Clinical trial NCT02944474: A Study to Assess the Safety, Tolerability and Pharmacokinetics of Lucerastat (CDP923) After Multiple Dosing in Healthy Subjects
Official title: A Randomised Double-blind, Placebo-controlled, Ascending Multiple Dose Phase 1 Study of CDP923 in Healthy Volunteers to Assess Safety, Tolerability, Pharmacokinetics and Food Effect
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Subjects
Keywords: Pharmacokinetics
Safety
Lead sponsor: Idorsia Pharmaceuticals Ltd.
Sponsor class: INDUSTRY
First posted: 2016-10-26
Enrollment: 37
Sex: MALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: The objectives of this study were to evaluate the safety and tolerability of lucerastat and to determine its pharmacokinetic profile after multiple dosing. Also, the potential effect of food on the pharmacokinetics of lucerastat was explored following a single dose of 500 mg.

Detailed description: The subjects were to be enrolled sequentially to three dose groups, starting with the lowest dose level. Subjects could participate in only one Group. Progression to an increased dose of lucerastat was permitted only after review of all data from the previous cohort suggested that it was safe to do so.

Eligibility criteria: 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.

Primary outcomes:
measure: Dose proportionality in lucerastat pharmacokinetics assessed by maximum plasma concentration (Cmax)
timeFrame: PK blood samples were collected on Day 7, at pre-dose and at scheduled time points up to 48 hours after the morning dose
measure: Dose proportionality in lucerastat pharmacokinetics assessed by area under the concentration-time curve (AUC)
timeFrame: PK blood samples were collected on Day 7, at pre-dose and at scheduled time points up to 48 hours after the morning dose on Day 7
measure: Terminal elimination half-life (t1/2)
timeFrame: PK blood samples were collected on Day 7, at pre-dose and at scheduled time points up to 48 hours after the morning dose on Day 7
measure: Food effect on lucerastat pharmacokinetics assessed by Cmax
timeFrame: PK blood samples were collected on Day 1, at pre-dose and at scheduled time points up to 12 hours after the morning dose
measure: Food effect on lucerastat pharmacokinetics assessed by AUC
timeFrame: PK blood samples were collected on Day 1, at pre-dose and at scheduled time points up to 12 hours after the morning dose
measure: Number of participants with adverse events (AEs)
timeFrame: From baseline up to Day 14 (end of study)
measure: Change from baseline in haematology after multiple doses of lucerastat
timeFrame: Up to Day 9
measure: Change from baseline in clinical chemistry after multiple doses of lucerastat
timeFrame: Up to Day 9
measure: Change from baseline in heart rate after multiple doses of lucerastat
timeFrame: Up to Day 9
Secondary outcomes:
measure: Change from baseline in haematology after a single dose of lucerastat
timeFrame: At 24 hours post dose
measure: Change from baseline in clinical chemistry after a single dose of lucerastat
timeFrame: At 24 hours post dose
measure: Change from baseline in heart rate after a single dose of lucerastat
timeFrame: At 24 hours post dose
measure: Change from baseline in blood pressure after a single dose of lucerastat
timeFrame: Up to 24 hours post dose
measure: Change from baseline in electrocardiogram (ECG) variables after a single dose of lucerastat
timeFrame: Up to 24 hours post dose
measure: Stool frequency after multiple doses of lucerastat
timeFrame: Every day up to Day 9
measure: Change from baseline in body weight after multiple doses of lucerastat
timeFrame: At Day 9
Other outcomes:
Locations:
city: Edinburgh
country: United Kingdom
facility: Investigator Site
Study officials:
affiliation: Idorsia Pharmaceuticals Ltd.
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.