Clinical trial NCT00897390: Bioequivalence Study of Saxagliptin and Glucophage Combination Formulations in Healthy Subjects (B)
Official title: Bioequivalence Study of the Fixed Dose Combination of 2.5 mg Saxagliptin and 1000 mg Metformin Immediate Release (IR) Tablet Relative to 2.5 mg Saxagliptin Tablet and 1000 mg Metformin IR Tablet Co-administered to Healthy Subjects in a Fasted and in a Fed State
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Type 2 Diabetes Mellitus
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2009-05-12
Enrollment: 24
Sex: ALL
Minimum age (years): 19
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER

Brief summary: To demonstrate bioequivalence of a 2.5 mg saxagliptin/1000 mg metformin (glucophage) immediate release (IR) fixed dose combination (FDC) tablet to the 2.5 mg saxagliptin tablet and 1000 mg metformin IR tablet co-administered to healthy subjects in a fasted and in a fed state.


Eligibility criteria: Inclusion Criteria:

* Men and women ages 19 to 45 inclusive
* Healthy subjects as determined by no clinically significant deviation from normal in medical history, physical examination, electrocardiograms (ECGs), and clinical laboratory determinations
* Body Mass Index (BMI) of 18 to 32 kg/m2, inclusive. BMI = weight (kg)/ \[height (m)\]2

Exclusion Criteria:

* Women of child-bearing potential (WOCBP) who are unwilling or unable to use acceptable barrier methods (condoms and spermicides) to avoid pregnancy for the entire study period and for up to 8 weeks after the last dose of investigational product
* Any significant acute or chronic medical illness
* Current or recent (within 3 months) gastrointestinal disease
* Any major surgery within 4 weeks of study drug administration
* History of allergy to Dipeptidyl peptidase 4 (DPP4) inhibitor or related compounds
* History of allergy or intolerance to metformin or other similar acting agents
* Prior exposure to saxagliptin
* Prior exposure to metformin within 3 months of study drug administration
* Estimated creatinine clearance (Clcr) of \< 80ml/min using the Cockcroft Gault formula

Primary outcomes:
measure: Saxagliptin Pharmacokinetic (PK) Parameter Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinite Time (AUC[INF])
timeFrame: pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period
measure: Saxagliptin PK Parameter Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Plasma Concentration (AUC[0-T])
timeFrame: pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period
measure: Saxagliptin PK Parameter Maximum Observed Plasma Concentration (Cmax)
timeFrame: pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period
measure: Saxagliptin PK Parameter Plasma Terminal Half-life (T-HALF)
timeFrame: pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period
measure: Saxagliptin PK Parameter Time of Maximum Observed Plasma Concentration (Tmax)
timeFrame: pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period
measure: Metformin PK Parameter AUC(INF)
timeFrame: pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period
measure: Metformin PK Parameter AUC(0-T)
timeFrame: pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period
measure: Metformin PK Parameter Cmax
timeFrame: pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period
measure: Metformin PK Parameter T-HALF
timeFrame: pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period
measure: Metformin PK Parameter Tmax
timeFrame: pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period
Secondary outcomes:
measure: BMS-510849 PK Parameter AUC(INF)
timeFrame: pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period
measure: BMS-510849 PK Parameter AUC(0-T)
timeFrame: pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period
measure: BMS-510849 PK Parameter Cmax
timeFrame: pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period
measure: BMS-510849 PK Parameter T-Half
timeFrame: pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period
measure: BMS-510849 PK Parameter T-Max
timeFrame: pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period
measure: Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), and Discontinuations Due to AEs
timeFrame: AEs collected from Day 1/Period 1 through study discharge (study duration: approximately 45 days). SAEs collected from date of written consent until 30 days post discontinuation of dosing or subject's participation in the study.
measure: AEs of Special Interest
timeFrame: AEs collected from Day 1/Period 1 through study discharge (study duration: approximately 45 days).
measure: Number of Participants With Marked Laboratory Abnormalities (MA)
timeFrame: Within 21 days of study Day 1, Days 1-3 of Periods 1, 2, 3, and 4.
measure: Number of Participants With Marked Urinalysis Abnormalities
timeFrame: Within 21 days of study Day 1, Days 1-3 of Periods 1, 2, 3, and 4.
measure: Electrocardiogram (ECG), Vital Sign, and Physical Finding Abnormalities
timeFrame: At Screening (within 21 days of Study Day 1), Day -1 of Period 1 (ECG and Physical only), Day 1 of Periods 1-4 (Vitals only), at Study Discharge (Day 3 of Period 4) or Discontinuation
Other outcomes:
Locations:
city: Lincoln
country: United States
facility: Mds Pharma Services
state: Nebraska
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: Upreti VV, Keung CF, Boulton DW, Chang M, Li L, Tang A, Hsiang BC, Quamina-Edghill D, Frevert EU, Lacreta FP. Bioequivalence of saxagliptin/metformin immediate release (IR) fixed-dose combination tablets and single-component saxagliptin and metformin IR tablets in healthy adult subjects. Clin Drug Investig. 2013 May;33(5):365-74. doi: 10.1007/s40261-013-0075-z.