Effect of Cimetidine on the Pharmacokinetics of Lucerastat in Healthy Subjects

A Single-center, Open-label Study to Investigate the Effect of Cimetidine on the Pharmacokinetics of Lucerastat in Healthy Male Subjects

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.

Study Overview

• Status: Completed
• Conditions: Healthy Subjects
• Intervention / Treatment: Drug: Lucerastat; Drug: Cimetidine

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Kiel, Germany, 24105
    • CRS Clinical Research Services Kiel GmbH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 43 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment period A & B; Treatment period A: Subjects receive a single oral dose of 500 mg lucerastat on Day 1 under fasted conditions. Treatment period B: From Day 3 to Day 9, subjects receive a b.i.d. (every 12 h) oral dose of 800 mg cimetidine under fasted conditions (Treatment period B1; from Day 3 to Day 5). On Day 6, subjects receive a single oral dose of 500 mg lucerastat concomitantly with the morning dose of 800 mg cimetidine under fasted conditions (Treatment period B2; from Day 6 to Day 10).

Drug: Lucerastat; Single oral dose of 500 mg lucerastat under fasted conditions; Drug: Cimetidine; Twice daily oral dose of 800 mg cimetidine under fasted conditions

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax of lucerastat	Plasma PK parameter of lucerastat after single-dose oral administration of lucerastat alone and in combination with cimetidine	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
Tmax of lucerastat	Plasma PK parameter of lucerastat after single-dose oral administration of lucerastat alone and in combination with cimetidine	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
AUC(0-t) of lucerastat	Plasma PK parameter of lucerastat after single-dose oral administration of lucerastat alone and in combination with cimetidine	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
AUC(0-inf) of lucerastat	Plasma PK parameter of lucerastat after single-dose oral administration of lucerastat alone and in combination with cimetidine	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
AUC(0-48) of lucerastat	Plasma PK parameter of lucerastat after single-dose oral administration of lucerastat alone and in combination with cimetidine	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
T1/2 of lucerastat	Plasma PK parameter of lucerastat after single-dose oral administration of lucerastat alone and in combination with cimetidine	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 Outcome Measures

Outcome Measure	Time Frame
Number of treatment-emergent AEs	From Day 1 to End-of-Study (for up to 13 days)
Number of treatment-emergent SAEs	From Screening to safety follow-up, i.e., 32 days after End-of-Study (for up to 63 days)

Collaborators and Investigators

• Sponsor: Idorsia Pharmaceuticals Ltd.
• Investigators: Study Director: Marie-Laure Boof, PhD, Idorsia Pharmaceuticals Ltd.

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): January 9, 2018
• Primary Completion (Actual): January 29, 2018
• Study Completion (Actual): January 29, 2018

Study Registration Dates

• First Submitted: December 15, 2017
• First Submitted That Met QC Criteria: December 15, 2017
• First Posted (Actual): December 21, 2017

Study Record Updates

• Last Update Posted (Actual): June 2, 2022
• Last Update Submitted That Met QC Criteria: June 1, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Gastrointestinal Agents; Cytochrome P-450 Enzyme Inhibitors; Anti-Ulcer Agents; Histamine Antagonists; Histamine Agents; Cytochrome P-450 CYP1A2 Inhibitors; Histamine H2 Antagonists; Cimetidine
• Other Study ID Numbers: ID-069-105

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No