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A Research Study to Compare Semaglutide to Insulin Aspart, When Taken Together With Metformin and Insulin Glargine, in People With Type 2 Diabetes (SUSTAIN 11)

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ClinicalTrials.gov Identifier: NCT03689374
Recruitment Status : Active, not recruiting
First Posted : September 28, 2018
Last Update Posted : December 5, 2019
Sponsor:
Information provided by (Responsible Party):
Novo Nordisk A/S

Brief Summary:
This study will compare the effect of semaglutide once weekly to insulin aspart 3 times daily as add on to metformin and insulin glargine in people with type 2 diabetes. Participants will either get insulin glargine and semaglutide or insulin glargine and insulin aspart - which treatment the participant get is decided by chance. Insulin glargine is taken once a day and semaglutide once a week. Insulin aspart is taken three times per day before a meal. All three medicines come in pre-filled pens for injection under the skin. The study will last for about 71 weeks. If participant's blood sugar gets under or over certain values participant will only participate in 14 weeks. The study doctor will inform the participant about this. The participant will have 15 clinic visits and 22 phone calls with the study doctor.

Condition or disease Intervention/treatment Phase
Diabetes Mellitus, Type 2 Drug: Semaglutide Drug: Insulin aspart Drug: Insulin glargine U100 Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 2275 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Effect of Semaglutide Once-weekly Versus Insulin Aspart Three Times Daily, Both as Add on to Metformin and Optimised Insulin Glargine (U100) in Subjects With Type 2 Diabetes A 52-week, Multi-centre, Multinational, Open-label, Active-controlled, Two Armed, Parallel-group, Randomised Trial in Subjects With Type 2 Diabetes
Actual Study Start Date : October 1, 2018
Estimated Primary Completion Date : October 2, 2020
Estimated Study Completion Date : February 22, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Semaglutide

Run-in period (12 weeks): subjects will be treated with metformin and insulin glargine (IGlar) U100.

Treatment period: Participants who are not in glycaemic control (defined as HbA1c of more than or equal to 7.5% to less than or equal to 10%) after run-in will receive semaglutide for 52 weeks in addition to metformin and IGlar U100.

Metformin will be considered as background therapy during the trial.

Drug: Semaglutide
Subjects will receive subcutaneous (s.c., under the skin) injections of semaglutide once weekly (OW) with a dose of 0.25 mg. The dose should be increased after four weeks to 0.5 mg semaglutide. After 4 more weeks the dose can be increased to 1.0 mg semaglutide if the study doctor decides and further dose adjusted throughout the study.

Drug: Insulin glargine U100
Run-in period: Subjects will receive s.c. injections of IGlar U100 OD in accordance with the approved local label of IGlar U100. The dose will be adjusted based on the mean of three pre-breakfast SMPG values (target SMPG: 4.0-6.9 mmol/L)

Active Comparator: Insulin aspart

Run-in period (12 weeks): subjects will be treated with metformin and insulin IGlar U100.

Treatment period: Participants who are not in glycaemic control (defined as HbA1c of more than or equal to 7.5% to less than or equal to 10%) after run-in receive insulin aspart for 52 weeks in addition to metformin and IGlar U100.

Metformin will be considered as background therapy during the trial.

Drug: Insulin aspart
Subjects should initiate treatment with 4U of Insulin aspart (s.c. injections) before each main meal, three times daily (TID). The dose will be adjusted individually based on pre-prandial and bedtime self measured plasma glucose (SMPG) from the preceding 3 days

Drug: Insulin glargine U100
Run-in period: Subjects will receive s.c. injections of IGlar U100 OD in accordance with the approved local label of IGlar U100. The dose will be adjusted based on the mean of three pre-breakfast SMPG values (target SMPG: 4.0-6.9 mmol/L)




Primary Outcome Measures :
  1. Change in HbA1c [ Time Frame: Baseline (week 0), week 52 ]
    Measured in %-point


Secondary Outcome Measures :
  1. Time to first event adjudication committee (EAC) confirmed severe hypoglycaemic episode (ADA) [ Time Frame: From randomisation (week 0) up to week 52 ]
    Measured in days

  2. Time to first EAC confirmed severe hypoglycaemic episode (ADA) requiring hospitalisation, documented medical help, or is life threatening [ Time Frame: From randomisation (week 0) up to week 52 ]
    Measured in days

