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Efficacy and Safety of Semaglutide Versus Canagliflozin as add-on to Metformin in Subjects With Type 2 Diabetes (SUSTAIN 8)

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ClinicalTrials.gov Identifier: NCT03136484
Recruitment Status : Completed
First Posted : May 2, 2017
Last Update Posted : December 6, 2018
Sponsor:
Information provided by (Responsible Party):
Novo Nordisk A/S

Brief Summary:
This trial is conducted in Africa, Asia, Europe, North and South America. The aim of the trial is 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

Condition or disease Intervention/treatment Phase
Diabetes Diabetes Mellitus, Type 2 Drug: Semaglutide Drug: Canagliflozin Drug: Placebo (canagliflozin) Drug: Placebo (semaglutide) Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 788 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Efficacy and Safety of Semaglutide Versus Canagliflozin as add-on to Metformin in Subjects With Type 2 Diabetes
Actual Study Start Date : March 15, 2017
Actual Primary Completion Date : October 16, 2018
Actual Study Completion Date : November 16, 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Semaglutide + canagliflozin placebo Drug: Semaglutide
Following a dose escalation phase of 8 weeks, semaglutide 1.0 mg once-weekly(administered subcutaneously, s.c., under the skin) and canagliflozin placebo once-daily (administered orally, as a tablet). Subjects will continue on their pre-trial daily dose of metformin.

Drug: Placebo (canagliflozin)
Following a dose escalation phase of 8 weeks, semaglutide 1.0 mg once-weekly(administered subcutaneously, s.c., under the skin) and canagliflozin placebo once-daily (administered orally, as a tablet). Subjects will continue on their pre-trial daily dose of metformin.

Active Comparator: Canagliflozin + semaglutide placebo Drug: Canagliflozin
Following a dose escalation phase of 8 weeks, canagliflozin 300 mg once-daily (administered orally, as a tablet) and semaglutide placebo (administered subcutaneously, s.c., under the skin). Subjects will continue on their pre-trial daily dose of metformin.

Drug: Placebo (semaglutide)
Following a dose escalation phase of 8 weeks, canagliflozin 300 mg once-daily (administered orally, as a tablet) and semaglutide placebo (administered subcutaneously, s.c., under the skin). Subjects will continue on their pre-trial daily dose of metformin.




Primary Outcome Measures :
  1. Change in HbA1c (glycosylated haemoglobin) [ Time Frame: Week 0, week 52 ]
    Measured in %


Secondary Outcome Measures :
  1. Change in body weight (kg) [ Time Frame: Week 0, week 52 ]
    Measured in kg

  2. In a sub-set of subjects assessed through dual X-ray absorptiometry (DXA): Change in total fat mass (kg) [ Time Frame: Week 0, week 52 ]
    Measured in kg

  3. Change in Fasting Plasma Glucose (FPG) [ Time Frame: Week 0, week 52 ]
    Measured in mg/dl or other equivalent SI units

  4. Change in Self-Measured Plasma Glucose (SMPG), 7-point profile: Mean 7-point profile [ Time Frame: Week 0, week 52 ]
    Mean glucose values

  5. Change in Self-Measured Plasma Glucose (SMPG), 7-point profile: Mean post prandial increment [ Time Frame: Week 0, week 52 ]
    Mean glucose values over all meals

  6. Change in body weight (%) [ Time Frame: Week 0, week 52 ]
    Measured in %

  7. Change in systolic blood pressure [ Time Frame: Week 0, week 52 ]
    Measured in mmHg

  8. Change in diastolic blood pressure [ Time Frame: Week 0, week 52 ]
    Measured in mmHg

  9. Change in Body Mass Index (BMI) [ Time Frame: Week 0, week 52 ]
    Measured in kg/m^2

  10. Change in waist circumference [ Time Frame: Week 0, week 52 ]
    Measured in cm

  11. Change in scores for selected patient reported outcomes: SF-36v2TM Short Form health survey: Total scores (physical component and mental component) and scores from the 8 domains [ Time Frame: Week 0, week 52 ]
    Short Form 36 v2.0 acute (SF-36) is a 36-item, patient-reported survey of patient health. SF-36 measures the subject's overall Health Related Quality of Life on 8 domains: physical functioning, role functioning, bodily pain, general health, vitality, social functioning, role emotional and mental health

  12. Change in scores for selected patient reported outcomes: Diabetes Treatment Satisfaction Questionnaire (DTSQ): Treatment satisfaction score (sum of 6 of 8 items) and the 8 items separately [ Time Frame: Week 0, week 52 ]
    The DTSQs questionnaire will be used to assess subject's treatment satisfaction. This instrument contains 8 items and measures the treatment for your diabetes (including insulin, tablets and/or diet) in terms of convenience, flexibility and general feelings regarding treatment.

