Effect of Cimetidine on the Pharmacokinetics of Lucerastat in Healthy Subjects

Study Overview
=================
Brief Summary
-----------------
A study in healthy male subjects to investigate whether repeated administrations of cimetidine (a medication which decreases the amount of acid in the stomach) can affect the fate in the body (amount and time of presence in the blood) of lucerastat. Safety of the concomitant administration of the two treatments will also be assessed.

Official Title
-----------------
A Single-center, Open-label Study to Investigate the Effect of Cimetidine on the Pharmacokinetics of Lucerastat in Healthy Male Subjects

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

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


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Signed informed consent in the local language prior to any study-mandated procedure. Body mass index from 18.0 to 30.0 kg/m2 (inclusive) at Screening. Normal renal function confirmed by creatinine clearance ≥ 80 mL/min using Cockroft-Gault formula at Screening. Exclusion Criteria: Known hypersensitivity to cimetidine, lucerastat, or drugs of the same class, or any of their excipients. History or clinical evidence of any disease and/or existence of any surgical or medical condition, which might interfere with the absorption, distribution, metabolism, or excretion of the study treatment(s) (appendectomy and herniotomy allowed, cholecystectomy not allowed). 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

Primary Purpose: Other
Intervention Model: Sequential Assignment
Interventional Model Description: Fixed sequence
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment period A & B<br>Treatment period A: Subjects receive a single oral dose of 500 mg lucerastat on Day 1 under fasted conditions. Treatment period B: From Day 3 to Day 9, subjects receive a b.i.d. (every 12 h) oral dose of 800 mg cimetidine under fasted conditions (Treatment period B1; from Day 3 to Day 5). On Day 6, subjects receive a single oral dose of 500 mg lucerastat concomitantly with the morning dose of 800 mg cimetidine under fasted conditions (Treatment period B2; from Day 6 to Day 10). | Drug: Lucerastat<br>* Single oral dose of 500 mg lucerastat under fasted conditions<br>Drug: Cimetidine<br>* Twice daily oral dose of 800 mg cimetidine under fasted conditions<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax of lucerastat | Plasma PK parameter of lucerastat after single-dose oral administration of lucerastat alone and in combination with cimetidine | Up to 48 h after lucerastat administration on Day 1 (i.e., up to Day 3) and from pre-dose up to 96 h after lucerastat administration on Day 6 (i.e., up to Day 10); in total for up to 7 days | 
| Tmax of lucerastat | Plasma PK parameter of lucerastat after single-dose oral administration of lucerastat alone and in combination with cimetidine | Up to 48 h after lucerastat administration on Day 1 (i.e., up to Day 3) and from pre-dose up to 96 h after lucerastat administration on Day 6 (i.e., up to Day 10); in total for up to 7 days | 
| AUC(0-t) of lucerastat | Plasma PK parameter of lucerastat after single-dose oral administration of lucerastat alone and in combination with cimetidine | Up to 48 h after lucerastat administration on Day 1 (i.e., up to Day 3) and from pre-dose up to 96 h after lucerastat administration on Day 6 (i.e., up to Day 10); in total for up to 7 days | 
| AUC(0-inf) of lucerastat | Plasma PK parameter of lucerastat after single-dose oral administration of lucerastat alone and in combination with cimetidine | Up to 48 h after lucerastat administration on Day 1 (i.e., up to Day 3) and from pre-dose up to 96 h after lucerastat administration on Day 6 (i.e., up to Day 10); in total for up to 7 days | 
| AUC(0-48) of lucerastat | Plasma PK parameter of lucerastat after single-dose oral administration of lucerastat alone and in combination with cimetidine | Up to 48 h after lucerastat administration on Day 1 (i.e., up to Day 3) and from pre-dose up to 96 h after lucerastat administration on Day 6 (i.e., up to Day 10); in total for up to 7 days | 
| T1/2 of lucerastat | Plasma PK parameter of lucerastat after single-dose oral administration of lucerastat alone and in combination with cimetidine | Up to 48 h after lucerastat administration on Day 1 (i.e., up to Day 3) and from pre-dose up to 96 h after lucerastat administration on Day 6 (i.e., up to Day 10); in total for up to 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of treatment-emergent AEs |  | From Day 1 to End-of-Study (for up to 13 days) | 
| Number of treatment-emergent SAEs |  | From Screening to safety follow-up, i.e., 32 days after End-of-Study (for up to 63 days) |