| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| maintenance of alcohol abstinence in recently abstinent alcohol-dependent patients |
|
| E.1.1.1 | Medical condition in easily understood language |
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| E.1.1.2 | Therapeutic area | Psychiatry and Psychology [F] - Behavioral Disciplines and Activities [F04] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 16.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10031519 |
| E.1.2 | Term | Other and unspecified alcohol dependence |
| 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 |
| To confirm the efficacy of SMO.IR in the maintenance of alcohol abstinence in recently abstinent alcohol-dependent patients. |
|
| E.2.2 | Secondary objectives of the trial |
To assess the safety of SMO.IR in this patient population including possible GHB craving or withdrawal reaction, abuse or misuse.
To assess the effect of SMO.IR on other clinically relevant secondary efficacy endpoints.
To compare the safety and efficacy of 4 dose regimens of SMO.IR in order to define the optimal dose or dose range of SMO.IR in this indication i.e. the dose or the dose range of SMO.IR associated with the highest benefit-to-risk ratio. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Patients must already have signed and dated an informed consent form.
2. Male or female patients of any ethnic group, aged 18 years to 75 years inclusive and with BMI between 18.5 and 30 kg/m2 inclusive.
3. Patients must meet at least four criteria of alcohol dependence as defined by the DSM-IV-TR.
4. Patients must confirm at least 7 drinking days including at least 2 heavy drinking days in the last 14 days preceding screening. Alcohol drinking will be documented in TLFB calendar filled retrospectively by the patient at screening visit.
5. Patients who, in the judgment of the investigator, are motivated to completely abstain from alcohol.
6. Patients must have been abstinent for at least 3 days but up to 14 days with or without inpatient or outpatient detoxification prior to the randomization. The detoxification treatment (benzodiazepine agent, Alcover® (Austria and Italy) or other) has to be washed out for at least 24 hours prior to the randomization.
7. Patients must be completely abstinent at the time of randomization and the Breath Alcohol Concentration test must be negative.
8. Patients who provided telephone number of the contact person who could be contacted in case of patient‘s unavailability. The presence of the contact person at the screening visit is not obligatory.
9. Patients agree to be contacted by the site during the study and provide valid phone contact to the investigator.
10. Laboratory parameters: ASAT and ALAT within 4 times upper limit of normal, and bilirubin level not greater or equal to 3.6 mg/dl. Other biochemical, urinalysis, and haematological tests except erythrocyte mean corpuscular volume (MCV) must be in the normal range or any deviation from the normal range must be rated as non clinically significant by the investigator. There is no limit for γ-GT.
11. Sexually active female patients must be postmenopausal, surgically sterile, or practicing an effective method of birth control (e.g., prescription oral contraceptives, contraceptive injections, intrauterine device, double-barrier method, contraceptive patch) at least 1 month before study entry and 1 month after the final treatment period. There is no need of contraception for male patients. |
|
| E.4 | Principal exclusion criteria |
1. Abstinence for more than 14 days prior to the randomization.
2. Patients treated with Alcover® in the last 6 months. Treatment of withdrawal with Alcover® at the time of study entry and/or during screening period is allowed. The wash-out period at least 24 hours between the last Alcover® administration and patient randomization has to be kept.
3. Patients who drunk between screening and randomization visit.
4. Positive urine screen for cannabis, cocaine, heroin, amphetamines, benzodiazepine, barbiturates, methadone, ecstasy, tricyclic antidepressants, other opiates or any other substance of addiction detectable by urinalysis at randomization. Repeat urinalysis is allowed before the time limit for randomization: a repeat positive test is an exclusion criterion.
In the case of patients receiving benzodiazepine (BZD) agents during alcohol detoxification, a positive BZD urine test will be accepted at randomization and Week 1 and Week 2 visits but at no other visits, provided there is no clinical evidence of BZD addiction.
