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 study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novo Nordisk A/S
ClinicalTrials.gov Identifier:
NCT01686945
First received: September 13, 2012
Last updated: April 15, 2013
Last verified: April 2013
  Purpose

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).


Condition Intervention Phase
Diabetes
Diabetes Mellitus, Type 2
Healthy
Drug: semaglutide
Drug: placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Novo Nordisk A/S:

Primary Outcome Measures:
  • Number of treatment emergent adverse events (TEAEs) recorded [ Time Frame: From the time of first dosing and until completion of the post treatment follow-up visits (Day 90 to 104) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Area under the plasma concentration curve over the dosing interval (0-24 hours) [ Time Frame: After the last 3 daily doses for semaglutide and carrier ] [ Designated as safety issue: No ]
  • Change from baseline in fasting plasma glucose (FPG) [ Time Frame: Week 0, week 10 (Day 69) ] [ Designated as safety issue: No ]
  • Change from baseline in C-peptide [ Time Frame: Week 0, week 10 (Day 69) ] [ Designated as safety issue: No ]
  • Change from baseline in insulin [ Time Frame: Week 0, week 10 (Day 69) ] [ Designated as safety issue: No ]
  • Change from baseline in glucagon [ Time Frame: Week 0, week 10 (Day 69) ] [ Designated as safety issue: No ]
  • Change from baseline in glycosylated haemoglobin type A1c (HbA1c) [ Time Frame: Week 0, week 10 (Day 69) ] [ Designated as safety issue: No ]

Enrollment: 107
Study Start Date: September 2012
Study Completion Date: April 2013
Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Healthy - 20 mg Drug: semaglutide
Start doses of 5 mg and 10 mg with end dose of 20 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 doses of either 20 mg or 40 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 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 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.

  Eligibility

Ages Eligible for Study:   18 Years to 64 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
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
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01686945

Locations
Germany
Berlin, Germany, 14050
Sponsors and Collaborators
Novo Nordisk A/S
Investigators
Study Director: Charlotte Granhall Novo Nordisk A/S
  More Information

Additional Information:
No publications provided

Responsible Party: Novo Nordisk A/S
ClinicalTrials.gov Identifier: NCT01686945     History of Changes
Other Study ID Numbers: NN9924-3991, 2012-000361-20, U1111-1127-4408
Study First Received: September 13, 2012
Last Updated: April 15, 2013
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases

ClinicalTrials.gov processed this record on July 23, 2014