| 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 metformin therapy at a dose of at least 1500 mg/day: (1) After 52 weeks, to assess the effect of the addition of MK-0431 compared with glipizide on HbA1C; (2) To assess the safety and the tolerability of MK-0431 compared with glipizide. |
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| E.2.2 | Secondary objectives of the trial |
Secondary objectives : After 52 and 104 weeks, to assess the effect of the addition of MK-0431 compared with glipizide on: (1) fasting plasma glucose (FPG); (2) Incidence of hypoglycemic events; (3) body weight; (4) indices of insulin secretion derived from the C-peptide, insulin, and glucose profile after a meal challenge, in a subset of patients undergoing a meal tolerance test. Over 104 weeks, to assess the effect of the addition of treatment of MK-0431 compared to glipizide on: (5) HbA1C; and (6) the durability of glycemic efficacy.
Exploratory objectives: After 12 and 24 weeks, to assess the effect of the addition of MK-0431 compared with glipizide on: Changes in appetite.
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| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria |
(letters used match those used in protocol)
a. Patient has type 2 diabetes mellitus (T2DM).
b. Patient is ≥18 and ≤78 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:
Patient is currently on monotherapy with metformin at a dose of ≥1500 mg/day and has a Screening Visit/Visit 1 HbA1C ≥6.5% and ≤10%.OR
Patient is in 1 of the following 4 categories and based upon review of the patient’s current diet, medical regimen, and Visit 1/Screening Visit HbA1C, patient is considered by the investigator to be likely to meet Visit 3 inclusion criteria of HbA1C ≥6.5% and ≤10% after a dose stable period on metformin monotherapy (at a dose of at least 1500 mg/day).
1) Patient is currently on monotherapy with metformin at a dose of ≥1500 mg/day and has a Visit 1/Screening Visit HbA1C >10%. (Note: Attempts to maximize the patient’s metformin dose and/or further adjust their diet regimen should be considered by the investigator when assessing the patient’s likelihood of meeting the Visit 3 HbA1C inclusion criteria.)
2) Patient is currently on monotherapy with metformin at a dose of <1500 mg/day or on monotherapy with another oral antihyperglycemic agent and has a Visit 1/Screening Visit HbA1C ≥6.5%.
3) Patient is currently on metformin in combination with another oral antihyperglycemic agent and has a Visit 1/Screening Visit HbA1C ≥5.5% and ≤10%.
4) Patient is not on an antihyperglycemic medication and has a Visit 1/Screening Visit HbA1C >7.5%.
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| E.4 | Principal exclusion criteria |
(letters used match those used in protocol)
a. Patient has a history of type 1 diabetes mellitus or a history of ketoacidosis.
b. Patient required insulin within the prior 8 weeks.
c. Hypersensitivity or contraindication to any sulfonylurea (e.g. glipizide) and biguanides (e.g. metformin) medications. (Note: Hypoglycemia is not considered a hypersensitivity to a sulfonylurea medication).
j. Patient has a serum 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.
k. 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.
l. Patient has >0.5 mg albumin per mg creatinine in the urine as measured by the central laboratory. Note: only patients whose urine dipstick at the site reveals greater than 1+ protein should have urine albumin and urine creatinine measured.
m. Patient has a triglyceride (TG) >600 mg/dL (6.78 mmol/L) and is considered by the investigator unlikely to respond to diet/exercise and/or medication so as to avoid exceeding TG >600 mg/dL (6.78 mmol/L) at Visit 3/Week -2.
n. Patient has a TSH <0.100 mU/mL or >15 mU/mL.
p. Patient has cirrhosis, active liver disease (other than fatty liver), or symptomatic gallbladder disease.
q. Patient has chronic myopathy, or a progressive neurological or neuromuscular disorder (e.g., multiple sclerosis or polymyositis).
r. 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
s. Patient has new or worsening signs or symptoms of coronary heart disease within the past 3 months.
t. Patient has severe peripheral vascular disease (e.g., manifested by claudication with minimal activity, a non-healing ischemic ulcer, or disease which is likely to require intervention such as with bypass or angioplasty).
u. Patient has congestive heart failure requiring pharmacological therapy or NYHA Class III or IV congestive heart failure (refer to Appendix 2).
v. Patient is HIV positive (as assessed by medical history).
w. Patient has a clinically important hematological disorder (e.g., aplastic anemia, myeloproliferative or myelodysplastic syndromes, thrombocytopenia).
x. Patient has a history of malignancy.
y. Patient has a BMI <20 kg/m2 or >43 kg/m2.
z. Patient is not willing to comply with restrictions on alcohol (regular intake of ≤3 drinks per day and no more than 14 drinks per week).
hh. Patient has viral hepatitis (Hepatitis B or C) as determined by the presence of any of the following:
• Hepatitis B Core Antibody (IgM)
• Surface Antigen for Hepatitis B
• Antibodies to Hepatitis C |
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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 | 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 | 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) | 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 | No |
| 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 |
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| 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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| 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 | 5 |
| 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 | 5 |
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