The objective of this study is to investigate the extent of respiratory depression at equi-analgesic dosages of tapentadol and oxycodone
ID
Source
Brief title
Condition
- Other condition
Synonym
Health condition
Opioid geïnduceerde ademdepressie
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Degree of respiratory depression defined as a decrease in the slope of the
Ventilation-CO2 curve, a rightward shift of the Ventilation-CO2 curve and
extrapolations at fixed et-CO2 (7 and 9 kPa), resting ventilation and resting
end-tidal PCO2.
Secondary outcome
A comparison of the degree of anti-nociception defined as the change in pain
pressure threshold.
Background summary
This novel potent opioid tapentadol (PallexiaTM) has a combined mechanism of
action where the single molecule acts at the *-opioid receptor (MOR) at spinal
and supraspinal sites and inhibits the reuptake of noradrenaline (NRI) in the
spinal cord. The combination of these two mechanisms has been designated as the
MOR-NRI concept. The affinity of tapentadol for the *-opioid receptor is
50-fold lower than that of morphine. However, due to synergy between the two
mechanisms of action, tapentadol produces potent analgesia by reducing
ascending nociceptive trafficking to the thalamus and is useful in the
treatment of moderate to severe acute and chronic pain. Tapentadol*s very low
affinity for the *-opioid receptor is an advantage as it coincides with a
limited side effect profile. Whether this also holds true for the respiratory
effects of tapentadol has not been studied yet. A potent analgesic with
opioidergic mechanisms with a limited respiratory depressant effect is of large
value as current opioid analgesics without any exception produce potent and
long-term respiratory depressant effects. Opioids are considered by the FDA and
the APSF (American Patient Safety Foundation) dangerous in the sense that
potential life threatening respiratory depression is an inherent property of
these drugs.
Study objective
The objective of this study is to investigate the extent of respiratory
depression at equi-analgesic dosages of tapentadol and oxycodone
Study design
A randomized, placebo and active comparator controlled study
Intervention
Oral administration of tablet: tapentadol (100 en 150 mg), oxycodone (20mg) and
placebo
Study burden and risks
The research is conducted in the anesthesiology department of a university
hospital, where all the necessary procedures are followed. The study will be
conducted by researchers with experience in the treatment of respiratory
depression. Naloxone injections are available in case of severe respiratory
depression and other measures to support the respiratory and hemodynamics are
available, such as administering fluids, oxygen and vasopressors.
Cardiovascular emergency measures such as defibrillation, magnesium sulfate
(IV) and antiarythmics are available. The overall risk / benefit analysis is
considered acceptable under the circumstances described above
Albinusdreef 2
Leiden 2333 ZA
NL
Albinusdreef 2
Leiden 2333 ZA
NL
Listed location countries
Age
Inclusion criteria
Healthy male and female subjects;Age of 18 to 45 years (inclusive);;Body Mass Index (BMI) between 18 and 35 kg/m2 (inclusive) and body weight between 50 kg and 100 kg (inclusive);
Subject is able to read and understand the written consent form, complete study-related procedures, and communicate with the study staff;
Subject is willing to comply with study restrictions.
Exclusion criteria
Clinically relevant abnormal history of physical and mental health, as determined by medical history taking and physical examinations obtained during the screening visit and/or prior to the administration of the initial dose of the study drug (as judged by the investigator);;A semi recumbent systolic blood pressure of >160 mmHg and/or diastolic blood pressure of > 95 mmHg at screening;;History of alcoholism or substance abuse within three years prior to screening;;Positive pregnancy test;;Positive drug screening or alcohol breath test;;Subjects using more than 21 units of alcohol per week;;Use of medication during the study period;;If sexually active, the subject is not using contraceptives, or surgically sterilized;;Subject has a history of severe allergies, or has had an anaphylactic reaction or significant
intolerability to prescription or non-prescription drugs or food;;Participation in an investigational drug trial in the 2 months prior to administration of the initial dose of study drug or more than 5 times per year;;Any other condition that in the opinion of the investigator would complicate or compromise the study, or the well being of the subject:
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2014-000455-91-NL |
| CCMO | NL48073.058.14 |