NCT05491785

Cebranopadol Effects on Ventilatory Drive, Central Nervous System (CNS) and Pain.

Randomized, Double-blind, Four Period, Six-treatment, Double-dummy, Placebo Controlled, Partial-crossover Study to Explore and Compare the Ventilatory Response to Hypercapnia (VRH) of Cebranopadol, Oxycodone, and Placebo in Healthy Subjects

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 30 (actual)
• Sponsor: Tris Pharma, Inc. · Industry
• Sex: All
• Age: 18 Years – 45 Years
• Healthy volunteers: Accepted

Summary

Opioids are potent painkillers but come with serious adverse effects ranging from addiction to potentially lethal respiratory depression via activation of μ-opioid receptors (MOP) at specific sites in the central nervous system. Cebranopadol is a first-in-class investigational drug to treat patients with acute and chronic pain. The molecule dually activates the Nociceptin/Orphanin FQ peptide (NOP) receptor and the classical MOP receptor. This is a unique mechanism of action and has demonstrated efficacy in multiple Phase 2 and Phase 3 clinical studies across several nociceptive and neuropathic indications as well as a superior safety profile, low potential for abuse and minimal risk of physical dependence. In animal studies, cebranopadol produced considerably less respiratory depression at comparably analgesic doses of oxycodone and fentanyl and appeared to have a ceiling to its respiratory effects. Preliminary clinical trials have suggested that these results will be similar in humans. The present study is designed to investigate if: 1) cebranopadol produces less respiratory depression than oxycodone 2) cebranopadol respiratory effects have a ceiling at very high doses and 3) cebranopadol does not produce significant respiratory depression, as measured in this study design with 30 subjects, at any dose in the VRH model.

Detailed description

This is a randomized, double blind, four period, six-treatment, double-dummy, placebo controlled, partial-crossover study will investigate the effects of cebranopadol on the ventilatory response to hypercapnia (VRH), nociceptive thresholds and safety. VRH testing is non-invasive and is an established technique to evaluate respiratory depression following the administration of opioids. The test will be performed using a rebreathing setup with the subjects comfortably seated or semi-supine in a hospital bed and breathing through a facemask. VRH will be performed at several timepoints post-administration of cebranopadol, oxycodone or placebo in a randomized fashion. At each time point, subjects will be allowed an acclimation period of ambient air to establish regular breathing pattern; immediately followed by rebreathing a hypercapnic gas mixture (7%CO2, in oxygen (50%)), for at least 3 min. Between timepoints, subjects will remove their face masks and breathe ambient air.

Conditions

• Pain

Interventions

Type	Name	Description
DRUG	Cebranopadol 600 µg	Participants will be administered a single dose of 8 identically appearing capsules containing: 3 oxycodone placebo capsules, 3 cebranopadol 200 µg tablets and 2 cebranopadol placebo tablets
DRUG	Cebranopadol 800 µg	Participants will be administered a single dose of 8 identically appearing capsules containing: 3 oxycodone placebo capsules, 4 cebranopadol 200 µg tablets and 1 cebranopadol placebo tablet
DRUG	Cebranopadol 1000 µg	Participants will be administered a single dose of 8 identically appearing capsules containing: 3 oxycodone placebo capsules, and 5 cebranopadol 200 µg tablets
DRUG	Oxycodone 30 mg	Participants will be administered a single dose of 8 identically appearing capsules containing: 3 oxycodone 10 mg capsules, and 5 cebranopadol placebo tablets
DRUG	Oxycodone 60 mg	Participants will be administered a single dose of 8 identically appearing capsules containing: 3 oxycodone 20 mg capsules, and 5 cebranopadol placebo tablets
DRUG	Placebo	Participants will be administered a single dose of 8 identically appearing capsules containing: 3 oxycodone placebo capsules, and 5 cebranopadol placebo tablets

Timeline

• Start date: 2022-07-29
• Primary completion: 2023-03-30
• Completion: 2024-01-02
• First posted: 2022-08-08
• Last updated: 2024-05-09

Locations

2 sites across 1 country: Netherlands

Regulatory

• FDA-regulated drug study