Effect of Clarithromycin on PK of Linaprazan, Linaprazan on PK of Clarithromycin and Linaprazan on PK of Midazolam
Study Details
Study Description
Brief Summary
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).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Arms and Interventions
| 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), 100 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
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), 100 mg twice daily for 13 days.
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).
|
Outcome Measures
Primary Outcome Measures
- Part I - Linaprazan glurate and linaprazan PK parameters with and without co-administration of clarithromycin - Area under the plasma concentration curve [Day 1 to day 13]
Area under the plasma concentration curve from 0 to infinity (AUCinf)
- Part I - Linaprazan glurate and linaprazan PK parameters with and without co-administration of clarithromycin - AUC 0-t [Day 1 to day 13]
AUC from time 0 to time t (AUC 0-t)
- Part I - Linaprazan glurate and linaprazan PK parameters with and without co-administration of clarithromycin - Maximum plasma concentration [Day 1 to day 13]
Maximum plasma concentration (Cmax)
- Part II- Midazolam PK parameters in the presence and absence of linaprazan glurate administration - Area under the plasma concentration curve [Day 1 to day 16]
AUCinf
- Part II- Midazolam PK parameters in the presence and absence of linaprazan glurate administration - AUC 0-t [Day 1 to day 16]
AUC 0-t
- Part II- Midazolam PK parameters in the presence and absence of linaprazan glurate [Day 1 to day 16]
Cmax
Eligibility Criteria
Criteria
Main Inclusion Criteria:
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Willing and able to give written informed consent for participation in the study.
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Healthy male and female subjects of non-childbearing potential aged 18 to 60 years, inclusive.
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Body mass index ≥ 18.0 and ≤ 30.0 kg/m2.
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Subjects as well as their partners, must agree to contraception requirements. Male subjects must refrain from donating sperm.
Main Exclusion Criteria:
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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.
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Use of CYP3A4 inhibitors, antacids, PPIs or any medication that changes gastric pH.
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Use of any prescribed or non-prescribed CYP3A4-inducing medication or other metabolic enzyme inducers.
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History of any clinically significant disease or disorder defined in the protocol.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | CTC Clinical Trials Consultants AB | Uppsala | Sweden | 75237 |
Sponsors and Collaborators
- Cinclus Pharma Holding AB
Investigators
- Study Director: Karin Palm, CTC Clinical Trial Consultants AB
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CX842A2105