Pain, Opioid-Induced Respiratory Depression (OIRD), Opioid-related side effects, opioid-related adverse events
Conditions
Interventions
All subjects will be tested 4 times on 4 separate occasions at least 1 week apart. On each visit they will receive one of the following doses:
- Oliceridine 0.5 mg IV
- Oliceridine 2.0 mg IV
- Morphin
Sponsors
LUMC
Eligibility
Inclusion criteria
Inclusion criteria: - Absence of any significant medical, neurologic, or psychiatric illness as determined by the investigators. - Age 55 yr or older; - Body mass index (BMI) of 19-35 kg/m2. - Willingness and competence to sign written informed consent. - Screening cold pressor test hand removal latencies of > 20 and < 120 seconds
Exclusion criteria
Exclusion criteria: 1. Clinically significant medical, surgical, psychiatric or substance abuse condition or history of such condition that would confound the interpretation of data in the study; 2. Clinically significant, immune mediated hypersensitivity reaction or intolerance to opioids; 3. Exposure to opioids or anesthesia within 30 days before the first treatment period of the study; 4. Positive urine drug screen or alcohol breathalyzer test at the screening visit or positive urine dipstick for substances of abuse or alcohol breath test at each visit; 5. Participation in a previous oliceridine clinical study; 6. Participation in another interventional clinical study within 30 days before the first treatment period of the study; 7. Body mass index outside 35 kg/m2; 8. Taking any prescribed medication which is considered a strong CYP3A4 or CYP2D6 inhibitor or inducer 9. Any clinically significant clinical laboratory abnormality, including total bilirubin > 2 × upper limit of normal [ULN] or elevated hepatic transaminases (aspartate aminotransferase [AST] ? 1.5 × ULN OR alanine aminotransferase [ALT] ? 1.5 × ULN); 10. Clinically significant abnormality on electrocardiogram, including a QT interval corrected for heart rate (QTcF interval) of > 450 milliseconds, at the screening visit; 11. Clinically significant, immune mediated hypersensitivity reaction or intolerance to 5-HT3 inhibitors; 12. Unsuitable screening HCVR test results (e.g., ability to tolerate the mask, breathe in a regular fashion, increase ventilation in response to increases in inhaled CO2), as judged by the investigators; 13. Alcohol intake of more than 4 units/day or more than 28 units/week; 14. The short version of the Mini Mental State Examination with a score less than 9. The latter exclusion criterion was to prevent that subjects with some form of cognitive impairment participated.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| - To evaluate the ventilatory and antinociceptive effects of intravenous doses of oliceridine and morphine by population PK/PD modeling in an older population across a range of body weights including subjects meeting the criteria for being overweight; - To evaluate the ventilatory and antinociceptive effects of intravenous doses of oliceridine and morphine by population PK/PD modeling as a function of body weight; - To evaluate the clinical utility of oliceridine as compared to intravenous morphine in an older population across a range of body weights | — |
Secondary
| Measure | Time frame |
|---|---|
| - To evaluate the safety and tolerability of oliceridine administered as single intravenous doses in an older population; - To evaluate the safety and tolerability of oliceridine administered as single intravenous doses as a function of body weight; - To compare the effects of oliceridine and morphine on other measures of respiratory function, including end-tidal carbon dioxide (PETCO2), oxygen saturation, and respiratory rate. | — |
Contacts
Public ContactPieter Simons
LUMC
Outcome results
None listed