Investigation on Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Doses of a Long-acting GLP-1 Analogue in Healthy Male Subjects and Male Subjects With Type 2 Diabetes

This trial is conducted in Europe. The aim of the trial is to investigate safety, tolerability, pharmacokinetics (the exposure of the trial drug in the body), and pharmacodynamics (the effect of the investigated drug on the body) of multiple doses of a long-acting GLP-1 analogue (oral semaglutide) and a carrier in healthy male subjects and male subjects with type 2 diabetes (T2D).

Study Overview

• Status: Completed
• Conditions: Healthy; Diabetes Mellitus, Type 2; Diabetes
• Intervention / Treatment: Drug: semaglutide; Drug: semaglutide; Drug: semaglutide; Drug: placebo; Drug: placebo

• Study Type: Interventional
• Enrollment (Actual): 107
• 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: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Male subject, who is considered to be generally healthy, based on the medical history, physical examination, and the results of vital signs, electrocardiogram (ECG) and laboratory safety tests performed during the screening visit, as judged by the investigator. This also applies to subjects with T2D, except for the underlying diabetes with or without associated hyperlipidaemia and/or hypertension
• Body mass index (BMI): a) Healthy subjects: above or equal to 20 and below 30 kg/m^2. b) Subjects with T2D: BMI above or equal to 20 and below or equal to 37 kg/m^2
• Glycosylated haemoglobin (HbA1c): a) Healthy subjects: below 6.0%. b) Subjects with T2D: between 6.5 and 9.0% (both inclusive)
• Additional inclusion criterion only for subjects with T2D: Male subjects with T2D (diagnosed within the past 10 years) treated with diet and exercise and/or who have been on stable doses of metformin for at least 12 weeks prior to Visit 3 (Day -1 or 0) and for whom no changes in treatment are planned for the trial period

Exclusion Criteria:

• History of, or presence of, cancer, diabetes (only for healthy subjects) or any clinically significant cardiovascular (only for healthy subjects), respiratory, metabolic, renal, hepatic, gastro-intestinal (GI), endocrinological (except diabetes in subjects with T2D), haematological, dermatological, venereal, neurological, psychiatric diseases or other major disorders, as judged by the investigator
• Blood pressure in supine position at the screening examination above: a) 140 mmHg systolic and/or above 90 mmHg diastolic for healthy subjects. b) 160 mmHg systolic and/or above 95 mmHg diastolic for subjects with T2D
• Use of prescription or non-prescription medicinal products (except routine vitamins) within three weeks preceding the dosing. Occasional use of paracetamol or acetylsalicylic acid is permitted. a. For subjects with T2D: Any other current diabetes treatment apart from metformin (e.g. treatment with incretin mimetics, Dipeptidyl Peptidase-IV (DPP-IV) inhibitors, insulin secretagogues, insulin or thiazolidinediones (TZDs)). Use of blood lipidregulating agents, as well as blood pressure regulating, and thrombo-embolic agents is allowed
• Exclusion criteria only for subjects with T2D:
• Proliferative retinopathy or maculopathy requiring acute treatment as determined by funduscopy/fundus photography and judged by the investigator. If subject presents a medical certificate for funduscopy/fundus photography performed within last 3 months this can substitute the funduscopy/fundus photography at screening
• Nephropathy stages 3 to 5, i.e. estimated glomerular filtration rate (eGFR) below 60. The eGFRshould be determined using the Modification of Diet in Renal Disease 4-variable method encompassing creatinine, age, gender, and race
• Diabetic peripheral neuropathy using the 10 g Semmes-Weinstein monofilament examination at the great toe or plantar aspect of the fifth metatarsal
• Clinically significant active cardiovascular disease including history of myocardial infarction and/or heart failure (New York Heart Association (NYHA) class III and IV1) at the discretion of the investigator

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Healthy - 20 mg	Drug: semaglutide; Start doses of 5 mg and 10 mg with end dose of 20 mg. For oral administration.; Drug: semaglutide; Start doses of 5 mg and 10 mg with end doses of either 20 mg or 40 mg. For oral administration.; Drug: semaglutide; Start doses of 5 mg and 10 mg with end doses of either 20 mg, 40 mg or 60 mg. For oral administration.; Drug: placebo; Placebo semaglutide. For oral administration.; Drug: placebo; Placebo semaglutide with carrier. For oral administration.
EXPERIMENTAL: Healthy - 40 mg	Drug: semaglutide; Start doses of 5 mg and 10 mg with end dose of 20 mg. For oral administration.; Drug: semaglutide; Start doses of 5 mg and 10 mg with end doses of either 20 mg or 40 mg. For oral administration.; Drug: semaglutide; Start doses of 5 mg and 10 mg with end doses of either 20 mg, 40 mg or 60 mg. For oral administration.; Drug: placebo; Placebo semaglutide. For oral administration.; Drug: placebo; Placebo semaglutide with carrier. For oral administration.
EXPERIMENTAL: Healthy - 60 mg	Drug: semaglutide; Start doses of 5 mg and 10 mg with end dose of 20 mg. For oral administration.; Drug: semaglutide; Start doses of 5 mg and 10 mg with end doses of either 20 mg or 40 mg. For oral administration.; Drug: semaglutide; Start doses of 5 mg and 10 mg with end doses of either 20 mg, 40 mg or 60 mg. For oral administration.; Drug: placebo; Placebo semaglutide. For oral administration.; Drug: placebo; Placebo semaglutide with carrier. For oral administration.
EXPERIMENTAL: T2D - 20/40/60 mg	Drug: semaglutide; Start doses of 5 mg and 10 mg with end dose of 20 mg. For oral administration.; Drug: semaglutide; Start doses of 5 mg and 10 mg with end doses of either 20 mg or 40 mg. For oral administration.; Drug: semaglutide; Start doses of 5 mg and 10 mg with end doses of either 20 mg, 40 mg or 60 mg. For oral administration.; Drug: placebo; Placebo semaglutide. For oral administration.; Drug: placebo; Placebo semaglutide with carrier. For oral administration.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of treatment emergent adverse events (TEAEs) recorded	From the time of first dosing and until completion of the post treatment follow-up visits (Day 90 to 104)

Secondary Outcome Measures

Outcome Measure	Time Frame
Area under the plasma concentration curve over the dosing interval (0-24 hours)	After the last 3 daily doses for semaglutide and carrier
Change from baseline in fasting plasma glucose (FPG)	Week 0, week 10 (Day 69)
Change from baseline in C-peptide	Week 0, week 10 (Day 69)
Change from baseline in insulin	Week 0, week 10 (Day 69)
Change from baseline in glucagon	Week 0, week 10 (Day 69)
Change from baseline in glycosylated haemoglobin type A1c (HbA1c)	Week 0, week 10 (Day 69)

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S

Publications and helpful links

General Publications

• Seco A, Aparicio S, Gonzalez-Camejo J, Jimenez-Benitez A, Mateo O, Mora JF, Noriega-Hevia G, Sanchis-Perucho P, Serna-Garcia R, Zamorano-Lopez N, Gimenez JB, Ruiz-Martinez A, Aguado D, Barat R, Borras L, Bouzas A, Marti N, Paches M, Ribes J, Robles A, Ruano MV, Serralta J, Ferrer J. Resource recovery from sulphate-rich sewage through an innovative anaerobic-based water resource recovery facility (WRRF). Water Sci Technol. 2018 Dec;78(9):1925-1936. doi: 10.2166/wst.2018.492.
• Granhall C, Donsmark M, Blicher TM, Golor G, Sondergaard FL, Thomsen M, Baekdal TA. Safety and Pharmacokinetics of Single and Multiple Ascending Doses of the Novel Oral Human GLP-1 Analogue, Oral Semaglutide, in Healthy Subjects and Subjects with Type 2 Diabetes. Clin Pharmacokinet. 2019 Jun;58(6):781-791. doi: 10.1007/s40262-018-0728-4.

Helpful Links

• Clinical Trials at Novo Nordisk

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 19, 2012
• Primary Completion (ACTUAL): April 8, 2013
• Study Completion (ACTUAL): April 8, 2013

Study Registration Dates

• First Submitted: September 13, 2012
• First Submitted That Met QC Criteria: September 13, 2012
• First Posted (ESTIMATE): September 18, 2012

Study Record Updates

• Last Update Posted (ACTUAL): January 4, 2019
• Last Update Submitted That Met QC Criteria: January 2, 2019
• Last Verified: January 1, 2019

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: NN9924-3991; 2012-000361-20 (EUDRACT_NUMBER); U1111-1127-4408 (OTHER: WHO)