Bioequivalence Study of Saxagliptin and Glucophage Combination Formulations in Healthy Subjects (A)
- Conditions
- Type 2 Diabetes Mellitus
- Interventions
- Drug: Co-administration of Saxagliptin and Metformin IR, FastedDrug: Saxagliptin/Metformin, FastingDrug: Co-administration of Saxagliptin and Metformin IR, FedDrug: Saxagliptin/Metformin, Fed
- Registration Number
- NCT00899470
- Lead Sponsor
- AstraZeneca
- Brief Summary
To demonstrate bioequivalence of a 2.5 mg saxagliptin/500 mg metformin (glucophage) immediate release (IR) fixed dose combination (FDC) tablet to the 2.5 mg saxagliptin tablet and 500 mg metformin IR tablet co-administered to healthy subjects in a fasted and in a fed state.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 24
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description S+ M, (fasted)> S/M (fed)> S/M (fasted)>S+M (fed) Co-administration of Saxagliptin and Metformin IR, Fed Participants were randomized to receive oral co-administration of a 2.5 mg tablet of saxagliptin plus a 500 mg tablet of metformin immediate release (IR) under fasted conditions (S + M \[fasted\]) followed by a fixed dose combination (FDC) tablet of 2.5 mg saxagliptin/500 mg metformin IR under fed conditions (S/M \[fed\]) followed by S/M under fasting conditions (S/M \[fasted\]) followed by S + M under fed conditions (S + M \[fed\]) S+M (fed)> S/M (fasted) >S/M (fed)> S+M (fasted) Co-administration of Saxagliptin and Metformin IR, Fasted Participants were randomized to receive S + M (fed) followed by S/M (fasted) followed by S/M (fed) followed by S+M (fasted) S+ M, (fasted)> S/M (fed)> S/M (fasted)>S+M (fed) Saxagliptin/Metformin, Fasting Participants were randomized to receive oral co-administration of a 2.5 mg tablet of saxagliptin plus a 500 mg tablet of metformin immediate release (IR) under fasted conditions (S + M \[fasted\]) followed by a fixed dose combination (FDC) tablet of 2.5 mg saxagliptin/500 mg metformin IR under fed conditions (S/M \[fed\]) followed by S/M under fasting conditions (S/M \[fasted\]) followed by S + M under fed conditions (S + M \[fed\]) S/M (fasted)> S+M (fasted)> S+M (fed)> S/M (fed) Saxagliptin/Metformin, Fasting Participants were randomized to receive S/M (fasted) followed by S + M (fasted) followed by S + M (fed) followed by S/M (fed) S/M (fasted)> S+M (fasted)> S+M (fed)> S/M (fed) Saxagliptin/Metformin, Fed Participants were randomized to receive S/M (fasted) followed by S + M (fasted) followed by S + M (fed) followed by S/M (fed) S+ M, (fasted)> S/M (fed)> S/M (fasted)>S+M (fed) Co-administration of Saxagliptin and Metformin IR, Fasted Participants were randomized to receive oral co-administration of a 2.5 mg tablet of saxagliptin plus a 500 mg tablet of metformin immediate release (IR) under fasted conditions (S + M \[fasted\]) followed by a fixed dose combination (FDC) tablet of 2.5 mg saxagliptin/500 mg metformin IR under fed conditions (S/M \[fed\]) followed by S/M under fasting conditions (S/M \[fasted\]) followed by S + M under fed conditions (S + M \[fed\]) S+ M, (fasted)> S/M (fed)> S/M (fasted)>S+M (fed) Saxagliptin/Metformin, Fed Participants were randomized to receive oral co-administration of a 2.5 mg tablet of saxagliptin plus a 500 mg tablet of metformin immediate release (IR) under fasted conditions (S + M \[fasted\]) followed by a fixed dose combination (FDC) tablet of 2.5 mg saxagliptin/500 mg metformin IR under fed conditions (S/M \[fed\]) followed by S/M under fasting conditions (S/M \[fasted\]) followed by S + M under fed conditions (S + M \[fed\]) S/M (fasted)> S+M (fasted)> S+M (fed)> S/M (fed) Co-administration of Saxagliptin and Metformin IR, Fasted Participants were randomized to receive S/M (fasted) followed by S + M (fasted) followed by S + M (fed) followed by S/M (fed) S/M (fasted)> S+M (fasted)> S+M (fed)> S/M (fed) Co-administration of Saxagliptin and Metformin IR, Fed Participants were randomized to receive S/M (fasted) followed by S + M (fasted) followed by S + M (fed) followed by S/M (fed) S/M (fed)> S+M (fed)> S+M (fasted)> S/M (fasted) Saxagliptin/Metformin, Fasting Participants were randomized to receive S/M (fed) followed by S+M (fed) followed by S+M (fasted) followed by S/M (fasted) S+M (fed)> S/M (fasted) >S/M (fed)> S+M (fasted) Saxagliptin/Metformin, Fasting Participants were randomized to receive S + M (fed) followed by S/M (fasted) followed by S/M (fed) followed by S+M (fasted) S+M (fed)> S/M (fasted) >S/M (fed)> S+M (fasted) Co-administration of Saxagliptin and Metformin IR, Fed Participants were randomized to receive S + M (fed) followed by S/M (fasted) followed by S/M (fed) followed by S+M (fasted) S+M (fed)> S/M (fasted) >S/M (fed)> S+M (fasted) Saxagliptin/Metformin, Fed Participants were randomized to receive S + M (fed) followed by S/M (fasted) followed by S/M (fed) followed by S+M (fasted) S/M (fed)> S+M (fed)> S+M (fasted)> S/M (fasted) Co-administration of Saxagliptin and Metformin IR, Fasted Participants were randomized to receive S/M (fed) followed by S+M (fed) followed by S+M (fasted) followed by S/M (fasted) S/M (fed)> S+M (fed)> S+M (fasted)> S/M (fasted) Co-administration of Saxagliptin and Metformin IR, Fed Participants were randomized to receive S/M (fed) followed by S+M (fed) followed by S+M (fasted) followed by S/M (fasted) S/M (fed)> S+M (fed)> S+M (fasted)> S/M (fasted) Saxagliptin/Metformin, Fed Participants were randomized to receive S/M (fed) followed by S+M (fed) followed by S+M (fasted) followed by S/M (fasted)
- Primary Outcome Measures
Name Time Method Saxagliptin Mean Area Under the Plasma Concentration Time Curve From Time Zero To Infinity (AUC [0-INF]) Day 1: 0 hr, 0.25 hr, 0.5 hr, 0.75 hr, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 18 hr, Day 2: 0 hr, 12 hr, Day 3: 0 hr AUC (0-T) for single-dose saxagliptin (2.5 mg), either coadministered with metformin IR (500 mg), or administered as FDC 2.5 mg saxagliptin/500 mg metformin IR, under fasted and fed conditions.
Metformin Mean AUC (0-T) Day 1: 0 hr, 0.25 hr, 0.5 hr, 0.75 hr, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 18 hr, Day 2: 0 hr, 12 hr, Day 3: 0 hr AUC (0-T for single-dose metformin (500 mg), either coadministered with saxagliptin (2.5 mg) or administerd as FDC 2.5 mg saxagliptin/500 mg metformin IR, under fasted and fed conditions.
Saxagliptin Mean Area Under the Plasma Concentration Time Curve From Time Zero To Time of Last Quantifiable Concentration (AUC [0-T]} Day 1: 0 hr, 0.25 hr, 0.5 hr, 0.75 hr, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 18 hr, Day 2: 0 hr, 12 hr, Day 3: 0 hr AUC (0-T) for single-dose saxagliptin (2.5 mg), either coadministered with metformin IR (500 mg), or administered as FDC 2.5 mg saxagliptin/500 mg metformin IR, under fasted and fed conditions.
Metformin T-half and T-max Day 1: 0 hr, 0.25 hr, 0.5 hr, 0.75 hr, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 18 hr, Day 2: 0 hr, 12 hr, Day 3: 0 hr T-half and T-max for single-dose metformin IR (500 mg), either coadministered with saxagliptin (2.5 mg), or administerd as FDC 2.5 mg saxagliptin/500 mg metformin IR, under fasted and fed conditions.
Saxagliptin Mean Maximum Observed Plasma Concentration (Cmax) Day 1: 0 hr, 0.25 hr, 0.5 hr, 0.75 hr, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 18 hr, Day 2: 0 hr, 12 hr, Day 3: 0 hr Cmax of single-dose saxagliptin (2.5 mg), either coadministered with metformin IR (500 mg), or administered as FDC 2.5 mg saxagliptin/500 mg metformin IR, under fasted and fed conditions.
Saxagliptin Mean Plasma Half-life (T-half) and Mean Time of Maximum Observed Plasma Concentration (T-max) Day 1: 0 hr, 0.25 hr, 0.5 hr, 0.75 hr, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 18 hr, Day 2: 0 hr, 12 hr, Day 3: 0 hr T-half and T-max for single-dose saxagliptin (2.5 mg), either coadministered with metformin IR (500 mg) or administered as FDC 2.5 mg saxagliptin/500 mg metformin IR, under fasted and fed conditions.
