Influence of Semaglutide on Pharmacokinetics and Pharmacodynamics of Warfarin and Pharmacokinetics of Metformin in Healthy Subjects

An Open-label, One-sequence Cross Over, Single Centre Trial, Investigating the Influence of Semaglutide on Pharmacokinetics and Pharmacodynamics of Warfarin and Pharmacokinetics of Metformin in Healthy Subjects

Sponsors

Lead Sponsor: Novo Nordisk A/S

Source Novo Nordisk A/S
Brief Summary

This trial is conducted in Europe and Asia. The aim of the trial is to investigate the influence of semaglutide on pharmacokinetics (the exposure of the trial drug in the body) and pharmacodynamics (the effect of the investigated drug on the body) of warfarin and pharmacokinetics of metformin in healthy subjects.

Overall Status Completed
Start Date December 17, 2013
Completion Date August 28, 2014
Primary Completion Date August 28, 2014
Phase Phase 1
Study Type Interventional
Primary Outcome
Measure Time Frame
Area under the metformin plasma concentration-time curve During a dosing interval (0−12 hours) after the last of 7 repeated doses of metformin without semaglutide exposure (Day 4) and at semaglutide steady state (Day 104)
Area under the S-warfarin plasma concentration-time curve From time 0 to 168 hours after a single dose of warfarin without semaglutide exposure (Day 11) and at semaglutide steady state (Day 111)
Area under the R-warfarin plasma concentration-time curve From time 0 to 168 hours after a single dose of warfarin without semaglutide exposure (Day 11) and at semaglutide steady state (Day 111)
Secondary Outcome
Measure Time Frame
Maximum observed metformin plasma concentration at steady state From dosing until 30 hours after the last of 7 repeated doses without semaglutide exposure and at semaglutide steady state (metformin administration on Days 4 and 104)
Maximum observed S-warfarin plasma concentration after single dose (0-168 hours) after a single dose of warfarin without semaglutide exposure and at semaglutide steady state (warfarin administrations on Days 11 and 111)
Maximum observed R-warfarin plasma concentration after single dose (0-168 hours) after a single dose of warfarin without semaglutide exposure and at semaglutide steady state (warfarin administrations on Days 11 and 110)
Incremental area under the INR (international normalised ratio) -curve From 0 to 168 hours
Enrollment 24
Condition
Intervention

Intervention Type: Drug

Intervention Name: semaglutide

Description: Subjects will initiate treatment with 0.25 mg for the first four weeks followed by dose doubling every four weeks up to a dose of 1.0 mg.

Arm Group Label: Semaglutide administrations

Intervention Type: Drug

Intervention Name: placebo

Description: Semaglutide placebo will be administered s.c.

Arm Group Label: Semaglutide administrations

Intervention Type: Drug

Intervention Name: metformin

Description: For oral administration twice daily, in two periods, each of 3.5 days duration. The first period is initiated before semaglutide treatment and the second period is initiated at the end of semaglutide treatment.

Arm Group Label: Semaglutide administrations

Intervention Type: Drug

Intervention Name: warfarin

Description: For oral administration, given as a single dose. The first dose is given before semaglutide treatment and the second dose is given at the end of semaglutide treatment.

Arm Group Label: Semaglutide administrations

Eligibility

Criteria:

Inclusion Criteria:

- Male and female, age between 18 and 55 years (both inclusive) at the time of signing informed consent

- Body mass index (BMI) between 23 and 30 kg/m^2 (both inclusive)

Exclusion Criteria:

- Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearingpotential and not using adequate contraceptive methods for the duration of the trial and for 5 weeks following the last dose of semaglutide. Adequate contraceptive measures are implants, injectables, combined oral contraceptives, hormonal intrauterine device, sexual abstinence or vasectomised partner

- Any clinically significant disease history, in the opinion of the investigator, or systemic or organ disease including: pulmonary, gastrointestinal, hepatic, neurologic, renal, genitourinary and endocrine, dermatologic or hematologic diseases

- Use of prescription or non-prescription systemic or topical medicinal products (including routine or non-routine vitamins or herbal products, but excluding paracetamol and contraceptives) within 3 weeks (or within 5 half-lives of the medicinal product, whichever is longest) prior to Visit 2

- Smoking, drug or alcohol abuse

Gender: All

Minimum Age: 18 Years

Maximum Age: 55 Years

Healthy Volunteers: Accepts Healthy Volunteers

Overall Official
Last Name Role Affiliation
Global Clinical Registry (GCR, 1452) Study Director Novo Nordisk A/S
Location
Facility: Novo Nordisk Investigational Site
Location Countries

Germany

Verification Date

March 2017

Responsible Party

Type: Sponsor

Has Expanded Access No
Condition Browse
Number Of Arms 1
Arm Group

Label: Semaglutide administrations

Type: Experimental

Study Design Info

Intervention Model: Crossover Assignment

Primary Purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov