Drug OverdosePhase 1OPI-15-002NCT02598856
Bioavailability of Nasal Naloxone and Injected Naloxone Compared
A Phase 1 study testing Intranasal (IN) naloxone 1x, Intranasal (IN) naloxone 2 and Intravenous (IV) naloxone in people with Drug Overdose, run by Norwegian University of Science and Technology at 1 site in Norway.
Trial summary
Opioid overdoses have in the last decade counted for about 230 untimely deaths annually in Norway. The government is currently implementing a strategy for combating this epidemic. Among the actions promoted in this strategy is the distribution of naloxone for intranasal administration. 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?
- Intranasal (IN) naloxone 1x, Intranasal (IN) naloxone 2 and Intravenous (IV) naloxone
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 1 siteNorway
- Study dates
- Mar 2016to Dec 2016
- Phase
- Phase 1
- 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
- In order to participate in this study the subjects must meet all of the following inclusion criteria:
- Provision of a signed written informed consent
- ECG without any pathological abnormalities
- Have a BMI range of 18.5- 26.0 kg/m
- Female subject with child bearing potential must use high efficacy contraception. For the purpose of this study acceptable contraception is defined as sterilization, oral contraceptives, patch, implants, vaginal ring, hormonal IUD or copper IUD through out the study until the last visit.
- Laboratory values within reference values for the following haematology and biochemistry tests:
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- Haemoglobin
- Creatinine
- ASAT
- ALAT
- Gamma GT
Who cannot join
- In order to participate in the study subjects must not meet any of the following exclusion criteria:
- using medication on a regular basis, including regular use of nasal spray of any form.
- History of prior drug allergy
- local nasal disease or nasal surgery for the last 2 months
- Pregnant or breast feeding women. A serum HCG below 3 U/L must be demonstrated in females of child-bearing potential at Screening Visit.
- Current drug or alcohol abuse, which in the opinion of the Investigator should preclude participation in the study.
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- Having received another new medical chemical entity (defined as a compound which has not been approved for marketing) or having participated in any other clinical study that included drug treatment within 3 months of the administration of investigational product in this study.
- Hypersensitivity to naloxone or any of its excipients.
- Investigator considers subject unlikely to comply with study procedures, restrictions and/or other requirements.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Bioavailability of Nasal Naloxone and Injected Naloxone Compared. A Randomized, Open Label, 4-way Cross-over Study
Opioid overdoses have in the last decade counted for about 230 untimely deaths annually in Norway. The government is currently implementing a strategy for combating this epidemic. Among the actions promoted in this strategy is the distribution of naloxone for intranasal administration. Such administration of naloxone is currently being implemented and tried out around the world, but very little has been done to pharmacologically study this new route of administration of this well known drug, and only 3 open label randomized controlled trials (RCTs) have been conducted. A recent guideline from the WHO on community management of opioid overdoses is a comprehensive review of many of the aspects the investigators cover in our research.
Regarding both dosage, routes of administration of naloxone and care of these patients in the pre hospital setting. The WHO calls for nasal formulations with a higher concentration, as well as focuses on the current wide spread off label use of nasal naloxone as a problem and identifies several research questions of critical importance and very low evidence.The current study, together with our research group's previous and future studies, aims to provide data for the development of a medicinal product with marketing authorisation for use in pre-hospital overdoses. This to contribute to public health measures for opioid users and those around them.
