A Study of TAS-205 for Duchenne Muscular Dystrophy

Study Overview
=================
Brief Summary
-----------------
The objective of this study is to evaluate the safety and pharmacokinetic of TAS-205 in patients with Duchenne Muscular Dystrophy.

Detailed Description
-----------------
Duchenne Muscular Dystrophy (DMD) is the most common fatal genetic disorder diagnosed in childhood, affecting approximately 1 in every 3500 lives male births. DMD patients suffer from a relentless decline in muscle strength that impairs the ability of walking and breathing, resulting in their lives with wheelchairs and loss of upper body function. The objective of this study is to evaluate the safety and pharmacokinetic of TAS-205 after single and multiple doses in DMD patients. It is also evaluated if TAS-205 affects the urinary excretion of pharmacodynamic (PD) marker in DMD patients.

Official Title
-----------------
A Phase I Study of Single and Multiple Doses of TAS-205 in Patients With Duchenne Muscular Dystrophy

Conditions
-----------------
Duchenne Muscular Dystrophy

Intervention / Treatment
-----------------
* Drug: TAS-205
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Able to give an informed consent. If applicable, able to give an informed assent. Male and >= 5 years and < 16 years of age. Bodyweight of >= 15.0 kg and < 75.0 kg. Phenotypic evidence of DMD. Able to take tablets. If taking oral glucocorticosteroids no significant change in total daily dosage or dosing regimen after enrollment. Confirmed the urinary PD marker over its criteria. Able to follow the study protocol. Exclusion Criteria: Current diagnosis or history of any drug allergy. A forced vital capacity (FVC) < 50% of predicted value. A left ventricular ejection fraction (EF) < 50% or fractional shortening (FS) < 25% based on echocardiogram (ECHO). Ongoing immunosuppressive therapy (other than corticosteroids). With severe disease such as hepatic disease, kidney disease and others. With any systemic allergic disease or any chronic inflammatory disease. Treated with any other investigational agents within 90 days. Positive reaction in hepatitis B surface antigen (HbsAg), hepatitis C antibody test (HCV), or human immunodeficiency virus (HIV) test.

Ages Eligible for Study
-----------------
Minimum Age: 5 Years
Maximum Age: 15 Years

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

Accepts Healthy Volunteers
-----------------
No

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

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Single-dose phase: 3steps (low dose, middle dose or high dose group), 2 patients/step, single oral administration after meals Multiple-dose phase: 3 steps (low dose, middle dose or high dose group), 2 patients/step (the same patients between single- and multiple-dose phases), repeated oral administration for 7 days, BID after meals<br>|
| Active Comparator: TAS-205 low dose<br> | Drug: TAS-205<br>* Single-dose phase: 3 steps (low dose, middle dose or high dose group), 5 patients/step, single oral administration after meals Multiple-dose phase: 3 steps (low dose, middle dose or high dose group), 5 patients/step (the same patients between single- and multiple-dose phases), repeated oral administration for 7 days, BID after meals<br>|
| Active Comparator: TAS-205 middle dose<br> | Drug: TAS-205<br>* Single-dose phase: 3 steps (low dose, middle dose or high dose group), 5 patients/step, single oral administration after meals Multiple-dose phase: 3 steps (low dose, middle dose or high dose group), 5 patients/step (the same patients between single- and multiple-dose phases), repeated oral administration for 7 days, BID after meals<br>|
| Active Comparator: TAS-205 high dose<br> | Drug: TAS-205<br>* Single-dose phase: 3 steps (low dose, middle dose or high dose group), 5 patients/step, single oral administration after meals Multiple-dose phase: 3 steps (low dose, middle dose or high dose group), 5 patients/step (the same patients between single- and multiple-dose phases), repeated oral administration for 7 days, BID after meals<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Adverse Events | Source Vocabulary Name for Table Default: CTCAE (4.03) | From the first administration day to the end of the observation period (ie. single-dose phase: 8 days, multiple-doses phase: 14 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak Plasma Concentration (Cmax) of TAS-205 | Due to inspection missing, some data were not analyzed. | Single-dose phase: immediately before dosing, 0, 0.5, 1, 2, 4, 8, 24, 48 hours post-dose, Multiple-dose phase: Days 1 and 7, immediately before morning dose, 0.5, 1, 2, 4, and 8 hours post-dose and Day 4, immediately before morning dose. | 
| Area Under the Plasma Concentration Versus Time Curve (AUC) of TAS-205 | Due to inspection missing, some data were not analyzed. | Administration period (ie. single-dose phase: from single administration day to 48 hours after the administration, multiple-dose phase: from the first administration day to 8 hours after the last administration) | 
| The Urinary Excretion of PD Marker | Ratio of prostaglandin E2 metabolite / creatinine Due to inspection missing, some data were not analyzed. | Single-dose: Day -1 before administration, 0-24 hr post-dose, and 24-48 hr post-dose, Multiple-doses: Day -1 before administration, 0 hr after administration on Day 1 and 4 to the following day (Day 2 and 5), and 0-24 hr after administration on Day 7. |