| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
Tardive dyskinesia usually occurs after prolonged exposure to antipsychotics and is characterized by abnormal choreiform, athetoic, choreathetoic or rhythmic involuntary movements.
The localizations of the neuroleptic-induced TD are mostly the tongue, jaw or extremities.
The abnormal movements increase with emotional arousal and decrease with relaxation. The movements are absent during sleep.
|
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 7.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10013928 |
|
| 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 |
| To compare the efficacy of levetiracetam up to 3000 mg/day in b.i.d. administration to placebo during an 8-week treatment period in the treatment of neuroleptic-induced tardive dyskinesia in subjects aged at least 18 years to 80 years with a stable axis I psychiatric disorder. |
|
| E.2.2 | Secondary objectives of the trial |
•To compare the efficacy of levetiracetam up to 3000 mg/day in b.i.d. administration to placebo on neuroleptic-induced akathisia and other extrapyramidal symptoms.
•To evaluate the effect of levetiracetam up to 3000mg/day in b.i.d. administration on the primary psychiatric disorder compared to placebo.
•To evaluate the safety of levetiracetam.
|
|
| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria |
•Written informed consent signed and dated by the subject.
•Male or female, age ≥18 and ≤ 80 years.
•In- or out patients
•Diagnosis of stable Axis I psychiatric disorder according to the Investigator since at least 6 months prior to the screening visit (V1).
•Stable Neuroleptic-Induced Tardive Dyskinesia (NITD) according to the DSM-IV criteria since at least 1 month prior to the screening visit (V1).
•Tardive Dyskinesia severity defined by a total mean score of hyperkinesia on the SHRS of at least 5 at screening visit (V1) and at baseline visit (V2) before randomization.
•Use of antipsychotics (all types and routes of administration) for at least 6 cumulative months prior to the screening visit (V1) and, if the subject is under treatment, at least one month on a stable dose regimen prior to the screening visit (V1).
•If applicable, stable dose regimen of anticholinergic agents and other drugs used for abnormal movement disorders for the last month prior to the screening visit (V1).
•Able to cooperate and to communicate adequately as judged by the investigator.
•Subjects willing to be videotaped.
•Female subjects without childbearing potential (premenarchal, 2 years post-menopausal, bilateral oophorectomy or bilateral salpingectomy, complete hysterectomy, congenital sterility, bilateral tubal ligation) are eligible. Female subjects with childbearing potential are eligible if they have a negative serum pregnancy test at the screening visit (V1) and if they use a medically accepted contraceptive method for the duration of the trial participation (i.e. oral or non-oral contraceptive method, intra-uterine device, diaphragm with spermicide, male condom with spermicide, female condom, monogamous relationship with vasectomized partner). Abstinence will be considered as an acceptable method of contraception on a case-by-case basis upon discussion with the UCB Clinical Research Physician (CRP) or his/her representative. The subject must understand the consequences and potential risks of inadequately protected sexual activity, be educated about and understand the proper use of contraceptive methods, and undertake to inform the Investigator of any potential change in status.
|
|
| E.4 | Principal exclusion criteria |
•Pregnant, lactating or sexually active women with childbearing potential who are not using a medically accepted birth control method.
•The presence of any Axis II condition within 6 months prior to the screening visit (V1).
•History of suicide attempts during the last 10 years prior to the screening visit (V1).
•Huntington’s disease, idiopathic dystonia, Wilson’s disease, Sydenham’s chorea, thyroid dysfunction or spontaneous dyskinesia.
•Dyskinesia due to ill-fitting denture.
•Start of drugs (other than neuroleptics) that can cause dyskinesia (e.g. L-dopa, bromocriptine) within one month prior to the screening visit (V1).
•The presence of alcohol, or other substance abuse disorder as defined by DSM-IV.
•Any medication that may interfere with the absorption, distribution, metabolism, or excretion of the concomitant neuroleptics or levetiracetam during the course of the study.
•Introduction or change in the dose of anticholinergic agents or other drugs intended to control abnormal movements disorders (i.e. branched chain amino acids, vitamin B6 or E, melatonin, neuroleptics,...) within the last month prior to the screening visit (V1).
•Benzodiazepine use not stable i.e. more than 50% change in the daily dose for more than 3 days in subjects with daily benzodiazepine intake, since at least 2 weeks prior to the screening visit (V1).
•Any participation in an investigation of a medication or device within 3 months prior to the screening visit (V1) or during this trial.
•Subject has clinically significant deviations from reference range values for renal function (creatinine clearance – estimated with Cockroft formula - below 50 ml/min) or any of the other laboratory parameters required for this study, as assessed by the Investigator.
•Clinically significant ECG abnormalities;
•Subject has any clinically significant acute or chronic illness (i.e. cardiac, renal or hepatic disease) (as determined during the physical examination or from other information available to the Investigator).
•Known allergic reaction or intolerance to pyrrolidine derivatives and/or excipients (not exclusively but principally to lactose, corn starch, and cellulose) or known history of multiple drug allergies.
•Subject is known to have a terminal illness.
•Subject has any medical condition that might interfere with the subject’s study participation (i.e., serious infection, scheduled elective surgery, etc).
•History of poor compliance with visit schedule or medication intake.
•Investigators, co-investigators, their spouses or children or any trial collaborators may not be included as subject in the trial.
•Subjects having been blood donors during the 3 months before V1 or planning to be blood donator during the trial.
•Subject previously allocated to a trial treatment within this trial.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Criteria for evaluation :
Efficacy Variables
•The primary efficacy variable is the change from baseline on the total mean score of hyperkinesia estimated at the evaluation visit (V6) as evaluated by the independent blinded central reviewer.
All analyses on the SHRS will be performed on the ratings by the independent blinded central reviewer unless specified otherwise.
The secondary efficacy variables are the following variables:
•The change from baseline on the total mean score of hyperkinesia estimated at the evaluation visit (V6) as evaluated by the investigators.
•The change from baseline on the individual SHRS items and subtotals.
•Changes from baseline on the total mean score of hyperkinesia at the evaluation visit (V6) will be evaluated by subdividing the subjects into the following categories :
•Subjects with ≥4 points decrease
•Subjects with 3 points or less change (either increase or decrease).
•Subjects with an increase of 4 points or more.
•Subjects with a decrease of at least 50% on the total mean score of hyperkinesia at the evaluation visit (V6) compared to baseline.
•Time evolution of the percent reduction from baseline in the total mean score of hyperkinesia.
•The subjects' maximum improvement/worsening over time on the individual SHRS items and subtotals.
•Time evolution of the BPRS.
•Investigator’s GES’s.
Exploratory Variables
•Correlations between the scores from the Investigator rated scales and the scores from the independent blinded central reviewer will be explored.
Safety Variables
•Adverse events (AEs);
•Laboratory tests;
•Physical and neurological examinations;
•Vital signs;
•Body weight;
•Electrocardiogram (ECG);
|
|
| 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 | Yes |
| 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 | 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.8.5 | 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 | 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 |
|
| 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
|
| The end of trial is defined as the date of database lock as, at that time, interactions between the Sponsor and the Investigator(s) with possible impact on subjects data have ended. |
|
| 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 | 12 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial months | 12 |
Print
