Cancer-related chronic pain: Investigation of the novel analgesic drug candidate cebranopadol in a randomized, double-blind, noninferiority trial

Eur J Pain. 2019 Mar;23(3):577-588. doi: 10.1002/ejp.1331. Epub 2019 Jan 9.

Abstract

Background: Cancer-related pain is a growing health problem given the increasing life expectancy of cancer patients. Opioids are commonly used to treat cancer-related pain, but carry the risk of severe side effects, limiting their use. Cebranopadol is a first-in-class drug candidate, combining nociceptin/orphanin FQ peptide and opioid peptide receptor agonism. This trial examined the analgesic efficacy of cebranopadol compared with morphine prolonged release (PR) in patients with moderate-to-severe cancer-related pain.

Methods: This double-blind, parallel-group, multiple-dose trial was designed as noninferiority trial for efficacy of cebranopadol versus morphine PR. Planned with 524 patients, finally 126 patients were treated for up to 7 weeks (low accrual). The primary efficacy endpoint was the average amount of daily rescue medication intake (morphine immediate release) over the last 2 weeks of treatment.

Results: For the primary endpoint, noninferiority of cebranopadol with and superiority over morphine PR were demonstrated (Full Analysis Set: ∆[95%CI] = -7.48 mg [-12.05, -2.92]; Per Protocol Set: ∆[95%CI] = -4.67 mg [-9.25, -0.10]). The vast majority of patients (≥75%, either treatment) had clinically relevant pain reduction, and noninferiority on this secondary endpoint was not shown. Mostly used doses were ≤800 μg cebranopadol or ≤120 mg morphine PR daily. A total of 83.1% of patients on cebranopadol and 82.0% on morphine PR experienced treatment-emergent adverse events.

Conclusions: Cebranopadol was effective, safe and well tolerated in the dose range tested (200-1,000 μg) in patients suffering from chronic moderate-to-severe cancer-related pain and was superior to morphine PR on the primary endpoint.

Significance: Cebranopadol presents a new approach to treat cancer pain. The drug candidate was easy to titrate, safe and well tolerated, and as effective as morphine PR in patients suffering from chronic moderate-to-severe cancer-related pain.

Trial registration: ClinicalTrials.gov NCT01964378.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Analgesics / therapeutic use*
  • Cancer Pain / drug therapy*
  • Chronic Pain / drug therapy*
  • Double-Blind Method
  • Female
  • Humans
  • Indoles / therapeutic use*
  • Male
  • Middle Aged
  • Morphine / therapeutic use
  • Neoplasms / complications
  • Neoplasms / drug therapy
  • Spiro Compounds / therapeutic use*

Substances

  • 6'-fluoro-4',9'-dihydro-N,N-dimethyl-4-phenylspiro(cyclohexane-1,1'(3'H)-pyrano(3,4-b)indol)-4-amine
  • Analgesics
  • Indoles
  • Spiro Compounds
  • Morphine

Associated data

  • ClinicalTrials.gov/NCT01964378