Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| U44AA027404 | U.S. NIH Grant/Contract | View source |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
DCR-AUD will be evaluated for safety, tolerability, pharmacokinetics, and pharmacodynamics in healthy volunteers.
DCR-AUD is being developed for the treatment of alcohol use disorder (AUD) in adults using an RNA interference (RNAi) technology platform. This is a 24-week, randomized, double-blind, placebo-controlled study to evaluate the safety, tolerability, PK, and PD of single-ascending doses (SAD) of DCR-AUD administered to adult HVs. The single doses of DCR-AUD will be administered to adult HVs across 4 sequential cohorts (3 planned [80 mg, 240 mg, 480 mg] and one optional [960 mg]). Each cohort will comprise a sentinel group of 3 participants (2 active, 1 placebo) and an expanded group of 6 participants (4 active, 2 placebo). The sentinel group will be followed for the assessment of safety and tolerability and characterization of PK but who will not undergo any EIAs. Participants will receive a single dose of study intervention on Day 1 and will be followed for 24 weeks. Participants who have positive ethanol reaction symptoms at the Day 169 EIA (e.g., nausea, vomiting, or substantial flushing) will return every 28 (±7) days for follow-up EIAs until the positive ethanol reaction symptoms abate. These conditional follow-up (CFU) EIAs will not require overnight admission to the clinic, but all other aspects of the EIA will be conducted (see Table 3). Participants will be observed for not less than 6 hours after ethanol administration and will not be discharged until the Investigator deems it medically safe to do so.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1: DCRAUD 80 mg | Experimental | Participant received a single dose of DCR-AUD 80 mg, subcutaneous injection on Day 1. |
|
| Cohort 2: DCRAUD 240 mg | Placebo Comparator | Participant received a single dose of DCR-AUD 240 mg, subcutaneous injection on Day 1. |
|
| Cohort 3: DCR-AUD 480 mg | Experimental | Participant received a single dose of DCR-AUD 480 mg, subcutaneous injection on Day 1. |
|
| Cohort 4: DCR-AUD 960 mg | Placebo Comparator | Participant received a single dose of DCR-AUD 960 mg, subcutaneous injection on Day 1. |
|
| Pooled Placebo | Experimental | Participant received a single dose of DCR-AUD matching placebo, subcutaneous injection on Day 1. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| DCR-AUD | Drug | DCR-A1203, the drug substance of DCR-AUD, is a synthetic double-stranded (hybridized duplex) RNA oligonucleotide conjugated to GalNAc ligands that enable specific hepatic access and uptake after subcutaneous administration. DCR-AUD is a sterile solution of DCR-A1203 at a concentration of 160 mg/mL in water for injection (WFI). |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | 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. | From Day 1 up to 24 Weeks |
| Number of Participants With Severity Grades of TEAEs | 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 life-threatening; 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. | From Day 1 up to 24 Weeks |
| Number of Participants With Dose-limiting Toxicities (DLTs) as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 | DLT is defined as an AE of greater than or equal to (>=) Grade 3 intensity (CTCAE Version 5.0) in one participant, unless it is clearly the result of a non-study-related event OR any 2 AEs of >= Grade 2 intensity in the same body system in one participant. |
| Measure | Description | Time Frame |
|---|---|---|
| AUC0-last: Area Under the Plasma Concentration Curve From Time Zero to the Last Quantifiable Concentration of DCR-AUD | AUC0-last is defined as the area under the plasma concentration curve from time zero to the last quantifiable concentration of DCR-AUD. | Day 1: Predose, at 15 and 30 minutes, 1, 2, 4, 6, 8, 24, 48, 72 hours post dose; Day 15: Once Post dose |
Not provided
Inclusion criteria
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Clinical Transparency (dept. 1452) | Novo Nordisk A/S | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Parexel Los Angeles Early Phase Clinical Unit | Glendale | California | 91206 | United States |
Not provided
Not provided
Not provided
Not provided
Not provided
In this trial 36 healthy participants were randomized to four ascending-dose cohorts (80 milligram [mg], 240 mg, 480 mg, 960 mg) and placebo.
