Pharmacokinetics of Omeprazole and Midazolam When Co-administered With ACT-1014-6470

Healthy Clinical Trial

Official title:

A Single-center, Open-label, Two-period, Fixed-sequence Study to Investigate the Effect of a Single Oral Dose of ACT-1014-6470 on the Pharmacokinetics of Omeprazole, Midazolam, and Their Metabolites in Healthy Male Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05123820
• Other study ID #: ID-087-105
• Secondary ID: 2021-003615-26
• Status: Completed
• Phase: Phase 1
• Start date: November 13, 2021
• Est. completion date: November 24, 2021

Study information

• Verified date: January 2022
• Source: Idorsia Pharmaceuticals Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: November 24, 2021
• Est. primary completion date: November 24, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 45 Years

Eligibility

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.

Related Conditions & MeSH terms

• Drug Drug Interaction
• Healthy

Intervention

Drug:
• Treatment period A
Midazolam solution for oral administration. Omeprazole hard capsule for oral administration.
• Treatment period B
ACT-1014-6470 soft capsule for oral administration. Midazolam solution for oral administration. Omeprazole hard capsule for oral administration.

Locations

Country	Name	City	State
Czechia	CEPHA s.r.o.	Pilsen

Sponsors (1)

Lead Sponsor	Collaborator
Idorsia Pharmaceuticals Ltd.

Country where clinical trial is conducted

Czechia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum plasma concentration (Cmax) of ACT-1014-6470, midazolam and omeprazole.	The plasma pharmacokinetic parameters of ACT-1014-6470, midazolam and omeprazole will be derived by non-compartmental analysis of the plasma concentration-time profiles.	Total duration: up to 11 days
Primary	Time to reach Cmax (tmax) of ACT-1014-6470, midazolam and omeprazole.	The plasma pharmacokinetic parameters of ACT-1014-6470, midazolam and omeprazole will be derived by non-compartmental analysis of the plasma concentration-time profiles.	Total duration: up to 11 days
Primary	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.	The plasma pharmacokinetic parameters of ACT-1014-6470, midazolam and omeprazole will be derived by non-compartmental analysis of the plasma concentration-time profiles.	Total duration: up to 11 days
Primary	Area under the plasma concentration-time curve [AUC(0-12)] of omeprazole.	The plasma pharmacokinetic parameters of omeprazole will be derived by non-compartmental analysis of the plasma concentration-time profile.	Total duration: up to 9 days
Primary	Area under the plasma concentration-time curve [AUC(0-24)] of midazolam and omeprazole.	The plasma pharmacokinetic parameters of midazolam and omeprazole will be derived by non-compartmental analysis of the plasma concentration-time profiles.	Total duration: up to 11 days
Primary	Area under the plasma concentration-time curve [AUC(0-inf)] of ACT-1014-6470, midazolam and omeprazole.	The plasma pharmacokinetic parameters of ACT-1014-6470, midazolam and omeprazole will be derived by non-compartmental analysis of the plasma concentration-time profiles.	Total duration: up to 11 days
Primary	Apparent total body clearance (CL/F) of ACT-1014-6470, midazolam and omeprazole.	The plasma pharmacokinetic parameters of ACT-1014-6470, midazolam and omeprazole will be derived by non-compartmental analysis of the plasma concentration-time profiles.	Total duration: up to 11 days
Primary	The terminal half-life (t½) of ACT-1014-6470, midazolam and omeprazole.	The plasma pharmacokinetic parameters of ACT-1014-6470, midazolam and omeprazole will be derived by non-compartmental analysis of the plasma concentration-time profiles.	Total duration: up to 11 days
Secondary	Maximum plasma concentration (Cmax) of 1-hydroxymidazolam and 5-hydroxyomeprazole.	The plasma pharmacokinetic parameters of 1-hydroxymidazolam and 5-hydroxyomeprazole will be derived by non-compartmental analysis of the plasma concentration-time profiles.	Total duration: up to 11 days
Secondary	Time to reach Cmax (tmax) of 1-hydroxymidazolam and 5-hydroxyomeprazole.	The plasma pharmacokinetic parameters of 1-hydroxymidazolam and 5-hydroxyomeprazole will be derived by non-compartmental analysis of the plasma concentration-time profiles.	Total duration: up to 11 days
Secondary	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.	The plasma pharmacokinetic parameters of 1-hydroxymidazolam and 5-hydroxyomeprazole will be derived by non-compartmental analysis of the plasma concentration-time profiles.	Total duration: up to 11 days
Secondary	Area under the plasma concentration-time curve [AUC(0-12)] of 5-hydroxyomeprazole.	The plasma pharmacokinetic parameters of 5-hydroxyomeprazole will be derived by non-compartmental analysis of the plasma concentration-time profiles.	Total duration: up to 11 days
Secondary	Area under the plasma concentration-time curve [AUC(0-24)] of 1-hydroxymidazolam and 5-hydroxyomeprazole.	The plasma pharmacokinetic parameters of 1-hydroxymidazolam and 5-hydroxyomeprazole will be derived by non-compartmental analysis of the plasma concentration-time profiles.	Total duration: up to 11 days
Secondary	Area under the plasma concentration-time curve [AUC(0-inf)] of 1-hydroxymidazolam and 5-hydroxyomeprazole.	The plasma pharmacokinetic parameters of 1-hydroxymidazolam and 5-hydroxyomeprazole will be derived by non-compartmental analysis of the plasma concentration-time profiles.	Total duration: up to 11 days
Secondary	The terminal half-life (t½) of 1-hydroxymidazolam and 5-hydroxyomeprazole.	The plasma pharmacokinetic parameters of 1-hydroxymidazolam and 5-hydroxyomeprazole will be derived by non-compartmental analysis of the plasma concentration-time profiles.	Total duration: up to 11 days
Secondary	The metabolic ratio (MR) of 1-hydroxymidazolam to midazolam .		Total duration: up to 11 days
Secondary	The metabolic ratio (MR) of 5-hydroxyomeprazole to omeprazole.		Total duration: up to 11 days
Secondary	Number of participants with treatment-emergent adverse events as a measure of safety and tolerability.	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.	Total duration: up to 11 days