Clinical trial NCT02022254: Influence of Semaglutide on Pharmacokinetics and Pharmacodynamics of Warfarin and Pharmacokinetics of Metformin in Healthy Subjects
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Diabetes
Diabetes Mellitus, Type 2
Healthy
Lead sponsor: Novo Nordisk A/S
Sponsor class: INDUSTRY
First posted: 2013-12-27
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Area under the metformin plasma concentration-time curve
timeFrame: 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)
measure: Area under the S-warfarin plasma concentration-time curve
timeFrame: From time 0 to 168 hours after a single dose of warfarin without semaglutide exposure (Day 11) and at semaglutide steady state (Day 111)
measure: Area under the R-warfarin plasma concentration-time curve
timeFrame: 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 outcomes:
measure: Maximum observed metformin plasma concentration at steady state
timeFrame: 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)
measure: Maximum observed S-warfarin plasma concentration after single dose
timeFrame: (0-168 hours) after a single dose of warfarin without semaglutide exposure and at semaglutide steady state (warfarin administrations on Days 11 and 111)
measure: Maximum observed R-warfarin plasma concentration after single dose
timeFrame: (0-168 hours) after a single dose of warfarin without semaglutide exposure and at semaglutide steady state (warfarin administrations on Days 11 and 110)
measure: Incremental area under the INR (international normalised ratio) -curve
timeFrame: From 0 to 168 hours
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Novo Nordisk Investigational Site
Study officials:
affiliation: Novo Nordisk A/S
name: Global Clinical Registry (GCR, 1452)
role: STUDY_DIRECTOR
References:
citation: Hausner H, Derving Karsbol 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 Nov;56(11):1391-1401. doi: 10.1007/s40262-017-0532-6.