| 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 | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10045242 |
| E.1.2 | Term | Type II diabetes mellitus |
|
| 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 |
| To assess the effect of treatment with a range of doses of MK-0893 compared to placebo on fasting plasma glucose after 12 weeks. |
|
| E.2.2 | Secondary objectives of the trial |
| To assess the safety and tolerability of MK-0893 |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
a. Patient has T2DM.
b. Patient is ≥21 and ≤70 years of age on day of signing the informed consent form.
c. Patient is either
• Not on oral antihyperglycemic medications for at least 10 weeks, with an HbA1c of ≥7.0% and ≤11.0%, OR
• On a single oral antihyperglycemic medication (but not on a PPAR-γ agonist), with an HbA1c of ≥6.5% and ≤10.0%, OR
• On a low-dose combination oral antihyperglycemic medication at a dose less than or equal to 50% of the maximum recommended dose of both components, with an HbA1c of ≥6.5% and ≤10.0%.
d. Patient is a male, or a female who is unlikely to conceive, as indicated by at least one “yes” answer to the following questions:
1) Patient is a male.
2) Patient is a surgically sterilized female.
3) Patient is a postmenopausal female ≥45 years of age with >2 years since last menses.
4) Patient is a non-sterilized, premenopausal female and agrees to: (1) use 2 adequate methods of contraception to prevent pregnancy (2 barrier methods) or abstain from heterosexual activity throughout the study starting with Visit 1/ Screening and for 28 days after the last dose of study medication.
Note: Acceptable methods of birth control are: intrauterine device (IUD), diaphragm with spermicide, contraceptive sponge, condom, or vasectomy. See Appendix 6.13 for details.
e. Patient understands the study procedures, alternative treatments available, and risks involved with the study, and voluntarily agrees to participate by giving informed written consent.
At Visit 3/Week -2
f. Patient has a HbA1c of ≥7.0% and ≤11.0%.
At Visit 4/Day -1/Randomization
g. Patient has ≥ 85% compliance with placebo treatment during the single-blind run-in as measured by site-performed tablet count.
|
|
| E.4 | Principal exclusion criteria |
a. 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).
b. Patient has symptomatic hyperglycemia requiring immediate initiation or addition of antihyperglycemic therapy.
c. Patient has been treated with a PPAR-γ agonist within the past 3 months.
d. Patient has been treated with insulin within the past 2 months.
e. Patient has been treated with a GLP-1 mimetic or agonist within the past 2 months.
f. Patient has a history of hypersensitivity or contraindication to metformin.
g. Patient is on a weight loss program and is not in the maintenance phase, or patient has been treated with a weight loss medication within 8 weeks of Visit 1.
h. Patient has received treatment with an investigational drug within the prior 3 months or is participating in another clinical trial.
i. Patient is on or likely to require treatment with immunosuppressive/ immunomodulating agents or patient is on or likely to require treatment of ≥14 consecutive days or repeated courses of pharmacologic doses of corticosteroids.
j. Patient has undergone surgery within 30 days prior to Visit 1 or has planned major surgery.
k. Patient has new or worsening signs or symptoms of coronary heart disease or congestive heart failure within the past 3 months, or has any of the following disorders within the past 6 months:
• acute coronary syndrome
• coronary artery intervention
l. Patient has had a stroke or TIA
m. Patient has NYHA Class I - IV cardiac status
n. Patient has a systolic blood pressure of >150 mm Hg or diastolic blood pressure of >85 mm Hg.
o. Patient has severe peripheral vascular disease, active liver disease, or active nephropathy
p. Patient is HIV positive (as assessed by medical history).
q. Patient has a clinically significant hematological disorder (e.g., aplastic anemia, myeloproliferative or myelodysplastic syndromes, thrombocytopenia).
r. Patient is under treatment for hyperthyroidism.
s. Patient has a history of malignancy.
Exception: (1) patients with adequately treated non-melanomatous skin carcinoma or carcinoma in situ of the cervix may participate; (2) patients with other malignancies which have been successfully treated ≥5 years prior to screening, where in the judgment of both the investigator and treating physician, appropriate follow-up has revealed no evidence of recurrence from the time of treatment through the time of screening; and (3) patients who, in the joint opinion of the Merck medical monitor and investigator, are highly unlikely to sustain a recurrence during the duration of the study. However, patients with a history of leukemia, lymphoma, malignant melanoma, myeloproliferative disease or renal cell carcinoma are ineligible for the study regardless of the time since treatment, and in such cases, no exceptions will apply.
t. Patient is, at the time of signing informed consent, a user of recreational or illicit drugs or has had a recent history (within the last year) of drug or alcohol abuse or dependence.
u. Patient does not agree to abstain from alcohol for 48 hours prior to each clinic visit.
v. Patient has donated blood products or has had phlebotomy of >300 mL within 8 weeks of signing informed consent, or intends to donate blood products or receive blood products within the projected duration of the study.
w. Patient is pregnant, has a positive urine pregnancy test at Visit 1/Screening, is expecting to conceive within the projected duration of the study (up to Week 15), is breast-feeding, or is expecting to donate eggs within the duration of the study.
x. 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.
y. Patient is unlikely to adhere to the study procedures, keep the appointments, or is planning to relocate during the study.
z. Patient has an exclusionary laboratory value as listed below:
• Creatine: male: ≥1.4 mg/dL (123.8 µmol/L)
o Female: ≥1.3 mg/dL (114.9 µmol/L)
• Estimated Creatinine Clearance: <60 mL/min
• ALT: >1 ½ times ULN
• AST: >1 ½ times ULN
• Total Bilirubin: > ULN
• TSH: Outside Normal Range
• TG: >500 mg/dL (5.7 mmol/L)
• Hemoglobin: Below Normal Range
aa. Patient has a clinically significant ECG abnormality which, in the opinion of the investigator, exposes the patient to risk by enrolling in the study or which indicates that the patient meets Visit 1 exclusion criterion “k”.
bb. Patient has a QTc interval >480 ms.
cc. Patient has a FPG consistently (i.e., measurement repeated and confirmed within 7 days) >270 mg/dL (15.0 mmol/L).
dd. Patient has symptomatic hyperglycemia requiring immediate initiation of antihyperglycemic therapy.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| fasting plasma glucose, HbA1c, safety |
|
| 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 | Yes |
| 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 | Yes |
| 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) | 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) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | Information not present in EudraCT |
| 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) | 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 | 4 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 27 |
| 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 | 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
|
| End of trial is Visit 11/Week 15 |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | |
| 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 months | 6 |
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