Evaluation of Sunobinop Tosilate on Alcohol Consumption and Craving in Patients with Moderate to Severe Alcohol Use Disorder: A Randomized, Double-Blind, Placebo-Controlled Study
- Trial ID
- 2024-517105-85-00
- Protocol
- SUN2023
- Sponsor
- Knoa Pharma LLC
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate whether **sunobinop** compared to placebo will reduce the percent of heavy drinking days in subjects diagnosed with moderate to severe **alcohol use disorder** (AUD) who are seeking treatment. This is clinically relevant as reducing heavy drinking days can significantly improve health outcomes and quality of life for individuals with AUD.
Secondary objectives include:
- Evaluating whether sunobinop compared to placebo will reduce the number of drinks ingested per day.
- Assessing whether sunobinop compared to placebo will reduce the percent of days of drinking.
- Determining whether sunobinop compared to placebo will reduce alcohol consumption that corresponds to a two-level reduction in WHO Risk Level, based on grams of alcohol consumed per day.
Participants
The clinical trial involves a total of **100 participants** diagnosed with **alcohol use disorder (AUD)**, as defined by the Diagnostic and Statistical Manual of Mental Disorders, 5th edition Text Revision (DSM-V-TR). The study population includes both male and female subjects aged 18 years and older. Participants are required to have experienced four or more heavy drinking days in each of the four weeks prior to the baseline visit. The trial does not include a vulnerable population. Participants are currently seeking treatment for AUD and must comply with specific lifestyle considerations, such as using reliable contraception methods if of childbearing potential. The selection criteria ensure that participants are willing to adhere to the protocol, including dosing instructions, daily electronic diary completion, and clinic visit attendance. The trial aims to evaluate the efficacy of sunobinop compared to placebo in reducing the percentage of heavy drinking days.
Plans and Procedures
The clinical trial is designed as a **randomized**, **double-blind**, **placebo-controlled**, parallel-group Phase 2 study aimed at evaluating the impact of Sunobinop (V117957) on alcohol consumption and craving in subjects diagnosed with moderate to severe **alcohol use disorder**. The trial is divided into two parts: Part A focuses on alcohol consumption, while Part B addresses alcohol craving. The primary objective is to assess whether Sunobinop, compared to placebo, reduces the percentage of heavy drinking days. Secondary endpoints include the number of standard unit drinks, the percentage of days drinking, and the WHO Risk Level of alcohol consumption, all assessed using the Timeline Followback interview.
The trial will commence with a screening visit to confirm eligibility based on inclusion criteria, such as age, diagnosis of alcohol use disorder, and treatment-seeking status. Participants must have experienced four or more heavy drinking days in each of the four weeks prior to the baseline visit. The study will involve multiple follow-up visits to monitor progress and adherence to the protocol, including dosing instructions and daily electronic diary completion. The trial is expected to last approximately eight weeks, with the estimated recruitment start date on March 31, 2025, and an estimated end date of September 30, 2025.
Participants will be randomly assigned to receive either Sunobinop at varying doses (0.5 mg, 1 mg, or 2 mg) or a placebo, administered orally in tablet form. The placebo tablets are identical in composition to the active formulation, except for the absence of the active pharmaceutical ingredient, replaced by microcrystalline cellulose. The maximum daily dose for Sunobinop is 2 mg, with a total maximum dose of 112 mg over the treatment period. The study will conclude with an end-of-study visit to evaluate the overall outcomes and any adverse events.
Participant involvement is expected to last for the duration of the treatment period, approximately eight weeks. Conditions that may lead to early termination from the study include non-compliance with the protocol, adverse reactions, or withdrawal of consent. The trial is not classified as low intervention and is conducted under the authorization of relevant regulatory bodies, ensuring adherence to ethical and scientific standards.
Treatment
The clinical trial involves the administration of **Sunobinop** in three different dosages: 0.5 mg, 1 mg, and 2 mg. Sunobinop is provided in tablet form and is administered orally. The active substance in these tablets is **Sunobinop Tosilate**, a chemical compound. The maximum daily doses for the 0.5 mg, 1 mg, and 2 mg tablets are 0.5 mg, 1 mg, and 2 mg, respectively. The total maximum dose over the treatment period is 28 mg for the 0.5 mg tablet, 56 mg for the 1 mg tablet, and 112 mg for the 2 mg tablet. The treatment period for each dosage is up to 8 weeks. Compliance with the dosing schedule is monitored throughout the trial.
The trial also includes a placebo group, which receives **V117957 Tablets Placebo**. The placebo tablets are identical in appearance to the active Sunobinop tablets but do not contain the active pharmaceutical ingredient (API). Instead, the API is replaced with an additional amount of microcrystalline cellulose. The placebo is administered in the same manner as the active drug, ensuring blinding of the study participants and investigators. The placebo serves as a control to evaluate the efficacy of Sunobinop in reducing alcohol consumption and craving in subjects diagnosed with moderate to severe alcohol use disorder.
Efficacy
Efficacy in this clinical trial will be assessed by evaluating the impact of **Sunobinop** on alcohol consumption and craving in subjects diagnosed with moderate to severe alcohol use disorder. The primary endpoint for efficacy evaluation is the percent of heavy drinking days (HDD), which will be assessed using the Timeline Followback interview. Secondary endpoints include the number of standard unit drinks, percent of days drinking (PDD), and the WHO Risk Level of alcohol consumption, all of which will also be measured using the Timeline Followback interview.
