E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Type II Diabetes mellitus. |
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MedDRA Classification |
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 evaluate the efficacy of SYR-322 as compared with placebo on glycosylated hemoglobin (HbA1c) change from baseline. |
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E.2.2 | Secondary objectives of the trial |
To evaluate other measures of glycemic control after treatment with SYR-322 as compared with placebo, including fasting plasma glucose, incidence of marked hyperglycemia (fasting plasma glucose ≥200 mg/dL), and incidence of rescue To evaluate changes in pancreatic function after treatment with SYR-322 as compared with placebo, determined by changes in fasting proinsulin, insulin, C-peptide, and glucagon To evaluate changes in body weight following treatment with SYR-322 as compared with placebo To evaluate the safety of SYR-322 as compared with placebo by evaluating adverse events (AEs), clinical laboratory parameters, electrocardiogram (ECG) readings, physical examinations, and hypoglycemic events To evaluate plasma concentrations of SYR-322 using a sparse sampling approach To evaluate clinically meaningful levels of response in HbA1c after treatment with SYR-322 as compared with placebo |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
In order to be eligible for this study, each of the following criteria must be satisfied with a “YES” answer (unless not applicable): Males or females, 18 to 80 years of age, inclusive, with type 2 diabetes mellitus who are experiencing inadequate glycemic control and who are receiving no current antidiabetic therapy. Subjects will qualify if both of the following conditions apply: Subject has failed treatment with diet and exercise Subject has received <7 days of any antidiabetic therapy within the 3 months prior to Screening Diagnosis of type 2 diabetes must be based on current American Diabetes Association criteria: fasting plasma glucose ≥126 mg/dL, oral glucose tolerance test at 2-hour postload must be ≥200 mg/dL, or symptoms of diabetes plus casual plasma glucose ≥200 mg/dL Body mass index ≥23 kg/m2 and ≤45 kg/m2 Fasting C-peptide concentration ≥0.8 ng/mL. (If this screening criterion is not met, the subject still qualifies if C-peptide ≥1.5 ng/mL after a challenge test. See Appendix E.) HbA1c concentration between 7.0% and 10.0%, inclusive If regular use of other, nonexcluded medications, must be on a stable dose for at least the 4 weeks prior to Screening. However, PRN (as needed) use of prescription or over-the-counter medications is allowed at the discretion of the investigator. Systolic blood pressure ≤180 mm Hg and diastolic pressure ≤110 mm Hg Hemoglobin ≥12 g/dL for males and ≥10 g/dL for females Alanine aminotransferase ≤3 x upper limit of normal Serum creatinine ≤2.0 mg/dL Thyroid-stimulating hormone level ≤ the upper limit of the normal range and the subject is clinically euthyroid Neither pregnant (confirmed by laboratory testing in females of childbearing potential) nor lactating Female subjects of childbearing potential (ie, not surgically sterile and/or not postmenopausal) must be practicing adequate contraception. Methods of adequate contraception include the following: intrauterine device; double-barrier device such as a diaphragm or condom plus spermicide; or a hormonal contraceptive (including injectable, implantable, or oral). Adequate contraception must be practiced for the duration of participation in the study. Able and willing to monitor their own blood glucose concentrations with a home glucose monitor No major illness or debility that in the investigator’s opinion prohibits the subject from completing the study Able and willing to provide written informed consent Additional Inclusion Criteria for Randomization: In order to be eligible for randomization, each of the following additional criteria must be satisfied with a “YES” answer: HbA1c concentration between 7.0% and 10.0%, inclusive at the Week -1 visit. (If the subject does not qualify for randomization based on this criterion, the assessment may be repeated on a weekly basis, for a maximum of 4 additional weeks.) Have been at least 75% compliant with the single-blind placebo regimen during the run-in/stabilization period, as assessed by tablet count No use of oral or systemically injected glucocorticoids or use of weight-loss drugs is allowed within the 3 months prior to randomization. (Inhaled corticosteroids are allowed.) |
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E.4 | Principal exclusion criteria |
In order to be eligible for this study, each of the following criteria must be satisfied with a “NO” answer: • Urine albumin/creatinine ratio of >1000 µg/mg at Screening. If elevated, the subject may be rescreened within 1 week. History of cancer, other than squamous cell or basal cell carcinoma of the skin, that has not been in full remission for at least 5 years prior to Screening. (A history of treated CIN I or CIN II [cervical intraepithelial neoplasia] is allowed.) History of laser treatment for proliferative diabetic retinopathy within the 6 months prior to Screening History of treated diabetic gastric paresis New York Heart Association Class III or IV heart failure regardless of therapy. Currently treated subjects who are stable at Class I or II are candidates for the study (see Appendix F). History of coronary angioplasty, coronary stent placement, coronary bypass surgery, or myocardial infarction within the 6 months prior to Screening History of any hemoglobinopathy that may affect determination of HbA1c History of infection with hepatitis B, hepatitis C, or human immunodeficiency virus History of a psychiatric disorder that will affect the subject’s ability to participate in the study History of angioedema in association with use of angiotensin-converting enzyme inhibitors or angiotensin-II receptor inhibitors History of alcohol or substance abuse within the 2 years prior to Screening Receipt of any investigational drug within the 30 days prior to Screening or a history of receipt of an investigational antidiabetic drug within the 3 months prior to Screening Prior treatment in an investigational study of SYR-322 |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint will be changed from baseline in HbA1c at week 26 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
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 |
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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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Last visit of the last subject. |
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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 | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |