A Study To Evaluate The Efficacy And Safety Of Ertugliflozin In Participants With Type 2 Diabetes Mellitus And Inadequate Glycemic Control On Metformin Monotherapy (MK-8835-007)

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by Merck Sharp & Dohme Corp.
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT02033889
First received: January 9, 2014
Last updated: September 17, 2014
Last verified: September 2014
  Purpose

This is an efficacy and safety study of ertugliflozin in participants with type 2 diabetes mellitus and inadequate glycemic control on metformin monotherapy. The primary study hypothesis is that at Week 26, the mean reduction from baseline in hemoglobin A1c (HbA1c) for ertugliflozin is greater than that for placebo.


Condition Intervention Phase
Type 2 Diabetes Mellitus
Drug: Ertugliflozin 5 mg
Drug: Ertugliflozin 15 mg
Drug: Placebo to Ertugliflozin
Other: Glimepiride
Drug: Placebo to Glimepiride
Biological: Basal Insulin
Drug: Metformin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 3, Randomized, Double-Blind, Placebo-Controlled, 26-Week Multicenter Study With a 78-Week Extension To Evaluate The Efficacy And Safety Of Ertugliflozin In Subjects With Type 2 Diabetes Mellitus And Inadequate Glycemic Control On Metformin Monotherapy

