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A Research Study Comparing a New Medicine Oral Semaglutide to Sitagliptin in People With Type 2 Diabetes (PIONEER 12)

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04017832
Recruitment Status : Recruiting
First Posted : July 12, 2019
Last Update Posted : December 4, 2020
Sponsor:
Information provided by (Responsible Party):
Novo Nordisk A/S

Brief Summary:
This study compares 2 medicines for type 2 diabetes: oral semaglutide (a new medicine) and sitagliptin (a medicine doctors can already prescribe). Participants will either get oral semaglutide or sitagliptin - which treatment is decided by chance. Participants will get 2 tablets a day to take first thing in the morning on an empty stomach. Only 1 tablet has study medicine in it. The other tablet is a dummy medicine (placebo). After taking the semaglutide tablet, participants may not eat or drink anything for at least 30 minutes. After the 30 minutes, participants must take the sitagliptin tablet. Then participants can have their first meal of the day and take any other medicines they may need, including their metformin. The study will last for about 7 months (33 weeks). Participants will have 8 clinic visits and 1 phone call with the study doctor. At all 8 of the clinic visits, participants will have blood samples taken.

Condition or disease Intervention/treatment Phase
Diabetes Mellitus, Type 2 Drug: Oral semaglutide Drug: Sitagliptin Drug: Placebo (oral semaglutide) Drug: Placebo (sitagliptin) Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1444 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Sponsor staff involved in the clinical trial is masked according to company standard procedures
Primary Purpose: Treatment
Official Title: China Multi-regional Clinical Trial: Efficacy and Safety of Oral Semaglutide Versus Sitagliptin in Subjects With Type 2 Diabetes Mellitus Treated With Metformin
Actual Study Start Date : July 29, 2019
Estimated Primary Completion Date : August 11, 2021
Estimated Study Completion Date : September 13, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Oral semaglutide 3 mg and placebo (sitagliptin)
Oral semaglutide tablets 3 mg and sitagliptin placebo tablets for 26 weeks
Drug: Oral semaglutide
Oral semaglutide to be taken every morning in a fasting state, to be followed by sitagliptin placebo after 30 minutes. Only then participants can have their first meal of the day and their pre-study metformin tablets

Drug: Placebo (sitagliptin)
Placebo tablet to be taken 30 minutes after oral semaglutide

Experimental: Oral semaglutide 7 mg and placebo (sitagliptin)
Oral semaglutide tablets and sitagliptin placebo tablets. The dose of oral semaglutide will be escalated over 4 weeks, after which the target dose of 7 mg is taken for 22 weeks
Drug: Oral semaglutide
Oral semaglutide to be taken every morning in a fasting state, to be followed by sitagliptin placebo after 30 minutes. Only then participants can have their first meal of the day and their pre-study metformin tablets

Drug: Placebo (sitagliptin)
Placebo tablet to be taken 30 minutes after oral semaglutide

Experimental: Oral semaglutide 14 mg and placebo (sitagliptin)
Oral semaglutide tablets and sitagliptin placebo tablets. The dose of oral semaglutide will be escalated over 8 weeks, after which the target dose of 14 mg is taken for 18 weeks
Drug: Oral semaglutide
Oral semaglutide to be taken every morning in a fasting state, to be followed by sitagliptin placebo after 30 minutes. Only then participants can have their first meal of the day and their pre-study metformin tablets

Drug: Placebo (sitagliptin)
Placebo tablet to be taken 30 minutes after oral semaglutide

Experimental: Sitagliptin 100 mg and placebo (oral semaglutide)
Sitagliptin tablets and oral semaglutide placebo tablets for 26 weeks
Drug: Sitagliptin
Sitagliptin to be taken every morning, 30 minutes after taking the oral semaglutide placebo tablet. Then participants can have their first meal of the day and their pre-study metformin tablets

Drug: Placebo (oral semaglutide)
Placebo tablet to be taken first thing in the morning




Primary Outcome Measures :
  1. Change in (glycosylated haemoglobin) HbA1c [ Time Frame: Week 0, week 26 ]
    percent


Secondary Outcome Measures :
  1. Change in body weight [ Time Frame: Week 0, week 26 ]
    kg

  2. Change in fasting plasma glucose (FPG) [ Time Frame: Week 0, week 26 ]
    mg/dl

  3. Change in fasting 7 point self-measured plasma glucose (SMPG) profile: Mean 7-point profile [ Time Frame: Week 0, week 26 ]
    Mean daytime glucose value

  4. Change in fasting 7 point self-measured plasma glucose (SMPG) profile: Mean postprandial increment (over all meals) [ Time Frame: Week 0, week 26 ]
    Mean glucose value over all meals

  5. Change in body weight [ Time Frame: Week 0, week 26 ]
    percent

  6. Change in body mass index (BMI) [ Time Frame: Week 0, week 26 ]
    kg/m^2

  7. Change in waist circumference [ Time Frame: Week 0, week 26 ]
    cm

  8. Change in fasting lipid profile: total cholesterol [ Time Frame: Week 0, week 26 ]
    mg/dl

  9. Change in fasting lipid profile: low-density lipoprotein (LDL) cholesterol [ Time Frame: Week 0, week 26 ]
    mg/dl

  10. Change in fasting lipid profile: very-low-density lipoprotein (VLDL) cholesterol [ Time Frame: Week 0, week 26 ]
    mg/dl

