It is expected that oliceridine has a better profile concerning dose-related analgesia and dose-related side effects, compared to morphine.
ID
Bron
Verkorte titel
Aandoening
Pain, Opioid-Induced Respiratory Depression (OIRD), Opioid-related side effects, opioid-related adverse events
Ondersteuning
Onderzoeksproduct en/of interventie
Uitkomstmaten
Primaire uitkomstmaten
- 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
Achtergrond van het onderzoek
Opioid analgesics, the cornerstone of contemporary treatment of acute moderate to severe
pain, come with numerous adverse effects, of which respiratory depression is potentially life-threatening.
Classical opioid analgesics, such as morphine, are full agonists at the μ-opioid
receptor. After receptor activation, these opioids engage two distinct transduction pathways,
the G-protein–coupled signaling pathway and the β-arrestin pathway, with separate
pharmacologic effects. The G-protein pathway is primarily involved in analgesia, reward, and
liking, whereas the β-arrestin pathway is involved in adverse effects such as respiratory
depression and gastrointestinal effects, as well as the attenuation of analgesic effects. Recent
focus has been on the development of a new class of opioids, biased ligands, which are μ-
receptor agonists that selectively engage the G-protein–coupled signaling pathway with
reduced activation of the β-arrestin pathway. Biased ligands may have an advantage over
nonbiased, or non-elective μ-opioid receptor agonists as they may be associated with less
respiratory depression. The experimental opioid oliceridine (formerly known as TRV130) is a
biased ligand that has been approved by FDA in the United States for treatment of moderate
to severe acute pain. In the current study, we will prospectively compare the utility of the
biased ligand oliceridine and the classical opioid morphine, now in an older population.
Doel van het onderzoek
It is expected that oliceridine has a better profile concerning dose-related analgesia and dose-related side effects, compared to morphine.
Onderzoeksopzet
Screening, Visit 1-4, post-study evaluation
Onderzoeksproduct en/of interventie
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
- Morphine 2 mg IV
- Morphine 8 mg IV
The following tests/procedures will be performed during each visit:
- Rebreathing
- Blood samples
- Cold pressor test
- VAS (nausea, vomiting, sedation, dizziness, lightheadedness, drug likability)
Publiek
Wetenschappelijk
Belangrijkste voorwaarden om deel te mogen nemen (Inclusiecriteria)
- 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
Belangrijkste redenen om niet deel te kunnen nemen (Exclusiecriteria)
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 <19 or > 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.
Opzet
Deelname
Voornemen beschikbaar stellen Individuele Patiënten Data (IPD)
Toelichting
Opgevolgd door onderstaande (mogelijk meer actuele) registratie
Geen registraties gevonden.
Andere (mogelijk minder actuele) registraties in dit register
Geen registraties gevonden.
In overige registers
| Register | ID |
|---|---|
| NTR-new | NL9524 |
| Ander register | METC Leiden-Den Haag-Delft. (METC-LDD) : P21.025 |