Effect of Clarithromycin on PK of Linaprazan, Linaprazan on PK of Clarithromycin and Linaprazan on PK of Midazolam

Study Overview
=================
Brief Summary
-----------------
This is a phase I, open-label, fixed design, drug-drug-interaction (DDI) study divided in 2 parts. Part I is designed to evaluate whether concomitant treatment with linaprazan glurate and clarithromycin, a strong inhibitor of cytochrome P450 3A4 (CYP3A4) and P-glycoprotein P (PgP), leads to an effect on the systemic exposure to linaprazan glurate and linaprazan and whether there is an effect on the pharmacokinetics of clarithromycin after a single dose of linaprazan glurate. Part II is designed to evaluate the effect of repeated doses of linaprazan glurate on the pharmacokinetics (PK) of a sensitive substrate of CYP3A (midazolam).

Official Title
-----------------
Effect of Repeated Dosing of Clarithromycin on PK of Linaprazan Glurate/Linaprazan, Effect of Single Dose of Linaprazan Glurate on PK of Clarithromycin, Single/Repeated Dosing of Linaprazan Glurate on PK of Midazolam to Healthy Subjects

Conditions
-----------------
Safety Issues, Pharmacokinetics, Drug Interaction, Tolerability

Intervention / Treatment
-----------------
* Drug: Linaprazan glurate
* Drug: Drug drug interaction (DDI) - Clarithromycin (Part I)
* Drug: Drug drug interaction (DDI) - Midazolam (Part 2)


Participation Criteria
=================
Eligibility Criteria
-----------------
Main Inclusion Criteria: Willing and able to give written informed consent for participation in the study. Healthy male and female subjects of non-childbearing potential aged 18 to 60 years, inclusive. Body mass index ≥ 18.0 and ≤ 30.0 kg/m2. Subjects as well as their partners, must agree to contraception requirements. Male subjects must refrain from donating sperm. Main Exclusion Criteria: Have known allergies to any components of the linaprazan glurate formulation, to clarithromycin/midazolam or to any drugs of a similar class including excipients associated with any of the drugs. Use of CYP3A4 inhibitors, antacids, PPIs or any medication that changes gastric pH. Use of any prescribed or non-prescribed CYP3A4-inducing medication or other metabolic enzyme inducers. History of any clinically significant disease or disorder defined in the protocol.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: linaprazan glurate<br>Part I: Linaprazan glurate in base form, 100 mg once daily will be administered under fasting conditions at day 1 and day 10. Part II: Linaprazan glurate hydrochloride (HCl), 75 mg twice a day for 13 days. The morning dose will be administered under fasting conditions on Day 2 and Day 14. | Drug: Linaprazan glurate<br>* Investigational Medicinal Product: Linaprazan glurate (tablets). Part I: Linaprazan glurate in base form, 100 mg once daily Day 1 and Day 10. Part II: Linaprazan glurate hydrochloride (HCl), 75 mg twice daily for 13 days.<br>Drug: Drug drug interaction (DDI) - Clarithromycin (Part I)<br>* Index inhibitor (perpetrator drug) Clarithromycin 500 mg twice daily for 9 days (tablets).<br>Drug: Drug drug interaction (DDI) - Midazolam (Part 2)<br>* Substrate for CYP3A. Midazolam 2.5 mg once daily (2.5 mL oral solution).<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part I - Linaprazan glurate and linaprazan PK parameters with and without co-administration of clarithromycin - Area under the plasma concentration curve | Area under the plasma concentration curve from 0 to infinity (AUCinf) | Day 1 to day 13 | 
| Part I - Linaprazan glurate and linaprazan PK parameters with and without co-administration of clarithromycin - AUC 0-t | AUC from time 0 to time t (AUC 0-t) | Day 1 to day 13 | 
| Part I - Linaprazan glurate and linaprazan PK parameters with and without co-administration of clarithromycin - Maximum plasma concentration | Maximum plasma concentration (Cmax) | Day 1 to day 13 | 
| Part II- Midazolam PK parameters in the presence and absence of linaprazan glurate administration - Area under the plasma concentration curve | AUCinf | Day 1 to day 16 | 
| Part II- Midazolam PK parameters in the presence and absence of linaprazan glurate administration - AUC 0-t | AUC 0-t | Day 1 to day 16 | 
| Part II- Midazolam PK parameters in the presence and absence of linaprazan glurate | Cmax | Day 1 to day 16 |