Detoxification/Medication or Placebo Phase (days 4C8) On days 4C8, no morphine was administered
Detoxification/Medication or Placebo Phase (days 4C8) On days 4C8, no morphine was administered. significant findings, the study was terminated early. On the study day time 5 MHOWS, subjects treated with lofexidine experienced significantly lower scores (equating to fewer/less severe withdrawal symptoms) than placebo subjects (Least squares means 19.5 2.1 versus 30.9 2.7; p=0.0019). Lofexidine subjects had significantly better retention in treatment than placebo subjects (38.2% versus 15.2%; Log rank test p=0.01). Conclusions Lofexidine is definitely well tolerated and more efficacious than placebo for reducing opioid withdrawal symptoms in inpatients undergoing medically supervised opioid detoxification. Trial Sign up trial registry name A Phase 3 Placebo-Controlled, Double-Blind Multi-Site Trial of Lofexidine for Opiate Withdrawal, sign up quantity “type”:”clinical-trial”,”attrs”:”text”:”NCT00032942″,”term_id”:”NCT00032942″NCT00032942, URL for the registry http://clinicaltrials.gov/ct/show/”type”:”clinical-trial”,”attrs”:”text”:”NCT00032942″,”term_id”:”NCT00032942″NCT00032942?order=4. ?) and placebo were from Britannia Pharmaceuticals, Ltd. Study medications were offered to the site pharmacists from the Cooperative Studies Program Clinical Study Pharmacy Coordinating Center (CSPCRPCC) in Albuquerque, NM in subject-specific packages for days 4 to 10. They were distributed to the three sites as 0.2 mg tablets of lofexidine or matching placebo. Placebo was used rather than an active control because the study was intended to support an FDA software. After tolerability is definitely assured, the next objective required from the FDA is definitely to show the effectiveness of a new molecular entity by showing that the medication is definitely significantly more efficacious than placebo. 2.3. Randomization and Blinding The Cooperative Studies Program Coordinating Center (CSPCC) in Perry Point, MD generated a randomization sequence for each site separately, in blocks of four, using non-sequential subject numbers. The site coordinator or investigator called the CSPCC just before the detoxification phase was to begin to randomize a subject to study treatment. After confirming eligibility, the CSPCC offered the site having a randomization quantity which corresponded to a specific drug therapy kit that experienced previously been shipped to the site from the Albuquerque CSPCRPCC. The study drug packages were labeled with the study name, a study drug name (the same on all packages), the number of tablets per cards, the randomization quantity, and the address and 24-hour emergency phone number for the CSPCRPCC. In an emergency, the blind Quinacrine 2HCl could be broken by phoning the CSPCRPCC 24-hour emergency phone number. 2.4. Design This was an 11-day time study that experienced three phases: 2.4.1. Opioid Agonist Stabilization Phase (days 1C3) Because of the extensive variations in the amount of heroin that the study population was Quinacrine 2HCl dependent upon, placing all subjects on a fixed dose of morphine decreased the variability of baseline opiate levels across subjects. Morphine sulfate was given subcutaneously to stabilize subjects on a fixed dose of opiate agonist. In this phase, participants received up to 100mg/day time (25 mg at 06:30h, 11:00h, 16:30h, 22:00h) of Quinacrine 2HCl subcutaneous morphine sulfate for three days. Secondly, the use of a stabilization phase was also suggested by the use of the MHOWS as the primary outcome measure. The choice of the MHOWS was based on discussions between the study sponsor, NIDA and the FDA. The 100mg/day time dose was chosen since it is equivalent to 50 mg of oral methadone which is definitely intermediate between the treatment initiation and maintenance average of 80 mg in the Philadelphia VAMC in 1997. This dose experienced previously been used in a lofexidine Phase 1 & 2 open tolerability study at Philadelphia VAMC and Los Angeles/Very long Fgfr2 Beach VAMC sites without subjects exhibiting intoxication, sedation or designated withdrawal and was well tolerated. 2.4.2. Detoxification/Medication or Placebo Phase (days 4C8) On days 4C8, no morphine was given. As explained above, a call was placed to the Cooperative Studies Program Coordinating Center (CSPCC) for randomization. The 1st dose of lofexidine/placebo was given at 0800h on day time 4. Participants were medicated with 3.2 mg/day time of lofexidine or placebo given as four 0.2 mg tablets of lofexidine.