Drug OverdoseOPI-15-001NCT02405988
Pharmacodynamics and Arteriovenous Differences of Naloxone in Healthy Participants Exposed to an Opioid
A study testing Intravenous naloxone and Remifentanil in people with Drug Overdose, run by Norwegian University of Science and Technology at 1 site in Norway.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 40 yearsHealthy volunteers can take part
- Conditions the study is for
- Drug Overdose
- What is being tested?
- Intravenous naloxone and Remifentanil
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteNorway
- Study dates
- Apr 2015to Feb 2016
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 40 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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)
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- 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
Who cannot join
- 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)
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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
- Being tested
- Intravenous naloxone, Remifentanil
- Keywords
- Emergency Treatment, Morphine Derivates, Heroin, Antidotes, Administration, Intravenous, Pharmacology, Naloxone, Healthy volunteers
- Medical subject headings
- Drug Overdose
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intravenous naloxoneDrug
Also called Naloxone B Braun 0,4 mg/ml
Administer 2,5 mL, dose intravenous naloxone 1,0 mg
RemifentanilDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Intravenous naloxone | Experimental | 0,4 mg/ml Naloxone B Braun 2,5 ML intravenously Receives: Drug: Intravenous naloxone; Drug: Remifentanil |
What is being measured
The primary outcome is the main question the study is designed to answer.
Serum-effect-site equilibration rate constant
Measured: up to 120 minutes
Secondary outcomes (7)
Pharmacokinetics: Area Under the Curve of IV naloxone in arterial and venous serum
Measurement of serum naloxone at times 2, 5, 10, 15, 20, 25, 30, 35, 45, 60, 90 and 120 minutes after naloxone administration
Measured: 120 minutes
Pharmacokinetics: maximum concentration (Cmax) of IV naloxone in arterial and venous serum
Measurement of serum naloxone at times 2, 5, 10, 15, 20, 25, 30, 35, 45, 60, 90 and 120 minutes after naloxone administration
Measured: 120 minutes
Pharmacokinetics: time to maximum concentration (Tmax) of IV naloxone in arterial and venous serum
Measurement of serum naloxone at times 2, 5, 10, 15, 20, 25, 30, 35, 45, 60, 90 and 120 minutes after naloxone administration
Measured: 120 minutes
Pharmacodynamics: measurement of naloxone antagonism of remifentanil effects, by measuring changes in pupillary size
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
Measured: 120 minutes
Quantitate serum concentrations of remifentanil in arterial and venous blood at specified time points
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
Measured: 120 minutes
the effect site equilibration rate constant (ke0) for remifentanil for arterial sampling with pupillary size
Measure serum concentration of remifentanil at -23, -9.5, -7, -2, 30, 60 and 90 minutes relative to naloxone administration
Measured: 120 minutes
serum concentration of remifentanil
Measure serum concentration of remifentanil at -23, -9.5, -7, -2, 30, 60 and 90 minutes relative to naloxone administration
Measured: 120 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Apr 2015 (estimated)
- Study startApr 2015
- Primary completionFeb 2016
- Study completionFeb 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Drug OverdoseStudies of the same condition, open and under way.
- More trials run by Norwegian University of Science and TechnologyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Norwegian University of Science and Technology
- Sponsor type
- University, hospital or other
- Collaborators
- St. Olavs Hospital
- Responsible party
- Sponsor
- Investigators
- Toril A Nagelhus Hernes, phd prof, Study director, Norwegian University of Science and Technology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02405988
- Sponsor's protocol ID
- OPI-15-001
- Other IDs
- 2014-005348-16, 2014
- Acronym
- OPI-15-001
- Status last verified
- Aug 2018
- First submitted
- 28 Mar 2015
- Last updated
- 29 Aug 2018
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 30143830
Study at a glance
From the registry record, last updated by the sponsor on 29 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacodynamics and Arteriovenous Differences of Naloxone in Healthy Participants Exposed to an Opioid
- ClinicalTrials.gov ID
- NCT02405988
- Acronym / sponsor ID
- OPI-15-001 / OPI-15-001
- Conditions
- Drug Overdose
- Keywords
- Emergency Treatment, Morphine Derivates, Heroin, Antidotes, Administration, Intravenous, Pharmacology, Naloxone, Healthy volunteers
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Norwegian University of Science and TechnologyUniversity, hospital or other
- Collaborators
- St. Olavs Hospital
- Study start
- Apr 2015
- Primary completion
- Feb 2016 (actual)
- Study completion
- Feb 2016 (actual)
- First posted
- 1 Apr 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Intravenous naloxone | Experimental | Drug: Intravenous naloxone, Drug: Remifentanil0,4 mg/ml Naloxone B Braun 2,5 ML intravenously |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (12 listed)
- 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:
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Intravenous naloxoneAlso: Naloxone B Braun 0,4 mg/mlAdminister 2,5 mL, dose intravenous naloxone 1,0 mg | Drug | Intravenous naloxone |
| RemifentanilAdminister 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. | Drug | Intravenous naloxone |
Primary outcome
Serum-effect-site equilibration rate constant
Time frame: up to 120 minutes
7 secondary outcomes
Pharmacokinetics: Area Under the Curve of IV naloxone in arterial and venous serum
Time frame: 120 minutes
Pharmacokinetics: maximum concentration (Cmax) of IV naloxone in arterial and venous serum
Time frame: 120 minutes
Pharmacokinetics: time to maximum concentration (Tmax) of IV naloxone in arterial and venous serum
Time frame: 120 minutes
Pharmacodynamics: measurement of naloxone antagonism of remifentanil effects, by measuring changes in pupillary size
Time frame: 120 minutes
Quantitate serum concentrations of remifentanil in arterial and venous blood at specified time points
Time frame: 120 minutes
the effect site equilibration rate constant (ke0) for remifentanil for arterial sampling with pupillary size
Time frame: 120 minutes
serum concentration of remifentanil
Time frame: 120 minutes
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Aug 2018.
- Results publication: PubMed 30143830Tylleskar 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Toril A Nagelhus Hernes, phd prof study director
Norwegian University of Science and Technology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Intravenous naloxone and Remifentanil in people with Drug Overdose, run by Norwegian University of Science and Technology at 1 site in Norway.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Norway. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Serum-effect-site equilibration rate constant (time frame: up to 120 minutes). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02405988, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Aug 2018.