InsomniaPhase 1NCT01655914
Safety and Pharmacokinetic Study of Sublingual Flumazenil (CRLS035) in Healthy Adults
A Phase 1 study testing Flumazenil in people with Insomnia, run by Coeruleus Ltd. at 1 site in Israel.
Trial summary
This study compare the pharmacokinetic (PK) profile of sublingual CRLS035 (two doses) to I.V flumazenil administration. Selection of study drug dosage: CRLS035 - sublingual Flumazenil will be administrated at a final dosage of 1.1 mg per 100 µl and 2.2 mg (200 µl) in a sublingual spray administration. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Insomnia
- What is being tested?
- Flumazenil
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteIsrael
- Study dates
- Jul 2010to Aug 2012
- 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 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- The subject understood and voluntarily signed an informed consent form prior to any study-mandated procedure.
- Male or female aged ≥18-at screening.
- Body mass index ≥ 18.5 and < 32 kg/m2.
- Subject is in good health as determined by a medical history, physical examination and ECG.
- Negative any use of illicit drug, alcohol (ethanol), stimulants.
Who cannot join
- Any use of medications within 1 month prior to screening visit, except for contraceptive pills.
- Previous exposure to Benzodiazepines and/or non-Benzodiazepine hypnotic drugs within 3 months prior to study initiation.
- History of Epilepsy and or anti-epileptic drugs.
- Pregnancy or breast feeding.
- Clinically relevant ECG abnormalities.
- History of alcohol or drug abuse within 3 years prior to the screening visit.
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- Known hypersensitivity to drugs of the same class as the study treatment, or any excipients of the drug formulation.
- Treatment with another investigational drug within 1 month prior to the screening visit.
- History of severe head injury.
- Any acute or chronic illness
- Xerostomia (endogenic or drug induced).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Open Label, Randomized, Three-way Crossover Study to Assess the Safety and the Pharmacokinetics of Sublingual Flumazenil (CRLS035) in Healthy Adults
This study compare the pharmacokinetic (PK) profile of sublingual CRLS035 (two doses) to I.V flumazenil administration.
Selection of study drug dosage: CRLS035 - sublingual Flumazenil will be administrated at a final dosage of 1.1 mg per 100 µl and 2.2 mg (200 µl) in a sublingual spray administration.
Read more
Currently, Flumazenil is given as an IV drug with a repetitive administration of doses of 0.2 mg up to 3 mg per hour. As the bioavailability of Flumazenil is expected to be lower than the IV administration, 1.1 mg and 2.2 mg will be tested in sublingual delivery. The suggested doses in this study are very safe according to the following data: first, sublingual and buccal administration of Flumazenil have been detailed previously with similar and higher doses with no side effects, secondly, IV dose may reach 3 mg and thirdly, oral administration has been reported as up to 600 mg/dose.
The purpose of this study is to determine the single dose PK profile of SL CRLS035. This study is designed to collect short-term safety data and to monitor the PK profile of CRLS035.
Primary Objective The primary objective is to determine the single dose safety and PK profile of SL CRLS035 using the marketed IV flumazenil formulation as the comparator.
Secondary Objectives The secondary objectives are to (1) characterize the concentration time course of two dose levels of SL CRLS035 to support dose selection for Phase 2 and 3 studies and to evaluate the safety and tolerability of flumazenil formulations; (2)To evaluate the effect of high fat diet and water consumption on the PK profile.
- Conditions
- Insomnia
- Being tested
- Flumazenil
- Medical subject headings
- Sleep Initiation and Maintenance Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FlumazenilDrug
| Study group | Role | What they receive |
|---|---|---|
| Arm A | Active comparator | Sequence of Exposure:
Sequence A (N=5) Week 1: S/L 1.1 mg Week 2: S/L 2.2 mg Week 3: IV 0.2 mg Week 4: S/L 2.2 mg with 240 ml water Receives: Drug: Flumazenil |
| Arm B | Active comparator | Sequence B (N=5) Week 1: IV 0.2 mg Week 2: S/L 2.2 mg Week 3: S/L 1.1 mg Week 4: S/L 2.2 mg with high fat diet Receives: Drug: Flumazenil |
What is being measured
The primary outcome is the main question the study is designed to answer.
Bioavailability & Bioequivalence study of sublingual CRLS035 (1.1 mg and 2.2 mg) in a single dose administration
To determine the Bioavailability and Bioequivalence of sublingual CRLS035 (1.1 and 2.2 mg) in a single dose administration using the marketed IV flumazenil formulation (0.2 mg) as the comparator [Cmax, Tmax, Cmin, Tmin, AUC0-∞, AUC0-t, T1/2, and F]
Measured: 3 months
Number of participants with adverse events
To determine the number of participants with adverse events to sublingual CRLS035 administration (1.1 mg and 2.2 mg)
Measured: 3 months
Secondary outcomes (2)
Dose Escalation
The secondary objectives are to characterize the concentration time course of two dose levels of SL CRLS035 to support dose selection for Phase 2 and 3 studies and to evaluate number of participants with adverse events and tolerability of flumazenil formulations.
