Type 2 Diabetes Mellitus MedDRA version: 14.0 Level: PT Classification code 10067585 Term: Type 2 diabetes mellitus System Organ Class: 10027433 - Metabolism and nutrition disorders
Conditions
Interventions
Trade Name: JANUVIA
Product Name: JANUVIA
Product Code: MK-0431
Pharmaceutical Form: Tablet
INN or Proposed INN: sitagliptin phosphate
Sponsors
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. (hereafter referred to as
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: At Visit 1/Screening Visit: 1. Patient has type 2 diabetes mellitus (T2DM). 2. Patient meets one of the following criteria: A. Patient was diagnosed with diabetes after age 40 years and insulin therapy was initiated at least 3 years after the diagnosis of diabetes, OR - B.Patient does not meet the criteria in (A) above (i.e., diagnosis 0.7 ng/mL. Note: Only patients who do not meet the criteria in (A) should have a C-peptide level measured. 3. Patient must be ?18 and ?80 years of age on the day of signing informed consent. 4. Patient is on a stable insulin regimen for ?10 weeks metformin (immediate-release or extended-release formulation) at ?1500 mg/day for ?10 weeks sulfonylurea for ?10 weeks, with one of the following insulins (at a dose of at least 15 U/day and a maximum dose of 150 U/day) and has a Visit 1/Screening Visit A1C ?7.5% and ?11.0% (for patients not on sulfonylurea) or A1C ?7.0% and ?10.0% (for patients on sulfonylurea): ? Pre-mixed insulin with at least 70% basal insulin (e.g., Novolog 70/30®, Novolin 70/30®, Humalog 75/25®, or Humulin 70/30®) once-daily or twice-daily. ? Intermediate-acting insulin (e.g., NPH/Isophane) once-daily or twicedaily. ? Long-acting insulin (e.g., Glargine [Lantus®] and Detemir [Levemir®]) once-daily or twice-daily. Note: A stable insulin regimen is defined as all daily doses within 10% (or within 2 units for patient taking ?20U/day) of the usual administered dose (e.g., if usual insulin dose is 50 U/day, then doses of 45-55 U/day would be considered stable). Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 400 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 200
Exclusion criteria
Exclusion criteria: At Visit 1/Screening Visit: 1. Patient has been treated with a DPP-4 inhibitor, a thiazolidinedione (TZD), or a GLP-1 mimetic or analogue, within the prior 12 weeks. 2. Patient is currently on treatment with daily use (one or more injections per day) of a pre-prandial short-acting or rapid-acting insulin (e.g., aspart, glulisine, lispro, regular insulin) alone or as part of a basal/bolus insulin regimen. Note: Patients using a pre-mixed insulin containing a short-acting insulin may participate. 3. Patient has symptomatic hyperglycemia that, in the investigator?s opinion, requires immediate initiation, adjustment, or addition of antihyperglycemic therapy. 4. Patient has a history of 2 or more episodes of hypoglycemia resulting in seizure, coma, or loss of consciousness, - or - patient has had recurrent (?3 times per week) episodes of hypoglycemia over the past 8 weeks. 5. Patient has a history of ketoacidosis. 6. Patient is, as assessed by the investigator, not appropriate for or does not agree to target a fasting glucose of 72-100 mg/dL [4.0-5.6 mmol/L]. 7. Patient has a history of intolerance or hypersensitivity to sitagliptin, insulin, or metformin (if patient on metformin at Visit 1) or any contraindication to sitagliptin, insulin, or metformin (if patient on metformin at Visit 1) based upon the label of the country of the investigational site. 8. Patient is pregnant or breast-feeding, or is expecting to conceive or donate eggs during the study, including 14 days following the last dose of study drug. 9. Patient has a medical history of active liver disease (other than non-alcoholic hepatic steatosis), including chronic active hepatitis B or C (assessed by medical history), primary biliary cirrhosis, or symptomatic gallbladder disease. 10. Patient has had new or worsening signs or symptoms of coronary heart disease or congestive heart failure within the past 3 months, or has any of the following disorders within the past 3 months: a. Acute coronary syndrome (e.g., MI or unstable angina) b. Coronary artery intervention (e.g., CABG or PTCA) c. Stroke or transient ischemic neurological disorder At Visit 4/Randomization: 11. Patient has a site FFSG of 270 mg/dL (15.0 mmol/L). Note: If the patient meets this exclusion criterion AND the investigator believes that the value is not consistent with the patient?s current Self-Monitoring Blood Glucose (SMBG) values and Visit 3/Week -2 FPG value, the patient should not be excluded at this time. This visit should be changed to an Unscheduled Visit and the patient should be rescheduled for Visit 4/Day 1 within 7 days. Additional single-blind placebo run-in medication should be dispensed if needed. If the patient meets this FFSG exclusion criterion at the rescheduled Visit 4/Day1, the patient MUST be excluded
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: After 24 weeks, to assess the effect of sitagliptin compared with placebo on the change in insulin dose in IU per day in patients with type 2 diabetes mellitus (T2DM) with inadequate glycemic control on insulin with or without metformin, who titrate insulin glargine (Treat-to-Target). To assess the safety and tolerability of sitagliptin.; Secondary Objective: In patients with T2DM with inadequate glycemic control on insulin with or without metformin, who titrate insulin glargine (Treat-to-Target): (1) After 24 weeks, to estimate the difference between sitagliptin and placebo on hemoglobin A1c . (2) After 24 weeks, to estimate the difference between sitagliptin and placebo on fasting plasma glucose. (3) After 24 weeks, to estimate the difference between sitagliptin and placebo on body weight. (4) After 24 weeks, to estimate the difference between sitagliptin and placebo in the proportion of patients who achieve the fasting glucose target of 72-100 mg/dL (4.0-5.6 mmol/L). (5) To estimate the difference between sitagliptin and placebo in the time to achieve the fasting glucose target of 72-100 mg/dL (4.0-5.6 mmol/L) for the first time. ;Primary end point(s): Change from baseline in daily insulin dose at Week 24.;Timepoint(s) of evaluation of this end point: Week 24 | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Week 24 (as defined in protocol); Secondary end point(s): LoEfficacy Endpoints: laboratory assessment of: A1C, FPG, and lipid panel endpoints and time when a patient meets the fasting glucose target. Safety endpoints: adverse events, additional hypoglycemia endpoints, percentages of patients meeting predefined limits of change (PDLC) in laboratory parameters (including blood chemistry and hematology), and change (or percent change) from baseline at Week 24 in laboratory parameters, body weight and vital signs. Serious adverse events (SAEs) consistent with vascular events (cardiovascular, cerebrovascular, and peripheral vascular events) and heart failure events, revascularization procedures, and all deaths, regardless of cause, will be subject to adjudication by an expert committee external to the SPONSOR. When an eligible event is identified, the SPONSOR will request copies of additional source documentation related to the event (e.g., hospital records) from the investigator. | — |
Countries
Australia, Belgium, Brazil, Canada, Denmark, France, Germany, Hungary, India, Ireland, Israel, Italy, Korea, Democratic People's Republic of, Lithuania, Mexico, New Zealand, Norway, Peru, Poland, Portugal, Puerto Rico, Russian Federation, South Africa, Spain, Turkey, United Kingdom, United States
Contacts
Public ContactThomas L. Seck
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. (hereafter referred to as
Outcome results
None listed