Asunaprevir/Beclabuvir/Daclatasvir (Clinical Trial) + Buprenorphine/Naloxone = Unknown or no reaction

Study Design

An open-label, 2-part study was conducted to assess the effects of a fixed dose combination of Daclatasvir/Asunaprevir/Beclabuvir (DCV/ASV/BCV) on the pharmacokinetics of Methadone, Buprenorphine (BUP), and active metabolite Norbuprenorphine (NorBUP). In part 2 of the study, participants received their once-daily dose of Buprenorphine/Naloxone (8/2mg to 24/6mg sublingual film) throughout. On days 2 through 12, participants received twice-daily doses of the fixed dose combination of DCV/ASV/BCV (30/200/75mg) + additional BCV 75mg BID to achieve the higher BCV exposures obserevd in HCV-infected patients. All study drugs were administered with food.A total of 16 participants were enrolled in part 2 of the study. One participants withdrew consent on day 6. PK blood samples were taken predose and through 24 hours post dose on day 1 and 12.

Study Results

Drug NameCmax GMR (90% CI)AUC GMR (90% CI)Buprenorphine0.76 (0.65-0.90)0.92 (0.81-1.05)Norbuprenorphine0.98 (0.81-1.18)0.98 (0.83 - 1.17)Coadministration of Buprenorphine/Naloxone with DCV/ASV/BCV + additional BCV showed no clinically meaningful effect on BUP or NorBUP PK (90% CI of GMRs were within the no effect range of 0.5 - 2.00).Authors stated that the PK profiles of DCV, ASV, and BCV were similar to historical data and did not indicate that Buprenorphine/Naloxone had any major effects on these agents. There were no adverse events of drug withdrawal or adjustments of opioid replacement therapy required.

Study Conclusions

References

X Tao, K Sims, M Hesney. Evaluation of drug-drug interactions between the fixed-dose combination of daclatasvir/asunaprevir/beclabuvir and methadone or buprenorphine/naloxone. 50th Annual Meeting Of The European Association For The Study Of The Liver. Vienna, Austria. ; 2015.