- Conditions
- Drug Overdose
- Being tested
- Intranasal (IN) naloxone 1x, Intranasal (IN) naloxone 2, Intravenous (IV) naloxone, Intramuscular (IM) naloxone
- Keywords
- Emergency Treatment, Morphine Derivates, Heroin, Antidotes, Administration, Intravenous, Pharmacology, Naloxone, Healthy volunteers, Administration, intramuscular, Administration, intranasal
- Medical subject headings
- Drug Overdose
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intranasal (IN) naloxone 1xDrug
Administered as 100 μl 14.0 mg/ml (1.4 mg naloxone) by Aptar Unitdose device as one puff in one nostril
Intranasal (IN) naloxone 2Drug
Administered as 2x 100 μl 14 mg/ml (2.8 mg naloxone) by Aptar Unitdose device as two puffs within the same nostril with 3 minutes interval
Intravenous (IV) naloxoneDrug
Administered as 1 ml Naloxon B Braun 0.4 mg/ml (0.4 mg naloxone), in an intravenous cannula in the opposite arm of which the blood samples are drawn from. IV bolus will be given rapidly (in less than 5 seconds)
Intramuscular (IM) naloxoneDrug
Naloxone administered as 2 ml Naloxon B Braun 0.4 mg/ml (0.8 mg naloxone) in a Braun Omnifix 2.5 ml syringe using a BD Microlance 3 21G (green) 0.8x40 mm needle in the deltoid muscle of the non-dominant arm
| Study group | Role | What they receive |
|---|---|---|
| Intranasal naloxone 1x | Experimental | Each subject will receive one dose of IN naloxone 1.4 mg, IN naloxone 2 x 1.4 mg, IV naloxone 0.4 mg and IM naloxone 0.8 mg in a randomized order. The four doses will be given at four different visits with a washout period of at least 72 hours between. One follow-up visit will be conducted within one month after the last exposure. Receives: Drug: Intranasal (IN) naloxone 1x; Drug: Intranasal (IN) naloxone 2; Drug: Intravenous (IV) naloxone; Drug: Intramuscular (IM) naloxone |
| Intranasal naloxone 2x | Active comparator | Each subject will receive one dose of IN naloxone 1.4 mg, IN naloxone 2 x 1.4 mg, IV naloxone 0.4 mg and IM naloxone 0.8 mg in a randomized order. The four doses will be given at four different visits with a washout period of at least 72 hours between. One follow-up visit will be conducted within one month after the last exposure. Receives: Drug: Intranasal (IN) naloxone 1x; Drug: Intranasal (IN) naloxone 2; Drug: Intravenous (IV) naloxone; Drug: Intramuscular (IM) naloxone |
| Intravenous naloxone | Active comparator | Each subject will receive one dose of IN naloxone 1.4 mg, IN naloxone 2 x 1.4 mg, IV naloxone 0.4 mg and IM naloxone 0.8 mg in a randomized order. The four doses will be given at four different visits with a washout period of at least 72 hours between. One follow-up visit will be conducted within one month after the last exposure. Receives: Drug: Intranasal (IN) naloxone 1x; Drug: Intranasal (IN) naloxone 2; Drug: Intravenous (IV) naloxone; Drug: Intramuscular (IM) naloxone |
| Intramuscular naloxone | Active comparator | Each subject will receive one dose of IN naloxone 1.4 mg, IN naloxone 2 x 1.4 mg, IV naloxone 0.4 mg and IM naloxone 0.8 mg in a randomized order. The four doses will be given at four different visits with a washout period of at least 72 hours between. One follow-up visit will be conducted within one month after the last exposure. Receives: Drug: Intranasal (IN) naloxone 1x; Drug: Intranasal (IN) naloxone 2; Drug: Intravenous (IV) naloxone; Drug: Intramuscular (IM) naloxone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Difference in Peak plasma concentration (Cmax)
Cmax will be compared for single dose IN, IM and IV naloxone
Measured: 4 days
Difference in systemic exposure: Area under the plasma concentration versus time curve (AUC-0last)
AUC 0-last will be compared for single dose IN, IM and IV naloxone
Measured: 4 days
Difference in dose adjusted systemic exposure: Area under the plasma concentration versus time curve (AUC-0inf)
AUC0-inf will be compared for single dose IN, IM and IV naloxone
Measured: 4 days
Difference in time at which the Cmax is observed (Tmax)
Tmax will be compared for single dose IN, IM and IV naloxone
Measured: 4 days
Secondary outcomes (3)
Dose proportionality
assessed by comparing systemic exposure (AUC0-last) following one and two doses of 1.4 mg of IN naloxone in the same nostril.
