Safety IssuesPhase 1NCT05633147

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

A Phase 1 study testing Linaprazan glurate, Drug drug interaction (DDI) - Clarithromycin (Part I) and Drug drug interaction (DDI) - Midazolam (Part 2) in people with Safety Issues and Pharmacokinetics, run by Cinclus Pharma Holding AB at 1 site in Sweden.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 60 yearsHealthy volunteers can take part
Conditions the study is for: Safety Issues, Pharmacokinetics, Drug Interaction
What is being tested?: Linaprazan glurate, Drug drug interaction (DDI) - Clarithromycin (Part I) and Drug drug interaction (DDI) - Midazolam (Part 2)
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 35 participants
Where: 1 siteSweden
Study dates: 27 Nov 2022to 30 May 2023
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 60 years
All sexes
Healthy volunteers accepted
Adult

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.

Trial locations and contacts

1 site in 1 country.

Sweden1 site

CTC Clinical Trials Consultants AB
Uppsala, 75237

Other trials in Sweden

About this study

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

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
Being tested: Linaprazan glurate, Drug drug interaction (DDI) - Clarithromycin (Part I), Drug drug interaction (DDI) - Midazolam (Part 2)

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Linaprazan glurateDrug
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).

Study groups in NCT05633147
Study group	Role	What they receive
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. Receives: Drug: Linaprazan glurate; Drug: Drug drug interaction (DDI) - Clarithromycin (Part I); Drug: Drug drug interaction (DDI) - Midazolam (Part 2)

What is being measured

The primary outcome is the main question the study is designed to answer.

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).
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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).

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

27 Nov 202230 May 2023

First posted1 Dec 2022
Study start27 Nov 2022
Primary completion30 May 2023
Study completion30 May 2023

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Safety IssuesStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Basic science
Allocation: Not applicable
Intervention model: Sequential
Masking: None (open label)
Enrolment: 35 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT05633147
Sponsor's protocol ID: CX842A2105
Status last verified: Nov 2024
First submitted: 21 Nov 2022
Last updated: 3 Jan 2025
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 3 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT05633147
Acronym / sponsor ID: CX842A2105
Conditions: Safety Issues, Pharmacokinetics, Drug Interaction, Tolerability
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 35 participants (actual)
Lead sponsor: Cinclus Pharma Holding ABIndustry (pharma, biotech, devices)
Study start: 27 Nov 2022 (actual)
Primary completion: 30 May 2023 (actual)
Study completion: 30 May 2023 (actual)
First posted: 1 Dec 2022 (actual)
Results: Posted 3 Jan 2025

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Basic science
Allocation: Not applicable
Intervention model: Sequential
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
linaprazan glurate	Experimental	Drug: Linaprazan glurate, Drug: Drug drug interaction (DDI) - Clarithromycin (Part I), Drug: Drug drug interaction (DDI) - Midazolam (Part 2)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.

Who may qualify

Ages: 18 to 60 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

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

Primary outcome

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).
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.
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.
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).
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.
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.

Results and safety

Results posted to the registry on 3 Jan 2025, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Period I, Part I	17	16
Period II, Part II	18	18

Primary outcome: 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).. Mean (Standard Deviation). Unit: h*nmol/L

Measure	Part I n = 16
Linaprazan (alone)	13950 (5649)
Linaprazan (co-admin)	42840 (16260)
Linaprazan glurate (alone)	137.3 (52.02)
Linaprazan glurate (co-admin)	165.9 (79.56)

Population analysed: Data is presented for: * Linaprazan (active metabolite) after 100 mg single dose administered alone * Linaprazan (active metabolite) after 100 mg single dose co-administered with clarithromycin * Linaprazan glurate (prodrug) after 100 mg single dose administered alone * Linaprazan glurate (prodrug) after 100 mg single dose co-administered with clarithromycin

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

Measure	Part I n = 16
Linaprazan (alone)	13870 (5346)
Linaprazan (co-admin)	39870 (13840)
Linaprazan glurate (alone)	133.6 (51.87)
Linaprazan glurate (co-admin)	160.6 (81.64)

Primary outcome: 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).. Mean (Standard Deviation). Unit: nmol/L

Measure	Part I n = 16
Linaprazan (alone)	1844 (712.4)
Linaprazan (co-admin)	2742 (1217)
Linaprazan glurate (alone)	131.1 (53.72)
Linaprazan glurate (co-admin)	176.8 (114.3)

Primary outcome: 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).. Mean (Standard Deviation). Unit: h*ng/mL

Measure	Part II n = 17
Midazolam (alone)	38.57 (13.98)
Midazolam (co-admin) Day 2	40.78 (16.04)
Midazolam (co-admin) Day 14	33.06 (10.46)

Population analysed: Data is presented for: * Midazolam alone, Day 1 * Midazolam co-administered with linaprazan glurate, Day 2 * Midazolam co-administered with linaprazan glurate, Day 14

Adverse events

Time frame: Period I, Part I: AEs (including SAEs) were collected from start of IMP administration (Day 1) until the end-of-study visit on Day 14. Period II, Part II: AEs (including SAEs) were collected from start of IMP administration (Day 1) until the end-of-study visit on Day 22.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Part I	0 of 17 (0%)	11 of 17 (64.7%)	0 of 17
Part II	0 of 18 (0%)	8 of 18 (44.4%)	0 of 18

Limitations and caveats (from the sponsor): None reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 3 Jan 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Karin Palm study director

CTC Clinical Trial Consultants AB

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 3 Jan 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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).). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05633147.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jan 2025.