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

NCT05633147 | Completed Phase 1 Results

• 1 other identifier: CX842A2105
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase I, open-label, fixed sequence 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).

Conditions

Safety Issues; Pharmacokinetics; Drug Interaction; Tolerability

Outcome Measures

Primary Outcomes (6)

• Period I, Part I - Linaprazan Glurate and Linaprazan PK Parameters With and Without Co-administration of Clarithromycin - AUC0-inf

  Area under the plasma concentration curve from 0 to infinity (AUC0-inf). The AUC were calculated to the time point of the last quantifiable plasma concentration and then extrapolated to infinity using the concentration in the last quantifiable sample and the estimated terminal elimination rate constant (Lambdaz).

  Timepoints collected: pre-dose, 15 min, 30 min, 45 min, 1.15 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 10 h, 12 h, 18 h, 24 h, 36 h, 48 h and 72 h after dosing (on dosing Days 1 and 10).

• Period I, Part I - Linaprazan Glurate and Linaprazan PK Parameters With and Without Co-administration of Clarithromycin - AUC0-t

  AUC from time 0 to time t (AUC0-t). AUC0-t were analyzed using a mixed model following a natural logarithmic transformation, with fixed effect for treatment and random effect for subject.

  Timepoints collected: pre-dose, 15 min, 30 min, 45 min, 1.15 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 10 h, 12 h, 18 h, 24 h, 36 h, 48 h and 72 h after dosing (on dosing Days 1 and 10).

• Period I, Part I - Linaprazan Glurate and Linaprazan PK Parameters With and Without Co-administration of Clarithromycin - Cmax

  Maximum plasma concentration (Cmax). Cmax were analyzed using a mixed model following a natural logarithmic transformation, with fixed effect for treatment and random effect for subject.

  and 72 h after dosing (on dosing Days 1 and 10).

• Period II, Part II- Midazolam PK Parameters in the Presence and Absence of Linaprazan Glurate Administration - AUC0-inf

  Area under the plasma concentration curve from 0 to infinity - AUCinf. AUC were calculated to the time point of the last quantifiable plasma concentration and then extrapolated to infinity using the concentration in the last quantifiable sample and the estimated terminal elimination rate constant (Lambdaz).

  Timepoints collected: Pre-dose, 15 min, 30 min, 1 h, 2 h, 4 h, 8 h, 12 h, 14 h, 20 h and 24 h (on day 1, 2 and 14).

• Period II, Part II- Midazolam PK Parameters in the Presence and Absence of Linaprazan Glurate Administration - AUC0-t

  AUC from time 0 to time t - AUC0-t. AUC0-t were analyzed using a mixed model following a natural logarithmic transformation, with fixed effect for treatment and random effect for subject.

  Timepoints collected: Pre-dose, 15 min, 30 min, 1 h, 2 h, 4 h, 8 h, 12 h, 14 h, 20 h and 24 h (on day 1, 2 and 14).

• Period II, Part II- Midazolam PK Parameters in the Presence and Absence of Linaprazan Glurate - Cmax

  Maximum plasma concentration - Cmax. Cmax were analyzed using a mixed model following a natural logarithmic transformation, with fixed effect for treatment and random effect for subject.

  Timepoints collected: Pre-dose, 15 min, 30 min, 1 h, 2 h, 4 h, 8 h, 12 h, 14 h, 20 h and 24 h (on day 1, 2 and 14).

Study Arms (1)

linaprazan glurate

EXPERIMENTAL

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; Drug: Drug drug interaction (DDI) - Clarithromycin (Part I); Drug: Drug drug interaction (DDI) - Midazolam (Part 2)

Interventions

Linaprazan glurate DRUG

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.

linaprazan glurate

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

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

linaprazan glurate

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

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

linaprazan glurate

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Cinclus Pharma Holding AB: lead

Study Sites (1)

CTC Clinical Trials Consultants AB

Uppsala, 75237, Sweden

Location

MeSH Terms

Interventions

Drug Interactions; Didanosine; Clarithromycin; Midazolam

Intervention Hierarchy (Ancestors)

Pharmacological Phenomena; Pharmacological and Toxicological Phenomena; Physiological Phenomena; Inosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Dideoxynucleosides; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals; Benzodiazepines; Benzazepines

Limitations and Caveats

None reported

Results Point of Contact

• Title: Kajsa Larsson, CMO
• Organization: Cinclus Pharma Holding AB

kajsa.larsson@cincluspharma.com

+46 706750128

Study Officials

• Karin Palm

  CTC Clinical Trial Consultants AB

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 21, 2022
• First Posted: December 1, 2022
• Study Start: November 27, 2022
• Primary Completion: May 30, 2023
• Study Completion: May 30, 2023
• Last Updated: January 3, 2025
• Results First Posted: January 3, 2025

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1)