A Phase 1b, Double-blind, Placebo-controlled, Repeat-dose, Safety, Tolerability, Pharmacokinetic, and Pharmacodynamic Study of DCR-AUD in Healthy Volunteers
概览
- 阶段
- 1 期
- 干预措施
- DCR-AUD
- 疾病 / 适应症
- Alcohol Use Disorder
- 发起方
- Dicerna Pharmaceuticals, Inc., a Novo Nordisk company
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
- 状态
- 已完成
- 最后更新
- 3个月前
概览
简要总结
The goal of this clinical trial is to test the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of of repeat doses of DCR-AUD in adult healthy volunteers who are social drinkers.
The main questions it aims to answer are:
- Are repeat doses of DCR-AUD safe and well-tolerated in healthy adults who are social drinkers?
- How does the drug behave inside the human body and how it is removed from the human body?
- What are the symptoms the drug may cause with alcohol consumption?
Participants will:
- Receive multiple doses of DCR-AUD.
- Have assessment visits through Week 24.
- Participate in up to 10 Ethanol Interaction Assessments (EIAs) to see how the body is affected by DCR-AUD.
Researchers will compare the groups of participates who receive study drug with the group of participants who receive placebo to see if the study drug is safe and tolerable and whether the study drug has any real effect.
研究者
入排标准
入选标准
- •21 to 65 years, inclusive, at the time of signing informed consent.
- •Overtly healthy volunteers, as determined by medical evaluation including medical history, physical examination, and laboratory testing.
- •No diagnosis of AUD within the preceding 12 months per Diagnostic and Statistical Manual of Mental Disorders (DSM-5).
- •Social drinkers who consume, on average, 5 to 20 drinks per week for men or 5 to 14 drinks per week for women over the 4 weeks prior to Screening, and not more than 8 drinks in a single day.
- •No evidence of overt or sub-clinical hepatic pathology, as manifest by serologic tests demonstrating hepatic inflammation or compromised hepatic synthetic function (i.e., AST, ALT, GGT, total bilirubin \< 1.5 times the ULN at Screening and Day -1).
- •eGFR ≥ 60 mL/min/1.73 m2 at Screening.
- •No history of significant adverse reaction(s) to alcohol. Participant should be expected to tolerate the amount of alcohol administered during EIAs.
- •Willing to participate in up to 10 EIAs.
- •Has a negative test for SARS-CoV-2 infection on Day -
- •Systolic BP in the range of 80 to 140 mmHg and diastolic BP in the range of 50 to 95 mmHg at Screening. If out of range, BP may be repeated once at the discretion of the Investigator.
排除标准
- •History of any medical condition that may interfere with the metabolism of study intervention or with the clinical and laboratory assessments in this study.
- •History of serious, persistent medical conditions, including liver, gastrointestinal, pulmonary, renal, or cardiovascular abnormalities.
- •History of suicidal attempt at any time or an answer of "yes" on any of the following items in the C-SSRS at Screening:
- •Items 1 or 2 of the Suicidal Ideation section, if ideation occurred in the previous 12 months.
- •Items 4 or 5 of the Suicidal Ideation section, in lifetime.
- •Any item of the Suicidal Behavior section of the C-SSRS, in lifetime.
- •Any history of severe or recent clinically significant depression, anxiety, bipolar disorder, schizophrenia, or other neuropsychiatric disorder that, in the judgement of the Investigator, represents a safety risk to the participant were they to participate in the trial, as informed by the participant's medical history and/or responses to the MINI Screen Questionnaire.
- •History of substance use disorder (SUD) or illicit drug use (excluding cannabis) within the preceding 12 months.
- •History of alcohol withdrawal symptoms including delirium tremens or alcohol-related seizures.
- •Any condition that, in the opinion of the Investigator, would make the participant unsuitable for participation or could interfere with participation in or completion of the study, including:
研究组 & 干预措施
DCR-AUD
Multiple doses of DCR-AUD. Subcutaneous administration of of DCR-AUD.
干预措施: DCR-AUD
DCR-AUD Placebo
Multiple doses of placebo comparator. Subcutaneous administration of Placebo for DCR-AUD, volume to match active single dose
干预措施: Placebo
结局指标
主要结局
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
时间窗: From Day 1 up to 24 Weeks
An Adverse event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study intervention. A TEAE is defined as an AE that begins or that worsens in severity after the study drug has been administered. An SAE is defined as any untoward medical occurrence that at any dose: results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, leads to a congenital anomaly /birth defect, is the other important medical event.
Number of Participants With Severity Grades of TEAEs
时间窗: From Day 1 up to 24 Weeks
An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. A TEAE is defined as an AE that begins or that worsens in severity after the study drug has been administered. As per the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0, Grade 1: mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; treatment not indicated; Grade 2: moderate; minimal, local, or noninvasive treatment indicated; limiting age-appropriate activities of daily living; Grade 3: severe or medically significant but not immediately lifethreatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living; Grade 4: life-threatening consequences; urgent treatment indicated; Grade 5: fatal.
Number of Participants With Change From Baseline in Clinically Significant Abnormal Vital Signs
时间窗: From Baseline (Day -1) up to 24 weeks
Number of participants with change from baseline in clinically significant abnormal vital signs (temperature, pulse rate, respiratory rate, and blood pressure) is presented.
Number of Participants With Change From Baseline in Clinically Significant Abnormal Electrocardiogram (ECG)
时间窗: From Baseline (Day -1) up to 24 weeks
Number of participants with change from baseline in clinically significant abnormal ECG findings (Heart rate, PR interval, QRS interval, QT interval and QT interval using Fridericia's correction \[QTcF\]) is presented.
Number of Participants With Change From Baseline in Clinically Significant Abnormal Laboratory Values
时间窗: From Baseline (Day -1) up to 24 weeks
Number of participants with change from baseline in clinically significant abnormal laboratory values (hematology, clinical chemistry, coagulation and routine urinalysis parameters) is presented.
Number of Participants With Change From Baseline in Clinically Significant Physical Examination Findings
时间窗: From Baseline (Day -1) up to 24 weeks
Number of participants with change from baseline in clinically significant physical examination findings (assessments of the cardiovascular, respiratory, gastrointestinal, neurological, and skin systems and inspection of the injection site) is presented.
次要结局
- Six Symptom Responses During Ethanol Interactions Assessments (EIAs)(Day -1 (baseline), Day 14, Day 28, Day 42, Day 56, Day 70, Day 84, Day 112, Day 140 and Day 168)
- AUC0-last: Area Under the Plasma Concentration Curve From Time Zero to the Last Quantifiable Concentration of DCR-AUD(Day 1, Day 29 and Day 57)
- Cmax: Maximum Observed Plasma Concentration of DCR-AUD(Day 1, Day 29 and Day 57)
- Tmax: Time to Reach the Maximum Plasma Concentration of DCR-AUD (Cmax)(Day 1, Day 29 and Day 57)
- Cmax: Maximum Observed Plasma Concentration of Acetaldehyde(Day -1 (baseline), Day 14, Day 28, Day 42, Day 56, Day 70, Day 84, Day 112, Day 140 and Day 168)
- AUC0-4: Area Under the Concentration Time Curve From Time 0 to Fixed Time 4 of Acetaldehyde(Day -1, Day 14, Day 28, Day 42, Day 56, Day 70, Day 84, Day 112, Day 140 and Day 168)
- Change From Baseline in Heart Rate(Baseline, Day 169)
- Change From Baseline in Facial Skin Temperature(Baseline, Day 169)