Anesthesia is to diminish the patients instinctive protective responses.
Conditions
Interventions
A single dose of midazolam 5 mg i.v. and a single dose of midazolam 5 mg i.n.
Midazolam intranasal spray will be administered as intranasal spray 2.5 mg/unit
dose. Midazolam for intravenous injectio
Sponsors
QPS Netherlands B.V.
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Adult, men and women (of non-childbearing potential), aged from 65 to 90 years old (both inclusive). 2. Body Mass Index (BMI) * 18 and * 30 kg/m², inclusive, and a total body weight >50 kg, at screening and check-in. 3. American Society of Anesthesiologists (ASA) Physical Status 1 or 2 4. Understand the study procedures in the informed consent form(s) (ICF(s)), and be willing and able to comply with the protocol.
Exclusion criteria
Exclusion criteria: 1. Current use of midazolam 2. Contraindications for the use of midazolam 3. History or presence of significant cardiovascular disease (ASA >2), or significant cardiovascular disease risk factors, significant coronary artery disease, or any known genetic pre disposition to cardiac arrhythmia (including long QT syndrome.) 4. History or presence of significant (ASA >2) pulmonary, hepatic, renal, hematological, gastrointestinal, endocrine, immunologic, dermatologic, neurological (inclusive of any seizure disorder), or psychiatric disease.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Development of a population pharmacokinetic-pharmacodynamic model for i.n. and i.v. administration of midazolam to elderly healthy volunteers: For this PK will be modelled with a two-compartment model with linear absorption into and elimination from the central compartment. Estimated parameters for this model are: central and peripheral volume of distribution (V1, V2), clearance from the central compartment (CL), distributional clearance between the centrale and peripheral compartment (Q2), absorption rate constant (ka) and absolute bioavailability (Fabs). The PD will be modelled through an effect-site compartment model and a sigmoid emax model. Estimated parameters are the equilibration constant between the central compartment and the effect-site (ke0), the maximum effect (Emax), the concentration where half of the maximum effect is achieved (EC50) and the steepness of the concentration-effect curve (hill factor). The estimated model parameters and the model performance (characterized by visual predictive checks, observed versus predicted plots, etc.) are the primary endpoints for this study. | — |
Secondary
| Measure | Time frame |
|---|---|
| PK metrics derived from the model such as: Cmax, Tmax, AUC, T1/2. PD metrics: (time to peak effect, time to 80 and 90% attenuation of effect and change from baseline of : o heart rate in beats per minute o blood pressure in mmHg o ECG parameters (e.g. QTc prolongations) in msec and mV o MOAA/S sedation score over time in MOAA/S-scores o BIS value in BIS values o Respiratory parameters: in percentage oxygenated hemoglobin as measured by pulse oximetry, respiration rate in breaths per minute and end-tidal CO2 in kPa o Time to recovery from sedation and discharge conditions as assessed by the Modified Aldrete score (APRS) o Nasal mucosal irritation after administration of midazolam intranasal spray assessed by 5 point numeric rating-scale and intranasal speculum inspection. | — |
Countries
Netherlands
Outcome results
None listed