A Study to Assess the Safety, Tolerability and Pharmacokinetics of Lucerastat (CDP923) After Multiple Dosing in Healthy Subjects

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Healthy Subjects

Intervention / Treatment
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* Drug: Lucerastat
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1 (200 mg)<br>Six subjects received 200 mg of lucerastat twice daily for 7 consecutive days in fasting conditions | Drug: Lucerastat<br>* Capsule for oral administration containing lucerastat<br>* Other names: CDP923;|
| Experimental: Cohort 2 (500 mg)<br>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 | Drug: Lucerastat<br>* Capsule for oral administration containing lucerastat<br>* Other names: CDP923;|
| Experimental: Cohort 3 (500 mg)<br>Six subjects received 500 mg of lucerastat twice daily for 7 consecutive days in fasting conditions | Drug: Lucerastat<br>* Capsule for oral administration containing lucerastat<br>* Other names: CDP923;|
| Experimental: Cohort 4 (1000 mg)<br>Six subjects received 1 g of lucerastat for 7 consecutive days in fasting conditions | Drug: Lucerastat<br>* Capsule for oral administration containing lucerastat<br>* Other names: CDP923;|
| Placebo Comparator: Placebo cohorts 1 to 4<br>Twelve subjects received matched placebo (3 subjects per cohort, except for Cohort 3 where 4 subjects received placebo) | Drug: Placebo<br>* Placebo capsules matching lucerastat capsules<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose proportionality in lucerastat pharmacokinetics assessed by maximum plasma concentration (Cmax) | Cmax was used to assess dose proportionality across all dose groups | PK blood samples were collected on Day 7, at pre-dose and at scheduled time points up to 48 hours after the morning dose | 
| Dose proportionality in lucerastat pharmacokinetics assessed by area under the concentration-time curve (AUC) | AUC from time zero to infinity [AUC(0-inf)] was used to assess dose proportionality across all dose groups | 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 | 
| Terminal elimination half-life (t1/2) | t1/2 was calculated from the plasma concentrations-time curves of lucerastat after multiple doses | 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 | 
| Food effect on lucerastat pharmacokinetics assessed by Cmax | 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) | PK blood samples were collected on Day 1, at pre-dose and at scheduled time points up to 12 hours after the morning dose | 
| Food effect on lucerastat pharmacokinetics assessed by AUC | 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) | PK blood samples were collected on Day 1, at pre-dose and at scheduled time points up to 12 hours after the morning dose | 
| 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 Day 14 (end of study) | 
| 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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| Change from baseline in body weight after multiple doses of lucerastat |  | At Day 9 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pharmacokinetics, Safety