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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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

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 Summary:

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.

Sponsor: Norwegian University of Science and Technology

Current Primary Outcome: Serum-effect-site equilibration rate constant [ Time Frame: up to 120 minutes ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

• Pharmacokinetics: Area Under the Curve of IV naloxone in arterial and venous serum [ Time Frame: 120 minutes ]
  Measurement of serum naloxone at times 2, 5, 10, 15, 20, 25, 30, 35, 45, 60, 90 and 120 minutes after naloxone administration
• Pharmacokinetics: maximum concentration (Cmax) of IV naloxone in arterial and venous serum [ Time Frame: 120 minutes ]
  Measurement of serum naloxone at times 2, 5, 10, 15, 20, 25, 30, 35, 45, 60, 90 and 120 minutes after naloxone administration
• Pharmacokinetics: time to maximum concentration (Tmax) of IV naloxone in arterial and venous serum [ Time Frame: 120 minutes ]
  Measurement of serum naloxone at times 2, 5, 10, 15, 20, 25, 30, 35, 45, 60, 90 and 120 minutes after naloxone administration
• Pharmacodynamics: measurement of naloxone antagonism of remifentanil effects, by measuring changes in pupillary size [ Time Frame: 120 minutes ]
  Measurement of pupillary size at times -20, -17, -14, -3, -1, 1, 4, 7, 9, 12, 14, 17, 19, 24, 29, 34, 39, 44, 49, 59, 69, 79, 89, 99, 109 and 119 minutes after naloxone administration
• Quantitate serum concentrations of remifentanil in arterial and venous blood at specified time points [ Time Frame: 120 minutes ]
  Measure serum concentration of remifentanil by Gas Chromatography-Mass Spectrometry (GCMS) at -23, -9.5, -7, -2, 30, 60 and 90 minutes relative to naloxone administration
• the effect site equilibration rate constant (ke0) for remifentanil for arterial sampling with pupillary size [ Time Frame: 120 minutes ]
  Measure serum concentration of remifentanil at -23, -9.5, -7, -2, 30, 60 and 90 minutes relative to naloxone administration
• serum concentration of remifentanil [ Time Frame: 120 minutes ]
  Measure serum concentration of remifentanil at -23, -9.5, -7, -2, 30, 60 and 90 minutes relative to naloxone administration

Original Secondary Outcome: Same as current

Information By: Norwegian University of Science and Technology

Dates:
Date Received: March 28, 2015
Date Started: April 2015
Date Completion:
Last Updated: February 2, 2017
Last Verified: February 2017