Evaluation of Dexamfetamine Sulfate in Reducing Illicit Amphetamine Use in Adults with Comorbid Amphetamine and Opioid Dependence Undergoing Opioid Agonist Therapy

The primary objective of this study is to evaluate the impact of 12 weeks of daily prescribed oral **dextroamphetamine** versus placebo on the use of illicit amphetamines and the total amount of amphetamines used in patients with comorbid dependencies to amphetamines and opioids undergoing opioid agonist treatment. This is clinically relevant as it aims to address the challenge of managing amphetamine dependence in individuals already receiving treatment for opioid dependence, potentially offering a therapeutic strategy to reduce illicit drug use and improve treatment outcomes.

Secondary objectives include assessing the impact of dextroamphetamine on various health and social parameters over two 12-week periods. These parameters are:

• Mental health
• Physical health
• Quality of life
• Cognitive functioning
• Treatment adherence
• Comorbid substance use
• Criminal activity
• Private economy

The clinical trial involves a **study population** of both male and female participants aged between 18 and 65 years. Participants are required to be overtly healthy, as determined by a comprehensive medical evaluation, including medical history, physical examination, laboratory tests, and cardiac monitoring. The trial specifically targets individuals with comorbid dependencies to amphetamines and opioids, as defined by the ICD-10 criteria, with a minimum duration of amphetamine dependence of three years and an average frequency of use of at least four days a week in the last 28 days. Participants must also have concurrent opioid dependence and be receiving a stabilized dose of opioid agonist treatment (OAT) medication for the last 28 days. The trial does not involve a vulnerable population. Lifestyle considerations such as diet and physical activity are not specified. The sponsor has not provided information regarding the total number of participants in the study. Key inclusion criteria include the ability to provide informed consent and, for females of child-bearing potential, the use of contraception consistent with local regulations. The eligibility of participants is determined through clinical assessment by a medical doctor.

The clinical trial is designed as a **randomized**, **double-blind**, **controlled** study to evaluate the impact of **dexamfetamine** substitution on the use of illicit amphetamines in adults with comorbid dependencies to amphetamines and opioids undergoing opioid agonist treatment. The trial will involve a comparison between daily prescribed oral **dexamfetamine** and a placebo over a period of 12 weeks. The primary objective is to assess the differences in the proportion of positive urinary tests for illicit amphetamines and the mean total self-reported quantity of amphetamines use between the intervention and control arms. Secondary endpoints include psychological distress, psychosis, ADHD, quality of life, executive cognitive performance, fatigue, treatment satisfaction, adherence to opioid agonist treatment, and other health-related outcomes.

The trial will commence with a screening visit to determine participant eligibility based on criteria such as age, health status, and dependency history. Participants must be between 18 and 65 years old, overtly healthy, and have a documented dependency on amphetamines and opioids according to ICD-10 criteria. Female participants of child-bearing potential must use contraception, and all participants must provide informed consent. Following the screening, eligible participants will be randomized to receive either **dexamfetamine** or placebo. Study visits will occur regularly throughout the 12-week treatment period to monitor safety, efficacy, and adherence to the treatment protocol. The end-of-study visit will involve a comprehensive evaluation of the primary and secondary endpoints.

Participant involvement is expected to last for the entire 12-week duration of the trial, with the possibility of early termination if significant adverse events occur or if the participant withdraws consent. The trial is estimated to conclude by December 31, 2027, with recruitment starting on February 1, 2024. The study is not classified as low intervention and is categorized under phase 4, allowing for publication of results upon completion. The trial will adhere to all ethical guidelines and regulatory requirements to ensure the safety and well-being of participants throughout the study.

The clinical trial involves the administration of **Dexamfetamine**, a pharmaceutical agent used to assess its impact on the use of illicit amphetamines in adults with comorbid dependencies to amphetamines and opioids. **Dexamfetamine** is provided in the form of a **tablet** and is administered orally. The active substance in the medication is **dexamfetamine sulfate**, a chemical compound known for its stimulant properties. The maximum daily dose of **Dexamfetamine** is 120 mg, with a total treatment period not exceeding 28 days. The medication is produced by Helse Bergen and is not formulated for pediatric use. Participants are required to adhere to the prescribed dosing schedule, and compliance will be monitored throughout the study.

The study also includes a **placebo** treatment, which is designed to match the active treatment in appearance but contains no active pharmaceutical ingredients. The placebo is used to maintain the double-blind nature of the trial, ensuring that neither the participants nor the investigators are aware of the treatment assignments. The placebo is administered orally in a form that mimics the **tablet** formulation of the active treatment. This allows for a direct comparison between the effects of **Dexamfetamine** and the placebo on the participants' use of illicit amphetamines. Compliance with the placebo administration will be monitored in the same manner as the active treatment to ensure the integrity of the study results.

Efficacy in this clinical trial will be assessed by evaluating the impact of daily prescribed oral **dexamfetamine** versus placebo on the use of illicit amphetamines in adults with comorbid dependencies to amphetamines and opioids undergoing opioid agonist treatment. The primary endpoints for efficacy evaluation include the differences in the proportion of positive urinary tests for illicit amphetamines and the mean total self-reported quantity of amphetamines use (mg/day) between the intervention and control arms during the first 12 weeks. The dosage of illicit amphetamines will be converted to the prescribed dexamfetamine dosage and added to the prescribed dosage for analysis.

Secondary endpoints will encompass a range of parameters, including psychological distress measured by the SCL-10, psychosis assessed using PANSS (P1, P3, A9) and LSHS-E, ADHD symptoms evaluated by ASRS, and quality of life assessed through EQ-5D-5L, ICECAP, and life satisfaction measures. Additional secondary endpoints include executive cognitive performance (TMT B), fatigue (FSS-3), treatment satisfaction (VAS), adherence to opioid agonist treatment (days of drop-out), days of use of illicit amphetamines, and the proportion of other illicit substances and alcohol use (self-reports and urinary tests). Other parameters include injection-related infections, HCV RNA incidence, violence risk (BVC and PANSS: P4 and P7), criminality, sleep (ISI), private economy, and craving and withdrawals to amphetamines.