E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with type II diabetes mellitus (T2DM) who are currently treated with a stable daily dose of metformin alone but experiencing inadequate glycemic control |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.0 |
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 durability (for up to approximately 2 years) of the efficacy of alogliptin plus metformin as compared to glipizide plus metformin as measured by glycosylated hemoglobin (HbA1c) change from baseline to Week 52 or 104 in adults with T2DM. |
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E.2.2 | Secondary objectives of the trial |
To evaluate other measures of glycemic control after treatment with alogliptin plus metformin as compared with glipizide plus metformin, including HbA1c change from baseline in other visit and FPG change from baseline in all visits. To evaluate clinically meaningful levels of response in HbA1c after treatment with alogliptin plus metformin as compared with glipizide plus metformin. To evaluate changes in body weight after treatment with alogliptin plus metformin as compared with glipizide plus metformin. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Male or female subjects, 18 to 80, years of age, inclusive with a historical diagnosis of T2DM. The subjects must meet one of the following: The subject has been inadequately controlled on a stable daily dose of &#61619;1500 mg (or documented MTD) of metformin for at least 2 months prior to Screening. Inadequate glycemic control is defined as an HbA1c concentration between 6.5 and 9.0%, inclusive. These subjects will immediately enter the stabilization period according to Study Schedule A or the subject has been inadequately controlled (as defined by an HbA1c 7.5 10%, inclusive) on metformin <1500 mg without documented MTD. After completing the Pre-screening visit, these subjects will have their metformin dose immediately increased to &#61619;1500 mg (or MTD) for an 8 week period according to Study Schedule B. Following this 8-week period, the subject must qualify for entry into the stabilization period by completing the Screening Visit having inadequate glycemic control defined as an HbA1c concentration between 6.5 and 9.0%, inclusive. No treatment with antidiabetic agents other than metformin within 2 months prior to Screening (Exception: if a subject has received other antidiabetic therapy for less than 7 days within the 2 months prior to Screening). Body mass index (BMI) &#61619;23 kg/m2 and &#61603;45 kg/m2. Fasting C-peptide concentration &#61619;0.8 ng/mL (&#61619;0.26 nmol/L). Subjects 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. Females of childbearing potential (ie, not surgically sterile and/or not postmenopausal) and male subjects who are sexually active must be practicing adequate contraception. Subject is able and willing to provide written informed consent. The subject is capable of understanding and complying with protocol requirements, including scheduled clinic appointments. The subject is able and willing to monitor their own blood glucose concentrations with a home glucose monitor and complete subject diaries. |
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E.4 | Principal exclusion criteria |
Subjects who have a systolic blood pressure &#61619;150 mm Hg and/or diastolic pressure &#61619;90 mm Hg at Screening Visit. Subjects who have the following clinical lab test results: Hemoglobin &#61603;12 g/dL (&#61603;120 gm/L) for males and &#61603;10 g/dL (&#61603;100 gm/L) for females, Alanine aminotransferase >2.5 x upper limit of normal, Serum creatinine &#61619;1.5 mg/dL for males and &#61619;1.4 mg/dL for females or creatinine clearance &#61603;50mL/min, based on calculation by central lab using the Cockcroft-Gault approximation. Subject plans to become pregnant during the study or is pregnant (confirmed by laboratory testing, i.e. serum/urine hCG, in females of childbearing potential) or is lactating. Subject has a 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, II or CIN III [cervical intraepithelial neoplasia] is allowed.) Subject has a history of laser treatment for proliferative diabetic retinopathy within the 6 months prior to Screening. Subject has a history of treatment for diabetic gastric paresis, gastric banding, or gastric bypass surgery. Subject has 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). Subject has a history of coronary angioplasty, coronary stent placement, coronary bypass surgery, myocardial infarction (MI), stroke or transient ischemic attack (TIA) within the 3 months prior to Screening. Subject has a history of any hemoglobinopathy that may affect determination of HbA1c. Subject has a known history of infection with human immunodeficiency virus (HIV), Hepatitis B Virus (HBV) or Hepatitis C virus (HCV). Subject has a history of any psychiatric disorder that will affect the subject�s ability to participate in the study. Subject has a history of alcohol or substance abuse within the 2 years prior to Screening. Subject has received any investigational drug within the 30 days prior to Screening or has received an investigational antidiabetic drug within the 3 months prior to Screening. Subject has received any antidiabetic drug in the DPP-IV inhibitors or GLP-1 mimetics classes at any time prior to Screening. Subject has any major illness or debility that in the investigator�s opinion prohibits the subject from completing the study. Subject has had prior treatment in an investigational study of alogliptin. 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. The subject has a history of hypersensitivity, allergies, or has had an anaphylactic reaction(s) to any DPP-IV inhibitor drug, metformin or glipizide. If female, the subject is pregnant or lactating or intending to become pregnant before, during, or within 1 month after participating in this study; or intending to donate ova during such time period. If male, the subject intends to impregnate others or donate sperm during such time period. 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. |
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E.5 End points |
E.5.1 | Primary end point(s) |
HbA1c change from baseline at Week 52 or 104 |
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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 | 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) | 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) | 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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 80 |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
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 | 3 |
E.8.9.2 | In all countries concerned by the trial months | 9 |