Metformin Mean Cmax Day 1: 0 hr, 0.25 hr, 0.5 hr, 0.75 hr, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 18 hr, Day 2: 0 hr, 12 hr, Day 3: 0 hr Cmax of single-dose metformin IR (500 mg), either coadministered with saxagliptin (2.5 mg) or administerd as FDC 2.5 mg saxagliptin/500 mg metformin IR, under fasted and fed conditions.
Metformin Mean AUC(0-INF) Day 1: 0 hr, 0.25 hr, 0.5 hr, 0.75 hr, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 18 hr, Day 2: 0 hr, 12 hr, Day 3: 0 hr AUC (0-INF) for single-dose metformin IR (500 mg), either coadministered with saxagliptin (2.5 mg) or administerd as FDC 2.5 mg saxagliptin/500 mg metformin IR, under fasted and fed conditions.
- Secondary Outcome Measures
Name Time Method BMS-510849 Mean T-half and T-max Day 1: 0 hr, 0.25 hr, 0.5 hr, 0.75 hr, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 18 hr, Day 2: 0 hr, 12 hr, Day 3: 0 hr T-half and Tmax of the saxagliptin metabolite BMS-510849, following single-dose saxagliptin (2.5 mg) coadministered with metformin IR (500 mg) or administerd as an FDC 2.5 mg saxagliptin/500 mg metformin IR tablet, under fasted and fed conditions.
BMS-510849 Mean AUC (0-T) Day 1: 0 hr, 0.25 hr, 0.5 hr, 0.75 hr, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 18 hr, Day 2: 0 hr, 12 hr, Day 3: 0 hr AUC (0-T) for the saxagliptin metabolite BMS-510849, following single-dose saxagliptin (2.5 mg) coadministered with metformin IR (500 mg) or administration as an FDC 2.5 mg saxagliptin/500 mg metformin IR tablet, under fasted and fed conditions.
BMS-510849 Mean Cmax Day 1: 0 hr, 0.25 hr, 0.5 hr, 0.75 hr, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 18 hr, Day 2: 0 hr, 12 hr, Day 3: 0 hr Cmax of the saxagliptin metabolite BMS-510849, following single-dose saxagliptin (2.5 mg) coadministered with metformin IR (500 mg) or administered as an FDC 2.5 mg saxagliptin/500 mg metformin IR tablet, under fasted and fed conditions.
Number of Participants With Clinically Relevant Electrocardiogram (ECG) Abnormalities Period 1 Day 1, Period 2 Day 1, Period 3 Day 1, Period 4 Day 1, Period 4 Day 3 PR interval, QRS complex, width of QRS, QT interval, and QT corrected for heart rate adjusting for heart rate using either Bazett formula or Fridericia formula were measured. ECG abnormalities were judged to be of medical importance by the Investigator.
Number of Participants With Clinically Relevant Vital Sign Abnormalities Period 1 Day 1, Period 2 Day 1, Period 3 Day 1, Period 4 Day 1, Period 4 Day 3 Mean systolic and diastolic blood pressure, heart rate, respiration, and temperature were assessed.Vital sign abnormalities abnormalities were judged to be of medical importance by the Investigator.
BMS-510849 Mean AUC (0-INF) Day 1: 0 hr, 0.25 hr, 0.5 hr, 0.75 hr, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 18 hr, Day 2: 0 hr, 12 hr, Day 3: 0 hr AUC (0-T)= for the saxagliptin metabolite BMS-510849, following single-dose saxagliptin (2.5 mg) coadministered with metformin IR (500 mg) or administered as an FDC 2.5 mg saxagliptin/500 mg metformin IR tablet, under fasted and fed conditions.
Number of Participants With at Least 1 Adverse Event (AE), Death, Serious AE (SAE), or AEs Leading to Discontinuation From Day 1 through Day 45, including up to 56 days after last dose of study medication 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.
Number of Participants With Laboratory Marked Abnormalities From Day 1 through Day 45, including up to 56 days after last dose of study medication High=greater than Upper Normal Limit (ULN), Low=lower than Lower Normal Limit (LLN). LLN/ULN= Leukocytes: \<0.9 x LLN/ \>1.2 x ULN; blood urea nitrogen (BUN): \>1.1 x ULN; creatinine: \>1.33 x BL; phosphorous (P): \<0.75 x LLN/ \>1.2 5 x ULN; creatinine kinase (CK): \>1.5 x ULN; urine blood=use ≥2 x BL if value ≥2+ or BL1+
Number of Participant With Clinically Relevant Physical Examination Abnormalities Screen, Period 1 Day -1, prior to discharge A physical examination was conducted which included height and weight measurements, from which the Body Mass Index was determined. Physical examination abnormalities were judged to be of medical importance by the Investigator.
Trial Locations
- Locations (1)
Mds Pharma Services
🇺🇸Lincoln, Nebraska, United States