Clinical trial

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

Name

CX842A2105

Description

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).

Trial arms

Trial start

2022-11-27

Estimated PCD

2023-05-30

Trial end

2023-05-30

Status

Completed

Phase

Early phase I

Treatment

Linaprazan glurate

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.

Arms:

linaprazan glurate

Drug drug interaction (DDI) - Clarithromycin (Part I)

Index inhibitor (perpetrator drug) Clarithromycin 500 mg twice daily for 9 days (tablets).

Arms:

linaprazan glurate

Drug drug interaction (DDI) - Midazolam (Part 2)

Substrate for CYP3A. Midazolam 2.5 mg once daily (2.5 mL oral solution).

Arms:

linaprazan glurate

Size

Primary endpoint

Part I - Linaprazan glurate and linaprazan PK parameters with and without co-administration of clarithromycin - Area under the plasma concentration curve

Day 1 to day 13

Part I - Linaprazan glurate and linaprazan PK parameters with and without co-administration of clarithromycin - 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

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

Day 1 to day 16

Part II- Midazolam PK parameters in the presence and absence of linaprazan glurate administration - AUC 0-t

Day 1 to day 16

Part II- Midazolam PK parameters in the presence and absence of linaprazan glurate

Day 1 to day 16

Eligibility criteria

Main Inclusion Criteria: 1. Willing and able to give written informed consent for participation in the study. 2. Healthy male and female subjects of non-childbearing potential aged 18 to 60 years, inclusive. 3. Body mass index ≥ 18.0 and ≤ 30.0 kg/m2. 4. Subjects as well as their partners, must agree to contraception requirements. Male subjects must refrain from donating sperm. Main Exclusion Criteria: 1. 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. 2. Use of CYP3A4 inhibitors, antacids, PPIs or any medication that changes gastric pH. 3. Use of any prescribed or non-prescribed CYP3A4-inducing medication or other metabolic enzyme inducers. 4. History of any clinically significant disease or disorder defined in the protocol.

Protocol

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE1'], 'designInfo': {'allocation': 'NA', 'interventionModel': 'SEQUENTIAL', 'primaryPurpose': 'BASIC_SCIENCE', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 35, 'type': 'ACTUAL'}}

Updated at

2023-08-31

1 organization

3 products

4 indications

Organization

Cinclus Pharma Holding

Product

Clarithromycin

Indication

Safety Issues

Indication