Efficacy and Safety of Oral Semaglutide Using a Flexible Dose Adjustment Based on Clinical Evaluation versus Sitagliptin in Subjects with Type 2 Diabetes Mellitus

• Register: EUCTR
• Last refreshed on: 25 November 2019
• Main ID: EUCTR2015-005593-38-AT
• Date of registration: 01/07/2016
• Prospective Registration: Yes
• Primary sponsor: Novo Nordisk A/S
• Public title: Efficacy and Safety of Oral Semaglutide Using a Flexible Dose Adjustment Based on Clinical Evaluation versus Sitagliptin in Subjects with Type 2 Diabetes Mellitus
• Scientific title: Efficacy and Safety of Oral Semaglutide Using a Flexible Dose Adjustment Based on Clinical Evaluation versus Sitagliptin in Subjects with Type 2 Diabetes Mellitus. A 52 week Randomised, Open-label, Active-controlled Trial with a 52-week Extension Phase - PIONEER 7 – Flexible dose adjustment
• Date of first enrolment: 02/08/2016
• Target sample size: 500
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-005593-38
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: yes; Single blind: no; Double blind: no; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: no; 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

Argentina, Austria, Belgium, Brazil, Egypt, European Union, Korea, Republic of, Norway, Switzerland, 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:
Main phase (the inclusion criteria for the main phase are not reassessed for the extension phase):
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. For Korea only: Male or female, age above or equal to 19 years at the time of signing informed consent.
3. Diagnosed with type 2 diabetes mellitus = 90 days prior to day of screening.
4. HbA1c 7.5-9.5% (58-80 mmol/mol) (both inclusive).
5. Treatment target of HbA1c < 7.0% (53 mmol/mol), as judged by the investigator.
6. Stable daily dose(s) of 1-2 of the following anti-diabetic drugs within 90 days prior to the day of screening:
– Metformin (=1500 mg or maximum tolerated dose as documented in the subject medical record).
– Sulfonylureas (= half of the maximum approved dose according to local label or maximum tolerated dose as documented in subject medical record).
– Sodium glucose co-transporter 2 inhibitors.
– Thiazolidinediones (= half of the maximum approved dose according to local label or maximum tolerated dose as documented in subject medical record).
Extension phase:
7. Informed consent for the extension phase obtained before any trial-related activities for the extension phase.
8. On randomised treatment with or without rescue medication at week 52.
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 375
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 125

Exclusion criteria:
Main phase (the exclusion criteria for the main phase are not reassessed for the extension phase):
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). For certain specific countries: Additional specific requirements apply.
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 Carcinoma.
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 other than stated in the inclusion criteria 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 carcinoma in situ).
14. History of diabetic ketoacidosis.
Extension phase:
There are no new exclusion criteria for the extension phase.


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

Health Condition(s) or Problem(s) studied

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

Diabetes Mellitus, Type 2
MedDRA version: 20.1 Level: LLT Classification code 10045242 Term: Type II diabetes mellitus System Organ Class: 100000004861

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-

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-

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-

Trade Name: Januvia
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Sitagliptin
CAS Number: 654671-77-9
Other descriptive name: SITAGLIPTIN PHOSPHATE MONOHYDRATE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-

Primary Outcome(s)

Main Objective: Main phase: To compare the effect of once-daily dosing of oral semaglutide using a flexible dose adjustment based on clinical evaluation versus sitagliptin once-daily, both in combination with 1-2 oral antidiabetic drugs (OADs) on glycaemic control in subjects with Type 2 diabetes mellitus (T2DM).

Primary end point(s): Main phase:
Glycosylated haemoglobin (HbA1c) < 7% (53 mmol/mol) American Diabetes Association target (yes/no)

Secondary Objective: Main phase
To compare
- the effect on body weight
- the safety and tolerability
of once-daily dosing of oral semaglutide using a flexible dose adjustment based on clinical evaluation versus sitagliptin once daily, both in combination with 1-2 OADs in subjects with T2DM.

Extension phase (sustainability)
To evaluate
- the sustainability of glycaemic control and body weight reduction
- the long term safety
of once-daily dosing of oral semaglutide using a flexible dose adjustment based on clinical evaluation in subjects with T2DM.

Extension phase (switch)
To compare
- the effect on glycaemic control
- the effect on body weight
- the safety and tolerability
of switching to once-daily dosing of oral semaglutide using a flexible dose adjustment based on clinical evaluation versus staying on once-daily sitagliptin in subjects with T2DM.

Timepoint(s) of evaluation of this end point: After week 52

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Main phase:
1.-3. From baseline to week 52
4.+ 5. Assessed up to approximately 52 weeks

Ext phase (sustainability)
1.: After week 104
2. – 4.: From baseline to week 104
5. – 6.: Assessed up to approximately 109 weeks

Ext phase (switch)
7.: After week 104
8. – 10.: From week 52 to 104
11. – 12.: Assessed from week 52 up to approximately 109 weeks

Secondary end point(s): Main phase:
1. Change in body weight (kg)
2. Change in HbA1c
3. Change in fasting plasma glucose
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

Ext phase (sustainability):
1. If a subject achieves (yes/no) HbA1c < 7% (53 mmol/mol) American Diabetes Association target.
2. Change in body weight (kg)
3. Change in HbA1c
4. Change in fasting plasma glucose (FPG)
5. Number of treatment-emergent adverse events during exposure to trial product,
6. Number of treatment-emergent severe or blood glucose-confirmed symptomatic hypoglycaemic episodes during exposure to trial product

Ext phase (switch):
7. If a subject achieves (yes/no) HbA1c < 7% (53 mmol/mol) American Diabetes Association target.
8. Change in body weight (kg)
9. Change in HbA1c
10. Change in fasting plasma glucose (FPG)
11. Number of treatment-emergent adverse events during exposure to trial product
12. Number of treatment-emergent severe or blood glucose-confirmed symptomatic hypoglycaemic episodes during exposure to trial product

Secondary ID(s)

2015-005593-38-BE

NN9924-4257

Source(s) of Monetary Support

Novo Nordisk A/S

Ethics review

Status: Approved
Approval date:
Contact: