Comparison of Repaglinide and Metformin Combination Tablet Versus Repaglinide and Metformin as Separate Tablets in Healthy Volunteers

A Randomised, 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 Male Volunteers

This trial is conducted in Asia. The aim of this clinical trial is to investigate the bioequivalence of repaglinide and metformin combination tablet versus repaglinide and metformin as coadministered tablets after meal.

The trial is designed as a three-period, six-sequence, single-dose, crossover pharmacokinetic trial where the trial participant is randomised to one of six possible treatment periods (Williams design). The trial participant will receive one single dose of each trial product in varying order.

Study Overview

• Status: Completed
• Conditions: Healthy; Diabetes
• Intervention / Treatment: Drug: repaglinide and metformin combination tablet; Drug: repaglinide and metformin combination tablet; Drug: repaglinide; Drug: metformin

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100032

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Willing to sign informed consent before initiating any trial related procedures
• BMI: 19.0-25.0 kg/m2
• Fasting plasma glucose: 3.9-6.1 mmol/L
• Trial participant is judged to be in good health on the basis of their medical history, physical examination, ECG, 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
• Any regular use of prescription or nonprescription drugs, including mega-vitamin or herbal supplement regimens that cannot be stopped at least two weeks prior to start of treatment and for the duration of the trial
• 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 (400 mL) within the last 2 months prior to trial product dose administration
• Recent history (within the last 2 years) of drug or alcohol abuse
• Known or suspected allergy to trial product or any of the excipients or a history of multiple and/or severe allergies to drugs or foods or of severe anaphylactic reactions
• Subject has taken an investigational drug in another clinical trial within the last 4 weeks.
• Recent history (within the last 3 month) of nausea, diarrhea or gastrointestinal complaints
• History of any illness that, in the opinion of the Investigator, might confound the results of the trial or pose additional risk in administering trial product to the trial participant

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A	Drug: repaglinide and metformin combination tablet; Combination tablet of repaglinide (1.0 mg)/metformin (500 mg) given just prior to a standard normal breakfast; Drug: repaglinide and metformin combination tablet; Combination tablet of repaglinide (2.0 mg)/metformin (500 mg) given just prior to a standard normal breakfast
Experimental: B	Drug: repaglinide and metformin combination tablet; Combination tablet of repaglinide (1.0 mg)/metformin (500 mg) given just prior to a standard normal breakfast; Drug: repaglinide and metformin combination tablet; Combination tablet of repaglinide (2.0 mg)/metformin (500 mg) given just prior to a standard normal breakfast
Active Comparator: C	Drug: repaglinide; Co-administration of metformin 500 mg tablet and repaglinide 2 mg tablet given just prior to a standard normal breakfast; Drug: metformin; Concomitant administration: Metformin 500 mg tablet and Repaglinide 2 mg tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
AUC0-t and Cmax (after repaglinide 2.0 mg and metformin 500 mg as co-administered tablets and combination tablet dosing under fed state)	24hr profile after single dose of trial drug in each treatment period

Secondary Outcome Measures

Outcome Measure	Time Frame
Repaglinide AUC(0-24 & 0-∞) and Cmax after combination tablet (repaglinide 1.0 mg/metformin 500 mg) during fed state	24hr profile after single dose of trial drug in each treatment period

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S

Publications and helpful links

Helpful Links

• Clinical Trials at Novo Nordisk

Study record dates

Study Major Dates

• Study Start: August 1, 2009
• Primary Completion (Actual): October 1, 2009
• Study Completion (Actual): October 1, 2009

Study Registration Dates

• First Submitted: August 13, 2009
• First Submitted That Met QC Criteria: August 13, 2009
• First Posted (Estimate): August 14, 2009

Study Record Updates

• Last Update Posted (Estimate): March 24, 2015
• Last Update Submitted That Met QC Criteria: March 23, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Metformin; Repaglinide
• Other Study ID Numbers: NN4440-1963