Clinical trial NCT03288740: A Trial to Assess the Pharmacokinetics, Safety and Tolerability of Semaglutide in Healthy Chinese Subjects
Official title: A Single-centre, Randomised, Double-blind, Placebo-controlled, Multiple-dose Trial to Assess the Pharmacokinetics, Safety and Tolerability of Semaglutide in Healthy Chinese Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Diabetes
Diabetes Mellitus, Type 2
Lead sponsor: Novo Nordisk A/S
Sponsor class: INDUSTRY
First posted: 2017-09-20
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Area under the semaglutide plasma concentration time curve at steady state (semaglutide 0.5 mg)
timeFrame: 0-168 hours after last administration of semaglutide
measure: Area under the semaglutide plasma concentration time curve at steady state (semaglutide 1.0 mg)
timeFrame: 0-168 hours after last administration of semaglutide
Secondary outcomes:
measure: Maximum observed semaglutide plasma concentration at steady state
timeFrame: 0-168 hours after last administration of semaglutide
measure: Time to maximum observed semaglutide plasma concentration at steady state
timeFrame: 0-168 hours after last administration of semaglutide
measure: Total apparent clearance of semaglutide at steady state
timeFrame: 0-168 hours after last administration of semaglutide
measure: Terminal elimination half-life of semaglutide at steady state
timeFrame: 0-840 hours after last administration of semaglutide
measure: Apparent volume of distribution of semaglutide at steady state
timeFrame: 0-840 hours after last administration of semaglutide
measure: Trough plasma semaglutide concentration
timeFrame: Before dosing at day 29, 57, 78, 85 and 92
measure: Dose-corrected accumulation ratio
timeFrame: 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
measure: Area under the semaglutide plasma concentration time curve
timeFrame: 0-168 hours after the first dose of semaglutide 0.25 mg (starting dose level)
measure: Maximum observed semaglutide plasma concentration
timeFrame: 0-168 hours after the first dose of semaglutide 0.25 mg (starting dose level)
measure: Time to maximum observed semaglutide plasma concentration
timeFrame: 0-168 hours after the first dose of semaglutide 0.25 mg (starting dose level)
measure: Number of treatment emergent adverse events (TEAEs)
timeFrame: Visit 2 (Day 1) - visit 23 (Day 120-127)
measure: Number of hypoglycaemic episodes
timeFrame: Visit 2 (Day 1) - visit 23 (Day 120-127)
measure: Incidence of anti-semaglutide antibodies (positive/negative) at follow-up
timeFrame: Visit 23 (Day 120-127)
Other outcomes:
Locations:
city: Beijing
country: China
facility: Novo Nordisk Investigational Site
Study officials:
References:
citation: Shi A, Xie P, Nielsen LL, Skjoth TV, He X, Haugaard SP. Pharmacokinetics, Safety and Tolerability of Once-Weekly Subcutaneous Semaglutide in Healthy Chinese Subjects: A Double-Blind, Phase 1, Randomized Controlled Trial. Adv Ther. 2021 Jan;38(1):550-561. doi: 10.1007/s12325-020-01548-y. Epub 2020 Nov 7.