Safety IssuesPhase 1NCT04113343
Oral Remimazolam With and Without Alcohol in Healthy Female Subjects
A Phase 1 study testing Remimazolam and Alcohol in people with Safety Issues, run by Paion UK Ltd. at 1 site in United States.
Trial summary
A Phase 1 Study to Determine the Single-dose Pharmacodynamics, Pharmacokinetics, and Safety and Tolerability of Remimazolam Following Oral Administration With and Without Alcohol in Healthy Female Subjects Read more about this study
- Who is it for?
- Ages 21 to 45 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Safety Issues
- What is being tested?
- Remimazolam and Alcohol
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 21 participants
- Where
- 1 siteUnited States
- Study dates
- 30 May 2017to 9 Aug 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 21 to 45 years
- Women 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 comply with the trial restrictions.
- Able to speak, read, and understand English sufficiently to allow completion of all Trial assessments.
- Gender : female
- Age : 21 to 45 years, inclusive
- Weight : ≥ 50 kg
- Body mass index (BMI) : 18.0 to 33.0 kg/m2, inclusive
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- Healthy status, defined by the absence of evidence of any clinically significant, in the opinion of the Investigator, active or chronic disease following a detailed medical and surgical history, a complete physical examination including vital signs, 12-lead electrocardiograms (ECG), hematology, blood chemistry, serology, and urinalysis.
- Current alcohol user classified as a moderate drinker, defined as drinking > 2 drinks/week and ≤ 14 drinks/week (1 drink equals approximately 12 oz/350 mL of beer, 5 oz/150 mL of wine, or 1.5 oz/45 mL of spirits).6
- Ability and willingness to abstain from alcohol, caffeine, and xanthine-containing beverages or food (eg, coffee, tea, cola, chocolate, energy drinks) from 48 hours (2 days) prior to admission to the clinical facility on Day -1 until trial 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.
- A negative pregnancy test at Screening and Day -1.
- Females of childbearing potential must have agreed to use 2 forms of contraception, one of which must have been a barrier method, during the trial and for 90 days after the last drug administration. Acceptable barrier forms of contraception were condom and diaphragm. Acceptable nonbarrier forms of contraception for this trial were oral contraceptives, injectable hormone contraceptives, implantable birth control, intrauterine devices, and/or spermicide. Injectable hormonal contraception was allowable as a nonbarrier method.
- Females who were not of childbearing potential, including postmenopausal females (defined as 12 months with no menses prior to Screening and a serum follicle-stimulating hormone [FSH] > 40 IU/L at Screening) or females who were surgically sterilized.
Who cannot join
- Females who were pregnant or lactating.
- Known intolerance towards alcohol (symptoms could include nausea, flushed face, vomiting, or hypotension upon drinking) or known alcohol dehydrogenase deficiency.
- of Asian descent (one or both parents) due to potential for genetic polymorphism related to aldehyde dehydrogenase deficiency.
- History of alcohol abuse or drug addiction (except nicotine or caffeine), 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).
- History of relevant food allergies.
- Use of any investigational drug or device within 30 days of the first dose of Trial medication.
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- Any disease which, in the opinion of the Investigator, posed 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 were contraindicated.
- Use of tobacco products within 60 days prior to the first drug administration.
- Routine or chronic use of more than 3 grams of acetaminophen daily.
- 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 had elapsed since intake of trial drug in the current trial.
- 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], cannabinoids, barbiturates, benzodiazepines, tricyclic antidepressants, and alcohol) at Screening and admission to the clinical research center.
- Average intake of > 14 drinks of alcohol per week (1 drink equals approximately 12 oz/350 mL of beer, 5 oz/150 mL of wine, or 1.5 oz/45 mL of spirits).
- Required concomitant treatment with any prescription or non-prescription medications (with the exception of hormonal contraceptives, hormone replacement, and acetaminophen) or natural health products (herbal remedies), or respiratory depressants, or could not safely discontinue these medications at least 7 days prior to receiving trial drug.
- Inability to be venipunctured or to tolerate venous access, as determined by the Investigator or designee.
- History of clinically significant, recent/current, and nonremote suicidal ideations or suicide attempts that, in the opinion of the Investigator, posed an unacceptable risk to the subject for participating in the trial.
- Any major surgery within 4 weeks of trial drug administration. NOTE: Any parameter/test could be repeated at the Investigator's discretion during Screening and/or on Day -1.
Trial locations and contacts
1 site in 1 country.
United States1 site
PRA Health Sciences (PRA) - Early Development Services
Salt Lake City, Utah, 84106
About this study
Official title: A Phase 1 Study to Determine the Single-dose Pharmacodynamics, Pharmacokinetics, and Safety and Tolerability of Remimazolam Following Oral Administration With and Without Alcohol in Healthy Female Subjects
A Phase 1 Study to Determine the Single-dose Pharmacodynamics, Pharmacokinetics, and Safety and Tolerability of Remimazolam Following Oral Administration With and Without Alcohol in Healthy Female Subjects
Read the detailed description
Evaluating the potential for additive or synergistic effects of alcohol when coadministered with remimazolam. Female subjects were selected because they represent the population at greatest risk for victimization in drug-facilitated sexual assault. In addition, females have a slower ethanol metabolism, therefore, the effects of remimazolam, if coadministered with alcohol, may last longer. Hence, this population represents the worst-case scenario in evaluating the risk of remimazolam misuse in drug-facilitated assault.
