Methods: Opioid-tolerant adults with 1-4 BTP episodes/day were enrolled in an IRB-approved study with 3 within-patient double-blind periods. After initial titration to a successful FBT dose (single dose providing adequate analgesia without unacceptable AEs), patients received open-label FBT at the successful dose for 4 weeks followed by 9 double-blind, randomized doses (6 FBT, 3 placebo) during an evaluation period. The open-label/evaluation sequence was repeated twice; evaluation periods occurred after 4, 8, and 12 weeks of treatment. Patients rated BTP intensity (PI, 0–10 scale) predose and 5–120 min postdose during double-blind treatment. The primary measure was the sum of PI differences (PID) 5–60 min postdose (SPID₆₀) following week 12. Secondary measures included pain relief (PR, 0–4 scale, 5–120 min), patient-assessed meaningful PR, and % episodes with ≥33% and ≥50% improvement in PI. Patients provided written informed consent.

Results: 148 patients were titrated, 105/148 (71%) achieved a successful dose, and 81/105 (77%) completed the study. 48% had back pain as the primary chronic pain condition. During the final double-blind period, results favored FBT over placebo for SPID₆₀ (mean [SEM], 7.7 [0.69] vs 4.6 [0.53]), PR (at ≥5 min), PID (≥15 min), meaningful PR (≥10 min), and % episodes with ≥33% (at 5 min 7% vs 3% of episodes) and ≥50% improvement (≥15 min) in PI (all p<0.05). Similar results were observed in the earlier double-blind periods. AEs were generally typical of opioids; no FBT-related respiratory depression occurred. Conclusion: FBT was efficacious and generally safe and well tolerated throughout and after 12 weeks of treatment in non—cancer-related BTP.