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

NCT ID: NCT01686945

Last Updated: 2019-01-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 107 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-09-19
• Study Completion Date: 2013-04-08

Brief Summary

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).

Conditions

Diabetes; Diabetes Mellitus, Type 2; Healthy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Healthy - 20 mg

Group Type: EXPERIMENTAL

semaglutide

Intervention Type: DRUG

Start doses of 5 mg and 10 mg with end dose of 20 mg. For oral administration.

placebo

Intervention Type: DRUG

Placebo semaglutide. For oral administration.

placebo

Intervention Type: DRUG

Placebo semaglutide with carrier. For oral administration.

Healthy - 40 mg

Group Type: EXPERIMENTAL

semaglutide

Intervention Type: DRUG

Start doses of 5 mg and 10 mg with end doses of either 20 mg or 40 mg. For oral administration.

placebo

Intervention Type: DRUG

Placebo semaglutide. For oral administration.

placebo

Intervention Type: DRUG

Placebo semaglutide with carrier. For oral administration.

Healthy - 60 mg

Group Type: EXPERIMENTAL

semaglutide

Intervention Type: DRUG

Start doses of 5 mg and 10 mg with end doses of either 20 mg, 40 mg or 60 mg. For oral administration.

placebo

Intervention Type: DRUG

Placebo semaglutide. For oral administration.

placebo

Intervention Type: DRUG

Placebo semaglutide with carrier. For oral administration.

T2D - 20/40/60 mg

Group Type: EXPERIMENTAL

semaglutide

Intervention Type: DRUG

Start doses of 5 mg and 10 mg with end doses of either 20 mg, 40 mg or 60 mg. For oral administration.

placebo

Intervention Type: DRUG

Placebo semaglutide. For oral administration.

placebo

Intervention Type: DRUG

Placebo semaglutide with carrier. For oral administration.

Interventions

semaglutide

Start doses of 5 mg and 10 mg with end dose of 20 mg. For oral administration.

Intervention Type: DRUG

semaglutide

Start doses of 5 mg and 10 mg with end doses of either 20 mg or 40 mg. For oral administration.

Intervention Type: 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.

Intervention Type: DRUG

placebo

Placebo semaglutide. For oral administration.

Intervention Type: DRUG

placebo

Placebo semaglutide with carrier. For oral administration.

Intervention Type: DRUG

Eligibility Criteria

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
• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 64 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

Novo Nordisk A/S

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Global Clinical Registry (GCR, 1452)

Role: STUDY_DIRECTOR

Novo Nordisk A/S

Locations

Novo Nordisk Investigational Site

Berlin, , Germany

Countries

Germany

References

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.

Reference Type: RESULT

PMID: 30566096 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 30565096 (View on PubMed)

Related Links

http://novonordisk-trials.com

Clinical Trials at Novo Nordisk

Other Identifiers

2012-000361-20

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

U1111-1127-4408

Identifier Type: OTHER

Identifier Source: secondary_id

NN9924-3991

Identifier Type: -

Identifier Source: org_study_id