Reversal of Opioid-induced Respiratory Depression With Opioid Antagonists
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18-70
SponsorLeiden University Medical Center
About this trial
n this pharmacokinetic/pharmacodynamic modelling study we will determine the ability of intranasal and intravenous naloxone and intravenous nalmefene to reverse opioid (fentanyl and sufentanil)- induced respiratory depression in healthy volunteers and chronic opioid users to develop dosing recommendations in case of opioid-induced respiratory depression from an opioid overdose in clinical practice and in the out-of-hospital overdose.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
Signed the informed consent form (ICF) and able to comply with the study requirements and restrictions listed therein;
Male and female subjects, age 18 to 70 years, inclusive;
Women of childbearing potential (defined as all women who are not surgically sterile or postmenopausal for at least 1 year prior to informed consent) must have a negative serum pregnancy test prior to enrolment and must agree to use a medically acceptable means of contraception from screening through at least 1 month after the last dose of study drug;
Body Mass Index (BMI) 18 to 30 kg/m2, inclusive;
Disqualifiers
Currently meet the criteria for diagnosis of substance use disorder according to the Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 criteria on any substance;
Any other active medical condition, organ disease or concurrent medication or treatment that may either compromise subject safety or interfere with study endpoints;
Consume, on average, >27 20 units/week of alcohol in men and > 20 13 units/week of alcohol in women (1 unit = 1 glass (250 mL) beer, 125 mL glass of wine or 25 mL of 40% spirit);
Previous or current treatment with opioid agonist, partial agonist, or antagonist treatment within 30 days prior to the first study drug administration;
Trial design
Design model
Crossover
Treatments tested in this trial
Narcan 40 MG/ML Nasal Spray
Drugnaloxone 4mg/0.1 mL intranasal spray, up to 4 doses intranasally, followed by 1ml 0.4 mg/ml naloxone hydrochloride intravenously
Naloxone Hydrochloride
DrugNaloxone 0.4mg/mL
Nalmefene HCl injection
DrugNalmefene 1 ng/mL
Treatment groups
24 Participants
are divided into 4 treatment groupsGroup A: Intravenous fentanyl year 1Experimental treatment 1 intervention
Group B: Intravenous sufentanil year 1Experimental treatment 1 intervention
Group C: Intravenous fentanyl year 2Experimental treatment 2 interventions
Group D: IV fentanyl year 2Experimental treatment 2 interventions
Trial outcomes
Primary outcomes
1
Minute ventilation
Minute ventilation (liters/minute)
Time frame
Minute ventilation will be measured for up to 180 minutes following the start of opioid infusion2
Plasma concentration sufentanil/fentanyl
50 samples of 2ml arterial blood
Time frame
at 2,5,10,15,20 and 30 minutes following opioid infusion and following every administration of intranasal/intravenous naloxone or nalmefene3
Plasma concentration naloxone
50 samples of 2ml arterial blood
Time frame
at 2,5,10,15,20 and 30 minutes following opioid infusion and following every administration of intranasal/intravenous naloxone or nalmefeneSecondary outcomes
1
Pupil diameter
Pupil diameter in millimeters
Time frame
at 2,5,10,15,20 and 30 minutes following opioid infusion and following every administration of intranasal/intramuscular/intravenous naloxone. After discontinuation of infusion every 20 min. up to 6 hrs. following the start of opioid infusionSponsors and contacts
Click on the lead sponsor to view all of their trials.
Leiden University Medical Center
Lead sponsor
Food and Drug Administration (FDA)
Collaborator
Source ClinicalTrials.gov