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Cohort 1: DCR-AUD 80 mg | Participant received a single dose of DCR-AUD 80 mg, subcutaneous injection on Day 1. |
| FG001 | Cohort 2: DCR-AUD 240 mg | Participant received a single dose of DCR-AUD 240 mg, subcutaneous injection on Day 1. |
| FG002 | Cohort 3: DCR-AUD 480 mg | Participant received a single dose of DCR-AUD 480 mg, subcutaneous injection on Day 1. |
| FG003 | Cohort 4: DCR-AUD 960 mg | Participant received a single dose of DCR-AUD 960 mg, subcutaneous injection on Day 1. |
| FG004 | Pooled Placebo | Participant received a single dose of DCR-AUD matching placebo, subcutaneous injection on Day 1. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Safety population included all participants randomly assigned to study intervention and who received the full dose of study intervention.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Cohort 1: DCR-AUD 80 mg | Participant received a single dose of DCR-AUD 80 mg, subcutaneous injection on Day 1. |
| BG001 | Cohort 2: DCR-AUD 240 mg | Participant received a single dose of DCR-AUD 240 mg, subcutaneous injection on Day 1. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | 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. | Safety population included all participants randomly assigned to study intervention and who received the full dose of study intervention. | Posted | Count of Participants | Participants | From Day 1 up to 24 Weeks |
From Day 1 until end of the study (24 weeks).
Safety population included all participants randomly assigned to study intervention and who received the full dose of study intervention. All serious and non-serious adverse events presented here are treatment emergent adverse events.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Cohort 1: DCR-AUD 80 mg | Participant received a single dose of DCR-AUD 80 mg, subcutaneous injection on Day 1. |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Dizziness | Nervous system disorders | MedDRA (24.0) | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Clinical Reporting Office (2834) | Novo Nordisk A/S | (+1) 866-867-7178 | clinicaltrials@novonordisk.com |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Mar 14, 2022 | Oct 29, 2024 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Feb 22, 2023 | Oct 29, 2024 | SAP_001.pdf |
Not provided
| ID | Term |
|---|---|
| D000437 | Alcoholism |
| ID | Term |
|---|---|
| D019973 | Alcohol-Related Disorders |
| D019966 | Substance-Related Disorders |
| D064419 | Chemically-Induced Disorders |
| D001523 | Mental Disorders |
Not provided
Not provided
Not provided
Not provided
Not provided
Participants, Investigators, site staff, the CRO staff, and the Sponsor Medical Monitor will be blinded to the randomization. Other members of the Sponsor staff will be unblinded for the duration of the study. Complete details will be presented in the Study Blinding Plan.
|
|
| Placebo for DCR-AUD | Drug | 0.9% saline for injection |
|
|
| From Day 1 up to 24 Weeks |
| Number of Participants With Change From Baseline in Clinically Significant Abnormal Vital Signs | Number of participants with change from baseline in clinically significant abnormal vital signs (temperature, pulse rate, respiratory rate, and blood pressure) is presented. | From Baseline (Day -1) up to 24 weeks |
| Number of Participants With Change From Baseline in Clinically Significant Abnormal Electrocardiogram (ECG) Findings | 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. | From Baseline (Day -1) up to 24 weeks |
| Number of Participants With Change From Baseline in Clinically Significant Abnormal Laboratory Values | Number of participants with change from baseline in clinically significant abnormal laboratory values (hematology, clinical chemistry, coagulation and routine urinalysis parameters) is presented. | From Baseline (Day -1) up to 24 weeks |
| Number of Participants With Change From Baseline in Clinically Significant Physical Examination Findings | 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. | From Baseline (Day -1) up to 24 weeks |
