Duchenne Muscular Dystrophy MedDRA version: 14.1 Level: PT Classification code 10013801 Term: Duchenne muscular dystrophy System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Sponsors
Eli Lilly and Company
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: • Males with proven DMD • Ages 7-14 years inclusive • Ambulant, defined as baseline 6MWD between 200 and 400 meters inclusive • 6MWD measurements within 20% of each other at a minimum of 2 pre-randomization assessments • Left ventricular ejection fraction (LVEF) =50% • Receiving corticosteroids for a minimum of 6 months immediately prior to screening, with no significant change in total daily dosage or dosing regimen (except those adjusting for weight changes) for a minimum of 3 months immediately prior to screening and a reasonable expectation that total daily dosage and dosing regimen will not change significantly (except for adjustments for weight) for the duration of the study. Corticosteroid treatment regimen can be daily, intermittent, high-dose weekend, or alternate days, but must be consistent with current clinical care recommendations. Are the trial subjects under 18? yes Number of subjects for this age range: 306 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • Symptomatic cardiomyopathy or heart failure (New York Heart Association Class III or IV) • Change (initiation, change in type of drug, dose modification, schedule modification, interruption, discontinuation, or reinitiating) in prophylactic treatment for heart failure within 3 months prior to start of study treatment • Cardiac rhythm disorder defined as sinus rhythm with ectopic contractions or conductance disturbances, or any rhythm other than sinus, observed on screening ECG • Use of continuous mechanical ventilator assistance. [Evening use of bilevel positive airway pressure (BPAP) or continuous positive airway pressure (CPAP) therapy is allowed] • Previous treatment with investigational drugs or interventions (including shock training system) within 3 months of the first administration of study medication, or planned use during the study • History of participation in gene or cell-based therapy • History of antisense oligonucleotide (AON) or stop codon read-through therapy • Unable to take orally administered tablets (without chewing, crushing or breaking), as assessed by the investigator • Use of L-arginine supplements within 4 weeks (+/- 1 day) of the first administration of study medication • Use of any pharmacologic treatment, other than corticosteroids, that might have an effect on muscle strength within 3 months prior to the start of study treatment (e.g., growth hormone, anabolic steroids including testosterone). Vitamin D, calcium, and combinations thereof will be allowed. • New or changed treatment with herbal or dietary supplements being taken with an expectation of an effect on muscle strength or function during 1 month prior to first dose of study drug. Patients taking herbal or dietary supplements as defined above with no change in type or dose for 1 month prior to first dose of study drug with no expectation of adding or changing supplements for the 48 week double-blind period may be enrolled. • Surgery that might have an effect on muscle strength or function within 3 months before study entry or planned surgery at any time during the study • Evidence of a lower limb injury that may in the judgment of the investigator affect performance on the 6MWD • Severe behavioral problems, including severe autism or attention deficit disorders, that may in the judgment of the investigator interfere with completion of the 6MWD • Any contraindication to tadalafil (use of any form of organic nitrate, either regularly and/or intermittently, or known serious hypersensitivity to tadalafil) • History of significant renal insufficiency, defined as receiving renal dialysis or having a screening serum cystatin C level = 2.35 mg/L • Clinical evidence of cirrhosis • Diagnosed with a retinal disorder (for example, hereditary retinal disorders, retinopathy of prematurity) • Have severe hypotension or uncontrolled hypertension as determined by the investigator • Current treatment with potent CYP3A4 inhibitors, such as antiretroviral therapy (protease inhibitor), systemic ketoconazole, or systemic itraconazole, or chronic use of potent CYP3A4 inducers, such as rifampicin • Currently receiving treatment with doxazosin, nitrates, or cancer therapy • Have known allergy to any of the excipients in tadalafil tablets, notably lactose • Current PDE5 inhibitor therapy or treatment within the past 6 months • Other medical condition deemed to place the patient at potential increased risk or reduced adherence to the st
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to test the hypothesis that once daily tadalafil administered orally for 48 weeks lessens the decline in ambulatory ability as measured by the 6MWD compared to placebo in boys with Duchenne muscular dystrophy (DMD).;Secondary Objective: Test the hypothesis that once daily tadalafil administered orally for 48 weeks compared with placebo in boys with DMD: o lessens the decline in North Star Ambulatory Assessment (NSAA) global score, o lessens the decline in performance on timed function tests: rise from floor from supine, 10 meter walk/run, stair climb and stair descend, o delays the time to persistent 10% worsening in the 6MWD, o delays the time to persistent 10% worsening in timed function tests: rise from floor from supine, 10 meter walk/run test, stair climb, and stair descend, o lessens the decline in Quality of Life (QoL), as measured by the Pediatric Outcomes Data Collection Instrument (PODCI) global functioning scale and the following core scales: Upper Extremity/Physical Functioning, Transfer/Basic Mobility and Sports/Physical Functioning. o Characterize the PK of tadalafil in pediatric DMD patients, and assess relationships between tadalafil exposure and efficacy and safety outcomes.;Primary end point(s): The primary efficacy measure is the 6MWD, and the primary endpoint will be the comparison of the change in the 6MWD after 48 weeks in tadalafil and placebo patients.;Timepoint(s) of evaluation of this end point: Screening, Week 0, Week 12, Week 24, Week 36, Week 48, Week 60, Week 96. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The North Star Ambulatory Assessment (NSAA) Timed function tests (rise from floor from supine, 10 meter walk/run, 4-stair climb/descend) Decline in Quality of Life (QoL), as measured by the Pediatric Outcomes Data Collection Instrument (PODCI);Timepoint(s) of evaluation of this end point: NSAA and 6MWD: Screening, Week 0, Week 12, Week 24, Week 36, Week 48, Week 60, Week 96. PODCI: Week 0, Week 12, Week 24, Week 48,Week 96 | — |
Countries
Argentina, Belgium, Canada, Denmark, France, Germany, Italy, Korea, Republic of, Netherlands, Russian Federation, Spain, Taiwan, United Kingdom, United States
Contacts
Public ContactClinical Trial Information
Eli Lilly
Outcome results
None listed