  13. Change in scores for selected patient reported outcomes: Control of Eating Questionnaire (CoEQ): Scores from the 4 domains and scores from 19 individual items [ Time Frame: Week 0, week 52 ]
    Scores from the 4 domains and scores from 19 individual items

  14. In a sub-set of subjects, assessed through DXA: Change in total fat mass (%) [ Time Frame: Week 0, week 52 ]
    Measured in %

  15. In a sub-set of subjects, assessed through DXA: Change in total lean mass (kg) [ Time Frame: Week 0, week 52 ]
    Measured in kg

  16. In a sub-set of subjects, assessed through DXA: Change in total lean mass (%) [ Time Frame: Week 0, week 52 ]
    Measured in %

  17. In a sub-set of subjects, assessed through DXA: Change in ratio between total fat mass and total lean mass [ Time Frame: Week 0, week 52 ]
    Measured in kg/kg

  18. Subjects who achieve (yes/no): HbA1c below 7.0% (53 mmol/mol), American Diabetes Association (ADA) target [ Time Frame: After 52 weeks ]
    Proportion of subjects

  19. Subjects who achieve (yes/no): HbA1c equal to or below 6.5% (48 mmol/mol), American Association of Clinical Endocrinologists (AACE) target [ Time Frame: After 52 weeks ]
    Proportion of subjects

  20. Subjects who achieve (yes/no): Weight loss equal to or above 3% [ Time Frame: After 52 weeks ]
    Proportion of subjects

  21. Subjects who achieve (yes/no): Weight loss equal to or above 5% [ Time Frame: After 52 weeks ]
    Proportion of subjects

  22. Subjects who achieve (yes/no): Weight loss equal to or above 10% [ Time Frame: After 52 weeks ]
    Proportion of subjects

  23. Subjects who achieve (yes/no): HbA1c below 7.0% (53 mmol/mol) without severe or blood glucose confirmed symptomatic hypoglycaemia episodes and no weight gain [ Time Frame: After 52 weeks ]
    Proportion of subjects - fulfilling all criteria

  24. Subjects who achieve (yes/no): HbA1c reduction equal to or above 1% [ Time Frame: After 52 weeks ]
    Proportion of subjects

  25. Subjects who achieve (yes/no): HbA1c reduction equal to or above 1% and weight loss equal to or above 3% [ Time Frame: After 52 weeks ]
    Proportion of subjects - fulfilling all criteria

  26. Subjects who achieve (yes/no): HbA1c reduction equal to or above 1% and weight loss equal to or above 5% [ Time Frame: After 52 weeks ]
    Proportion of subjects - fulfilling all criteria

  27. Subjects who achieve (yes/no): HbA1c reduction equal to or above 1% and weight loss equal to or above 10% [ Time Frame: After 52 weeks ]
    Proportion of subjects - fulfilling all criteria

  28. Number of treatment emergent adverse events (TEAEs) [ Time Frame: Week 0 - week 52 ]
    Count of adverse events

  29. Number of treatment emergent severe or blood glucose confirmed symptomatic hypoglycaemic episodes [ Time Frame: Week 0 - week 52 ]
    Count of events

  30. Change in fasting blood lipids: total cholesterol [ Time Frame: Week 0, week 52 ]
    Measured in mg/dl or other equivalent SI units

  31. Change in fasting blood lipids: low density lipoprotein cholesterol (LDL) [ Time Frame: Week 0, week 52 ]
    Measured in mg/dl or other equivalent SI units

  32. Change in fasting blood lipids: high density lipoprotein cholesterol (HDL) [ Time Frame: Week 0, week 52 ]
    Measured in mg/dl or other equivalent SI units

  33. Change in fasting blood lipids: triglycerides [ Time Frame: Week 0, week 52 ]
    Measured in mg/dl or other equivalent SI units



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 equal to or above18 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 (equal to or above1500 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 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) above 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 below 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03136484


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Sponsors and Collaborators
Novo Nordisk A/S

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Novo Nordisk A/S
ClinicalTrials.gov Identifier: NCT03136484     History of Changes
Other Study ID Numbers: NN9535-4270
2016-000989-35 ( EudraCT Number )
U1111-1180-3651 ( Other Identifier: World Health Organization (WHO) )
First Posted: May 2, 2017    Key Record Dates
Last Update Posted: December 6, 2018
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: According to the Novo Nordisk disclosure commitment on novonordisk-trials.com

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Metformin
Canagliflozin
Hypoglycemic Agents
Physiological Effects of Drugs
Sodium-Glucose Transporter 2 Inhibitors
Molecular Mechanisms of Pharmacological Action