Effect of Cimetidine on the Pharmacokinetics of Lucerastat in Healthy Subjects

NCT03380455 | Completed Phase 1 FDA Drug

• 1 other identifier: ID-069-105
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy Subjects

Outcome Measures

Primary Outcomes (6)

• 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 Outcomes (2)

• 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)

Study Arms (1)

Treatment period A & B

EXPERIMENTAL

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; Drug: Cimetidine

Interventions

Lucerastat DRUG

Single oral dose of 500 mg lucerastat under fasted conditions

Treatment period A & B

Cimetidine DRUG

Twice daily oral dose of 800 mg cimetidine under fasted conditions

Treatment period A & B

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Idorsia Pharmaceuticals Ltd.: lead

Study Sites (1)

CRS Clinical Research Services Kiel GmbH

Kiel, 24105, Germany

Location

Related Publications (1)

• 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.

  PMID: 31836927 DERIVED

MeSH Terms

Interventions

migalastat; Cimetidine

Intervention Hierarchy (Ancestors)

Guanidines; Amidines; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Marie-Laure Boof, PhD

  Idorsia Pharmaceuticals Ltd.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Fixed sequence

Study Record Dates

• First Submitted: December 15, 2017
• First Posted: December 21, 2017
• Study Start: January 9, 2018
• Primary Completion: January 29, 2018
• Study Completion: January 29, 2018
• Last Updated: June 2, 2022

Record last verified: 2022-06

Locations

DE (1)