Procedural SedationPhase 1NCT03329014
A Trial of Intranasal Remimazolam Pharmacokinetics, Pharmacodynamics, Safety and Bioavailability
A Phase 1 study testing Remimazolam in people with Procedural Sedation, run by Paion UK Ltd. at 1 site in United States.
Trial summary
A prospective dose escalation, nine period cross-over trial assessing the safety, pharmacokinetics, bioavailability and pharmacodynamics of escalating doses of Remimazolam when administered intranasally as powder and solution in healthy subjects and compared to an intravenous control Read more about this study
- Who is it for?
- Ages 18 to 45 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Procedural Sedation
- What is being tested?
- Remimazolam
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- 15 May 2017to 14 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 45 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Willing to participate in the trial, give written informed consent prior to the initiation of any protocol specific procedures, and to comply with the study restrictions.
- Able to speak, read and understand English sufficiently to allow completion of all study assessments.
- Gender: males
- Age: 18 45 years, inclusive, at screening
- Weight: 50 to 120 kg, inclusive, at screening
- Body mass index: 19.0 to 33.0 kg/m2, inclusive, at screening
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- Healthy status, defined by the absence of evidence of any clinically significant, active or chronic diseases, in the opinion of the Investigator, following a detailed medical and surgical history, a complete physical examination, and evaluation of vital signs, 12 lead ECG, hematology, blood chemistry, serology, and urinalysis.
- Previous experience with intranasal drug application (within the last year)
- Ability and willingness to abstain from alcohol, caffeine, and xanthine containing beverages or food (e.g., coffee, tea, cola, chocolate, energy drinks) from 24 hours (1 day) prior to admission to the clinical facility on Day 0 until study discharge.
- All values for hematology and for clinical chemistry tests of blood and urine within the normal range or showing no clinically relevant deviations as judged by the Investigator.
Who cannot join
- Use of any intranasally applied medication within two weeks from randomization.
- Use of benzodiazepines or other central nervous system (CNS) active drugs within 4 weeks of inclusion.
- History of alcohol abuse or drug addiction (except nicotine), as defined by the Diagnostic and Statistical Manual of Mental Disorders, fifth edition, text revision (DSM V TR), or any self reported dependence or "addiction" within the subject's lifetime (except nicotine or caffeine).
- Abnormal 12 lead ECG at screening, including:
- QTcF ≥ 450 ms
- QRS ≥ 110 ms
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- PR ≥ 220 ms
- Second or third degree AV block
- Use of any investigational drug or device within 30 days of the first dose of study medication.
- History of relevant food allergies.
- Any disease which, in the opinion of the Investigator, poses an unacceptable risk to the subjects.
- Known allergy, hypersensitivity or prior intolerance to benzodiazepine derivatives or flumazenil, or a medical condition such that these agents are contraindicated.
- Strenuous activity, sunbathing, and contact sports within 48 hours (2 days) prior to (first) admission to the clinical facility and for the duration of the study.
- History of donation or loss of more than 450 mL of blood or blood products within 60 days prior to dosing in the clinical research center or planned donation before 30 days has elapsed since intake of study drug in the current study.
- Positive screening test for hepatitis B surface antigen (HBsAg), anti hepatitis C virus (HCV) antibodies, or anti human immunodeficiency virus (HIV) 1 and 2 antibodies.
- Positive drug and alcohol screen (opiates, methadone, cocaine, amphetamines [including ecstasy], barbiturates, benzodiazepines, tricyclic antidepressants and alcohol) at screening and at admission to the clinical research center; subjects positive for cannabinoids will be allowed only at the discretion of the Investigator.
- Inability to be venipunctured or tolerate venous access as determined by the Investigator.
- History of clinically significant, non remote suicidal ideations or suicide attempts based on the C SSRS that, in the opinion of the Investigator, pose an unacceptable risk to the subject for participating in the study.
- Had had any major surgery within 4 weeks of study drug administration.
- Requires concomitant treatment with any prescription or non prescription medications (with the exception of acetaminophen) or natural health products (herbal remedies), or respiratory depressants, or cannot safely discontinue these medications at least 7 days prior to receiving study drug.
- Subject is an employee of the sponsor or research site personnel directly affiliated with this study or their immediate family member defined as a spouse, parent, child or sibling, whether biological or legally adopted.
