Drug OverdosePhase 1NCT02733822
Buccal Versus Injectable Naloxone: a Phase I Healthy Volunteer Study
A Phase 1 study testing Naloxone in people with Drug Overdose and Opioid-Related Disorders, run by King's College London.
Trial summary
Naloxone is the standard treatment in response to cases of suspected opiate overdose. Buccal formulation of naloxone is a novel alternative to the licensed naloxone injection which, by removing the risk of accidental needle-stick, may be safer and easier to administer. Read more about this study
- Who is it for?
- Ages 18 to 64 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Drug Overdose, Opioid-Related Disorders
- What is being tested?
- Naloxone
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4 participants
- Where
- No sites listed yet
- Study dates
- Jun 2016to Jun 2017
- 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 64 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Adult males aged 18 to 64 years inclusive and between 19 and 29.9 kg/m2 body mass index (BMI).
- Subjects who are healthy as determined by pre-study medical history and physical examination.
- Subjects who are able and willing to give written informed consent.
- Medical history must be verified by either a personal physician or medical practitioner as appropriate.
Who cannot join
- Subjects who do not conform to the above inclusion criteria.
- Subjects who have a clinical condition (such as abnormal liver function, renal or cardiac issues) which, in the opinion of their personal physician or other examining medical practitioner, makes participation in the study inappropriate.
- Subjects who have a clinically relevant surgical history.
- Subjects who have a clinically relevant family history.
- Subjects who have a history of relevant atopy.
- Subjects who have a history of drug hypersensitivity relevant to naloxone.
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- Subjects who have a history of alcoholism.
- Subjects who have a history of drug abuse.
- Subjects who consume more than 42 units of alcohol a week. (unit = 1 glass of wine (125 mL) = 1 measure of spirits = ½ pint of beer)
- Subjects who have an acute infection (such as influenza) or relevant lesion (such as oral tract) at the time of screening or admission. Subjects can be rescreened once they have recovered. At re-screening, a urine test of drugs of abuse and alcohol parameters will need to be repeated.
- Subjects who have used prescription drugs within 4 weeks of first dosing.
- Subjects who have used over the counter medications containing codeine or other opiates within 7 days of first dosing, unless agreed as not clinically relevant by the Principal Investigator. Details will be documented in source data.
- Subjects who have used any investigational drug in any clinical trial within 3 months of receiving the last dose.
- Subjects who have received the last dose of IMP greater than 3 months ago but who are on extended follow-up
- Subjects who cannot communicate reliably with the Investigator.
- Subjects who are unlikely to co-operate with the requirements of the study.
Trial locations and contacts
No sites are listed yet.
About this study
Official title: A Pilot, Phase 1, Open-Labelled, 4 Period, Randomised, Crossover Study to Evaluate the Pharmacokinetics of Naloxone When Given by the IV, IM and Buccal Routes of Administration in Healthy Male Subjects
Naloxone is the standard treatment in response to cases of suspected opiate overdose.
Buccal formulation of naloxone is a novel alternative to the licensed naloxone injection which, by removing the risk of accidental needle-stick, may be safer and easier to administer.
Read more
Current UK policy allows the emergency administration of naloxone by any member of the general public (Strang, Kelleher, Best, Mayet, \& Manning, 2006), and the preventative provision of naloxone to drug users and their family members ("take-home naloxone") is possible on a prescription basis. Thus, buccal naloxone may be particularly suitable for administration by family members who are providing interim overdose management care while awaiting the arrival of an ambulance.
The aim of this study is to examine the bioavailability and dose proportionality of buccal naloxone compared with the licensed injection standards (intravenous, intramuscular).
The investigators hypothesise that buccal naloxone is not inferior to the injection reference in absorption kinetics, i.e. time elapsed till peak concentration (Tmax; primary outcome), peak plasma concentration (Cmax), overall absorption (AUC), bioavailability (F%) and, duration of action (mean terminal half-life; T1/2).
The investigators propose a pharmacokinetic pilot investigation with within-subjects (crossover) design, comparing two doses (0.8 mg; 1.6 mg) of buccal naloxone hydrochloride solution to the licensed intramuscular (IM; 0.8 mg) and intravenous (IV; 0.8 mg) routes of injection. The investigators will invite four healthy (i.e., non-opioid using) male volunteers (n=4, not powered), each of whom will attend four experimental sessions at counterbalanced sequence. Each volunteer will receive naloxone hydrochloride doses of 0.8 mg IM, 0.8 mg IV, 0.8 mg buccal, and 1.6 mg buccal, with only one dose administered per session.