  11. Change in fasting lipid profile: high-density lipoprotein (HDL) cholesterol [ Time Frame: Week 0, week 26 ]
    mg/dl

  12. Change in fasting lipid profile: triglycerides [ Time Frame: Week 0, week 26 ]
    mg/dl

  13. Change in fasting lipid profile: free fatty acids [ Time Frame: Week 0, week 26 ]
    mg/dl

  14. Change in Short Form-36 version 2 (SF-36v2™) (acute version) health survey [ Time Frame: Week 0, week 26 ]
    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. Range of score: 1-100 (1 representing worst results and 100 representing best results)

  15. If a subject achieves HbA1c below 7.0 percent (53 mmol/mol) (American Diabetes Association (ADA) target) (yes/no) [ Time Frame: After 26 weeks ]
    Proportion of subjects

  16. If a subject achieves HbA1c equal to or below 6.5 percent (48 mmol/mol) (American Association of Clinical Endocrinologists (AACE) target) (yes/no) [ Time Frame: After 26 weeks ]
    Proportion of subjects

  17. If a subject achieves HbA1c reduction equal to or above 1 percent-point (10.9 mmol/mol) (yes/no) [ Time Frame: After 26 weeks ]
    Proportion of subjects

  18. If a subject achieves body weight loss equal to or above 3 percent (yes/no) [ Time Frame: After 26 weeks ]
    Proportion of subjects

  19. If a subject achieves body weight loss equal to or above 5 percent (yes/no) [ Time Frame: After 26 weeks ]
    Proportion of subjects

  20. If a subject achieves body weight loss equal to or above 10 percent (yes/no) [ Time Frame: After 26 weeks ]
    Proportion of subjects

  21. If a subject achieves HbA1c below 7.0 percent (53 mmol/mol) without hypoglycaemia (treatment-emergent severe or BG confirmed symptomatic hypoglycaemic episodes) and no body weight gain (yes/no) [ Time Frame: After 26 weeks ]
    Proportion of subjects fullfilling the criteria

  22. If a subject achieves HbA1c reduction equal to or above 1 percent-point (10.9 mmol/mol) and body weight loss equal to or above 3 percent (yes/no) [ Time Frame: After 26 weeks ]
    Proportion of subjects fullfilling the criteria

  23. Time to rescue medication [ Time Frame: Week 0 - week 31 ]
    Days/weeks/months

  24. Number of treatment-emergent adverse events (TEAEs) during exposure to trial product [ Time Frame: Week 0 - week 31 ]
    Count

  25. Number of treatment-emergent severe or BG confirmed symptomatic hypoglycaemic episodes during exposure to trial product [ Time Frame: Week 0 - week 31 ]
    Count

  26. Number of treatment-emergent severe or BG confirmed symptomatic hypoglycaemic episodes during exposure to trial product (yes/no) [ Time Frame: Week 0 - week 31 ]
    Count



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:

  • 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 Algeria only: Male or female, age above or equal to 19 years at the time of signing informed consent.

For Taiwan only: Male or female, age above or equal to 20 years at the time of signing informed consent

  • Diagnosed with type 2 diabetes mellitus 60 days or more prior to day of screening.
  • HbA1c between 7.0-10.5% (53-91 mmol/mol) (both inclusive).
  • Stable daily dose of metformin (equal to or above 1500 mg or maximum tolerated dose as documented in the subject medical record) 60 days or more prior to day of screening

Exclusion Criteria:

  • Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using a highly effective contraceptive method (adequate contraceptive measure as required by local regulation or practice).
  • Family or personal history of multiple endocrine neoplasia type 2 (MEN 2) or medullary thyroid carcinoma (MTC). Family is defined as a first degree relative.
  • History or presence 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, hospitalization 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 (NYHA) Class IV.
  • Planned coronary, carotid or peripheral artery revascularisation known on the day of screening.
  • Renal impairment measured as estimated glomerular filtration rate (eGFR) below 60 mL/min/1.73 m^2 as per Chronic Kidney Disease Epidemiology Collaboration formula (CKD-EPI).
  • Subjects with alanine aminotransferase (ALT) above 2.5 x upper limit of the normal (ULN).
  • Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a pharmacologically pupil-dilated fundus examination performed by an ophthalmologist or another suitably qualified health care provider within the past 90 days prior to screening or in the period between screening and randomisation. Fundus examination without dilation is only allowed if the digital camera used for fundus photography has this feature.
  • 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.

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): NCT04017832


Contacts
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Contact: Novo Nordisk (+1) 866-867-7178 clinicaltrials@novonordisk.com

Locations
Show Show 90 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: NCT04017832    
Other Study ID Numbers: NN9924-4309
U1111-1188-1256 ( Other Identifier: World Health Organization (WHO) )
2018-002589-38 ( Registry Identifier: European Medicines Agency (EudraCT) )
First Posted: July 12, 2019    Key Record Dates
Last Update Posted: December 4, 2020
Last Verified: December 2020
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: No
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