E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients diagnosed with benzodiazepine dependence with an average daily dose of at least 30 mg of diazepam equivalence. |
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E.1.1.1 | Medical condition in easily understood language |
Patients with high dose benzodiazepine dependence who cannot succeed in detoxification otherwise |
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E.1.1.2 | Therapeutic area | Psychiatry and Psychology [F] - Mental Disorders [F03] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10004099 |
E.1.2 | Term | Barbiturate and similarly acting sedative or hypnotic dependence, continuous use |
E.1.2 | System Organ Class | 100000004873 |
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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 is to demonstrate that detoxification of benzodiazepines in high-dose benzodiazepine dependent patients using continuous subcutaneous infusion of flumazenil is feasible and safe.
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E.2.2 | Secondary objectives of the trial |
Secondary goals of the study are to explore 1) the effect of flumazenil detoxification on anxiety levels during and after detoxification, 2) the effects of flumazenil detoxification on sleep quality during and after detoxification, 3) patient satisfaction with flumazenil detoxification, 4) efficacy of flumazenil detoxification.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• A primary diagnosis of benzodiazepine dependence with an average daily dose of at least 30 mg of diazepam or equivalent according table 2 OR A diagnosis of benzodiazepine dependence with an average daily dose of at least 30 mg of diazepam or an equivalent with a co-morbid diagnosis of alcohol or cannabis dependence. Prior to the baseline measurement and flumazenil infusion patients must be abstinent from alcohol and cannabis for at least two months. • Age between 21 and 65 years. • Participants should master Dutch language sufficiently to provide informed consent and participate in all measurements (including self report questionnaires). • Motivation for and availability of a regular treatment after the detoxification procedure at a regional (addiction) care facility.
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E.4 | Principal exclusion criteria |
• History of epilepsy or IEDs on EEG or other serious neurological disorders; • History of a serious medical condition, including heart disease (myocardial infarction or arrhythmias), lung disease (COPD gold stage II or higher), acute liver or kidney disease (indexed by ASAT ALAT max three times the norm or increased Creatinine/Ureum); • Diagnosis of a current severe psychiatric disorder (psychosis, mania, severe depression); • Diagnosis of a primary organic sleep disorders e.g. hypersomnia, disorders of the sleep wake schedule and sleep apnoea; • A positive urine screening for cocaine, heroin, amphetamine, ecstasy, cannabis, opiates, buprenorphine and methadone;
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E.5 End points |
E.5.1 | Primary end point(s) |
Only mild and transient withdrawal symptoms during and after detoxification, Without the occurrence of any adverse events. Without IEDs on EEG/PSG recording.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
during detoxification an after one month and three month. |
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E.5.2 | Secondary end point(s) |
After detoxification 1) Decreased anxiety levels, 2) Improve sleep quality, 3) A satisfactory method for detoxification reviewing the detoxified patients, 4) Show 100% completers, 75% abstinence after 3-months and improved quality of life.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
during detoxification and after one and three month. |
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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 | 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 | No |
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.8.2.4 | Number of treatment arms in the trial | 1 |
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.8.5 | 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 | No |
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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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 | |
E.8.9.1 | In the Member State concerned days | |