Healthy subjects MedDRA version: 17.1 Level: LLT Classification code 10049475 Term: Chronic pain System Organ Class: 100000004867
Conditions
Interventions
Trade Name: Naloxon "B. Braun"
Product Name: not relevant
Product Code: not relevant
Pharmaceutical Form: Solution for injection/infusion
Sponsors
Rigshospitalet, Copenhagen University Hospitals
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: • Healthy male • Age above 18 yrs and below 35 yrs • Signed informed consent • Urin-sample without traces of opioids (morphine, methadon, buprenorphine, codeine, tramadol, ketobemidone, oxycodone, hydromorphone, dextro-methorphan) • American Society of Anesthesthesiologists' Physical Status score: ASA I • Body mass index (BMI): 18 =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • Participants, who do not speak or understand Danish • Participants, who cannot cooperate with the investigation • Participants with pain at rest > 3 (NRS) • Allergic reaction against morphine or other opioids (including naloxone), • Abuse of alcohol or drugs – according to investigator’s evaluation • Use of psychotropic drugs (exception of SSRI) • Neurologic or psychiatric disease • Chronic pain condition • Regular use of analgesic drugs • Use of prescription drugs one week before the trial • Use of over-the-counter drugs 48 hours before the trial
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The pharmacokinetics of naloxone and its main-metabolites at the dose-levels used in this study (< 3.5 mg/kg), are unknown. We examine the pharmacokinetic construct validity of the target-controlled-infusion (TCI) model in volunteer participants.;Secondary Objective: Not applicable;Primary end point(s): The primary endpoints are standard pharmacokinetic parameters. These pharmacokinetic analyses will be undertaken using NONMEM (7.3 ICON Development Solutions, Manchester, U.K. [property of UCSF, U.S.]). One-, two- and three-compartment models will be assessed to decide the best structural model and different error models for the unexplained residual variability will be tested. Between-subject variability will be assessed and covariates such as age and weight might be included in the model. Model selection decisions will be based on a number of different criteria, including a reduction in the objective function value produced by NONMEM, plots of predicted concentrations and visual predictive plots generated from simulations. The final model and pharmacokinetic parameters obtained from this study (high naloxone dose) will be compared with the model and pharmacokinetic parameters used for the simulations (low naloxone dose data) in order to verify the simulations done. ;Timepoint(s) of evaluation of this end point: Blood-samples (BS) for pharmacokinetic (PK) analyses will be taken: * Baseline (preinfusion; 0 min) * Step 1 (TCI-infusion 1 [naloxone: 0.25 mg/kg; 0 to 25 min]: BS 17, 20 and 23 min) * Step 2 (TCI-infusion 2 [naloxone: 0.75 mg/kg; 25 to 50 min]: BS 41, 44 and 47 min) * Step 3 (TCI-infusion 3 [naloxone: 2.25 mg/kg; 50 to 75 min]): BS 67, 70 and 75 min) * Post-TCI-infusion (75 to 340 min): BS 76, 77, 78, 79, 80, 82, 86, 94, 110, 142, 206 and 334 min | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Not applicable;Timepoint(s) of evaluation of this end point: Not applicable | — |
Countries
Denmark
Contacts
Public ContactThomas K. Ringsted
Rigshospitalet, Copenhagen University Hospitals
Outcome results
None listed