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

• ClinicalTrials.gov Identifier: NCT04097600
• Recruitment Status: Completed
• First Posted: September 20, 2019
• Last Update Posted: September 13, 2022
• Sponsor: Novo Nordisk A/S
• Information provided by (Responsible Party): Novo Nordisk A/S

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Healthy Volunteers; Type 2 Diabetes	Drug: Oral semaglutide	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 274 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: September 30, 2019
• Actual Primary Completion Date: December 16, 2020
• Actual Study Completion Date: January 20, 2021

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 64 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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).

Contacts and Locations

Locations

Germany

Novo Nordisk Investigational Site

Berlin, Germany, 14050

Sponsors and Collaborators

Novo Nordisk A/S

Investigators

• Study Director: Clinical Reporting Anchor and Disclosure (1452); Novo Nordisk A/S

More Information

• Responsible Party: Novo Nordisk A/S
• ClinicalTrials.gov Identifier: NCT04097600
• Other Study ID Numbers: NN9924-4486; U1111-1226-6257 ( Other Identifier: World Health Organization (WHO) ); 2019-000279-17 ( Registry Identifier: European Medicines Agency (EudraCT) )
• First Posted: September 20, 2019
• Last Update Posted: September 13, 2022
• Last Verified: September 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: According to the Novo Nordisk disclosure commitment on novonordisk-trials.com
• URL: http://novonordisk-trials.com

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No