Safety and Efficacy of Ertugliflozin in the Treatment of Participants With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Metformin and Sitagliptin (MK-8835-006)

Overview[ - collapse ][ - ]

Purpose This is a safety and efficacy study of ertugliflozin (MK-8835/PF-04971729) in the treatment of participants with type 2 diabetes mellitus who have inadequate glycemic control on metformin and sitagliptin. The primary objective of the trial is to assess the hemoglobin A1C (A1C)-lowering efficacy of the addition of ertugliflozin compared to the addition of placebo with an underlying hypothesis that addition of treatment with ertugliflozin provides greater reduction in A1C compared with the addition of placebo; the primary objective will be tested for both 5-mg and 15-mg doses of ertugliflozin.
ConditionType 2 Diabetes Mellitus
InterventionDrug: Ertugliflozin (5 mg)
Drug: Ertugliflozin (15 mg)
Drug: Placebo
Drug: Metformin
Drug: Sitagliptin
Drug: Glimepiride
Biological: Insulin
PhasePhase 3
SponsorMerck Sharp & Dohme Corp.
Responsible PartyMerck Sharp & Dohme Corp.
ClinicalTrials.gov IdentifierNCT02036515
First ReceivedJanuary 13, 2014
Last UpdatedApril 24, 2014
Last verifiedApril 2014

Tracking Information[ + expand ][ + ]

First Received DateJanuary 13, 2014
Last Updated DateApril 24, 2014
Start DateMarch 2014
Estimated Primary Completion DateApril 2016
Current Primary Outcome Measures
  • Change from baseline in hemoglobin A1C at Week 26 [Time Frame: Baseline and Week 26] [Designated as safety issue: No]
  • Number of Participants Experiencing An Adverse Event (AE) [Time Frame: Up to Week 54] [Designated as safety issue: Yes]
  • Number of Participants Discontinuing Study Treatment Due to an AE [Time Frame: Up to Week 52] [Designated as safety issue: Yes]
Current Secondary Outcome Measures
  • Change from baseline in fasting plasma glucose (FPG) at Week 26 [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 an A1C <7% (53 mmol/mol) at Week 26 [Time Frame: Week 26] [Designated as safety issue: No]
  • Change from baseline in systolic blood pressure at Week 26 [Time Frame: Baseline and Week 26] [Designated as safety issue: No]

Descriptive Information[ + expand ][ + ]

Brief TitleSafety and Efficacy of Ertugliflozin in the Treatment of Participants With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Metformin and Sitagliptin (MK-8835-006)
Official TitleA Phase III, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Clinical Trial to Evaluate the Safety and Efficacy of Ertugliflozin (MK-8835/PF-04971729) in the Treatment of Subjects With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Metformin and Sitagliptin
Brief Summary
This is a safety and efficacy study of ertugliflozin (MK-8835/PF-04971729) in the treatment
of participants with type 2 diabetes mellitus who have inadequate glycemic control on
metformin and sitagliptin. The primary objective of the trial is to assess the hemoglobin
A1C (A1C)-lowering efficacy of the addition of ertugliflozin compared to the addition of
placebo with an underlying hypothesis that addition of treatment with ertugliflozin provides
greater reduction in A1C compared with the addition of placebo; the primary objective will
be tested for both 5-mg and 15-mg doses of ertugliflozin.
Detailed Description
The duration of the trial will be approximately 69 weeks. This will include a 1-week
Screening Period, an up to 12-week wash-off/titration /dose-stabilization period, a 2-week
single-blind, placebo run-in period, a 52-week double-blind, placebo-controlled treatment
period (including a 26-week Phase A and 26-week Phase B), and a post-treatment telephone
contact 14 days after the last dose of blinded investigational product.
Study TypeInterventional
Study PhasePhase 3
Study DesignAllocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
ConditionType 2 Diabetes Mellitus
InterventionDrug: Ertugliflozin (5 mg)
Ertugliflozin, oral, 5 mg tablet once daily for 52 weeks
Other Names:
  • MK-8835
  • PF-04971729
Drug: Ertugliflozin (15 mg)
Ertugliflozin, oral, 5 mg and 10 mg tablet once daily for 52 weeks
Other Names:
  • MK-8835
  • PF-04971729
Drug: Placebo
Matching placebo for ertugliflozin 5 mg, oral, and matching placebo for ertugliflozin 10 mg, oral, once daily for 52 weeks
Drug: Metformin
Participants are to remain on their stable doses of metformin (oral, >=1500 mg/day) while receiving blinded investigational product during the double-blind treatment period.
Other Names:
  • Glucophage
  • Glucophage XR
Drug: Sitagliptin
Participants are to remain on their stable doses of sitagliptin (oral, 100 mg once daily) while receiving blinded investigational product during the double-blind treatment period.
Other Names:
JANUVIA®Drug: Glimepiride
Glimepiride rescue medication, oral, once daily, open-label glimepiride; dose determined per the investigator's discretion
Other Names:
AMARYLBiological: Insulin
Insulin glargine rescue medication, injectable, as required. In the event that an investigator considers use of glimepiride to not be appropriate for a participant meeting protocol specified glycemic rescue criteria, insulin glargine can be initiated as the rescue medication, and managed by the investigator according to clinical practice guidelines of the local country.
Study Arm (s)
  • Experimental: Ertugliflozin (5 mg)
    Ertugliflozin, 5 mg, oral, once daily for 52 weeks
  • Experimental: Ertugliflozin (15 mg)
    Ertugliflozin, 15 mg, oral, once daily for 52 weeks
  • Placebo Comparator: Placebo
    Matching placebo to ertuglifozin, oral, once daily for 52 weeks

