A Double-blind, Escalating Dose, Randomized, Placebo-controlled Study Assessing PK, Safety, Tolerability in Non-ambulant DMD Subjects (DEMAND I)

A Double-blind, Escalating Dose, Randomized, Placebo-controlled Study to Assess the Pharmacokinetics, Safety and Tolerability of Single Subcutaneous Injections of GSK2402968 in Non-ambulant Subjects With Duchenne Muscular Dystrophy

The purpose of this study is investigate the pharmacokinetics, safety and tolerability of single subcutaneous administration of GSK2402968 in non-ambulant boys with Duchenne muscular dystrophy

Study Overview

• Status: Completed
• Conditions: Muscular Dystrophies
• Intervention / Treatment: Drug: 3 mg/kg GSK2402968; Other: Placebo; Drug: 6 mg/kg GSK2402968; Drug: 9 mg/kg GSK2402968; Drug: 12 mg/kg GSK2402968

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• France
  • Paris cedex 13, France, 75651
    • GSK Investigational Site
• United States
  • Ohio
    • Columbus, Ohio, United States, 43205
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 9 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Duchenne muscular dystrophy resulting from a mutation in the DMD gene, confirmed by a sponsor approved DNA diagnostic technique covering all DMD gene exons, including but not limited to MLPA (Multiplex Ligation-dependent Probe Amplification), CGH (Comparative Genomic Hybridisation), SCAIP (Single Condition Amplification/Internal Primer) or H-RMCA (High-Resolution Melting Curve Analysis), and correctable by treatment with GSK2402968.
• Age 9 years old or greater at Screening;
• Male;
• Non-ambulant (at least 1 year in a wheelchair) within the last 4 years;
• Life expectancy at least three years;
• Willingness and ability to comply with all protocol requirements and procedures;
• QTc <450msec (based on single or average QTc value of triplicate ECGs obtained over a brief recording period). Note: QTc may be either QTcB or QTcF, machine read or manual overread;
• Subjects must be willing to use adequate contraception (condoms or abstinence), from Screening until at least 5 months after the last dose of study drug;
• Informed assent and/or consent in writing signed by the subject and/or parent(s)/legal guardian (according to local regulations).

Exclusion Criteria:

• Any additional mutation (such as an additional missing exon for DMD) that cannot be treated with GSK2402968;
• Current or history of liver or renal disease;
• Acute illness within 4 weeks of anticipated administration of study medication, which may interfere with study assessments;
• Use of anticoagulants, antithrombotics or antiplatelet agents, previous treatment with investigational drugs, idebenone or other forms of Coenzyme Q10, within 6 months of the first administration of study medication;
• Start of glucocorticosteroids within 6 months or non-stable use of glucocorticosteroids within 3 months of the anticipated first administration of study medication;
• Positive hepatitis B surface antigen (HbsAg), hepatitis C antibody test (HCV), or human immunodeficiency virus (HIV) test at Screening;
• Symptomatic cardiomyopathy;
• Use of alcohol from Screening through to the 1 month Follow-up visit ;
• Any Child in Care.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; 3 mg/kg GSK2402968 / placebo	Drug: 3 mg/kg GSK2402968; Weekly subcutaneous injection; Other: Placebo; Weekly Placebo
Experimental: Cohort 2; 6 mg/kg GSK2402968 / placebo	Other: Placebo; Weekly Placebo; Drug: 6 mg/kg GSK2402968; Weekly subcutaneous injection
Experimental: Cohort 3; 9 mg/kg GSK2402968 / placebo	Other: Placebo; Weekly Placebo; Drug: 9 mg/kg GSK2402968; Weekly subcutaneous injection
Experimental: Cohort 4; 12 mg/kg GSK2402968 / placebo	Other: Placebo; Weekly Placebo; Drug: 12 mg/kg GSK2402968; Weekly subcutaneous injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Primary Pharmacokinetic Variables:AUC, Cmax,t-max, CL/F	35 days
Incidence of Adverse Events	35 days
Incidence of Injection Site Reactions	35 days

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start (Actual): July 12, 2010
• Primary Completion (Actual): October 25, 2011
• Study Completion (Actual): October 25, 2011

Study Registration Dates

• First Submitted: May 20, 2010
• First Submitted That Met QC Criteria: May 21, 2010
• First Posted (Estimate): May 24, 2010

Study Record Updates

• Last Update Posted (Actual): July 18, 2017
• Last Update Submitted That Met QC Criteria: July 13, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Keywords: Duchenne Muscular Dystrophy; DMD; Duchenne; 968
• Additional Relevant MeSH Terms: Nervous System Diseases; Genetic Diseases, Inborn; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Muscular Disorders, Atrophic; Muscular Dystrophies
• Other Study ID Numbers: 114118