| Cmax: Maximum Observed Plasma Concentration of DCR-AUD | Cmax is defined as maximum observed plasma concentration of DCR-AUD during a dosing interval. | Day 1: Predose, at 15 and 30 minutes, 1, 2, 4, 6, 8, 24, 48, 72 hours post dose; Day 15: Once Post dose |
| Tmax: Time to Reach the Maximum Plasma Concentration of DCR-AUD (Cmax) | Tmax is defined as time to reach the maximum plasma concentration (Cmax) of DCR-AUD. | Day 1: Predose, at 15 and 30 minutes, 1, 2, 4, 6, 8, 24, 48, 72 hours post dose; Day 15: Once Post dose |
| t1/2: Apparent Terminal Elimination Half-life of DCR-AUD | t1/2 is defined as apparent terminal elimination half-life of DCR-AUD. | Day 1: Predose, at 15 and 30 minutes, 1, 2, 4, 6, 8, 24, 48, 72 hours post dose; Day 15: Once Post dose |
| Fe%0-72: Urinary Cumulative Excretion as % of Unchanged DCR-AUD up to 72 Hours | Urinary cumulative excretion as % of DCR-AUD at each interval collection (0- 4 hours, 0- 8 hours, 0-12 hours, 0-24 hours, 0-48 hours, 0-72 hours) is reported in this outcome measure. | At time interval between 0- 4 hours, 0- 8 hours, 0-12 hours, 0-24 hours, 0-48 hours, 0-72 hours |
| CLR: Renal Clearance of the DCR-AUD From Plasma | Renal clearance of the DCR-AUD from plasma is reported in this outcome measure. | Day 1: 0-4, 4-8, 8-12, 12-24, 24-48, and 48-72-hours post-dose |
| Six Symptom Responses During Ethanol Interactions Assessments (EIAs) | The degree of aldehyde dehydrogenase 2 (ALDH2) reduction was measured by quantitative assessment of 6 symptom (flushing, headache, palpitations, light-headedness, nausea, and vomiting) responses during EIAs. Each of 6 symptoms was assessed at each of the 4 time points during each EIA. Composite score at each time point was the sum of severity ratings for each of the 6 symptoms. Peak composite score (of the 3 post-alcohol initiation composite scores at each EIA test) was used as the subject's peak score for that EIA test. The point system was as follows: 0 point = symptom not present, 1 point = mild severity of symptom, 2 points = moderate severity of symptom and 3 points = severe severity of symptom. Participants were given a composite score, which was the sum of the scores of all 6 symptoms (highest possible score is 18). | Day -1, Day 4, Day 15, Day 29, Day 57, Day 85, Day 113 and Day 169 |
| Cmax: Maximum Observed Plasma Concentration of Acetaldehyde | Maximum plasma concentration of acetaldehyde was measured to evaluate the pharmacodynamic effects of ALDH2 reduction by DCR-AUD during serial EIAs days. | Day -1, Day 4, Day 15, Day 29, Day 57, Day 85, Day 113 and Day 169 |
| AUC0-2.5: Area Under the Concentration Time Curve From Time 0 to Fixed Time 2.5 of Acetaldehyde | Area under the concentration time curve from time 0 to fixed time 2.5 of acetaldehyde was measured to evaluate the pharmacodynamic effects of ALDH2 reduction by DCR-AUD during serial EIAs days. | Day -1, Day 4, Day 15, Day 29, Day 57, Day 85, Day 113 and Day 169 |
| Change From Baseline in Heart Rate | Heart rate is measured to evaluate the PD effects of ALDH2 reduction by DCR-AUD during serial EIA. Heart rate was monitored by telemetry during the EIAs. | Baseline (Day -1), Day 169 |
| Change From Baseline in Facial Skin Temperature | Change in facial skin temperature was measured to evaluate the PD effects of ALDH2 reduction by DCR-AUD during serial EIAs for the expanded group. Facial skin temperature was measured using a surface scanning thermometer. | Baseline (Day -1), Day 169 |
| Change From Baseline in Subjective Effects of Alcohol Scale (SEAS) Score | Subjective feelings of alcohol intoxication or intolerance is measured to evaluate the PD effects of ALDH2 reduction by DCR-AUD during serial EIAs. Participants' subjective experience of the effects of alcohol was assessed using the SEAS. The SEAS is a 14-item tool that allows participants to rate the subjective effects of alcohol. Participants rated the extent to which they were feeling (high/low arousal positive: relaxed, wobbly, lively, secure, woozy, fun, calm, dizzy, mellow, funny, talkative and high/low arousal negative: demanding, rude and aggressive) on an 11-point scale from (0 = not at all, 10 = extremely). higher values represent more effects. | Baseline (Day -1), Day 169 |
