Single Dose Pharmacokinetics of Repaglinide, Metformin and Combination Tablet in 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 administered as an individual tablets with repaglinide and metformin administered as a combination tablet.

Official Title
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A Randomized, Single-Blind, Four-Period Crossover Study Examining the Single Dose Pharmacokinetics of Repaglinide, Metformin and Combination Tablet Dosing (NN4440) in Fasting and 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, health food or dietary supplement regimens, with the exception of contraceptives, that cannot be stopped at least 1 week prior to Visit 2 (trial product 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 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>* Subjects will receive 850 mg metformin alone on a fasting state, 2 mg repaglinide alone on a fasting state, 2 mg repaglinide/850 mg metformin (NN4440 2/850) in the fasting state or 2 mg repaglinide/850 mg metformin (NN4440 2/850) immediately prior to a standardised high fat meal on 4 separate dosing visits in varying order<br>Drug: metformin<br>* Subjects will receive 850 mg metformin alone on a fasting state, 2 mg repaglinide alone on a fasting state, 2 mg repaglinide/850 mg metformin (NN4440 2/850) in the fasting state or 2 mg repaglinide/850 mg metformin (NN4440 2/850) immediately prior to a standardised high fat meal on 4 separate dosing visits in varying order<br>Drug: repaglinide and metformin combination tablet<br>* Subjects will receive 850 mg metformin alone on a fasting state, 2 mg repaglinide alone on a fasting state, 2 mg repaglinide/850 mg metformin (NN4440 2/850) in the fasting state or 2 mg repaglinide/850 mg metformin (NN4440 2/850) immediately prior to a standardised high fat meal on 4 separate dosing visits in varying order<br>|
| Experimental: Treatment period 2<br> | Drug: repaglinide<br>* Subjects will receive 850 mg metformin alone on a fasting state, 2 mg repaglinide alone on a fasting state, 2 mg repaglinide/850 mg metformin (NN4440 2/850) in the fasting state or 2 mg repaglinide/850 mg metformin (NN4440 2/850) immediately prior to a standardised high fat meal on 4 separate dosing visits in varying order<br>Drug: metformin<br>* Subjects will receive 850 mg metformin alone on a fasting state, 2 mg repaglinide alone on a fasting state, 2 mg repaglinide/850 mg metformin (NN4440 2/850) in the fasting state or 2 mg repaglinide/850 mg metformin (NN4440 2/850) immediately prior to a standardised high fat meal on 4 separate dosing visits in varying order<br>Drug: repaglinide and metformin combination tablet<br>* Subjects will receive 850 mg metformin alone on a fasting state, 2 mg repaglinide alone on a fasting state, 2 mg repaglinide/850 mg metformin (NN4440 2/850) in the fasting state or 2 mg repaglinide/850 mg metformin (NN4440 2/850) immediately prior to a standardised high fat meal on 4 separate dosing visits in varying order<br>|
| Experimental: Treatment period 3<br> | Drug: repaglinide<br>* Subjects will receive 850 mg metformin alone on a fasting state, 2 mg repaglinide alone on a fasting state, 2 mg repaglinide/850 mg metformin (NN4440 2/850) in the fasting state or 2 mg repaglinide/850 mg metformin (NN4440 2/850) immediately prior to a standardised high fat meal on 4 separate dosing visits in varying order<br>Drug: metformin<br>* Subjects will receive 850 mg metformin alone on a fasting state, 2 mg repaglinide alone on a fasting state, 2 mg repaglinide/850 mg metformin (NN4440 2/850) in the fasting state or 2 mg repaglinide/850 mg metformin (NN4440 2/850) immediately prior to a standardised high fat meal on 4 separate dosing visits in varying order<br>Drug: repaglinide and metformin combination tablet<br>* Subjects will receive 850 mg metformin alone on a fasting state, 2 mg repaglinide alone on a fasting state, 2 mg repaglinide/850 mg metformin (NN4440 2/850) in the fasting state or 2 mg repaglinide/850 mg metformin (NN4440 2/850) immediately prior to a standardised high fat meal on 4 separate dosing visits in varying order<br>|
| Active Comparator: Treatment period 4<br> | Drug: repaglinide<br>* Subjects will receive 850 mg metformin alone on a fasting state, 2 mg repaglinide alone on a fasting state, 2 mg repaglinide/850 mg metformin (NN4440 2/850) in the fasting state or 2 mg repaglinide/850 mg metformin (NN4440 2/850) immediately prior to a standardised high fat meal on 4 separate dosing visits in varying order<br>Drug: metformin<br>* Subjects will receive 850 mg metformin alone on a fasting state, 2 mg repaglinide alone on a fasting state, 2 mg repaglinide/850 mg metformin (NN4440 2/850) in the fasting state or 2 mg repaglinide/850 mg metformin (NN4440 2/850) immediately prior to a standardised high fat meal on 4 separate dosing visits in varying order<br>Drug: repaglinide and metformin combination tablet<br>* Subjects will receive 850 mg metformin alone on a fasting state, 2 mg repaglinide alone on a fasting state, 2 mg repaglinide/850 mg metformin (NN4440 2/850) in the fasting state or 2 mg repaglinide/850 mg metformin (NN4440 2/850) immediately prior to a standardised high fat meal on 4 separate dosing visits in varying order<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fasting repaglinide and metformin Area under the Curve (AUC) following NN4440 administration |  |  | 
| Fasting repaglinide and metformin Area under the Curve (AUC) following individual administration |  |  | 
| Fasting repaglinide and metformin Cmax (maximum drug concentration) following NN4440 administration |  |  | 
| Fasting repaglinide and metformin Cmax (maximum drug concentration) following individual administration |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Repaglinide and metformin tmax (time to maximum) following individual administration fasting state |  |  | 
| Repaglinide and metformin tmax (time to maximum) following NN4440 administration fasting state |  |  | 
| Physical examinations |  |  | 
| Vital signs |  |  |