- Conditions
- Safety Issues
- Being tested
- Remimazolam, Alcohol
- Keywords
- remimazolam
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RemimazolamDrug
Also called CNS7056
Remimazolam via oral administration
AlcoholOther
Alcohol
| Study group | Role | What they receive |
|---|---|---|
| Treatment A: remimazolam | Active comparator | Oral administration of 360 mg remimazolam Receives: Drug: Remimazolam |
| Treatment B: remimazolam + 5% v/v alcohol | Experimental | Oral administration of 360 mg remimazolam and 5% v/v alcohol Receives: Drug: Remimazolam; Other: Alcohol |
| Treatment C: remimazolam + 15% v/v alcohol | Experimental | Oral administration of 360 mg remimazolam + 15% v/v alcohol Receives: Drug: Remimazolam; Other: Alcohol |
| Treatment D: remimazolam + 40% v/v alcohol | Experimental | Oral administration of 360 mg remimazolam + 40% v/v alcohol Receives: Drug: Remimazolam; Other: Alcohol |
| Treatment E: placebo + 40% v/v alcohol | Placebo comparator | Oral administration of Placebo + 40% v/v alcohol Receives: Other: Alcohol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Paired Associates Learning (PAL) Test
PAL Test was conducted using the software CANTAB (Cambridge Cognition)
Measured: Predose to 4 hours postdose
Modified Observer Assessment of Alertness/Sedation (MOAA/S)
The MOAA/S scale is a validated, 6-point rating scale that involves an observer rating subjects' responsiveness to stimuli of increasing intensity (5 = alert, 0 = sedated).
Measured: Predose to 4 hours postdose
Alertness/Drowsiness Visual Analog Scale (VAS)
The Alertness/Drowsiness VAS was administered as a 100-point bipolar scale, with 50 being the neutral point, as follows:0: Very drowsy, 50: Neither drowsy nor alert, 100: Very alert
Measured: Predose to 4 hours postdose
Reaction Time Test (RTI)
RTI was conducted using the software CANTAB (Cambridge Cognition).
Measured: Predose to 4 hours postdose
Maximum observed plasma concentration (Cmax)
Measured: Predose to 8 hours postdose
Time to Maximum observed plasma concentration (Tmax)
Measured: Predose to 8 hours postdose
Area under the plasma concentration-time curve (AUC) from zero to the last measurable concentration
Measured: Predose to 8 hours postdose
Terminal elimination half-life (T1/2)
Measured: Predose to 8 hours postdose
Apparent oral clearance (CL/F)
Measured: Predose to 8 hours postdose
Apparent volume of distribution at terminal Phase (Vz/F)
Measured: Predose to 8 hours postdose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Oct 2019
- Study start30 May 2017
- Primary completion9 Aug 2017
- Study completion9 Aug 2017
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 Safety IssuesStudies 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
- Other
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- Paion UK Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- PRA Health Sciences
- Responsible party
- Sponsor
- Investigators
- Ahad Sabet, MD, Principal investigator, PRA Health Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04113343
- Sponsor's protocol ID
- CNS7056-020
- Status last verified
- Oct 2019
- First submitted
- 27 Sep 2019
- Last updated
- 2 Oct 2019
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Pesic M, Stohr T, Ossig J, Borkett K, Donsbach M, Dao VA, Webster L, Schippers F. Remimazolam Has Low Oral Bioavailability and No Potential for Misuse in Drug-Facilitated Sexual Assaults, with or Without Alcohol: Results from Two Randomised Clinical Trials. Drugs R D. 2020 Sep;20(3):267-277. doi: 10.1007/s40268-020-00317-0.
PubMed 32757149
Study at a glance
From the registry record, last updated by the sponsor on 2 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Study to Determine the Single-dose Pharmacodynamics, Pharmacokinetics, and Safety and Tolerability of Remimazolam Following Oral Administration With and Without Alcohol in Healthy Female Subjects
- ClinicalTrials.gov ID
- NCT04113343
- Acronym / sponsor ID
- CNS7056-020
- Conditions
- Safety Issues
- Keywords
- remimazolam
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- Paion UK Ltd.Industry (pharma, biotech, devices)
- Collaborators
- PRA Health Sciences
- Study start
- 30 May 2017 (actual)
- Primary completion
- 9 Aug 2017 (actual)
- Study completion
- 9 Aug 2017 (actual)
- First posted
- 2 Oct 2019 (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 Phase 1 Study to Determine the Single-dose Pharmacodynamics, Pharmacokinetics, and Safety and Tolerability of Remimazolam Following Oral Administration With and Without Alcohol in Healthy Female Subjects
Detailed description
Evaluating the potential for additive or synergistic effects of alcohol when coadministered with remimazolam. Female subjects were selected because they represent the population at greatest risk for victimization in drug-facilitated sexual assault. In addition, females have a slower ethanol metabolism, therefore, the effects of remimazolam, if coadministered with alcohol, may last longer. Hence, this population represents the worst-case scenario in evaluating the risk of remimazolam misuse in drug-facilitated assault.
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Treatment A: remimazolam | Active comparator | Drug: RemimazolamOral administration of 360 mg remimazolam |
| Treatment B: remimazolam + 5% v/v alcohol | Experimental | Drug: Remimazolam, Other: AlcoholOral administration of 360 mg remimazolam and 5% v/v alcohol |
| Treatment C: remimazolam + 15% v/v alcohol | Experimental | Drug: Remimazolam, Other: AlcoholOral administration of 360 mg remimazolam + 15% v/v alcohol |
| Treatment D: remimazolam + 40% v/v alcohol | Experimental | Drug: Remimazolam, Other: AlcoholOral administration of 360 mg remimazolam + 40% v/v alcohol |
| Treatment E: placebo + 40% v/v alcohol | Placebo comparator | Other: AlcoholOral administration of Placebo + 40% v/v alcohol |
Who may qualify
- Ages
- 21 to 45 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (13 listed)
- Willing to participate in the trial, give written informed consent prior to the initiation of any protocol-specific procedures, and comply with the trial restrictions.
- Able to speak, read, and understand English sufficiently to allow completion of all Trial assessments.
- Gender : female
- Age : 21 to 45 years, inclusive
- Weight : ≥ 50 kg
Key exclusion criteria (18 listed)
- Females who were pregnant or lactating.
- Known intolerance towards alcohol (symptoms could include nausea, flushed face, vomiting, or hypotension upon drinking) or known alcohol dehydrogenase deficiency.
- of Asian descent (one or both parents) due to potential for genetic polymorphism related to aldehyde dehydrogenase deficiency.
- History of alcohol abuse or drug addiction (except nicotine or caffeine), 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).
- History of relevant food allergies.
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: CNS7056Remimazolam via oral administration | Drug | Treatment A: remimazolam, Treatment B: remimazolam + 5% v/v alcohol, Treatment C: remimazolam + 15% v/v alcohol, Treatment D: remimazolam + 40% v/v alcohol |
| AlcoholAlcohol | Other | Treatment B: remimazolam + 5% v/v alcohol, Treatment C: remimazolam + 15% v/v alcohol, Treatment D: remimazolam + 40% v/v alcohol, Treatment E: placebo + 40% v/v alcohol |
Primary outcome
Paired Associates Learning (PAL) Test
Time frame: Predose to 4 hours postdose
PAL Test was conducted using the software CANTAB (Cambridge Cognition)
Modified Observer Assessment of Alertness/Sedation (MOAA/S)
Time frame: Predose to 4 hours postdose
The MOAA/S scale is a validated, 6-point rating scale that involves an observer rating subjects' responsiveness to stimuli of increasing intensity (5 = alert, 0 = sedated).
Alertness/Drowsiness Visual Analog Scale (VAS)
Time frame: Predose to 4 hours postdose
The Alertness/Drowsiness VAS was administered as a 100-point bipolar scale, with 50 being the neutral point, as follows:0: Very drowsy, 50: Neither drowsy nor alert, 100: Very alert
Reaction Time Test (RTI)
Time frame: Predose to 4 hours postdose
RTI was conducted using the software CANTAB (Cambridge Cognition).
Maximum observed plasma concentration (Cmax)
Time frame: Predose to 8 hours postdose
Time to Maximum observed plasma concentration (Tmax)
Time frame: Predose to 8 hours postdose
Area under the plasma concentration-time curve (AUC) from zero to the last measurable concentration
Time frame: Predose to 8 hours postdose
Terminal elimination half-life (T1/2)
Time frame: Predose to 8 hours postdose
Apparent oral clearance (CL/F)
Time frame: Predose to 8 hours postdose
Apparent volume of distribution at terminal Phase (Vz/F)
Time frame: Predose to 8 hours 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 2 Oct 2019.
- Derived from this study: PubMed 32757149Pesic M, Stohr T, Ossig J, Borkett K, Donsbach M, Dao VA, Webster L, Schippers F. Remimazolam Has Low Oral Bioavailability and No Potential for Misuse in Drug-Facilitated Sexual Assaults, with or Without Alcohol: Results from Two Randomised Clinical Trials. Drugs R D. 2020 Sep;20(3):267-277. doi: 10.1007/s40268-020-00317-0.
- 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.
Ahad Sabet, MD 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 and Alcohol in people with Safety Issues, 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 13 inclusion and 18 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 2 Oct 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?
Paired Associates Learning (PAL) Test (time frame: Predose to 4 hours postdose). The study lists 10 primary outcomes in all. 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 NCT04113343, 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 2 Oct 2019.