BioavailabilityPhase 1NCT04113564
Absolute Oral Bioavailability of Remimazolam
A Phase 1 study testing Remimazolam in people with Bioavailability, run by Paion UK Ltd. at 1 site in United States.
Trial summary
A randomized, open-label, single-dose, 2-way crossover study to compare the relative bioavailability of orally administered remimazolam to an intravenous formulation in healthy volunteers Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Bioavailability
- What is being tested?
- Remimazolam
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 1 siteUnited States
- Study dates
- 3 Nov 2015to 20 Nov 2015
- 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 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Willing to participate in the study, willing to give written informed consent prior to the initiation of any protocol-specific procedures, and willing to comply with the study restrictions.
- Had to be able to speak, read, and understand English sufficiently to allow completion of all study assessments.
- Gender : males and/or females
- Age : 18 - 55 years, inclusive
- Body mass index (BMI) : 18.0 - 32.0 kg/m2
- Weight : ≥50 kg
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- Healthy status was 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 ECG, hematology, clinical chemistry, serology, and urinalysis.
- 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 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.
- Females of childbearing potential and males and their female partner(s) of childbearing potential had to agree to use 2 forms of contraception, 1 of which had to be a barrier method, during the study and for 90 days after the last drug administration. Acceptable barrier forms of contraception were condom and diaphragm. Acceptable non-barrier forms of contraception for this study were an intrauterine device (IUD) and/or spermicide.
- For females: a negative pregnancy test at Screening and Day -1.
- Postmenopausal females: defined as 12 months with no menses prior to Screening and a serum follicle stimulating hormone (FSH) >40 IU/L at Screening.
- All non-regular medication (including over-the-counter [OTC] medication, health supplements, and herbal remedies such as St. John's Wort extract) must have been stopped at least 14 days prior to admission to the clinical research center. An exception was made for paracetamol (acetaminophen), which was allowed up to admission to the clinical research center.
Who cannot join
- Women who were pregnant or lactating.
- Males with female partners who were pregnant or lactating.
- Use of any investigational drug or device within 30 days of the first dose of study medication.
- Any disease which, in the opinion of the Investigator, posed an unacceptable risk to the subjects.
- Known allergy, hypersensitivity or prior intolerance to benzodiazepine derivates or flumazenil, or a medical condition such that these agents were contraindicated.
- The use of tobacco products within 60 days prior to the first drug administration.
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- Routine or chronic use of more than 3 grams of acetaminophen daily.
- Strenuous activity, sunbathing and contact sports within 48 hours (2 days) prior to admission to the clinical facility and for the duration of the study.
- History of donation of more than 450 mL of blood within 60 days prior to dosing in the clinical research center or planned donation before 30 days had elapsed since intake of study drug.
- Plasma or platelet donation within 7 days of dosing and throughout the entire study.
- History of alcohol consumption exceeding 2 standard drinks per day on average (1 standard drink = 10 grams of alcohol). Alcohol consumption was prohibited from 48 hours prior to admission to the clinical facility and throughout the entire study until discharge.
- 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 results for drugs of abuse, including cotinine, in the urine at Screening or Day -1.
- Positive results for alcohol abuse, as determined by alcohol breath test, at Screening or Day -1.
- Inability to be venipunctured or 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 study.
- Any major surgery within 4 weeks of study 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 (EDS)
Salt Lake City, Utah, 84106
About this study
Official title: A Randomized, Open-label, Single-dose, 2-way Crossover Study to Compare the Relative Bioavailability of Orally Administered Remimazolam to an Intravenous Formulation in Healthy Volunteers
A randomized, open-label, single-dose, 2-way crossover study to compare the relative bioavailability of orally administered remimazolam to an intravenous formulation in healthy volunteers
- Conditions
- Bioavailability
- Being tested
- Remimazolam
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RemimazolamDrug
Also called CNS7056
| Study group | Role | What they receive |
|---|---|---|
| IV remimazolam | Experimental | IV remimazolam administration of 0.025 mg/kg body weight Receives: Drug: Remimazolam |
| Oral remimazolam | Experimental | Oral remimazolam Administration of 0.14 mg/kg Body weight Receives: Drug: Remimazolam |
What is being measured
The primary outcome is the main question the study is designed to answer.
