A 24-week, multicenter, double-blind, randomized, placebo-controlled trial1
PIVOTAL STUDY DATA1
-
Patients met the DSM-IV criteria for active 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
- 627 outpatients were randomized to receive VIVITROL 380 mg (n=208), extended-release naltrexone (XR-NTX) 190 mg (n=210), or placebo (n=209)
-
Participants received an intramuscular injection every 4 weeks—a total of 6 injections over 24 weeks
- Patients also received psychosocial support every other week
ALCOHOL STUDY DESIGN1
STUDY LIMITATIONS
-
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
- 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
- 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) may not reflect the experience of individual patients
PRIMARY ENDPOINT: EVENT RATE OF HEAVY DRINKING1
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
BASELINE CHARACTERISTICS
| VIVITROL 380 mg (n=205) |
Placebo (n=209) |
|
|---|---|---|
| Demographics | ||
| 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 ≥20h/wk | 144 (70.2%) | 151 (72.2%) |
| Other drug use | ||
| Current smoker* | 99 (48.3%) | 88 (42.1%) |
| Antidepressants | 62 (30.2%) | 61 (29.2%) |
| Drinking behavior | ||
| Abstinence goal | 90.0 (43.9%) | 90.0 (43.1%) |
| Abstinence for 7 days before randomization | 17 (8.3%) | 19 (9.1%) |
| Self-help group attendance* | 24 (11.7%) | 23 (11.0%) |
| Mean % heavy drinking in 30 days before randomization | 64.0% (±25.9) | 65.2% (±24.8) |
Data are mean (standard deviation [SD]) or number (%).
*P<0.05 (significant difference between men and women in the overall study population [n=624]).
PRIMARY ENDPOINT: EVENT RATE OF HEAVY DRINKING
Patients treated with VIVITROL and counseling demonstrated a significant reduction in heavy drinking days1
Heavy drinking was defined as a self-report of 5 or more standard drinks consumed on a given day for male patients and 4 or more drinks for female patients.1
Patients treated with VIVITROL 380 mg (n=205) demonstrated a 25% greater reduction in days of heavy drinking than those treated with placebo (n=209; HR=0.75 [0.60–0.94]; P=0.02).1
SUBSET POPULATION: PATIENTS WHO ABSTAINED FROM DRINKING DURING THE 7 CONSECUTIVE DAYS PRIOR TO THE FIRST INJECTION1-3
A predefined subpopulation of lead-in abstinent VIVITROL, XR-NTX 190-mg, and placebo patients (n=53, or 8% of the total study population) was defined as those who reported no drinking during the 7 consecutive days prior to the first injection.
- 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
- Only data for VIVITROL 380 mg and placebo are presented here
SUBSET POPULATION: PATIENTS TREATED WITH VIVITROL HAD GREATER REDUCTION IN THE NUMBER OF HEAVY DRINKING DAYS1-3
SUBSET POPULATION: GREATER REDUCTION IN THE NUMBER OF ANY DRINKING DAYS1-3
Patients treated with VIVITROL and psychosocial counseling saw reductions in median drinking days for the average month during the 6-month trial:
0.2 drinking days
in the VIVITROL group:
Patients receiving VIVITROL with psychosocial support† (n=17) had a median of 0.2 drinking days per average month
6.6 drinking days
in the placebo group:
Patients receiving placebo with psychosocial support† (n=19) had a median of 6.6 drinking days per average month
- At baseline, the median 7-day abstinent patient had 15.2 drinking days and 15.2 abstinent days per average month (30.4 days)
†Psychosocial support was defined as bi-weekly counseling.
SUBSET POPULATION: COMPLETE ABSTINENCE FROM ALCOHOL1-3
SUBSET POPULATION: PATIENTS TREATED WITH VIVITROL WERE MORE LIKELY TO MAINTAIN COMPLETE ABSTINENCE THROUGHOUT TREATMENT1-3
A predefined subpopulation of lead-in abstinent VIVITROL, XR-NTX 190-mg, and placebo patients (n=53, or 8% of the total study population) was defined as those who reported no drinking during the 7 consecutive days prior to the first injection.
- 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
- Only data for VIVITROL 380 mg and placebo are presented here
A greater proportion of patients with a 7-day lead-in abstinence on VIVITROL maintained abstinence throughout the 6-month study period vs those treated with placebo.
At baseline, the median 7-day abstinent patient had 15.2 drinking days and 15.2 abstinent days per average month (30.4 days).
‡Psychosocial support was defined as bi-weekly counseling.
ADVERSE REACTIONS IN
ALCOHOL-DEPENDENCE PIVOTAL TRIAL2
Adverse reactions that occurred in ≥5% of patients with alcohol dependence treated with VIVITROL and occurred more frequently in the VIVITROL group vs the placebo group
ADVERSE REACTIONS
| VIVITROL 380 mg with Psychosocial Support (n=205) |
Placebo with Psychosocial Support (n=214) |
|
|---|---|---|
| Any ISR | 69% | 50% |
| Injection site tenderness | 45% | 39% |
| Injection site induration | 35% | 8% |
| Nausea | 33% | 11% |
| Headache | 25% | 18% |
| Asthenic conditions | 23% | 12% |
| Injection site pain | 17% | 7% |
| Other ISR (primarily nodules, swelling) | 15% | 4% |
| Insomnia, sleep disorder | 14% | 12% |
| Vomiting NOS | 14% | 6% |
| Anorexia, appetite decreased NOS, appetite disorder NOS | 14% | 3% |
| Diarrhea | 13% | 10% |
| Dizziness, syncope | 13% | 4% |
| Anxiety | 12% | 8% |
| Arthralgia, arthritis, joint stiffness | 12% | 5% |
| Pharyngitis | 11% | 11% |
| Abdominal pain | 11% | 8% |
| Injection site pruritus | 10% | 0% |
| Depression | 8% | 4% |
| Muscle cramps | 8% | 1% |
| Injection site ecchymosis | 7% | 5% |
| Back pain, back stiffness | 6% | 5% |
| Rash | 6% | 4% |
| Dry mouth | 5% | 4% |
| Somnolence, sedation | 4% | 1% |
ISR=injection site reaction NOS=not otherwise specified
Please see the complete list of adverse events in the VIVITROL Prescribing Information.
DISCONTINUATION RATE1,2
Discontinuation rates due to adverse events in controlled clinical trials of 6 months or less were similar in alcohol-dependent patients treated with VIVITROL vs patients treated with placebo.
In clinical trials, the majority of patients treated with VIVITROL experienced adverse reactions with a maximum intensity of "mild" or "moderate."
VIVITROL is not right for everyone. There are significant risks from VIVITROL treatment, including risk of opioid overdose, injection site reactions and sudden opioid withdrawal.
See Important Safety Information below. Discuss all benefits and risks with your patients. See Prescribing Information. Review Medication Guide with your patients.
