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Efficacy and Safety of Oral Semaglutide Using a Flexible Dose Adjustment Based on Clinical Evaluation Versus Sitagliptin in Subjects With Type 2 Diabetes Mellitus. (PIONEER 7)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02849080
Recruitment Status : Completed
First Posted : July 29, 2016
Results First Posted : February 17, 2020
Last Update Posted : February 17, 2020
Sponsor:
Information provided by (Responsible Party):
Novo Nordisk A/S

Brief Summary:
This trial is globally conducted. The aim of this trial is to investigate Efficacy and Safety of Oral Semaglutide Using a Flexible Dose Adjustment Based on Clinical Evaluation versus Sitagliptin in Subjects with Type 2 Diabetes Mellitus.

Condition or disease Intervention/treatment Phase
Diabetes Diabetes Mellitus, Type 2 Drug: semaglutide Drug: sitagliptin Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 504 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official 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
Actual Study Start Date : September 20, 2016
Actual Primary Completion Date : February 28, 2018
Actual Study Completion Date : March 27, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Semaglutide flexible dosing (3, 7 or 14 mg) Drug: semaglutide
Oral administration once-daily.

Active Comparator: Sitagliptin 100 mg Drug: sitagliptin
Oral administration once-daily.




Primary Outcome Measures :
  1. Participants Who Achieve HbA1c <7.0% (53 mmol/Mol) ADA Target (Yes/no) [ Time Frame: Week 52 ]
    Participants who achieved HbA1c <7.0% (American Diabetes Association (ADA) target) (yes/no), was evaluated at week 52. The endpoint was evaluated based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product. The endpoint was also evaluated based on the data from the on-treatment without rescue medication observation period, which was the time period when a participant was on treatment with trial product, excluding any period after initiation of rescue medication and/or premature trial product discontinuation.


Secondary Outcome Measures :
  1. Change in Body Weight: Week 52 [ Time Frame: Week 0, week 52 ]
    Change from baseline (week 0) in body weight was evaluated at week 52. The endpoint was evaluated based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product. The endpoint was also evaluated based on the data from the on-treatment without rescue medication observation period, which was the time period when a participant was on treatment with trial product, excluding any period after initiation of rescue medication and/or premature trial product discontinuation.

  2. Change in HbA1c: Week 52 [ Time Frame: Week 0, week 52 ]
    Change from baseline (week 0) in HbA1c was evaluated at week 52. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

  3. Change in FPG [ Time Frame: Week 0, week 52 ]
    Change from baseline (week 0) in fasting plasma glucose (FPG) was evaluated at week 52. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

  4. Change in Body Weight (%) [ Time Frame: Week 0, week 52 ]
    Relative change from baseline (week 0) in body weight (kg) was evaluated at week 52. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

  5. Change in BMI [ Time Frame: Week 0, Week 52 ]
    Change from baseline (week 0) in body mass index (BMI) was evaluated at week 52. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

  6. Change in Waist Circumference [ Time Frame: Week 0, week 52 ]
    Change from baseline (week 0) in waist circumference was evaluated at week 52. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

  7. Change in Total Cholesterol (Ratio to Baseline) [ Time Frame: Week 0, Week 52 ]
    Change from baseline (week 0) in total cholesterol (mmol/L) at week 52 is presented as ratio to baselineResults are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

  8. Change in LDL Cholesterol (Ratio to Baseline) [ Time Frame: Week 0, week 52 ]
    Change from baseline (week 0) in low-density lipoprotein (LDL) cholesterol (mmol/L) at week 52 is presented as ratio to baseline. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

  9. Change in HDL Cholesterol (Ratio to Baseline) [ Time Frame: Week 0, week 52 ]
    Change from baseline (week 0) in high-density lipoprotein (HDL) cholesterol (mmol/L) at weeks 26, 52 and 78 is presented as ratio to baseline. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

  10. Change in Triglycerides (Ratio to Baseline) [ Time Frame: Week 0, week 52 ]
    Change from baseline (week 0) in triglycerides (mmol/L) at week 52 is presented as ratio to baseline. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

  11. Change in SF-36v2 (Acute Version) Health Survey: Scores From the 8 Domains, the Physical Component Summary (PCS) and the Mental Component Summary (MCS) [ Time Frame: Week 0, week 52 ]
    SF-36 is a 36-item patient-reported survey of patient health that measures the participant's overall health-related quality of life (HRQoL). SF-36v2™ (acute version) questionnaire measured eight domains of functional health and well-being as well as two component summary scores (physical component summary (PCS) and mental component summary (MCS)). The 0-100 scale scores (where higher scores indicated a better HRQoL) from the SF-36 were converted to norm-based scores to enable a direct interpretation in relation to the distribution of the scores in the 2009 U.S. general population. In the metric of norm-based scores, 50 and 10 corresponds to the mean and standard deviation respectively of the 2009 U.S. general population. Change from baseline (week 0) in the domain scores and component summary (PCS and MCS) scores were evaluated at week 52. A positive change score indicates an improvement since baseline. Results are based on the data from the in-trial observation period.

  12. Change in DTSQ [ Time Frame: Week 0, Week 52 ]
    Change from baseline (week 0) in diabetes treatment satisfaction questionnaire - status (DTSQs) was evaluated at week 52. The DTSQs items are scored on a 7-point graded response scale ranging from 6 to 0. Higher scores indicate higher levels of treatment satisfaction for DTSQs items 1, 4 -8. For items 2 and 3 a higher score indicates a higher patient perceived experience of high blood sugars and low blood sugars, respectively. Thus, lower scores indicate a perception of blood glucose levels being "none of the time" unacceptably high (item 2) or low (item 3). The domain score of total treatment satisfaction (total treatment satisfaction score) was computed by adding the six items scores 1, 4-8. The score ranges 0-36. A higher treatment satisfaction score indicates a higher level of treatment satisfaction. Results are based on the data from the in-trial observation period.

  13. Participants Who Achieve HbA1c ≤6.5% (48 mmol/Mol) AACE Target (Yes/no) [ Time Frame: Week 52 ]
    Participants who achieved HbA1c less than or equal to 6.5% (American Association of Clinical Endocrinologists (AACE) target) (yes/no) at week 52 is presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

  14. Participants Who Achieve Weight Loss ≥5% (Yes/no) [ Time Frame: Week 52 ]
    Participants who achieved weight loss more than or equal to 5% of their baseline body weight (yes/no) at weeks 52 is presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

  15. Participants Who Achieve Weight Loss ≥10% (Yes/no) [ Time Frame: Week 52 ]
    Participants who achieved weight loss more than or equal to 10% of their baseline body weight (yes/no) at week 52 is presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

  16. Participants Who Achieve HbA1c <7.0 % (53 mmol/Mol) Without Hypoglycaemia (Severe or BG Confirmed Symptomatic Hypoglycaemia) and no Weight Gain (Yes/no) [ Time Frame: Week 52 ]
    Participants who achieved HbA1c less than 7.0 % without severe or blood glucose (BG) confirmed symptomatic hypoglycaemia and without weight gain (yes/no) at week 52 is presented. Severe hypoglycaemia was defined as an episode requiring assistance of another person to actively administer carbohydrate or glucagon, or take other corrective actions. BG-confirmed symptomatic hypoglycaemia was defined as an episode with plasma glucose value <3.1 mmol/L with symptoms consistent with hypoglycaemia. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

  17. Participants Who Achieve HbA1c Reduction ≥1% (10.9 mmol/Mol) and Weight Loss ≥3% (Yes/no) [ Time Frame: Week 52 ]
    Participants who achieved HbA1c reduction more than or equal to 1% of their baseline HbA1c and weight loss of more than or equal to 3% of their baseline body weight (yes/no) at week 52 is presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

  18. Time to Rescue Medication [ Time Frame: Weeks 0-52 ]
    Presented results are the number of participants who had taken rescue medication anytime during the periods, from week 0 to week 52. Rescue medication was defined as any new anti-diabetic medication used as add-on to trial product and used for more than 21 days with the initiation at or after randomisation (week 0) and before last day on trial product, and/or intensification of anti-diabetic medication (a more than 20% increase in dose relative to baseline) for more than 21 days with the intensification at or after randomisation and before last day on trial product. Results are based on the data from the on-treatment without rescue medication observation period, which was the time period when a participant was on treatment with trial product, excluding any period after initiation of rescue medication and/or premature trial product discontinuation.

  19. Time to Additional Anti-diabetic Medication [ Time Frame: Weeks 0-52 ]
    Presented results are the number of participants who had taken additional anti-diabetic medication anytime during the period from week 0 to week 52. Additional anti-diabetic medication was defined as any new anti-diabetic medication used for more than 21 days with the initiation at or after randomisation (week 0) and before (planned) end-of-treatment (week 52), and/or intensification of anti-diabetic medication (a more than 20% increase in dose relative to baseline) for more than 21 days with the intensification at or after randomisation and before (planned) end-of-treatment. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

  20. Number of TEAEs During Exposure to Trial Product [ Time Frame: Week 0-57 ]
    Treatment emergent adverse events (TEAEs) were recorded from week 0 to week 57 (52-week treatment period for participants who continued in the extension phase; 52-week treatment period plus the 5-week follow-up period for participants who did not continue in the extension phase). Adverse events (AEs) with onset during the on-treatment observation period were considered treatment-emergent. On-treatment observation period: Time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

  21. Number of Treatment-emergent Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes [ Time Frame: Week 0-57 ]
    Treatment emergent severe or BG confirmed symptomatic hypoglycaemic episodes were recorded during weeks 0-57 (52-week treatment period for participants who continued in the extension phase; 52-week treatment period plus the 5-week follow-up period for participants who did not continue in the extension phase). Hypoglycaemic episodes with onset during the on-treatment observation period were considered treatment-emergent. On-treatment observation period was defined as the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication. Severe hypoglycaemia was defined as an episode requiring assistance of another person to actively administer carbohydrate or glucagon, or take other corrective actions. BG-confirmed symptomatic hypoglycaemia: Confirmed by a glucose value <3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia.