Measured: 3 months
High Fat Diet and Water Consumption effect
To evaluate the effect of high fat diet and water consumption on the PK profile.
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Aug 2012 (estimated)
- Study startJul 2010
- Primary completionDec 2010
- Study completionAug 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for InsomniaStudies of the same condition, open and under way.
- 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Coeruleus Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01655914
- Sponsor's protocol ID
- CRLS002
- Status last verified
- Jan 2015
- First submitted
- 30 Jul 2012
- Last updated
- 30 Jan 2015
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Jan 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Open Label, Randomized, Three-way Crossover Study to Assess the Safety and the Pharmacokinetics of Sublingual Flumazenil (CRLS035) in Healthy Adults
- ClinicalTrials.gov ID
- NCT01655914
- Acronym / sponsor ID
- CRLS002
- Conditions
- Insomnia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Coeruleus Ltd.Industry (pharma, biotech, devices)
- Study start
- Jul 2010
- Primary completion
- Dec 2010 (actual)
- Study completion
- Aug 2012 (actual)
- First posted
- 2 Aug 2012 (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.
This study compare the pharmacokinetic (PK) profile of sublingual CRLS035 (two doses) to I.V flumazenil administration.
Selection of study drug dosage: CRLS035 - sublingual Flumazenil will be administrated at a final dosage of 1.1 mg per 100 µl and 2.2 mg (200 µl) in a sublingual spray administration.
Currently, Flumazenil is given as an IV drug with a repetitive administration of doses of 0.2 mg up to 3 mg per hour. As the bioavailability of Flumazenil is expected to be lower than the IV administration, 1.1 mg and 2.2 mg will be tested in sublingual delivery. The suggested doses in this study are very safe according to the following data: first, sublingual and buccal administration of Flumazenil have been detailed previously with similar and higher doses with no side effects, secondly, IV dose may reach 3 mg and thirdly, oral administration has been reported as up to 600 mg/dose.
The purpose of this study is to determine the single dose PK profile of SL CRLS035. This study is designed to collect short-term safety data and to monitor the PK profile of CRLS035.
Primary Objective The primary objective is to determine the single dose safety and PK profile of SL CRLS035 using the marketed IV flumazenil formulation as the comparator.
Secondary Objectives The secondary objectives are to (1) characterize the concentration time course of two dose levels of SL CRLS035 to support dose selection for Phase 2 and 3 studies and to evaluate the safety and tolerability of flumazenil formulations; (2)To evaluate the effect of high fat diet and water consumption on the PK profile.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A | Active comparator | Drug: FlumazenilSequence of Exposure: Sequence A (N=5) Week 1: S/L 1.1 mg Week 2: S/L 2.2 mg Week 3: IV 0.2 mg Week 4: S/L 2.2 mg with 240 ml water |
| Arm B | Active comparator | Drug: FlumazenilSequence B (N=5) Week 1: IV 0.2 mg Week 2: S/L 2.2 mg Week 3: S/L 1.1 mg Week 4: S/L 2.2 mg with high fat diet |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- The subject understood and voluntarily signed an informed consent form prior to any study-mandated procedure.
- Male or female aged ≥18-at screening.
- Body mass index ≥ 18.5 and < 32 kg/m2.
- Subject is in good health as determined by a medical history, physical examination and ECG.
- Negative any use of illicit drug, alcohol (ethanol), stimulants.
Key exclusion criteria (11 listed)
- Any use of medications within 1 month prior to screening visit, except for contraceptive pills.
- Previous exposure to Benzodiazepines and/or non-Benzodiazepine hypnotic drugs within 3 months prior to study initiation.
- History of Epilepsy and or anti-epileptic drugs.
- Pregnancy or breast feeding.
- Clinically relevant ECG abnormalities.
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 |
|---|---|---|
| Flumazenil | Drug | Arm A, Arm B |
Primary outcome
Bioavailability & Bioequivalence study of sublingual CRLS035 (1.1 mg and 2.2 mg) in a single dose administration
Time frame: 3 months
To determine the Bioavailability and Bioequivalence of sublingual CRLS035 (1.1 and 2.2 mg) in a single dose administration using the marketed IV flumazenil formulation (0.2 mg) as the comparator [Cmax, Tmax, Cmin, Tmin, AUC0-∞, AUC0-t, T1/2, and F]
Number of participants with adverse events
Time frame: 3 months
To determine the number of participants with adverse events to sublingual CRLS035 administration (1.1 mg and 2.2 mg)
2 secondary outcomes
Dose Escalation
Time frame: 3 months
High Fat Diet and Water Consumption effect
Time frame: 3 months
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 30 Jan 2015.
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 Flumazenil in people with Insomnia, run by Coeruleus Ltd. at 1 site in Israel.
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 5 inclusion and 11 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 30 Jan 2015. 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 Israel. 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?
Bioavailability & Bioequivalence study of sublingual CRLS035 (1.1 mg and 2.2 mg) in a single dose administration (time frame: 3 months). The study lists 2 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 30 Jan 2015.