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

Healthy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02022254
• Other study ID #: NN9535-3817
• Secondary ID: 2012-005072-33U1
• Status: Completed
• Phase: Phase 1
• First received: December 16, 2013
• Last updated: March 31, 2017
• Start date: December 17, 2013
• Est. completion date: August 28, 2014

Study information

• Verified date: March 2017
• Source: Novo Nordisk A/S
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: August 28, 2014
• Est. primary completion date: August 28, 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes
• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Healthy

Intervention

Drug:
• semaglutide
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.
• placebo
Semaglutide placebo will be administered s.c.
• metformin
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.
• warfarin
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.

Locations

Country	Name	City	State
Germany	Novo Nordisk Investigational Site	Berlin

Sponsors (1)

Lead Sponsor	Collaborator
Novo Nordisk A/S

Country where clinical trial is conducted

Germany, 

References & Publications (1)

Hausner H, Derving Karsbøl J, Holst AG, Jacobsen JB, Wagner FD, Golor G, Anderson TW. Effect of Semaglutide on the Pharmacokinetics of Metformin, Warfarin, Atorvastatin and Digoxin in Healthy Subjects. Clin Pharmacokinet. 2017 Mar 27. doi: 10.1007/s40262- — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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)
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	Incremental area under the INR (international normalised ratio) -curve		From 0 to 168 hours

External Links

•   Clinical Trials at Novo Nordisk