Single Dose Pharmacokinetics of Repaglinide, Metformin and Combination Tablet in Fed Healthy Volunteers

Study Overview
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Brief Summary
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This trial is conducted in the United States of America (USA). The aim of this trial is to compare repaglinide and metformin as co-administered tablets and as a combination tablet.

Official Title
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A Randomized, Single-Blind, Three-Period Crossover Study Examining the Single Dose Pharmacokinetics of Concomitantly Administered Repaglinide and Metformin Versus Combination Tablet Dosing (NN4440) in Fed Healthy Volunteers

Conditions
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Diabetes, Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: repaglinide
* Drug: metformin
* Drug: repaglinide and metformin combination tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male and female volunteers (female not pregnant, lactating or breastfeeding) BMI (Body Mass Index) between 19-29 kg/m^2, both inclusive Fasting plasma glucose from 70-115 mg/dl Subject is judged to be in good health on the basis of their medical history, physical examination, ECG (electrocardiogram), and routine laboratory data Exclusion Criteria: Any clinically significant disease history, in the opinion of the Investigator, of systemic or organ disease Clinically significant abnormalities on pre-study clinical examination or any laboratory measurements during screening Positive results on screening for Hepatitis B surface antigen, Hepatitis C antibody and HIV (human immunodeficiency virus) antibody Positive results on the drug abuse/alcohol screen Any regular use of prescription or nonprescription drugs, including mega-vitamin or herbal supplement regimens, other than contraceptives, that cannot be stopped at least 1 week prior to Visit 2 (trial product dose administration) and for the duration of the study Subject is currently a smoker (more than one cigarette per day or equivalent) Use of grapefruit or grapefruit juice within 7 days of trial product dose administration Blood donation, surgery or trauma with significant blood loss (500 mL) within the last 2 months prior to dosing

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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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment period 1<br> | Drug: repaglinide<br>* Single dose of 2 mg tablets administered immediately prior to a standard high fat breakfast concomitantly with metformin as separate tablets. Subjects will be randomised to receive trial drug on 3 separate dosing visits in varying order out of 6 possible treatment periods<br>Drug: metformin<br>* Single dose of 500 mg tablets administered immediately prior to a standard high fat breakfast concomitantly with repaglinide as separate tablets. Subjects will be randomised to receive trial drug on 3 separate dosing visits in varying order out of 6 possible treatment periods<br>Drug: repaglinide and metformin combination tablet<br>* Single dose of 2 mg repaglinide/500 mg metformin (NN4440 2/500) or 1 mg repaglinide/500 mg metformin (NN4440 1/500)administered immediately prior to a standard high fat breakfast. Subjects will be randomised to receive trial drug on 3 separate dosing visits in varying order out of 6 possible treatment periods<br>|
| Experimental: Treatment period 2<br> | Drug: repaglinide<br>* Single dose of 2 mg tablets administered immediately prior to a standard high fat breakfast concomitantly with metformin as separate tablets. Subjects will be randomised to receive trial drug on 3 separate dosing visits in varying order out of 6 possible treatment periods<br>Drug: metformin<br>* Single dose of 500 mg tablets administered immediately prior to a standard high fat breakfast concomitantly with repaglinide as separate tablets. Subjects will be randomised to receive trial drug on 3 separate dosing visits in varying order out of 6 possible treatment periods<br>Drug: repaglinide and metformin combination tablet<br>* Single dose of 2 mg repaglinide/500 mg metformin (NN4440 2/500) or 1 mg repaglinide/500 mg metformin (NN4440 1/500)administered immediately prior to a standard high fat breakfast. Subjects will be randomised to receive trial drug on 3 separate dosing visits in varying order out of 6 possible treatment periods<br>|
| Active Comparator: Treatment period 3<br> | Drug: repaglinide<br>* Single dose of 2 mg tablets administered immediately prior to a standard high fat breakfast concomitantly with metformin as separate tablets. Subjects will be randomised to receive trial drug on 3 separate dosing visits in varying order out of 6 possible treatment periods<br>Drug: metformin<br>* Single dose of 500 mg tablets administered immediately prior to a standard high fat breakfast concomitantly with repaglinide as separate tablets. Subjects will be randomised to receive trial drug on 3 separate dosing visits in varying order out of 6 possible treatment periods<br>Drug: repaglinide and metformin combination tablet<br>* Single dose of 2 mg repaglinide/500 mg metformin (NN4440 2/500) or 1 mg repaglinide/500 mg metformin (NN4440 1/500)administered immediately prior to a standard high fat breakfast. Subjects will be randomised to receive trial drug on 3 separate dosing visits in varying order out of 6 possible treatment periods<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Repaglinide and metformin AUC (Area under the Curve) fed state concomitant tablet administration |  |  | 
| Repaglinide and metformin AUC (Area under the Curve) NN4440 (2/500) combination tablet |  |  | 
| Repaglinide and metformin Cmax (maximum plasma concentration) fed state concomitant tablet administration |  |  | 
| NN4440 (2/500) Cmax (maximum plasma concentration) combination tablet |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Repaglinide AUC after NN4440 (1/500) during fed state |  |  | 
| Repaglinide Cmax after NN4440 ((1/500) during fed state |  |  | 
| Change in physical examinations from screening |  |  | 
| Vital signs |  |  |