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

Single-centre, randomised, prospective, open-label, three-period, Phase 1 clinical trial for assessment of the pharmacodynamic and pharmacokinetic interaction of remimazolam and remifentanil - Remix2 study

Status

Active, not recruiting

Phases

Unknown

Study type

Interventional

Source

NL-OMON

Registry ID

NL-OMON51001

Enrollment

Registered

2021-01-18

Start date

2021-03-31

Completion date

Unknown

Last updated

2024-04-09

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

general anesthesia sedation unconsiousness

Interventions

In each cohort, 2 males and 2 females will be randomised to each Treatment Sequence (1 or 2, respectively). Sequences 1 and 2 will be identical for Periods 1 and 2. Dosing for remifentanil will be r

Eligibility

Age

18 Years to 99 Years

Inclusion criteria

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

Exclusion criteria

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 (

Design outcomes

Primary

Measure	Time frame
An exposure-response model describing the relationship between effect-site concentrations of remimazolam and plasma concentrations of remifentanil and MOAA/S corresponding to mild, moderate and deep sedation	—

Secondary

Measure	Time frame
Pharmacokinetics An exposure-response model describing the relationship between effect-site concentrations of remimazolam and plasma concentrations of remifentanil and BIS corresponding to mild, moderate and deep sedation Performance characteristics for the TCI models used (RMZ and remifentanil) according to Varvel et al. [1]. These include median absolute prediction error, median prediction error, wobble and divergence. Pharmacodynamics Exposure response models for: 1. tolerance to laryngoscopy, 2. tolerance to tetanic stimulus, 3. BIS, 4. hemodynamic alterations in terms of heart rate, arterial blood pressure (ABP), mean arterial pressure (MAP), stroke volume and cardiac output. 5. respiratory depression. 6. raw EEG data will be used for explorative comparison with the listed PD parameters Safety * Heart rate and arterial blood pressure * Number and incidence of adverse events by drug-relatedness, seriousness, and severity during each treatment period. * Clinical laboratory parameters (at screening, prior to each period and End of Trial), ECG, vital signs, physical examination at Screening and End-of-Trial (end of Treatment Period 3). Modified Aldrete score (prior to discharge after each treatment period).	—

Measure

Time frame

Pharmacokinetics An exposure-response model describing the relationship between effect-site concentrations of remimazolam and plasma concentrations of remifentanil and BIS corresponding to mild, moderate and deep sedation Performance characteristics for the TCI models used (RMZ and remifentanil) according to Varvel et al. [1]. These include median absolute prediction error, median prediction error, wobble and divergence. Pharmacodynamics Exposure response models for: 1. tolerance to laryngoscopy, 2. tolerance to tetanic stimulus, 3. BIS, 4. hemodynamic alterations in terms of heart rate, arterial blood pressure (ABP), mean arterial pressure (MAP), stroke volume and cardiac output. 5. respiratory depression. 6. raw EEG data will be used for explorative comparison with the listed PD parameters Safety * Heart rate and arterial blood pressure * Number and incidence of adverse events by drug-relatedness, seriousness, and severity during each treatment period. * Clinical laboratory parameters (at screening, prior to each period and End of Trial), ECG, vital signs, physical examination at Screening and End-of-Trial (end of Treatment Period 3). Modified Aldrete score (prior to discharge after each treatment period).

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Countries

Netherlands

Outcome results

None listed

Source: NL-OMON (via WHO ICTRP)