A Research Study Comparing Active Drug in the Blood in Healthy Participants Following Dosing of the Current and a New Formulation (D) Semaglutide Tablets

A Comparative Bioavailability Trial of Steady State Semaglutide Exposure With the Current Formulation (Semaglutide) and a New Formulation (Semaglutide D) of Oral Semaglutide in Healthy Subjects

In this study two different tablets for oral use of a known investigational medicinal product, called semaglutide, will be tested. One is the current formulation and the other one is a new formulation of semaglutide. Both will be administered as a tablet and are for the treatment of diabetes. Currently, semaglutide is only prescribed as injections for the treatment of diabetes in some countries. The aim of this study is to find out if the dosage strength of the current formulation of semaglutide can be reduced in the new tablet formulation. For this purpose, it will be measured how much semaglutide is taken up in the body from the two (2) different tablet formulations each with three (3) different dosage strengths. The tablet version of the study medicine is a new medicine that cannot yet be prescribed. Participants will either get semaglutide in the current tablet formulation previously tested in many large studies, or get the tablet that contains semaglutide in a new formulation - which treatment is decided by chance. Participants will get one tablet per day over 4 weeks in each of the 3 treatment periods (i.e. treatment in a total of 12 weeks). The tablets should be taken in the morning together with half a glass of water (120 mL), after an overnight fast of at least 6 hours (no food or drinks). Furthermore, water is not allowed from 2 hours before dosing. After dosing participants must wait 30 minutes before they may eat or drink. At home, participants must take their breakfast 30-45 minutes after dosing.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes; Healthy Volunteers
• Intervention / Treatment: Drug: Oral semaglutide

• Study Type: Interventional
• Enrollment (Actual): 274
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 14050
    • Novo Nordisk Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 64 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female, aged 18-64 years (both inclusive) at the time of signing informed consent.
• Body mass index between 20.0 kg/m^2 and 29.9 kg/m^2 (both inclusive).
• Considered to be generally healthy based on the medical history, physical examination, and the results of vital signs, electrocardiogram and clinical laboratory tests performed during the screening visit, as judged by the investigator.

Exclusion Criteria:

• Glycated haemoglobin (HbA1c) equal to or above 6.5 % (48 mmol/mol) at screening.
• Use of tobacco and nicotine products, defined as any of the below:
• Smoking more than 5 cigarettes or the equivalent per day
• Not willing to refrain from smoking and use of nicotine substitute products during the in-house period(s)
• History (as declared by the subject) of major surgical procedures involving the stomach potentially affecting absorption of trial products (e.g. subtotal and total gastrectomy, sleeve gastrectomy, gastric bypass surgery).
• Presence of clinically significant gastrointestinal disorders or symptoms of gastrointestinal disorders potentially affecting absorption of drugs or nutrients, as judged by the investigator.
• Personal or first degree relative(s) history of multiple endocrine neoplasia type 2 or medullary thyroid carcinoma (as declared by the subject).
• History (as declared by the subject) or presence of pancreatitis (acute or chronic).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sequence 1; Current form 3 mg in treatment period 1, followed by current form 7 mg in treatment period 2, followed by new form 11.2 mg in treatment period 3	Drug: Oral semaglutide; Oral semaglutide current formulation and oral semaglutide new formulation, each in 3 different strengths, administered once daily during 6 treatment periods, each lasting 12 weeks
Experimental: Sequence 2; Current form 3 mg in treatment period 1, followed by new form 5.6 mg in treatment period 2, followed by current form 14 mg in treatment period 3	Drug: Oral semaglutide; Oral semaglutide current formulation and oral semaglutide new formulation, each in 3 different strengths, administered once daily during 6 treatment periods, each lasting 12 weeks
Experimental: Sequence 3; New form 2.4 mg in treatment period 1, followed by current form 7 mg in treatment period 2, followed by current form 14 mg in treatment period 3	Drug: Oral semaglutide; Oral semaglutide current formulation and oral semaglutide new formulation, each in 3 different strengths, administered once daily during 6 treatment periods, each lasting 12 weeks
Experimental: Sequence 4; New form 2.4 mg in treatment period 1, followed by new form 5.6 mg in treatment period 2, followed by current form 14 mg in treatment period 3	Drug: Oral semaglutide; Oral semaglutide current formulation and oral semaglutide new formulation, each in 3 different strengths, administered once daily during 6 treatment periods, each lasting 12 weeks
Experimental: Sequence 5; New form 2.4 mg in treatment period 1, followed by current form 7 mg in treatment period 2, followed by new form 11.2 mg in treatment period 3	Drug: Oral semaglutide; Oral semaglutide current formulation and oral semaglutide new formulation, each in 3 different strengths, administered once daily during 6 treatment periods, each lasting 12 weeks
Experimental: Sequence 6; Current form 3 mg in treatment period 1, followed by new form 5.6 mg in treatment period 2, followed by new form 11.2 mg in treatment period 3	Drug: Oral semaglutide; Oral semaglutide current formulation and oral semaglutide new formulation, each in 3 different strengths, administered once daily during 6 treatment periods, each lasting 12 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC0-24h,sema,SS; area under the semaglutide plasma concentration-time curve during a dosing interval at steady state	nmol*h/L	From 0 to 24 hours after the last dosing of oral semaglutide low, medium and high dose on days 28, 56 and 84, respectively

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax,sema,SS; maximum semaglutide plasma concentration at steady state	nmol/L	From 0 to 24 hours after the last dosing of oral semaglutide low, medium and high dose on days 28, 56 and 84, respectively
tmax,sema,SS; time to maximum semaglutide plasma contraction at steady state	h	From 0 to 24 hours after the last dosing of oral semaglutide low, medium and high dose on days 28, 56 and 84, respectively
t½,sema,SS; terminal half-life of semaglutide at steady state	h	Determined by concentrations measured between day 84 and follow-up at day 119 of semaglutide at steady state

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S

Study record dates

Study Major Dates

• Study Start (Actual): September 30, 2019
• Primary Completion (Actual): December 16, 2020
• Study Completion (Actual): January 20, 2021

Study Registration Dates

• First Submitted: September 19, 2019
• First Submitted That Met QC Criteria: September 19, 2019
• First Posted (Actual): September 20, 2019

Study Record Updates

• Last Update Posted (Actual): September 13, 2022
• Last Update Submitted That Met QC Criteria: September 12, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Other Study ID Numbers: NN9924-4486; U1111-1226-6257 (Other Identifier: World Health Organization (WHO)); 2019-000279-17 (Registry Identifier: European Medicines Agency (EudraCT))

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: No
• Studies a U.S. FDA-regulated device product: No