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 | 7.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10045242 |
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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 |
Main objective : In patients with type 2 diabetes mellitus with inadequate glycemic control on diet and exercise: (1) After 24 weeks, to assess the effect of treatment with MK-0431 compared with placebo on HbA1C. (2) To assess the safety and tolerability of MK-0431. |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives : After 24 weeks, to assess the effect of treatment with MK-0431 compared with placebo on: (1) fasting plasma glucose (FPG) and fructosamine; and (2) the plasma glucose profile after a standard meal challenge. Over 104 weeks, to assess the effect of treatment with MK-0431 on: (3) HbA1C and FPG; (4) the durability of glycemic efficacy; (5) In a subset of patients undergoing more extensive blood sampling after a standard meal challenge: indices of insulin secretion derived from the C-peptide, insulin, and glucose profile. (6) In a subset of patients undergoing intravenous glucose tolerance testing: indices of insulin secretion derived from the C-peptide, insulin, and glucose profile. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
a. Patient has type 2 diabetes mellitus (T2DM). b. Patient is 18 and 75 years of age. c. Patient has an understanding of the study procedures and agrees to participate in the study by giving written informed consent. d. 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. e. Patient is a male, or a female who is highly unlikely to conceive f. HbA1c 7% and 10% measured at, or within 2 weeks prior to, Visit 3. |
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E.4 | Principal exclusion criteria |
a. Patient has a history of type 1 diabetes mellitus or a history of ketoacidosis b. Patient has an ALT or AST >2.0-fold the Upper Limit of Normal (ULN) c. Patient’s renal function is reflected below as indicated by a “yes” answer to one of the following: 1) Patient is a male ≤ 65 years of age and serum creatinine >1.8 mg/dL (159.1 µmol/L). 2) Patient is a male > 65 years of age and serum creatinine >1.6 mg/dL (141.4 µmol/L). 3) Patient is a female ≤ 65 years of age and serum creatinine >1.6 mg/dL (141.4 µmol/L). 4) Patient is a female > 65 years of age and serum creatinine >1.3 mg/dL (114.9 µmol/L). 5) Creatinine clearance is <50 mL/min. d. Patient has any of the following disorders within the past 6 months: • Acute coronary syndrome (e.g., MI or unstable angina) • Coronary artery intervention (e.g., CABG or PTCA) • Stroke or transient ischemic neurological disorder • Patient has new or worsening signs or symptoms of coronary heart disease within the past 3 months. e. Patient has new or worsening signs or symptoms of coronary heart disease within the past 3 months. f. Patient has a BMI <20 kg/m2 or >43 kg/m2 g. Patient has a positive urine pregnancy test h. Patient has any other condition or therapy which, in the opinion of the investigator or Merck medical monitor, might pose a risk to the patient or make participation not in the patient’s best interest. i. Patient has poor mental function or any other reason to expect that the patient may have difficulty in complying with the requirements of the study. a. Patient has a history of type 1 diabetes mellitus or a history of ketoacidosis b. Patient has an ALT or AST >2.0-fold the Upper Limit of Normal (ULN) c. Patient’s renal function is reflected below as indicated by a “yes” answer to one of the following: 1) Patient is a male ≤ 65 years of age and serum creatinine >1.8 mg/dL (159.1 µmol/L). 2) Patient is a male > 65 years of age and serum creatinine >1.6 mg/dL (141.4 µmol/L). 3) Patient is a female ≤ 65 years of age and serum creatinine >1.6 mg/dL (141.4 µmol/L). 4) Patient is a female > 65 years of age and serum creatinine >1.3 mg/dL (114.9 µmol/L). 5) Creatinine clearance is <50 mL/min. d. Patient has any of the following disorders within the past 6 months: • Acute coronary syndrome (e.g., MI or unstable angina) • Coronary artery intervention (e.g., CABG or PTCA) • Stroke or transient ischemic neurological disorder • Patient has new or worsening signs or symptoms of coronary heart disease within the past 3 months. e. Patient has new or worsening signs or symptoms of coronary heart disease within the past 3 months. f. Patient has a BMI <20 kg/m2 or >43 kg/m2 g. Patient has a positive urine pregnancy test h. Patient has any other condition or therapy which, in the opinion of the investigator or Merck medical monitor, might pose a risk to the patient or make participation not in the patient’s best interest. i. Patient has poor mental function or any other reason to expect that the patient may have difficulty in complying with the requirements of the study.
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E.5 End points |
E.5.1 | Primary end point(s) |
a. Patient has a history of type 1 diabetes mellitus or a history of ketoacidosis b. Patient has an ALT or AST >2.0-fold the Upper Limit of Normal (ULN) c. Patient’s renal function is reflected below as indicated by a “yes” answer to one of the following: 1) Patient is a male ≤ 65 years of age and serum creatinine >1.8 mg/dL (159.1 µmol/L). 2) Patient is a male > 65 years of age and serum creatinine >1.6 mg/dL (141.4 µmol/L). 3) Patient is a female ≤ 65 years of age and serum creatinine >1.6 mg/dL (141.4 µmol/L). 4) Patient is a female > 65 years of age and serum creatinine >1.3 mg/dL (114.9 µmol/L). 5) Creatinine clearance is <50 mL/min. d. Patient has any of the following disorders within the past 6 months: • Acute coronary syndrome (e.g., MI or unstable angina) • Coronary artery intervention (e.g., CABG or PTCA) • Stroke or transient ischemic neurological disorder • Patient has new or worsening signs or symptoms of coronary heart disease within the past 3 months. e. Patient has new or worsening signs or symptoms of coronary heart disease within the past 3 months. f. Patient has a BMI <20 kg/m2 or >43 kg/m2 g. Patient has a positive urine pregnancy test h. Patient has any other condition or therapy which, in the opinion of the investigator or Merck medical monitor, might pose a risk to the patient or make participation not in the patient’s best interest. i. Patient has poor mental function or any other reason to expect that the patient may have difficulty in complying with the requirements of the study.
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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 | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Information not present in EudraCT |
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 | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
E.8.5 | The trial involves multiple Member States | Information not present in EudraCT |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Information not present in EudraCT |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
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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Definition of the end of trial and justification, in the case where it is not the last visit of the last subject undergoing the trial : The last visit of the trial is at Visit 18/Week 104. Randomized patients who discontinue due to a clinical or laboratory adverse experience will have a discontinuation visit as soon as possible. |
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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 | 3 |
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 | 3 |