The efficacy of VIVITROL in the treatment of alcohol dependence was evaluated in a 24-week, placebo-controlled, multicenter, double-blind randomized trial of patients with alcohol dependence (DSM-IV criteria) in an outpatient setting.2
The primary endpoint was the event rate of heavy drinking over the 24 weeks of treatment, defined as the number of heavy drinking days divided by the number of days at risk for heavy drinking.2
Patients in the VIVITROL and counseling group had a greater reduction in days of heavy drinking than those in the placebo and counseling group.1
Fewer heavy drinking days per month vs placebo
VIVITROL 380 mg (n=205) vs placebo (n=209; HR=0.75 [0.60-0.94]; P=0.02).HR=hazard ratio.
A predefined subpopulation of lead-in abstinent patients (n=53, or 8% of the total study population) was defined as those who reported no drinking during the 7 consecutive days preceding the first injection.
Among the subset of patients, those treated with VIVITROL 380 mg had greater reductions than placebo-treated patients in the number of drinking days and the number of heavy drinking days.
In the subset population
Heavy drinking days1
Median heavy drinking days: ≥7-day abstinent subset (n=53) over 6 months1,3
In the subset population
Any drinking days1
Median any drinking days per month: ≥7-day abstinent subset (n=53) over 6 months4
At baseline, the median 7-day abstinent patient had 15.2 drinking days and 15.2 abstinent days per average month (30.4 days).4
In the subset population
Complete abstinence throughout treatment1
Patients maintaining complete abstinence (%): ≥7-day abstinent subset (n=53) over 6 months2,3
A greater proportion of patients with a 7-day lead-in abstinence on VIVITROL maintained abstinence throughout the 6-month study period vs those on placebo.*Psychosocial support was defined as biweekly counseling.
Pivotal study post hoc analysis
A post hoc analysis of a subset of patients in the pivotal trial who were able to abstain completely from drinking for the 4 consecutive days prior to first injection3
This post hoc analysis was not prespecified and included a small sample size; thus, the results could represent chance findings and should be interpreted with caution. A post hoc analysis of the alcohol dependence pivotal trial was performed on data from 624 alcohol-dependent outpatients who were randomly assigned to receive VIVITROL 380 mg, XR-NTX 190 mg, or placebo every 4 weeks for 24 weeks, along with psychosocial support every other week. In the subanalysis, 82 patients were voluntarily abstinent for ≥4 days prior to treatment initiation. Evaluations occurred weekly for the first 4 weeks and then every 2 weeks for the next 20 weeks until the final visit.
Median heavy drinking† days per month ≥4-day abstinent subset (n=82)3:
- VIVITROL 380 mg with psychosocial support‡ (n=28): 0.2 heavy drinking days
- Placebo with psychosocial support‡ (n=28): 2.9 heavy drinking days
Median number of days to first heavy drinking event ≥4-day abstinent subset population (n=82)3,4†Heavy drinking was defined as a self-report of ≥5 standard drinks consumed on a given day for male patients and ≥4 for female patients. ‡Psychosocial support was defined as biweekly counseling.
Patients met the DSM-IV criteria for alcohol dependence and had a minimum of 2 episodes of heavy drinking per week in the 30 days before screening. Heavy drinking was defined as ≥5 standard drinks per day for men and ≥4 standard drinks per day for women.
Participants received an intramuscular (IM) injection every 4 weeks in an outpatient setting for a total of 6 injections over 24 weeks, along with psychosocial support every other week. A total of 208 patients were randomized to the VIVITROL 380 mg group. Three patients did not receive any treatment due to enrollment failures based on investigator decision, leaving 205 patients included in the primary analysis and safety evaluation for the VIVITROL 380 mg group. A total of 209 patients were randomized to the placebo group.
|VIVITROL 380 mg (n=205)||Placebo (n=209)|
|Mean age in years¶||45.0 (±10.1)||44.7 (±10.8)|
|White||172 (83.9%)||180 (86.1%)|
|Mean weight in kg¶||84.2 (±20.7)||81.6 (±17.0)|
|Employed ≥20 hours/week||144 (70.2%)||151 (72.2%)|
|Other drug use|
|Current smoker¶||99 (48.3%)||88 (42.1%)|
|Antidepressants||62 (30.2%)||61 (29.2%)|
|Patient treatment goal of total abstinence||90 (43.9%)||90 (43.1%)|
|Abstinence for 7 days beforerandomization||17 (8.3%)||19 (9.1%)|
|Self help group attendance¶||24 (11.7%)||23 (11.0%)|
|Mean % heavy drinking in30 days before randomization||64.0% (±25.9)||65.2% (±24.8)|
- Men and women in this study differed on a number of important variables, including the prevalence of smoking and antidepressant use, weight, and commitment to abstinence
- The men and women in this sample may have differed on other variables that may positively influence naltrexone response but were not assessed in this study, such as family history of alcoholism
- The study was not designed to answer whether naltrexone may or may not work for women
- The women who participated may not be representative of women with alcohol dependence in the general population, and the number of women studied was small
- Clinical trials may enroll patients with a greater degree of motivation for change than is seen among patients who are treated in traditional outpatient settings
- Although treatment attendance was relatively high in this study, dropouts reduce the extent to which the findings generalize to all of those with alcohol dependence. Drinking data for dropouts were not obtained once they left the study, so it is not known how these drinking outcomes would have affected the results
- Analyses of group central tendencies (median, mean) do not reflect the experience of individual patients
Subset analysis limitations1,2:
- Due to the small numbers, this analysis should be interpreted with caution
- The same treatment effects were not evident among the subset of patients (n=571, 92% of the total study population) who were actively drinking at the time of treatment initiation
- Secondary data analysis. No adjustments were made for multiple comparisons; therefore, treatment differences could represent chance findings
Adverse reactions in alcohol dependence pivotal trial1
Treatment-emergent adverse reactions that occurred in ≥5% of patients with alcohol dependence treated with VIVITROL and that occurred more frequently in the VIVITROL group vs the placebo group
380 mg with psychosocial support (n=205)
with psychosocial support (n=214)
|Injection site tenderness||45%||39%|
|Injection site induration||35%||8%|
|Injection site pain||17%||7%|
|Other ISR (primarily nodules, swelling)||15%||4%|
|Insomnia, sleep disorder||14%||12%|
|Anorexia, appetite decreased NOS,
appetite disorder NOS
|Arthralgia, arthritis, joint stiffness||12%||5%|
|Injection site pruritus||10%||0%|
|Injection site ecchymosis||7%||5%|
|Back pain, back stiffness||6%||5%|
Discontinuation rates due to adverse events1
Alcohol dependence controlled clinical trial of ≤6 months#Psychosocial support was defined as biweekly counseling.