The Timeline Followback interview is a validated tool used to collect detailed information on alcohol consumption patterns. Efficacy parameters will be collected at specified timepoints throughout the trial, although specific timepoints are not detailed in the provided data. The analysis will focus on comparing the outcomes between the treatment group receiving Sunobinop and the placebo group to determine the drug's effectiveness in reducing alcohol consumption and craving.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Male and females age >= 18 years.
- Diagnosis of moderate or severe alcohol use disorder as defined by the Diagnostic and Statistical Manual of Mental Disorders 5th edition Text Revision (DSM-V-TR) and confirmed by Structured Clinical Interview for DSM Disorders (SCID-5).
- Currently seeking treatment for alcohol use disorder
- Has 4 or more heavy drinking days (HDD) in each of the 4 weeks prior to baseline visit as assessed by Timeline Followback interview. HDD is defined as 4 or more standard drinks per day for females and 5 or more standard drinks per day for males. A standard drink is defined as 12 ounces (~355 mL) of 5% beer, 5 ounces (150 mL) of 12% wine, or 1.5 ounces (44mL) of 80-proof (40%) distilled spirits.
- Males and females: - A male subject with a heterosexual partner who is a woman of childbearing potential must either be vasectomized or agree to use condoms during the trial and for 30 days following the treatment period. - A female subject is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: * Not a woman of childbearing potential (WOCBP). Females who are postmenopausal mush have beem postmenopausal > = 1 year and have elevated serum FSH. * Female subjects of childbearing potential must agree to use a reliable method of contraception with a failure rate of less than 1% per year when used consistently and correctly such as implants, injectables, combined oral contraceptives, some intra uterine devices [IUDs], heterosexual abstinence or vasectomized partner during the trial and for 30 days following the tratment period. A female is considered to be of childbearing potential unless she has had a hysterectomy, has undergone tubal litigation or is at least one year post-menopausal with elevated serum FSH.
- Willing to be compliant with the protocol (including dosing instructions, daily electronic diary completion and clinic visit attendance) and able to read and understand questionnaires.
Exclusion Criteria
- Subjects that meet current DSM-5 criteria for moderate or severe substance use disorder other than alcohol and nicotine.
- Subjects with clinically unstable medical, neurologic or psychiatric conditions, or any other medical condition that, in the investigator's opinion, is inadequately treated and precludes entry into the study. Minor or well-controlled medical conditions that in the opinion of the investigator would not affect the subject's safety or interfere with study assessments may be allowed.
- Subjects at significant risk of acute withdrawal syndrome in the opinion of the investigator; or score >8 on the Clinical Institute Withdrawal Assessment of Alcohol Scale Revised (CIW A-Ar) at screening; or had prior seizures (other than febrile seizure) or other conditions that would place the patient at increased risk of seizure; or are taking anticonvulsants.
- Subjects who are prescribed prohibited medications for medical or psychiatric indications (see Section 6.6.1.). NOTE: Subjects should not discontinue medically indicated treatments to meet criteria for study participation.
- Subjects with clinically significant kidney disease in the opinion of the investigator or screening estimated glomerular filtration rate (eGFR) < 60mL/min/1.73 m2
- Subjects with clinically significant liver disease in the opinion of the investigator or screening value > = 3 times the upper limit of normal for aspartate transaminase (AST/SGOT) or alanine transaminase (ALT/SGTP) or a screening bilirubin value > = 1.5 mg/dL.
- Subjects with a screening electrocardiogram showing a QTcF value (QT data corrected for heart rate using the Fridericia formula) of >= 470 msec for females or >= 450 msec for males, or other ECG findings that, in the investigator's opinion, would preclude participation in the study.
- Subjects with suicidal ideation associated with actual intent and a method or plan in the past 1 year ("Yes" answer on items 4 or 5 of the C-SSRS); subjects with active suicidal ideation ("Yes" answer on item 2 or 3 of the C-SSRS); a previous history of suicidal behaviors in the past 2 years ("Yes" answer to any of the suicidal behavior items of the C-SSRS), or any lifetime history of serious or recurrent suicidal behavior.
- Subjects that have used an investigational drug within 30 days (90 days for biologics) or participated in an investigational study within 30 days prior to screening.
- Females who are pregnant or lactating or planning to become pregnant during the study.
- Subjects who have ongoing legal issues that require abstinence from alcohol or have legal charges that have the risk of incarceration during the study period.
- Subjects that do not have a stable living situation or plan to move during the study period.
- Subjects who, in the opinion of the investigator, are unsuitable to participate in this study for any other reason.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Romania | Not Recruiting | 31 Mar 2025 | 100 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
V117957 Tablets Placebo - The placebo formulation has the same qualitative composition as the corresponding active formulation of V117957 Tablets, with the absence of the API. The only difference in the dosage forms of V117957 Tablets and the placebo are that V117957 is replaced in the placebo tablet with an additional amount of microcrystalline cellulose. | Placebo | N/A | — | — | — | N/A |
Sunobinop 1 mg | Test | TABLET | ORAL | 1 | 8 | PRD11668509 |
Sunobinop 2 mg | Test | TABLET | ORAL | 2 | 8 | PRD11668510 |
Sunobinop 0.5 mg | Test | TABLET | ORAL | 0.5 | 8 | PRD11668508 |