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Change from Baseline in Hemoglobin A1c [ Time Frame: Baseline and Week 26 ] [ Designated as safety issue: No ]
  • Number of Participants Experiencing An Adverse Event (AE) [ Time Frame: Up to Week 106 ] [ Designated as safety issue: Yes ]
  • Number of Participants Discontinuing Study Treatment Due to an AE [ Time Frame: Up to Week 104 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Change from Baseline in Fasting Plasma Glucose [ Time Frame: Baseline and Week 26 ] [ Designated as safety issue: No ]
  • Change from Baseline in Body Weight at Week 26 [ Time Frame: Baseline and Week 26 ] [ Designated as safety issue: No ]
  • Number of participants with a HbA1c of <7% (53 mmol/mol) at Week 26 [ Time Frame: Week 26 ] [ Designated as safety issue: No ]
  • Change from Baseline in Systolic Blood Pressure [ Time Frame: Baseline and Week 26 ] [ Designated as safety issue: No ]
  • Change from Baseline in Diastolic Blood Pressure [ Time Frame: Baseline and Week 26 ] [ Designated as safety issue: No ]
  • Change from Baseline in Bone Mineral Density at Week 26 [ Time Frame: Baseline and Week 26 ] [ Designated as safety issue: Yes ]
  • Change from Baseline in Bone Mineral Density at Week 52 [ Time Frame: Baseline and Week 52 ] [ Designated as safety issue: Yes ]
  • Change from Baseline in Bone Mineral Density at Week 104 [ Time Frame: Baseline and Week 104 ] [ Designated as safety issue: Yes ]
  • Number of participants with HbA1c <=6.5% (48 mmol/mol) at Week 26 [ Time Frame: Week 26 ] [ Designated as safety issue: No ]
  • Number of participants requiring glycemic rescue therapy up to Week 26 [ Time Frame: Up to Week 26 ] [ Designated as safety issue: No ]
  • Time to glycemic rescue therapy up to Week 26 [ Time Frame: Up to Week 26 ] [ Designated as safety issue: No ]
  • Change from baseline in bone biomarkers at Week 26 [ Time Frame: Baseline and Week 26 ] [ Designated as safety issue: Yes ]
  • Change from baseline in bone biomarkers at Week 52 [ Time Frame: Baseline and Week 52 ] [ Designated as safety issue: Yes ]
  • Change from baseline in bone biomarkers at Week 104 [ Time Frame: Baseline and Week 104 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 600
Study Start Date: January 2014
Estimated Study Completion Date: June 2017
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ertuglifozin 5 mg
Ertugliflozin 5 mg orally, once daily from Day 1 to Week 104. Participants will receive 1 ertugliflozin 5 mg tablet and 1 placebo ertugliflozin 10 mg tablet per day. Participants requiring glycemic rescue during the 26-week initial treatment period (Phase A) will receive open-label glimepiride. This rescue will continue through the 78-week, double-blind, extension period (Phase B). If not rescued during Phase A, participants will receive placebo to glimepiride (up to a maximum of 6 or 8 mg per day, based on the local label of glimepiride) during Phase B. All participants will also receive metformin at a dose >=1500 mg/day in Phase A and B.
Drug: Ertugliflozin 5 mg
Ertugliflozin 5 mg orally, once daily from Day 1 to Week 104.
Other Name: MK-8835
Other: Glimepiride
Glimepiride will be used for glycemic rescue therapy (up to a maximum of 6 or 8 mg per day, based on the local label of glimepiride) in the 26-week initial period. Blinded Glimepiride (up to a maximum of 6 or 8 mg per day, based on the local label of glimepiride will be used in the 78-week extension period in participants who were not rescued with open-label glimepiride during the 26-week initial period. Dosing and titration of blinded glimepiride is at the discretion of the investigator.
Other Names:
  • Amaryl
  • GLIMPID
  • GLIMY
Drug: Placebo to Glimepiride
Placebo to glimepiride will be used in the 78-week extension period in participants who were not rescued with open-label glimepiride during the 26-week initial period. Dosing and titration of placebo to glimepiride is at the discretion of the investigator.
Biological: Basal Insulin
Basal insulin will be used for participants requiring rescue therapy in Phase B. Dosing and titration of basal insulin is at the discretion of the Investigator.
Other Names:
  • Insulin glargine
  • Insulin detemir
  • NPH insulin
  • Degludec
Drug: Metformin
Metformin >=1500 mg/day, orally, once a day
Other Names:
  • Glucophage XR
  • Carbophage SR
  • Riomet
  • Fortamet
  • Glumetza
  • Obimet
  • Gluformin
  • Dianben
  • Diabex
  • Diaformin
  • Siofor
  • Metfogamma
Experimental: Ertugliflozin 15 mg
Ertugliflozin 15 mg orally, once daily from Day 1 to Week 104. Participants will receive 1 ertugliflozin 5 mg tablet and 1 ertugliflozin 10 mg tablet per day. Participants requiring glycemic rescue during the 26-week initial treatment period (Phase A) will receive open-label glimepiride. This rescue will continue through the 78-week, double-blind, extension period (Phase B). If not rescued during Phase A, participants will receive placebo to glimepiride (up to a maximum of 6 or 8 mg per day, based on the local label of glimepiride) during Phase B. All participants will also receive metformin at a dose >=1500 mg/day in Phase A and B.
Drug: Ertugliflozin 15 mg
Ertugliflozin 15 mg orally, once daily from Day 1 to Week 104.
Other Name: MK-8835
Other: Glimepiride
Glimepiride will be used for glycemic rescue therapy (up to a maximum of 6 or 8 mg per day, based on the local label of glimepiride) in the 26-week initial period. Blinded Glimepiride (up to a maximum of 6 or 8 mg per day, based on the local label of glimepiride will be used in the 78-week extension period in participants who were not rescued with open-label glimepiride during the 26-week initial period. Dosing and titration of blinded glimepiride is at the discretion of the investigator.
Other Names:
  • Amaryl
  • GLIMPID
  • GLIMY
Drug: Placebo to Glimepiride
Placebo to glimepiride will be used in the 78-week extension period in participants who were not rescued with open-label glimepiride during the 26-week initial period. Dosing and titration of placebo to glimepiride is at the discretion of the investigator.
Biological: Basal Insulin
Basal insulin will be used for participants requiring rescue therapy in Phase B. Dosing and titration of basal insulin is at the discretion of the Investigator.
Other Names:
  • Insulin glargine
  • Insulin detemir
  • NPH insulin
  • Degludec
Drug: Metformin
Metformin >=1500 mg/day, orally, once a day
Other Names:
  • Glucophage XR
  • Carbophage SR
  • Riomet
  • Fortamet
  • Glumetza
  • Obimet
  • Gluformin
  • Dianben
  • Diabex
  • Diaformin
  • Siofor
  • Metfogamma
Placebo Comparator: Placebo to Ertugliflozin
Placebo to ertuglioflozin, orally once daily from Day 1 to Week 104. Participants will receive 1 placebo ertugliflozin 5 mg tablet and 1 placebo ertugliflozin 10 mg tablet per day. Participants requiring glycemic rescue during the 26-week initial treatment period (Phase A) will receive open-label glimepiride. This rescue will continue through the 78-week, double-blind, extension period (Phase B). If not rescued during Phase A, participants will receive blinded glimepiride (up to a maximum of 6 or 8 mg per day, based on the local label of glimepiride) during Phase B. All participants will also receive metformin at a dose >=1500 mg/day in Phase A and B.
Drug: Placebo to Ertugliflozin
Placebo to ertuglioflozin, orally once daily from Day 1 to Week 104.
Other: Glimepiride
Glimepiride will be used for glycemic rescue therapy (up to a maximum of 6 or 8 mg per day, based on the local label of glimepiride) in the 26-week initial period. Blinded Glimepiride (up to a maximum of 6 or 8 mg per day, based on the local label of glimepiride will be used in the 78-week extension period in participants who were not rescued with open-label glimepiride during the 26-week initial period. Dosing and titration of blinded glimepiride is at the discretion of the investigator.
Other Names:
  • Amaryl
  • GLIMPID
  • GLIMY
Biological: Basal Insulin
Basal insulin will be used for participants requiring rescue therapy in Phase B. Dosing and titration of basal insulin is at the discretion of the Investigator.
Other Names:
  • Insulin glargine
  • Insulin detemir
  • NPH insulin
  • Degludec
Drug: Metformin
Metformin >=1500 mg/day, orally, once a day
Other Names:
  • Glucophage XR
  • Carbophage SR
  • Riomet
  • Fortamet
  • Glumetza
  • Obimet
  • Gluformin
  • Dianben
  • Diabex
  • Diaformin
  • Siofor
  • Metfogamma

