Phase II Clinical Study on the Efficacy and Safety of Naltrexone Implant in Patients With Alcohol Use Disorder

A Multicenter, Randomized, Double-blind, Placebo-controlled Phase II Clinical Study to Evaluate the Efficacy and Safety of Different Doses of Naltrexone Implant in Patients With Alcohol Use Disorder

This is a multicenter, randomized, double-blind, placebo-controlled Phase II clinical trial. The study plans to enroll 210 adult patients with alcohol use disorder. After signing the informed consent form and undergoing screening based on inclusion/exclusion criteria, eligible participants will be randomly assigned to the low-dose group (naltrexone implant 0.9 g + general supportive psychological counseling), high-dose group (naltrexone implant 1.5 g + general supportive psychological counseling), and control group (placebo + general supportive psychological counseling) in a 1:1:1 ratio. On Day 0, participants will receive a single subcutaneous abdominal incision implantation with either 0.9 g or 1.5 g of naltrexone implant or placebo. Efficacy assessment will follow up to 24 weeks after randomization/dosing, while safety assessment will follow up to 48 weeks. There will be a total of 13 follow-up visits. Except for Day 3 (Visit 3) and Week 36 (Visit 12), which are telephone follow-ups, all other visits will be outpatient follow-ups. The first 24 weeks of the study will be double-blind. After completing the Week 24 follow-up, all participants will undergo efficacy assessment. Then they will enter the open-label observation period, followed up until Week 48.

Inclusion Criteria:

1. Voluntarily participate in the clinical study; fully understand and are informed about the study and sign the informed consent form; willing and able to comply with and complete all trial procedures; |
2. Age ≥18 years at the time of signing the informed consent form; |
3. Diagnosis of moderate or severe Alcohol Use Disorder based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) (meeting four or more diagnostic criteria, see Appendix 1 for details); |
4. Completed detoxification treatment and had no significant alcohol withdrawal symptoms for at least one week (≥7 days) prior to randomization/administration [Clinical Institute Withdrawal Assessment for Alcohol-Revised (CIWA-Ar) score <7 points (see Appendix 2 for specific assessment method)]; |
5. Able to provide Timeline Followback (TLFB) alcohol use information for the 2 weeks during detoxification and/or prior to screening; |
6. Had at least two heavy drinking days per week during the 4 weeks of detoxification and/or prior to screening; |
7. Qualified subjects of childbearing potential (male and female) must agree to use effective contraceptive methods (hormonal or barrier method or abstinence) with their partner during the trial period.

Exclusion Criteria:

1. The investigator judges that participation in this study is not in the best interest of the subject, or any other condition that would make it unsafe for the subject to participate in the study; |
2. Pregnancy, positive pregnancy test for women of childbearing potential, or lactating women, including women of childbearing potential planning to become pregnant during the study period. Note: Women of childbearing potential here refer to women capable of becoming pregnant. Must meet the following criteria, regardless of sexual orientation or tubal ligation: 1) No hysterectomy or bilateral oophorectomy; or 2) Have not been naturally postmenopausal for more than 12 consecutive months (i.e., have had menses at any time in the preceding 12 consecutive months); |
3. Significant abnormal liver function (e.g., AST or ALT >2 times the upper limit of normal) or liver failure [including but not limited to: ascites, prolonged prothrombin time, International Normalized Ratio (INR) ≥1.7, esophageal variceal disease] or hepatobiliary ultrasound shows results that significantly impact the judgment of the study drug's efficacy and safety; |
4. Suffering from clinically uncontrolled active infectious diseases, such as active Hepatitis B [Hepatitis B surface antigen (HBsAg) positive and Hepatitis B virus (HBV) DNA copy number >1000 IU/ml], active Hepatitis C [Hepatitis C virus antibody positive and Hepatitis C virus (HCV)-RNA positive], etc.; |
5. History of congenital bleeding disorders (e.g., hemophilia) or any clinically significant active bleeding, or platelet dysfunction, or prothrombin time (PT) exceeding the upper normal limit by more than 3 seconds, or platelet count <50×10⁹/L; |
6. Previous history of severe pancreatitis or severe delirium tremens;
7. In the investigator's judgment, the subject has any severe/uncontrolled systemic disease (e.g., respiratory, circulatory, digestive, nervous, hematological, urogenital, endocrine systems) or mental illness (e.g., major depressive disorder, schizophrenia, bipolar disorder, etc.) or other major diseases that the investigator believes would prevent providing informed consent, make participation in the study unsafe, complicate the interpretation of study outcome data, or otherwise affect the achievement of study objectives;
8. Likely to require hospitalization or surgery during the study period, including planned elective surgery or hospitalization that cannot be postponed;
9. Diagnosed with substance use disorder (other than alcohol) according to DSM-5 criteria within the current (within one year prior to randomization/administration) period, such as: benzodiazepines, amphetamines, opioids, or cocaine, etc.; |
10. Used medications for relapse prevention (e.g., naltrexone, etc.) or received systematic psychological support therapy within 30 days prior to randomization/administration;
11. Currently receiving treatment for opioid, amphetamine, alcohol, or other substance use disorders, or received opioids within 7 days prior to randomization/administration, likely to require opioid treatment during the study period, or positive urine test for opioids, marijuana, amphetamines, etc., or positive naloxone challenge test on the day of randomization/administration; 12. Allergy to the investigational drug or its excipients (polylactic acid, magnesium stearate), or local anesthetics; |

13. Currently participating in any investigational drug or device study, or used any investigational drug or device within 30 days prior to randomization/administration; 14. Skin infection at the implantation site or systemic skin disease judged to potentially affect the efficacy and safety evaluation of the investigational drug; | 15. Clinical or laboratory evidence of Human Immunodeficiency Virus (HIV) or syphilis carrier/infection. |