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

Pharmacokinetics Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05633147
• Other study ID #: CX842A2105
• Status: Completed
• Phase: Phase 1
• Start date: November 27, 2022
• Est. completion date: May 30, 2023

Study information

• Verified date: August 2023
• Source: Cinclus Pharma Holding AB
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 35
• Est. completion date: May 30, 2023
• Est. primary completion date: May 30, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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.

Related Conditions & MeSH terms

• Drug Interaction
• Pharmacokinetics
• Safety Issues
• Tolerability

Intervention

Drug:
• 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.
• Drug drug interaction (DDI) - Clarithromycin (Part I)
Index inhibitor (perpetrator drug) Clarithromycin 500 mg twice daily for 9 days (tablets).
• Drug drug interaction (DDI) - Midazolam (Part 2)
Substrate for CYP3A. Midazolam 2.5 mg once daily (2.5 mL oral solution).

Locations

Country	Name	City	State
Sweden	CTC Clinical Trials Consultants AB	Uppsala

Sponsors (1)

Lead Sponsor	Collaborator
Cinclus Pharma Holding AB

Country where clinical trial is conducted

Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	Part II- Midazolam PK parameters in the presence and absence of linaprazan glurate	Cmax	Day 1 to day 16