A Study of TAS-205 for Duchenne Muscular Dystrophy

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

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

Study Overview

• Status: Completed
• Conditions: Duchenne Muscular Dystrophy
• Intervention / Treatment: Drug: Placebo; Drug: TAS-205

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.

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Tokyo, Japan, 187-8551
    • National Center of Neurology and Psychiatry

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 15 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; 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
Active Comparator: TAS-205 low dose	Drug: TAS-205; 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
Active Comparator: TAS-205 middle dose	Drug: TAS-205; 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
Active Comparator: TAS-205 high dose	Drug: TAS-205; 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

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.

Collaborators and Investigators

• Sponsor: Taiho Pharmaceutical Co., Ltd.
• Investigators: Study Director: Taiho Pharmaceutical Co.,Ltd., Taiho Pharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start: September 1, 2014
• Primary Completion (Actual): June 1, 2015
• Study Completion (Actual): September 1, 2015

Study Registration Dates

• First Submitted: September 9, 2014
• First Submitted That Met QC Criteria: September 18, 2014
• First Posted (Estimate): September 22, 2014

Study Record Updates

• Last Update Posted (Actual): June 4, 2021
• Last Update Submitted That Met QC Criteria: May 11, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Muscular Disorders, Atrophic; Muscular Dystrophies; Muscular Dystrophy, Duchenne
• Other Study ID Numbers: Taiho10053030