E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Amphetamine dependence and ADHD (Attention-Deficit/Hyperactivity
Disorder) |
|
E.1.1.1 | Medical condition in easily understood language |
Patients who fulfil DSMIV/5 criteria for amphetamine dependence and
ADHD (Attention-Deficit/Hyperactivity Disorder), respectively |
|
E.1.1.2 | Therapeutic area | Psychiatry and Psychology [F] - Mental Disorders [F03] |
MedDRA Classification |
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 |
Evaluation of naltrexone as relapse prevention for substance use in
patients with ADHD who are currently using central stimulant
medication. |
|
E.2.2 | Secondary objectives of the trial |
Proportion of urine samples free of drugs of abuse (with the exclusion of
THC), (ITT and completers analysis) without imputing missing data
Proportion of urine samples free of THC (qualitative measure; below the
laboratory's standard cutoff) in all randomized participants who took at
least 1 study medication dose (ITT)
Time to first relapse (first positive urine toxicology; any of tested drugs)
Self-reported days of drug and alcohol use as measured by TLFB
Proportion of urine samples positive of benzodiazepines
Craving as measured by VAS scale
Depression rating as measured by MADRS-S Scale
Levels of NTX and its metabolite in plasma and correlation with
measures of drug use, craving and side effects over the course of
treatment
Levels of ASAT and ALAT
Levels of PEth
Cognitive function as measured by CANTAB between 2 treatment arms
Change in observer-rated ADHD-symptoms as measured with Conners'
Adult ADHD Scale
Observer version (CAARS-O: SV) |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Adult male or female aged 18-70 years
2) Written, informed consent to participate
3) Fulfil DSM-5 criteria for ADHD
4) Ongoing central stimulant pharmacotherapy (e.g. methylphenidate,
amphetamines) for ADHD,
irrespective of duration or dose, formulation or brand.
5) Fulfil DSM-5 criteria for alcohol use disorder, and/or stimulant use
disorder, and/or opioid use
disorder, having a minimum of 2 relapses (=drug use on two separate
days, and/or two heavy drinking
days) in the last 30 days as defined by self-report and/or by urine
toxicology
6) One negative urine sample (amphetamine, cocaine, opiates, THC and
benzodiazepines) and
negative alcohol breathalyser test within four days prior to the day of
inclusion
7) One negative urine sample for opiates (dip stick test) immediately
prior to administering the first
dose of study medication
8) Address and telephone in the metropolitan area of each participating
centre, respectively, where the
participant can be reached |
|
E.4 | Principal exclusion criteria |
1) Current DSM-5 diagnosis of severe opioid substance use disorder,
2) Manifestation of withdrawal symptoms or reports of current withdrawal symptoms of opioids
3) Current psychiatric condition considered by the study physician to be severe and/or unstable (e.g., psychosis, schizophrenia, bipolar, suicidal or homicidal)
4) Known or suspected use of any opioid medication or illicit opiates in the last 7 days prior to inclusion
5) Ongoing benzodiazepine pharmacotherapy (medically motivated doses for e g withdrawal treatment during the trial do not constitute a reason for exclusion)
6) Somatic disorder (e.g., cancer, seizure disorder, severe hypertension and liver cirrhosis) determined to be serious in the clinical judgement of the study physician
7) Acute hepatitis or liver damage as evidenced by serum aspartate (AST) or alanine aminotransferase (ALT) concentration greater than three times the upper normal reference range, or serum bilirubin greater than 10% above the upper normal limit.
8) Female subjects who are pregnant or lactating or of child bearing potential who are not using acceptable methods of birth control. Specified as combined hormonal contraception associated with inhibition of ovulation (orally, intravaginal or transdermal), progesterone-only hormonal contraception associated with inhibition of ovulation (oral, injectable,
implantable), intrauterine device (IUD), intrauterine hormone-releasing system (IUS), bilateral tubal occlusion, vasectomized partner, condom or sexual abstinence.
9) Known hypersensitivity to naltrexone, polylactide-co-glycolide (PLG), carboxymethylcellulose or any other compounds of the diluent
10) Likely to receive opioid analgesics in the next 6-months associated with possible or scheduled surgery or procedure
11) Use of an investigational agent in the last 30 days
11) Subjects with a body abnormality precluding the use of the customized needle for intramuscularinjection, based on clinical judgement |
|
E.5 End points |
E.5.1 | Primary end point(s) |
a) Proportion of urine samples free of drugs, where missing urine data is
considered as a positive
sample (with the exclusion of THC), with intention-to-treat analysis and
completers analysis,
respectively.
b) Percent of heavy drinking days defined as five or more drinks for men,
four or more for women
assessed by TLFB.
c) Change in self-rated ADHD symptoms as measured by the Adult ADHD
self-report scale (ASRS v.
1.1) in all participants who took at least the 1st study medication dose. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
Proportion of urine samples free of drugs of abuse (with the exclusion of
THC), in all randomized
participants who took at least 1 study medication dose (ITT and
completers analysis) without imputing
missing data for positives
Proportion of urine samples free of THC (qualitative measure; below the
laboratory's standard cutoff)
in all randomized participants who took at least 1 study medication dose
(ITT)
Time to first relapse (first positive urine toxicology; any of tested drugs)
Self-reported days of drug and alcohol use as measured by TLFB
Proportion of urine samples positive of benzodiazepines
Craving as measured by VAS scale
Depression rating as measured by MADRS-S Scale
Levels of NTX and its metabolite in plasma and correlation with
measures of drug use, craving and
side effects over the course of treatment
Levels of ASAT and ALAT to evaluate medication safety and tolerability-
Levels of PEth to monitor heavy alcohol use Cognitive function as measured by CANTAB between 2 treatment arms
Change in observer-rated ADHD-symptoms as measured with Conners'
Adult ADHD Scale Observer version (CAARS-O: SV)
Drug and alcohol use as measured by TLFB at the follow-up period, post
12 weeks treatment. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
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 | 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.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 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 | 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 | 3 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |