A Study Comparing the Amount of Metformin and After Taking a Combination Tablet vs. Separate Tablets

Study Overview
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Brief Summary
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The primary objective of the study is to establish if the same amount of drug is absorbed into the blood after ingesting a combination dapagliflozin/metformin tablet vs. the individual dapagliflozin tablet and individual metformin tablet.

Official Title
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A Two Part, Open Label, Randomized, Phase I Bioequivalence Study Comparing the Fixed Dose Combination Dapagliflozin/Metformin IR Tablet (2.5 mg/850 mg or 5 mg/1000 mg) vs. the Free Combination of Dapagliflozin and Metformin IR Tablets, in Healthy Volunteers, in the Fed State

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: Dapagliflozin/Metformin
* Drug: Dapagliflozin
* Drug: Metformin
* Drug: Dapagliflozin/Metformin
* Drug: Dapagliflozin
* Drug: Metformin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female healthy volunteers must be post-menopausal (cessation of menses >1year), be surgically sterile (documented) or hysterectomy or on abstinence Have normal physical exam, vital signs Electrocardiogram (ECG) findings, and laboratory values Exclusion Criteria: Use of prescription medication for a chronic or acute medical condition within 3 weeks of randomization History of allergy to metformin Previous participation in an AstraZeneca (AZ) or BristolMyers-Sqibb dapagliflozin study

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

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Fixed dose combination dapagliflozin/metformin IR tablets followed by free combination of dapagliflozin tablet and metform IR tablet | Drug: Dapagliflozin/Metformin<br>* Fixed dose combination dapagliflozin/metformin IR tablet 2.5 mg/850 mg Oral Single dose<br>Drug: Dapagliflozin<br>* dapagliflozin tablet 2.5 mg Oral Single dose<br>Drug: Metformin<br>* metformin IR tablet 850 mg Oral Single dose<br>* Other names: Glucophage;|
| Experimental: 2<br>Free combination of dapagliflozin tablet and metform IR tablet followed by fixed dose combination dapagliflozin/metformin IR tablets | Drug: Dapagliflozin/Metformin<br>* Fixed dose combination dapagliflozin/metformin IR tablet 2.5 mg/850 mg Oral Single dose<br>Drug: Dapagliflozin<br>* dapagliflozin tablet 2.5 mg Oral Single dose<br>Drug: Metformin<br>* metformin IR tablet 850 mg Oral Single dose<br>* Other names: Glucophage;|
| Experimental: 3<br>Fixed dose combination dapagliflozin/metformin IR tablets followed by free combination of dapagliflozin tablet and metform IR tablet | Drug: Dapagliflozin/Metformin<br>* Fixed dose combination dapagliflozin/metformin IR tablet 5 mg/1000 mg Oral Single dose<br>Drug: Dapagliflozin<br>* dapagliflozin tablet 5 mg Oral Single dose<br>Drug: Metformin<br>* metformin IR tablet 1000 mg Oral Single dose<br>* Other names: Glucophage;|
| Experimental: 4<br>Free combination of dapagliflozin tablet and metform IR tablet followed by fixed dose combination dapagliflozin/metformin IR tablets | Drug: Dapagliflozin/Metformin<br>* Fixed dose combination dapagliflozin/metformin IR tablet 5 mg/1000 mg Oral Single dose<br>Drug: Dapagliflozin<br>* dapagliflozin tablet 5 mg Oral Single dose<br>Drug: Metformin<br>* metformin IR tablet 1000 mg Oral Single dose<br>* Other names: Glucophage;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| bioequivalence will be demonstrated if the 90% confidence interval (CI) for the formulation effect is contained within the interval of 0.8000-1.2500 for AUC(0-t), AUCinf and Cmax with respect to both dapagliflozin and metformin. |  | Immediately prior to administration of the investigational product (IP). After intake of IP PK blood samples will be drawn every 15 minutes for the first hour, every 30 minutes for the second hour and every hour up to 72 h after intake of IP. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To examine the safety and tolerability of the combination of dapagliflozin and metformin. |  | Throughout study (for 4 days in each period and a follow-up visit  6 days later) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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healthy volunteers, bioequivalence, dapagliflozin, metformin