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

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

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.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2; Diabetes
• Intervention / Treatment: Drug: Semaglutide 0.5 mg; Drug: Placebo (semaglutide 0.5 mg); Drug: Semaglutide 1.0 mg; Drug: Placebo (semaglutide 1.0 mg)

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100730
    • Novo Nordisk Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Semaglutide 0.5 mg; 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; A dose of 0.25 mg semaglutide gradually increased to 0.5 mg injected subcutaneously (under the skin) once weekly for 13 weeks.
Placebo Comparator: Semaglutide 0.5 mg placebo; 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); A dose of 0.25 mg semaglutide placebo gradually increased to 0.5 mg injected subcutaneously (under the skin) once weekly for 13 weeks.
Experimental: Semaglutide 1.0 mg; 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; A dose of 0.25 mg semaglutide gradually increased to 1.0 mg injected subcutaneously (under the skin) once weekly for 13 weeks.
Placebo Comparator: Semaglutide 1.0 mg placebo; 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); A dose of 0.25 mg semaglutide placebo gradually increased to 1.0 mg injected subcutaneously (under the skin) once weekly for 13 weeks.

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): September 21, 2017
• Primary Completion (Actual): July 10, 2018
• Study Completion (Actual): August 7, 2018

Study Registration Dates

• First Submitted: September 18, 2017
• First Submitted That Met QC Criteria: September 18, 2017
• First Posted (Actual): September 20, 2017

Study Record Updates

• Last Update Posted (Actual): February 15, 2021
• Last Update Submitted That Met QC Criteria: February 11, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: NN9535-3686; U1111-1149-6572 (Other Identifier: World Health Organization (WHO))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: According to the Novo Nordisk disclosure commitment on novonordisk-trials.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes