Dataset Information

Efficacy and tolerability of buccal buprenorphine in opioid-experienced patients with moderate to severe chronic low back pain: results of a phase 3, enriched enrollment, randomized withdrawal study.

ABSTRACT: A buccal film of buprenorphine (BBUP) was evaluated for safety and efficacy in a multicenter, double-blind, placebo-controlled, enriched-enrollment, randomized-withdrawal study in opioid-experienced patients (30 to ?160 mg/d morphine sulfate equivalent) with moderate to severe chronic low back pain taking around-the-clock opioid analgesics. Patients' opioid doses were tapered to ?30 mg morphine sulfate equivalent before open-label titration with BBUP (range, 150-900 ?g every 12 hours). Patients who responded (received adequate analgesia that was generally well tolerated for 14 days) were randomized to receive buprenorphine (n = 254) or placebo (n = 257) buccal film. The primary efficacy variable was the change from baseline to week 12 of double-blind treatment in mean average daily pain-intensity scores using a rating scale of 0 (no pain) to 10 (worst pain imaginable). In the intent-to-treat population, mean pain scores were 6.7 after opioid taper and declined to 2.8 after the BBUP titration period. After randomization, mean pain scores were lower in the BBUP group than in the placebo group; the difference between groups in the mean change from baseline to week 12 was -0.98 (95% CI, -1.32 to -0.64; P < 0.001). A significantly larger percentage of patients receiving BBUP than placebo had pain reductions ?30% and ?50% (P < 0.001 for both). In the double-blind portion of the study, the only adverse event reported more frequently with BBUP than placebo and in ?5% of patients was vomiting (5.5% vs 2.3%). These findings demonstrate the efficacy and tolerability of BBUP in opioid-experienced patients taking around-the-clock opioid treatment for chronic low back pain.

SUBMITTER: Gimbel J

PROVIDER: S-EPMC5065057 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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Efficacy and tolerability of buccal buprenorphine in opioid-experienced patients with moderate to severe chronic low back pain: results of a phase 3, enriched enrollment, randomized withdrawal study.

Gimbel Joseph J Spierings Egilius L H ELH Katz Nathaniel N Xiang Qinfang Q Tzanis Evan E Finn Andrew A

Pain 20161101 11

A buccal film of buprenorphine (BBUP) was evaluated for safety and efficacy in a multicenter, double-blind, placebo-controlled, enriched-enrollment, randomized-withdrawal study in opioid-experienced patients (30 to ≤160 mg/d morphine sulfate equivalent) with moderate to severe chronic low back pain taking around-the-clock opioid analgesics. Patients' opioid doses were tapered to ≤30 mg morphine sulfate equivalent before open-label titration with BBUP (range, 150-900 μg every 12 hours). Patients ...[more]

PMID: 27434505

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Project description:ImportanceBuprenorphine is an effective yet underused treatment for opioid use disorder (OUD).ObjectiveTo evaluate the feasibility (acceptability, tolerability, and safety) of 7-day injectable extended-release buprenorphine in patients with minimal to mild opioid withdrawal.Design, setting, and participantsThis nonrandomized trial comprising 4 emergency departments in the Northeast, mid-Atlantic, and Pacific geographic areas of the US included adults aged 18 years or older with moderate to severe OUD and Clinical Opiate Withdrawal Scale (COWS) scores less than 8 (minimal to mild), in which scores range from 0 to 7, with higher scores indicating increasing withdrawal. Exclusion criteria included methadone-positive urine, pregnancy, overdose, or required admission. Outcomes were assessed at baseline, daily for 7 days by telephone surveys, and in person at 7 days. Patient recruitment occurred between July 13, 2020, and May 25, 2023.InterventionInjection of a 24-mg dose of a weekly extended-release formulation of buprenorphine (CAM2038) and referral for ongoing OUD care.Main outcomes and measuresPrimary feasibility outcomes included the number of patients who (1) experienced a 5-point or greater increase in the COWS score or (2) transitioned to moderate or greater withdrawal (COWS score ≥13) within 4 hours of extended-release buprenorphine or (3) experienced precipitated withdrawal within 1 hour of extended-release buprenorphine. Secondary outcomes included injection pain, satisfaction, craving, use of nonprescribed opioids, adverse events, and engagement in OUD treatment.ResultsA total of 100 adult patients were enrolled (mean [SD] age, 36.5 [8.7] years; 72% male). Among the patients, 10 (10.0% [95% CI, 4.9%-17.6%]) experienced a 5-point or greater increase in COWS and 7 (7.0% [95% CI, 2.9%-13.9%]) transitioned to moderate or greater withdrawal within 4 hours, and 2 (2.0% [95% CI, 0.2%-7.0%]) experienced precipitated withdrawal within 1 hour of extended-release buprenorphine. A total of 7 patients (7.0% [95% CI, 2.9%-13.9%]) experienced precipitated withdrawal within 4 hours of extended-release buprenorphine, which included 2 of 63 (3.2%) with a COWS score of 4 to 7 and 5 of 37 (13.5%) with a COWS score of 0 to 3. Site pain scores (based on a total pain score of 10, in which 0 indicated no pain and 10 was the worst possible pain) after injection were low immediately (median, 2.0; range, 0-10.0) and after 4 hours (median, 0; range, 0-10.0). On any given day among those who responded, between 29 (33%) and 31 (43%) patients reported no cravings and between 59 (78%) and 75 (85%) reported no use of opioids; 57 patients (60%) reported no days of opioid use. Improving privacy (62%) and not requiring daily medication (67%) were deemed extremely important. Seventy-three patients (73%) were engaged in OUD treatment on day 7. Five serious adverse events occurred that required hospitalization, of which 2 were associated with medication.Conclusions and relevanceThis nonrandomized trial of the feasibility of a 7-day buprenorphine injectable in patients with minimal to mild opioid withdrawal (COWS scores, 0-7) found the formulation to be acceptable, well tolerated, and safe in those with COWS scores of 4 to 7. This new medication formulation could substantially increase the number of patients with OUD receiving buprenorphine.Trial registrationClinicalTrials.gov Identifier: NCT04225598.