  3. Change in body weight [ Time Frame: Baseline (week 0), week 52 ]
    Measured in kg

  4. Change in fasting plasma glucose (FPG) [ Time Frame: Baseline (week 0), week 52 ]
    Measured in mmol/L

  5. Change in 7-point self-measured plasma glucose profile: Mean 7-point profile [ Time Frame: Baseline (week 0), week 52 ]
    Measured in mmol/L

  6. Change in 7-point self-measured plasma glucose profile: Mean post-prandial increment (over all meals) [ Time Frame: Baseline (week 0), week 52 ]
    Measured in mmol/L

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

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

  9. Change in total cholesterol [ Time Frame: Baseline (week 0), week 52 ]
    Measured in mmol/L

  10. Change in low-density lipoprotein (LDL) cholesterol [ Time Frame: Baseline (week 0), week 52 ]
    Measured in mmol/L

  11. Change in high-density lipoprotein (HDL) cholesterol [ Time Frame: Baseline (week 0), week 52 ]
    Measured in mmol/L

  12. Change in triglycerides [ Time Frame: Baseline (week 0), week 52 ]
    Measured in mmol/L

  13. Change in body mass index (BMI) [ Time Frame: Baseline (week 0), week 52 ]
    Measured in kg/m^2

  14. Change in waist circumference [ Time Frame: Baseline (week 0), week 52 ]
    Measured in cm

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

  16. Change in pulse [ Time Frame: Baseline (week 0), week 52 ]
    Measured in beats per minute

  17. Number of EAC confirmed severe hypoglycaemic episodes (ADA) [ Time Frame: From randomisation (week 0) up to week 52 ]
    Number of episodes

  18. Number of EAC confirmed severe (ADA) or blood glucose confirmed, symptomatic hypoglycaemic episodes (plasma glucose less than 3.1 mmol/L [56 mg/dL]) [ Time Frame: From randomisation (week 0) up to week 52 ]
    Number of episodes

  19. Number of EAC confirmed severe (ADA) or blood glucose confirmed, symptomatic hypoglycaemic episodes (plasma glucose less than 3.9 mmol/L [70 mg/dL]) [ Time Frame: From randomisation (week 0) up to week 52 ]
    Number of episodes

  20. Number of EAC confirmed severe hypoglycaemic episodes (ADA) requiring hospitalisation, documented medical help, or is life threatening [ Time Frame: From randomisation (week 0) up to week 52 ]
    Number of episodes

  21. Change in 36-item Short Form Health Survey version 2 (SF-36v2™): Physical Component Summary (PCS) score [ Time Frame: Baseline (week 0), week 52 ]
    SF-36v2™ questionnaire contains 36 items and measures the individual overall Health Related Quality of Life (HRQoL) on 8 domains; physical functioning, role functioning, body pain, general health, vitality, social functioning, role emotional and mental health. PCS score range: 7.32-70.14. Higher scores are indicative of a better health state.

  22. Change in SF-36v2™: Mental Component Summary (MCS) score [ Time Frame: Baseline (week 0), week 52 ]
    SF-36v2™ questionnaire contains 36 items and measures the individual overall HRQoL on 8 domains; physical functioning, role functioning, body pain, general health, vitality, social functioning, role emotional and mental health. MCS score range: 5.79-69.91. Higher scores are indicative of a better health state.

  23. Change in SF-36v2™: Physical Functioning (PF) domain score [ Time Frame: Baseline (week 0), week 52 ]
    SF-36v2™ questionnaire contains 36 items and measures the individual overall HRQoL on 8 domains; physical functioning, role functioning, body pain, general health, vitality, social functioning, role emotional and mental health. PF domain score range: 19.26-57.54. Higher scores are indicative of a better health state.

  24. Change in SF-36v2™: Role-Physical (RP) domain score [ Time Frame: Baseline (week 0), week 52 ]
    SF-36v2™ questionnaire contains 36 items and measures the individual overall HRQoL on 8 domains; physical functioning, role functioning, body pain, general health, vitality, social functioning, role emotional and mental health. RP domain score range: 21.23-57.16. Higher scores are indicative of a better health state.

  25. Change in SF-36v2™: Bodily Pain (BP) domain score [ Time Frame: Baseline (week 0), week 52 ]
    SF-36v2™ questionnaire contains 36 items and measures the individual overall HRQoL on 8 domains; physical functioning, role functioning, body pain, general health, vitality, social functioning, role emotional and mental health. BP domain score range: 21.68-62.00. Higher scores are indicative of a better health state.