- A subject who, in the opinion of the investigator, is considered unsuitable or unlikely to comply with the study protocol for any reason.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomized, Double-blind, Placebo-controlled 9-period Crossover, Dose-Escalation Study on the Safety, Bioavailability and Pharmacodynamics of Remimazolam Administered Intranasally as Powder and as Solution in Healthy Subjects
A prospective dose escalation, nine period cross-over trial assessing the safety, pharmacokinetics, bioavailability and pharmacodynamics of escalating doses of Remimazolam when administered intranasally as powder and solution in healthy subjects and compared to an intravenous control
Read the detailed description
The design will be a randomized, double-blind, comparative, placebo- and active-controlled nine-period crossover study in healthy male volunteers. Subjects will be randomized and will receive each of the 9 treatments which will be separated by a minimum of 48 hours.The first treatment arm will always be the intravenous remimazolam. Eligible subjects will then be randomized to treatment sequence prior to study drug administration in treatment period 2. Each subject will participate in the study for up to 51 days, from Screening until Follow-up.
- Conditions
- Procedural Sedation
- Being tested
- Remimazolam, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RemimazolamDrug
Also called CNS7056
For induction and maintenance of sedation
PlaceboDrug
Control arm
| Study group | Role | What they receive |
|---|---|---|
| Intravenous Remimazolam | Experimental | 4 mg intravenous remimazolam as an intravenous control Receives: Drug: Remimazolam |
| 10 mg Powder Remimazolam | Experimental | Powder containing 10 mg remimazolam for intranasal administration Receives: Drug: Remimazolam |
| 10 mg Solution Remimazolam | Experimental | Solution containing 10 mg remimazolam for intranasal administration Receives: Drug: Remimazolam |
| 20 mg Powder Remimazolam | Experimental | Powder containing 20 mg remimazolam for intranasal administration Receives: Drug: Remimazolam |
| 20 mg solution Remimazolam | Experimental | Solution containing 20 mg remimazolam for intranasal administration Receives: Drug: Remimazolam |
| 40 mg Powder Remimazolam | Experimental | Powder containing 40 mg remimazolam for intranasal administration Receives: Drug: Remimazolam |
| 40 mg Solution Remimazolam | Experimental | Solution containing 40 mg remimazolam for intranasal administration Receives: Drug: Remimazolam |
| Placebo Powder | Placebo comparator | Powder containing 20 mg placebo for intranasal administration Receives: Drug: Placebo |
| Placebo solution | Placebo comparator | Solution containing 20 mg placebo for intranasal administration Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants with Treatment-related Adverse Events
Adverse events assessment will include: change in clinical laboratory assessments from baseline, change in vital signs from baseline, change in 12-lead electrocardiograms from baseline, drop in oxygen saturation measured using continuous pulse oximetry, nasal effect using the Nasal Effect Questionnaire (NEQ) and nose and throat examination. Adverse events with a respiratory or cardiovascular focus and adverse events related to effects seen with medications known to be associated with abuse will be analysed separately. The intensity, causality, outcome, seriousness and expectedness of adverse events will be assessed
Measured: Predose until 180 minutes postdose
Secondary outcomes (12)
Alertness/Drowsiness using a bipolar 100-point Visual Analogue Scale (VAS)
maximum effect (Emax), time to Emax (TEmax), minimum effect (Emin) and area under the effect curve (AUEC) determined pre-dose, 5, 10, 30, 60 and 180 minutes post dose
Measured: Predose until 180 minutes postdose
Agitation/Relaxation using a bipolar 100-point Visual Analogue Scale (VAS)
maximum effect (Emax), time to Emax (TEmax), minimum effect (Emin) and area under the effect curve (AUEC) determined pre-dose, 5, 10, 30, 60 and 180 minutes post dose
Measured: Predose until 180 minutes postdose
Any Drug Effects using a unipolar 100-point Visual Analogue Scale (VAS)
maximum effect (Emax), time to Emax (TEmax), minimum effect (Emin) and area under the effect curve (AUEC) determined pre-dose, 5, 10, 30, 60 and 180 minutes post dose
Measured: Predose until 180 minutes postdose
Memory/Amnestic Effects using the Paired Associates Learning (PALs) test
maximum effect (Emax), time to Emax (TEmax), minimum effect (Emin) and area under the effect curve (AUEC) determined pre-dose,10, 30, 60 and 180 minutes post dose
Measured: Predose until 180 minutes postdose
Reaction Time using the Reaction Time Test
maximum effect (Emax), time to Emax (TEmax), minimum effect (Emin) and area under the effect curve (AUEC) determined pre-dose, 20, 30, 60, 90, 120, 150 and 180 post dose
Measured: Predose until 180 minutes postdose
Time to Maximum Observed Plasma Concentration (Tmax)
