Trial Outcomes & Findings for Dutasteride Treatment for the Reduction of Heavy Drinking in Men (NCT NCT01758523)

NCT ID: NCT01758523

Last Updated: 2019-04-26

Results Overview

Number of days / study week with 5 or more drinks consumed

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 189 participants
• Primary outcome timeframe: 12-week treatment period
• Results posted on: 2019-04-26

Participant Flow

47 subjects not randomized: 23 excluded at in person screening visit; 24 subjects withdrew prior to randomization

Participant milestones

Measure	Dutasteride 4 mg oral loading dose of dutasteride followed by 1 mg/day dutasteride for 12 weeks. Dutasteride	Sugar Pill Placebo pills prepared to appear the same as active medication and taken in the same number as active medication for 12 weeks. sugar pill
Overall Study STARTED	74	68
Overall Study Attended >/= 1 Visit Post-randomization	68	67
Overall Study COMPLETED	53	54
Overall Study NOT COMPLETED	21	14

Reasons for withdrawal

Measure	Dutasteride 4 mg oral loading dose of dutasteride followed by 1 mg/day dutasteride for 12 weeks. Dutasteride	Sugar Pill Placebo pills prepared to appear the same as active medication and taken in the same number as active medication for 12 weeks. sugar pill
Overall Study Adverse Event	2	1
Overall Study Lack of Efficacy	4	2
Overall Study Lost to Follow-up	3	4
Overall Study Withdrawal by Subject	12	7

Baseline Characteristics

Dutasteride Treatment for the Reduction of Heavy Drinking in Men

Baseline characteristics by cohort

Measure	Dutasteride n=68 Participants 4 mg oral loading dose of dutasteride followed by 1 mg/day dutasteride for 12 weeks. Dutasteride	Sugar Pill n=67 Participants Placebo pills prepared to appear the same as active medication and taken in the same number as active medication for 12 weeks. sugar pill	Total n=135 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	64 Participants n=5 Participants	62 Participants n=7 Participants	126 Participants n=5 Participants
Age, Categorical >=65 years	4 Participants n=5 Participants	5 Participants n=7 Participants	9 Participants n=5 Participants
Age, Continuous	53.0 years STANDARD_DEVIATION 7.9 • n=5 Participants	53.1 years STANDARD_DEVIATION 9.4 • n=7 Participants	53.0 years STANDARD_DEVIATION 8.6 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	68 Participants n=5 Participants	67 Participants n=7 Participants	135 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	67 Participants n=5 Participants	67 Participants n=7 Participants	134 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) White	66 Participants n=5 Participants	65 Participants n=7 Participants	131 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	68 participants n=5 Participants	67 participants n=7 Participants	135 participants n=5 Participants
Heavy Drinking Days (HDD)/wk	5.2 heavy drinking days / week STANDARD_DEVIATION 2.2 • n=5 Participants	5.2 heavy drinking days / week STANDARD_DEVIATION 2.1 • n=7 Participants	5.2 heavy drinking days / week STANDARD_DEVIATION 2.1 • n=5 Participants
Drinks/week	48.8 drinks/week STANDARD_DEVIATION 24 • n=5 Participants	47.3 drinks/week STANDARD_DEVIATION 20.4 • n=7 Participants	48.0 drinks/week STANDARD_DEVIATION 22.2 • n=5 Participants
AbstinentDays/week	0.67 days STANDARD_DEVIATION 1.1 • n=5 Participants	0.62 days STANDARD_DEVIATION 1.1 • n=7 Participants	0.64 days STANDARD_DEVIATION 1.1 • n=5 Participants
DSM-IV Alcohol Dependence criteria	4.3 units on a scale STANDARD_DEVIATION 1.6 • n=5 Participants	4.0 units on a scale STANDARD_DEVIATION 1.6 • n=7 Participants	4.2 units on a scale STANDARD_DEVIATION 1.6 • n=5 Participants
Short Inventory of Problems	17.2 units on a scale STANDARD_DEVIATION 8.2 • n=5 Participants	16.8 units on a scale STANDARD_DEVIATION 8.8 • n=7 Participants	17.0 units on a scale STANDARD_DEVIATION 8.4 • n=5 Participants
Smoker	12 Participants n=5 Participants	12 Participants n=7 Participants	24 Participants n=5 Participants

PRIMARY outcome

Timeframe: 12-week treatment period

Population: Modified Intention to Treat (ITT) all subjects who attended one or more post-randomization visit.