Absolute oral bioavailability of remimazolam
Single-dose bioavailability of an oral formulation of remimazolam relative to an IV formulation of remimazolam in healthy male and female subjects
Measured: Day 1 (pre-dode) to Day 3
Secondary outcomes (7)
Maximum Plasma concentration (Cmax)
Maximum observed plasma concentration
Measured: Day 1 (pre-dode) to Day 3
Time to Maximum Plasma concentration (Tmax)
Time to attain maximum observed plasma concentration
Measured: Day 1 (pre-dode) to Day 3
Area under the plasma concentration-time curve (AUC0-t)
Area under the plasma concentration-time curve from time 0 up to the time of the last measurable concentration
Measured: Day 1 (pre-dode) to Day 3
Elimination half-life (T1/2)
Terminal elimination half-life
Measured: Day 1 (pre-dode) to Day 3
Clearance (CL/F)
Apparent oral clearance
Measured: Day 1 (pre-dode) to Day 3
Volume of Distribution (Vz/F)
Apparent volume of distribution at terminal phase
Measured: Day 1 (pre-dode) to Day 3
Incidences of Treatment-emergent adverse events
Incidences of Treatment-emergent adverse events
Measured: Day 1 (pre-dode) to Day 3
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 start3 Nov 2015
- Primary completion20 Nov 2015
- Study completion20 Nov 2015
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 BioavailabilityStudies 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
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 14 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 Searle, MD, Principal investigator, PRA Health Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04113564
- Sponsor's protocol ID
- CNS7056-016
- 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 Randomized, Open-label, Single-dose, 2-way Crossover Study to Compare the Relative Bioavailability of Orally Administered Remimazolam to an Intravenous Formulation in Healthy Volunteers
- ClinicalTrials.gov ID
- NCT04113564
- Acronym / sponsor ID
- CNS7056-016
- Conditions
- Bioavailability
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Paion UK Ltd.Industry (pharma, biotech, devices)
- Collaborators
- PRA Health Sciences
- Study start
- 3 Nov 2015 (actual)
- Primary completion
- 20 Nov 2015 (actual)
- Study completion
- 20 Nov 2015 (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 randomized, open-label, single-dose, 2-way crossover study to compare the relative bioavailability of orally administered remimazolam to an intravenous formulation in healthy volunteers
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| IV remimazolam | Experimental | Drug: RemimazolamIV remimazolam administration of 0.025 mg/kg body weight |
| Oral remimazolam | Experimental | Drug: RemimazolamOral remimazolam Administration of 0.14 mg/kg Body weight |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (13 listed)
- Willing to participate in the study, willing to give written informed consent prior to the initiation of any protocol-specific procedures, and willing to comply with the study restrictions.
- Had to be able to speak, read, and understand English sufficiently to allow completion of all study assessments.
- Gender : males and/or females
- Age : 18 - 55 years, inclusive
- Body mass index (BMI) : 18.0 - 32.0 kg/m2
Key exclusion criteria (17 listed)
- Women who were pregnant or lactating.
- Males with female partners who were pregnant or lactating.
- Use of any investigational drug or device within 30 days of the first dose of study medication.
- Any disease which, in the opinion of the Investigator, posed an unacceptable risk to the subjects.
- Known allergy, hypersensitivity or prior intolerance to benzodiazepine derivates or flumazenil, or a medical condition such that these agents were contraindicated.
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: CNS7056 | Drug | IV remimazolam, Oral remimazolam |
Primary outcome
Absolute oral bioavailability of remimazolam
Time frame: Day 1 (pre-dode) to Day 3
Single-dose bioavailability of an oral formulation of remimazolam relative to an IV formulation of remimazolam in healthy male and female subjects
7 secondary outcomes
Maximum Plasma concentration (Cmax)
Time frame: Day 1 (pre-dode) to Day 3
Time to Maximum Plasma concentration (Tmax)
Time frame: Day 1 (pre-dode) to Day 3
Area under the plasma concentration-time curve (AUC0-t)
Time frame: Day 1 (pre-dode) to Day 3
Elimination half-life (T1/2)
Time frame: Day 1 (pre-dode) to Day 3
Clearance (CL/F)
Time frame: Day 1 (pre-dode) to Day 3
Volume of Distribution (Vz/F)
Time frame: Day 1 (pre-dode) to Day 3
Incidences of Treatment-emergent adverse events
Time frame: Day 1 (pre-dode) to Day 3
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.
Shawn Searle, 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 in people with Bioavailability, 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 17 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. 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?
Absolute oral bioavailability of remimazolam (time frame: Day 1 (pre-dode) to Day 3). 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 NCT04113564, 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.