Bioequivalence Study of the Fixed Dose Combination of 2.5 mg Saxagliptin and 850 mg Metformin Tablet Relative to a 2.5 mg Saxagliptin (Onglyza) Tablet and a 850 mg Metformin (Glucophage Marketed by Merck Serono) Tablet Co-Administered to Healthy Subjects in the Fasted and Fed Conditions
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- AstraZeneca
- Enrollment
- 24
- Locations
- 1
- Primary Endpoint
- Metformin PK Parameter AUC(0-inf)
Study Overview
Brief Summary
To demonstrate bioequivalence of a 2.5 mg saxagliptin/850 mg metformin fixed dose combination (FDC) tablet relative to the 2.5 mg saxagliptin tablet and 850 mg metformin (Glucophage Marketed by Merck-Serono) tablet co-administered to healthy subjects in the fasted and fed condition.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 55 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Men and women ages 18 to 55 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/m^2, inclusive. BMI = weight (kg)/ [height (m)]^2
Exclusion Criteria
- •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 a dipeptidyl peptidase-IV (DPP4) inhibitor or related compound
- •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 < 80 mL/min using the Cockcroft Gault formula
Arms & Interventions
Arm A (saxagliptin 2.5 mg + metformin 850 mg; Fasting)
A single oral dose of 2.5-mg Onglyza tablet and 850-mg Glucophage (marketed by Merck Serono) tablet administered together in the fasted condition.
Intervention: saxagliptin (Drug)
Arm A (saxagliptin 2.5 mg + metformin 850 mg; Fasting)
A single oral dose of 2.5-mg Onglyza tablet and 850-mg Glucophage (marketed by Merck Serono) tablet administered together in the fasted condition.
Intervention: metformin (Drug)
Arm B (saxagliptin 2.5 mg + metformin 850 mg FDC; Fasting)
A single oral dose of 2.5-mg saxagliptin/850-mg metformin fixed dose combination (FDC) administered in the fasted condition.
Intervention: saxagliptin + metformin (FDC tablet) (Drug)
Arm C (saxagliptin 2.5 mg + metformin 850 mg; Fed)
A single oral dose of 2.5-mg Onglyza tablet and 850-mg Glucophage (marketed by Merck Serono) tablet administered together in the fed condition.
Intervention: saxagliptin (Drug)
Arm C (saxagliptin 2.5 mg + metformin 850 mg; Fed)
A single oral dose of 2.5-mg Onglyza tablet and 850-mg Glucophage (marketed by Merck Serono) tablet administered together in the fed condition.
Intervention: metformin (Drug)
Arm D (saxagliptin 2.5 mg + metformin 850 mg FDC; Fed)
A single oral dose of 2.5-mg saxagliptin/850-mg metformin FDC administered in the fed condition.
Intervention: saxagliptin + metformin (FDC tablet) (Drug)
Outcomes
Primary Outcomes
Metformin PK Parameter AUC(0-inf)
Time Frame: Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosing
PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. AUC (0-inf) is the area under the plasma concentration-time curve from time zero extrapolated to infinite time.
Metformin PK Parameter Cmax
Time Frame: Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosing
PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. Cmax is the maximum observed concentration of drug substance in plasma.
Saxagliptin PK Parameter Observed Maximum Plasma Concentration (Cmax)
Time Frame: Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosing
PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. Cmax is the maximum observed concentration of drug substance in plasma.
Saxagliptin Pharmacokinetic (PK) Parameter Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity (AUC[0-inf])
Time Frame: Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosing
PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. AUC (0-inf) is the area under the plasma concentration-time curve from time zero extrapolated to infinite time.
Secondary Outcomes
- 5-hydroxy Saxagliptin PK Parameter Terminal Half-life (T 1/2)(Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosing)
- 5-hydroxy Saxagliptin PK Parameter Time to Achieve the Observed Maximum Plasma Concentration (Tmax)(Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosing)
- 5-hydroxy Saxagliptin PK Parameter Cmax(Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosing)
- 5-hydroxy Saxagliptin PK Parameter AUC(0-inf)(Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosing)
- 5-hydroxy Saxagliptin PK Parameter Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC[0-t])(Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosing)
- Safety: Adverse Events (AEs), Discontinuations Due to AEs, Deaths, and Serious AEs (SAEs).(AEs: from study drug administration Day 1/Period 1 till study discharge. SAEs: from date of written consent until 30 days after discontinuation of dosing or study participation. Duration of the study was approximately 45 days (including screening).)
- Safety: Clinically Significant Laboratory, Vital Sign, Physical Examination, and/or 12-Lead Electrocardiogram (ECG) Abnormalities(From Day 1/Period 1 to study discharge or premature discontinuation. Duration of study was approximately 45 days (including screening).)