| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| 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 |
|
| 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 |
| In patients with type 2 diabetes mellitus who have inadequate glycemic control on glimepiride at a dose of ≥4 mg/day, alone or in combination with metformin at a dose of ≥ 1500 mg/day: (1) After 24 weeks, to assess the effect of the addition of treatment with MK-0431 compared with the addition of placebo on HbA1c; (2) To assess the safety and the tolerability of MK-0431. |
|
| E.2.2 | Secondary objectives of the trial |
| (1) In patients with type 2 diabetes mellitus who have inadequate glycemic control on glimepiride in monotherapy at a dose of ≥4 mg/day, to assess the effect of the addition of treatment with MK-0431 compared with the addition of placebo after 24 weeks on glycemic control;(2) In patients with type 2 diabetes mellitus who have inadequate glycemic control on glimepiride at a dose of ≥4 mg/day in combination with metformin at a dose of ≥1500 mg/day; (3) In patients with type 2 diabetes mellitus who have inadequate glycemic control on glimepiride at a dose of ≥4 mg/day, alone or in combination with metformin at a dose of ≥1500 mg/day; (4) After 54 weeks, to assess the effect of the addition of treatment with MK-0431 in patients with type 2 diabetes mellitus who have inadequate glycemic control on glimepiride at a dose of ≥4 mg/day, alone or in combination with metformin at a dose of ≥1500 mg/day |
|
| 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.
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.
f. Patient meets one of the following criteria as indicated by a “yes” answer to one of the following:
1) Patient is currently on glimepiride (at a dose of at least 4 mg/day) alone or in combination with metformin (at a dose of at least 1500 mg/day) for ≥10 weeks and has a Screening Visit/Visit 1 HbA1c ≥7.5% and ≤10.5%.
OR
Patient is in 1 of the following categories (2-5) and based upon review of the patient’s current diet, medical regimen, and Screening Visit/Visit 1
HbA1c, patient is considered by the investigator to be likely to meet Visit 3 inclusion criterion of HbA1c ≥7.5% and ≤10.5% after a dose stable period on glimepiride monotherapy (at a dose of at least 4 mg/day) alone or in combination with metformin (at a dose of at least 1500 mg/day).
2) Patient is not on any antihyperglycemic medication and has a Screening Visit/Visit 1 HbA1c ≥ 9%.
3) Patient is currently on glimepiride at a dose of less than 4 mg/day or is on any other sulfonylurea agent in monotherapy and has a Screening Visit/Visit 1 HbA1c ≥7.5%.
4) Patient is currently on monotherapy with any other oral antihyperglycemic agent (e.g., metformin, an alpha-glucosidase inhibitor, or a PPARĪ³ agent [rosiglitazone or pioglitazone]) and has a Screening Visit/Visit 1 HbA1c ≥7.5 %.
5) Patient is currently on oral combination antihyperglycemic agent therapy and has a Screening Visit/Visit 1 HbA1c ≥ 6.5 and ≤ 10.5%.
|
|
| E.4 | Principal exclusion criteria |
a. Patient has a history of type 1 diabetes mellitus or a history of ketoacidosis, or required insulin within the prior 8 weeks.
f. Patient has a hypersensitivity to the use of glimepiride, sulfonylurea agents, or pioglitazone or according to the label of the country of the investigational site, has any contraindication to the use of these medications or that limits the allowed doses to below those required by the protocol.
g. Patient has a hypersensitivity to metformin and will be on metformin during the study.
h. Patient has an ALT or AST >2.0-fold the Upper Limit of Normal (ULN). Note: Patients whose serum ALT or AST exceeds this limit may be retested one time if the investigator does not believe the value reflects the patient’s clinical status.
i. Patient is on and will be on metformin during the study and serum creatinine ≥1.4 mg/dL (123.8 µmol/L) in men and ≥1.3 mg/dL (114.9 µmol/L) in women or estimated creatinine clearance (using Cockcroft-Gault formula) <60 mL/min. Note: Patients whose serum creatinine exceeds this limit may be retested one time if the investigator does not believe the value reflects the patient’s clinical status.
OR
Patient is not on or will not be on metformin during the study and 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 >2.0 mg/dL (176.8 µmol/L).
2) Patient is a male >65 years of age and serum creatinine >1.7 mg/dL (150.3 µmol/L).
3) Patient is a female ≤65 years of age and serum creatinine >1.7 mg/dL (150.3 µmol/L).
4) Patient is a female >65 years of age and serum creatinine >1.4 mg/dL (123.8 µmol/L).
5) Creatinine clearance is <45 mL/min.
Note: Patients whose serum creatinine exceeds this limit may be retested one time if the investigator does not believe the value reflects the patient’s clinical status.
j. Patient has new or worsening signs or symptoms of coronary heart disease within the past 3 months or 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.
k. Patient has congestive heart failure requiring pharmacological therapy or NYHA Class II, III or IV congestive heart failure.
l. Patient is HIV positive (as assessed by medical history).
m. Patient has a clinically important hematological disorder (e.g., aplastic anemia, myeloproliferative or myelodysplastic syndromes, thrombocytopenia).
n. Patient has cirrhosis or active liver disease (other than fatty liver) or active nephropathy (i.e., nephrotic syndrome or glomerulonephritis) or chronic progressive neuromuscular disorder (e.g., multiple sclerosis or polymyositis) or 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.
o. Patient has a history of malignancy.
p. Patient has a history of alcohol or drug abuse within the past 3 years.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
|
| 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 | 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) | Information not present in EudraCT |
| E.7.1.1 | First administration to humans | Information not present in EudraCT |
| E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
| E.7.1.3 | Other | Information not present in EudraCT |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Information not present in EudraCT |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
| 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) | No |
| 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.8.5 | The trial involves multiple Member States | Yes |
| 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 |
|
| 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
|
| end of trial is approximately 2 weeks after the last patient’s visit. A 2 week telephone contact is conducted to inquire about serious adverse events. |
|
| 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 | 10 |
| 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 | 10 |
Print
