Presentation on theme: "DOUBLE BLIND RANDOMIZED PLACEBO CONTROLLED STUDY OF EFFECTIVENESS OF IMPLANTABLE NALTREXONE (PRODETOXONE) FOR TREATMENT OF HEROIN ADDICTION (Interim analysis)"— Presentation transcript:
DOUBLE BLIND RANDOMIZED PLACEBO CONTROLLED STUDY OF EFFECTIVENESS OF IMPLANTABLE NALTREXONE (PRODETOXONE) FOR TREATMENT OF HEROIN ADDICTION (Interim analysis) Е. Krupitsky, E. Zvartau, V. Egorova, D. Masalov, А. Burakov, М. Tsoy, N. Bushara, Т. Romanova, Е. Verbitskaya, Ch. О’Brian, G. Woody St.-Petersburg Pavlov State Medical University, University of Pennsylvania Supported by NIDA Grant R01-DA-017317
Implantable Naltrexone: Route and Dosage PRODETOXONE, tablets for implantation 1000 mg of naltrexone PRODETOXONE, tablets for implantation 1000 mg of naltrexone
Pharmacokinetics of Prodetoxone (data from the manufacturer) Blood samples were collected in one week, one and two months after implantation 0 10203040506070 Time after implantation, days Concentration, ng/ml Naltrexone metaboliteNaltrexone
METHODS 306 male and female heroin addicts after detoxification, giving informed consent and passing a Naloxone challenge had been randomly assigned to one of three treatment groups (102 PATIENTS EACH). Three cell study design: 1. Naltrexone Implant (1000 mg) (3 times, every 2 months) + Oral Placebo (OP+NI). 2. Oral Naltrexone (50mg/day) + Implant Placebo (3 times, every 2 months) (ON+PI). 3. Implant Placebo (3 times, every 2 months) + Oral Placebo (OP+PI). All patients received biweekly clinical management / compliance enhancement counseling. Treatment lasted 6 months. Control of abstinence, compliance, psychiatric symptoms, and side effects – every other week. All patients had at least one family member who was able to supervise medication compliance. Study design: Double blind double dummy placebo controlled randomized clinical trial.
Demographics and Clinical Characteristics Group OP+PION+PIOP+NI N102 Gender (female) 27,5% Age (M±SEM) 28,0±0,4027,9±0,4028,7±0,45 Duration of heroin dependence (M±SEM) 7,8±0,387,9±0,418,3±0,39 Number of previous treatments (M±SEM) 3,8±0,314,3±0,374,9±0,41
Genetic Analysis Thomas Kosten, MD David Nielsen, PhD Baylor College of Medicine I). Gens of µ-opiate receptors: 1)OPRM11, 2) OPRM12, 3) OPRM13 II). Gene of ζ-opiate receptor: OPRK1 III). Gene of the enzyme COMT: COMT
Effect of genotype on the completion of the treatment: Uncertainty Coefficients (I) [OPRM13,COMT,OPRK1] 0,0 0,1 0,2 0,3 0,4 0,5 0,6 PO/NI (p=0.9)ON/PI (p=0.056)PO/PI (p=0.031) [AAAGTT] or [AGAGTT]the others
Effect of genotype on the completion of the treatment: Uncertainty Coefficients (II) [OPRM11,COMT,OPRK1] 0 0,1 0,2 0,3 0,4 0,5 0,6 PO/NI (p=0.89)ON/PI (p=0.075)PO/PI (p=0.056) [CCAGTT] or [CTAGTT]the others
Effect of genotype on the completion of the treatment: Kaplan-Meier Survival Functions (p=0.02)(p=0.03)
Effect of genotype on the completion of the treatment: Treatment Effectiveness Score p=0.063 p=0.043
Use of other drugs Fisher's Exact Test P=0,003 Benzos Amphetamines THC
Summary Implantable naltrexone demonstrated greater effectiveness in the treatment of heroin dependence in comparison to oral naltrexone and placebo. Implantable naltrexone is basically comparable to oral naltrexone and placebo in terms of safety and tolerability except surgical adverse events.
LIMITATIONS for PRODETOXONE 1.Surgical procedure 2.Wound infections (particularly in HIV+ individuals) 3.Cosmetic defects 4.Relatively easy to take out within the first few weeks after implantation 5.Dos not provide 2 months long blockade in some patients (small proportion)