| BG002 | Cohort 3: DCR-AUD 480 mg | Participant received a single dose of DCR-AUD 480 mg, subcutaneous injection on Day 1. |
| BG003 | Cohort 4: DCR-AUD 960 mg | Participant received a single dose of DCR-AUD 960 mg, subcutaneous injection on Day 1. |
| BG004 | Pooled Placebo | Participant received a single dose of DCR-AUD matching placebo, subcutaneous injection on Day 1. |
| BG005 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| ID |
|---|
| Title |
|---|
| Description |
|---|
| OG000 | Cohort 1: DCR-AUD 80 mg | Participant received a single dose of DCR-AUD 80 mg, subcutaneous injection on Day 1. |
| OG001 | Cohort 2: DCR-AUD 240 mg | Participant received a single dose of DCR-AUD 240 mg, subcutaneous injection on Day 1. |
| OG002 | Cohort 3: DCR-AUD 480 mg | Participant received a single dose of DCR-AUD 480 mg, subcutaneous injection on Day 1. |
| OG003 | Cohort 4: DCR-AUD 960 mg | Participant received a single dose of DCR-AUD 960 mg, subcutaneous injection on Day 1. |
| OG004 | Pooled Placebo | Participant received a single dose of DCR-AUD matching placebo, subcutaneous injection on Day 1. |
|
|
| Primary | Number of Participants With Severity Grades of TEAEs | 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 life-threatening; 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. | Safety population included all participants randomly assigned to study intervention and who received the full dose of study intervention. | Posted | Count of Participants | Participants | From Day 1 up to 24 Weeks |
|
|
|
| Primary | Number of Participants With Dose-limiting Toxicities (DLTs) as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 | DLT is defined as an AE of greater than or equal to (>=) Grade 3 intensity (CTCAE Version 5.0) in one participant, unless it is clearly the result of a non-study-related event OR any 2 AEs of >= Grade 2 intensity in the same body system in one participant. | Safety population included all participants randomly assigned to study intervention and who received the full dose of study intervention. | Posted | Count of Participants | Participants | From Day 1 up to 24 Weeks |
|
|
|
| Primary | Number of Participants With Change From Baseline in Clinically Significant Abnormal Vital Signs | Number of participants with change from baseline in clinically significant abnormal vital signs (temperature, pulse rate, respiratory rate, and blood pressure) is presented. | Safety population included all participants randomly assigned to study intervention and who received the full dose of study intervention. | Posted | Count of Participants | Participants | From Baseline (Day -1) up to 24 weeks |
|
|
|
| Primary | Number of Participants With Change From Baseline in Clinically Significant Abnormal Electrocardiogram (ECG) Findings | 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. | Safety population included all participants randomly assigned to study intervention and who received the full dose of study intervention. | Posted | Count of Participants | Participants | From Baseline (Day -1) up to 24 weeks |
|
|
|
| Primary | Number of Participants With Change From Baseline in Clinically Significant Abnormal Laboratory Values | Number of participants with change from baseline in clinically significant abnormal laboratory values (hematology, clinical chemistry, coagulation and routine urinalysis parameters) is presented. | Safety population included all participants randomly assigned to study intervention and who received the full dose of study intervention. | Posted | Count of Participants | Participants | From Baseline (Day -1) up to 24 weeks |
|
|
|
| Primary | Number of Participants With Change From Baseline in Clinically Significant Physical Examination Findings | 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. | Safety population included all participants randomly assigned to study intervention and who received the full dose of study intervention. | Posted | Count of Participants | Participants | From Baseline (Day -1) up to 24 weeks |