Measured: From first dose of study drug until 240 minutes postdose
Maximum Observed Plasma Concentration (Cmax)
Measured: From first dose of study drug until 240 minutes postdose
Area Under the Plasma Concentration-time Curve from Zero to the last Measurable Concentration (AUC0-last)
Measured: From first dose of study drug until 240 minutes postdose
Area Under the Plasma Concentration-time Curve from Zero to Infinity (AUC0-∞)
Measured: From first dose of study drug until 240 minutes postdose
Terminal Elimination Half-life (t1/2) for Remimazolam and its Metabolite (CNS7054)
Measured: From first dose of study drug until 240 minutes postdose
Concentration at Time Zero (C0) for Intravenous Remimazolam and its Metabolite (CNS7054) Only
Measured: From first dose of study drug until 240 minutes postdose
The Fraction in Percent as a Measurement of the Rate and Extent to Which a Drug Reaches the Site of Action (F%)
F% will be calculated for the highest dose level (40 mg) and dose-proportionality will be evaluated across the dose range of 10 - 40 mg for each formulation (powder and solution) as available. Dose proportionality is AUC0-∞ and Cmax based. Bioavailability will be dose adjusted.
Measured: From first dose of study drug until 240 minutes postdose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Nov 2017
- Study start15 May 2017
- Primary completion9 Jun 2017
- Study completion14 Jun 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Procedural SedationStudies 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
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Paion UK Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- PRA Health Sciences
- Responsible party
- Sponsor
- Investigators
- Shawn Searly, M.D, Principal investigator, PRA Health Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03329014
- Sponsor's protocol ID
- CNS7056-019
- Status last verified
- Apr 2019
- First submitted
- 2 Oct 2017
- Last updated
- 4 Apr 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-blind, Placebo-controlled 9-period Crossover, Dose-Escalation Study on the Safety, Bioavailability and Pharmacodynamics of Remimazolam Administered Intranasally as Powder and as Solution in Healthy Subjects
- ClinicalTrials.gov ID
- NCT03329014
- Acronym / sponsor ID
- CNS7056-019
- Conditions
- Procedural Sedation
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Paion UK Ltd.Industry (pharma, biotech, devices)
- Collaborators
- PRA Health Sciences
- Study start
- 15 May 2017 (actual)
- Primary completion
- 9 Jun 2017 (actual)
- Study completion
- 14 Jun 2017 (actual)
- First posted
- 1 Nov 2017 (actual)
- 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.
A prospective dose escalation, nine period cross-over trial assessing the safety, pharmacokinetics, bioavailability and pharmacodynamics of escalating doses of Remimazolam when administered intranasally as powder and solution in healthy subjects and compared to an intravenous control
Detailed description
The design will be a randomized, double-blind, comparative, placebo- and active-controlled nine-period crossover study in healthy male volunteers. Subjects will be randomized and will receive each of the 9 treatments which will be separated by a minimum of 48 hours.The first treatment arm will always be the intravenous remimazolam. Eligible subjects will then be randomized to treatment sequence prior to study drug administration in treatment period 2. Each subject will participate in the study for up to 51 days, from Screening until Follow-up.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 9
| Arm | Type | Receives |
|---|---|---|
| Intravenous Remimazolam | Experimental | Drug: Remimazolam4 mg intravenous remimazolam as an intravenous control |
| 10 mg Powder Remimazolam | Experimental | Drug: RemimazolamPowder containing 10 mg remimazolam for intranasal administration |
| 10 mg Solution Remimazolam | Experimental | Drug: RemimazolamSolution containing 10 mg remimazolam for intranasal administration |
| 20 mg Powder Remimazolam | Experimental | Drug: RemimazolamPowder containing 20 mg remimazolam for intranasal administration |
| 20 mg solution Remimazolam | Experimental | Drug: RemimazolamSolution containing 20 mg remimazolam for intranasal administration |
| 40 mg Powder Remimazolam | Experimental | Drug: RemimazolamPowder containing 40 mg remimazolam for intranasal administration |
| 40 mg Solution Remimazolam | Experimental | Drug: RemimazolamSolution containing 40 mg remimazolam for intranasal administration |
| Placebo Powder | Placebo comparator | Drug: PlaceboPowder containing 20 mg placebo for intranasal administration |
| Placebo solution | Placebo comparator | Drug: PlaceboSolution containing 20 mg placebo for intranasal administration |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (10 listed)
- Willing to participate in the trial, give written informed consent prior to the initiation of any protocol specific procedures, and to comply with the study restrictions.
