A Randomized Acceptability and Safety Study of Suboxone Induction in Heroin Users (P05042)

Condition(s) targeted: Opiate Dependence; Drug Dependence; Substance Dependence

Intervention: Suboxone (SCH 000484) (Drug); Subutex (SCH 028444) (Drug)

Phase: Phase 4

Status: Recruiting

Sponsored by: Schering-Plough

Official(s) and/or principal investigator(s):
Leslie Amass, PhD, Study Director, Affiliation: Schering-Plough

Overall contact:
SP Clinical Trial Registry Call Center, Phone: 1-888-772-8734

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 subjects who are inducted directly onto Suboxone with that of subjects who are inducted first to Subutex and then transferred to Suboxone.

Official title: A Randomized Acceptability and Safety Study of Suboxone Induction in Heroin Users

Study design: Treatment, Randomized, Double Blind (Subject, Investigator), Active Control, Parallel Assignment, Safety/Efficacy Study

Primary outcome: To demonstrate that direct Suboxone induction is not inferior to a Subutex-to-Suboxone induction: response rate at Day 3, assessed by determining the proportion of subjects in each group who receive the scheduled dose of Suboxone at the Day 3 study visit

Secondary outcome:

Illicit opioid and non-opioid drug use: UDS

Illicit opioid and non-opioid drug use: SUI

Self-reported opioid withdrawal symptoms: SOWS

Observer-rated opioid withdrawal symptoms: OOWS

Addiction-related problem profiles: ASI-Lite

Compliance rate

Response rate

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 subjects who are inducted directly onto Suboxone with that of subjects 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 subjects assigned to Suboxone received 16 mg of Suboxone (administered as two 8-mg tablets) on Day 3, and the 105 subjects 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.

Minimum age: 15 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Subjects must be males or non-pregnant, non-lactating females.

- Subjects must be at least 15 years of age, of either sex, and any race.

- Subjects (and/or the parent or guardian for subjects under the age of legal consent or

who otherwise are unable to provide independent consent) must demonstrate willingness to participate in the study and to adhere to dose and visit schedules.

- Subjects must meet Diagnostic and Statistical Manual of Mental Disorders, Fourth

Edition, Text Revision (DSM-IV-TR) criteria for opioid dependence.

- Subjects must have a methadone- and buprenorphine-negative UDS result prior to

randomization.

- Each subject must confirm that he or she is practicing adequate contraception. Female

volunteers of childbearing potential (including women who are less than 1 year postmenopausal and women who will be sexually active during the study) must agree to use a medically accepted method of contraception or must be surgically sterilized prior to screening, while receiving protocol-specified medication, and for 30 days after stopping the medication. Women who have been postmenopausal for >=1 year (ie, women who have experienced 12 or more consecutive months of amenorrhea) will be exempted from the requirement to use contraception during the study. Acceptable methods of contraception include condoms (male and female) with or without a spermicidal agent, diaphragm or cervical cap with a spermicidal agent, medically prescribed intrauterine device, oral or injectable hormonal contraceptives, and surgical sterilization (eg, hysterectomy or tubal ligation).

- Female subjects of childbearing potential must have a negative urine beta-human

chorionic gonadotropin (beta-hCG) test prior to enrollment in the study

Exclusion Criteria:

- Subjects for whom treatment with either Subutex or Suboxone as required in the

protocol would be inconsistent with national labeling.

- Subjects who are unwilling or unable to comply with the requirements of the protocol

(eg, pending incarceration) or are in a situation or condition that, in the opinion of the investigator, may interfere with participation in the study.

- Subjects who are participating in any other clinical study in which medication(s) are

being delivered.

- Subjects with known allergy or sensitivity to buprenorphine or naloxone.

- Subjects who are on the staff, affiliated with, or a family member of the staff

personnel directly involved with this study.

- Subjects with serious untreated Axis I DSM-IV-TR psychiatric co-morbidity (eg, those

who are actively suicidal or homicidal, have untreated schizophrenia, etc). Polysubstance abuse or dependence will not exclude subjects except in the case of unauthorized and significant benzodiazepine use requiring medical detoxification or alcohol dependence requiring medical detoxification.

- HIV-positive subjects with clinical acquired immunodeficiency syndrome (AIDS).

- Methadone or buprenorphine maintenance or detoxification within 30 days of

enrollment.

SP Clinical Trial Registry Call Center, Phone: 1-888-772-8734

Investigational Site 15, Zagreb 10000, Croatia; Recruiting

Investigational Site 16, Zagreb 10000, Croatia; Recruiting

Investigational Site 17, Rijeka 51000, Croatia; Recruiting

Investigational Site 4, Nimes Cedex 9 30029, France; Recruiting

Investigational Site 5, Tours 37000, France; Recruiting

Investigational Site 7, Clermont-Ferrand Cedex 63003, France; Recruiting

Investigational Site 6, Paris Cedex 14 75674, France; Recruiting

Investigational Site 36, Bondy Cedex 93143, France; Recruiting

Investigational Site 33, Aveiro 3810-176, Portugal; Recruiting

Investigational Site 34, Olhao 8700-414, Portugal; Recruiting

Investigational Site 35, Lisbon 1749-002, Portugal; Recruiting

Investigational Site 10, Koper 6000, Slovenia; Recruiting

Investigational Site 11, Piran 6320, Slovenia; Recruiting

Investigational Site 13, Hastings TN34 1LY, United Kingdom; Recruiting

Starting date: February 2008
Ending date: December 2009
Last updated: October 29, 2008