Evaluate the Efficacy and Safety of Naltrexone Hydrochloride Implant in Patients With Alcohol Use Disorder

Phase 3Not Yet RecruitingNCT07433413

Shenzhen Sciencare Medical Industries Co., Ltd.240 enrolled

Overview

This is a multicenter, randomized, double-blind, placebo-controlled Phase III clinical trial. The study plans to enroll 240 adult patients with Alcohol Use Disorder (AUD). After providing written informed consent and undergoing screening for eligibility criteria, eligible subjects will be randomized in a 2:1 ratio to receive treatment in either the experimental group (1.5 g Naltrexone Hydrochloride Implant plus non-specific supportive psychotherapy) or the control group (placebo implant plus non-specific supportive psychotherapy). On Day 1, subjects will receive a single subcutaneous implantation via a small abdominal incision, receiving either the Naltrexone Hydrochloride Implant or the placebo implant. Following implantation, subjects will be hospitalized for at least 2 hours (the investigator may extend this observation period up to 3 days based on the patient's condition). Subjects will change the wound dressing by themselves on postoperative Day 3. Efficacy and safety assessments will continue through Week 24 post-randomization/dosing, involving a total of 11 visits. Among these, Visit 5 (Week 3) will be conducted via telephone, while all other visits will be performed as outpatient clinic visits.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

240

Conditions

Alcohol Use Disorder (AUD)

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

Inclusion Criteria: Diagnosis of moderate to severe Alcohol Use Disorder (AUD) based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria (meeting four or more diagnostic criteria; refer to Appendix 1 for details). Exclusion Criteria: Pregnant, breastfeeding, or pregnant with a positive pregnancy test at screening. This includes women of childbearing potential planning to become pregnant during the study. Note: Women of childbearing potential are defined as those who are biologically capable of becoming pregnant. To be considered not of childbearing potential, a female subject must meet one of the following: 1) Have had a hysterectomy or bilateral oophorectomy; or 2) Be post-menopausal, defined as having no menses for more than 12 consecutive months. Significant abnormality in liver function (e.g., AST or ALT \> 3 times the upper limit of normal), liver failure (e.g., presence of ascites, jaundice, coagulopathy, hepatorenal syndrome, or hepatic encephalopathy), or liver/gallbladder ultrasound findings that may significantly impact the assessment of the investigational drug's efficacy and safety. History of severe pancreatitis or severe delirium tremens. Presence of any severe/uncontrolled systemic diseases (e.g., respiratory, cardiovascular, gastrointestinal, neurological, hematological, urogenital, or endocrine disorders) or psychiatric disorders (e.g., Major Depressive Disorder, Schizophrenia, Bipolar Disorder) or other major illnesses, which in the Investigator's judgment could interfere with the provision of informed consent, make study participation unsafe, complicate the interpretation of study outcome data, or otherwise affect the achievement of study objectives. Potential need for hospitalization or surgery during the study period, including scheduled elective surgeries that cannot be postponed. Diagnosis of a Substance Use Disorder (other than alcohol or tobacco) based on DSM-5 criteria within the past year (prior to randomization/dosing), such as benzodiazepines, amphetamines, opioids, or cocaine. Use of anti-relapse medication (e.g., Naltrexone) or receipt of systemic psychological support therapy within 30 days prior to randomization/dosing. Currently receiving treatment for substance use disorders (e.g., opioids, amphetamines, alcohol), or received opioids within 7 days prior to randomization/dosing, or may require opioid treatment during the study; or positive urine drug screen for opioids, cannabis, amphetamines, etc., or positive naloxone challenge test on the day of randomization/dosing. Suicidal risk based on Investigator's clinical judgment, or history of suicidal or self-mutilating behavior. Allergy to the investigational product or its excipients (polylactic acid, magnesium stearate) or local anesthetics. Currently participating in any investigational drug or device study, or has used any investigational drug or device within 30 days prior to randomization/dosing. Skin infection at the implantation site, systemic skin disease, or keloid scarring that may affect the assessment of the investigational drug's efficacy and safety. Clinical or laboratory evidence of Human Immunodeficiency Virus (HIV) or Syphilis infection.

Outcomes

Primary Outcomes

Proportion of Heavy Drinking Days During the 24-Week Observation Period Post-Randomization/Post-Dosing

Specifically, this is calculated as the number of heavy drinking days divided by the number of days at risk for heavy drinking, with the aforementioned days counted up to the date of discontinuation of efficacy observation. "Days at risk for heavy drinking" are defined as the number of days a subject is under efficacy observation starting from the date of hospital discharge following implant administration. Drinking rates are assessed based on the Timeline Follow-Back (TLFB) method, utilizing the daily drinking record form (Appendix 11) completed by the subject and their family members. Heavy drinking is defined as consumption of ≥5 standard drinks per day for males and ≥4 standard drinks per day for females.