|
|
|
| Secondary | AUC0-last: Area Under the Plasma Concentration Curve From Time Zero to the Last Quantifiable Concentration of DCR-AUD | AUC0-last is defined as the area under the plasma concentration curve from time zero to the last quantifiable concentration of DCR-AUD. | Pharmacokinetic (PK) analysis population included all participants randomly assigned to study intervention and who received a full dose of DCR-AUD and had sufficient data for at least 1 postdose PK assessment. | Posted | Geometric Mean | Geometric Coefficient of Variation | hour*nanogram per millilitre (h*ng/mL) | Day 1: Predose, at 15 and 30 minutes, 1, 2, 4, 6, 8, 24, 48, 72 hours post dose; Day 15: Once Post dose |
|
|
|
| Secondary | Cmax: Maximum Observed Plasma Concentration of DCR-AUD | Cmax is defined as maximum observed plasma concentration of DCR-AUD during a dosing interval. | PK analysis population included all participants randomly assigned to study intervention and who received a full dose of DCR-AUD and had sufficient data for at least 1 postdose PK assessment. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram per millilitre (ng/mL) | Day 1: Predose, at 15 and 30 minutes, 1, 2, 4, 6, 8, 24, 48, 72 hours post dose; Day 15: Once Post dose |
|
|
|
| Secondary | Tmax: Time to Reach the Maximum Plasma Concentration of DCR-AUD (Cmax) | Tmax is defined as time to reach the maximum plasma concentration (Cmax) of DCR-AUD. | PK analysis population included all participants randomly assigned to study intervention and who received a full dose of DCR-AUD and had sufficient data for at least 1 postdose PK assessment. | Posted | Median | Full Range | hours | Day 1: Predose, at 15 and 30 minutes, 1, 2, 4, 6, 8, 24, 48, 72 hours post dose; Day 15: Once Post dose |
|
|
|
| Secondary | t1/2: Apparent Terminal Elimination Half-life of DCR-AUD | t1/2 is defined as apparent terminal elimination half-life of DCR-AUD. | PK analysis population included all participants randomly assigned to study intervention and who received a full dose of DCR-AUD and had sufficient data for at least 1 postdose PK assessment. Here, Overall Number of Participants Analyzed" signifies participants with available data for this outcome measure. | Posted | Median | Full Range | hours | Day 1: Predose, at 15 and 30 minutes, 1, 2, 4, 6, 8, 24, 48, 72 hours post dose; Day 15: Once Post dose |
|
|
|
| Secondary | Fe%0-72: Urinary Cumulative Excretion as % of Unchanged DCR-AUD up to 72 Hours | Urinary cumulative excretion as % of DCR-AUD at each interval collection (0- 4 hours, 0- 8 hours, 0-12 hours, 0-24 hours, 0-48 hours, 0-72 hours) is reported in this outcome measure. | PK analysis population included all participants randomly assigned to study intervention and who received a full dose of DCR-AUD and had sufficient data for at least 1 postdose PK assessment. | Posted | Geometric Mean | Geometric Coefficient of Variation | percentage of unchanged DCR-AUD | At time interval between 0- 4 hours, 0- 8 hours, 0-12 hours, 0-24 hours, 0-48 hours, 0-72 hours |
|
|
|
| Secondary | CLR: Renal Clearance of the DCR-AUD From Plasma | Renal clearance of the DCR-AUD from plasma is reported in this outcome measure. | PK analysis population included all participants randomly assigned to study intervention and who received a full dose of DCR-AUD and had sufficient data for at least 1 postdose PK assessment. | Posted | Geometric Mean | Geometric Coefficient of Variation | Liter per hour (L/h) | Day 1: 0-4, 4-8, 8-12, 12-24, 24-48, and 48-72-hours post-dose |
|
|
|
