A Study in Healthy Subjects to Investigate Whether Administration of Lucerastat Can Affect Normal Heart Function

NCT03832452 | Completed Phase 1 FDA Drug

• 2 other identifiers: ID-069-1062018-004546-42
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief Summary

Two-part Phase 1 study to assess the effect of single therapeutic and supra-therapeutic doses of lucerastat on the QT/QTc interval duration in healthy subjects (Part A: Pilot study; Part B: TQT study)

Conditions

Healthy

Outcome Measures

Primary Outcomes (1)

• Part B: Placebo-corrected, change-from-baseline QTcF (ΔΔQTcF)

  QTcF = QT interval corrected with Fridericia's formula; ΔΔQTcF = Placebo-corrected change-from-baseline QTcF

  From 1 h pre-dose to 36 hour after study treatment administration (duration: up to 37 hours)

Study Arms (6)

Part A: Treatment 1

EXPERIMENTAL

A single oral dose of 2000 mg lucerastat on Day 1 and of 4000 mg lucerastat on Day 3

Drug: Lucerastat (Treatment A)

Part A: Treatment 2

PLACEBO COMPARATOR

A single oral dose of placebo on Day 1 and 3

Other: Placebo

Part B: Treatment A

ACTIVE COMPARATOR

A single oral dose of 400 mg moxifloxacin

Drug: Moxifloxacin

Part B: Treatment B

EXPERIMENTAL

A single oral dose of 1000 mg lucerastat

Drug: Lucerastat (Treatment B)

Part B: Treatment C

EXPERIMENTAL

A single oral dose of 4000 mg lucerastat

Drug: Lucerastat (Treatment C)

Part B: Treatment D

PLACEBO COMPARATOR

A single oral dose of placebo

Other: Placebo

Interventions

Lucerastat (Treatment A) DRUG

2000 and 4000 mg; hard capsules for oral administration

Part A: Treatment 1

Placebo OTHER

hard capsules for oral administration

Part A: Treatment 2; Part B: Treatment D

Moxifloxacin DRUG

400 mg; film-coated tablets for oral administration

Part B: Treatment A

Lucerastat (Treatment B) DRUG

1000 mg; hard capsules for oral administration

Part B: Treatment B

Lucerastat (Treatment C) DRUG

4000 mg; hard capsules for oral administration

Part B: Treatment C

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Part A only:
• \- Healthy male subjects aged between 18 and 55 years.
• Part B only:
• Healthy male and female subjects aged between 18 and 55 years.
• Women of childbearing potential must have a negative serum pregnancy test at Screening and a negative urine pregnancy test on Day 1 pre-dose of the first period. They must consistently and correctly use a highly effective method of contraception, or be sexually inactive, or have a vasectomized partner.
• Women of nonchildbearing potential (i.e., postmenopausal, XY genotype, Turner syndrome, uterine agenesis).
• Part A and B:
• Signed informed consent prior to any study-mandated procedure.
• Body mass index of 18.0 to 30.0 kg/m2 (inclusive) at Screening. Body weight at least 50.0 kg at Screening and prior to first study treatment administration.
• Healthy on the basis of medical history, physical examination, cardiovascular assessments and clinical laboratory tests.

You may not qualify if:

• Part B only:
• Known hypersensitivity to moxifloxacin or any of its excipients.
• Pregnant or lactating women.
• Women planning to become pregnant.
• Part A and B:
• Previous exposure to lucerastat.
• Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol.
• History or presence of rhythm disorders.

Sponsors & Collaborators

• Idorsia Pharmaceuticals Ltd.: lead

Study Sites (1)

QPS Netherlands B.V.

Groningen, 9713, Netherlands

Location

Related Publications (1)

• Mueller MS, Sidharta PN, Voors-Pette C, Darpo B, Xue H, Dingemanse J. The effect of the glucosylceramide synthase inhibitor lucerastat on cardiac repolarization: results from a thorough QT study in healthy subjects. Orphanet J Rare Dis. 2020 Oct 27;15(1):303. doi: 10.1186/s13023-020-01582-7.

  PMID: 33109218 DERIVED

MeSH Terms

Interventions

migalastat; Moxifloxacin

Intervention Hierarchy (Ancestors)

Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Clinical Trials

  Idorsia Pharmaceuticals Ltd.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Prospective, single-center, randomized, double-blind, placebo-controlled, two-part Phase 1 study (Part A: parallel, 2 treatments; Part B: crossover, 4 treatments)

Study Record Dates

• First Submitted: February 5, 2019
• First Posted: February 6, 2019
• Study Start: February 14, 2019
• Primary Completion: April 22, 2019
• Study Completion: April 22, 2019
• Last Updated: October 31, 2019

Record last verified: 2019-10

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)