINE PROLAPSE¹,^†

# participants affected / at risk

0/16 (0.00%)

1/20 (5.00%)

REPRODUCTIVE SYSTEM AND BREAST DISORDERS

ENDOMETRIAL HYPERTROPHY¹,^†

# participants affected / at risk

1/16 (6.25%)

0/20 (0.00%)

REPRODUCTIVE SYSTEM AND BREAST DISORDERS

PROSTATIC CALCIFICATION¹,^†

# participants affected / at risk

0/16 (0.00%)

1/20 (5.00%)

REPRODUCTIVE SYSTEM AND BREAST DISORDERS

BENIGN PROSTATIC HYPERPLASIA¹,^†

# participants affected / at risk

0/16 (0.00%)

1/20 (5.00%)

INJURY, POISONING AND PROCEDURAL COMPLICATIONS

LIMB INJURY¹,^†

# participants affected / at risk

1/16 (6.25%)

0/20 (0.00%)

INJURY, POISONING AND PROCEDURAL COMPLICATIONS

MUSCLE STRAIN¹,^†

# participants affected / at risk

0/16 (0.00%)

1/20 (5.00%)

INJURY, POISONING AND PROCEDURAL COMPLICATIONS

ANKLE FRACTURE¹,^†

# participants affected / at risk

0/16 (0.00%)

1/20 (5.00%)

INJURY, POISONING AND PROCEDURAL COMPLICATIONS

HEAT EXHAUSTION¹,^†

# participants affected / at risk

0/16 (0.00%)

1/20 (5.00%)

INJURY, POISONING AND PROCEDURAL COMPLICATIONS

PROCEDURAL PAIN¹,^†

# participants affected / at risk

1/16 (6.25%)

0/20 (0.00%)

INJURY, POISONING AND PROCEDURAL COMPLICATIONS

ROAD TRAFFIC ACCIDENT¹,^†

# participants affected / at risk

1/16 (6.25%)

1/20 (5.00%)

INJURY, POISONING AND PROCEDURAL COMPLICATIONS

POST PROCEDURAL SWELLING¹,^†

# participants affected / at risk

0/16 (0.00%)

1/20 (5.00%)

MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS

MYALGIA¹,^†

# participants affected / at risk

1/16 (6.25%)

1/20 (5.00%)

MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS

BACK PAIN¹,^†

# participants affected / at risk

2/16 (12.50%)

2/20 (10.00%)

MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS

NECK PAIN¹,^†

# participants affected / at risk

0/16 (0.00%)

1/20 (5.00%)

MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS

ARTHRALGIA¹,^†

# participants affected / at risk

1/16 (6.25%)

1/20 (5.00%)

MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS

TENDONITIS¹,^†

# participants affected / at risk

0/16 (0.00%)

1/20 (5.00%)

MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS

MUSCLE SPASMS¹,^†

# participants affected / at risk

0/16 (0.00%)

5/20 (25.00%)

MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS

JOINT SWELLING¹,^†

# participants affected / at risk

1/16 (6.25%)

0/20 (0.00%)

MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS

PAIN IN EXTREMITY¹,^†

# participants affected / at risk

0/16 (0.00%)

2/20 (10.00%)

MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS

MUSCULOSKELETAL PAIN¹,^†

# participants affected / at risk

2/16 (12.50%)

0/20 (0.00%)

RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS

COUGH¹,^†

# participants affected / at risk

3/16 (18.75%)

0/20 (0.00%)

RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS

ASTHMA¹,^†

# participants affected / at risk

1/16 (6.25%)

0/20 (0.00%)

RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS

SINUS CONGESTION¹,^†

# participants affected / at risk

2/16 (12.50%)

0/20 (0.00%)

RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS

OROPHARYNGEAL PAIN¹,^†

# participants affected / at risk

1/16 (6.25%)

1/20 (5.00%)

RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS

SLEEP APNOEA SYNDROME¹,^†

# participants affected / at risk

0/16 (0.00%)

1/20 (5.00%)

GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS

PAIN¹,^†

# participants affected / at risk

1/16 (6.25%)

0/20 (0.00%)

GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS

FATIGUE¹,^†

# participants affected / at risk

2/16 (12.50%)

2/20 (10.00%)

GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS

CHEST PAIN¹,^†

# participants affected / at risk

1/16 (6.25%)

0/20 (0.00%)

GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS

HERNIA PAIN¹,^†

# participants affected / at risk

0/16 (0.00%)

1/20 (5.00%)

GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS

CHEST DISCOMFORT¹,^†

# participants affected / at risk

1/16 (6.25%)

0/20 (0.00%)

GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS

OEDEMA PERIPHERAL¹,^†

# participants affected / at risk

1/16 (6.25%)

2/20 (10.00%)

GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS

INFUSION SITE PAIN¹,^†

# participants affected / at risk

2/16 (12.50%)

4/20 (20.00%)

GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS

INFUSION SITE DISCOMFORT¹,^†

# participants affected / at risk

0/16 (0.00%)

1/20 (5.00%)

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 12.1
2	Term from vocabulary,

Certain Agreements

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

There IS 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.

The agreement is:

	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.
	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 more than 60 days but less than or equal to 180 days . The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: 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.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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Results Point of Contact

Name/Title:	Boaz Hirschberg
Organization:	AstraZeneca Pharmaceuticals
E-mail:	[email protected]

Documents available

BMS Clinical Trials Disclosure
Download
For FDA Safety Alerts and Recalls refer to the following link www.fda.gov/MEDWATCH/safety.htm
Download
PhRMA posting
Download
Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

information.center@astrazeneca.com

Investigators

Principal Investigator

Bristol-Myers Squibb

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Va San Diego Healthcare System

Diabetes & Glandular Disease Research Assoc,, Inc.

Pennington Biomedical Research Center

BMS Clinical Trials Disclosure

For FDA Safety Alerts and Recalls refer to the following link www.fda.gov/MEDWATCH/safety.htm

PhRMA posting

Trial Results Summaries