Abuse, DrugPhase 1NCT04110535
Abuse Potential of Intravenous Remimazolam Compared to Midazolam and Placebo in Recreational CNS Depressant Users
A Phase 1 study testing Remimazolam, Midazolam and Saline in people with Abuse, Drug, run by Paion UK Ltd. at 1 site in United States.
Trial summary
A double-blind, randomized crossover study to assess the subjective abuse potential of intravenous remimazolam compared to midazolam and placebo in recreational CNS depressant users Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Abuse, Drug
- What is being tested?
- Remimazolam, Midazolam and Saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 83 participants
- Where
- 1 siteUnited States
- Study dates
- 23 Jun 2015to 6 Oct 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
- Must have provided written informed consent prior to the initiation of any protocolspecific procedures.
- Male and female adults, between 18 and 55 years of age, inclusive.
- Body mass index (BMI) within 19.0 to 33.0 kg/m2, inclusive (minimum weight of at least 50.0 kg at Screening).
- Healthy, as determined by having no clinically significant medical history, physical examination, 12-lead ECG, vital signs, or laboratory (including hematology, clinical chemistry, urinalysis, and serology) findings, as judged by the investigator.
- Recreational CNS depressant user, defined as follows:
- ≥ 10 lifetime non-therapeutic experiences (ie, for psychoactive effects) with CNS depressants (eg, benzodiazepines, barbiturates, opioids, zolpidem, zopiclone, propofol/fospropofol, gamma-hydroxybutyrate)
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- ≥ 1 non-therapeutic use of a CNS depressant within the 8 weeks prior to Screening
- ≥ 1 non-therapeutic use of benzodiazepines within the 12 months prior to Screening
- Must pass Qualification Phase (Drug Discrimination and Tolerability) eligibility criteria (Section 9.3.1 and 9.3.2, respectively).
- Female subjects must be of non-childbearing potential (postmenopausal, with > 1 year since last menses and a follicular stimulating hormone (FSH) value > 40 mIU/mL, or surgically or congenitally sterile), or, if of childbearing potential, must be using and willing to continue using highly effective contraception, defined as methods of birth control that result in a low failure rate (ie, less than 1% per year) when used consistently and correctly, such as implants, injectables, combined oral contraceptives, some intrauterine devices, sexual abstinence, or a vasectomized partner, for at least 1 month prior to Screening (at least 3 months for oral and transdermal contraceptives) and for at least 14 days after last study drug administration.
- Able to speak, read, and understand English sufficiently to allow completion of all study assessments.
- Must be willing to comply with the requirements and restrictions of the study.
Who cannot join
- Drug or alcohol dependence within the 12 months prior to Screening (except nicotine), as defined by the Diagnostic and Statistical Man ual of Mental Disorders, fourth edition, text revision (DSM-IV-TR), or any self-reported dependence or "addiction" within the subject's lifetime (except nicotine or caffeine).
- Subjects who have ever been in treatment for substance use disorder(s) (except smoking cessation).
- History or presence of any clinically significant cardiac, psychiatric, endocrine, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, renal, or other major disease at Screening, which in the opinion of the investigator would jeopardize the safety of the subject or the validity of the study results, including subjects with chronic renal failure or congestive heart failure.
- In the opinion of the investigator, the subject was at risk for respiratory depression, including subjects with obstructive apnea, upper airway obstruction, chronic obstructive pulmonary disease, acute or severe bronchial asthma, hypercarbia, or other severe cardio-respiratory disease.
- Positive for hepatitis B, hepatitis C, or human immunodeficiency virus (HIV).
- History of, or evidence at the time for, suicidal ideation with intent, with or without a plan or method, in the past 5 years or suicidal behavior in their lifetime or those who were actively suicidal based on the Columbia-Suicide Severity Rating Scale (C-SSRS).
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- Unexplained significant and recent loss of consciousness, or history of significant head trauma with loss of consciousness.
- Reported history of acute narrow-angle glaucoma.
- 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), including strong cytochrome P450 (CYP) 3A4 inhibitors or respiratory depressants, or could not safely discontinue these medications within 7 days or 5 half -lives (whichever is longer) prior to receiving study drug in the Qualification Phase and for the Duration of the study.
- Subject was using an investigational drug or device or had used such within the 30 days (or 5 half-lives, whichever is longer) prior to first drug administration in the Qualification Phase.
- Female subjects who were pregnant or lactating or who were planning to become pregnant within 14 days of last study drug administration.
- Subject had a prior history of any significant adverse reactions (including rash) to benzodiazepines and/or flumazenil, or known allergies to midazolam and/or flumazenil, or formulation components.
- Subject had unsuitable or difficult venous access or was unwilling or unable to undergo catheter insertion.
- Subject was 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, was considered unsuitable or unlikely to comply with the study protocol for any reason (in each case, the investigator had to specify the reason).
Trial locations and contacts
1 site in 1 country.
United States1 site
PRA Health Sciences Early Development Services
Salt Lake City, Utah, 84106
About this study
Official title: A Double-blind, Randomized Crossover Study to Assess the Subjective Abuse Potential of Intravenous Remimazolam Compared to Midazolam and Placebo in Recreational CNS Depressant Users
A double-blind, randomized crossover study to assess the subjective abuse potential of intravenous remimazolam compared to midazolam and placebo in recreational CNS depressant users
- Conditions
- Abuse, Drug
- Being tested
- Remimazolam, Midazolam, Saline
- Keywords
- remimazolam
- Medical subject headings
- Substance-Related Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RemimazolamDrug
Also called CNS7056
IV administration over 1 minute
MidazolamDrug
IV administration over 1 minute
SalineOther
IV administration over 1 minute
| Study group | Role | What they receive |
|---|---|---|
| Remimazolam 5 mg | Experimental | IV administration of remimazolam 5 mg Receives: Drug: Remimazolam |
| Remimazolam 10 mg | Experimental | IV administration of remimazolam 10 mg Receives: Drug: Remimazolam |
| Midazolam 2.5 mg | Active comparator | IV administration of midazolam 2.5 mg Receives: Drug: Midazolam |
| Midazolam 5 mg | Active comparator | IV administration of midazolam 5 mg Receives: Drug: Midazolam |
| Placebo | Placebo comparator | Saline injection Receives: Other: Saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Drug Liking VAS maximum effect (Emax)
Maximum effect (Emax) on the bipolar Drug Liking visual analogue scale (VAS)
Measured: 2 to 480 minutes postdose
Secondary outcomes (9)
Drug Liking VAS Minimum effect [Emin]
Minimum effect (Emin) on the bipolar Drug Liking visual analogue scale (VAS)
Measured: 2 to 480 minutes postdose
Overall Drug Liking VAS (Emax/Emin)
Emax/Emin on the bipolar Drug Liking visual analogue scale (VAS)
Measured: 240 to 480 minutes postdose
Take Drug Again VAS (Emax)
Maximum effect (Emax) on the unipolarTake Drug Again visual analogue scale (VAS)
Measured: 240 to 480 minutes postdose
Good Effects VAS (Emax and TA_AUE)
Maximum effect (Emax) and TA_AUE on the unipolar Good Effects visual analogue scale (VAS)
Measured: 2 to 480 minutes postdose
Bad Effects VAS (Emax and TA_AUE)
Maximum effect (Emax) and TA_AUE on the unipolar Bad Effects visual analogue scale (VAS)
Measured: 2 to 480 minutes postdose
Alertness/Drowsiness VAS (Emin and TA_AUE)
Minimum effect (Emin) and TA_AUE on the bipolar Alertness/Drowsiness visual analogue scale (VAS)
Measured: Predose to 480 minutes postdose
Agitation/Relaxation VAS (Emin and TA_AUE)
Minimum effect (Emin) and TA_AUE on the bipolar Agitation/Relaxation visual analogue scale (VAS)
Measured: Predose to 480 minutes postdose
Any Effects VAS (Emax and TA_AUE)
Maximum effect (Emax) and TA_AUE on the unipolar Any Effects visual analogue scale (VAS)
Measured: 2 to 480 minutes postdose
Paired Associates Learning (PAL) total error score (Emax and TA_AUE)
PAL test was conducted using the software CANTAB (Cambridge Cognition)
Measured: Predose to 480 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 Oct 2019
- Study start23 Jun 2015
- Primary completion6 Oct 2015
- Study completion6 Oct 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Abuse, DrugStudies 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
- 83 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
- NCT04110535
- Sponsor's protocol ID
- CNS7056-014
- Status last verified
- Sep 2019
- First submitted
- 27 Sep 2019
- Last updated
- 1 Oct 2019
- Results posted
- No
- 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 1 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double-blind, Randomized Crossover Study to Assess the Subjective Abuse Potential of Intravenous Remimazolam Compared to Midazolam and Placebo in Recreational CNS Depressant Users
- ClinicalTrials.gov ID
- NCT04110535
- Acronym / sponsor ID
- CNS7056-014
- Conditions
- Abuse, Drug
- Keywords
- remimazolam
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 83 participants (actual)
- Lead sponsor
- Paion UK Ltd.Industry (pharma, biotech, devices)
- Collaborators
- PRA Health Sciences
- Study start
- 23 Jun 2015 (actual)
- Primary completion
- 6 Oct 2015 (actual)
- Study completion
- 6 Oct 2015 (actual)
- First posted
- 1 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 double-blind, randomized crossover study to assess the subjective abuse potential of intravenous remimazolam compared to midazolam and placebo in recreational CNS depressant users
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Remimazolam 5 mg | Experimental | Drug: RemimazolamIV administration of remimazolam 5 mg |
| Remimazolam 10 mg | Experimental | Drug: RemimazolamIV administration of remimazolam 10 mg |
| Midazolam 2.5 mg | Active comparator | Drug: MidazolamIV administration of midazolam 2.5 mg |
| Midazolam 5 mg | Active comparator | Drug: MidazolamIV administration of midazolam 5 mg |
| Placebo | Placebo comparator | Other: SalineSaline injection |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (12 listed)
- Must have provided written informed consent prior to the initiation of any protocolspecific procedures.
