E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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 |
(1) After 30 weeks, to assess the effect of the addition of sitagliptin compared with glimepiride on HbA1c. Hypothesis: After 30 weeks of treatment, the mean change from baseline in HbA1c in patients treated with sitagliptin is non-inferior compared with that in patients treated with glimepiride. Note: The criteria for determining non-inferiority can be found in the Data Analysis Summary section. (2) To assess the safety and the tolerability of sitagliptin compared with glimepiride. Hypothesis: Sitagliptin is well tolerated. |
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E.2.2 | Secondary objectives of the trial |
After 30 weeks, to assess the effect of the addition of sitagliptin compared with glimepiride on: (1) The incidence of hypoglycemic events Hypothesis: The addition of treatment with sitagliptin compared with glimepiride leads to a lower incidence of hypoglycemic events. (2) Body weight Hypothesis: The addition of treatment with sitagliptin compared with glimepiride leads to less gain in body weight from baseline. (3) Fasting plasma glucose (FPG). (4) Proportion of patients achieving at goal HbA1c (<6.5%, <7.0%). |
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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. 2. Patient is 18 years of age on day of signing informed consent. 3. Patient is on a stable dose and is expected to be able to remain on stable dose of metformin (at a dose of at least 1500 mg per day, for at least 12 weeks) with inadequate glycemic control, i.e., HbA1c &#8805; 6.5% and &#8804; 9.0%. 4. Patient understands the study procedures, alternative treatments available, and risks involved with the study and voluntarily agrees to participate by giving written informed consent. 5. Patient is not pregnant or breast-feeding and does not plan to become pregnant for the duration of the study and poststudy follow-up period. 6. Patient is unlikely to conceive, as indicated by at least one es following questions: a. Patient is a male. b. Patient is a surgically sterilized female. c. Patient is a postmenopausal female 45 years of age with >2 years since last menses d. Patient is a non-sterilized premenopausal female and agrees to abstain from heterosexual activity or to use an adequate method of contraception to prevent pregnancy. Note: Acceptable methods of birth control are: hormonal contraceptive, intrauterine device (IUD), diaphragm with spermacide, contraceptive sponge, condom, or vasectomy. At Visit 3 7. Patient has 85% compliance (as measured by tablet count) with single-blind placebo tablets during run-in. 0431, Protocol 803-01 Issue Date: 20-Dec-2007 17. |
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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 a history of ketoacidosis. - OR - Patient is assessed by the investigator as possibly having type 1 diabetes confirmed with a C-peptide <0.7 ng/mL (<0.23 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 required insulin within the prior 12 weeks. Patients Requiring Specific Treatments 3. Patient has been on an investigational or approved DPP-4 inhibitor agent, a sulfonylurea agent, a meglitinide agent, biguanides other than metformin, &#945;-glucosidase inhibitors, GLP-1 analogues (e.g., exenatide), PPAR&#947; agents or insulin, within the prior 12 weeks. 4. Patient has a hypersensitivity or contraindication to any sulfonylurea (e.g., glimepiride) medications. Note: Hypoglycemia is not considered a hypersensitivity to a sulfonylurea medication. 5. Patient is on a weight loss program and is not in the maintenance phase. 6. Patient started on a weight loss medication (e.g., orlistat, sibutramine, or rimonabant) within the prior 8 weeks. 7. Patient is on or likely to require treatment with &#8805;14 consecutive days or repeated courses of pharmacologic doses of corticosteroids. Note: inhaled, nasal, and topical corticosteroids are permitted. 8. Patient is on or likely to require an immunosuppressive/immunomodulating agent (e.g., cyclosporin, methotrexate, etanercept). 9. Patient has undergone surgery requiring general anesthesia within the prior 30 days or patient has planned surgery. Note: Patients with planned minor surgery may be enrolled upon approval by the Merck medical monitor. 10. Patient has received treatment with an investigational drug within the prior 8 weeks. |
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E.5 End points |
E.5.1 | Primary end point(s) |
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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 | Yes |
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 | No |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 50 |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |