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

NCT ID: NCT02405988

Last Updated: 2018-08-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-04-30
• Study Completion Date: 2016-02-29

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.

Detailed Description

Healthy volunteers will be brought into a state of opioid influence in a well-known, short acting, controlled and safe manner using remifentanil. This will create a strong opioid effect inducing a miosis, reduced respiration and reduced sensation to pain, all three strong indicators of opiates. Naloxone will counteract these effects, which can be measured as a change in pupillary size. Blood samples for both naloxone and remifentanil will be also be taken.

Naloxone is a well-known, well-tolerated drug with an excellent safety profile over many decades of use. The formulation used in this trial holds market authorization. Care will be taken not to include opioid users in this study as naloxone would precipitate acute withdrawal. Also possible drug misusers will be excluded as well as people who have access to remifentanil and infusion equipment in their daily work, although the abuse potential of this highly specialised drug is minimal. By weighing syringes before and after discharge the reliability of the dose delivered will be confirmed.

Conditions

Drug Overdose

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Intravenous naloxone

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

Group Type: EXPERIMENTAL

Intravenous naloxone

Intervention Type: DRUG

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

Remifentanil

Intervention Type: 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.

Interventions

Intravenous naloxone

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

Intervention Type: DRUG

Remifentanil

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.

Intervention Type: DRUG

Other Intervention Names

Naloxone B Braun 0,4 mg/ml

Eligibility Criteria

Inclusion Criteria

• 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
• lab values within reference values at St Olav's Hospital for the relevant haematological and biochemical test for inclusion:

• 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

Exclusion Criteria

• 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
• Pregnant women (HCG over 3 ye/L at inclusion)
• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

St. Olavs Hospital

OTHER

Sponsor Role: collaborator

Norwegian University of Science and Technology

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Toril A Nagelhus Hernes, phd prof

Role: STUDY_DIRECTOR

Norwegian University of Science and Technology

Locations

Department of Circulation and Medical Imaging

Trondheim, , Norway

Countries

Norway

References

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.

Reference Type: RESULT

PMID: 30143830 (View on PubMed)

Other Identifiers

2014-005348-16

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

OPI-15-001

Identifier Type: -

Identifier Source: org_study_id