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A Trial Investigating the Cardiovascular Safety of Oral Semaglutide in Subjects With Type 2 Diabetes (PIONEER 6)

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ClinicalTrials.gov Identifier: NCT02692716
Recruitment Status : Completed
First Posted : February 26, 2016
Results First Posted : February 27, 2020
Last Update Posted : July 20, 2022
Sponsor:
Information provided by (Responsible Party):
Novo Nordisk A/S

Study Description
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Brief Summary:
This trial is conducted globally. The aim of the trial is to investigate the cardiovascular safety of oral semaglutide in subjects with type 2 diabetes.

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

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 3183 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Trial Investigating the Cardiovascular Safety of Oral Semaglutide in Subjects With Type 2 Diabetes
Actual Study Start Date : January 17, 2017
Actual Primary Completion Date : September 25, 2018
Actual Study Completion Date : September 25, 2018

Resource links provided by the National Library of Medicine

Drug Information available for: Semaglutide

Arms and Interventions
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Arm Intervention/treatment
Experimental: Oral semaglutide Drug: semaglutide
For oral use once daily.
Placebo Comparator: Placebo Drug: placebo
For oral use once daily.


Outcome Measures
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Primary Outcome Measures :
  1. Time From Randomisation to First Occurrence of a Major Adverse Cardiovascular Event (MACE) Composite Endpoint Consisting of: Cardiovascular Death, Non-fatal Myocardial Infarction or Non-fatal Stroke [ Time Frame: Maximum treatment duration is dependent on event rates and is estimated to be no longer than 19 months + 5 weeks of follow-up period. ]
    Number of participants experiencing a first event of a MACE, defined as cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke are presented. Results are based on the in-trial observation period which started at the date of randomisation, included the period after permanent trial product discontinuation, if any and ended at the date of the follow-up visit regardless of adherence to treatment.


Secondary Outcome Measures :
  1. Time From Randomisation to First Occurrence of an Expanded Composite Cardiovascular Endpoint Consisting of: Cardiovascular Death, Non-fatal Myocardial Infarction, Non-fatal Stroke, UAP Requiring Hospitalisation or Hospitalisation for Heart Failure [ Time Frame: Maximum treatment duration is dependent on event rates and is estimated to be no longer than 19 months + 5 weeks of follow-up period. ]
    Participants experiencing first occurrence of an expanded composite CV endpoint [defined as cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, UAP (unstable angina pectoris) requiring hospitalisation or heart failure requiring hospitalisation] are presented. Results are based on the in-trial observation period which started at the date of randomisation, included the period after permanent trial product discontinuation, if any and ended at the date of the follow-up visit regardless of adherence to treatment.

  2. Time From Randomisation to First Occurrence of Each of the Individual Components in the Expanded Composite Cardiovascular Endpoint [ Time Frame: Maximum treatment duration is dependent on event rates and is estimated to be no longer than 19 months + 5 weeks of follow-up period. ]
    Participants experiencing an event onset for each individual component of the expanded composite cardiovascular outcomes (defined as cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, unstable angina requiring hospitalisation or heart failure requiring hospitalisation) are presented. Results are based on the in-trial observation period which started at the date of randomisation, included the period after permanent trial product discontinuation, if any and ended at the date of the follow-up visit regardless of adherence to treatment.

  3. Time From Randomisation to First Occurrence of a Composite Endpoint Consisting of: All-cause Death, Non-fatal Myocardial Infarction or Nonfatal Stroke [ Time Frame: Maximum treatment duration is dependent on event rates and is estimated to be no longer than 19 months + 5 weeks of follow-up period. ]
    Participants experiencing first occurrence of a composite CV endpoint (defined as all-cause death, non-fatal myocardial infarction or nonfatal stroke) are presented. Results are based on the in-trial observation period which started at the date of randomisation, included the period after permanent trial product discontinuation, if any and ended at the date of the follow-up visit regardless of adherence to treatment.

