Trial Investigating the Effect of Semaglutide on Energy Intake, Appetite Sensations, Postprandial Glucose and Triglyceride Metabolism and Gastric Emptying in Obese Subjects Compared With Placebo

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 effect of semaglutide on energy intake, appetite sensations, postprandial glucose and triglyceride metabolism and gastric emptying in obese subjects compared with placebo.

Official Title
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A Single-centre, Randomised, Double-blind Two-period Cross-over Trial Investigating the Effect of Semaglutide on Energy Intake, Appetite Sensations, Postprandial Glucose and Triglyceride Metabolism and Gastric Emptying in Obese Subjects Compared With Placebo

Conditions
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Diabetes, Metabolism and Nutrition Disorder, Obesity

Intervention / Treatment
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* Drug: semaglutide
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, age above or equal to 18 years at the time of signing informed consent HbA1c (glycosylated haemoglobin A1c) below 6.5% A BMI (body mass index) between 30-45 kg/m^2 (both inclusive) Exclusion Criteria: Females who are pregnant, breast-feeding or intend to become pregnant or is of childbearing potential and not using adequate contraceptive method (adequate contraceptive measures as required by local law or practice, UK requirements: adequate contraceptive measures are defined as established use of oral, injected or implanted hormonal methods of contraception, sterilisation, intrauterine device or intrauterine system, or consistent use of barrier methods together with the use of spermicide, and sexual abstinence) Any disorder which, in the opinion of the investigator, might jeopardise subject's safety or compliance with the protocol Diagnosis of type 1 or 2 diabetes mellitus Anticipated change in lifestyle (e.g. eating, exercise or sleeping pattern) during the trial Use of any prescription or non-prescription medication which could interfere with trial pharmacokinetic or pharmacodynamic results, as judged by the investigator or specifically: 1) within 12 months prior to screening any weight lowering pharmacotherapy or pharmacotherapy that may cause weight gain, including systemic corticosteroids (except for a short course of treatment, i.e., 7-10 days), tri-cyclic antidepressants, atypical antipsychotic and mood stabilizers, 2) within 3 months prior to screening use of statins, antihyperlipidemics including fibrates or nicotinic acid and its derivates, 3) supplementation with omega 3 fatty acids from 1 month prior to screening, 4) co-treatment with antihypertensive drugs is allowed if treatment has been stable for at least 1 month prior to screening and treatment should be kept unchanged during the trial Significant history of alcoholism or drug/chemical abuse within 1 year from screening, or a positive result of the urine drug screen or alcohol breath test, or consuming more than 21 units of alcohol per week for females and 28 units of alcohol per week for males (1 unit of alcohol equals ½ pint [285 mL] of beer or lager, 1 glass [125 mL] of wine, or 1/6 gill [25 mL] of spirits) Smoking or use of any nicotine products (including nicotine patches, gum etc.) in the last 3 months prior to screening or a positive cotinine test

Ages Eligible for Study
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Minimum Age: 18 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: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sema<br>Two 12-week treatment periods separated by a wash-out period of 5-7 weeks. Finally, a follow-up visit is performed 5-7 weeks after last dosing | Drug: semaglutide<br>* Solution for subcutaneous (s.c. - under the skin) injection. 0.25 mg semaglutide once weekly for four weeks, 0.5 mg semaglutide once weekly for four weeks followed by 1.0 mg semaglutide once weekly for five weeks<br>|
| Placebo Comparator: Placebo<br> | Drug: placebo<br>* Solution for subcutaneous (s.c. - under the skin) injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ad libitum energy intake during a lunch meal (following a standardised breakfast meal) |  | After 12 weeks of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean postprandial increase (iAUC30-300min/270 min) in rating of overall appetite score (OAS) using Visual Analogue Scales (VAS) before and up to 300 minutes after intake of a standardised breakfast meal |  | After 12 weeks of treatment during a standardised meal test day | 
| Incremental area under the 0-300 minutes glucose profile (iAUC0-300min,Glucose) following intake of a standardised breakfast meal |  | After 12 weeks of treatment during a standardised meal test day | 
| Gastric emptying measured by the area under the 0-300 minutes plasma paracetamol concentration curve (AUC0-300min,para) following intake of a standardised breakfast meal (including 1500 mg paracetamol) |  | After 12 weeks of treatment during a standardised meal test day | 
| Incremental area under the 0-480 minutes triglyceride profile (iAUC0-480min,TG) following intake of a standardised fat-rich meal |  | After 12 weeks of treatment during a standardised meal test day | 
| Incidence of adverse events |  | From baseline to follow-up (5-7 weeks after last trial drug administration) |