Clinical trial NCT02212067: A Trial Investigating the Effects of Semaglutide on ß-cell Function in Subjects With Type 2 Diabetes
Official title: A Single-centre, Randomised, Double-blind, Multiple-dose, Placebo-controlled, Parallel-group Trial Investigating the Effects of Semaglutide on ß-cell Function in Subjects With Type 2 Diabetes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Diabetes
Diabetes Mellitus, Type 2
Lead sponsor: Novo Nordisk A/S
Sponsor class: INDUSTRY
First posted: 2014-08-08
Enrollment: 87
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This trial is conducted in Europe. The aim of the trial is to investigate the effects of semaglutide on ß-cell function in subjects with type 2 diabetes.


Eligibility criteria: Inclusion Criteria:

* Age: 18-64 years (both inclusive) at the time of signing the informed consent
* For subjects with type 2 diabetes:
* Male and female subjects diagnosed with type 2 diabetes
* Treated with diet and exercise and/or metformin monotherapy. Metformin dose should be unchanged in a period of 30 days prior to screening
* Body Mass Index (BMI) between 20.0-35.0 kg/m\^2 (both inclusive)
* Glycosylated haemoglobin (HbA1c) between 6.5-9.0 % (both inclusive)
* For healthy control group for graded glucose infusion:
* Healthy male and female subjects
* BMI between 24.0-32.0 kg/m\^2 (both inclusive)
* HbA1c less than 6.5 %

Exclusion Criteria:

* Female who is pregnant, breast-feeding or intends to become pregnant or is of child bearing potential and not using an adequate contraceptive method. Women of child bearing potential must use an effective method of birth control for the duration of the trial and for subjects with type 2 diabetes for 5 weeks following the last dose of semaglutide. Only highly effective methods of birth control are accepted (i.e. one that results in less than 1% per year failure rate when used consistently and correctly such as implants, injectables, combined oral contraceptives, some intrauterine devices), or sexual abstinence or vasectomised partner
* Any clinically significant disease history, in the opinion of the investigator, or systemic or organ disease including: cardiac, pulmonary, gastrointestinal, hepatic, neurologic, renal, genitourinary and endocrine, dermatologic or hematologic
* Use of any prescription or non-prescription medication which could interfere with trial pharmacokinetic or pharmacodynamic results, as judged by the investigator or specifically: a) current treatment with systemic (oral or i.v.) corticosteroids, non-selective betablockers, b) thyroid hormones are not allowed unless the use of these have been stable during the past 2 month prior to screening
* History of drug/chemical substance abuse within 1 year prior to screening, or a positive result in the urine drug test
* History of alcohol abuse within 1 year prior to screening, or a positive result in the alcohol breath test
* Smoker (defined as a subject who is smoking more than 5 cigarettes or the equivalent per day)
* Not able or willing to refrain from smoking and use of nicotine gum or transdermal nicotine patches during the inpatient period

Primary outcomes:
measure: Area under the serum insulin concentration time curve from 0 to 10 minutes after a 25 g glucose bolus i.v. infusion (IVGTT,intravenous glucose tolerance test) over 2 minutes
timeFrame: Day -1, day 86
measure: Area under the serum insulin concentration time curve from 10-120 minutes after a 25 g glucose bolus i.v. infusion (IVGTT).
timeFrame: Day -1, day 86
Secondary outcomes:
measure: Area under the insulin secretion rate (ISR)-time curve within 0 to 10 min after i.v. glucose challenge
timeFrame: Day -1, day 86
measure: Area under the ISR-time curve within 10 to 120 min after i.v. glucose challenge
timeFrame: Day -1, day 86
measure: 24-hour plasma glucose, glucagon, serum insulin, and C-peptide measured as total AUC0-24h during a test day with 3 standardised meals
timeFrame: Day -1, day 85
measure: Area under the insulin secretion rate (ISR)-time curve within 0 to 10 min after i.v. arginine application; ISR will be derived from the C-peptide concentration profile
timeFrame: Day -1, day 86
measure: Area under the ISR curve over the 5-12 mmol/L (90-216 mg/dL) glucose interval; ISR will be derived from the C-peptide concentration profile
timeFrame: Day -1, day 87
measure: Slope of the ISR vs. glucose curve (dose-response relationship)
timeFrame: Day -1, day 87
Other outcomes:
Locations:
city: Neuss
country: Germany
facility: Novo Nordisk Investigational Site
Study officials:
affiliation: Novo Nordisk A/S
name: Global Clinical Registry (GCR, 1452)
role: STUDY_DIRECTOR
References:
citation: Kapitza C, Dahl K, Jacobsen JB, Axelsen MB, Flint A. Effects of semaglutide on beta cell function and glycaemic control in participants with type 2 diabetes: a randomised, double-blind, placebo-controlled trial. Diabetologia. 2017 Aug;60(8):1390-1399. doi: 10.1007/s00125-017-4289-0. Epub 2017 May 19.