| Secondary | Six Symptom Responses During Ethanol Interactions Assessments (EIAs) | The degree of aldehyde dehydrogenase 2 (ALDH2) reduction was measured by quantitative assessment of 6 symptom (flushing, headache, palpitations, light-headedness, nausea, and vomiting) responses during EIAs. Each of 6 symptoms was assessed at each of the 4 time points during each EIA. Composite score at each time point was the sum of severity ratings for each of the 6 symptoms. Peak composite score (of the 3 post-alcohol initiation composite scores at each EIA test) was used as the subject's peak score for that EIA test. The point system was as follows: 0 point = symptom not present, 1 point = mild severity of symptom, 2 points = moderate severity of symptom and 3 points = severe severity of symptom. Participants were given a composite score, which was the sum of the scores of all 6 symptoms (highest possible score is 18). | Pharmacodynamic population (PP) included all participants randomly assigned to study intervention and who received a full dose of study intervention and had sufficient data for at least 1 postdose pharmacodynamic (PD) assessment. Here, number analysed signifies participants with available data for each specified category. | Posted | Mean | Standard Deviation | score on a scale | Day -1, Day 4, Day 15, Day 29, Day 57, Day 85, Day 113 and Day 169 |
|
|
|
| Secondary | Cmax: Maximum Observed Plasma Concentration of Acetaldehyde | Maximum plasma concentration of acetaldehyde was measured to evaluate the pharmacodynamic effects of ALDH2 reduction by DCR-AUD during serial EIAs days. | Pharmacodynamic Population (PP) included all participants randomly assigned to study intervention and who received a full dose of study intervention and had sufficient data for at least 1 postdose PD assessment. | Posted | Mean | Standard Deviation | micromolar (μM) | Day -1, Day 4, Day 15, Day 29, Day 57, Day 85, Day 113 and Day 169 |
|
|
|
| Secondary | AUC0-2.5: Area Under the Concentration Time Curve From Time 0 to Fixed Time 2.5 of Acetaldehyde | Area under the concentration time curve from time 0 to fixed time 2.5 of acetaldehyde was measured to evaluate the pharmacodynamic effects of ALDH2 reduction by DCR-AUD during serial EIAs days. | Pharmacodynamic Population (PP) included all participants randomly assigned to study intervention and who received a full dose of study intervention and had sufficient data for at least 1 postdose PD assessment. | Posted | Mean | Standard Deviation | hour*nanomolar (h*uM) | Day -1, Day 4, Day 15, Day 29, Day 57, Day 85, Day 113 and Day 169 |
|
|
|
| Secondary | Change From Baseline in Heart Rate | Heart rate is measured to evaluate the PD effects of ALDH2 reduction by DCR-AUD during serial EIA. Heart rate was monitored by telemetry during the EIAs. | Pharmacodynamic Population (PP) included all participants randomly assigned to study intervention and who received a full dose of study intervention and had sufficient data for at least 1 postdose PD assessment. Here, Overall Number of Participants Analyzed" signifies participants with available data for this outcome measure. | Posted | Mean | Standard Deviation | beats/min | Baseline (Day -1), Day 169 |
|
|
|
| Secondary | Change From Baseline in Facial Skin Temperature | Change in facial skin temperature was measured to evaluate the PD effects of ALDH2 reduction by DCR-AUD during serial EIAs for the expanded group. Facial skin temperature was measured using a surface scanning thermometer. | Pharmacodynamic Population (PP) included all participants randomly assign ed to study intervention and who received a full dose of study intervention and had sufficient data for at least 1 postdose PD assessment. Here, Overall Number of Participants Analyzed" signifies participants with available data for this outcome measure. | Posted | Mean | Standard Deviation | degree celsius | Baseline (Day -1), Day 169 |
|
|
|
| Secondary | Change From Baseline in Subjective Effects of Alcohol Scale (SEAS) Score | Subjective feelings of alcohol intoxication or intolerance is measured to evaluate the PD effects of ALDH2 reduction by DCR-AUD during serial EIAs. Participants' subjective experience of the effects of alcohol was assessed using the SEAS. The SEAS is a 14-item tool that allows participants to rate the subjective effects of alcohol. Participants rated the extent to which they were feeling (high/low arousal positive: relaxed, wobbly, lively, secure, woozy, fun, calm, dizzy, mellow, funny, talkative and high/low arousal negative: demanding, rude and aggressive) on an 11-point scale from (0 = not at all, 10 = extremely). higher values represent more effects. | Pharmacodynamic Population (PP) included all participants randomly assigned to study intervention and who received a full dose of study intervention and had sufficient data for at least 1 postdose PD assessment. | Posted | Mean | Standard Deviation | score on a scale | Baseline (Day -1), Day 169 |
