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 | 10021750 |
E.1.2 | Term | Infantile spasms |
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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 |
To evaluate the safety, tolerability, and antiepileptic activity of variable ascending doses of ganaxolone and to determine the therapeutic dose of ganaxolone in subjects (ages 4 to 24 months) with infantile spasms (IS). |
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E.2.2 | Secondary objectives of the trial |
To determine the PK profile of ganaxolone in subjects 4 to 24 months of age. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subjects accepted for this clinical study must: (a) Be diagnosed with IS (regardless of etiology- except for a progressive neurologic illness, see protocol Section 9.3.3 Exclusion Criteria c). Diagnostic Criteria: Seizures consisting of single or repetitive short muscular contractions leading to flexion or extension. Spasms may be characterized as tonic or myoclonic contractions, may occur singly or in clusters, and typically occur bilaterally and symmetrically. The EEG pattern must be consistent with the diagnosis of IS (hypsarrhythmia, modified hypsarrhythmia, multifocal spike wave discharges, etc). (b) Have a vEEG recording confirming the diagnosis of IS. (c) Have had a magnetic resonance imaging (MRI) performed to determine any possible causes of IS. (d) Have been previously treated with 3 or fewer AEDs. (e) If being treated with concomitant AEDs (also see protocol Section 9.2.2) 1) Current AEDs have been at a constant daily dose for at least 2 weeks; Note: Subjects with minor dose adjustments may be allowed to enter the study after shorter periods after detailed discussion with the medical monitor. 2) Have a stable clinical response/plateau for at least 2 weeks 3) Are able to continue treatment with no more than 2 concomitant AEDs (ACTH, corticosteroids, felbamate, and vigabatrin are not allowed concomitantly). 4) A ketogenic diet is permitted if it can be maintained for the duration of the study. (f) Be a male or female, 4 to 24 months of age (inclusive). (g) Have a Parent/Guardian who is properly informed of the nature and risks of the clinical study, who is willing and capable of complying with all clinical study procedures, and has given informed consent in writing prior to entering the clinical study. (h) Be able to participate for the full term of the clinical study. |
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E.4 | Principal exclusion criteria |
Any of the following conditions are cause for exclusion from the clinical study: (a) Treatment with corticosteriods, ACTH, vigabtrin, felbamate, or any AED not approved by Regulatory Agencies 2 weeks prior to randomization. Up to 0.5 mg/kg/day of prednisone (or equivalent) is allowed at baseline if subjects are being tapered off prednisone following ACTH or corticosteroid treatment. Subjects being tapered on prednisone (up to 0.5 mg/kg/day at baseline) may be randomized. (b) Treatment with more than two AEDs at baseline. (c) Have an active CNS infection, demyelinating disease, degenerative neurological disease, or CNS disease deemed progressive (with the exception of tuberous sclerosis) as evaluated by brain imaging (MRI). (d) Have any disease or condition (medical or surgical) at screening that might compromise the hematologic, cardiovascular, pulmonary, renal, gastrointestinal, or hepatic systems; or other conditions that might interfere with the absorption, distribution, metabolism, or excretion of the investigational product, or would place the subject at increased risk. (e) Aspartate aminotransferase (AST), alanine aminotransferase (ALT), or total bilirubin greater than four times the upper limit of normal (ULN) or clinical laboratory value deemed clinically significant by the Investigator. (f) History of recurrent status epilepticus. (g) Have been exposed to any other investigational drug within 30 days prior to randomization. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy variable is the spasm frequency as measured from 24-hour vEEG by a central reader on Visit 5. |
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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 | Yes |
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 | No |
E.8.1.6 | Cross over | Yes |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 7 |
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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All test results from screening through the end of the study (eg, clinical data, allspecial test results). Information properly recorded in the eCRFs by appropriate study personnel and electronically signed and dated by the Investigator. Completed drug accountability records. Copies of protocol amendments and IRB approval/notification, if appropriate. A summary of the study prepared by the Principal Investigator (an IRB summary close letter is acceptable). |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | |
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 |