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

Healthy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01686945
• Other study ID #: NN9924-3991
• Secondary ID: 2012-000361-20U1
• Status: Completed
• Phase: Phase 1
• Start date: September 19, 2012
• Est. completion date: April 8, 2013

Study information

• Verified date: January 2019
• Source: Novo Nordisk A/S
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 107
• Est. completion date: April 8, 2013
• Est. primary completion date: April 8, 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 64 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes
• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Healthy

Intervention

Drug:
• semaglutide
Start doses of 5 mg and 10 mg with end dose of 20 mg. For oral administration.
• semaglutide
Start doses of 5 mg and 10 mg with end doses of either 20 mg or 40 mg. For oral administration.
• semaglutide
Start doses of 5 mg and 10 mg with end doses of either 20 mg, 40 mg or 60 mg. For oral administration.
• placebo
Placebo semaglutide. For oral administration.
• placebo
Placebo semaglutide with carrier. For oral administration.

Locations

Country	Name	City	State
Germany	Novo Nordisk Investigational Site	Berlin

Sponsors (1)

Lead Sponsor	Collaborator
Novo Nordisk A/S

Country where clinical trial is conducted

Germany, 

References & Publications (1)

Seco A, Aparicio S, González-Camejo J, Jiménez-Benítez A, Mateo O, Mora JF, Noriega-Hevia G, Sanchis-Perucho P, Serna-García R, Zamorano-López N, Giménez JB, Ruiz-Martínez A, Aguado D, Barat R, Borrás L, Bouzas A, Martí N, Pachés M, Ribes J, Robles A, Rua — View Citation

Outcome

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

External Links

•   Clinical Trials at Novo Nordisk