| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
Type II diabetes mellitus (T2DM)
|
|
| E.1.1.1 | Medical condition in easily understood language |
| A metabolic disease in which a person has high blood sugar, either because the body does not produce enough insulin, or because cells do not respond to the insulin that is produced. |
|
| E.1.1.2 | Therapeutic area | Body processes [G] - Metabolic Phenomena [G03] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 14.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10045242 |
| E.1.2 | Term | Type II diabetes mellitus |
| E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
|
| 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 combination of alogliptin BID plus metformin BID as compared with alogliptin BID alone or metformin BID alone on HbA1c change from Baseline at Week 26 (or at time of discontinuation of double-blind study medication or hyperglycemic rescue). |
|
| E.2.2 | Secondary objectives of the trial |
- To evaluate the efficacy comparison between alogliptin BID alone and alogliptin QD alone on HbA1c change from Baseline at Week 26.
- To evaluate other measures of glycemic control including change from Baseline of fasting plasma glucose at all visits, and HbA1c at visits other than Week 26.
Safety objective:
To evaluate the safety by adverse events, hypoglycemic events, clinical laboratory parameters, ECG
readings, physical examination, and vital signs. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Subject eligibility is determined according to the following criteria:
1. Male or female subjects, 18 to 80 years of age, with a historical diagnosis of T2DM.
2. The subject has been treated with diet and exercise for at least 2 months prior to Screening and has an HbA1c concentration between 7.5% and 10.0%, inclusive at Screening.
3. The subject has received less than 7 days of any antidiabetic medication within 2 months prior to Screening.
4. Body mass index (BMI) ≥23 kg/m2 and ≤45 kg/m2 (except for Asian or Asian descendant subjects for whom the range is between 20 and 35 kg/ m2, inclusive).
5. Fasting C-peptide concentration ≥0.8 ng/mL (≥0.26 nmol/L).
6. Subjects regularly using 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.
7. A female subject of childbearing potential and males who are sexually active agree to routinely use adequate contraception from Screening throughout the duration of the study.
NOTE: Women NOT of childbearing potential are defined as those who have been surgically sterilized (ie, hysterectomy, bilateral salpingo-oophorectomy, bilateral tubal ligation) or who are postmenopausal (defined as at least 45 years of age AND 1 year since last regular menses). Acceptable methods of contraception are defined in Section 9.1.12 of the Protocol.
8. Subject is able and willing to monitor their own blood glucose concentrations with a home glucose monitor and complete subject diaries.
9. Subject is able and willing to provide written informed consent.
10. The subject is capable of understanding and complying with the protocol requirements, including scheduled clinic appointments. |
|
| E.4 | Principal exclusion criteria |
Any subject who meets any of the following criteria will not qualify for entry into the study:
1. Hemoglobin ≤12 g/dL (≤120 gm/L) for males and ≤10 g/dL (≤100 gm/L) for females at Screening Visit.
2. Subject has a history of any hemoglobinopathy that may affect determination of HbA1c.
3. Subject has a history of laser treatment for proliferative diabetic retinopathy within the 6 months prior to Screening.
4. Subject has a history of treatment for diabetic gastric paresis, gastric banding, or gastric bypass surgery.
5. Subject has a history of diabetic ketoacidosis or hyperosmolar non-ketotic coma.
6. Subject has systolic blood pressure ≥150 mmHg and /or diastolic pressure 90 mmHg at Screening visit.
7. Subject has New York Heart Association (NYHA) Class III to IV heart failure (See
Appendix E) regardless of therapy. (Currently treated subjects who are stable at NYHA Class I or II are candidates for the study.)
8. Subject has a history of coronary angioplasty, coronary stent placement, coronary bypass surgery, or myocardial infarction within the 90 days prior to Screening.
9. Alanine aminotransferase (ALT) >3x upper limit of normal at Screening.
10. Subject has a history of alcohol or substance abuse with the 2 years prior to Screening.
11. Serum creatinine ≥ 1.5 mg/dL for males or ≥1.4 mg/dL for females, or creatinine clearance <60 mL/min based on calculation by central lab using the MDRD approximation at Screening.
12. Subject has 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 cervical intraepithelial neoplasia [CIN] I or CIN II is allowed).
13. Subject has a history of infection with human immunodeficiency virus, hepatitis B virus, or hepatitis C virus.
14. Subject has any major illness or debility that in the investigator’s opinion prohibits the subject from completing the study.
15. Subject has received any investigational drug within the 90 days prior to Screening.
16. Subject has a history of hypersensitivity or allergy to alogliptin, other DPP-4 inhibitors, metformin, or related compounds.
17. If female, the subject is pregnant or lactating or intending to become pregnant during or within 1 month after participating in this study. Subject has used oral or systemically injected glucocorticoids (including intra-articular injection) or use of weight-loss drugs within 2 months prior to screening. (Inhaled or topical corticosteroids are allowed.)
18. The subject is unable to understand verbal or written English, or any other language for which a certified translation of the approved informed consent is available.
19. The subject is a study site employee, or is an immediate family member (ie, spouse, parent, child, and sibling) of a study site employee who is involved in conduct of this study.
20. Subject has used oral or systemically injected glucocorticoids (including intra-articular injection) or use of weight-loss drugs within 2 months prior to screening. (Inhaled or topical corticosteroids are allowed.) |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| HbA1c change from Baseline at Week 26. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
Change from Baseline in HbA1c at Weeks 4, 8, 12, 16, and 20.
Change from Baseline in fasting plasma glucose at Weeks 1, 2, 4, 8, 12, 16, 20, and 26. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
Change from Baseline in HbA1c at Weeks 4, 8, 12, 16, and 20.
Change from Baseline in fasting plasma glucose at Weeks 1, 2, 4, 8, 12, 16, 20, and 26. |
|
| 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 | 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) | 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 | 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.8.2.4 | Number of treatment arms in the trial | 3 |
| 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 | 6 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 45 |
| 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 | No |
| 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 |
| Czech Republic |
| Hungary |
| India |
| Israel |
| Lithuania |
| Mexico |
| Poland |
| Romania |
| Russian Federation |
| Slovakia |
| Ukraine |
| United States |
|
| 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
|
| The end of the trial is defined as the last follow up visit of the last subject participating in the study. |
|
| 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 | 4 |
| E.8.9.1 | In the Member State concerned days | 0 |
| 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 | 7 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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