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.1.2 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 |
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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 |
To evaluate the efficacy of alogliptin as compared with glipizide on glycosylated hemoglobin (HbA1c) change from baseline at Week 52 in adults 65 years to 90 years of age with type 2 diabetes. |
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E.2.2 | Secondary objectives of the trial |
•To evaluate other measures of glycemic control after treatment with alogliptin as compared with glipizide, including fasting plasma (FPG) glucose and incidence of marked hyperglycemia (FPG ≥200 mg/dL [≥11.10 mmol/L]) and incidence of hyperglycemic rescue. •To evaluate changes in 2-hour postprandial glucose levels, changes in pancreatic function and changes in body weight after treatment with alogliptin compared with glipizide. •To evaluate inflammatory responses and serum lipids, specifically total cholesterol, high-density lipoprotein, low-density lipoprotein, and triglycerides. •To evaluate clinically meaningful levels of response in HbA1c after treatment with alogliptin as compared with glipizide. •To evaluate changes in Quality of Life (QOL) and Patient Reported Outcome (PRO)Measures. •To further evaluate the safety of alogliptin as compared with glipizide by evaluating AEs, vital signs, clinical laboratory parameters, ECG readings, vital signs, and physical examinations. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. The subject is male or female, between the ages of 65 and 90, inclusive, with a diagnosis of type 2 diabetes mellitus who has either: a) Failed diet and exercise therapy alone as demonstrated by inadequate glycemic control (defined as an HbA1c concentration between 6.5% and 9.0%, inclusive) while receiving no antidiabetic treatment (defined as less than 7 days of any antidiabetic treatment) within the three months prior to Screening (Study Schedule A). Subjects following Schedule A may be randomized immediately upon confirmation of eligibility. OR b) Failed treatment with oral monotherapy alone (may include treatment with two or more antidiabetic agents if for less than 7 days) as demonstrated by inadequate glycemic control (defined as an HbA1c concentration between 6.5% and 8.0%, inclusive) within the three months prior to Screening (Study Schedule B). Subjects following Schedule B will undergo a 4-week washout period including an assessment at the end of washout to re-confirm eligibility prior to randomization (see additional inclusion criteria). 2. Body mass index ≥23 kg/m2 and ≤45 kg/m2. 3. Subject is capable of understanding and complying with protocol requirements. 4. Subject or the subject’s legally acceptable representative signs a written, informed consent form prior to the initiation of any study procedures. 5. If regularly using other, non-excluded 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. 6. Neither pregnant (confirmed by laboratory testing in females of childbearing potential) nor lactating. 7. Female subjects of childbearing potential who is sexually active agrees to use adequate contraception (as defined in the informed consent form) from screening throughout the duration of the study. 8. Able and willing to monitor their own blood glucose concentrations with a home glucose monitor. 9. No major illness or debility that in the investigator’s opinion prohibits the subject fromcompleting the study. |
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E.4 | Principal exclusion criteria |
1. Systolic blood pressure ≥160 mm Hg and/or diastolic pressure ≥100 mm Hg. 2. Hemoglobin ≤12 g/dL (≤120 gm/L) for males or ≤10 g/dL (≤100 gm/L) for females. 3. Alanine aminotransferase ≥3 x upper limit of normal. 4. Calculated creatinine clearance ≤50 mL/min. 5. Thyroid-stimulating hormone level outside of the normal range. 6. 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.) 7. History of laser treatment for proliferative diabetic retinopathy within the 6 months prior to Screening. 8. History of treated diabetic gastroparesis, gastric banding, or gastric bypass surgery. 9. 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 E). 10. History of coronary angioplasty, coronary stent placement, coronary bypass surgery, or myocardial infarction within the 6 months prior to Screening. 11. History of any hemoglobinopathy that may affect determination of HbA1c. 12. History of infection with HIV. 13. History of a psychiatric disorder that will affect the subject’s ability to participate in the study. 14. History of angioedema in association with use of angiotensin-converting enzyme inhibitors or angiotensin-II receptor inhibitors. 15. History of alcohol or substance abuse within the 2 years prior to Screening. 16. History of treatment with any weight-loss drugs or oral or systemically injected glucocorticoids within the 3 months prior to Screening. 17. Receipt of any investigational drug within the 30 days prior to Screening. 18. Prior treatment in an investigational study of alogliptin. 19. Clinically significant medical abnormality or disease or clinically significant abnormal findings at Screening (other than type 2 diabetes) that, in the opinion of the investigator, should exclude the subject from the study. 20. Subject is a study site employee, or is an immediate family member of a study site employee who is involved in the conduct of this study. 21. Subject has donated more than 400 mL of blood within the 90 days preceding their participation in the study. 22. Subjects who have hypersensitivity or have had an anaphylactic reaction(s) to any DPP-4 inhibitor drug. |
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E.5 End points |
E.5.1 | Primary end point(s) |
HbA1c change from baseline at week 52. |
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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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | No |
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 | No |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 15 |
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 | 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
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 7 |
E.8.9.2 | In all countries concerned by the trial days | 0 |