  26. Change in SF-36v2™: General Health (GH) domain score [ Time Frame: Baseline (week 0), week 52 ]
    SF-36v2™ questionnaire contains 36 items and measures the individual overall HRQoL on 8 domains; physical functioning, role functioning, body pain, general health, vitality, social functioning, role emotional and mental health. GH domain score range: 18.95-66.50. Higher scores are indicative of a better health state.

  27. Change in SF-36v2™: Vitality (VT) domain score [ Time Frame: Baseline (week 0), week 52 ]
    SF-36v2™ questionnaire contains 36 items and measures the individual overall HRQoL on 8 domains; physical functioning, role functioning, body pain, general health, vitality, social functioning, role emotional and mental health. VT domain score range: 22.89-70.42. Higher scores are indicative of a better health state.

  28. Change in SF-36v2™: Social Functioning (SF) domain score [ Time Frame: Baseline (week 0), week 52 ]
    SF-36v2™ questionnaire contains 36 items and measures the individual overall HRQoL on 8 domains; physical functioning, role functioning, body pain, general health, vitality, social functioning, role emotional and mental health. VT domain score range: 22.89-70.42. Higher scores are indicative of a better health state.

  29. Change in SF-36v2™: Role-Emotional (RE) domain score [ Time Frame: Baseline (week 0), week 52 ]
    SF-36v2™ questionnaire contains 36 items and measures the individual overall HRQoL on 8 domains; physical functioning, role functioning, body pain, general health, vitality, social functioning, role emotional and mental health. RE domain score range: 14.39-56.17. Higher scores are indicative of a better health state.

  30. Change in SF-36v2™: Mental Health (MH) domain score [ Time Frame: Baseline (week 0), week 52 ]
    SF-36v2™ questionnaire contains 36 items and measures the individual overall HRQoL on 8 domains; physical functioning, role functioning, body pain, general health, vitality, social functioning, role emotional and mental health. MH domain score range: 11.63-63.95. Higher scores are indicative of a better health state.

  31. Change in Diabetes Quality Of Life Clinical Trial Questionnaire (DQLCTQ-R): Physical functioning domain score [ Time Frame: Baseline (week 0), week 52 ]
    The DQLCTQ-R questionnaire will be used to assess subjects' HRQoL. The questionnaire contains 57 items and measures and provide scores for each of the 8 included domains; Physical Function, Energy/Fatigue, Health Distress, Mental Health, Satisfaction, Treatment Satisfaction, Treatment Flexibility and Frequency of Symptoms. Range: 0-100. Higher scores are indicative of better health state.

  32. Change in DQLCTQ-R: Energy / fatigue domain score [ Time Frame: Baseline (week 0), week 52 ]
    The DQLCTQ-R questionnaire will be used to assess subjects' HRQoL. The questionnaire contains 57 items and measures and provide scores for each of the 8 included domains; Physical Function, Energy/Fatigue, Health Distress, Mental Health, Satisfaction, Treatment Satisfaction, Treatment Flexibility and Frequency of Symptoms. Range: 0-100. Higher scores are indicative of better health state.

  33. Change in DQLCTQ-R: Health distress domain score [ Time Frame: Baseline (week 0), week 52 ]
    The DQLCTQ-R questionnaire will be used to assess subjects' HRQoL. The questionnaire contains 57 items and measures and provide scores for each of the 8 included domains; Physical Function, Energy/Fatigue, Health Distress, Mental Health, Satisfaction, Treatment Satisfaction, Treatment Flexibility and Frequency of Symptoms. Range: 0-100. Higher scores are indicative of better health state.

  34. Change in DQLCTQ-R: Mental health domain score [ Time Frame: Baseline (week 0), week 52 ]
    The DQLCTQ-R questionnaire will be used to assess subjects' HRQoL. The questionnaire contains 57 items and measures and provide scores for each of the 8 included domains; Physical Function, Energy/Fatigue, Health Distress, Mental Health, Satisfaction, Treatment Satisfaction, Treatment Flexibility and Frequency of Symptoms. Range: 0-100. Higher scores are indicative of better health state.