Time frame: 24-Week

Secondary Outcomes

Reduction of ≥2 levels in WHO alcohol risk grading

Specifically, this refers to the change from the baseline WHO alcohol risk level to the level assessed during weeks 21-24. The baseline WHO alcohol risk level is calculated based on TLFB alcohol consumption data collected during the 2-week period prior to detoxification. The WHO alcohol risk level assessed at weeks 21-24 post-randomization/post-dosing is calculated based on the daily drinking record form completed by the subject and their family members.

Time frame: 24-week

Alcohol Consumption (Total Amount Consumed Over 24 Weeks)

Calculated based on the daily drinking record form (completed by the subject and their family members) using the Timeline Follow-Back (TLFB) method.

Time frame: 24-week

Percentage of Days Abstinent (PDA)

Specifically, this is calculated as the number of days with no alcohol consumption divided by the number of days at risk. The aforementioned days are counted up to the date of discontinuation of efficacy observation. "Days at risk" are defined as the number of days a subject is under efficacy observation, starting from the date of hospital discharge following implant administration. This metric is calculated based on the drinking record form using the Timeline Follow-Back (TLFB) method. Alcohol consumption is defined as any recorded drinking behavior, regardless of the amount or frequency consumed.

Time frame: 24-week

Longest Continuous Abstinence Duration

Specifically, this refers to the longest consecutive number of days without alcohol consumption from the time of randomization/dosing until loss to follow-up or study completion. This metric is calculated based on the daily drinking record form (completed by the subject and their family members) using the Timeline Follow-Back (TLFB) method.

Time frame: 24-week

Proportion of Participants Without Heavy Drinking During the Study Observation Period

Specifically, this refers to the proportion of subjects who did not engage in heavy drinking from randomization/dosing until loss to follow-up or study completion. This metric is calculated based on the daily drinking record form (completed by the subject and their family members) using the Timeline Follow-Back (TLFB) method.

Time frame: 24-week

Alcohol Craving Score

Craving scores are assessed at 1, 2, 4, 8, 12, 16, 20, and 24 weeks post-randomization/post-dosing using a Visual Analog Scale (VAS). VAS Assessment: The VAS consists of a horizontal line. The left end is marked as "0," indicating "No craving," and the right end is marked as "10," indicating "Extreme craving." The intermediate sections represent varying degrees of craving. Subjects are asked to self-evaluate and select a numerical value between 0 and 10 that best represents their current level of craving. A higher numerical value indicates a higher degree of craving.

Time frame: 24-week

Personal and Social Functioning

Assessment of personal and social functioning at 4, 8, 12, 16, 20, and 24 weeks post-randomization/post-dosing using the Personal and Social Performance scale (PSP). PSP Total Score Rating Guidelines 71-100: These ratings reflect mild difficulties. 31-70: These ratings reflect various degrees of functional impairment. 0-30: These ratings reflect functional disability, indicating that the patient requires active support or close supervision

Time frame: 24-week

Pleasure Scale Score (Snaith-Hamilton Pleasure Scale, SHAPS)

Assessment of the level of agreement regarding pleasure responses in various enjoyable situations at 4, 8, 12, 16, 20, and 24 weeks post-randomization/post-dosing. This is evaluated using the Snaith-Hamilton Pleasure Scale (SHAPS).

Time frame: 24-week

Family APGAR Questionnaire

A qualitative assessment of family members' satisfaction regarding five basic family functions at 4, 8, 12, 16, 20, and 24 weeks post-randomization/post-dosing. This assessment is conducted using the Family APGAR Questionnaire.

Time frame: 24-week

Breath Alcohol Concentration (BrAC)

Measurement of breath alcohol concentration at 1, 2, 4, 8, 12, 16, 20, and 24 weeks post-randomization/post-dosing using a digital breath alcohol tester.

Time frame: 24-week

Proportion of Participants Requiring Hospitalization for Detoxification

Specifically, this refers to the proportion of subjects who required hospitalization for alcohol detoxification following randomization/dosing.

Time frame: 24-week

Evaluate the Efficacy and Safety of Naltrexone Hydrochloride Implant in Patients With Alcohol Use Disorder

Overview

Conditions

Interventions

Eligibility

Outcomes

Primary Outcomes

Secondary Outcomes