Investigation of Optimal Dosing Conditions for a Long Acting GLP-1 Analogue 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 evaluate the optimal dosing conditions for semaglutide (a long acting GLP-1 analogue) in healthy male subjects.

Official Title
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A Single Centre, Multiple Dose, Open Label Randomised Trial to Evaluate the Effect of Post Dose Meal Timings and the Effect of Volume of Water With Dosing on the Pharmacokinetic Properties of Oral Semaglutide 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: semaglutide
* Drug: semaglutide
* Drug: semaglutide
* Drug: semaglutide
* Drug: semaglutide
* Drug: semaglutide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Good general health as judged by the investigator, based on medical history, physical examination, electrocardiogram (ECG), vital signs and clinical laboratory Body mass index (BMI) of 18.5-30.0 kg/m^2 (both inclusive) Exclusion Criteria: Males who are sexually active and not surgically sterilised, who or whose partner(s): a. are not using adequate contraceptive methods (e.g. condom with spermicidal foam/gel/film/cream or contraceptives with a Pearl Index below 1%, such as implants, injectables, combined oral contraceptives, or hormonal intrauterine devices or diaphragm + spermicide) or b. do not refrain from sexual intercourse during the trial and until 30 days following the last dose of trial medication. In addition, subjects must not donate sperm for the duration of the trial and for 30 days following the last dose of trial medication or c. sterilization of either partner Suffer from a life threatening disease or has a history of any clinically significant disease or disorder History of acute idiopathic or chronic pancreatitis Calcitonin value equal to or above 50 ng/L Any clinically significant abnormal laboratory test results (haematology, biochemistry and urinalysis), as judged by the investigator and any of the following laboratory safety results (based on screening results): Amylase, lipase and creatinine, above upper normal range. Aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT) and gamma-glutamyl-transpeptidase (gamma-GT) above 1.5 times upper normal range (UNR). Thrombocytes below 0.75 times lower normal range (LNR) or above 1.25 times UNR. Leucocytes outside 3.0 to 11.0x10^9/L (normal range is 3.91 to 8.77x10^9/L. Sodium outside the range 130.0 to 150.0 mmol/L (normal range is 136-145 mmol/L). Potassium outside the range 3.0 to 5.5 mmol/L (normal range is 3.5 to 5.1 mmol/L) Any clinically significant abnormal ECG, as judged by the investigator Subjects who are smokers

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Post-dose fasting 120 mins/50 ml water<br> | Drug: semaglutide<br>* Subjects will be dosed in the morning, for 10 days, after an overnight fast (liquid will not be allowed from 2 hours before dosing). Dose to be taken with 50 ml of water. During the post-dose fasting period of 120 mins, no food or liquid is allowed.<br>|
| Experimental: Post-dose fasting 60 mins/50 ml water<br> | Drug: semaglutide<br>* Subjects will be dosed in the morning, for 10 days, after an overnight fast (liquid will not be allowed from 2 hours before dosing). Dose to be taken with 50 ml of water. During the post-dose fasting period of 60 mins, no food or liquid is allowed.<br>|
| Experimental: Post-dose fasting 30 mins/50 ml water<br> | Drug: semaglutide<br>* Subjects will be dosed in the morning, for 10 days, after an overnight fast (liquid will not be allowed from 2 hours before dosing). Dose to be taken with 50 ml of water. During the post-dose fasting period of 30 mins, no food or liquid is allowed.<br>|
| Experimental: Post-dose fasting 15 mins/50 ml water<br> | Drug: semaglutide<br>* Subjects will be dosed in the morning, for 10 days, after an overnight fast (liquid will not be allowed from 2 hours before dosing). Dose to be taken with 50 ml of water. During the post-dose fasting period of 15 mins, no food or liquid is allowed.<br>|
| Experimental: Post-dose fasting 120 mins/120 ml water<br> | Drug: semaglutide<br>* Subjects will be dosed in the morning, for 10 days, after an overnight fast (liquid will not be allowed from 2 hours before dosing). Dose to be taken with 120 ml of water. During the post-dose fasting period of 120 mins, no food or liquid is allowed.<br>|
| Experimental: Post-dose fasting 60 mins/120 ml water<br> | Drug: semaglutide<br>* Subjects will be dosed in the morning, for 10 days, after an overnight fast (liquid will not be allowed from 2 hours before dosing). Dose to be taken with 120 ml of water. During the post-dose fasting period of 60 mins, no food or liquid is allowed.<br>|
| Experimental: Post-dose fasting 30 mins/120 ml water<br> | Drug: semaglutide<br>* Subjects will be dosed in the morning, for 10 days, after an overnight fast (liquid will not be allowed from 2 hours before dosing). Dose to be taken with 120 ml of water. During the post-dose fasting period of 30 mins, no food or liquid is allowed.<br>|
| Experimental: Post-dose fasting 15 mins/120 ml water<br> | Drug: semaglutide<br>* Subjects will be dosed in the morning, for 10 days, after an overnight fast (liquid will not be allowed from 2 hours before dosing). Dose to be taken with 120 ml of water. During the post-dose fasting period of 15 mins, no food or liquid is allowed.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC 0-24h; Area under the semaglutide concentration curve from time 0-24 hours after the 10th dosing |  | 0-24hrs after the 10th dosing | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax; The maximum plasma semaglutide concentration |  | Post-dose at day 10 | 
| tmax; Time to maximum plasma semaglutide concentration |  | Post-dose at day 10 | 
| t1/2; the terminal half-life of semaglutide |  | Post-dose at day 10 |