  22. Paticipants With Treatment-emergent Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes (Yes/no) [ Time Frame: Week 0-57 ]
    Treatment emergent severe or BG confirmed symptomatic hypoglycaemic episodes were recorded during weeks 0-57 (52-week treatment period for participants who continued in the extension phase; 52-week treatment period plus the 5-week follow-up period for participants who did not continue in the extension phase). Hypoglycaemic episodes with onset during the on-treatment observation period were considered treatment-emergent. On-treatment observation period was defined as the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication. Severe hypoglycaemia was defined as an episode requiring assistance of another person to actively administer carbohydrate or glucagon, or take other corrective actions. BG-confirmed symptomatic hypoglycaemia: Confirmed by a glucose value <3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia.

  23. Change in Amylase (Ratio to Baseline) [ Time Frame: Week 0, Week 52 ]
    Change from baseline (week 0) in biochemical parameter- amylase (units per liter [U/L]) to week 52 is presented as ratio to baseline. Results are based on the data from the on-treatment observation period which was the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

  24. Change in Lipase (Ratio to Baseline) [ Time Frame: Week 0, Week 52 ]
    Change from baseline (week 0) in lipase (U/L) to week 52 is presented as ratio to baseline. Results are based on the data from the on-treatment observation period which was the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

  25. Change in Pulse Rate [ Time Frame: Week 0, week 52 ]
    Change from baseline (week 0) in pulse rate was evaluated at week 52. Results are based on the data from the on-treatment observation period which was the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

  26. Change in Blood Pressure (Systolic and Diastolic Blood Pressure) [ Time Frame: Week 0, week 52 ]
    Change from baseline (week 0) in systolic blood pressure (SBP) and diastolic blood pressure (DBP) was evaluated at week 52. Results are based on the data from the on-treatment observation period which was the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.



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:

Main phase (the inclusion criteria for the main phase are not reassessed for the extension phase):

  • 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 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
  • Diagnosed with type 2 diabetes mellitus for at least 90 days prior to day of screening
  • HbA1c (glycosylated haemoglobin) 7.5-9.5% (58-80 mmol/mol) (both inclusive)
  • Treatment target of HbA1c below 7.0% (53 mmol/mol), as judged by the investigator
  • Stable daily dose(s) of 1-2 of the following anti-diabetic drugs within 90 days prior to the day of screening:
  • Metformin (equal or above 1500 mg or maximum tolerated dose as documented in the subject medical record)
  • Sulfonylureas (equal or above 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 (equal or above half of the maximum approved dose according to local label or maximum tolerated dose as documented in subject medical record)

Extension phase:

  • Informed consent for the extension phase obtained before any trial-related activities for the extension phase.
  • On randomised treatment with or without rescue medication at week 52.

Exclusion Criteria:

Main phase (the exclusion criteria for the main phase are not reassessed for the extension phase):

  • 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
  • Any disorder, which in the investigator's opinion might jeopardise subject's safety or compliance with the protocol
  • Family or personal history of Multiple Endocrine Neoplasia Type 2 or Medullary Thyroid Carcinoma
  • History of pancreatitis (acute or chronic)
  • 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)
  • 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
  • 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
  • Subjects with alanine aminotransferase above 2.5 x upper normal limit
  • Renal impairment defined as Estimated Glomerular Filtration rate 60 mL/min/1.73 m^2 as per Chronic Kidney Disease Epidemiology Collaboration formula
  • 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 below or equal to 14 days
  • Proliferative retinopathy or maculopathy requiring acute treatment. Verified by fundus photography or dilated fundoscopy performed within 90 days prior to randomisation
  • History or presence of malignant neoplasms within the last 5 years (except basal and squamous cell skin cancer and carcinoma in situ)
  • History of diabetic ketoacidosis

Extension phase: There are no new exclusion criteria for the extension phase


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): NCT02849080


Locations
Show Show 83 study locations
Sponsors and Collaborators
Novo Nordisk A/S
  Study Documents (Full-Text)

Documents provided by Novo Nordisk A/S:
Study Protocol  [PDF] October 25, 2018
Statistical Analysis Plan  [PDF] October 25, 2018


Additional Information:
Publications of Results:
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Responsible Party: Novo Nordisk A/S
ClinicalTrials.gov Identifier: NCT02849080    
Other Study ID Numbers: NN9924-4257
2015-005593-38 ( EudraCT Number )
U1111-1177-5103 ( Other Identifier: WHO )
First Posted: July 29, 2016    Key Record Dates
Results First Posted: February 17, 2020
Last Update Posted: February 17, 2020
Last Verified: February 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: According to 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
Sitagliptin Phosphate
Hypoglycemic Agents
Physiological Effects of Drugs
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action