|
|
|
| 0 |
| 6 |
| 0 |
| 6 |
| 4 |
| 6 |
| EG001 | Cohort 2: DCR-AUD 240 mg | Participant received a single dose of DCR-AUD 240 mg, subcutaneous injection on Day 1. | 0 | 6 | 0 | 6 | 5 | 6 |
| EG002 | Cohort 3: DCR-AUD 480 mg | Participant received a single dose of DCR-AUD 480 mg, subcutaneous injection on Day 1. | 0 | 6 | 0 | 6 | 4 | 6 |
| EG003 | Cohort :4 DCR-AUD 960 mg | Participant received a single dose of DCR-AUD 960 mg, subcutaneous injection on Day 1. | 0 | 6 | 0 | 6 | 2 | 6 |
| EG004 | Pooled Placebo | Participant received a single dose of DCR-AUD matching placebo, subcutaneous injection on Day 1. | 0 | 12 | 0 | 12 | 9 | 12 |
| Headache | Nervous system disorders | MedDRA (24.0) | Systematic Assessment |
|
| Somnolence | Nervous system disorders | MedDRA (24.0) | Systematic Assessment |
|
| Viral infection | Infections and infestations | MedDRA (24.0) | Systematic Assessment |
|
| COVID-19 | Infections and infestations | MedDRA (24.0) | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA (24.0) | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA (24.0) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA (24.0) | Systematic Assessment |
|
| Abdominal distension | Gastrointestinal disorders | MedDRA (24.0) | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA (24.0) | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA (24.0) | Systematic Assessment |
|
| Food poisoning | Gastrointestinal disorders | MedDRA (24.0) | Systematic Assessment |
|
| Gastric disorder | Gastrointestinal disorders | MedDRA (24.0) | Systematic Assessment |
|
| Toothache | Gastrointestinal disorders | MedDRA (24.0) | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (24.0) | Systematic Assessment |
|
| Muscle fatigue | Musculoskeletal and connective tissue disorders | MedDRA (24.0) | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (24.0) | Systematic Assessment |
|
| Injection site pain | General disorders | MedDRA (24.0) | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA (24.0) | Systematic Assessment |
|
| Vessel puncture site bruise | General disorders | MedDRA (24.0) | Systematic Assessment |
|
| Flushing | Vascular disorders | MedDRA (24.0) | Systematic Assessment |
|
| Hot flush | Vascular disorders | MedDRA (24.0) | Systematic Assessment |
|
| SARS-CoV-2 test positive | Investigations | MedDRA (24.0) | Systematic Assessment |
|
| Palpitations | Cardiac disorders | MedDRA (24.0) | Systematic Assessment |
|
| Tachycardia | Cardiac disorders | MedDRA (24.0) | Systematic Assessment |
|
| Dysphonia | Respiratory, thoracic and mediastinal disorders | MedDRA (24.0) | Systematic Assessment |
|
| Dysmenorrhoea | Reproductive system and breast disorders | MedDRA (24.0) | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA (24.0) | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (24.0) | Systematic Assessment |
|
SPONSOR agrees that the Principal Investigator shall have the right to publish or permit the publication of any information or material relating to or arising out of the work after prior submittal to SPONSOR provided that if SPONSOR shall so request, the investigator will delay publication for a maximum of ninety (90) days after submittal to SPONSOR to enable SPONSOR to protect its rights. SPONSOR will comment on such documents within thirty (30) days.
| Grade 2 |
|
| Grade 3 |
|
| Grade 4 |
|
| Grade 5 |
|
| Fe%0-8 |
|
| Fe%0-12 |
|
| Fe%0-24 |
|
| Fe%0-48 |
|
| Fe%0-72 |
|
|
| Day 4 |
|
|
| Day 15 |
|
|
| Day 29 |
|
|
| Day 57 |
|
|
| Day 85 |
|
|
| Day 113 |
|
|
| Day 169 |
|
|
| Day 4 |
|
| Day 15 |
|
| Day 29 |
|
| Day 57 |
|
| Day 85 |
|
| Day 113 |
|
| Day 169 |
|
| Day 4 |
|
| Day 15 |
|
| Day 29 |
|
| Day 57 |
|
| Day 85 |
|
| Day 113 |
|
| Day 169 |
|
| High Arousal Positive |
|
| Low Arousal Negative |
|
| Low Arousal Positive |
|