Opiate Induced Respiratory Depression
Conditions
Brief summary
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.
Interventions
DRUGCX1739 - 300 mg
Ampakine CX1739 - 300 mg
DRUGCX1739 - 600 mg
CX1739 - 600 mg
DRUGCX1739 - 900 mg
CX1739 - 900 mg
DRUGPlacebo
Placebo to 300 mg CX1739
Sponsors
Duke University
RespireRx
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
MALE
Age
18 Years to 50 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Respiratory depression | Sequence #1 - 30 minutes | Respiratory rate, tidal volume, minute volume as determined by plethysmography |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pain tolerance threshold | Sequence #2 - 20 minutes | Analgesia assessed by pain tolerance threshold to 5, 250, and 2000 Hertz sine-wave electrical stimulation using the quantitative sensory testing device - Neurometer |
| Maintenance of sedation | Sequence #1 - 30 minutes | Bispectral index (BIS) measure of sedation |
| The number of patients that experience an adverse drug reaction upon ingestion of CX1739 when used alone or in conjunction with remifentanil | up to 5 weeks | Vital signs, including noninvasive blood pressure, heart rate, RR, end-tidal carbon dioxide, pulse oximetry saturation, and temperature * Electrocardiograms * Focused physical examinations * Adverse events |
| Change in pupil size | Sequence #2 - 20 minutes | Pupil size will be assessed intermittently with a noninvasive pupillometer incorporated into a pair of glasses placed on the subject's head |
Countries
United States
Outcome results
None listed