Blood concentrations will be measured at selected times during each session to establish speed of naloxone absorption, time to peak concentration, estimated half-life, and overall bioavailability. This dose-ranging pilot will inform future work by providing preliminary data on buccal naloxone absorption into the bloodstream and by establishing feasibility of the buccal route for naloxone delivery.
Read the detailed description
Blood samples (3 ml) will be collected at -5, +1, 2, 3, 4, 6, 8, 10, 12.5, 15, 30, 45, 60, 75, 90, 120, 150, 180, 240, 300, 360, 420, and 480 minutes.
- Conditions
- Drug Overdose, Opioid-Related Disorders
- Being tested
- Naloxone
- Keywords
- opiate, heroin, opioid, overdose, naloxone
- Medical subject headings
- Drug Overdose, Opioid-Related Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NaloxoneDrug
Also called naloxone-hydrochloride
| Study group | Role | What they receive |
|---|---|---|
| IMP: buccal naloxone (single dose) | Experimental | 0.8 mg buccal (solution) of 1 mg/ml Naloxone Hydrochloride Injection Receives: Drug: Naloxone |
| IMP: buccal naloxone (double dose) | Experimental | 1.6 mg buccal (solution) of 1 mg/ml Naloxone Hydrochloride Injection Receives: Drug: Naloxone |
| Intramuscular (IM) reference | Active comparator | 0.8 mg IM injection of 1 mg/ml Naloxone Hydrochloride Injection Receives: Drug: Naloxone |
| Intravenous (IV) reference | Active comparator | 0.8 mg IV injection of 1 mg/ml Naloxone Hydrochloride Injection Receives: Drug: Naloxone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Tmax
Time elapsed till peak concentration
Measured: Within 8-hour sampling period
Secondary outcomes (4)
Peak plasma concentration is assessed as Cmax
Peak concentration
Measured: Within 8-hour sampling period
Absorption of the active ingredient is determined as Area under the Curve (AUC)
Overall absorption (AUC = Area Under the Curve)
Measured: Within 8-hour sampling period
Absolute bioavailability of buccal naloxone relative to intravenous naloxone is assessed as F%
Absolute bioavailability relative to the IV reference (dose-corrected AUC for non-intravenous Buccal AUC divided by intravenous AUC multiplied by 100
Measured: Within 8-hour sampling period
Mean terminal half-life is assessed for all participants as T1/2
mean terminal half-life
Measured: Within 8-hour sampling period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Apr 2016 (estimated)
- Study startJun 2016
- Primary completionJun 2017 (estimated)
- Study completionJun 2017 (estimated)
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 King's College LondonThe 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
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 4 participants (estimated)
Sponsor and investigators
- Lead sponsor
- King's College London
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- John Strang, MBBS, MD, Principal investigator, King's College London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02733822
- Sponsor's protocol ID
- KCL/NALOX/01/14
- Status last verified
- May 2016
- First submitted
- 8 Mar 2016
- Last updated
- 17 May 2016
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided: There is no plan to provide access to to raw data.
Study at a glance
From the registry record, last updated by the sponsor on 17 May 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot, Phase 1, Open-Labelled, 4 Period, Randomised, Crossover Study to Evaluate the Pharmacokinetics of Naloxone When Given by the IV, IM and Buccal Routes of Administration in Healthy Male Subjects
- ClinicalTrials.gov ID
- NCT02733822
- Acronym / sponsor ID
- KCL/NALOX/01/14
- Conditions
- Drug Overdose, Opioid-Related Disorders
- Keywords
- opiate, heroin, opioid, overdose, naloxone
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 4 participants (estimated)
- Lead sponsor
- King's College LondonUniversity, hospital or other
- Study start
- Jun 2016
- Primary completion
- Jun 2017 (estimated)
- Study completion
- Jun 2017 (estimated)
- First posted
- 12 Apr 2016 (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.
Naloxone is the standard treatment in response to cases of suspected opiate overdose.
Buccal formulation of naloxone is a novel alternative to the licensed naloxone injection which, by removing the risk of accidental needle-stick, may be safer and easier to administer.
Current UK policy allows the emergency administration of naloxone by any member of the general public (Strang, Kelleher, Best, Mayet, \& Manning, 2006), and the preventative provision of naloxone to drug users and their family members ("take-home naloxone") is possible on a prescription basis. Thus, buccal naloxone may be particularly suitable for administration by family members who are providing interim overdose management care while awaiting the arrival of an ambulance.