Number of days / study week with 5 or more drinks consumed

Outcome measures

Measure	Dutasteride n=68 Participants 4 mg oral loading dose of dutasteride followed by 1 mg/day dutasteride for 12 weeks. Dutasteride	Sugar Pill n=67 Participants Placebo pills prepared to appear the same as active medication and taken in the same number as active medication for 12 weeks. sugar pill	Dutasteride - AKR1C3*2 G-carrier dutasteride treated AKR1C3\*2 G-carrier genotype subjects	Sugar Pill - AKR1C3*2 G-carrier placebo treated AKR1C3\*2 G-carrier genotype subjects
Heavy Drinking Days Per Week	1.75 heavy drinking days/week Standard Error 0.33	2.67 heavy drinking days/week Standard Error 0.34	—	—

PRIMARY outcome

Timeframe: 12-week treatment period

Population: Modified ITT (all subjects who attended one or more post-randomization visit)

Total number of drinks aggregated by week

Outcome measures

Measure	Dutasteride n=68 Participants 4 mg oral loading dose of dutasteride followed by 1 mg/day dutasteride for 12 weeks. Dutasteride	Sugar Pill n=67 Participants Placebo pills prepared to appear the same as active medication and taken in the same number as active medication for 12 weeks. sugar pill	Dutasteride - AKR1C3*2 G-carrier dutasteride treated AKR1C3\*2 G-carrier genotype subjects	Sugar Pill - AKR1C3*2 G-carrier placebo treated AKR1C3\*2 G-carrier genotype subjects
Drinks Per Week	22.0 drinks/week Standard Error 2.6	27.2 drinks/week Standard Error 2.4	—	—

PRIMARY outcome

Timeframe: Last 4 weeks of treatment

Population: Per protocol 12-week completer

Number of participants with no heavy drinking days (days with 5 or more drinks) during the last 4 weeks of treatment.

Outcome measures

Measure	Dutasteride n=53 Participants 4 mg oral loading dose of dutasteride followed by 1 mg/day dutasteride for 12 weeks. Dutasteride	Sugar Pill n=54 Participants Placebo pills prepared to appear the same as active medication and taken in the same number as active medication for 12 weeks. sugar pill	Dutasteride - AKR1C3*2 G-carrier dutasteride treated AKR1C3\*2 G-carrier genotype subjects	Sugar Pill - AKR1C3*2 G-carrier placebo treated AKR1C3\*2 G-carrier genotype subjects
Number of Participants With no Heavy Drinking Days	16 Participants	8 Participants	—	—

PRIMARY outcome

Timeframe: Last 4 weeks of treatment

Population: Per protocol 12 week treatment completers

Number of participants with no hazardous drinking (not more than 4 drinks on one day and not more than 14 drinks per week) during the last 4 weeks of treatment.

Outcome measures

Measure	Dutasteride n=53 Participants 4 mg oral loading dose of dutasteride followed by 1 mg/day dutasteride for 12 weeks. Dutasteride	Sugar Pill n=54 Participants Placebo pills prepared to appear the same as active medication and taken in the same number as active medication for 12 weeks. sugar pill	Dutasteride - AKR1C3*2 G-carrier dutasteride treated AKR1C3\*2 G-carrier genotype subjects	Sugar Pill - AKR1C3*2 G-carrier placebo treated AKR1C3\*2 G-carrier genotype subjects
Number of Participants With no Hazardous Drinking	13 Participants	3 Participants	—	—

SECONDARY outcome

Timeframe: 12-week treatment period

Population: Modified ITT (all subjects who attended one or more post-randomization visit)

Change in Number of days / week with 5 or more drinks consumed contrasting AKR1C3*2 CC vs. G-carrier genotype and treatment group

Outcome measures

Measure	Dutasteride n=19 Participants 4 mg oral loading dose of dutasteride followed by 1 mg/day dutasteride for 12 weeks. Dutasteride	Sugar Pill n=25 Participants Placebo pills prepared to appear the same as active medication and taken in the same number as active medication for 12 weeks. sugar pill	Dutasteride - AKR1C3*2 G-carrier n=49 Participants dutasteride treated AKR1C3\*2 G-carrier genotype subjects	Sugar Pill - AKR1C3*2 G-carrier n=42 Participants placebo treated AKR1C3\*2 G-carrier genotype subjects
HDD/ Week by Treatment Group and AKR1C3*2 Genotype	1.06 heavy drinking days/week Standard Error 0.48	2.9 heavy drinking days/week Standard Error 0.53	2.05 heavy drinking days/week Standard Error 0.42	2.5 heavy drinking days/week Standard Error 0.44

SECONDARY outcome

Timeframe: end of 12-week treatment vs. baseline

Population: Per protocol 12-week completers (serum sample not available for 1 placebo subject).

Carbohydrate-deficient transferrin (CDT) at end of treatment as percentage of baseline. Serum CDT is a biochemical measure of heavy alcohol use.

Outcome measures

Measure	Dutasteride n=53 Participants 4 mg oral loading dose of dutasteride followed by 1 mg/day dutasteride for 12 weeks. Dutasteride	Sugar Pill n=53 Participants Placebo pills prepared to appear the same as active medication and taken in the same number as active medication for 12 weeks. sugar pill	Dutasteride - AKR1C3*2 G-carrier dutasteride treated AKR1C3\*2 G-carrier genotype subjects	Sugar Pill - AKR1C3*2 G-carrier placebo treated AKR1C3\*2 G-carrier genotype subjects
Carbohydrate-deficient Transferrin	94 percentage of baseline CDT Standard Error 3.8	107 percentage of baseline CDT Standard Error 4.0	—	—

Adverse Events

Dutasteride

Serious events: 4 serious events

Other events: 37 other events

Deaths: 0 deaths

Sugar Pill

Serious events: 2 serious events

Other events: 27 other events

Deaths: 0 deaths

Serious adverse events

Measure	Dutasteride n=68 participants at risk 4 mg oral loading dose of dutasteride followed by 1 mg/day dutasteride for 12 weeks. Dutasteride	Sugar Pill n=67 participants at risk Placebo pills prepared to appear the same as active medication and taken in the same number as active medication for 12 weeks. sugar pill
Nervous system disorders alcohol withdrawal	2.9% 2/68 • Bi-weekly during 12-week active treatment then bi-monthly for 6 months At each patient visit the study nurse used a 16-item adverse events questionnaire to screen for presence of adverse events.	1.5% 1/67 • Bi-weekly during 12-week active treatment then bi-monthly for 6 months At each patient visit the study nurse used a 16-item adverse events questionnaire to screen for presence of adverse events.
Infections and infestations Tonsillar abscess	1.5% 1/68 • Bi-weekly during 12-week active treatment then bi-monthly for 6 months At each patient visit the study nurse used a 16-item adverse events questionnaire to screen for presence of adverse events.	0.00% 0/67 • Bi-weekly during 12-week active treatment then bi-monthly for 6 months At each patient visit the study nurse used a 16-item adverse events questionnaire to screen for presence of adverse events.
Musculoskeletal and connective tissue disorders Chronic back pain	0.00% 0/68 • Bi-weekly during 12-week active treatment then bi-monthly for 6 months At each patient visit the study nurse used a 16-item adverse events questionnaire to screen for presence of adverse events.	1.5% 1/67 • Bi-weekly during 12-week active treatment then bi-monthly for 6 months At each patient visit the study nurse used a 16-item adverse events questionnaire to screen for presence of adverse events.
Respiratory, thoracic and mediastinal disorders COPD exacerbation	1.5% 1/68 • Bi-weekly during 12-week active treatment then bi-monthly for 6 months At each patient visit the study nurse used a 16-item adverse events questionnaire to screen for presence of adverse events.	0.00% 0/67 • Bi-weekly during 12-week active treatment then bi-monthly for 6 months At each patient visit the study nurse used a 16-item adverse events questionnaire to screen for presence of adverse events.

Other adverse events

Measure	Dutasteride n=68 participants at risk 4 mg oral loading dose of dutasteride followed by 1 mg/day dutasteride for 12 weeks. Dutasteride	Sugar Pill n=67 participants at risk Placebo pills prepared to appear the same as active medication and taken in the same number as active medication for 12 weeks. sugar pill
Gastrointestinal disorders Stomach discomfort	16.2% 11/68 • Bi-weekly during 12-week active treatment then bi-monthly for 6 months At each patient visit the study nurse used a 16-item adverse events questionnaire to screen for presence of adverse events.	4.5% 3/67 • Bi-weekly during 12-week active treatment then bi-monthly for 6 months At each patient visit the study nurse used a 16-item adverse events questionnaire to screen for presence of adverse events.
Musculoskeletal and connective tissue disorders Muscle or joint pain	16.2% 11/68 • Bi-weekly during 12-week active treatment then bi-monthly for 6 months At each patient visit the study nurse used a 16-item adverse events questionnaire to screen for presence of adverse events.	10.4% 7/67 • Bi-weekly during 12-week active treatment then bi-monthly for 6 months At each patient visit the study nurse used a 16-item adverse events questionnaire to screen for presence of adverse events.
General disorders Headache	14.7% 10/68 • Bi-weekly during 12-week active treatment then bi-monthly for 6 months At each patient visit the study nurse used a 16-item adverse events questionnaire to screen for presence of adverse events.	16.4% 11/67 • Bi-weekly during 12-week active treatment then bi-monthly for 6 months At each patient visit the study nurse used a 16-item adverse events questionnaire to screen for presence of adverse events.
Reproductive system and breast disorders Reduced Libido	8.8% 6/68 • Bi-weekly during 12-week active treatment then bi-monthly for 6 months At each patient visit the study nurse used a 16-item adverse events questionnaire to screen for presence of adverse events.	0.00% 0/67 • Bi-weekly during 12-week active treatment then bi-monthly for 6 months At each patient visit the study nurse used a 16-item adverse events questionnaire to screen for presence of adverse events.
General disorders Fatigue	7.4% 5/68 • Bi-weekly during 12-week active treatment then bi-monthly for 6 months At each patient visit the study nurse used a 16-item adverse events questionnaire to screen for presence of adverse events.	10.4% 7/67 • Bi-weekly during 12-week active treatment then bi-monthly for 6 months At each patient visit the study nurse used a 16-item adverse events questionnaire to screen for presence of adverse events.
General disorders Sleep disturbance	7.4% 5/68 • Bi-weekly during 12-week active treatment then bi-monthly for 6 months At each patient visit the study nurse used a 16-item adverse events questionnaire to screen for presence of adverse events.	4.5% 3/67 • Bi-weekly during 12-week active treatment then bi-monthly for 6 months At each patient visit the study nurse used a 16-item adverse events questionnaire to screen for presence of adverse events.
Gastrointestinal disorders Nausea	5.9% 4/68 • Bi-weekly during 12-week active treatment then bi-monthly for 6 months At each patient visit the study nurse used a 16-item adverse events questionnaire to screen for presence of adverse events.	7.5% 5/67 • Bi-weekly during 12-week active treatment then bi-monthly for 6 months At each patient visit the study nurse used a 16-item adverse events questionnaire to screen for presence of adverse events.
Reproductive system and breast disorders Impotence	5.9% 4/68 • Bi-weekly during 12-week active treatment then bi-monthly for 6 months At each patient visit the study nurse used a 16-item adverse events questionnaire to screen for presence of adverse events.	3.0% 2/67 • Bi-weekly during 12-week active treatment then bi-monthly for 6 months At each patient visit the study nurse used a 16-item adverse events questionnaire to screen for presence of adverse events.

Additional Information

Dr. Jonathan Covault

University of Connecticut School of Medicine

Phone: 860-679-7560

Email: jocovault@uchc.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place