Phase 1
N=36
Study of DCR-AUD in Healthy Volunteers
Alcohol Use Disorder (AUD)
Bottom Line
View on ClinicalTrials.gov: NCT05021640 ↗Enrolled (actual)
36
Serious AEs
0.0%
Results posted
Dec 2024
Primary outcome: Primary: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) — 4; 5; 4; 2 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- DCR-AUD (Drug); Placebo for DCR-AUD (Drug)
- Age
- Adult, Older Adult · 21+ yrs
- Sex
- All
- Sponsor
- Dicerna Pharmaceuticals, Inc., a Novo Nordisk company
- Primary completion
- Dec 2022
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) |
4; 5; 4; 2; 9; 0 | — |
| PRIMARY Number of Participants With Severity Grades of TEAEs |
4; 5; 4; 2; 9; 2 | — |
| PRIMARY Number of Participants With Dose-limiting Toxicities (DLTs) as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 |
0; 0; 0; 0; 0 | — |
| PRIMARY Number of Participants With Change From Baseline in Clinically Significant Abnormal Vital Signs |
0; 0; 0; 0; 0 | — |
| PRIMARY Number of Participants With Change From Baseline in Clinically Significant Abnormal Electrocardiogram (ECG) Findings |
0; 0; 0; 0; 0 | — |
| PRIMARY Number of Participants With Change From Baseline in Clinically Significant Abnormal Laboratory Values |
0; 0; 0; 0; 0 | — |
| PRIMARY Number of Participants With Change From Baseline in Clinically Significant Physical Examination Findings |
0; 0; 0; 0; 0 | — |
| SECONDARY AUC0-last: Area Under the Plasma Concentration Curve From Time Zero to the Last Quantifiable Concentration of DCR-AUD |
5710; 19300; 49000; 106000 | — |
| SECONDARY Cmax: Maximum Observed Plasma Concentration of DCR-AUD |
371; 956; 2580; 5350 | — |
| SECONDARY Tmax: Time to Reach the Maximum Plasma Concentration of DCR-AUD (Cmax) |
4.00; 7.17; 4.05; 6.00 | — |
| SECONDARY t1/2: Apparent Terminal Elimination Half-life of DCR-AUD |
7.67; 7.62; NA; NA | — |
| SECONDARY Fe%0-72: Urinary Cumulative Excretion as % of Unchanged DCR-AUD up to 72 Hours |
1.47; 2.51; 4.23; 3.85; 7.22; 8.68 | — |
| SECONDARY CLR: Renal Clearance of the DCR-AUD From Plasma |
3760; 3590; 4170; 4180 | — |
| SECONDARY Six Symptom Responses During Ethanol Interactions Assessments (EIAs) |
0.8; 1.3; 1.0; 0.3; 0.3; 1.0 | — |
| SECONDARY Cmax: Maximum Observed Plasma Concentration of Acetaldehyde |
33.7; 26.7; 11.3; 15.4; 29.4; 30.9 | — |
| SECONDARY AUC0-2.5: Area Under the Concentration Time Curve From Time 0 to Fixed Time 2.5 of Acetaldehyde |
44.4; 42.2; 10.3; 14.2; 39.1; 41.8 | — |
| SECONDARY Change From Baseline in Heart Rate |
10.0; 17.0; 13.0; 11.5; 18.4 | — |
| SECONDARY Change From Baseline in Facial Skin Temperature |
0.55; 0.48; 0.28; 0.53; 0.51 | — |
| SECONDARY Change From Baseline in Subjective Effects of Alcohol Scale (SEAS) Score |
-0.335; 1.333; 0.915; -0.083; 0; 0.938 | — |
Summary
DCR-AUD will be evaluated for safety, tolerability, pharmacokinetics, and pharmacodynamics in healthy volunteers.
Eligibility Criteria
Inclusion criteria
- Male and female participants, between 21 and 65 years of age (inclusive), who were social drinkers of modest amounts of alcohol (less than or equal to (≤) 2 drinks/day, ≤ 3 days/week) and would be able to refrain from drinking alcohol during the outpatient portion of the trial
- Overtly healthy, as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring.
- Negative screen for drugs of abuse (to include at minimum: amphetamines, barbiturates, cocaine, opioids, and benzodiazepines) at Screening and Day 1. Cannabis will not be recorded as a drug of abuse for this study.
- Had a negative test for Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) infection on Day -1 and prior to admission to the clinical unit.
- Systolic BP in the range of 90 to 140 millimetre(s) of mercury (mmHg) and diastolic BP in the range of 50 to 95 mmHg, and body mass index (BMI) within the range of 18.0 to 32.0 kilogram per square meter (kg/m^2) (inclusive).
Exclusion Criteria
- History of any medical condition that may interfere with the absorption, distribution, or elimination of study intervention, or with the clinical and laboratory assessments in this study, including (but not limited to): chronic or recurrent renal disease, functional bowel disorders (e.g., frequent diarrhea or constipation), clinically significant cardiovascular or pulmonary disease or has cardiovascular or pulmonary disease requiring pharmacologic medication, GI tract disease, pancreatitis, seizure disorder, mucocutaneous, or musculoskeletal disorder.
- Any history of severe or recent clinically significant depression, anxiety, bipolar disorder, schizophrenia, or other neuropsychiatric disorder that, in the judgment of the Investigator, represents a safety risk to the individual were they to participate in the trial
- History of delirium tremens or alcohol-related seizures.
- History of significant adverse reaction(s) to alcohol.
- History of substance use disorder (SUD), including alcohol (AUD) or illicit drug use (excluding cannabis) within the preceding 12 months. Nicotine use is permitted.
- History of any concomitant medical condition for which alcohol consumption is prohibited or advised against by the participant's physician or health care provider.
- History of multiple drug allergies or a history of allergic reaction to an oligonucleotide based therapy
Data sourced from ClinicalTrials.gov (NCT05021640). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.