Measured: 4 days
Absolute bioavailability
assessed by comparing dose adjusted systemic exposure (AUC0-last) of IN and IV naloxone
Measured: 4 days
Relative bioavailability
assessed by comparing dose adjusted systemic exposure (AUC0-last) of IN and IM naloxone
Measured: 4 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Nov 2015 (estimated)
- Study startMar 2016
- Primary completionDec 2016
- Study completionDec 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Norwegian University of Science and Technology
- Sponsor type
- University, hospital or other
- Collaborators
- St. Olavs Hospital, A/S Den norske Eterfabrikk, Smerud Medical Research International AS
- 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
- NCT02598856
- Sponsor's protocol ID
- OPI 15-002
- Other IDs
- 2015-002355-10, 2015
- Acronym
- OPI-15-002
- Status last verified
- Feb 2017
- First submitted
- 2 Nov 2015
- Last updated
- 3 Feb 2017
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 3 Feb 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Bioavailability of Nasal Naloxone and Injected Naloxone Compared. A Randomized, Open Label, 4-way Cross-over Study
- ClinicalTrials.gov ID
- NCT02598856
- Acronym / sponsor ID
- OPI-15-002 / OPI 15-002
- Conditions
- Drug Overdose
- Keywords
- Emergency Treatment, Morphine Derivates, Heroin, Antidotes, Administration, Intravenous, Pharmacology, Naloxone, Healthy volunteers
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Norwegian University of Science and TechnologyUniversity, hospital or other
- Collaborators
- St. Olavs Hospital, A/S Den norske Eterfabrikk, Smerud Medical Research International AS
- Study start
- Mar 2016
- Primary completion
- Dec 2016 (actual)
- Study completion
- Dec 2016 (actual)
- First posted
- 6 Nov 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.
Opioid overdoses have in the last decade counted for about 230 untimely deaths annually in Norway. The government is currently implementing a strategy for combating this epidemic. Among the actions promoted in this strategy is the distribution of naloxone for intranasal administration. Such administration of naloxone is currently being implemented and tried out around the world, but very little has been done to pharmacologically study this new route of administration of this well known drug, and only 3 open label randomized controlled trials (RCTs) have been conducted. A recent guideline from the WHO on community management of opioid overdoses is a comprehensive review of many of the aspects the investigators cover in our research.
Regarding both dosage, routes of administration of naloxone and care of these patients in the pre hospital setting. The WHO calls for nasal formulations with a higher concentration, as well as focuses on the current wide spread off label use of nasal naloxone as a problem and identifies several research questions of critical importance and very low evidence.The current study, together with our research group's previous and future studies, aims to provide data for the development of a medicinal product with marketing authorisation for use in pre-hospital overdoses. This to contribute to public health measures for opioid users and those around them.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Intranasal naloxone 1x | Experimental | Drug: Intranasal (IN) naloxone 1x, Drug: Intranasal (IN) naloxone 2, Drug: Intravenous (IV) naloxone, Drug: Intramuscular (IM) naloxoneEach subject will receive one dose of IN naloxone 1.4 mg, IN naloxone 2 x 1.4 mg, IV naloxone 0.4 mg and IM naloxone 0.8 mg in a randomized order. The four doses will be given at four different visits with a washout period of at least 72 hours between. One follow-up visit will be conducted within one month after the last exposure. |
| Intranasal naloxone 2x | Active comparator | Drug: Intranasal (IN) naloxone 1x, Drug: Intranasal (IN) naloxone 2, Drug: Intravenous (IV) naloxone, Drug: Intramuscular (IM) naloxoneEach subject will receive one dose of IN naloxone 1.4 mg, IN naloxone 2 x 1.4 mg, IV naloxone 0.4 mg and IM naloxone 0.8 mg in a randomized order. The four doses will be given at four different visits with a washout period of at least 72 hours between. One follow-up visit will be conducted within one month after the last exposure. |
| Intravenous naloxone | Active comparator | Drug: Intranasal (IN) naloxone 1x, Drug: Intranasal (IN) naloxone 2, Drug: Intravenous (IV) naloxone, Drug: Intramuscular (IM) naloxoneEach subject will receive one dose of IN naloxone 1.4 mg, IN naloxone 2 x 1.4 mg, IV naloxone 0.4 mg and IM naloxone 0.8 mg in a randomized order. The four doses will be given at four different visits with a washout period of at least 72 hours between. One follow-up visit will be conducted within one month after the last exposure. |
| Intramuscular naloxone | Active comparator | Drug: Intranasal (IN) naloxone 1x, Drug: Intranasal (IN) naloxone 2, Drug: Intravenous (IV) naloxone, Drug: Intramuscular (IM) naloxoneEach subject will receive one dose of IN naloxone 1.4 mg, IN naloxone 2 x 1.4 mg, IV naloxone 0.4 mg and IM naloxone 0.8 mg in a randomized order. The four doses will be given at four different visits with a washout period of at least 72 hours between. One follow-up visit will be conducted within one month after the last exposure. |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (11 listed)
- In order to participate in this study the subjects must meet all of the following inclusion criteria:
- Provision of a signed written informed consent
- ECG without any pathological abnormalities
- Have a BMI range of 18.5- 26.0 kg/m
- Female subject with child bearing potential must use high efficacy contraception. For the purpose of this study acceptable contraception is defined as sterilization, oral contraceptives, patch, implants, vaginal ring, hormonal IUD or copper IUD through out the study until the last visit.
