A Study to Assess the Safety and Pharmacokinetics of Lucerastat (OGT 923) in Healthy Subjects

A Randomised, Double-blind, Placebo-controlled Ascending Dose Tolerance Study of OGT 923 in Healthy Male Volunteers

The objectives of this study were to evaluate the safety and tolerability of lucerastat, and to determine its pharmacokinetic profile as single oral doses at different strengths.

Study Overview

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

Detailed Description

The subjects were enrolled sequentially to five dose groups, starting with the lowest dose level. Subjects could participate in only one Group.

• Study Type: Interventional
• Enrollment (Actual): 39
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Tranent, United Kingdom, EH33 2NE
    • Investigator site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Signed informed consent form.
• Male subjects aged from 18 to 45 years at screening.
• Body weight between 50 and 100 kg and body mass index (BMI) between 18.0 and 29.0 kg/m2 at screening.
• Healthy on the basis of physical examination, cardiovascular assessments and laboratory tests.

Exclusion Criteria:

• History or clinical evidence of any disease or medical / surgical condition or treatment, which may put the subject at risk of participation in the study or may interfere with the absorption, distribution, metabolism or excretion of the study treatments.
• Serious adverse reaction or hypersensitivity to any drug.
• 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

• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Single ascending doses of lucerastat; Subjects were enrolled sequentially in 4 groups and received a single oral dose of lucerastat from 100 mg to 1000 mg in the morning of Day 1	Drug: Lucerastat; Hard gelatin capsule for oral administration containing lucerastat; Other Names: ACT-434964; OGT-923
EXPERIMENTAL: B.i.d. Dose Group; Subjects received two doses of lucerastat (2 x 1 g) 12 hours apart on Day 1	Drug: Lucerastat; Hard gelatin capsule for oral administration containing lucerastat; Other Names: ACT-434964; OGT-923
PLACEBO_COMPARATOR: Placebo for singe ascending doses; These subjects received matching placebo administered orally in the morning of Day 1	Drug: Placebo; Matching placebo capsules
PLACEBO_COMPARATOR: Placebo for b.i.d.Group; These subjects received matching placebo administered orally in the morning and in the evening of Day 1	Drug: Placebo; Matching placebo capsules

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with Adverse Events (AEs)	An AE was defined as any untoward medical occurrence in a clinical investigation subject, which did not necessarily have a causal relationship with the treatment.	From baseline up to 7 days post-administration
Maximum plasma concentration (Cmax) of lucerastat after single ascending doses of lucerastat	Cmax was determined directly from the observed plasma concentration-time curves of lucerastat in subjects receiving a single dose.	PK Blood samples were collected at pre-dose and at scheduled time points up to 24 hours post administration
Maximum plasma concentration (Cmax) of lucerastat after two daily doses of lucerastat	Cmax was determined directly from the observed plasma concentration-time curves of lucerastat in subjects receiving lucerastat twice daily.	PK Blood samples were collected at pre-dose and at scheduled time points up to 48 hours after the first administration
Time to reach Cmax (tmax) of lucerastat after single ascending doses of lucerastat	tmax was determined directly from the observed plasma concentration-time curves of lucerastat in subjectsreceiving a single dose.	PK Blood samples were collected at pre-dose and at scheduled time points up to 24 hours post administration
Time to reach Cmax (tmax) of lucerastat after two daily doses of lucerastat	tmax was determined directly from the observed plasma concentration-time curves of lucerastat in subjects receiving lucerastat twice daily.	PK Blood samples were collected at pre-dose and at scheduled time points up to 48 hours after the first administration
Area under the plasma concentration-time curves (AUC) of lucerastat after single ascending doses of lucerastat	AUC was calculated from time zero to time t (last PK blood sample in which drug was detected) and extrapolated to infinity for subjects receiving a single dose.	PK Blood samples were collected at pre-dose and at scheduled time points up to 24 hours post administration
Area under the plasma concentration-time curves (AUC) of lucerastat after two daily doses of lucerastat	AUC was calculated from time zero to time t (last PK blood sample in which drug was detected) and extrapolated to infinity for subjects receiving lucerastat twice daily	PK Blood samples were collected at pre-dose and at scheduled time points up to 48 hours after the first administration
Terminal elimination half-life (t1/2) of lucerastat after single ascending doses of lucerastat	t1/2 was calculated from the corresponding plasma concentrations-time curves for subjects receiving a single dose	PK Blood samples were collected at pre-dose and at scheduled time points up to 24 hours post administration
Terminal elimination half-life (t1/2) of lucerastat after two daily doses of lucerastat	t1/2 was calculated from the plasma concentrations-time curves for subjects receiving lucerastat twice daily	PK Blood samples were collected at pre-dose and at scheduled time points up to 48 hours after the first administration

Secondary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in heart rate	Up to 24 hours post administration
Change from baseline in blood pressure	Up to 24 hours post administration
Change from baseline in electrocardiogram (ECG) variables	Up to 24 hours post administration
Change from baseline in laboratory tests	Up to 24 hours post administration

Collaborators and Investigators

• Sponsor: Actelion
• Investigators: Nicolas Guérard, Actelion

Publications and helpful links

General Publications

• Guerard N, Morand O, Dingemanse J. Lucerastat, an iminosugar with potential as substrate reduction therapy for glycolipid storage disorders: safety, tolerability, and pharmacokinetics in healthy subjects. Orphanet J Rare Dis. 2017 Jan 14;12(1):9. doi: 10.1186/s13023-017-0565-9.

Study record dates

Study Major Dates

• Study Start: October 1, 2002
• Primary Completion (ACTUAL): December 1, 2002
• Study Completion (ACTUAL): December 1, 2002

Study Registration Dates

• First Submitted: October 24, 2016
• First Submitted That Met QC Criteria: October 24, 2016
• First Posted (ESTIMATE): October 26, 2016

Study Record Updates

• Last Update Posted (ESTIMATE): October 26, 2016
• Last Update Submitted That Met QC Criteria: October 24, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Keywords: safety; pharmacokinetics
• Other Study ID Numbers: OGT923-001

Plan for Individual participant data (IPD)

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