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

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

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).

Study Overview

• Status: Completed
• Conditions: Pharmacokinetics; Safety Issues; Tolerability; Drug Interaction
• Intervention / Treatment: Drug: Drug drug interaction (DDI) - Clarithromycin (Part I); Drug: Drug drug interaction (DDI) - Midazolam (Part 2); Drug: Linaprazan glurate

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Teresa Sandvall; Phone Number: +46 (0)76 492 21 63; Email: teresa.sandvall@sdslifescience.com
• Study Contact Backup: Name: Kajsa Larsson, PhD; Phone Number: +46 (0)70 675 01 28; Email: kajsa.larsson@cincluspharma.com

Study Locations

• Sweden
  • Uppsala, Sweden, 75237
    • CTC Clinical Trials Consultants AB

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 58 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

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

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

Collaborators and Investigators

• Sponsor: Cinclus Pharma Holding AB
• Investigators: Study Director: Karin Palm, CTC Clinical Trial Consultants AB

Study record dates

Study Major Dates

• Study Start (Actual): November 27, 2022
• Primary Completion (Actual): May 30, 2023
• Study Completion (Actual): May 30, 2023

Study Registration Dates

• First Submitted: November 21, 2022
• First Submitted That Met QC Criteria: November 21, 2022
• First Posted (Actual): December 1, 2022

Study Record Updates

• Last Update Posted (Estimated): August 31, 2023
• Last Update Submitted That Met QC Criteria: August 30, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Central Nervous System Depressants; Enzyme Inhibitors; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Anti-Bacterial Agents; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Protein Synthesis Inhibitors; Midazolam; Clarithromycin
• Other Study ID Numbers: CX842A2105

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No