E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10049746 |
E.1.2 | Term | Insulin-requiring type II diabetes mellitus |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Objective: After 24 weeks, to assess the effect of the co-administration of sitagliptin and pioglitazone compared with pioglitazone monotherapy and sitagliptin monotherapy on HbA1c. Hypothesis: After 24 weeks, the co-administration of sitagliptin and pioglitazone provides greater reduction in HbA1c compared with pioglitazone monotherapy and sitagliptin monotherapy. Objective: After 24 and 54 weeks, to assess the safety and tolerability of the coadministration of sitagliptin and pioglitazone compared with pioglitazone monotherapy and sitagliptin monotherapy. Hypothesis: After 24 and 54 weeks, the co-administration of sitagliptin and pioglitazone is well tolerated. |
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E.2.2 | Secondary objectives of the trial |
Objective: After 24 weeks, to assess the effect of the co-administration of sitagliptin and pioglitazone compared with pioglitazone monotherapy and sitagliptin monotherapy on fasting plasma glucose (FPG). Hypothesis: After 24 weeks, the co-administration of sitagliptin and pioglitazone provides greater reduction in FPG compared with pioglitazone monotherapy and sitagliptin monotherapy. Objective: After 24 weeks, to assess the effect of the co-administration of sitagliptin and pioglitazone compared with pioglitazone monotherapy and sitagliptin monotherapy on the 2-hour post meal glucose (PMG) following a standard meal challenge. Hypothesis: After 24 weeks, the co-administration of sitagliptin and pioglitazone provides greater reduction in 2-hour PMG following a standard meal challenge compared with pioglitazone monotherapy and sitagliptin monotherapy. Objective: After 54 weeks, to assess the effect of the co-administration of sitagliptin and pioglitazone compared with piogl |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
At Visit 1 1. Patient has T2DM and is ≥18 and ≤ 78 years of age on day of signing informed consent. 2. Patient is highly unlikely to conceive, as indicated by at least one "yes" answer to the following questions: a. Patient is a male. b. Patient is a surgically sterilized female. Patient is not pregnant or breast feeding and is not intending to become pregnant or donate eggs within the projected duration of the study and post-study follow-up period. d. Patient is a postmenopausal female ≥45 years of age with >2 years since last menses. e. Patient is a non-sterilized, premenopausal female and agrees to use adequate contraception. 3. Patient understands the study procedures, alternative treatments available, and risks involved with the study and voluntarily agrees to participate by giving informed written consent. Glycemic Entry Criteria 4. Patient is in one of the following 3 categories. a. Patient is naïve to all AHA therapies (off all AHA therapies for at least 3 months and not on an AHA for more than 4 weeks cumulatively in the last 3 years prior to Visit 1) and has an HbA1c ≥7.5% and ≤11% on diet and exercise alone. Or
Patient is in one of the following 2 non-naïve categories AND based upon review of the patients current diet, medical regimen, and Visit 1/Screening HbA1c, patient is considered likely to meet Visit 3 inclusion criterion of HbA1c ≥7.5% and ≤11.0%: b. Patient is currently not on an AHA (i.e., off therapy for ≥8 weeks) and has a Visit 1/Screening Visit HbA1c ≥7.5% and ≤11.0% on diet and exercise alone. c. Patient is currently on either metformin monotherapy or sulfonylurea monotherapy and has a Visit 1/Screening Visit HbA1c ≥7% and ≤10.5%. At Visit 3 5. HbA1c ≥7.5% and ≤11% at Visit 3 or measured within 2 weeks prior to Visit 3. At Visit 4 6. Patient has ≥85% compliance with placebo treatment during the single-blind run-in, as measured by site performed tablet count (e.g., for a patient with a 14-day interval between Visit 3 and Visit 4, at least 12 tablets taken per bottle). b. Patient is a surgically sterilized female. |
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E.4 | Principal exclusion criteria |
At Visit 1 Glucose Metabolism and Therapy Criteria 1. Patient has a history of type 1 diabetes mellitus or history of ketoacidosis or patient has a C-peptide ≤0.8 ng/mL (0.26 nmol/L). Note: Only patients assessed by the investigator as possibly having type 1 diabetes should have C-peptide measured at Visit 1. 2. Patient has previously been treated with insulin, a thiazolidinedione (rosiglitazone or pioglitazone), any DPP-4 inhibitor (sitagliptin, vildagliptin, saxagliptin or alogliptin), exenatide, or has previously been in a clinical study with any DPP-4 inhibitor or incretin mimetic. NOTE: A patient who has received only minimal therapy with an excluded AHA (e.g., <7 tablets of an oral AHA or brief insulin therapy during an acute illness) may be considered for study participation after approval from the Merck Clinical Monitor. Patients Requiring Specific Treatments 3. Patient is on a weight loss program and is not in the maintenance phase or has started a weight loss medication (e.g. orlistat, phentermine, sibutramine or rimonabant) within the prior 8 weeks. 4. Patient is on or is likely to require treatment with ≥14 consecutive days or repeated courses of pharmacologic doses of corticosteroids. Note: Inhaled, nasal, or topical corticosteroids are permitted. 5. Patient has received treatment with an investigational drug within 12 weeks prior to Visit 1/Screening Visit or is currently participating in any other clinical study (drug or non-drug studies). 6. Patient has undergone surgery within the prior 30 days or has major surgery planned during the study. 7. Patient has any contraindication to sitagliptin or pioglitazone based upon the label of the country of the investigational site. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Safety parameters and adverse experiences of special interest that are identified a priori (i.e., hypoglycemia, edema, and body weight) constitute "Tier 1" safety endpoints. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
- same IMP used at different dosage |
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E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 42 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 1 |