  35. Change in DQLCTQ-R: Satisfaction domain score [ Time Frame: Baseline (week 0), week 52 ]
    The DQLCTQ-R questionnaire will be used to assess subjects' HRQoL. The questionnaire contains 57 items and measures and provide scores for each of the 8 included domains; Physical Function, Energy/Fatigue, Health Distress, Mental Health, Satisfaction, Treatment Satisfaction, Treatment Flexibility and Frequency of Symptoms. Range: 0-100. Higher scores are indicative of better health state.

  36. Change in DQLCTQ-R: Treatment satisfaction domain score [ Time Frame: Baseline (week 0), week 52 ]
    The DQLCTQ-R questionnaire will be used to assess subjects' HRQoL. The questionnaire contains 57 items and measures and provide scores for each of the 8 included domains; Physical Function, Energy/Fatigue, Health Distress, Mental Health, Satisfaction, Treatment Satisfaction, Treatment Flexibility and Frequency of Symptoms. Range: 0-100. Higher scores are indicative of better health state.

  37. Change in DQLCTQ-R: Treatment flexibility domain score [ Time Frame: Baseline (week 0), week 52 ]
    The DQLCTQ-R questionnaire will be used to assess subjects' HRQoL. The questionnaire contains 57 items and measures and provide scores for each of the 8 included domains; Physical Function, Energy/Fatigue, Health Distress, Mental Health, Satisfaction, Treatment Satisfaction, Treatment Flexibility and Frequency of Symptoms. Range: 0-100. Higher scores are indicative of better health state.

  38. Change in DQLCTQ-R: Frequency of symptoms domain score [ Time Frame: Baseline (week 0), week 52 ]
    The DQLCTQ-R questionnaire will be used to assess subjects' HRQoL. The questionnaire contains 57 items and measures and provide scores for each of the 8 included domains; Physical Function, Energy/Fatigue, Health Distress, Mental Health, Satisfaction, Treatment Satisfaction, Treatment Flexibility and Frequency of Symptoms. Range: 0-100. Higher scores are indicative of better health state.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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:

  • Male or female, age greater than or equal to 18 years at the time of signing informed consent
  • Diagnosed with type 2 diabetes greater than or equal to 180 days prior to the day of screening
  • Treated with basal insulin once daily or twice daily for greater than or equal to 90 days prior to the day of screening
  • Stable daily dose for 90 days prior to the day of screening of the following anti-diabetic drugs or combination regimens: Any metformin formulations (greater than or equal to 1500 mg to less than or equal to 3000 mg or maximum tolerated or effective dose documented in subject's medical record), alone or in combination (including fixed-dose drug combination) with up to one additional of the following oral antidiabetic drugs: sulfonylureas, meglitinides, dipeptidyl peptidase-4 inhibitors or alpha-glucosidase inhibitors
  • Glycated haemoglobin (HbA1c) of greater than 7.5% to less than or less than or equal to 10.0% (greater than 58 mmol/mol to less than or equal to 86 mmol/mol)

Exclusion Criteria:

  • History or presence of pancreatitis (acute or chronic)
  • Any of the following: myocardial infarction, 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 Class IV
  • Planned coronary, carotid or peripheral artery revascularisation known on the day of 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 bolus insulin treatment for a maximum of 14 days prior to the day of screening is allowed
  • Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a pharmacologically pupil-dilated fundus examination performed by an ophthalmologist or an equally qualified health care provider (for example, optometrist) within the past 90 days prior to run-in

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): NCT03689374


  Show 210 Study Locations
Sponsors and Collaborators
Novo Nordisk A/S
Investigators
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Study Director: Clinical Reporting Anchor and Disclosure (1452) Novo Nordisk A/S

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Responsible Party: Novo Nordisk A/S
ClinicalTrials.gov Identifier: NCT03689374     History of Changes
Other Study ID Numbers: NN9535-4386
U1111-1200-0164 ( Other Identifier: World Health Organization (WHO) )
2017-003219-20 ( Registry Identifier: EudraCT )
First Posted: September 28, 2018    Key Record Dates
Last Update Posted: December 5, 2019
Last Verified: December 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: According to the Novo Nordisk disclosure commitment on novonordisk-trials.com
URL: http://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
Product Manufactured in and Exported from the U.S.: Yes
Additional relevant MeSH terms:
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Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Insulin
Insulin, Globin Zinc
Metformin
Insulin Glargine
Insulin Aspart
Insulin, Long-Acting
Insulin degludec, insulin aspart drug combination
Hypoglycemic Agents
Physiological Effects of Drugs