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OpenTrials
Completed

NCT Number: NCT05633147

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

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).

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Key information

Conditions

Safety Issues Drug Interaction Pharmacokinetics Tolerability

Age range

18 year–60 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

CTC Clinical Trials Consultants AB

Uppsala, 75237, Sweden

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

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.

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

Drug

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

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

Drug

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

Primary outcomes

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

    Time frame: 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).

    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).

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

    Time frame: 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).

    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.

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

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

    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.

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

    Time frame: 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).

    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).

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

    Time frame: 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).

    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.

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

    Time frame: 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).

    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.

Sponsors and collaborators

Lead sponsor

Cinclus Pharma Holding AB

Industry

Registry information

Official study 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

Important dates

Study start
2022
Primary completion
2023
Study completion
2023
First posted
Dec 1, 2022
Registry last updated
Jan 3, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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