The aim of this study is to examine the bioavailability and dose proportionality of buccal naloxone compared with the licensed injection standards (intravenous, intramuscular).
The investigators hypothesise that buccal naloxone is not inferior to the injection reference in absorption kinetics, i.e. time elapsed till peak concentration (Tmax; primary outcome), peak plasma concentration (Cmax), overall absorption (AUC), bioavailability (F%) and, duration of action (mean terminal half-life; T1/2).
The investigators propose a pharmacokinetic pilot investigation with within-subjects (crossover) design, comparing two doses (0.8 mg; 1.6 mg) of buccal naloxone hydrochloride solution to the licensed intramuscular (IM; 0.8 mg) and intravenous (IV; 0.8 mg) routes of injection. The investigators will invite four healthy (i.e., non-opioid using) male volunteers (n=4, not powered), each of whom will attend four experimental sessions at counterbalanced sequence. Each volunteer will receive naloxone hydrochloride doses of 0.8 mg IM, 0.8 mg IV, 0.8 mg buccal, and 1.6 mg buccal, with only one dose administered per session.
Blood concentrations will be measured at selected times during each session to establish speed of naloxone absorption, time to peak concentration, estimated half-life, and overall bioavailability. This dose-ranging pilot will inform future work by providing preliminary data on buccal naloxone absorption into the bloodstream and by establishing feasibility of the buccal route for naloxone delivery.
Detailed description
Blood samples (3 ml) will be collected at -5, +1, 2, 3, 4, 6, 8, 10, 12.5, 15, 30, 45, 60, 75, 90, 120, 150, 180, 240, 300, 360, 420, and 480 minutes.
Study design
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| IMP: buccal naloxone (single dose) | Experimental | Drug: Naloxone0.8 mg buccal (solution) of 1 mg/ml Naloxone Hydrochloride Injection |
| IMP: buccal naloxone (double dose) | Experimental | Drug: Naloxone1.6 mg buccal (solution) of 1 mg/ml Naloxone Hydrochloride Injection |
| Intramuscular (IM) reference | Active comparator | Drug: Naloxone0.8 mg IM injection of 1 mg/ml Naloxone Hydrochloride Injection |
| Intravenous (IV) reference | Active comparator | Drug: Naloxone0.8 mg IV injection of 1 mg/ml Naloxone Hydrochloride Injection |
Who may qualify
- Ages
- 18 to 64 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Adult males aged 18 to 64 years inclusive and between 19 and 29.9 kg/m2 body mass index (BMI).
- Subjects who are healthy as determined by pre-study medical history and physical examination.
- Subjects who are able and willing to give written informed consent.
- Medical history must be verified by either a personal physician or medical practitioner as appropriate.
Key exclusion criteria (16 listed)
- Subjects who do not conform to the above inclusion criteria.
- Subjects who have a clinical condition (such as abnormal liver function, renal or cardiac issues) which, in the opinion of their personal physician or other examining medical practitioner, makes participation in the study inappropriate.
- Subjects who have a clinically relevant surgical history.
- Subjects who have a clinically relevant family history.
- Subjects who have a history of relevant atopy.
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 |
|---|---|---|
| NaloxoneAlso: naloxone-hydrochloride | Drug | IMP: buccal naloxone (double dose), IMP: buccal naloxone (single dose), Intramuscular (IM) reference, Intravenous (IV) reference |
Primary outcome
Tmax
Time frame: Within 8-hour sampling period
Time elapsed till peak concentration
4 secondary outcomes
Peak plasma concentration is assessed as Cmax
Time frame: Within 8-hour sampling period
Absorption of the active ingredient is determined as Area under the Curve (AUC)
Time frame: Within 8-hour sampling period
Absolute bioavailability of buccal naloxone relative to intravenous naloxone is assessed as F%
Time frame: Within 8-hour sampling period
Mean terminal half-life is assessed for all participants as T1/2
Time frame: Within 8-hour sampling period
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 May 2016.
- Individual participant dataSharing planned: Undecided. There is no plan to provide access to to raw data.
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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.
John Strang, MBBS, MD principal investigator
King's College London
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Naloxone in people with Drug Overdose and Opioid-Related Disorders, run by King's College London.
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 4 inclusion and 16 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: status not confirmed, as of the sponsor's last update on 17 May 2016. Status can change between updates, so confirm with the study contact before making plans.
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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Rebecca McDonald, MSc (+44-207-848-0628, rebecca.s.mcdonald@kcl.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Tmax (time frame: Within 8-hour sampling period). 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 17 May 2016.