Antagonism of Opioid-Induced Respiratory Depression by CX1739 With Preservation of Opioid Analgesia

The study is an investigation to assess the capacity of ascending doses of CX1739 to antagonize the respiratory depressive effect of remifentanil. The study will also investigate whether ascending doses of CX1739 reduce the analgesic effect of remifentanil or alter the BIS measure of sedation and will evaluate the safety of CX1739 when used in conjunction with remifentanil.

Study Overview

• Status: Unknown
• Conditions: Opiate Induced Respiratory Depression
• Intervention / Treatment: Drug: CX1739 - 300 mg; Drug: Placebo; Drug: CX1739 - 600 mg; Drug: CX1739 - 900 mg

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke Clinical Research Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• To be eligible for this trial, subjects must meet all of the following criteria:

  1. Males 18 to 50 years of age, inclusive
  2. Body mass index of 18.0 to 30.0 kg/m2, inclusive, using the formula: weight (kg)/height (m)2
  3. Healthy, as determined by medical history, physical examination including vital signs, and clinical laboratory test results
  4. American Society of Anesthesiologists Physical Status Classification 1
  5. Willing and able to provide voluntary, written informed consent

Exclusion Criteria:

• If a subject meets any of the following criteria, he cannot be enrolled in the study:

  1. History of any chronic illness or evidence of clinically significant organic or psychiatric disease on medical history or physical examination which, in the opinion of the principal investigator (PI), would confound the study results or present a risk to the subject
  2. Acute illness within 2 weeks before dosing
  3. History of any clinically significant pulmonary condition (eg, asthma) within the last 2 years requiring admission to the hospital
  4. Previous diagnosis of obstructive sleep apnea based on polysomnography
  5. Currently using any prescription medication or use within the last 30 days
  6. Laboratory values (clinical chemistry, hematology, urinalysis) outside the laboratory reference range considered clinically significant (NOTE: in the event of any parameter lying outside of the normal range, the sample may be repeated once; this value will be accepted if it lies within the normal range)
  7. Presence of QT interval corrected > 440 msec on ECG
  8. Resting HR while awake < 45 or > 90 beats/minute
  9. History of daily use of tobacco or other nicotine-containing products within 1 year of study entry or positive cotinine test at screening and subsequent study visits
  10. History of allergic hypersensitivity to ampakines (CX717, CX1739), remifentanil, naloxone, or any component of these formulations; history of multiple drug allergies
  11. History or current evidence of abuse of any drug substance, licit or illicit, including alcohol; positive urine drug screen (UDS) for drugs of abuse at screening
  12. Inability to understand the protocol requirements; instructions; study-related restrictions; or nature, scope, and possible consequences of the study
  13. Unlikely to complete the study, eg, because of inability to return for follow-up visits
  14. Participation in another study with any investigational drug in the 3 months preceding this study
  15. Blood or plasma donation of more than 500 mL during the month before randomization and more than 50 mL in the 2 weeks before randomization

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Placebo to 300 mg CX1739; Other Names: Placebo to 300 mg CX1739
Experimental: CX1739 - 300 mg; Study Drug - low dose	Drug: CX1739 - 300 mg; Ampakine CX1739 - 300 mg; Other Names: Low dose
Experimental: CX1739 - 600 mg; Study drug - mid Dose	Drug: CX1739 - 600 mg; CX1739 - 600 mg; Other Names: mid dose
Experimental: CX1739 - 900 mg; Study drug - high dose	Drug: CX1739 - 900 mg; CX1739 - 900 mg; Other Names: high dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Respiratory depression	Respiratory rate, tidal volume, minute volume as determined by plethysmography	Sequence #1 - 30 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain tolerance threshold	Analgesia assessed by pain tolerance threshold to 5, 250, and 2000 Hertz sine-wave electrical stimulation using the quantitative sensory testing device - Neurometer	Sequence #2 - 20 minutes
Maintenance of sedation	Bispectral index (BIS) measure of sedation	Sequence #1 - 30 minutes
The number of patients that experience an adverse drug reaction upon ingestion of CX1739 when used alone or in conjunction with remifentanil	Vital signs, including noninvasive blood pressure, heart rate, RR, end-tidal carbon dioxide, pulse oximetry saturation, and temperature; Electrocardiograms; Focused physical examinations; Adverse events	up to 5 weeks
Change in pupil size	Pupil size will be assessed intermittently with a noninvasive pupillometer incorporated into a pair of glasses placed on the subject's head	Sequence #2 - 20 minutes

Collaborators and Investigators

• Sponsor: RespireRx
• Collaborators: Duke University
• Investigators: Study Director: Richard Purcell, RespireRx Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: March 1, 2016
• Primary Completion (Anticipated): August 1, 2016
• Study Completion (Anticipated): September 1, 2016

Study Registration Dates

• First Submitted: March 23, 2016
• First Submitted That Met QC Criteria: April 6, 2016
• First Posted (Estimate): April 13, 2016

Study Record Updates

• Last Update Posted (Estimate): July 28, 2016
• Last Update Submitted That Met QC Criteria: July 27, 2016
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Respiratory Tract Diseases; Mood Disorders; Respiration Disorders; Depression; Depressive Disorder; Respiratory Insufficiency
• Other Study ID Numbers: CRTX-05

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO