Clinical trial NCT04016974: A Research Study of How Oral Semaglutide Tablets Work in Healthy People Who Are Chinese
Official title: A Multiple-dose, Single-centre, Randomised, Double-blind, Placebo-controlled Trial to Investigate the Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of Oral Semaglutide in Healthy Chinese Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Diabetes Mellitus, Type 2
Lead sponsor: Novo Nordisk A/S
Sponsor class: INDUSTRY
First posted: 2019-07-12
Enrollment: 32
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: This study looks at the way a new medicine tablet called semaglutide moves in and throughout the body over time. It will also look at if the medicine is safe and the body can accept it. The new medicine is planned to treat diabetes. The aim of the study is to see how semaglutide tablets work in healthy people who are Chinese. Participants will either get oral semaglutide tablets or placebo (dummy) tablets - which treatment is decided by chance. The tablet form of semaglutide is a new medicine that cannot be prescribed. Doctors can prescribe semaglutide as an injection only. It is for the treatment of diabetes in some countries. Participants will get 1 tablet per day for 12 weeks (84 days). Participants will get 1 tablet a day to take with up to half a glass of water (maximum 120 mL). Participants must take the tablet first thing in the morning on an empty stomach (water is allowed until 2 hours before taking the tablet). After taking the tablet, participants must not eat or drink anything for at least 30 minutes. After 30 minutes, they can have their first meal of the day and take any other medicines they may need, such as birth control tablets, routine vitamins and use of paracetamol at times.


Eligibility criteria: Inclusion Criteria:

* Chinese male or female, aged 18-55 years (both inclusive) at the time of signing informed consent.
* Body weight equal to or above 54.0 kg
* Body mass index (BMI) between 20.0 and 24.9 kg/m\^2 (both inclusive)
* Considered to be generally healthy based on the medical history, physical examination, and the results of vital signs, ECG and clinical laboratory tests performed during the screening visit, as judged by the investigator.

Exclusion Criteria:

* Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using highly effective contraceptive methods
* History of pancreatitis (acute or chronic) as declared by the subject.
* Family or personal history of multiple endocrine neoplasia type 2 (MEN2) or medullary thyroid carcinoma (MTC) as declared by the subject.
* History or presence of malignant neoplasms within the last 5 years (except basal and squamous cell skin cancer and in-situ carcinomas) as declared by the subject.
* History of major surgical procedures involving the stomach potentially affecting absorption of trial product (e.g., subtotal and total gastrectomy, sleeve gastrectomy, gastric bypass surgery) as declared by the subject.
* Smoker (defined as a subject who is smoking equal to or more than 1 cigarette or the equivalent per day).
* Unable or unwilling to refrain from smoking and use of nicotine substitute products during the inpatient periods, as judged by the investigator.
* Any blood draw in excess of 25 mL in the past month, or donation of blood or plasma in excess of 400 mL within the 3 months preceding screening.

Primary outcomes:
measure: AUC0-24h,sema,SS, area under the semaglutide concentration-time curve during a dosing interval (0-24 hours) at steady state
timeFrame: After the last dose of oral semaglutide at dose levels of 3 mg on day 28 and 7 mg on day 56, and after the last 3 daily doses of oral semaglutide at dose level 14 mg on day 82, 83 and 84
Secondary outcomes:
measure: Cmax,sema,SS, maximum observed semaglutide plasma concentration during a dosing interval (0-24 hours) at steady state
timeFrame: After the last dose of oral semaglutide at dose levels of 3 mg on day 28 and 7 mg on day 56, and after the last 3 daily doses of oral semaglutide at dose level 14 mg on day 82, 83 and 84
measure: tmax,sema,SS, time to maximum observed semaglutide plasma concentration during a dosing interval (0-24 hours) at steady state
timeFrame: After the last dose of oral semaglutide at dose levels of 3 mg on day 28 and 7 mg on day 56, and after the last 3 daily doses of oral semaglutide at dose level 14 mg on day 82, 83 and 84
measure: CL/Fsema,SS, total apparent clearance of semaglutide at steady state
timeFrame: After the last dose of oral semaglutide at dose levels of 3 mg on day 28 and 7 mg on day 56, and after the last 3 daily doses of oral semaglutide at dose level 14 mg on day 82, 83 and 84
measure: Ctrough,sema,SS, trough semaglutide plasma concentration at steady state
timeFrame: After the last 3 daily doses of oral semaglutide administration at 3, 7 and 14 mg dose levels on day 27-29, 55-57 and 83-85
measure: t½,sema,SS, terminal half-life of semaglutide at steady state
timeFrame: After the last dose of oral semaglutide 14 mg on day 84
measure: Vss/Fsema, apparent volume of distribution of semaglutide at steady state
timeFrame: After the last dose of oral semaglutide 14 mg on day 84
measure: MRTsema,SS, mean residence time of semaglutide at steady state
timeFrame: After the last dose of oral semaglutide 14 mg on day 84
measure: Rtheor,sema,SS, theoretical accumulation index, which is defined as [1/(1-Exp (-λZ,sema,SS*24h))], where λZ,sema,SS=log(2)/t½,sema,SS
timeFrame: After the last dose of oral semaglutide 14 mg on day 84
measure: Change in body weight from baseline
timeFrame: Day 1, day 85
measure: Change in fasting plasma glucose from baseline
timeFrame: Day 1, day 85
measure: Number of treatment-emergent adverse events
timeFrame: From the time of first dosing (day 1) until completion of the follow-up visit (day 119-121)
measure: Number of treatment-emergent hypoglycaemic episodes
timeFrame: From the time of first dosing (day 1) until completion of the follow-up visit (day 119-121)
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Hospital-phase I
state: Beijing
Study officials:
affiliation: Novo Nordisk A/S
name: Clinical Reporting Anchor and Disclosure (1452)
role: STUDY_DIRECTOR
References:
citation: Xie P, Abildlund MT, Baekdal TA, He X, Lyauk YK, Patted URH, Ning Z, Shi A. A phase 1, randomized, double-blind, placebo-controlled trial investigating the pharmacokinetics, pharmacodynamics, safety and tolerability of oral semaglutide in healthy Chinese subjects. Diabetes Obes Metab. 2024 Aug;26(8):3068-3077. doi: 10.1111/dom.15624. Epub 2024 May 29.