  4. Time From Randomisation to First Occurrence of Fatal or Non-fatal Myocardial Infarction [ Time Frame: Maximum treatment duration is dependent on event rates and is estimated to be no longer than 19 months + 5 weeks of follow-up period. ]
    Number of participants experiencing a first event of a fatal or non-fatal myocardial infarction are presented. Results are based on the in-trial observation period which started at the date of randomisation, included the period after permanent trial product discontinuation, if any and ended at the date of the follow-up visit regardless of adherence to treatment.

  5. Time From Randomisation to First Occurrence of Fatal or Non-fatal Stroke [ Time Frame: Maximum treatment duration is dependent on event rates and is estimated to be no longer than 19 months + 5 weeks of follow-up period. ]
    Number of participants experiencing a first event of a fatal or non-fatal stroke are presented. Results are based on the in-trial observation period which started at the date of randomisation, included the period after permanent trial product discontinuation, if any and ended at the date of the follow-up visit regardless of adherence to treatment.

  6. Time From Randomisation to All-cause Death [ Time Frame: Maximum treatment duration is dependent on event rates and is expected to be no longer than 19 months + 5 weeks of follow-up period. ]
    Number of all-cause deaths in the study are presented. Results are based on the in-trial observation period which started at the date of randomisation, included the period after permanent trial product discontinuation, if any and ended at the date of the follow-up visit regardless of adherence to treatment.

  7. Time to First AE Leading to Permanent Trial Product Discontinuation [ Time Frame: Maximum treatment duration is dependent on event rates and is expected to be no longer than 19 months + 38 days of ascertainment window. ]
    Number of participants who permanently discontinued trial product in ths study are presented. Results are based on the on-treatment observation period which starts at the date of first dose on trial product; ends on last date on trial product +38 days (ascertainment window).

  8. Number of Serious Adverse Events [ Time Frame: Maximum treatment duration is dependent on event rates and is expected to be no longer than 19 months + 38 days of ascertainment window. ]
    Number of serious adverse events were recorded from week 0 to week 87 in the study. Results are based on the on-treatment observation period which started at the date of first dose on trial product and ended on last date on trial product +38 days (ascertainment window).

  9. Change in Eye Examination Category [ Time Frame: Week -3, End of treatment ]
    Participants with eye examination findings, normal, abnormal non clinically significant (NCS) and abnormal clinically significant (CS) at baseline (week -3) and end of treatment visit (week 83) are presented. Results are based on the in-trial observation period which started at the date of randomisation, included the period after permanent trial product discontinuation, if any and ended at the date of the follow-up visit regardless of adherence to treatment.

  10. Change in Pulse Rate [ Time Frame: Week 0, End of treatment ]
    Change from baseline (week 0) in pulse rate measured at the end of treatment visit (week 83) is reported. Results are based on the on-treatment observation period which started at the date of first dose on trial product, ended on last date on trial product +38 days (ascertainment window).

  11. Change in Systolic and Diastolic Blood Pressure [ Time Frame: Week 0, End of treatment ]
    Change from baseline (week 0) in systolic and diastolic blood pressure measured at the end of treatment visit (week 83) is reported. Results are based on the on-treatment observation period which started at the date of first dose on trial product, ended on last date on trial product +38 days (ascertainment window).

  12. Change in Glycosylated Haemoglobin (HbA1c) [ Time Frame: Week 0, End of treatment ]
    Change from baseline (week 0) in HbA1c measured at the end of treatment visit (week 83) is reported. Results are based on the in-trial observation period which started at the date of randomisation, included the period after permanent trial product discontinuation, if any and ended at the date of the follow-up visit regardless of adherence to treatment.

  13. Change in Body Weight [ Time Frame: Week 0, End of treatment ]
    Change from baseline (week 0) in body weight measured at the end of treatment visit (week 83) is reported. Results are based on the in-trial observation period which started at the date of randomisation, included the period after permanent trial product discontinuation, if any and ended at the date of the follow-up visit regardless of adherence to treatment.

