A trial investigating the cardiovascular safety of oral semaglutide in subjects with type 2 diabetes

• Register: EUCTR
• Last refreshed on: 15 October 2018
• Main ID: EUCTR2015-003563-10-ES
• Date of registration: 19/04/2016
• Prospective Registration: Yes
• Primary sponsor: Novo Nordisk A/S
• Public title: A trial investigating the cardiovascular safety of oral semaglutide in subjects with type 2 diabetes
• Scientific title: A trial investigating the cardiovascular safety of oral semaglutide in subjects with type 2 diabetes - PIONEER 6 ? Cardiovascular outcomes
• Date of first enrolment: 30/05/2016
• Target sample size: 3176
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-003563-10
• 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: 2
• 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, Argentina, Brazil, Canada, Denmark, European Union, Germany, India, Israel, Malaysia, Mexico, Netherlands, Poland, South Africa, Spain, Taiwan, Thailand, Turkey, United Kingdom, 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. Male or female diagnosed with type 2 diabetes
2. Age ? 50 years at screening and presence of cardiovascular disease, or age ? 60 years at screening and presence of at least one cardiovascular risk factor
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 1588
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 1588

Exclusion criteria:
1. Current or previous (within 90 days prior to screening) treatment with any GLP-1 receptor agonist, DPP-4 inhibitor or pramlintide
2. Family or personal history of multiple endocrine neoplasia type 2 (MEN 2) or medullary thyroid carcinoma (MTC)
3. History of pancreatitis (acute or chronic)
4. 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)
5. Subjects presently classified as being in New York Heart Association (NYHA) Class IV heart failure
6. Planned coronary, carotid or peripheral artery revascularisation known on the day of screening
7. Any of the following: myocardial infarction, stroke or hospitalisation for unstable angina or transient ischaemic attack within the past 60 days prior to screening
8. Chronic or intermittent hemodialysis or peritoneal dialysis or severe renal impairment (corresponding to eGFR <30 mL/min/1.73 m^2)
9. History or presence of malignant neoplasms within the last 5 years (except basal and squamous cell skin cancer and carcinoma in situ)


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

Health Condition(s) or Problem(s) studied

Diabetes Mellitus, Type 2
MedDRA version: 19.0 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: Maximum treatment duration is dependent on event rates and is estimated to be no longer than 19 months

Main Objective: The primary objective is to confirm that treatment with oral semaglutide does not result in an unacceptable increase in cardiovascular risk compared to placebo (rule out 80% excess risk) in subjects with type 2 diabetes at high risk of cardiovascular events

Primary end point(s): Time from randomisation to first occurrence of a major adverse cardiovascular event (MACE) composite endpoint consisting of: cardiovascular death, non-fatal myocardial infarction or non-fatal stroke

Secondary Objective: The secondary objectives are to compare the efficacy and safety of oral semaglutide versus placebo in subjects with type 2 diabetes at high risk of cardiovascular events

Secondary Outcome(s)

Secondary end point(s): 1. Time from randomisation to first occurrence of an expanded composite cardiovascular endpoint consisting of: cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, unstable angina requiring hospitalisation or hospitalisation for heart failure
2. Time from randomisation to first occurrence of each of the individual components in the expanded composite cardiovascular endpoint
3. Time from randomisation to first occurrence of a composite endpoint consisting of: all-cause death, non-fatal myocardial infarction or non-fatal stroke

Timepoint(s) of evaluation of this end point: All endpoints: Maximum treatment duration is dependent on event rates and is estimated to be no longer than 19 months

Secondary ID(s)

2015-003563-10-GB

NN9924-4221

Source(s) of Monetary Support

Novo Nordisk A/S