Feasibility of Double-Blind Clinical Trials with Oral Diacetylmorphine: A Randomized Controlled Phase II Study in an Inpatient Setting

The aim of this study was to evaluate the feasibility of con- ducting double-blind controlled randomized clinical trials using twice-a-day immediate-release oral diacetylmorphine (DAM) in heroin-dependent patients, by means of measur- ing the capacity of oral DAM to block opiate withdrawal and clinicians’ ability to distinguish it from morphine and metha- done. This was a randomized, phase II, double-blind, multi- center pilot study comparing immediate-release oral DAM, slow-release oral morphine and oral methadone adminis- tered twice a day during 10 days. Forty-five heroin-depen- dent patients were randomly assigned to these three treat- ment groups in an inpatient regime. Patients were stabilized with a mean of 350 mg (SD = 193) of immediate-release oral DAM, 108 mg (SD = 46.2) of slow-release oral morphine and 40 mg (SD = 17.9) of methadone. No statistically significant differences were found between any studied medication in clinical outcome. Neither patients nor clinicians were able to identify the administered medication. This study shows the feasibility of double-blind clinical trials using b.i.d. immedi- ate-release oral DAM allowing further phase III clinical trials in the process of introducing oral DAM as a medication for heroin-dependent patients not responding to standard maintenance treatments.