Alcohol use disorder
Conditions
Interventions
0.75mg group:Second stage: random reassignment of groups
Placebo group
:In the second stage, re-randomization was performed to receive 0.3 mg of
1.5mg group:Second stage: random reassignment of groups
0.3mg group:Second stage: random reassignment of groups
Sponsors
Hangzhou Seventh People's Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Are 18 to 75 years of age, inclusive, at the time of signing the informed consent; 2. Must report an average alcohol consumption using TLFB during the 28 days prior to screening (V1) and during the screening period leading up to randomization (V3) as follows: (1). for individuals AMAB: >=20 standard drinks per week (equivalent to at least 280 grams of alcohol per week), and for individuals AFAB: >=10 standard drinks per week (equivalent to at least 140 grams of alcohol per week). Note: For purposes of conversion to grams of alcohol, use the conversion that 1 standard drink is equivalent to 14 grams of alcohol. 3. Alcohol consumption pattern should reflect the participant’s average monthly alcohol intake, sustained for a minimum period of 12 months, as determined through participant self-report and investigator’s clinical judgment; 4. Must report having at least a pre-specified number of HDDs per month at screening (V1) and during the screening period leading up to randomization (V3), as assessed by TLFB. Note: A participant will be excluded from the study if a pre-defined reduction in alcohol consumption is identified between screening (V1) and randomization (V3). To mitigate bias and placebo response, the minimum number of HDDs and the pre-defined reduction in alcohol consumption will be specified in a separate ERB supplement. HDD is defined as for individuals AMAB: >=5 standard drinks per day, and for individuals AFAB: >=4 standard drinks per day. Note: To avoid biased reporting, study participants must not be told the definition of HDDs; 5. Have a current AUD diagnosis as defined by meeting 2 to 3 DSM-5 criteria, at screening (V1); 6. Are seeking treatment and are motivated to stop or cut down on drinking; 7. Have a BMI >=22.0 kg/m^2 at screening (V1) and randomization (V3); 8. Have had a stable body weight for the 90 days prior to randomization (V3) defined as less than 5% body weight reduction. Sex assigned at birth and contraceptive/barrier requirements ; 9. Are individuals AMAB or AFAB, including both IOCBP and INOCBP. Contraceptive use by participants should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. For the reproduction definitions and the contraception requirements of this protocol, refer to Section 10.4. Study procedures ; 10. Are reliable and willing to make themselves available for the duration of the study and attend required study visits, and are willing and able to follow study procedures as required, such as self-inject study intervention Note: Participants who are not able to perform the injections must receive assistance from a support person trained to administer the study intervention. store and use the provided blinded study intervention, as directed maintain electronic and paper study diaries, as applicable, and complete the required questionnaires. Informed consent 11. Are capable of giving signed informed consent as described in Section 10.1.3, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
Exclusion criteria
Exclusion criteria: 1.AUD-related 12. Between screening (V1) and randomization (V3), have initiated cognitive behavioral therapy or other psychotherapy focused on treatment of AUD, or are planning to initiate such therapy during the trial. Exception: Alcoholics Anonymous (AA), self-help groups, supportive psychotherapy, or other general counseling that has already been initiated and has been ongoing for at least 30 days before screening (V1) is permitted; 2. Within 180 days prior to screening (V1) or between screening (V1) and randomization (V3): Have required inpatient management for severe or complicated alcohol withdrawal syndrome, in the opinion of the investigator (Section 10.9 details the categorization of withdrawal severity) Have required a medication to prevent or treat alcohol withdrawal in an outpatient setting, or Are currently at significant risk of suffering an acute (defined as immediately following the cessation of alcohol use) alcohol withdrawal syndrome, for example, seizure and delirium tremens, in the opinion of the investigator, or as determined by CIWA-Ar score >=10 at screening (V1) and randomization (V3); 3. Have a known history of alcoholic ketoacidosis or Mallory-Weiss syndrome (esophageal tears secondary to vomiting); 4. Have evidence of current or within the past 180 days prior to screening (V1), history of any substance use disorder(s) of any severity with a pattern of persistent illicit or nonprescribed substance use as indicated by clinical interview, except alcohol, nicotine, or caffeine; 5. Meet the DSM-5 criteria of moderate-to-severe cannabis use disorder as per SCID-5 at screening (V1). Note: Participants with mild cannabis use disorder are permitted; 6. Cannot agree to refrain from all use of drug(s) of abuse, except for alcohol, nicotine, and cannabis, during the study; 7. Have a positive urine drug screen for drugs of abuse (other than nicotine or cannabis) at screening (V1) and/or randomization (V3). Note: Positive urine drug screen for use of any drugs of abuse will not be considered illicit if it is a prescribed concomitant medication for a known preexisting condition; 8. Have required acute care or inpatient treatment for clinically significant alcohol-related injury or related illness in the 30 days before screening (V1) or between screening (V1) and randomization (V3); 9. Have a lifetime history or current diagnosis of any eating disorder according to the DSM- 5 criteria; 10. Have modified psychoactive medication dosing regimens for a current psychiatric condition or disorder including, but not limited to, antidepressants, antipsychotics, or mood stabilizers, in the past 90 days prior to screening (V1). Exception: Prescription benzodiazepines on a pro re nata (as needed) basis for any symptom relief of anxiety or insomnia is allowed. Note: Use for alcohol withdrawal symptoms is not permitted; 11. Have a history of significant active or unstable DSM-5 major depressive disorder, suicidal ideation, or other severe psychiatric disorder (such as schizophrenia, schizoaffective disorder, or other serious mood disorder) within the past 180 days prior to screening (V1). OR In the investigator’s assessment, have any significant mental health disorder that may put the individual at higher risk of study participation. Note: In the investigator’s assessment, individuals whose disease state is considered stable for the past 180 days prior to screening (V1) and expected to remain stable throughout the course of the study ma
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Dual primary endpoint (overall reduction in alcohol consumption from baseline to endpoint);For brenipatide responders in Phase Ib: Demonstrate that brenipatide (combined doses) is superior to placebo in reducing total alcohol consumption; | — |
Secondary
| Measure | Time frame |
|---|---|
| Percentage of participants without HDD;Daily alcohol intake;Drinking cravings (desires);Number of days of abstinence;Weight;Quit drinking; | — |
Countries
China
Contacts
Public ContactWanjun Guo
Hangzhou Seventh People's Hospital
Outcome results
None listed