5. Current or recent history of a substance abuse or dependence on benzodiazepine, amphetamines, cocaine, heroin, other opiates or any other substance except nicotine and caffeine as defined by the DSM-IV TR
6. History of or current epileptic syndrome 7. known medical history of succinic semialdehyde dehydrogenase deficiency.
8. Concomitant psychotropic drugs including anti-epileptic and sedative antihistamine agents.
9. Concomitant treatment with disulfiram, acamprosate, topiramate, baclofen or naltrexone.
10. Conditions that require treatment with concomitant medications that are not allowed according to the study protocol.
11. Patients with current psychiatric symptoms that meet axis 1 diagnostic criteria on DSM IV and require medication treatment.
12. Patients with psychiatric disorder within the past 6 months that are not clinically stable and receiving or require any psychotropic medications.
13. Patients with moderate to severe depression measured by Hamilton Depression Scale of 21 points (HAM-D > 15) at the screening visit.
14. Patients with moderate to severe anxiety measured by Hamilton Anxiety Scale of 14 points (HAM-A > 15) at the screening visit.
15. Patients with impaired hepatic function 16. Patients with impaired renal function
17. Any chronic gastrointestinal disease or previous major abdominal surgery
18. Any significant cerebral vascular and/or cardiovascular disease
19. Chronic headaches and / or migraine, recurrent nausea and / or vomiting.
20. Patients who have suffered any of the following within 1 year prior to the screening: mild/moderate traumatic brain injury, stroke, transient ischemic attack, brain neoplasm. Severe traumatic brain injury within the last 15 years lasting or residual sequelae suggesting transient changes in consciousness.
21. Any neurological or psychiatric disorders resulting in disorientation, memory impairment, inability to report accurately.
22. Any clinically significant disease that in the investigator's opinion may affect efficacy or safety assessments or may compromise the patient‘s safety during trial participation
23. History of malignancy within the past 2 years, with the exception of basal cell skin carcinoma and cervical cancer in situ with normal pap smear.
24. Patient who, in the judgment of the investigator, is likely to be non-compliant or uncooperative during the study, or unable to cooperate because of a language problem or poor mental development.
25. Patients protected by law
26. Concurrent participation in another trial, or within 3 months of enrollment into this trial.
27. Employees of the investigator or trial site or sponsor, with direct involvement in the proposed trial or other trials under the direction of that investigator or trial site, as well as family members of employees or the investigator.
28. Women who are pregnant or lactating. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary efficacy endpoint will be the Percentage of Days Abstinent (PDA) at the end of the study. The PDA is calculated as the ratio expressed as a percentage of the number of days with no alcohol intake to the number of days corresponding to the Double-blind treatment phase (84 days). |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
Secondary criteria of efficacy include those related directly to alcohol abstinence, alcohol consumption if the patient is not abstinent completely, and a description of trends in alcohol consumption over the study period.
Secondary criteria of safety:
• Assessment of AEs and SAEs
• Assessment of vital signs and physical examination.
• ECG
• Laboratory parameters
• Search for study drug abuse, misuse, craving or withdrawal reaction.
• Sodium oxybate abuse
• HAM-D Scale of 21 points
• HAM-A of 14 points
• C-SSRS |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
at each study visit, at the end of the double blind treatment phase, and during the follow-up period;
AE and SAE - at all visits;
HAM-A, HAM-D, C-SSRS, laboratory - screening, monthly visits, and follow-ups;
ECG- screening, visit W12
sodium oxybate craving - monthly visits, intermediate visits, follow-ups; sodiume oxybate abuse - monthly visits and intermediate visits
|
|
| 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 | 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 | Yes |
| E.8.2.3.1 | Comparator description |
| different concentrations of the SMO.IR |
|
| E.8.2.4 | Number of treatment arms in the trial | 5 |
| 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 | 3 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 50 |
| 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 | 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
|
| Last visit of the last patient |
|
| 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 | 4 |
| E.8.9.1 | In the Member State concerned days | 0 |
| 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 | 4 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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