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

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.

Conditions

• Pain

Interventions

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

Sponsors & Collaborators

• Tris Pharma, Inc.

  lead INDUSTRY

Principal Investigators

• Albert Dahan, MD, PhD · LUMC

• Geert Jan Groeneveld, MD, PhD · CHDR

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

CROSSOVER

Eligibility

Min Age

18 Years

Max Age

45 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2022-07-29

Primary Completion

2023-03-30

Completion

2024-01-02

FDA Drug

Yes

Countries

• Netherlands

Study Locations