Buprenorphine implants for treatment of opioid dependence: randomized comparison to placebo and sublingual buprenorphine/naloxone

Addiction. 2013 Dec;108(12):2141-9. doi: 10.1111/add.12315. Epub 2013 Sep 18.

Abstract

Aims: To evaluate the safety and efficacy of buprenorphine implants (BI) versus placebo implants (PI) for the treatment of opioid dependence. A secondary aim compared BI to open-label sublingual buprenorphine/naloxone tablets (BNX).

Design: Randomized, double-blind, placebo-controlled trial. Subjects received either four buprenorphine implants (80 mg/implant) (n = 114), four placebo implants (n = 54) or open-label BNX (12-16 mg/day) (n = 119).

Setting: Twenty addiction treatment centers.

Participants: Adult out-patients (ages 18-65) with DSM-IV-TR opioid dependence.

Measurements: The primary efficacy end-point was the percentage of urine samples negative for opioids collected from weeks 1 to 24, examined as a cumulative distribution function (CDF).

Findings: The BI CDF was significantly different from placebo (P < 0.0001). Mean [95% confidence interval (CI)] proportions of urines negative for opioids were: BI = 31.2% (25.3, 37.1) and PI = 13.4% (8.3, 18.6). BI subjects had a higher study completion rate relative to placebo (64 versus 26%, P < 0.0001), lower clinician-rated (P < 0.0001) and patient-rated (P < 0.0001) withdrawal, lower patient-ratings of craving (P < 0.0001) and better subjects' (P = 0.031) and clinicians' (P = 0.022) global ratings of improvement. BI also resulted in significantly lower cocaine use (P = 0.0016). Minor implant-site reactions were comparable in the buprenorphine [27.2% (31 of 114)] and placebo groups [25.9% (14 of 54)]. BI were non-inferior to BNX on percentage of urines negative for opioids [mean (95% CI) = 33.5 (27.3, 39.6); 95% CI for the difference of proportions = (-10.7, 6.2)].

Conclusions: Compared with placebo, buprenorphine implants result in significantly less frequent opioid use and are non-inferior to sublingual buprenorphine/naloxone tablets.

Trial registration: ClinicalTrials.gov NCT01114308.

Keywords: Buprenorphine; drug addiction; drug implants; maintenance therapy; opioid dependence; treatment adherence.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, American Recovery and Reinvestment Act
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Sublingual
  • Adolescent
  • Adult
  • Aged
  • Buprenorphine / administration & dosage*
  • Buprenorphine / adverse effects
  • Double-Blind Method
  • Drug Implants
  • Female
  • Humans
  • Male
  • Middle Aged
  • Naloxone / administration & dosage*
  • Naloxone / adverse effects
  • Narcotic Antagonists / administration & dosage*
  • Narcotic Antagonists / adverse effects
  • Opiate Substitution Treatment / methods
  • Opioid-Related Disorders / drug therapy*
  • Tablets
  • Treatment Outcome
  • Young Adult

Substances

  • Drug Implants
  • Narcotic Antagonists
  • Tablets
  • Naloxone
  • Buprenorphine

Associated data

  • ClinicalTrials.gov/NCT01114308