Clinical trial NCT00604188
Conditions: Opiate Dependence Drug Dependence Substance Dependence
Sponsor: Merck Sharp & Dohme LLC
Start date: 2008-02-22; Completion date: 2009-12-10
Enrollment: 188 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to assess the acceptability and safety of Suboxone in heroin users as a replacement therapy for opioid dependency by comparing the clinical response of participants who are inducted directly onto Suboxone with that of participants who are inducted first to Subutex and then transferred to Suboxone.

Detailed description:
Rationale: Once Suboxone becomes available for widespread clinical use, it is anticipated that opioid-dependent patients seeking treatment with buprenorphine will be placed directly onto Suboxone. Two strategies that have had good success for inducting patients onto Suboxone have been developed: 1) a "bridging" procedure in which patients initiate therapy with Subutex and then transfer to Suboxone, and 2) a direct Suboxone induction procedure. However, there have been no controlled studies of direct Suboxone induction, and it is not clear whether using a Subutex-to-Suboxone induction procedure would produce any added clinical benefit for the patient relative to direct Suboxone induction.

This study addresses a post-marketing commitment to the European Medicines Agency to conduct a prospective, controlled study of induction with Suboxone. Using a prospective, randomized, active-drug-controlled, double-blind and double-dummy design, this study will assess the acceptability and safety of Suboxone in heroin users by comparing the clinical response of participants who are inducted directly onto Suboxone with that of participants who are inducted first to Subutex and then transferred to Suboxone. The dose regimen used during the induction phase of this study is identical to that used in the pivotal efficacy study comparing Suboxone and Subutex (Fudala et al, 2003), which is included in the Suboxone Summary of Product Characteristics. The data collected in this study will include information on the extent of opioid use before treatment initiation.

Two strategies for inducting opioid-dependent patients using short-acting opioids (eg, heroin) onto Suboxone have emerged from published US studies. One involves using Subutex to "bridge" the transition to Suboxone by using Subutex over the first 2 days before transferring directly to Suboxone on the third day. The other involves direct Suboxone induction, in which patients receive Suboxone as the initial dose followed by continued rapid Suboxone dose titration.

In the pivotal efficacy study, opiate-dependent heroin users assigned to either Subutex or Suboxone groups received an induction dose of 8 mg of Subutex (administered as a single 8-mg tablet) on Day 1 and 16 mg of Subutex (administered as two 8-mg tablets) on Day 2. The 109 participants assigned to Suboxone received 16 mg of Suboxone (administered as two 8-mg tablets) on Day 3, and the 105 participants assigned to Subutex received 16 mg of Subutex (administered as two 8-mg tablets) on Day 3. The induction schedule used in the pivotal trial, in which a Subutex-to-Suboxone bridging procedure was used, was successful for inducting heroin-dependent patients onto Suboxone, achieving good compliance and resulting in relatively few AEs accounting for treatment discontinuation.

Overall, several large-scale studies using Suboxone as an initial medication have been conducted with good results, and it appears clear that, as was the case in the pivotal study, most patients safely tolerate a total dose of at least 8 mg on the first day of treatment. However, as these studies were not controlled, it remains unclear whether using a Subutex-to-Suboxone induction procedure would produce any added clinical benefit to the patient relative to a direct Suboxone induction procedure. Furthermore, there have been no studies of direct Suboxone induction outside of the United States.

Arms: arm 1: Participants received 8 mg of Suboxone and placebo Subutex on Day 1, 16 mg of Suboxone and placebo Subutex on Day 2, and all participants received open label Suboxone from Day 3 to Day 28. Suboxone dosage may be titrated from Day 4 to Day 28 up to 24 mg per day. arm 2: Participants received 8 mg Subutex and placebo Suboxone on Day 1, 16 mg Subutex and placebo Suboxone on Day 2, and all participants received open label Suboxone from Day 3 to Day 28. Suboxone dosage may be titrated from Day 4 to Day 28 up to 24 mg per day.
Interventions: intervention 1: Suboxone (SCH 000484) intervention 2: Subutex (SCH 028444)
Intervention descriptions: intervention 1: 2 mg and 8 mg sublingual tablets, Contains Buprenorphine Hydrochloride and Naloxone. Daily dosage of 8 mg - 24 mg. Duration: 28 Days intervention 2: 2 mg and 8 mg sublingual tablets, Contains Buprenorphine Hydrochloride. Daily dosage of 8 mg - 24 mg. Duration: 28 Days

Protocol documents: