Efficacy and safety of oral semaglutide versus placebo in subjects with type 2 diabetes mellitus treated with diet and exercise only

• Register: EUCTR
• Last refreshed on: 23 July 2018
• Main ID: EUCTR2015-005622-19-BG
• Date of registration: 06/07/2016
• Prospective Registration: Yes
• Primary sponsor: Novo Nordisk A/S
• Public title: Efficacy and safety of oral semaglutide versus placebo in subjects with type 2 diabetes mellitus treated with diet and exercise only
• Scientific title: Efficacy and safety of oral semaglutide versus placebo in subjects with type 2 diabetes mellitus treated with diet and exercise only. A 26-week, randomised, double-blind, placebo-controlled trial - PIONEER 1 - Monotherapy
• Date of first enrolment: 18/08/2016
• Target sample size: 704
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-005622-19
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 4
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Algeria, Bulgaria, Czech Republic, European Union, Japan, Mexico, Russian Federation, Serbia, Turkey, United States

Contacts

• Name: Global Clinical Registry (GCR,1452)
• Affiliation: Novo Nordisk A/S

• Name: Global Clinical Registry (GCR,1452)
• Affiliation: Novo Nordisk A/S

Key inclusion & exclusion criteria

Inclusion criteria:
1. Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial.
2. Male or female, age above or equal to 18 years at the time of signing informed consent.
3. Diagnosed with type 2 diabetes mellitus = 30 days prior to day of screening.
4. HbA1c between 7.0-9.5% (53-80 mmol/mol) (both inclusive).
5. Treatment with diet and exercise for =30 days prior to day of screening.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 680
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 24

Exclusion criteria:
1. Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using an adequate contraceptive method (adequate contraceptive measure as required by local regulation or practice).
2. Any disorder, which in the investigator’s opinion might jeopardise subject’s safety or compliance with the protocol.
3. Family or personal history of multiple endocrine neoplasia type 2 or medullary thyroid carcinomas.
4. History of pancreatitis (acute or chronic).
5. History of major surgical procedures involving the stomach potentially affecting absorption of trial product (e.g. subtotal and total gastrectomy, sleeve gastrectomy, gastric bypass surgery).
6. Any of the following: myocardial infarction, stroke or hospitalisation for unstable angina or transient ischaemic attack within the past 180 days prior to the day of screening and randomisation.
7. Subjects presently classified as being in New York Heart Association Class IV.
8. Planned coronary, carotid or peripheral artery revascularisation known on the day of screening.
9. Subjects with alanine aminotransferase > 2.5 x upper normal limit.
10. Renal impairment defined as estimated glomerular filtration rate <60 mL/min/1.73 m^2 as per Chronic Kidney Disease Epidemiology Collaboration formula.
11. Treatment with any medication for the indication of diabetes or obesity in a period of 90 days before the day of screening. An exception is short-term insulin treatment for acute illness for a total of = 14 days.
12. Proliferative retinopathy or maculopathy requiring acute treatment. Verified by fundus photography or dilated fundoscopy performed within 90 days prior to randomisation.
13. History or presence of malignant neoplasms within the last 5 years (except basal and squamous cell skin cancer and in-situ carcinomas)



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Diabetes Mellitus, Type 2
MedDRA version: 20.0 Level: LLT Classification code 10045242 Term: Type II diabetes mellitus System Organ Class: 100000004861

Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

Intervention(s)

Product Name: Semaglutide 3 mg
Pharmaceutical Form: Tablet
INN or Proposed INN: SEMAGLUTIDE
CAS Number: 910463-68-2
Other descriptive name: SEMAGLUTIDE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 3-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Product Name: Semaglutide 7 mg
Pharmaceutical Form: Tablet
INN or Proposed INN: SEMAGLUTIDE
CAS Number: 910463-68-2
Other descriptive name: SEMAGLUTIDE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 7-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Product Name: Semaglutide 14 mg
Pharmaceutical Form: Tablet
INN or Proposed INN: SEMAGLUTIDE
CAS Number: 910463-68-2
Other descriptive name: SEMAGLUTIDE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 14-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: From baseline to week 26

Secondary Objective: 1. To compare the effects of three dose levels of once-daily oral semaglutide (3, 7 and 14 mg) versus once-daily placebo on body weight in subjects with type 2 diabetes mellitus treated with diet and exercise only.
2. To compare the safety and tolerability of three dose levels of once-daily oral semaglutide (3, 7 and 14 mg) versus once-daily placebo in subjects with type 2 diabetes mellitus treated with diet and exercise only.

Main Objective: To compare the effects of three dose levels of once-daily oral semaglutide (3, 7 and 14 mg) versus once-daily placebo on glycaemic control in subjects with type 2 diabetes mellitus treated with diet and exercise only.

Primary end point(s): Change in HbA1c

Secondary Outcome(s)

Secondary end point(s): 1. Change in body weight (kg)
2. Change in fasting plasma glucose
3. HbA1c < 7.0% (53 mmol/mol) (American Diabetes Association target) (yes/no)
4. Number of treatment-emergent adverse events during exposure to trial product
5. Number of treatment-emergent severe or blood glucose-confirmed symptomatic hypoglycaemic episodes during exposure to trial product

Timepoint(s) of evaluation of this end point: 1. + 2. From baseline to week 26
3. After week 26
4. + 5. Assessed up to approximately 31 weeks

Secondary ID(s)

NN9924-4233

Source(s) of Monetary Support

Novo Nordisk A/S