Pharmacokinetic Drug Interaction Study of Dapagliflozin and Glimepiride or Sitagliptin in Healthy Subjects

Study Overview
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Brief Summary
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To assess the effect of glimepiride on the PK of dapagliflozin and the effect of dapagliflozin on the PK of glimepiride, when co-administered in healthy subjects (Phase A) and to assess the effect of sitagliptin on the PK of dapagliflozin and the effect of dapagliflozin on the PK of sitagliptin, when co-administered in healthy subjects (Phase B)

Official Title
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Pharmacokinetic Drug Interaction Study of Dapagliflozin and Glimepiride or Sitagliptin in Healthy Subjects

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Dapagliflozin
* Drug: Glimepiride
* Drug: Sitagliptin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy subjects as determined by no clinically significant deviation from normal in medical history, physical examination, ECGs, and clinical laboratory determinations Body mass index (BMI) of 18 to 32 kg/m2, inclusive BMI = weight (kg)/[height(m)]2 Exclusion Criteria: WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 12 weeks after the last dose of investigational product Abnormal liver functions tests (ALT, AST or total bilirubin > 10% above ULN) History of chronic or recurrent UTI (defined as 3 occurrences per year) or UTI in the past 3 months History of allergy to SGLT@ inhibitors, DPP$ inhibitors or sulfonylurea or related compounds Prior exposure to dapagliflozin, sitagliptin and glimepiride within 3 months of Day -1 History of recurrent (defined as 3 occurrences per year) or recent vulvovaginal mycotic infections

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Dapagliflozin<br> | Drug: Dapagliflozin<br>* Tablets, Oral, 20 mg, Single Dose<br>* Other names: BMS-512148;|
| Active Comparator: Glimepiride<br> | Drug: Glimepiride<br>* Tablets, Oral, 4 mg, Single Dose<br>* Other names: Amaryl;|
| Active Comparator: Dapagliflozin + Glimepiride<br> | Drug: Dapagliflozin<br>* Tablets, Oral, 20 mg, Single Dose<br>* Other names: BMS-512148;Drug: Glimepiride<br>* Tablets, Oral, 4 mg, Single Dose<br>* Other names: Amaryl;|
| Active Comparator: Sitagliptin<br> | Drug: Sitagliptin<br>* Tablets, Oral, 100 mg, Single Dose<br>* Other names: Januvia;|
| Active Comparator: Dapagliflozin + Sitagliptin<br> | Drug: Dapagliflozin<br>* Tablets, Oral, 20 mg, Single Dose<br>* Other names: BMS-512148;Drug: Sitagliptin<br>* Tablets, Oral, 100 mg, Single Dose<br>* Other names: Januvia;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Exposure to the investigational drug will be measured to compare with and without the co-administration of other drugs |  | 72 hours after dosing | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the safety and tolerability in healthy subjects |  | 15 time points up to 72 hours after dosing |