Healthy Subjects
Conditions
Keywords
Pharmacokinetics, Safety
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.
Interventions
DRUGLucerastat
Capsule for oral administration containing lucerastat
DRUGPlacebo
Placebo capsules matching lucerastat capsules
Sponsors
Idorsia Pharmaceuticals Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in heart rate after multiple doses of lucerastat | Up to Day 9 | — |
| Dose proportionality in lucerastat pharmacokinetics assessed by area under the concentration-time curve (AUC) | 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 | AUC from time zero to infinity \[AUC(0-inf)\] was used to assess dose proportionality across all dose groups |
| Terminal elimination half-life (t1/2) | 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 | t1/2 was calculated from the plasma concentrations-time curves of lucerastat after multiple doses |
| Food effect on lucerastat pharmacokinetics assessed by Cmax | PK blood samples were collected on Day 1, at pre-dose and at scheduled time points up to 12 hours after the morning dose | Potential food effect on pharmacokinetic parameters of lucerastat was tested by comparing Cmax in fed vs fasted state in the 500 mg cohort (cohort 2) |
| Food effect on lucerastat pharmacokinetics assessed by AUC | PK blood samples were collected on Day 1, at pre-dose and at scheduled time points up to 12 hours after the morning dose | Potential food effect on pharmacokinetic parameters of lucerastat was tested by comparing AUC in fed versus fasted state in the 500 mg cohort (cohort 2) |
| Number of participants with adverse events (AEs) | From baseline up to Day 14 (end of study) | 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 |
| Change from baseline in haematology after multiple doses of lucerastat | Up to Day 9 | — |
| Change from baseline in clinical chemistry after multiple doses of lucerastat | Up to Day 9 | — |
| Dose proportionality in lucerastat pharmacokinetics assessed by maximum plasma concentration (Cmax) | PK blood samples were collected on Day 7, at pre-dose and at scheduled time points up to 48 hours after the morning dose | Cmax was used to assess dose proportionality across all dose groups |
Secondary
| Measure | Time frame |
|---|---|
| Change from baseline in electrocardiogram (ECG) variables after a single dose of lucerastat | Up to 24 hours post dose |
| Change from baseline in haematology after a single dose of lucerastat | At 24 hours post dose |
| Change from baseline in clinical chemistry after a single dose of lucerastat | At 24 hours post dose |
| Change from baseline in heart rate after a single dose of lucerastat | At 24 hours post dose |
| Stool frequency after multiple doses of lucerastat | Every day up to Day 9 |
| Change from baseline in body weight after multiple doses of lucerastat | At Day 9 |
| Change from baseline in blood pressure after a single dose of lucerastat | Up to 24 hours post dose |
Countries
United Kingdom
Outcome results
None listed