Clinical trial NCT03380455: Effect of Cimetidine on the Pharmacokinetics of Lucerastat in Healthy Subjects
Official title: A Single-center, Open-label Study to Investigate the Effect of Cimetidine on the Pharmacokinetics of Lucerastat in Healthy Male Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Subjects
Lead sponsor: Idorsia Pharmaceuticals Ltd.
Sponsor class: INDUSTRY
First posted: 2017-12-21
Enrollment: 14
Sex: MALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SEQUENTIAL
Intervention model description: Fixed sequence
Primary purpose: OTHER

Brief summary: A study in healthy male subjects to investigate whether repeated administrations of cimetidine (a medication which decreases the amount of acid in the stomach) can affect the fate in the body (amount and time of presence in the blood) of lucerastat. Safety of the concomitant administration of the two treatments will also be assessed.


Eligibility criteria: Inclusion Criteria:

* Signed informed consent in the local language prior to any study-mandated procedure.
* Body mass index from 18.0 to 30.0 kg/m2 (inclusive) at Screening.
* Normal renal function confirmed by creatinine clearance ≥ 80 mL/min using Cockroft-Gault formula at Screening.

Exclusion Criteria:

* Known hypersensitivity to cimetidine, lucerastat, or drugs of the same class, or any of their excipients.
* History or clinical evidence of any disease and/or existence of any surgical or medical condition, which might interfere with the absorption, distribution, metabolism, or excretion of the study treatment(s) (appendectomy and herniotomy allowed, cholecystectomy not allowed).
* Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol.

Primary outcomes:
measure: Cmax of lucerastat
timeFrame: Up to 48 h after lucerastat administration on Day 1 (i.e., up to Day 3) and from pre-dose up to 96 h after lucerastat administration on Day 6 (i.e., up to Day 10); in total for up to 7 days
measure: Tmax of lucerastat
timeFrame: Up to 48 h after lucerastat administration on Day 1 (i.e., up to Day 3) and from pre-dose up to 96 h after lucerastat administration on Day 6 (i.e., up to Day 10); in total for up to 7 days
measure: AUC(0-t) of lucerastat
timeFrame: Up to 48 h after lucerastat administration on Day 1 (i.e., up to Day 3) and from pre-dose up to 96 h after lucerastat administration on Day 6 (i.e., up to Day 10); in total for up to 7 days
measure: AUC(0-inf) of lucerastat
timeFrame: Up to 48 h after lucerastat administration on Day 1 (i.e., up to Day 3) and from pre-dose up to 96 h after lucerastat administration on Day 6 (i.e., up to Day 10); in total for up to 7 days
measure: AUC(0-48) of lucerastat
timeFrame: Up to 48 h after lucerastat administration on Day 1 (i.e., up to Day 3) and from pre-dose up to 96 h after lucerastat administration on Day 6 (i.e., up to Day 10); in total for up to 7 days
measure: T1/2 of lucerastat
timeFrame: Up to 48 h after lucerastat administration on Day 1 (i.e., up to Day 3) and from pre-dose up to 96 h after lucerastat administration on Day 6 (i.e., up to Day 10); in total for up to 7 days
Secondary outcomes:
measure: Number of treatment-emergent AEs
timeFrame: From Day 1 to End-of-Study (for up to 13 days)
measure: Number of treatment-emergent SAEs
timeFrame: From Screening to safety follow-up, i.e., 32 days after End-of-Study (for up to 63 days)
Other outcomes:
Locations:
city: Kiel
country: Germany
facility: CRS Clinical Research Services Kiel GmbH
Study officials:
affiliation: Idorsia Pharmaceuticals Ltd.
name: Marie-Laure Boof, PhD
role: STUDY_DIRECTOR
References:
citation: Boof ML, Halabi A, Ufer M, Dingemanse J. Impact of the organic cation transporter 2 inhibitor cimetidine on the single-dose pharmacokinetics of the glucosylceramide synthase inhibitor lucerastat in healthy subjects. Eur J Clin Pharmacol. 2020 Mar;76(3):431-437. doi: 10.1007/s00228-019-02808-9. Epub 2019 Dec 13.