Recruitment Information[ + expand ][ + ]

Recruitment StatusRecruiting
Estimated Enrollment405
Estimated Completion DateApril 2016
Estimated Primary Completion DateOctober 2015
Eligibility Criteria
Inclusion Criteria:

- Diagnosis of type 2 diabetes mellitus (T2DM)

- On stable diabetes therapy of metformin with either sitagliptin or another dipeptidyl
peptidase-4 (DPP-4) inhibitor or a sulfonylurea (SU) prior to study participation and
is willing to wash-off/switch from another DPP-4 inhibitor/SU to sitagliptin

- Body Mass Index (BMI) greater than or equal to 18.0 kg/m^2

- Male, postmenopausal female or surgically sterile female

- If a female of reproductive potential, agrees to remain abstinent or to use (or have
their partner use) 2 acceptable combinations of birth control while participating in
the trial and for 14 days after the last use of study drug

Exclusion Criteria:

- History of type 1 diabetes mellitus or a history of ketoacidosis

- History of other specific types of diabetes (e.g., genetic syndromes, secondary
pancreatic diabetes, diabetes due to endocrine disorders, drug- or chemical-induced,
and post-organ transplant)

- A known hypersensitivity or intolerance to any sodium-glucose co-transporter 2
(SGLT2) or DPP-4 inhibitor

- On a weight-loss program or weight-loss medication or other medication associated
with weight changes and is not weight stable

- Has undergone bariatric surgery within the past 12 months or >12 months and is not
weight stable

- Has been treated with insulin (except for short-term use [<= 7 days]), injectable
antihyperglycemic agents (AHAs) (e.g., pramlintide, exenatide, liraglutide),
pioglitazone or rosiglitazone, other sodium-glucose co-transporter 2 (SGLT2)
inhibitors, alpha glucosidase inhibitors or meglitinides, bromocriptine (Cycloset™),
colesevelam (Welchol™), or any other nonapproved AHAs within 12 weeks of study
participation

- Has active, obstructive uropathy or indwelling urinary catheter

- 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 history of malignancy ≤5 years prior to study participation, except for adequately
treated basal or squamous cell skin cancer or in situ cervical cancer

- Known history of Human Immunodeficiency Virus (HIV)

- Has blood dyscrasias or any disorders causing hemolysis or unstable red blood cells
or any other clinically significant hematological disorder (such as aplastic anemia,
myeloproliferative or myelodysplastic syndromes, thrombocytopenia)

- A medical history of active liver disease (other than nonalcoholic hepatic
steatosis), including chronic active hepatitis B or C, primary biliary cirrhosis, or
active symptomatic gallbladder disease

- Has any clinically significant malabsorption condition

- If taking thyroid replacement therapy, has not been on a stable dose for at least 6
weeks prior to study participation

- Has been previously randomized in a study with ertugliflozin

- Has participated in other studies involving an investigational drug within 30 days
prior or during study participation

- Has undergone a surgical procedure within 6 weeks prior to or planned major surgery
during study participation

- Has a positive urine pregnancy test

- Is pregnant or breast-feeding, or is planning to conceive during the trial, including
14 days following the last dose of study medication

- Planning to undergo hormonal therapy in preparation to donate eggs during the trial,
including 14 days following the last dose of study medication

- Excessive consumption of alcoholic beverages or binge drinking

- Has donated blood or blood products within 6 weeks of study participation or plans to
donate blood or blood products at any time during the trial
GenderBoth
Ages18 Years
Accepts Healthy VolunteersNo
ContactsContact: Toll Free Toll Free Number
1-888-577-8839
Location CountriesUnited States

Administrative Information[ + expand ][ + ]

NCT Number NCT02036515
Other Study ID Numbers8835-006
Has Data Monitoring CommitteeYes
Information Provided ByMerck Sharp & Dohme Corp.
Study SponsorMerck Sharp & Dohme Corp.
CollaboratorsPfizer
Investigators Study Director: Medical Director Merck Sharp & Dohme Corp.
Verification DateApril 2014

Locations[ + expand ][ + ]

Call for Information (Investigational Site 0030)
Lincoln, California, United States, 95648
Recruiting