Sustained-Release Buprenorphine (RBP-6000) Blocks the Effects of Opioid Challenge With Hydromorphone in Subjects With Opioid Use Disorder

Abstract

A major goal for the treatment of opioid use disorder is to reduce or eliminate the use of illicit opioids. Buprenorphine, a μ-opioid receptor partial agonist and kappa opioid receptor antagonist, is now being developed as a monthly, sustained-release formulation (RBP-6000). The objective of this study was to demonstrate that RBP-6000 blocks the subjective effects and reinforcing efficacy of the μ-opioid receptor agonist hydromorphone (intramuscularly administered) in subjects with moderate or severe opioid use disorder. Subjects were first inducted and dose stabilized on sublingual buprenorphine/naloxone (8-24 mg daily; dose expressed as the buprenorphine component), then received two subcutaneous injections of RBP-6000 (300 mg) on Day 1 and Day 29. Hydromorphone challenges (6 mg, 18 mg or placebo administered in randomized order) occurred on 3 consecutive days of each study week before and after receiving RBP-6000. Subjects reported their responses to each challenge on various 100-mm Visual Analogue Scales (VAS). Subjects also completed a choice task to assess the reinforcing efficacy of each hydromorphone dose relative to money. At baseline, mean "drug liking" VAS scores for hydromorphone 18 mg and 6 mg versus placebo were 61 mm (95% confidence interval, 52.3-68.9) and 45 mm (95% confidence interval, 37.2-53.6), respectively. After 300 mg RBP-6000 was administered, mean VAS score differences from placebo were less than 10 mm through week 12. The reinforcing efficacy of hydromorphone decreased in a parallel manner. This study demonstrated that RBP-6000 at a 300 mg dose provides durable and potent blockade of the subjective effects and reinforcing efficacy of hydromorphone in subjects with moderate or severe opioid use disorder.

Figures

FIGURE 1

Study design.

FIGURE 2

Plot of mean difference and 95% confidence interval for drug liking VAS score. A, Comparison of 18-mg hydromorphone versus placebo. B, Comparison of 6-mg hydromorphone versus placebo.

FIGURE 3

Mean scores for the 6 VAS assessments. A, Mean drug liking VAS scores by hydromorphone challenge dose. B, Mean “any drug effect” VAS scores by hydromorphone challenge dose. C, Mean “bad drug effect” VAS scores by hydromorphone challenge dose. D, Mean “drug high” VAS scores by hydromorphone challenge dose. E, Mean “good drug effect” VAS scores by hydromorphone challenge dose. F, Mean “sedation” VAS scores by hydromorphone challenge dose.

FIGURE 4

Mean breakpoint values for the drug versus money choice task.