Investigation on Safety, Tolerability and Pharmacokinetics of Single and Multiple Doses of a Long-acting GLP-1 Analogue (Semaglutide) in an Oral Formulation in Healthy Male 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 safety, tolerability and pharmacokinetics (the effect of the investigated drug on the body) of single and multiple doses of a long-acting GLP-1 analogue (semaglutide) in an oral formulation in healthy male subjects.

Official Title
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Investigation on Safety, Tolerability and Pharmacokinetics of Single and Multiple Doses of a Long-acting GLP-1 Analogue (Semaglutide) in an Oral Formulation in Healthy Male Subjects

Conditions
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Diabetes, Diabetes Mellitus, Type 2, Healthy

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male subject, who is considered to be generally healthy, based on the medical history, physical examination, and the results of vital signs, electrocardiogram (ECG) and laboratory safety tests performed during the screening visit, as judged by the investigator Body Mass Index (BMI) between 20 and 30 kg/m^2 Glycosylated haemoglobin (HbA1c) below 6.0% (only in Part B) Exclusion Criteria: History of, or presence of, cancer, diabetes or any clinically significant cardiovascular, respiratory, metabolic, renal, hepatic, gastrointestinal (GI), endocrinological, haematological, dermatological, venereal, neurological, psychiatric diseases or other major disorders, as judged by the investigator Use of prescription or non-prescription medicinal and herbal products (except routine vitamins) within three weeks preceding the dosing. Occasional use of paracetamol or acetylsalicylic acid is permitted

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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Male

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: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A (single dose)<br> | Drug: semaglutide<br>* A maximum of six single-dose cohorts of oral semaglutide administered according to an ascending dose design. Starting dose 2 mg, max. dose 60 mg. Progression to next dose will be based on safety evaluation. Sequential cohorts.<br>Drug: placebo<br>* In each cohort of 10, eight subjects will randomised to active treatment and two to placebo.<br>|
| Experimental: Part B (multiple dose)<br> | Drug: semaglutide<br>* Oral semaglutide administered as five multiple dose cohorts, where one of the cohorts will test a different dosing condition compared to the others. End doses from 10 mg/day to 60 mg/day. Progression to next dose will be based on safety evaluation. Semi-parallel cohorts.<br>Drug: placebo<br>* In each cohort of 24, 16 subjects will be randomised to active treatment, four to placebo and four to a enhancer-containing placebo (placebo C).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A: Number of treatment emergent adverse events (TEAEs) |  | Day -1 to Day 24 | 
| Part B: Number of treatment emergent adverse events (TEAEs) |  | Recorded from the time of first dosing (Visit 3, Day -1 to day +2) and until completion of the post treatment follow-up visit (Visit 18, Day 90-104) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A: AUC0-24h,semaglutide: the area under the semaglutide plasma concentration curve |  | From time 0 to 24 hours after a single dose (Day 0) | 
| Part B: AUCτ,semaglutide: area under the semaglutide plasma concentration curve |  | Over the dosing interval (0-24 hours) after the last 3 daily doses (Days 67-69) | 
| Part B: Change in fasting plasma glucose (FPG) from baseline |  | Day 0 (pre-dose), day 70 | 
| Part B: Change in body weight from baseline |  | Day -1, day 70 |