Cebranopadol, a novel first-in-class analgesic drug candidate: First experience in patients with chronic low back pain in a randomized clinical trial

Annette Christoph, Marie Henriette Eerdekens, Maurits Kok, Gisela Volkers, Rainer Freynhagen

Research output: Contribution to journalArticlepeer-review

77 Scopus citations

Abstract

Chronic low back pain (LBP) is a common condition, usually with the involvement of nociceptive and neuropathic pain components, high economic burden and impact on quality of life. Cebranopadol is a potent, first-in-class drug candidate with a novel mechanistic approach, combining nociceptin/orphanin FQ peptide and opioid peptide receptor agonism. We conducted the first phase II, randomized, double-blind, placebo- and active-controlled trial, evaluating the analgesic efficacy, safety, and tolerability of cebranopadol in patients with moderate-to-severe chronic LBP with and without neuropathic pain component. Patients were treated for 14 weeks with cebranopadol 200, 400, or 600 g once daily, tapentadol 200 mg twice daily, or placebo. The primary efficacy endpoints were the change from baseline pain to the weekly average 24-hour pain during the entire 12 weeks and during week 12 of the maintenance phase. Cebranopadol demonstrated analgesic efficacy, with statistically significant and clinically relevant improvements over placebo for all doses as did tapentadol. The responder analysis (≥30% or ≥50% pain reduction) confirmed these results. Cebranopadol and tapentadol displayed beneficial effects on sleep and functionality. Cebranopadol treatment was safe, with higher doses leading to higher treatment discontinuations because of treatment-emergent adverse events occurring mostly during titration. Those patients reaching the target doses had an acceptable tolerability profile. The incidence rate of most frequently reported treatment-emergent adverse events during maintenance phase was ≤10%. Although further optimizing the titration scheme to the optimal dose for individual patients is essential, cebranopadol is a new drug candidate with a novel mechanistic approach for potential chronic LBP treatment.

Original languageEnglish
Pages (from-to)1813-1824
Number of pages12
JournalPain
Volume158
Issue number9
DOIs
StatePublished - 1 Sep 2017
Externally publishedYes

Keywords

  • Cebranopadol
  • Chronic low back pain
  • First human phase II RCT
  • First-in-class drug
  • Nociceptin/orphanin FQ
  • Placebo control
  • Randomized controlled trial

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