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

GlaxoSmithKline (GSK)

Status and phase: Completed; Phase 1

Conditions: Muscular Dystrophies

Treatments: Drug: 3 mg/kg GSK2402968; Drug: 9 mg/kg GSK2402968; Other: Placebo; Drug: 6 mg/kg GSK2402968; Drug: 12 mg/kg GSK2402968

Study type: Interventional

Funder types: Industry

Identifiers

NCT01128855

114118

Details and patient eligibility

About

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

Enrollment: 20 patients

Sex: Male

Ages: 9+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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20 participants in 4 patient groups

Cohort 1

Experimental group

Description:

3 mg/kg GSK2402968 / placebo

Treatment:

Drug: 3 mg/kg GSK2402968

Other: Placebo

Cohort 2

Experimental group

Description:

6 mg/kg GSK2402968 / placebo

Treatment:

Drug: 6 mg/kg GSK2402968

Other: Placebo

Cohort 3

Experimental group

Description:

9 mg/kg GSK2402968 / placebo

Treatment:

Other: Placebo

Drug: 9 mg/kg GSK2402968

Cohort 4

Experimental group

Description:

12 mg/kg GSK2402968 / placebo

Treatment:

Other: Placebo

Drug: 12 mg/kg GSK2402968