Comparative Efficacy of Buprenorphine/Naloxone Versus Methadone in Opioid Use Disorder and Chronic Non-Cancer Pain: A Randomized Clinical Trial

The primary objective of this study is to compare the **effectivity** of Suboxone (buprenorphine/naloxone) and methadone in reducing self-reported opioid misuse among patients with **opioid use disorder** and chronic non-cancer pain. This is clinically relevant as it addresses the challenge of managing opioid dependency while mitigating the risk of misuse, which is a significant concern in the treatment of chronic pain.

Secondary objectives include:

• Comparing the effectivity of Suboxone and methadone on reducing pain.
• Assessing the effects of Suboxone and methadone on well-being.
• Evaluating the impact of Suboxone and methadone on cognition.
• Investigating the effects of Suboxone and methadone on drug use.

The clinical trial involves participants diagnosed with **opioid use disorder** and chronic non-cancer pain. The study population includes both male and female subjects aged 18 and over. Participants are required to have been using a prescribed opioid with a morphine equivalent dose of over 60 mg per day for at least three months. They must meet the criteria for opioid use disorder as per DSM-5 and wish to be treated for this condition. The trial does not include a vulnerable population. The sponsor has not provided the total number of participants. Participants were selected based on their ability to comply with study procedures and provide informed consent. Lifestyle factors such as diet and physical activity are not specified in the available data.

The clinical trial is designed to evaluate the effectiveness of **Suboxone** (buprenorphine/naloxone) compared to **methadone** in reducing self-reported opioid misuse among patients with **opioid use disorder** and chronic non-cancer pain. This study is a randomized, double-blind, controlled trial, ensuring that neither the participants nor the researchers know which treatment the participants are receiving, thus minimizing bias. The trial is expected to last until January 2028, with recruitment having commenced in May 2022. Participants will be involved in the study for a maximum treatment period of 100 days, with the possibility of early termination if they fail to comply with study procedures or if adverse effects necessitate withdrawal.

The sequence of study visits begins with an inclusion (screening) visit, where eligibility is assessed based on criteria such as age (18 or over), diagnosis of chronic non-cancer pain, and opioid use disorder according to DSM-5. Participants must also be using a prescribed opioid with a morphine equivalent dose of over 60 mg per day for at least three months and express a desire to be treated for opioid use disorder. Following the screening, participants will be randomized to receive either Suboxone or methadone. Follow-up visits will occur at regular intervals to monitor treatment efficacy and safety, with primary endpoints assessed using the Current Opioid Misuse Measure (COMM) questionnaire at baseline and two months post-treatment initiation. Secondary endpoints will be evaluated using various questionnaires and tests, including VAS-pain, BPI, and urine toxicology, at two and six months after treatment initiation. The end-of-study visit will conclude the participant's involvement, ensuring all data is collected and any necessary post-trial care is arranged.

The clinical trial involves the administration of **methadone hydrochloride**, a chemical substance used as an experimental medication. Methadone is provided in a pharmaceutical form identified as PHF00169MIG, and is administered orally. The maximum daily dose is 60 mg, with a total maximum dose of 60 mg over a treatment period of up to 100 days. The administration schedule is designed to ensure consistent dosing, and participant compliance is monitored throughout the trial to maintain adherence to the prescribed regimen. Methadone is classified under the ATC code N07BC02.

The comparator treatment in this study is **Suboxone**, which contains the active substances **buprenorphine** and **naloxone**. Suboxone is provided as sublingual tablets, with each tablet containing 2 mg of buprenorphine and 0.5 mg of naloxone. The maximum daily dose for Suboxone is 36 mg, with a total maximum dose of 36 mg over a treatment period of up to 100 days. The sublingual route of administration is employed to optimize absorption and efficacy. Compliance with the dosing schedule is closely monitored to ensure accurate assessment of the treatment's effectiveness. Suboxone is classified under the ATC code N07BC51.

Efficacy in this clinical trial will be assessed by comparing the effectivity of Suboxone (buprenorphine/naloxone) and **methadone** on reducing self-reported opioid misuse. The primary endpoint for evaluating efficacy is the mean score on the Current Opioid Misuse Measure (COMM) questionnaire. This score will be compared from baseline to two months after the initiation of treatment between the Suboxone and methadone treatment groups.

Secondary endpoints include the mean scores on various measures, compared between both treatments from baseline to two and six months after initiation of treatment. These measures include a range of questionnaires such as COMM, VAS-pain, BPI, CSI, VAS-QOL, WHOQOL-BREF, DASS, VAS-craving, OCDS, GPE, ORSDS, FFMQ-SF, SCS, TCQ, and CFQ. Additionally, tests such as quantitative sensory testing, 6-minute walking test, urine toxicology, MoCA, 15WT, SCWT, and PASAT will be utilized. Other parameters include the dose of the drug and treatment retention.