A Trial to Assess the Pharmacokinetics, Safety and Tolerability of Semaglutide in Healthy Chinese Subjects

Study Overview
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Brief Summary
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The main purpose of the trial is to assess the pharmacokinetics of semaglutide (i.e. the way the drug is distributed in the body over a period of time) following once-weekly administration of semaglutide in healthy Chinese subjects. Different dose levels (0.5 and 1.0 mg) will be investigated in this trial. Participants will be administered semaglutide or placebo once-weekly by subcutaneous injection (under the skin fold of the abdominal wall) using a pen injector with a very small, thin needle by the trial doctor at the trial site for 13 weeks. The trial consists of 23 visits in total, including visit for screening and safety tests, visit for dose administration and blood sample collection. The total time of participation will be approximately 18-22 weeks depending on participant's individual visit schedule.

Official Title
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A Single-centre, Randomised, Double-blind, Placebo-controlled, Multiple-dose Trial to Assess the Pharmacokinetics, Safety and Tolerability of Semaglutide in Healthy Chinese Subjects

Conditions
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Diabetes, Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Semaglutide 0.5 mg
* Drug: Placebo (semaglutide 0.5 mg)
* Drug: Semaglutide 1.0 mg
* Drug: Placebo (semaglutide 1.0 mg)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male and female Chinese subjects Age between 18 to 55 years (both inclusive) at the time of signing informed consent Body mass index (BMI) between 20 and 24.9 kg/sqm (both inclusive) Body weight greater than or equal to 54.0 kg Exclusion Criteria: Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential not using an adequate contraceptive method throughout the trial including follow-up period. Adequate contraceptive measures are sterilisation, intrauterine device (IUD), oral contraceptives or barrier methods 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 products (including routine or non-routine vitamins or herbal products) or topical medicinal products (except paracetamol and oral contraceptives) within 3 weeks (or within 5 half-lives of the medicinal product, whichever is longest) prior to Visit 2 (randomisation) Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2 History of pancreatitis (acute or chronic) Calcitonin greater than or equal to 50 ng/L Blood donation, surgery or trauma with significant blood loss (400 mL) within the last 12 weeks prior to screening

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Semaglutide 0.5 mg<br>Participants will enter a 13 weeks treatment with 4 weeks dosing at dose level 0.25 mg and 9 weeks at 0.5 mg semaglutide. | Drug: Semaglutide 0.5 mg<br>* A dose of 0.25 mg semaglutide gradually increased to 0.5 mg injected subcutaneously (under the skin) once weekly for 13 weeks.<br>|
| Placebo Comparator: Semaglutide 0.5 mg placebo<br>Participants will enter a 13 weeks treatment with 4 weeks dosing at dose level 0.25 mg and 9 weeks at 0.5 mg semaglutide placebo. | Drug: Placebo (semaglutide 0.5 mg)<br>* A dose of 0.25 mg semaglutide placebo gradually increased to 0.5 mg injected subcutaneously (under the skin) once weekly for 13 weeks.<br>|
| Experimental: Semaglutide 1.0 mg<br>Participants will have 13 weeks treatment with 4 weeks dosing at dose level of 0.25 mg, 4 weeks at 0.5 mg, and 5 weeks at 1.0 mg semaglutide. | Drug: Semaglutide 1.0 mg<br>* A dose of 0.25 mg semaglutide gradually increased to 1.0 mg injected subcutaneously (under the skin) once weekly for 13 weeks.<br>|
| Placebo Comparator: Semaglutide 1.0 mg placebo<br>Participants will have 13 weeks treatment with 4 weeks dosing at dose level of 0.25 mg, 4 weeks at 0.5 mg, and 5 weeks at 1.0 mg semaglutide placebo. | Drug: Placebo (semaglutide 1.0 mg)<br>* A dose of 0.25 mg semaglutide placebo gradually increased to 1.0 mg injected subcutaneously (under the skin) once weekly for 13 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the semaglutide plasma concentration time curve at steady state (semaglutide 0.5 mg) | Calculated based on semaglutide measured in blood. | 0-168 hours after last administration of semaglutide | 
| Area under the semaglutide plasma concentration time curve at steady state (semaglutide 1.0 mg) | Calculated based on semaglutide measured in blood. | 0-168 hours after last administration of semaglutide | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum observed semaglutide plasma concentration at steady state | Calculated based on semaglutide measured in blood. | 0-168 hours after last administration of semaglutide | 
| Time to maximum observed semaglutide plasma concentration at steady state | Calculated based on semaglutide measured in blood. | 0-168 hours after last administration of semaglutide | 
| Total apparent clearance of semaglutide at steady state | Calculated based on semaglutide measured in blood. | 0-168 hours after last administration of semaglutide | 
| Terminal elimination half-life of semaglutide at steady state | Calculated based on semaglutide measured in blood. | 0-840 hours after last administration of semaglutide | 
| Apparent volume of distribution of semaglutide at steady state | Calculated based on semaglutide measured in blood. | 0-840 hours after last administration of semaglutide | 
| Trough plasma semaglutide concentration | Calculated based on semaglutide measured in blood. | Before dosing at day 29, 57, 78, 85 and 92 | 
| Dose-corrected accumulation ratio | Calculated based on semaglutide measured in blood. | Based on the area under the semaglutide plasma concentration curve from 0-168 hours after the first dose and the area under the semaglutide plasma concentration curve 0-168 hours after the last dose | 
| Area under the semaglutide plasma concentration time curve | Calculated based on semaglutide measured in blood. | 0-168 hours after the first dose of semaglutide 0.25 mg (starting dose level) | 
| Maximum observed semaglutide plasma concentration | Calculated based on semaglutide measured in blood. | 0-168 hours after the first dose of semaglutide 0.25 mg (starting dose level) | 
| Time to maximum observed semaglutide plasma concentration | Calculated based on semaglutide measured in blood. | 0-168 hours after the first dose of semaglutide 0.25 mg (starting dose level) | 
| Number of treatment emergent adverse events (TEAEs) | Count and % of adverse events | Visit 2 (Day 1) - visit 23 (Day 120-127) | 
| Number of hypoglycaemic episodes | Count of episodes | Visit 2 (Day 1) - visit 23 (Day 120-127) | 
| Incidence of anti-semaglutide antibodies (positive/negative) at follow-up | Count of episodes | Visit 23 (Day 120-127) |