Pharmacodynamics and Arteriovenous Differences of Naloxone in Healthy Participants Exposed to an Opioid

NCT02405988 | Completed DMC

• 2 other identifiers: OPI-15-0012014-005348-16
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

Overdose with potential deadly outcome is a serious problem among opioid abusers, not least in Norway. To save lives, immediate treatment with a μ-opioid antidote such as naloxone is required. The purpose of this study is to explore the pharmacokinetics and pharmacodynamics of naloxone in healthy volunteers under opioid influence.

Conditions

Drug Overdose

Keywords

Emergency Treatment; Morphine Derivates; Heroin; Antidotes; Administration, Intravenous; Pharmacology; Naloxone; Healthy volunteers

Outcome Measures

Primary Outcomes (1)

• Serum-effect-site equilibration rate constant

  up to 120 minutes

Secondary Outcomes (7)

• Pharmacokinetics: Area Under the Curve of IV naloxone in arterial and venous serum

  120 minutes

• Pharmacokinetics: maximum concentration (Cmax) of IV naloxone in arterial and venous serum

  120 minutes

• Pharmacokinetics: time to maximum concentration (Tmax) of IV naloxone in arterial and venous serum

  120 minutes

• Pharmacodynamics: measurement of naloxone antagonism of remifentanil effects, by measuring changes in pupillary size

  120 minutes

• Quantitate serum concentrations of remifentanil in arterial and venous blood at specified time points

  120 minutes

Study Arms (1)

Intravenous naloxone

EXPERIMENTAL

0,4 mg/ml Naloxone B Braun 2,5 ML intravenously

Drug: Intravenous naloxone; Drug: Remifentanil

Interventions

Intravenous naloxone DRUG

Administer 2,5 mL, dose intravenous naloxone 1,0 mg

Also known as: Naloxone B Braun 0,4 mg/ml

Intravenous naloxone

Remifentanil DRUG

Administer remifentanil intravenously by way of Target Control Infusion, Minto's model at a target of 1,3 ng/ml. This to achieve a state of safe and predictable opioid influence to assess pharmacodynamic response to naloxone.

Intravenous naloxone

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• American Society of Anesthesiologists (ASA) class I
• ECG without pathologic abnormalities
• BMI range of 18,5 - 26 kg/m2
• pass the modified allens test to determine collateral circulation of the hand
• Haemoglobin (male: 13.4-17.0 g/dL, female 11.7 - 15.3 g/dL)
• Creatinine (male: 60-105 micromole/L, female 45 - 90 micromole/L)
• Aspartate aminotransferases (ASAT) (male: 15-45 U/L, female: 15-35 U/L)
• Alanine transaminase (ALAT) (male: 10-70 U/L, female: 10-45 U/L)
• Gamma glutamyl transpeptidase (GT) (male: 10-80 U/L, female: 10-45 U/L)
• For women in reproductive age: serum HCG (normal under 3 ye/L)
• Signed informed consent and expected cooperation of the subjects for the treatment

You may not qualify if:

• Taking any medications including herbal medicines the last week prior to treatment visits
• Current or history of drug and/or alcohol abuse (To assess problematic drug or alcohol use we use the CAGE AID screening tool)
• History of contact with police or authorities in relation to alcohol or drug offences
• History of prolonged use of opioid analgesics
• History of prior drug allergy
• Women in reproductive age not using high efficacy contraceptives (Oral contraceptives, Patch (Evra), Implants, Vaginal ring, Hormonal IUD, Copper intra-uterine device (IUD), Sterilization) throughout the study period until their last visit.
• Breastfeeding women
• Participants with access to remifentanil or other potent opioids in their daily workplace.
• Hypersensitivity to naloxone, remifentanil hydrochloride or lidocaine and/or to any of its excipients.
• Participants that have participated in previous trials where they have received remifentanil or other opioids.
• Participants who have donated 450 ml or more blood within 6 weeks prior to visit 2, or who plan to donate blood within 6 weeks after visit 2
• Any reason why, in the opinion of the investigator, the patient should not participate.

Sponsors & Collaborators

• Norwegian University of Science and Technology: lead
• St. Olavs Hospital: collaborator

Study Sites (1)

Department of Circulation and Medical Imaging

Trondheim, Norway

Location

Related Publications (1)

• Tylleskar I, Skulberg AK, Skarra S, Nilsen T, Dale O. Pharmacodynamics and arteriovenous difference of intravenous naloxone in healthy volunteers exposed to remifentanil. Eur J Clin Pharmacol. 2018 Dec;74(12):1547-1553. doi: 10.1007/s00228-018-2545-y. Epub 2018 Aug 24.

  PMID: 30143830 RESULT

MeSH Terms

Conditions

Drug Overdose

Interventions

Remifentanil

Condition Hierarchy (Ancestors)

Prescription Drug Misuse; Drug Misuse; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Propionates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Toril A Nagelhus Hernes, phd prof

  Norwegian University of Science and Technology

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 28, 2015
• First Posted: April 1, 2015
• Study Start: April 1, 2015
• Primary Completion: February 1, 2016
• Study Completion: February 1, 2016
• Last Updated: August 29, 2018

Record last verified: 2018-08

Locations

NO (1)