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

Tris Pharma, Inc.2 sites in 1 country30 target enrollmentJuly 29, 2022

ConditionsPain

InterventionsCebranopadol 600 µg Cebranopadol 800 µg Cebranopadol 1000 µg Oxycodone 30 mg Oxycodone 60 mg Placebo

DrugsCebranopadol 600 µg Cebranopadol 800 µg Cebranopadol 1000 µg Oxycodone 30 mg Oxycodone 60 mg Placebo

Overview

Phase: Phase 1
Intervention: Cebranopadol 600 µg
Conditions: Pain
Sponsor: Tris Pharma, Inc.
Enrollment: 30
Locations: 2
Primary Endpoint: Ventilatory response to hypercapnia (VRH) by maximum decrease in minute ventilation (L)
Status: Completed
Last Updated: last year

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief 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.

Registry

clinicaltrials.gov

Start Date

July 29, 2022

End Date

January 2, 2024

Last Updated

last year

Study Type

Interventional

Study Design

Crossover

Sex

All

Investigators

Sponsor

Tris Pharma, Inc.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Signed informed consent prior to any study-mandated procedure.
•Subject is able to speak, read, and understand Dutch and voluntarily provide written informed consent to participate in the study.
•Adult men or women aged 18 to 45 years, inclusive.
•Subjects are in good health as indicated by medical history, physical examination, vital signs, oxygen saturation, clinical laboratory tests, and 12-lead ECG.
•Body mass index between 18.0 kg/m2 and 32.0 kg/m2 and body weight greater than 50 kg, inclusive.
•Adequate contraception is being used or women of nonchildbearing potential may be enrolled if surgically sterile (i.e., after hysterectomy) or postmenopausal for at least 2 years (based on subject's report).

Exclusion Criteria

•History or presence of clinically significant cardiovascular (incl. a history of risk factors for torsade de pointes e.g., heart failure, hypokalaemia, family history of long QT syndrome, history of myocardial infarction, ischaemic heart disease, clinically significant arrhythmia or uncontrolled arrhythmia or cardiac failure), pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, oncologic, or psychiatric disease (e.g., anxiety); or any other condition (e.g., hyperventilation disorder), which, in the opinion of the Investigator, would jeopardize the safety of the subject or the validity of the study results.
•History of known difficult airway access or uncontrolled gastroesophageal reflux disease (GERD), gastric motility disorders, or delayed gastric emptying
•Has clinically significant abnormalities on ECG at screening or Day -1, as defined by the following:
•prolonged corrected QT interval (Fridericia-corrected QT interval \[QTcF\] \>450 ms in males and \>470 ms in females) demonstrated on ECG;
•Left bundle branch block at Screening or Baseline
•Systolic blood pressure (BP) \>150 or \<90 mmHg or diastolic BP \>90 or \<50 mmHg at Screening or Baseline, or history of clinically significant orthostatic hypotension.
•Heart rate (HR) \<40 beats per minute (bpm) or \>100 bpm at Screening.
•Is currently enrolled in another clinical study or used any investigational drug or device within 3 months prior to dosing or has participated in more than 4 investigational drug studies within 1 year prior to Screening.
•Has any condition in which an opioid is contraindicated (e.g., significant respiratory depression, acute or severe bronchial asthma or hypercarbia, or has or is suspected of having paralytic ileus).
•Have a history of chronic obstructive pulmonary disease or any other lung disease (e.g., asthma, bronchitis, obstructive sleep apnoea, exercise-induced asthma) that would cause CO2 retention.