A Trial Investigating the Influence of Oral Semaglutide on the Pharmacokinetics of Lisinopril and Warfarin in Healthy Subjects

Study Overview
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Brief Summary
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This trial is conducted in Europe. The aim of the trial is to investigate the influence of oral semaglutide (NNC0113-0217) on the pharmacokinetics of lisinopril and warfarin in healthy subjects.

Official Title
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An Open-label, Single Arm, Sequential, Single Centre Trial Investigating the Influence of Oral Semaglutide (NNC0113-0217) on Pharmacokinetics of Lisinopril and Warfarin in Healthy Subjects

Conditions
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Diabetes, Healthy

Intervention / Treatment
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* Drug: semaglutide
* Drug: lisinopril
* Drug: warfarin
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female aged 18-75 years (both inclusive) at time of signing informed consent Body mass index 20.0-29.9 kg/m^2 (both inclusive) A good general health based on medical history, physical examination, and results of vital signs, electrocardiogram and laboratory safety tests performed during the screening visit, as judged by the investigator Exclusion Criteria: Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using adequate contraceptive methods. Female of child bearing potential must use effective methods of birth control for the duration of the trial and for 5 weeks following last dose. Only highly effective methods of birth control are accepted (i.e. one that results in a less than 1% per year failure rate when used consistently and correctly, such as implants, injectables, combined oral contraceptives, and some intrauterine devices) History of Crohn's disease, ulcerative colitis, or other inflammatory bowel disease Hypertension (defined as sitting systolic blood pressure above 140 mmHg and/or diastolic blood pressure above 90 mmHg). If white-coat hypertension is suspected at the screening visit, a repeated measurement is allowed Any blood draw in excess of 50 mL in the past month, or donation of blood or plasma in excess of 400 mL within the 3 months preceding screening

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Victim and perpetrator compounds<br>Subjects receive two different victim compounds (lisinopril and warfarin) and two different perpetrator compounds (placebo semaglutide with carrier and oral semaglutide). Each dosing occasion is separated by a 7-day wash-out period. | Drug: semaglutide<br>* For oral administration once daily. Doses of 5 mg and 10 mg, respectively, will be given for 7 days followed by 20 mg administered on days 43-84.<br>Drug: lisinopril<br>* For oral administration. A single dose of 20 mg is administered three times either alone or conconmitantly with a perpetrator compound (days 1, 15 and 71).<br>Drug: warfarin<br>* For oral administration. A single dose of 5 mg is administered three times either alone or conconmitantly with a perpetrator compound (days 8, 22 and 78).<br>Drug: placebo<br>* A single dose of SNAC is administered conconmitantly with victim compounds (days 15 and 22).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the S-warfarin concentration-time curve |  | From dosing to infinity calculated from a 0-168 hours S-warfarin concentration-time-curve based on 18 sampling time points | 
| Area under the R-warfarin concentration-time curve |  | From dosing to infinity calculated from a 0-168 hours S-warfarin concentration-time-curve based on 18 sampling time points | 
| Area under the lisinopril concentration-time curve |  | From dosing to infinity calculated from a 0-60 hours lisinopril concentration-time-curve based on 13 sampling time points | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum observed S-warfarin plasma concentration |  | 0 to 168 hours after single dose | 
| Maximum observed R-warfarin plasma concentration |  | 0 to 168 hours after single dose | 
| Maximum observed lisinopril plasma concentration |  | 0 to 60 hours after single dose |