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

Prospective, Single-center, Randomized, Double-blind, Placebo-controlled, 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

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)

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Lucerastat (Treatment A); Other: Placebo; Drug: Moxifloxacin; Drug: Lucerastat (Treatment B); Drug: Lucerastat (Treatment C)

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Groningen, Netherlands, 9713
    • QPS Netherlands B.V.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

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.

Exclusion Criteria:

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A: Treatment 1; A single oral dose of 2000 mg lucerastat on Day 1 and of 4000 mg lucerastat on Day 3	Drug: Lucerastat (Treatment A); 2000 and 4000 mg; hard capsules for oral administration
Placebo Comparator: Part A: Treatment 2; A single oral dose of placebo on Day 1 and 3	Other: Placebo; hard capsules for oral administration
Active Comparator: Part B: Treatment A; A single oral dose of 400 mg moxifloxacin	Drug: Moxifloxacin; 400 mg; film-coated tablets for oral administration
Experimental: Part B: Treatment B; A single oral dose of 1000 mg lucerastat	Drug: Lucerastat (Treatment B); 1000 mg; hard capsules for oral administration
Experimental: Part B: Treatment C; A single oral dose of 4000 mg lucerastat	Drug: Lucerastat (Treatment C); 4000 mg; hard capsules for oral administration
Placebo Comparator: Part B: Treatment D; A single oral dose of placebo	Other: Placebo; hard capsules for oral administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)

Collaborators and Investigators

• Sponsor: Idorsia Pharmaceuticals Ltd.

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): February 14, 2019
• Primary Completion (Actual): April 22, 2019
• Study Completion (Actual): April 22, 2019

Study Registration Dates

• First Submitted: February 5, 2019
• First Submitted That Met QC Criteria: February 5, 2019
• First Posted (Actual): February 6, 2019

Study Record Updates

• Last Update Posted (Actual): October 31, 2019
• Last Update Submitted That Met QC Criteria: October 30, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Moxifloxacin; 1-Deoxynojirimycin
• Other Study ID Numbers: ID-069-106; 2018-004546-42 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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