- Able to speak, read and understand English sufficiently to allow completion of all study assessments.
- Gender: males
- Age: 18 45 years, inclusive, at screening
- Weight: 50 to 120 kg, inclusive, at screening
Key exclusion criteria (22 listed)
- Use of any intranasally applied medication within two weeks from randomization.
- Use of benzodiazepines or other central nervous system (CNS) active drugs within 4 weeks of inclusion.
- History of alcohol abuse or drug addiction (except nicotine), as defined by the Diagnostic and Statistical Manual of Mental Disorders, fifth edition, text revision (DSM V TR), or any self reported dependence or "addiction" within the subject's lifetime (except nicotine or caffeine).
- Abnormal 12 lead ECG at screening, including:
- Use of any investigational drug or device within 30 days of the first dose of study medication.
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 |
|---|---|---|
| RemimazolamAlso: CNS7056For induction and maintenance of sedation | Drug | 10 mg Powder Remimazolam, 10 mg Solution Remimazolam, 20 mg Powder Remimazolam, 20 mg solution Remimazolam, 40 mg Powder Remimazolam, 40 mg Solution Remimazolam, Intravenous Remimazolam |
| PlaceboControl arm | Drug | Placebo Powder, Placebo solution |
Primary outcome
Number of Participants with Treatment-related Adverse Events
Time frame: Predose until 180 minutes postdose
Adverse events assessment will include: change in clinical laboratory assessments from baseline, change in vital signs from baseline, change in 12-lead electrocardiograms from baseline, drop in oxygen saturation measured using continuous pulse oximetry, nasal effect using the Nasal Effect Questionnaire (NEQ) and nose and throat examination. Adverse events with a respiratory or cardiovascular focus and adverse events related to effects seen with medications known to be associated with abuse will be analysed separately. The intensity, causality, outcome, seriousness and expectedness of adverse events will be assessed
12 secondary outcomes
Alertness/Drowsiness using a bipolar 100-point Visual Analogue Scale (VAS)
Time frame: Predose until 180 minutes postdose
Agitation/Relaxation using a bipolar 100-point Visual Analogue Scale (VAS)
Time frame: Predose until 180 minutes postdose
Any Drug Effects using a unipolar 100-point Visual Analogue Scale (VAS)
Time frame: Predose until 180 minutes postdose
Memory/Amnestic Effects using the Paired Associates Learning (PALs) test
Time frame: Predose until 180 minutes postdose
Reaction Time using the Reaction Time Test
Time frame: Predose until 180 minutes postdose
Time to Maximum Observed Plasma Concentration (Tmax)
Time frame: From first dose of study drug until 240 minutes postdose
Maximum Observed Plasma Concentration (Cmax)
Time frame: From first dose of study drug until 240 minutes postdose
Area Under the Plasma Concentration-time Curve from Zero to the last Measurable Concentration (AUC0-last)
Time frame: From first dose of study drug until 240 minutes postdose
Area Under the Plasma Concentration-time Curve from Zero to Infinity (AUC0-∞)
Time frame: From first dose of study drug until 240 minutes postdose
Terminal Elimination Half-life (t1/2) for Remimazolam and its Metabolite (CNS7054)
Time frame: From first dose of study drug until 240 minutes postdose
Concentration at Time Zero (C0) for Intravenous Remimazolam and its Metabolite (CNS7054) Only
Time frame: From first dose of study drug until 240 minutes postdose
The Fraction in Percent as a Measurement of the Rate and Extent to Which a Drug Reaches the Site of Action (F%)
Time frame: From first dose of study drug until 240 minutes postdose
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 4 Apr 2019.
- Individual participant dataSharing planned: No
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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.
Shawn Searly, M.D principal investigator
PRA Health Sciences
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 Remimazolam in people with Procedural Sedation, run by Paion UK Ltd. at 1 site in United States.
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 10 inclusion and 22 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 4 Apr 2019. 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 United States. 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. Some participants in this study may receive a placebo. 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?
Number of Participants with Treatment-related Adverse Events (time frame: Predose until 180 minutes postdose). 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 4 Apr 2019.