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

Study Overview
=================
Brief Summary
-----------------
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.

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

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

Conditions
-----------------
Healthy Subjects

Intervention / Treatment
-----------------
* Drug: Lucerastat
* Drug: Placebo


Participation Criteria
=================
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.

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

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single ascending doses of lucerastat<br>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<br>* Hard gelatin capsule for oral administration containing lucerastat<br>* Other names: ACT-434964;|
| Experimental: B.i.d. Dose Group<br>Subjects received two doses of lucerastat (2 x 1 g) 12 hours apart on Day 1 | Drug: Lucerastat<br>* Hard gelatin capsule for oral administration containing lucerastat<br>* Other names: ACT-434964;|
| Placebo Comparator: Placebo for singe ascending doses<br>These subjects received matching placebo administered orally in the morning of Day 1 | Drug: Placebo<br>* Matching placebo capsules<br>|
| Placebo Comparator: Placebo for b.i.d.Group<br>These subjects received matching placebo administered orally in the morning and in the evening of Day 1 | Drug: Placebo<br>* Matching placebo capsules<br>|

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 | Measure Description | 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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
safety, pharmacokinetics