Claims for Patent: 12,458,649

Summary for Patent: 12,458,649

Title:	Contraceptive compositions with reduced adverse effects
Abstract:	The present invention relates to a combined oral contraceptive with a reduced risk for side effects, including a reduced risk for QT interval prolongation, a reduced risk for testosterone decrease and a reduced risk for elevated C-reactive protein levels when compared to other combined oral contraceptives. The estetrol/drospirenone combined oral contraceptive described herein shows favorable pharmacokinetics for the progestogenic component. Use of a specific estrogenic component in the combined oral contraceptive entails multiple benefits over currently available combined oral contraceptives.
Inventor(s):	Jean-Michel Foidart
Assignee:	Estetra SRL
Application Number:	US17/701,588
Patent Claims:	1. A method of treating or reducing the risks of one or more drospirenone (DRSP)-related adverse effects associated with use of a combined oral contraceptive (COC) comprising a progestogenic component comprising DRSP and an estrogenic component in a female subject in need thereof, wherein the female subject has experienced one or more DRSP-related adverse effects, the method comprising administering daily to the female subject a daily active dosage unit of an estetrol/DRSP COC comprising 10 mg to 20 mg of estetrol as the estrogenic component and 1 mg to 5 mg of DRSP as the progestogenic component, wherein the method is effective to treat or reduce the risks of one or more DRSP-related adverse effects selected from (i) QT interval prolongation of at least 5 milliseconds and (ii) increase of C-reactive protein blood plasma concentration to an elevated level, each as compared to a comparator COC comprising DRSP and an estrogenic component comprising an estrogen other than estetrol, and wherein the daily administration of the estetrol/DRSP COC results in a pharmacokinetic profile for DRSP in blood plasma of the female subject having one or both of (i) a geometric mean AUC0-24 of DSRP between about 150 and about 1000 ng·h/ml and (ii) a geometric mean Cmax of DSRP between about 10 ng/ml and 100 ng/ml. 2. The method of claim 1, wherein the daily active dosage unit is provided in a contraceptive kit comprising one or more packaging units each comprising 21 to 28 of the daily active dosage units. 3. The method of claim 1, wherein the daily active dosage unit is administered continuously in cycles of 21 to 28 daily administrations. 4. The method of claim 1, wherein the comparator COC comprises ethinyl-estradiol (EE) as the estrogen other than estetrol. 5. The method of claim 1, wherein the method is effective to reduce the risks of QT interval prolongation of at least 5 milliseconds. 6. The method of claim 5, wherein a risk of experiencing QT interval prolongation of at least 5 milliseconds is reduced by at least 10% as compared to the risk associated with the comparator COC. 7. The method of claim 5, wherein a mean QT interval prolongation of the female subject administered the estetrol/DRSP COC is at least 20% shorter than that of a subject administered the comparator COC. 8. The method of claim 5, wherein the daily active dosage unit has reduced estrogenic-related effects on the QT interval as compared to the comparator COC. 9. The method of claim 1, wherein the method is effective to reduce the risks of an increase in C-reactive protein blood plasma concentration to an elevated level. 10. The method of claim 9, wherein the method is effective to reduce the risks of an increase in C-reactive protein blood plasma concentration to an elevated level that is at least 10% higher than a baseline value, wherein the baseline value is the C-reactive protein blood plasma concentration in the female subject before administration of a COC comprising DRSP. 11. The method of claim 9, wherein the C-reactive protein blood plasma concentration in the female subject administered the estetrol/DRSP COC is less than 2.00 mg/L. 12. The method of claim 1, wherein the daily active dosage unit is administered in periodic cycles each comprising an administration-free interval of 4 to 7 days. 13. The method of claim 1, wherein a single daily active dosage unit comprises about 15 mg drospirenone and about 3 mg estetrol.