A Double-blind, Escalating Dose, Randomized, Placebo-controlled Study Assessing PK, Safety, Tolerability in Non-ambulant DMD Subjects (DEMAND I)
Primary Purpose
Muscular Dystrophies
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
3 mg/kg GSK2402968
6 mg/kg GSK2402968
9 mg/kg GSK2402968
12 mg/kg GSK2402968
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Muscular Dystrophies focused on measuring Duchenne, Duchenne Muscular Dystrophy, DMD, 968
Eligibility Criteria
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.
Sites / Locations
- GSK Investigational Site
- GSK Investigational Site
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
Cohort 1
Cohort 2
Cohort 3
Cohort 4
Arm Description
3 mg/kg GSK2402968 / placebo
6 mg/kg GSK2402968 / placebo
9 mg/kg GSK2402968 / placebo
12 mg/kg GSK2402968 / placebo
Outcomes
Primary Outcome Measures
Primary Pharmacokinetic Variables:AUC, Cmax,t-max, CL/F
Incidence of Adverse Events
Incidence of Injection Site Reactions
Secondary Outcome Measures
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01128855
Brief Title
A Double-blind, Escalating Dose, Randomized, Placebo-controlled Study Assessing PK, Safety, Tolerability in Non-ambulant DMD Subjects
Acronym
DEMAND I
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
July 2017
Overall Recruitment Status
Completed
Study Start Date
July 12, 2010 (Actual)
Primary Completion Date
October 25, 2011 (Actual)
Study Completion Date
October 25, 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
GlaxoSmithKline
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Muscular Dystrophies
Keywords
Duchenne, Duchenne Muscular Dystrophy, DMD, 968
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
20 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cohort 1
Arm Type
Experimental
Arm Description
3 mg/kg GSK2402968 / placebo
Arm Title
Cohort 2
Arm Type
Experimental
Arm Description
6 mg/kg GSK2402968 / placebo
Arm Title
Cohort 3
Arm Type
Experimental
Arm Description
9 mg/kg GSK2402968 / placebo
Arm Title
Cohort 4
Arm Type
Experimental
Arm Description
12 mg/kg GSK2402968 / placebo
Intervention Type
Drug
Intervention Name(s)
3 mg/kg GSK2402968
Intervention Description
Weekly subcutaneous injection
Intervention Type
Drug
Intervention Name(s)
6 mg/kg GSK2402968
Intervention Description
Weekly subcutaneous injection
Intervention Type
Drug
Intervention Name(s)
9 mg/kg GSK2402968
Intervention Description
Weekly subcutaneous injection
Intervention Type
Drug
Intervention Name(s)
12 mg/kg GSK2402968
Intervention Description
Weekly subcutaneous injection
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Weekly Placebo
Primary Outcome Measure Information:
Title
Primary Pharmacokinetic Variables:AUC, Cmax,t-max, CL/F
Time Frame
35 days
Title
Incidence of Adverse Events
Time Frame
35 days
Title
Incidence of Injection Site Reactions
Time Frame
35 days
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
9 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
GSK Clinical Trials
Organizational Affiliation
GlaxoSmithKline
Official's Role
Study Director
Facility Information:
Facility Name
GSK Investigational Site
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43205
Country
United States
Facility Name
GSK Investigational Site
City
Paris cedex 13
ZIP/Postal Code
75651
Country
France
12. IPD Sharing Statement
Learn more about this trial
A Double-blind, Escalating Dose, Randomized, Placebo-controlled Study Assessing PK, Safety, Tolerability in Non-ambulant DMD Subjects
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