E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
This is a double-blind phase 2 clinical study to evaluate the effects of alagebrium chloride (ALT-711) versus placebo on albumin excretion rate (as an early marker of diabetic nephropathy) in subjects with type 1 diabetes with microalbuminuria receiving concomitant antihypertensive therapy. |
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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 | 10061835 |
E.1.2 | Term | Diabetic nephropathy |
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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 |
The primary objective of this double-blind phase 2 clinical study is to evaluate the effects of alagebrium chloride (ALT-711) versus placebo on albumin excretion rate (as an early marker of diabetic nephropathy) in subjects with type 1 diabetes with microalbuminuria receiving concomitant antihypertensive therapy (ramipril). |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are to evaluate the safety of alagebrium in combination with ramipril and the effects of the combination on kidney fibrosis (by measuring markers of collagen turnover), the renin-angiotensin pathway, and 24-hour mean blood pressure measured with an ambulatory blood pressure monitoring device. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-Insulin-dependent type 1 diabetes -Age 18-65 -Diagnosis of established microalbuminuria (albumin:creatinine ratio = 30-300 mg/g) by at least 2 independent analyses over a period 6 months or at least 3 independent analyses over a period of at least 12 months prior to screening and confirmed at screening -Presence of microalbuminuria reconfirmed at baseline, visit 3 (albumin:creatinine ratio = 30-300 mg/g) -Office cuff systolic blood pressure less than or equal to 140 mm Hg, diastolic blood pressure less than or equal to 90 mm Hg -HbAlc less than 10% -The subject is able to understand content of and has provided written informed consent.
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E.4 | Principal exclusion criteria |
-Body mass index greater than 40 kg/m^2. -Cardiovascular event within 6 months prior to screening, including angina, or any revascularization procedures -History of acute myocardial infarction within 12 months prior to screening. -Receiving chronic nonsteroidal anti-inflammatory (NSAID) therapay. -Receiving antihypertensive therapy except for angiotensin-coverting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs). -Use of systemic corticosteriods (topical and inhaled corticosteriods are permitted) -Stroke or any sequelae of a stroke, transient ischemic attack, or reversible ischemic neurological defect within 24 months prior to screening. -Any significant ECG abnormalities, including second-degree A-V block or complete A-V block. Any known significant arrhythmia including atrial flutter, ventricular tachycardia, WPW syndrome. Any hemodynamically significant valvular heart disease.
See protocol for additional exclusion criteria. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline in albumin excretion rate (ug/min) (based on 3 overight urine collections) after 24 weeks will be the primary measure of efficacy. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
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 | 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 | 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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | Information not present in EudraCT |
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) | 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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | No |
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 | No |
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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The expected overall total duration of subject participation is 42 weeks (after approximately 2 weeks of screening, 8-week single-blind run-in-treatment followed by 24-week double-blind treatment, followed by 8-week single-blind run-out treatment). |
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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 | |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 8 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 8 |