  14. Change in Total Cholesterol - Ratio to Baseline [ Time Frame: Week 0, End of treatment ]
    Change from baseline (week 0) in total cholesterol (mmol/L) at the end of treatment (week 83) visit is presented as ratio to baseline. Results are based on the in-trial observation period which started at the date of randomisation, included the period after permanent trial product discontinuation, if any and ended at the date of the follow-up visit regardless of adherence to treatment.

  15. Change in LDL-cholesterol - Ratio to Baseline [ Time Frame: Week 0, End of treatment ]
    Change from baseline (week 0) in LDL cholesterol (mmol/L) at end of treatment visit (week 83) is presented as ratio to baseline. Results are based on the in-trial observation period which started at the date of randomisation, included the period after permanent trial product discontinuation, if any and ended at the date of the follow-up visit regardless of adherence to treatment.

  16. Change in HDL-cholesterol - Ratio to Baseline [ Time Frame: Week 0, End of treatment ]
    Change from baseline (week 0) in HDL cholesterol (mmol/L) at end of treatment visit (week 83) is presented as ratio to baseline. Results are based on the in-trial observation period which started at the date of randomisation, included the period after permanent trial product discontinuation, if any and ended at the date of the follow-up visit regardless of adherence to treatment.

  17. Change in Triglycerides - Ratio to Baseline [ Time Frame: Week 0, End of treatment ]
    Change from baseline (week 0) in triglycerides (mmol/L) at end of treatment visit (week 83) is presented as ratio to baseline. Results are based on the in-trial observation period which started at the date of randomisation, included the period after permanent trial product discontinuation, if any and ended at the date of the follow-up visit regardless of adherence to treatment.


Eligibility Criteria
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Ages Eligible for Study:   50 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female diagnosed with type 2 diabetes
  • Age at least 50 years at screening and presence of cardiovascular disease, or age at least 60 years at screening and presence of at least one cardiovascular risk factor

Exclusion Criteria:

  • Current or previous (within 90 days prior to screening) treatment with any GLP-1 (glucagon-like peptide-1) receptor agonist, DPP-4 (dipeptidyl peptidase-4) inhibitor or pramlintide
  • Family or personal history of multiple endocrine neoplasia type 2 (MEN 2) or medullary thyroid carcinoma (MTC)
  • 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)
  • Subjects presently classified as being in New York Heart Association (NYHA) Class IV heart failure
  • Planned coronary, carotid or peripheral artery revascularisation known on the day of screening
  • Any of the following: myocardial infarction, stroke or hospitalisation for unstable angina or transient ischaemic attack within the past 60 days prior to screening
  • Chronic or intermittent hemodialysis or peritoneal dialysis or severe renal impairment (corresponding to eGFR (glomerular filtration rate, estimated) below 30 mL/min/1.73 m^2)
  • History or presence of malignant neoplasms within the last 5 years (except basal and squamous cell skin cancer and carcinoma in situ)
Contacts and Locations
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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): NCT02692716


Locations
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Sponsors and Collaborators
Novo Nordisk A/S
Investigators
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Study Director: Global Clinical Registry (GCR, 1452) Novo Nordisk A/S
  Study Documents (Full-Text)

Documents provided by Novo Nordisk A/S:
Study Protocol  [PDF] February 11, 2019
Statistical Analysis Plan  [PDF] February 11, 2019

More Information
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Additional Information:

Publications of Results:

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: NCT02692716    
Other Study ID Numbers: NN9924-4221
2015-003563-10 ( EudraCT Number )
U1111-1173-0750 ( Other Identifier: WHO )
NL56580.091.16 ( Other Identifier: CCMO )
First Posted: February 26, 2016    Key Record Dates
Results First Posted: February 27, 2020
Last Update Posted: July 20, 2022
Last Verified: July 2022
Additional relevant MeSH terms:
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Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases