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Oral Ifetroban in Subjects With Duchenne Muscular Dystrophy (DMD)

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ClinicalTrials.gov Identifier: NCT03340675
Recruitment Status : Not yet recruiting
First Posted : November 13, 2017
Last Update Posted : October 17, 2018
Sponsor:
Collaborator:
Vanderbilt University Medical Center
Information provided by (Responsible Party):
Cumberland Pharmaceuticals

November 3, 2017
November 13, 2017
October 17, 2018
February 2019
December 2021   (Final data collection date for primary outcome measure)
Incidence of Treatment-Emergent Adverse Events (safety & tolerability) [ Time Frame: Baseline through 12 months ]
Percentage of subjects with one or more treatment emergent adverse event
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [ Time Frame: Baseline through 12 months ]
number of subjects with one or more treatment emergent adverse event
Complete list of historical versions of study NCT03340675 on ClinicalTrials.gov Archive Site
  • Pharmacokinetics [ Time Frame: Day 0 and Day 7 ]
    Peak plasma concentration of ifetroban and its acyl glucuronide metabolite after administration
  • Change from baseline in left ventricular ejection fraction [ Time Frame: Baseline through 12 months ]
    There should be no change in left ventricular ejection fraction. Patients with DMD have a decline.
  • Change from baseline in pulmonary function [ Time Frame: Baseline through 12 months ]
    Change from baseline in forced expiratory volume in 1 second
  • Change from baseline in quality-of-life [ Time Frame: Baseline through 12 months ]
    The 23 items PedQL measure these core dimensions of health as delineated by the World Health Organization, as well as role (school) functioning. Items measured include 1) Physical Functioning (8 items), 2) Emotional Functioning (5 items), 3) Social Functioning (5 items), and 4) School Functioning (5 items). Each item is measured on a 5 point Likert scale with 0 indicating never and 4 indicating almost always.The Likert scores are reversed scored and linearly transform to a 0-100 scale with 0=100, 1-75, 2=50, 5=25, and 4=0. A higher score indicates better health-related quality of life.
  • Peak plasma concentration of ifetroban and its acyl glucuronide metabolite after administration [Pharmacokinetics] [ Time Frame: Day 0 (first dose) and at Month 6 (steady state) ]
    Peak plasma concentration of ifetroban and its acyl glucuronide metabolite after administration.
  • Change from baseline in myocardial strain (a sensitive measure of heart function using cardiac MRI) [Efficacy] [ Time Frame: Baseline and 12 months ]
    There should be no change in myocardial strain. Patients with DMD are likely to have an increase in myocardial strain over time (2% or more in 12 months)
  • Change from baseline in forced expiratory volume in 1 second (FEV1) [Pulmonary function] [ Time Frame: Baseline and 12 months ]
    a low FEV1 indicates poor pulmonary function; normal values for FEV1 vary from person to person. Each person has their own predicted FEV1 value.
  • Pediatric Quality of Life Inventory including Neuromuscular module [Quality of life] [ Time Frame: Baseline and 12 months ]
    0-100 scale; the higher the score indicates better health-related quality of life
Not Provided
Not Provided
 
Oral Ifetroban in Subjects With Duchenne Muscular Dystrophy
A Randomized, Double-Blind, Placebo-Controlled, Multiple Dose Study With an Open-Label Extension to Determine the Safety, Pharmacokinetics and Efficacy of Oral Ifetroban in Subjects With Duchenne Muscular Dystrophy
Duchenne muscular dystrophy (DMD) is a devastating X-linked disease which leads to loss of ambulation between ages 7 and 13, respiratory failure and cardiomyopathy (CM) at any age, and inevitably premature death of affected young men in their late twenties. DMD is the most common fatal genetic disorder diagnosed in childhood. It affects approximately 1 in every 3,500 live male births across all races and cultures, and results in 20,000 new cases each year worldwide.Significant advances in respiratory care have unmasked CM as the leading cause of death. As there are yet no specific cardiac treatments to extend life, the current study aims to address this unmet medical need using a new therapeutic strategy for patients with DMD.
This is a phase 2 randomized, double-blind, placebo-controlled, multiple dose study with an optional open-label extension to determine the safety, pharmacokinetics and efficacy of two doses of oral ifetroban in subjects with DMD. DMD patients who meet the inclusion criteria and none of the exclusion criteria will receive oral ifetroban or placebo once daily for 12 months. Subjects will be enrolled onto one of three treatment groups, low-dose ifetroban, high-dose ifetroban or placebo. Each dose level will be evaluated by eight subjects with early stage (LVEF > 45%) DMD-associated cardiomyopathy and eight subjects with more advanced stage (LVEF 35-45%) cardiac disease as there may be differences in the treatment effect based on cardiac involvement. Each subject treated will be evaluated for first-dose and steady-state exposure PK. All subjects who receive treatment will be assessed for safety. All subjects with at least one efficacy assessment post-baseline will be evaluated for efficacy. Blood and urine will be collected for standard and novel cardiac biomarkers.
Interventional
Phase 2
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Randomized, placebo-controlled, double-blind, dose-ranging
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
Each individual bottle is labelled with a unique numeric code that identifies the contents to the unblinded sponsor representative.
Primary Purpose: Treatment
  • Duchenne Muscular Dystrophy Cardiomyopathy
  • Cardiomyopathy, Dilated
  • Drug: Ifetroban
    Weight based, once daily oral ifetroban
  • Drug: Placebo
    Matching oral placebo
  • Experimental: Oral Ifetroban - Low Dose
    Weight based, once daily oral ifetroban
    Intervention: Drug: Ifetroban
  • Experimental: Oral Ifetroban - High Dose
    Weight based, once daily oral ifetroban
    Intervention: Drug: Ifetroban
  • Placebo Comparator: Placebos
    Matching Placebo
    Intervention: Drug: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Not yet recruiting
48
32
December 2021
December 2021   (Final data collection date for primary outcome measure)

Inclusion criteria:

  1. Males 7 years of age and older with the diagnosis of DMD, defined as phenotype consistent with DMD and either positive genotype, first degree relative with positive genotype, or confirmatory muscle biopsy.
  2. Stable dose of oral corticosteroids for at least 8 weeks or has not received corticosteroids for at least 30 days.
  3. Stable cardiac function defined as change in left ventricular ejection fraction (LVEF) of < 15% and no heart failure admission over the last 12 months; LVEF 35% or greater by cine cardiac magnetic resonance imaging (MRI) or echocardiography; myocardial damage in one or more left ventricular segments evident by late gadolinium enhancement allowed; concurrent angiotensin-converting enzyme inhibitors (ACEI), beta-blocker (BB) or angiotensin receptor blocker (ARB) therapy allowed (selection of which dictated by clinical care) if started three months or greater from first dose of IMP without change in dose. Aldosterone receptor antagonists (eg. Spironolactone or eplerenone) allowed if started 12 months or greater from first dose of Investigational Medicinal Product (IMP). No changes throughout the study allowed.
  4. Subjects aged 18 years and older, informed consent obtained directly. For subjects ages 7-17 years old (yo), both assent from the subject and permission from a parent or guardian.

Exclusion criteria:

  1. Clinically significant illness other than DMD
  2. Clinically significant laboratory abnormality not associated with DMD
  3. Major surgery within six weeks prior to the first dose of study drug, or planned surgery during this study which would interfere with the ability to perform study procedures
  4. Require antiarrhythmic therapy and/or initiation of diuretic therapy for management of acute heart failure in the last 6 months
  5. A LVEF of < 35% by CMR and/or fractional shortening of < 15% based on echocardiography (ECHO) during screening
  6. A known bleeding disorder or has received anticoagulant treatment within 2 weeks of study entry
  7. Allergy to gadolinium contrast or known renal insufficiency defined as abnormal cystatin C or creatinine above the upper limit of normal for age. The male serum reference ranges as follows:

    • Age 7-9 years - 0.2-0.6 mg/dL
    • Age 10-11 years - 0.3-0.7 mg/dL
    • Age 12-13 years - 0.4-0.8 mg/dL
    • Age 14-15 years - 0.5-0.9 mg/dL
    • Age 16 years or older - 0.8-1.3 mg/dL
  8. Non-MR compatible implants (e.g. neurostimulator, automatic implantable cardioverter-defibrillator [AICD])
  9. Subjects who participated in a therapeutic clinical trial within 30 days or five half-lives (whichever is longer) of study entry
  10. Any other condition that could interfere with the subject's participation
Sexes Eligible for Study: Male
7 Years and older   (Child, Adult, Older Adult)
No
Contact: Ines M Macias-Perez, PhD 6159795778 imaciasperez@cumberlandpharma.com
Contact: Byron Kaelin, RN 6156274121 bkaelin@cumberlandpharma.com
Not Provided
 
 
NCT03340675
CPI-IFE-007
Yes
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Plan to Share IPD: No
Cumberland Pharmaceuticals
Cumberland Pharmaceuticals
Vanderbilt University Medical Center
Principal Investigator: Larry Markham, MD Vanderbilt University School of Medicine
Cumberland Pharmaceuticals
October 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP