and/or HIV infections. Krupitsky (2013) 1-yr safety and effectiveness observational extension study 114 patients from RCT who continued on or were switched from PBO to ER-NTX Responses seen in the DB RCT were maintained during the extension trial: 62.3% of patients the phase 50.9% were abstinent from opioids No new safety concerns. Table Study Methods: Naltrexone ER Injection in Opioid Dependence Methods Participants Interventions Outcomes Funding, Quality, Krupitsky E, Nunes EV, Ling W, Illeperuma A, Gastfriend DR, Silverman BL. Injectable extended-release naltrexone for opioid dependence: a double-blind, placebo-controlled, multicentre randomised trial. Lancet. 2011 Apr 30;377(9776):1506-13. 24-wk, 13-site MC DB PC phase III RCT in Russia ITT, LOCF. Multiplicity correction was used for craving and retention outcomes. ≥ 18 yo; DSM-IV dx of opioid dependence; completing inpatient opioid detoxification (≤ 30 d); off opioids for at least 7 d; voluntarily seeking tx (not under justice system coercion); supervised by significant other to adhere to study procedures. Primarily young (29 yo), male (88%), white (99%), addicted to ER-NTX 380 mg i.m. within 1 wk of detox then q4wk thereafter PBO 24 wk (6 injections) Offered 12 biweekly session of individual drug counseling UDS for morphine and POM: Confirmed abstinence response profiles (i.e., the cumulative percent of opioid-free weeks) during wks 5–24; confirmed abstinence responders. Confirmed abstinence was defined as a negative urine drug test and no Sponsor: Alkermes Moderate Pts may have challenged the tx and been unblinded (pts on PBO could get high on opioids). Wks 1–4 were prospectively omitted from the POM. Results reflect the more stable period of abstinence
heroin for about 10 years. Excluded pregnancy, breastfeeding, significant medical conditions, naloxone challenge; hepatic failure; hx of AIDS-indicator disease; active hepatitis or AST or ALT >3x ULN; intolerance or hypersensitivity to naltrexone, carmellose, or psychosis; bipolar disorder; major depressive disorder with suicidal ideation; present dependence on substances other than opioids or heroin, including alcohol; positive urine test for cocaine or amphetamines; naltrexone use within past 6 mo. Prohibited drugs: naltrexone, buprenorphine, levacetylmethadol, methadone, other prescription opioids, antipsychotics, anticonvulsants, antidepressants, and anxiolytics. Permitted anticonvulsants if dosing was stable; and short-acting insomnia drugs, such as zopiclone, as required. methadone qwk opioid use on the timeline follow-back (TLFB) survey. SOMs: opioid-free days on TLFB; opioid craving scores (VAS number of days of retention; relapse to physiologic opioid dependence (naloxone challenge test). Other: HIV risk; SF-36; EuroQol-5 general health; CGI. Safety: TEAEs; VS; labs including LFTs; injection site; EKGs (5–24 wk) and may be biased. Only 45.6% of all patients completed the study, with a relatively large absolute diff of 15.3% in completion rates between tx groups favoring NTX IMI. External Validity to VA: Possible in some pts, particularly in young age, male, HIV+, HCV+, without serious active medical or psychiatric illnesses, and not on the excluded Diffs in country and health care system. Study authors suggested that ER-NTX may be a tx to consider in those whose employment prohibits opioid use, those with a relatively recent addiction to opioids, and those who wish to secure their recovery after a successful course of agonist therapy. reported reported
NNT 8 (5–55) Secondary Outcome Measures Proportion of self-reported opioid-free days, % 99.2 60.4 Diff 38.7 0.0004 Craving: mean change in VAS score from BL –10.1 to 0.7 to 4.4) Diff to 6.4) <0.0001 Number of days of retention >168 (CI not calculable) 96 RR 0.61 0.0042 Pts with positive naloxone challenge test, % 0.8 13.7 RR 17.3 <0.0001 Other Outcomes Pts who completed DB tx period, % 53.2 37.9 RR 1.40 0.0171 Risk for HIV: mean change in behavior scores from BL –0.187 to –0.130 (–0.173 to Diff (–0.113 to 0.0212 EQ-5D: mean change in VAS self-ratings from BL 14.1 2.7 Diff 11.4 0.0005 Rated much or very much improved on CGI, % 85.9 57.5 (45.7 1.49 0.0002 Safety SAEs, % of pts 2 3 Diff –1 NSD % of pts 2 2 Diff 0 — % of pts 26 10 Diff 16 0.001
ER-NTX Baseline 0 / 74 (0.0) 0 / 52 (0.0) 0 / 126 (0.0) Peak of 11/103 (10.7) at Wk 4. NSDs for ER-NTX vs. PBO and for HIV– vs. HIV+ gps. Postbaseline 9 / 62 (14.5) 12 / 45 (26.7) 21 / 107 (19.6) PBO Baseline 0 / 70 (0.0) 0 / 54 (0.0) 0 / 124 (0.0) Peak of 5 / 81 (6.2) at Wk 4. NSD for HIV– vs. HIV+ gps. Postbaseline 8 / 51 (15.7) 3 / 34 (8.8) 11 / 85 (12.9) Aspartate aminotransferase 3 x ULN, n/N (%) ER-NTX Baseline 0 / 74 (0.0) 0 / 52 (0.0) 0 / 126 (0.0) Peak of 9 / 103 (8.7) at Wk 4. NSDs for ER-NTX vs. PBO and for HIV– vs. HIV+ gps Postbaseline 2 / 62 (3.2) 13 / 45 (28.9) 15 / 107 (14.0) PBO Baseline 0 / 70 (0.0) 0 / 54 (0.0) 0 / 124 (0.0) Peak of 5 / 81 (6.2) at Wk 4. NSD between and HIV+ gps. Postbaseline 5 / 51 (9.8) 4 / 34 (11.8) 9 / 85 (10.6) transferase 3 x ULN, n/N (%) ER-NTX Baseline 10 / 74 (13.5) 13 / 52 (25) 23 / 126 (18.3) Highest % was at BL. Postbaseline peak of 18 / 103 (17.5) at Wk 4. NSDs for ER-NTX vs. PBO and for Postbaseline 11 / 62 (17.7) 14 / 45 (31.1) 25 / 107 (23.4)