Drug Drug Interaction, Healthy
Conditions
Keywords
ACT-1014-6470, Omeprazole, Midazolam
Brief summary
A study on whether ACT-1014-6470 has an effect on how the body takes up, distributes and gets rid of omeprazole and midazolam in healthy male subjects
Interventions
DRUGTreatment period A
Midazolam solution for oral administration. Omeprazole hard capsule for oral administration.
DRUGTreatment period B
ACT-1014-6470 soft capsule for oral administration. Midazolam solution for oral administration. Omeprazole hard capsule for oral administration.
Sponsors
Idorsia Pharmaceuticals Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Intervention model description
Two-period, fixed-sequence study
Eligibility
Sex/Gender
MALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Signed informed consent in a language understandable to the participant prior to any study-mandated procedure. * Healthy male participant aged between 18 and 45 years (inclusive) at Screening. * Body mass index of 18.5 to 28.0 kg/m2 (inclusive) at Screening. * Systolic blood pressure 100-140 mmHg, diastolic blood pressure 50-90 mmHg, and pulse rate 45-90 beats per minute (inclusive), measured on either arm, after 5 min in the supine position at Screening and on Day -1.
Exclusion criteria
* Previous exposure to ACT-1014-6470. * Known hypersensitivity to ACT-1014-6470, omeprazole, substituted benzimidazoles, midazolam, or treatments of the same pharmacological classes, or any of their excipients. * History or clinical evidence of any disease and/or existence of any surgical or medical condition, which in the opinion of the investigator, are likely to interfere with the absorption, distribution, metabolism, or excretion of the study treatment (appendectomy and herniotomy allowed if performed more than 12 weeks prior to administration of \[first\] study treatment, cholecystectomy not allowed). * Previous treatment with any prescribed medications (including vaccines \[Vaccination regimen against COVID-19 completed less than 2 weeks prior to first study treatment administration or any vaccination against COVID-19 planned before end-of-study\]) or over-the-counter (OTC) medications (including herbal medicines such as St John's Wort, homeopathic preparations, vitamins, and minerals) within 3 weeks prior to first study treatment administration. * Legal incapacity or limited legal capacity at Screening. * Participant with rare inherited issues of fructose intolerance, glucose-galactose malabsorption, or sucrase-isomaltase insufficiency.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum plasma concentration (Cmax) of ACT-1014-6470, midazolam and omeprazole. | Total duration: up to 11 days | The plasma pharmacokinetic parameters of ACT-1014-6470, midazolam and omeprazole will be derived by non-compartmental analysis of the plasma concentration-time profiles. |
| Time to reach Cmax (tmax) of ACT-1014-6470, midazolam and omeprazole. | Total duration: up to 11 days | The plasma pharmacokinetic parameters of ACT-1014-6470, midazolam and omeprazole will be derived by non-compartmental analysis of the plasma concentration-time profiles. |
| The area under the plasma concentration-time curve (AUC) from zero to time t of the last measured concentration above the limit of quantification (AUC0-t) of ACT-1014-6470, midazolam and omeprazole. | Total duration: up to 11 days | The plasma pharmacokinetic parameters of ACT-1014-6470, midazolam and omeprazole will be derived by non-compartmental analysis of the plasma concentration-time profiles. |
| Area under the plasma concentration-time curve [AUC(0-12)] of omeprazole. | Total duration: up to 9 days | The plasma pharmacokinetic parameters of omeprazole will be derived by non-compartmental analysis of the plasma concentration-time profile. |
| Area under the plasma concentration-time curve [AUC(0-24)] of midazolam and omeprazole. | Total duration: up to 11 days | The plasma pharmacokinetic parameters of midazolam and omeprazole will be derived by non-compartmental analysis of the plasma concentration-time profiles. |
| Area under the plasma concentration-time curve [AUC(0-inf)] of ACT-1014-6470, midazolam and omeprazole. | Total duration: up to 11 days | The plasma pharmacokinetic parameters of ACT-1014-6470, midazolam and omeprazole will be derived by non-compartmental analysis of the plasma concentration-time profiles. |
| Apparent total body clearance (CL/F) of ACT-1014-6470, midazolam and omeprazole. | Total duration: up to 11 days | The plasma pharmacokinetic parameters of ACT-1014-6470, midazolam and omeprazole will be derived by non-compartmental analysis of the plasma concentration-time profiles. |
| The terminal half-life (t½) of ACT-1014-6470, midazolam and omeprazole. | Total duration: up to 11 days | The plasma pharmacokinetic parameters of ACT-1014-6470, midazolam and omeprazole will be derived by non-compartmental analysis of the plasma concentration-time profiles. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The metabolic ratio (MR) of 5-hydroxyomeprazole to omeprazole. | Total duration: up to 11 days | — |
| Maximum plasma concentration (Cmax) of 1-hydroxymidazolam and 5-hydroxyomeprazole. | Total duration: up to 11 days | The plasma pharmacokinetic parameters of 1-hydroxymidazolam and 5-hydroxyomeprazole will be derived by non-compartmental analysis of the plasma concentration-time profiles. |
| Number of participants with treatment-emergent adverse events as a measure of safety and tolerability. | Total duration: up to 11 days | An adverse event is an unfavorable and unintended sign (including an abnormal laboratory finding, an abnormal electrocardiogram). A treatment-emergent adverse event is any adverse event temporally associated with the use of a study treatment, whether or not considered related to the study treatment. |
| Time to reach Cmax (tmax) of 1-hydroxymidazolam and 5-hydroxyomeprazole. | Total duration: up to 11 days | The plasma pharmacokinetic parameters of 1-hydroxymidazolam and 5-hydroxyomeprazole will be derived by non-compartmental analysis of the plasma concentration-time profiles. |
| The area under the plasma concentration-time curve (AUC) from zero to time t of the last measured concentration above the limit of quantification (AUC0-t) of 1-hydroxymidazolam and 5-hydroxyomeprazole. | Total duration: up to 11 days | The plasma pharmacokinetic parameters of 1-hydroxymidazolam and 5-hydroxyomeprazole will be derived by non-compartmental analysis of the plasma concentration-time profiles. |
| Area under the plasma concentration-time curve [AUC(0-12)] of 5-hydroxyomeprazole. | Total duration: up to 11 days | The plasma pharmacokinetic parameters of 5-hydroxyomeprazole will be derived by non-compartmental analysis of the plasma concentration-time profiles. |
| Area under the plasma concentration-time curve [AUC(0-24)] of 1-hydroxymidazolam and 5-hydroxyomeprazole. | Total duration: up to 11 days | The plasma pharmacokinetic parameters of 1-hydroxymidazolam and 5-hydroxyomeprazole will be derived by non-compartmental analysis of the plasma concentration-time profiles. |
| Area under the plasma concentration-time curve [AUC(0-inf)] of 1-hydroxymidazolam and 5-hydroxyomeprazole. | Total duration: up to 11 days | The plasma pharmacokinetic parameters of 1-hydroxymidazolam and 5-hydroxyomeprazole will be derived by non-compartmental analysis of the plasma concentration-time profiles. |
| The terminal half-life (t½) of 1-hydroxymidazolam and 5-hydroxyomeprazole. | Total duration: up to 11 days | The plasma pharmacokinetic parameters of 1-hydroxymidazolam and 5-hydroxyomeprazole will be derived by non-compartmental analysis of the plasma concentration-time profiles. |
| The metabolic ratio (MR) of 1-hydroxymidazolam to midazolam . | Total duration: up to 11 days | — |
Countries
Czechia
Outcome results
None listed