Efficacy and safety of semaglutide versus canagliflozin as add-on to metformin in subjects with type 2 diabetes

• Register: EUCTR
• Last refreshed on: 16 December 2019
• Main ID: EUCTR2016-000989-35-SE
• Date of registration: 28/10/2016
• Prospective Registration: Yes
• Primary sponsor: Novo Nordisk A/S
• Public title: Efficacy and safety of semaglutide versus canagliflozin as add-on to metformin in subjects with type 2 diabetes
• Scientific title: Efficacy and safety of semaglutide versus canagliflozin as add-on to metformin in subjects with type 2 diabetes - SUSTAIN 8 – semaglutide versus canagliflozin
• Date of first enrolment: 23/01/2017
• Target sample size: 784
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-000989-35
• 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: yes Other trial design description: Double-dummy 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, Brazil, Canada, European Union, India, Ireland, Lebanon, Malaysia, Mexico, Sweden, 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:
- 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.
- Male or female, age =18 years at the time of signing informed consent.
- Diagnosed with type 2 diabetes mellitus (T2D).
-. HbA1c of 7.0-10.5% (53-91 mmol/mol, both inclusive).
- Stable daily dose of metformin (=1500 mg or maximum tolerated dose as documented in the subject medical record and in compliance with current local label) for at least 90 days prior to the 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 627
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 157

Exclusion criteria:
- Known or suspected hypersensitivity to trial product(s) or related products.
- Previous participation in this trial. Participation is defined as signed informed consent.
- 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).
- Participation in any clinical trial of an approved or non-approved investigational medicinal product within 90 days prior to the day of screening.
- Any disorder which in the investigator’s opinion might jeopardise subject’s safety or compliance with the protocol.
- Subject with alanine aminotransferase (ALT) >2.5 x upper normal limit (UNL).
- Family or personal history of multiple endocrine neoplasia type 2 or medullary thyroid carcinoma. Family is defined as a first degree relative.
- History or presence of pancreatitis (acute or chronic).
- History of diabetic ketoacidosis (DKA).
- Any of the following: myocardial infarction (MI), stroke, hospitalization for unstable angina or transient ischaemic attack within the past 180 days prior to the day of screening.
- Subjects presently classified as being in New York Heart Association (NYHA) Class IV.
- Planned coronary, carotid or peripheral artery revascularisation known on the day of screening.
- Renal impairment measured as eGFR <60 ml/min/1.73 m^2 as defined by Kidney Disease Improving global outcomes (KDIGO 2012) classification using isotope dilution mass spectrometry (IDMS) for serum creatinine measured at screening.
- Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria within the past 90 days prior to the day of screening. However, short term insulin treatment for a maximum of 14 days prior to the day of screening is allowed.
- Proliferative retinopathy or maculopathy requiring acute treatment. Verified by fundus
photography or dilated fundoscopy performed within the past 90 days prior to
randomisation.
- Presence or history of malignant neoplasms within the past 5 years prior to the day of screening. Basal and squamous cell skin cancer and any carcinoma in-situ is allowed.
- Medical history of diabetes-related lower limb amputations or signs of critical lower limb ischemia, (e.g. skin ulcer, osteomyelitis, or gangrene) within the last 26 weeks prior to screening.


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: 19.0 Level: LLT Classification code 10045242 Term: Type II diabetes mellitus System Organ Class: 100000004861

Intervention(s)

Product Name: Semaglutide B 1.34 mg/ml PDS290
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Semaglutide
CAS Number: 910463-68-2
Other descriptive name: SEMAGLUTIDE
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 1.34-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subcutaneous use

Trade Name: Invokana
Product Name: Invokana 100 mg
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: canagliflozin
CAS Number: 842133-18-0
Other descriptive name: CANAGLIFLOZIN
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Trade Name: Invokana
Product Name: Invokana 300 mg
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: CANAGLIFLOZIN
CAS Number: 842133-18-0
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 300-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: From baseline to week 52

Main Objective: To compare the effect of once-weekly (OW) dosing of subcutaneous semaglutide (1.0 mg) versus once-daily dosing of oral canagliflozin (300 mg) on glycaemic control in subjects with type 2 diabetes (T2D) on a background treatment of metformin.

Primary end point(s): Change in HbA1c

Secondary Objective: To compare the effects of semaglutide s.c. 1.0 mg once-weekly versus canagliflozin 300 mg once daily after 52 weeks of treatment in subjects with T2D with regards to:
- Weight management
- Other parameters of effect, safety and Patient Reported Outcomes

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 1. + 2.: From baseline to week 52

Secondary end point(s): Change in:
1. Fasting Plasma Glucose (FPG)*
2. Systolic and diastolic blood pressure*
3. Diabetes Treatment Satisfaction Questionnaire (DTSQ)*: Treatment satisfaction
score (sum of 6 of 8 items) and the 8 items separately

Secondary ID(s)

NN9535-4270

Source(s) of Monetary Support

Novo Nordisk A/S

Ethics review

Status: Approved
Approval date:
Contact:

Results

• Results available: Yes
• Date Posted: 03/12/2019
• Date Completed: 16/11/2018
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2016-000989-35/results