Key exclusion criteria (9 listed)
- In order to participate in the study subjects must not meet any of the following exclusion criteria:
- using medication on a regular basis, including regular use of nasal spray of any form.
- History of prior drug allergy
- local nasal disease or nasal surgery for the last 2 months
- Pregnant or breast feeding women. A serum HCG below 3 U/L must be demonstrated in females of child-bearing potential at Screening Visit.
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 |
|---|---|---|
| Intranasal (IN) naloxone 1xAdministered as 100 μl 14.0 mg/ml (1.4 mg naloxone) by Aptar Unitdose device as one puff in one nostril | Drug | Intramuscular naloxone, Intranasal naloxone 1x, Intranasal naloxone 2x, Intravenous naloxone |
| Intranasal (IN) naloxone 2Administered as 2x 100 μl 14 mg/ml (2.8 mg naloxone) by Aptar Unitdose device as two puffs within the same nostril with 3 minutes interval | Drug | Intramuscular naloxone, Intranasal naloxone 1x, Intranasal naloxone 2x, Intravenous naloxone |
| Intravenous (IV) naloxoneAdministered as 1 ml Naloxon B Braun 0.4 mg/ml (0.4 mg naloxone), in an intravenous cannula in the opposite arm of which the blood samples are drawn from. IV bolus will be given rapidly (in less than 5 seconds) | Drug | Intramuscular naloxone, Intranasal naloxone 1x, Intranasal naloxone 2x, Intravenous naloxone |
| Intramuscular (IM) naloxoneNaloxone administered as 2 ml Naloxon B Braun 0.4 mg/ml (0.8 mg naloxone) in a Braun Omnifix 2.5 ml syringe using a BD Microlance 3 21G (green) 0.8x40 mm needle in the deltoid muscle of the non-dominant arm | Drug | Intramuscular naloxone, Intranasal naloxone 1x, Intranasal naloxone 2x, Intravenous naloxone |
Primary outcome
Difference in Peak plasma concentration (Cmax)
Time frame: 4 days
Cmax will be compared for single dose IN, IM and IV naloxone
Difference in systemic exposure: Area under the plasma concentration versus time curve (AUC-0last)
Time frame: 4 days
AUC 0-last will be compared for single dose IN, IM and IV naloxone
Difference in dose adjusted systemic exposure: Area under the plasma concentration versus time curve (AUC-0inf)
Time frame: 4 days
AUC0-inf will be compared for single dose IN, IM and IV naloxone
Difference in time at which the Cmax is observed (Tmax)
Time frame: 4 days
Tmax will be compared for single dose IN, IM and IV naloxone
3 secondary outcomes
Dose proportionality
Time frame: 4 days
Absolute bioavailability
Time frame: 4 days
Relative bioavailability
Time frame: 4 days
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 3 Feb 2017.
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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 Phase 1 study testing Intranasal (IN) naloxone 1x, Intranasal (IN) naloxone 2 and Intravenous (IV) naloxone 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 11 inclusion and 9 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 3 Feb 2017. 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.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Difference in Peak plasma concentration (Cmax) (time frame: 4 days). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 3 Feb 2017.