E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Leriche-Fontaine stage II PAD (Peripheral Arterial Disease) presenting symptoms of intermittent claudicatio |
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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 | 10034633 |
E.1.2 | Term | Peripheral vascular disease |
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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 study is to evaluate the best dosage of Betaine to be used in PAD (Peripheral Arterial Occlusive Disease) in regard of clinical parameters. |
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E.2.2 | Secondary objectives of the trial |
• Secondary objectives are to select concentration dependent parameters which may be responsible of the MoA and to evaluate the safety of the product • Evaluation of the product safety profile
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male and female subjects with Leriche-Fontaine stage II PAD presenting symptoms of intermittent claudication for at least 6 months. 2. Age between 50 and 80 years. 3. Objective evidence confirming the clinical diagnosis of PAD (ankle/brachial index < 0.9 and, in diabetic patients, toe index <0.7). 4. Absolute claudication distance < 700, and initial claudication distance > 50 m in the standardized treadmill testing. 5. Clinical stability before inclusion (i.e. changes in ACD not exceeding 25 % in two standardized treadmill testings during run-in). 6. Signed informed content, willing and able to comply with all procedures and scheduled visits 7. Availability for the planned study duration. 8. Negative pregnancy testing for women of childbearing potential (to be made during the screening phase and just before the first administration) and use of an acceptable means of contraception (condom, hormonal or mechanical methods) for one month prior to randomization and the duration of the study.
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E.4 | Principal exclusion criteria |
1. Unstable symptoms and/or rapid deterioration of PAD during the previous 3 months. 2. Presence of clinically significant renal or hepatic insufficiency, or insulin-dependent type 1 diabetes. 3. Uncontrolled type 2 diabetes, arterial hypertension or dyslipidemia 4. Any clinical conditions limiting the subject’s ability to exercise (angina pectoris, congestive heart failure, respiratory disease, orthopaedic disease, neurological disorders). 5. Subjects with high variability in walking distance (treadmill testing performed at interval ≥ 1 week; maximum change in absolute claudication distance < 25%). 6. Active peptic ulcer disease during the previous 6 months. 7. Any haemorrhagic condition or history of bleeding. 8. Acute coronary syndrome or acute cerebrovascular episodes during the previous 6 months. 9. Previous revascularisation procedures or PTA during the last 6 months or indication for vascular surgery. 10. Ischemic rest pain or gangrene. 11. Medical or psychiatric condition or occupational responsibilities which preclude subject compliance with the protocol. 12. History of serious allergic reaction to any substance, requiring hospitalization or emergent medical care (e.g. bronchospasm, or hypotension). 13. Known history of cystathionine beta-synthase (CBS) deficiency. 14. Known or suspected alcohol, drug or medication abuse. 15. Life expectancy < 5 months. 16. Pregnancy or lactation. 17. Participation in other investigational trials within 3 months prior to inclusion.
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E.5 End points |
E.5.1 | Primary end point(s) |
To evaluate the best dosage of Betaine to be used in the clinical treatment of subjects affected by PAD according to a dose-response study model. |
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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) | 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 | 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
| 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 | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 17 |
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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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 | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |