E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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 | 10041582 |
E.1.2 | Term | Spinal muscular atrophy |
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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 |
the primary objective of this study is to evaluate the effect on SMN2 transcripts of salbutamol administered at the daily oral dose of 12 mg for one year, as add on therapy, in patients affected by SMA type III, often referred to as Kugelberg-Welander or Juvenile Spinal Muscular Atrophy, in comparison with placebo under double blind conditions.Safety will be assessed for all subjects, for the entire duration of the study. |
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E.2.2 | Secondary objectives of the trial |
Secondary objective will be to evaluate the therapeutic efficacy of salbutamol. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
male or female out-patients; clinical diagnosis of SMA III, confirmed by molecular analysis; range of age between 18-50 years; females should be either of non-childbearing potential (surgical sterilization or postmenopausal) or of childbearing potential. Females of childbearing potential must agree to be astinent or to use at least one medically acceptable method of contraception; patients able to understand and give the informed consent and to perform evaluation tests; absence of contra-indications to the use of salbutamol; written informed consent. |
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E.4 | Principal exclusion criteria |
severe respiratory failure, asthma, cardiovascular disorders (especially coronary insufficiency, hypertension, and cardiac arrhythmia) convulsive disorders, hyperthyroidism, diabetes mellitus, hepatic or renal disorders; concomitant treatment with thiazide diuretics, monoamine oxidase inhibitors or tricyclic antidepressants, or within 2 weeks of discontinuation of such agents; use of beta2-stimulants or other drugs known to induce SMN2 up-regulation in vitro or in pilot open label study within 6 months before the study; pregnant or lactating women; subjects who have received an experimental drug or have participated in a clinical trial within 3 months prior to screening; employees of the investigator or study centre with direct involvement in the proposed study or other studies under the direction of that investigator or study centre. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint will be the number of responding patients (responders), defined as patients which after one year of treatment show an increment of SMN2 transcripts of at least 90%. |
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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 | 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 | 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
| 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 | No |
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 | 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
| |
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 | 6 |
E.8.9.1 | In the Member State concerned days | |
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 | 6 |