Buvidal therapeutic indications
Buvidal is indicated for the treatment of opioid dependence within a framework of medical, social and psychological treatment.
Treatment is intended for use in adults and adolescents aged 16 years or over.
Buvidal mechanism of action
Buprenorphine is an opioid partial agonist/antagonist which binds to the μ (mu) and K (kappa) opioid receptors of the brain.
Its activity in opioid maintenance treatment is attributed to its slowly reversible properties with the μ-opioid receptors, which, over a prolonged period, might minimise the need for illicit opioids in patients with opioid dependence.
The efficacy and safety of Buvidal in the treatment of opioid dependence have been investigated in a randomised, double-blind, phase 3 study and a long-term, open-label, phase 3 safety study in patients with moderate to severe opioid dependence.
Phase 3 double-blind study
(Lofwall MR, Walsh SL, Nunes EV, et al. JAMA Intern Med. 2018;178(6):764–773.)
The efficacy and safety of Buvidal in the treatment of opioid dependence were established in a pivotal phase 3, randomised, double-blind, double-dummy, active-controlled, flexible-dose study in patients with moderate to severe opioid dependence. In this study, 428 patients were randomised to one of two treatment groups.
Patients in the Buvidal group (n=213) received weekly injections (16–32 mg) during the first 12 weeks followed by monthly injections (64–160 mg) during the last 12 weeks, plus daily doses of sublingual placebo tablets during the complete treatment period.
Patients in the sublingual buprenorphine/naloxone group (n=215) received weekly placebo injections during the first 12 weeks and monthly placebo injections during the last 12 weeks, plus daily sublingual buprenorphine/naloxone tablets during the complete treatment period (8–24 mg during the first 12 weeks and 8–32 mg during the last 12 weeks).
During the 12 weeks with monthly injections, patients in both groups could receive one additional 8 mg weekly Buvidal dose per month, if needed.
Patients attended 12 weekly visits during the first 12 weeks and 6 visits during the last 12 weeks (3 scheduled monthly visits and 3 random urine toxicology visits). At each visit, efficacy and safety outcome measures were assessed.
The study met the primary endpoint of non-inferiority in the mean percentage of urine samples negative for illicit opioids during treatment weeks 1–24 for the Buvidal group compared with the sublingual buprenorphine/naloxone group (Table 1).
Table 1. Efficacy variables in a pivotal phase 3, randomised, double-blind, double-dummy, active-controlled, flexible-dose study in patients with moderate to severe opioid dependence
|Efficacy variable||Statistic||Buvidal||SL BPN/NX||Treatment difference (%)a (95% CI)||P-value|
|Percentage of urine samples negative for illicit opioids||N||213||215|
|LS mean (%) (SE)||35.1 (2.48)||28.4 (2.47)||6.7||<0.001|
|95% CI||30.3–40.0||23.5–33.3||–0.1 to 13.6|
|CDF of the percentage of urine samples negative for illicit opioids over weeks 4–24||N||213||215|
CDF = cumulative distribution function, CI = confidence interval, LS = least squares; SE = standard error, SL BPN/NX = sublingual buprenorphine/naloxone.
a Difference = Buvidal – SL BPN/NX.
b The p-value was for superiority.
Figure 1. Percentage of patients with urine samples negative for illicit opioids over the 24-week treatment period
(EPAR December 2018 EMEA/H/C/004651/0000 https://www.ema.europa.eu/documents/assessment-report/buvidal-epar-public-assessment-report_en.pdf).
The superiority of Buvidal versus sublingual buprenorphine/naloxone was met (pre-specified test order) for the secondary endpoint of the cumulative distribution function (CDF) for the percentage of opioid-negative urine samples during treatment weeks 4–24 (Table 1).
Of the 428 randomised patients, 69.0% (147/213) of the patients in the Buvidal treatment group and 72.6% (156/215) of the patients in the sublingual buprenorphine/naloxone treatment group completed the 24-week treatment period.
Phase 3 open-label study
(EPAR December 2018 EMEA/H/C/004651/0000 https://www.ema.europa.eu/documents/assessment-report/buvidal-epar-public-assessment-report_en.pdf; Buvidal Summary of Product Characteristics)
A long-term, open-label, phase 3 safety study with flexible dosing of weekly and monthly Buvidal for 48 weeks was conducted. The study enrolled a total of 227 patients with moderate to severe opioid dependence, of which 190 patients were switched from sublingual buprenorphine (with or without naloxone), and 37 patients were new to buprenorphine treatment.
During the 48-week treatment period, patients could be transitioned between weekly and monthly injections with Buvidal and between doses (8–32 mg weekly Buvidal and 64–160 mg monthly Buvidal) according to the physician’s clinical judgement.
For patients who were switched from sublingual buprenorphine, the percentage of patients with illicit opioid-negative urine samples was 78.8% at baseline and 84.0% at the end of the 48-week treatment period.
For the new-to-treatment patients, the percentage of patients with illicit opioid-negative urine samples was 0.0% at baseline and 63.0% at the end of the 48-week treatment period.
Overall, 156 patients (68.7%) completed the 48-week treatment period.
© 2020 Camurus AB. All rights reserved | INT-BUV-1900007 | Date of preparation: February 2019