E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | pref |
E.1.2 | Classification code | 10020365 |
|
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To investigate the efficacy and safety of a 3 month 5-MTHF treatment in terms of decreasing total plasma Hcy (tHcy) in homocystinuric patients, while co-administered with an individual established therapy as a folic acid substitute. |
|
E.2.2 | Secondary objectives of the trial |
Change from baseline values of plasma tHcy after 2 weeks and 1 month of treatment Change of tHcy plasma values from screening (folic acid treatment) to baseline and after 3 months of treatment Change from baseline values of: urine homocystine, S-adenosylhomocysteine, S-adenosyl methionine, methionine, endothelial dysfunction factors as the tissue-type plasminogen activated antigen (t-PA) and Plasminogen activator inhibitor type-1 antigen (PAI-1) in plasmaafter 2 weeks, 1 and 3 months of treatment Change from baseline of the isoprostane 8-iso-PGF2a concentrations in urine as a marker of the enhanced peroxidation of arachidonic acid and platelet activation after 2 weeks, 1 and 3 months of treatment. Change from baseline of fibrinogen levels, partial prothrombine time (PTT), prothrombine time (PT) and coagulation factor V Leiden in plasma after 2 weeks, 1 month and 3 months of treatment.
|
|
E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1. signed informed consent (patient or Legal responsible) 2. >16 years of age 3. classical (non-pyridoxine responsive) homocystinuria (CBS deficiency) 4. stable clinical condition 5. willing to complete all phases and all procedures of the study 6. on B6, B12, betaine and folic acid treatment 7. ability to comprehend the full nature and purpose of the study, including possible risks and side effects; ability to co-operate with the Investigator and to comply with the requirements of the entire study; signed written informed consent prior to inclusion in the study
|
|
E.4 | Principal exclusion criteria |
1. patients taking multivitamin supplements, folic acid or creatine treatment at inclusion and throughout the duration of the study 2. episodes of thrombosis and/or embolism one year before inclusion in the study 3. history of drug and/or alcohol abuse during the 6 months before the beginning of the study 4. patients with serious illness(es) or diseases (e.g., haematological, renal, hepatic, respiratory, endocrine, psychiatric) that may interfere with, or put patients at additional risk for their ability to receive the treatment outlined in the protocol 5. donation or receipt of blood or blood products (within 2 months before baseline) 6. pregnant or lactating female
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
To determine: Reduction from baseline of total Hcy (tHcy) in plasma after a 3 month treatment with 5-MTHF 15 mg. Baseline will be defined as the values obtained after the wash-out phase before 5-MTHF first intake.
|
|
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 | Yes |
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 | Information not present in EudraCT |
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 | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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 | No |
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.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
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
| |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |