Single-centre, randomised, prospective, open-label, three-period, Phase 1 clinical trial for assessment of the pharmacodynamic and pharmacokinetic interaction of remimazolam and remifentanil

Completed

• Conditions: sedation; unconsiousness; general anesthesia

• Registration Number: NL-OMON51001
• Lead Sponsor: PAION UK Limited

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Last Update Posted: 9 April 2024

Recruitment & Eligibility

• Status: Completed
• Sex: Not specified
• Target Recruitment: 24

Inclusion Criteria

* Healthy male or female adults *18 to *70 years old
* American Society of Anesthesiologists (ASA) Physical Status 1
* Body mass index (BMI) >18 or <30 kg/m2
* Bilateral patent a. radialis
* For female volunteers of childbearing potential: Negative results of 2
pregnancy tests, the first test taken at the start of Screening and the second
test taken from the morning urine within 3 hours before the start of the
administration of the IMP as well as consent to use highly effective birth
control from the last menstrual cycle prior to the start of the IMP until the
end of the trial follow-up procedures. For definition of childbearing potential
and highly effective birth control, see protocol.
* For male participants, their partner must not become pregnant during the
trial. They should inform their partner about this.
* Subject agrees not to use alcohol for 2 days, not to use nicotine for 1 week,
and not to use recreational drugs for 2 weeks prior to the first period until
End of Trial
* Understanding of the trial procedures and be willing to follow the
instructions of the Investigator or centre staff during the course of the
clinical trial
* Written informed consent obtained from the subject

Exclusion Criteria

* Known intolerance to benzodiazepines, flumazenil, opioids or any ingredients
of the remimazolam drug products (e.g., dextran, lactose)
* Pregnancy, or currently breastfeeding
* Have current neurological disorder(s) (epilepsy, the presence of a brain
tumour, a history of brain surgery, hydrocephalic disorders, depression needing
treatment with anti-depressive drugs, a history of brain trauma, a
subarachnoidal bleeding, TIA or cerebral infarct, psychosis or dementia,
schizophrenia, alcohol or drug abuse).
* Have a disease(s) involving the cardiovascular system (hypertension, coronary
artery disease, prior acute myocardial infarction, any valvular and/or
myocardial disease involving decrease in ejection fraction, arrhythmias, which
are either symptomatic or require continuous medication/pacemaker/automatic
internal cardioverter defibrillator)
* Recent (<3 months) use of psycho-active medication (benzodiazepines,
anti-epileptic drugs, Parkinson*s medication, neuroleptics, anxiolytics,
anti-depressant drugs, opioid analgesics)
* A history of illicit drug or alcohol abuse within two years prior to screening
* Any ongoing condition considered by the Investigator as potentially relevant
to the trial
* Any medical history considered by the Investigator as potentially relevant to
the trial
* An employee or direct relative of an employee of the trial site, the CRO or
the Sponsor.
* Resting HR <45 bpm or *90 bpm OR resting SABP <90 mmHg or *140 mmHg OR
resting DABP <50 mmHg or *90 mmHg, except for those cases of mild hypertension
or tachycardia which is considered to be secondary to anxiety or known white
coat hypertension.
* Positive urine drug screening test (amphetamines, methamphetamines,
benzodiazepines, barbiturates, marijuana, cocaïne, and opioids).
* Positive Covid-19 screening test
* Any participant as judged by the PI or Sub-Investigator to be inappropriate
for the trial for any other reason
* Clinically significant, as judged by the Investigator abnormal ECG
* Clinically significant abnormal laboratory values
* Participation in a clinical trial of an Investigational Drug or Medical
Device within three months prior to the Screening Visit
* Blood donation of *500mL within three months prior to Screening Visit
* Prior participation in this clinical trial. However, non-dosed drop-outs can
participate in the trial again but will need to be-rescreened.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>An exposure-response model describing the relationship between effect-site<br /><br>concentrations of remimazolam and plasma concentrations of remifentanil and<br /><br>MOAA/S corresponding to mild, moderate and deep sedation</p><br>