A Study to Assess the Safety, Tolerability and Pharmacokinetics of Lucerastat (CDP923) After Multiple Dosing in Healthy Subjects
- Registration Number
- NCT02944474
- Lead Sponsor
- Actelion
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 37
- 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.
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohort 2 (500 mg) Lucerastat Six subjects received 500 mg of lucerastat as a single dose in the morning of Day 1 in fed conditions. After a 5-day washout, they received the same dose twice daily for 7 consecutive days in fasting conditions Placebo cohorts 1 to 4 Placebo Twelve subjects received matched placebo (3 subjects per cohort, except for Cohort 3 where 4 subjects received placebo) Cohort 1 (200 mg) Lucerastat Six subjects received 200 mg of lucerastat twice daily for 7 consecutive days in fasting conditions Cohort 3 (500 mg) Lucerastat Six subjects received 500 mg of lucerastat twice daily for 7 consecutive days in fasting conditions Cohort 4 (1000 mg) Lucerastat Six subjects received 1 g of lucerastat for 7 consecutive days in fasting conditions
- Primary Outcome Measures
Name Time Method 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)
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
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 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 mutliple doses of lucerastat Up to Day 9 Change from baseline in heart rate after mutliple doses of lucerastat Up to Day 9
- Secondary Outcome Measures
Name Time Method Change from baseline in body weight after multiple doses of lucerastat At Day 9 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 Change from baseline in blood pressure after a single dose of lucerastat Up to 24 hours post dose Change from baseline in electrocardiogram (ECG) variables after a single dose of lucerastat Up to 24 hours post dose Stool frequency after multiple doses of lucerastat Every day up to Day 9
Trial Locations
- Locations (1)
Investigator Site
🇬🇧Edinburgh, United Kingdom