Detailed Description:

The trial includes a 13-15 week run-in period prior to randomization, and a 26-week, double-blind, placebo-controlled treatment period (Phase A) followed by a 78-week double-blind, extension period (Phase B).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of T2DM in accordance to American Diabetes Association guidelines
  • Participants must be receiving metformin monotherapy for less than 8 weeks prior to study participation or require change in their diabetes regimen to remain eligible to participate in the trial (including discontinuing anti-hyperglycemic agent [AHA] therapy) and must have a hemoglobin A1c of 7.0 to 10.5% (53-91 mmol/mol) after at least 8 weeks on a regimen of metformin monotherapy

Exclusion Criteria: - History of myocardial infarction, unstable angina, arterial revascularization, stroke, transient ischemic attack, or New York Heart Association (NYHA) functional class III-IV heart failure within 3 months of study participation

  • A clinically significant electrocardiogram abnormality
  • A history of malignancy ≤5 years prior to study participation, except for adequately treated basal or squamous cell skin cancer or in situ cervical cancer
  • A known hypersensitivity or intolerance to any sodium-glucose co-transporter 2 (SGLT2) inhibitor or glimepiride
  • On a blood pressure or lipid altering medication that have not been on a stable dose for at least 4 weeks prior to study participation
  • A surgical procedure within 6 weeks prior to study participation or planned major surgery during the trial
  • Donation of blood or blood products within 6 weeks of study participation or plans to donate blood or blood products at any time during the trial
  • Pregnant or breast-feeding, or is expecting to conceive during the trial, including 14 days following the last dose of study drug
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02033889

Contacts
Contact: Toll Free Number 1-888-577-8839

  Show 27 Study Locations
Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Pfizer
Investigators
Study Director: Medical Director Merck Sharp & Dohme Corp.
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT02033889     History of Changes
Other Study ID Numbers: 8835-007, 2013-003290-95, B1521017
Study First Received: January 9, 2014
Last Updated: September 17, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Insulin, Globin Zinc
Glimepiride
Metformin
Insulin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Arrhythmia Agents
Cardiovascular Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors

ClinicalTrials.gov processed this record on September 18, 2014