- Male and female adults, between 18 and 55 years of age, inclusive.
- Body mass index (BMI) within 19.0 to 33.0 kg/m2, inclusive (minimum weight of at least 50.0 kg at Screening).
- Healthy, as determined by having no clinically significant medical history, physical examination, 12-lead ECG, vital signs, or laboratory (including hematology, clinical chemistry, urinalysis, and serology) findings, as judged by the investigator.
- Recreational CNS depressant user, defined as follows:
Key exclusion criteria (15 listed)
- Drug or alcohol dependence within the 12 months prior to Screening (except nicotine), as defined by the Diagnostic and Statistical Man ual of Mental Disorders, fourth edition, text revision (DSM-IV-TR), or any self-reported dependence or "addiction" within the subject's lifetime (except nicotine or caffeine).
- Subjects who have ever been in treatment for substance use disorder(s) (except smoking cessation).
- History or presence of any clinically significant cardiac, psychiatric, endocrine, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, renal, or other major disease at Screening, which in the opinion of the investigator would jeopardize the safety of the subject or the validity of the study results, including subjects with chronic renal failure or congestive heart failure.
- In the opinion of the investigator, the subject was at risk for respiratory depression, including subjects with obstructive apnea, upper airway obstruction, chronic obstructive pulmonary disease, acute or severe bronchial asthma, hypercarbia, or other severe cardio-respiratory disease.
- Positive for hepatitis B, hepatitis C, or human immunodeficiency virus (HIV).
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: CNS7056IV administration over 1 minute | Drug | Remimazolam 10 mg, Remimazolam 5 mg |
| MidazolamIV administration over 1 minute | Drug | Midazolam 2.5 mg, Midazolam 5 mg |
| SalineIV administration over 1 minute | Other | Placebo |
Primary outcome
Drug Liking VAS maximum effect (Emax)
Time frame: 2 to 480 minutes postdose
Maximum effect (Emax) on the bipolar Drug Liking visual analogue scale (VAS)
9 secondary outcomes
Drug Liking VAS Minimum effect [Emin]
Time frame: 2 to 480 minutes postdose
Overall Drug Liking VAS (Emax/Emin)
Time frame: 240 to 480 minutes postdose
Take Drug Again VAS (Emax)
Time frame: 240 to 480 minutes postdose
Good Effects VAS (Emax and TA_AUE)
Time frame: 2 to 480 minutes postdose
Bad Effects VAS (Emax and TA_AUE)
Time frame: 2 to 480 minutes postdose
Alertness/Drowsiness VAS (Emin and TA_AUE)
Time frame: Predose to 480 minutes postdose
Agitation/Relaxation VAS (Emin and TA_AUE)
Time frame: Predose to 480 minutes postdose
Any Effects VAS (Emax and TA_AUE)
Time frame: 2 to 480 minutes postdose
Paired Associates Learning (PAL) total error score (Emax and TA_AUE)
Time frame: Predose to 480 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 1 Oct 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 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, Midazolam and Saline in people with Abuse, Drug, 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 12 inclusion and 15 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 1 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?
Drug Liking VAS maximum effect (Emax) (time frame: 2 to 480 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 1 Oct 2019.