Clinical trial NCT05633147: Effect of Clarithromycin on PK of Linaprazan, Linaprazan on PK of Clarithromycin and Linaprazan on PK of Midazolam
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Safety Issues
Pharmacokinetics
Drug Interaction
Tolerability
Lead sponsor: Cinclus Pharma Holding AB
Sponsor class: INDUSTRY
First posted: 2022-12-01
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: BASIC_SCIENCE

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).


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.

Primary outcomes:
measure: Period I, Part I - Linaprazan Glurate and Linaprazan PK Parameters With and Without Co-administration of Clarithromycin - AUC0-inf
timeFrame: 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).
measure: Period I, Part I - Linaprazan Glurate and Linaprazan PK Parameters With and Without Co-administration of Clarithromycin - AUC0-t
timeFrame: 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).
measure: Period I, Part I - Linaprazan Glurate and Linaprazan PK Parameters With and Without Co-administration of Clarithromycin - Cmax
timeFrame: and 72 h after dosing (on dosing Days 1 and 10).
measure: Period II, Part II- Midazolam PK Parameters in the Presence and Absence of Linaprazan Glurate Administration - AUC0-inf
timeFrame: 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).
measure: Period II, Part II- Midazolam PK Parameters in the Presence and Absence of Linaprazan Glurate Administration - AUC0-t
timeFrame: 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).
measure: Period II, Part II- Midazolam PK Parameters in the Presence and Absence of Linaprazan Glurate - Cmax
timeFrame: 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).
Secondary outcomes:
Other outcomes:
Locations:
city: Uppsala
country: Sweden
facility: CTC Clinical Trials Consultants AB
Study officials:
affiliation: CTC Clinical Trial Consultants AB
name: Karin Palm
role: STUDY_DIRECTOR
References: