Pharmacodynamics and Arteriovenous Differences of Naloxone in Healthy Participants Exposed to an Opioid (OPI-15-001)

Norwegian University of Science and Technology

Status

Completed

Conditions

Drug Overdose

Treatments

Drug: Remifentanil

Drug: Intravenous naloxone

Study type

Interventional

Funder types

Other

Identifiers

NCT02405988

2014-005348-16 (EudraCT Number)

OPI-15-001

Details and patient eligibility

About

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.

Full 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.

Enrollment

12 patients

Sex

All

Ages

18 to 40 years old

Volunteers

Accepts Healthy Volunteers

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.