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

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

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.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2; Diabetes
• Intervention / Treatment: Drug: repaglinide; Drug: metformin; Drug: repaglinide and metformin combination tablet

• Study Type: Interventional
• Enrollment (Actual): 62
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33169
      • Novo Nordisk Investigational Site
  • Washington
    • Tacoma, Washington, United States, 98418
      • Novo Nordisk Investigational Site

Participation Criteria

Eligibility Criteria

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

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment period 1	Drug: repaglinide; 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; Drug: metformin; 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; Drug: repaglinide and metformin combination tablet; 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
Experimental: Treatment period 2	Drug: repaglinide; 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; Drug: metformin; 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; Drug: repaglinide and metformin combination tablet; 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
Experimental: Treatment period 3	Drug: repaglinide; 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; Drug: metformin; 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; Drug: repaglinide and metformin combination tablet; 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
Active Comparator: Treatment period 4	Drug: repaglinide; 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; Drug: metformin; 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; Drug: repaglinide and metformin combination tablet; 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

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S

Publications and helpful links

General Publications

• Reilley S, Chang C-T, Lyness W. Single-Dose Pharmacokinetics of a Repaglinide/Metformin Fixed-Dose Combination Tablet in Fasted and Fed Conditions. Diabetes 2008; 57 (Suppl 1): 2449 in 01-D

Helpful Links

• Clinical Trials at Novo Nordisk

Study record dates

Study Major Dates

• Study Start: June 1, 2006
• Primary Completion (Actual): July 1, 2006
• Study Completion (Actual): July 1, 2006

Study Registration Dates

• First Submitted: December 8, 2011
• First Submitted That Met QC Criteria: December 8, 2011
• First Posted (Estimate): December 9, 2011

Study Record Updates

• Last Update Posted (Actual): February 10, 2017
• Last Update Submitted That Met QC Criteria: February 9, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Metformin; Repaglinide
• Other Study ID Numbers: NN4440-1779