Methods of improving myocardial performance in fontan patients using udenafil compositions
Inventors
Yeager, James L. • Goldberg, David J. • Paridon, Stephen M.
Assignees
Mezzion Pharma Co Ltd • Childrens Hospital of Philadelphia CHOP
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Publication Number
US-10137128-B2
Publication Date
2018-11-27
Expiration Date
Abstract
The present invention relates generally to the field of using udenafil or a pharmaceutically acceptable salt thereof in patients who have undergone the Fontan operation.
Core Innovation
The invention relates to a method of treating an adolescent with single ventricle heart disease whose exercise capacity is adversely affected due to a decline in the adolescent’s heart function after Fontan palliation. The method improves the adolescent’s exercise capacity or increases the likelihood of improving the adolescent’s exercise capacity as determined by maximum oxygen uptake at maximum exercise output (VO2 measurement). The human adolescent is between about 12 years old and under about 18 years old, and has undergone Fontan surgery.
The method comprises orally administering, in accordance with a treatment regimen, an oral dosage form comprising an effective dose of udenafil or a pharmaceutically acceptable salt thereof. The oral dosage is administered to improve the adolescent’s VO2 measurement or to increase the likelihood of improving the adolescent’s VO2 measurement for improving the adolescent’s exercise capacity or increasing the likelihood of improving the adolescent’s exercise capacity.
The invention further specifies an effective dose and regimen for udenafil in the adolescent Fontan population. One embodiment specifies an effective dose of about 87.5 mg with the treatment regimen comprising orally administering the oral dosage form twice daily. Another embodiment specifies that the total daily dose is from about 125 mg to about 175 mg.
Claims Coverage
The document includes two independent claims directed to oral administration of udenafil, or a pharmaceutically acceptable salt thereof, to adolescents between about 12 years old and under about 18 years old with single ventricle heart disease after Fontan surgery, aiming to improve exercise capacity or the likelihood of improvement as determined by VO2 measurement. The two independent claims differ in the quantitative dosing constraints.
Oral udenafil to improve VO2-based exercise capacity after Fontan surgery
Orally administering to a human adolescent who has undergone Fontan surgery and has single ventricle heart disease an oral dosage form comprising an effective dose of udenafil, or a pharmaceutically acceptable salt thereof, to improve the adolescent’s VO2 measurement or to increase the likelihood of improving the adolescent’s VO2 measurement for improving the adolescent’s exercise capacity or increasing the likelihood of improving the adolescent’s exercise capacity.
87.5 mg twice-daily oral regimen for VO2 improvement
Wherein the effective dose of udenafil, or a pharmaceutically acceptable salt thereof, is about 87.5 mg and the treatment regimen comprises orally administering the oral dosage form twice daily.
Total daily dose range for VO2-based exercise capacity improvement
Wherein the human adolescent is between about 12 years old and under about 18 years old and the total daily dose of udenafil, or a pharmaceutically acceptable salt thereof, is from about 125 mg to about 175 mg.
Overall, the claim coverage centers on treating adolescents with single ventricle heart disease after Fontan surgery using orally administered udenafil, or a pharmaceutically acceptable salt thereof, to improve exercise capacity measured by VO2 at maximum exercise output, with quantitative constraints defined as about 87.5 mg administered twice daily or a total daily dose range of about 125 mg to about 175 mg.
Stated Advantages
Improving the adolescent’s exercise capacity.
Increasing the likelihood of improving the adolescent’s exercise capacity.
Improving the adolescent’s VO2 measurement or increasing the likelihood of improving the adolescent’s VO2 measurement.
Documented Applications
Treating adolescents with single ventricle heart disease after Fontan palliation/surgery to ameliorate decline in myocardial performance, pulmonary vascular resistance, and exercise capacity, using endpoints including ventricular performance, vascular function, and quality/safety considerations.
Phase I/II pharmacokinetic/safety and short-term pharmacodynamic exercise/vascular/echo studies in adolescents (12 to <18), with reported exercise/vascular/MPI measurements and no serious AEs.
Planned Phase III randomized double-blind trial using 87.5 mg twice daily in adolescents post-Fontan.
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