Project description:Background and objectiveBuprenorphine has been shown to be effective in treating infants with neonatal opioid withdrawal syndrome. However, an evidence-based buprenorphine dosing strategy has not been established in the treatment of neonatal opioid withdrawal syndrome because of a lack of exposure-response data. The aim of this study was to develop an integrated pharmacokinetic and pharmacodynamic model to predict buprenorphine treatment outcomes in newborns with neonatal opioid withdrawal syndrome.MethodsClinical data were obtained from 19 newborns with a median (range) gestational age of 37 (34-41) weeks enrolled in a pilot pharmacokinetic study of buprenorphine. Sparse blood sampling, comprising three specimens obtained around the second dose of buprenorphine, was performed using heel sticks with dried blood spot technology. Standardized neonatal opioid withdrawal syndrome severity scores (Finnegan scores) were collected every 3-4 h based on symptoms by bedside nursing staff. Mean Finnegan scores were used as a pharmacodynamic marker in the exposure-response modeling. The blood concentration-Finnegan score relationship was described using a physiologic indirect response model with inclusion of natural disease remission.ResultsA total of 52 buprenorphine blood concentrations and 780 mean Finnegan scores were available for the pharmacokinetic/pharmacodynamic modeling and exposure-response analysis. A one-compartment model with first-order absorption adequately described the pharmacokinetic data. The buprenorphine blood concentration at 50% of maximum effect for the inhibition of disease progression was 0.77 ng/mL (95% confidence interval 0.32-1.2). The inclusion of natural disease remission described as a function of postnatal age significantly improved the model fit.ConclusionsA buprenorphine pharmacokinetic/pharmacodynamic model was successfully developed. The model could facilitate model-informed optimization of the buprenorphine dosing regimen in the treatment of neonatal opioid withdrawal syndrome.

Project description:OBJECTIVE:To evaluate the SUMMIT-07 trial opioid withdrawal results of NKTR-181 (oxycodegol), a new molecular entity mu-opioid receptor agonist. DESIGN:Phase 3, enriched-enrollment, double-blind, randomized-withdrawal study in patients with chronic low back pain (CLBP). SETTING:Conducted in the United States at multiple sites. METHODS:SUMMIT-07 was comprised of five periods: screening; NKTR-181 open-label titration (100 to 400?mg twice daily); 12-week randomized, double-blind study drug (NKTR-181 or placebo); one-week study drug taper; and two-week safety follow-up. Permitted rescue medication included hydrocodone 5?mg/acetaminophen 300?mg (two tablets daily) for two weeks after randomization, then acetaminophen 1.0?gm daily for the remainder of the trial. Signs and symptoms of drug withdrawal were evaluated using the Clinical Opiate Withdrawal Scale (COWS); Subjective Opiate Withdrawal Scale (SOWS); Misuse, Abuse, and Diversion Drug Event Reporting System (MADDERS); and withdrawal-related adverse events. RESULTS:Of 1,190 patients entering titration, one patient had moderate withdrawal (COWS score 13/48 maximum) three days after discontinuing NKTR-181. Of 610 patients randomized (N?=?309, NKTR-181; N?=?301, placebo), no COWS scores indicating withdrawal at a moderate level or greater (i.e., score ?13) were observed at any time point. At day 8 after randomization, week 12, and the end of tapering, COWS scores indicating mild withdrawal (<13) were observed in seven (2.4%), one (0.4%), and one (0.5%) placebo patients, respectively, and three (1.0%), one (0.4%), and five (2.3%) NKTR-181 patients, respectively. Mean SOWS scores in both arms were ?2.8 of 64 possible points at all time points. During the randomized period, of 35 events identified by MADDERS, adjudicators identified 20 possible "withdrawal" events (9 [2.9%] NKTR-181 and 11 [3.7%] placebo). CONCLUSIONS:NKTR-181 exhibited a low rate and severity of opioid withdrawal in SUMMIT-07 patients with CLBP.

Dataset Information

Efficacy and tolerability of buccal buprenorphine in opioid-experienced patients with moderate to severe chronic low back pain: results of a phase 3, enriched enrollment, randomized withdrawal study.

Publications

Efficacy and tolerability of buccal buprenorphine in opioid-experienced patients with moderate to severe chronic low back pain: results of a phase 3, enriched enrollment, randomized withdrawal study.

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