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

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

Tracking Information
First Submitted Date  ICMJE February 23, 2016
First Posted Date  ICMJE February 26, 2016
Results First Submitted Date  ICMJE October 15, 2019
Results First Posted Date  ICMJE February 27, 2020
Last Update Posted Date February 27, 2020
Actual Study Start Date  ICMJE January 17, 2017
Actual Primary Completion Date September 25, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 14, 2020)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: February 23, 2016)
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: From randomisation up to 19 months ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 14, 2020)
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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).
  • 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).
  • 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.
  • 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).
  • 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).
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: February 23, 2016)
  • From randomisation to first occurrence of an expanded composite cardiovascular endpoint consisting of: cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, unstable angina requiring hospitalisation or hospitalisation for heart failure [ Time Frame: From randomisation up to 19 months ]
  • Time from randomisation to first occurrence of each of the individual components in the expanded composite cardiovascular endpoint [ Time Frame: From randomisation up to 19 months ]
  • Time from randomisation to first occurrence of a composite endpoint consisting of: all-cause death, non-fatal myocardial infarction or non-fatal stroke [ Time Frame: From randomisation up to 19 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Trial Investigating the Cardiovascular Safety of Oral Semaglutide in Subjects With Type 2 Diabetes
Official Title  ICMJE A Trial Investigating the Cardiovascular Safety of Oral Semaglutide in Subjects With Type 2 Diabetes
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE
  • Diabetes
  • Diabetes Mellitus, Type 2
Intervention  ICMJE
  • Drug: semaglutide
    For oral use once daily.
  • Drug: placebo
    For oral use once daily.
Study Arms  ICMJE
  • Experimental: Oral semaglutide
    Intervention: Drug: semaglutide
  • Placebo Comparator: Placebo
    Intervention: Drug: placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 23, 2018)
3183
Original Estimated Enrollment  ICMJE
 (submitted: February 23, 2016)
3176
Actual Study Completion Date  ICMJE September 25, 2018
Actual Primary Completion Date September 25, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 50 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Algeria,   Argentina,   Brazil,   Canada,   Denmark,   Germany,   India,   Israel,   Italy,   Malaysia,   Mexico,   Netherlands,   Poland,   Romania,   South Africa,   Spain,   Taiwan,   Thailand,   Turkey,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02692716
Other Study ID Numbers  ICMJE NN9924-4221
2015-003563-10 ( EudraCT Number )
U1111-1173-0750 ( Other Identifier: WHO )
NL56580.091.16 ( Other Identifier: CCMO )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Novo Nordisk A/S
Study Sponsor  ICMJE Novo Nordisk A/S
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Global Clinical Registry (GCR, 1452) Novo Nordisk A/S
PRS Account Novo Nordisk A/S
Verification Date February 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP