Induction of opioid-dependent individuals onto buprenorphine and buprenorphine/naloxone soluble-films

Abstract

A sublingual soluble-film formulation of buprenorphine/naloxone (B/N) has been approved by the US Food and Drug Administration for the treatment of opioid dependency. This preparation provides unit-dose, child-resistant packaging amenable to tracking and accountability, offers more rapid dissolution, and has a potentially preferred taste vs. tablets. This study compared the ability of buprenorphine (B) and B/N films to suppress spontaneous withdrawal in opioid-dependent volunteers. Participants were maintained on morphine and underwent challenge sessions to confirm sensitivity to naloxone-induced opioid withdrawal. Subjects were randomized to receive either B (16 mg, n = 18) or B/N (16/4 mg, n = 16) soluble films for 5 days. The primary outcome measure was the Clinical Opiate Withdrawal Scale (COWS) score. Thirty-four subjects completed induction onto soluble films. There was a significant decrease in COWS scores but no significant differences between the groups. The results support the use of B and B/N soluble films as safe and effective delivery methods for opioid induction.

Conflict of interest statement

Funding for the study described in this article was provided by Reckitt Benckiser Pharmaceuticals Inc. The company also manufactures drugs used in the study. Dr. Strain is a consultant to and paid member of the Scientific Advisory Board of Reckitt Benckiser Pharmaceuticals. The terms of this arrangement are being managed by the Johns Hopkins University in accordance with its conflict of interest policies. Through his university, Dr. Bigelow has received research support from Titan Pharmaceuticals, Inc., developer/manufacturer of a different B formulation.

Figures

Figure 1

Participant enrollment and disposition.

Figure 2

Results from the challenge sessions during the morphine maintenance phase of the study. Participants received an intramuscular injection of either placebo or naloxone (0.4 mg). Mean (SEM) peak ratings for COWS (Clinical Opioid Withdrawal Scale), visual analog scale (VAS) ratings of Bad Effects, and maximum pupil diameter increase are shown. Asterisks indicate a significant difference (p

Figure 3

Time course results for the first five days of soluble film (SF) administration. Shown are mean (SEM) ratings on the COWS (Clinical Opioid Withdrawal Scale), Visual analog scale ratings of High, Good Effects, and Bad Effects, and pupil diameter. Filled symbols indicate a significant difference from the baseline value (−0.5 hours on each day of assessment).

Figure 4

Schedule of study procedures. The vertical arrow between challenge sessions 1 and 2 indicates there was at least one day off between the sessions. RRU = Residential Research Unit; OP = outpatient.