The effects of 1-month administration of asoprisnil (J867), a selective progesterone receptor modulator, in healthy premenopausal women.
BACKGROUND
Asoprisnil (J867) is a novel selective progesterone receptor modulator (SPRM) that exhibits partial agonist and antagonist activities and tissue selective effects. This double-blind, dose-escalation study was conducted to evaluate the effects of asoprisnil in 60 regularly cycling premenopausal women.


METHODS
Asoprisnil or placebo was administered orally for 28 days starting at the beginning of the menstrual cycle in doses of 5 mg once daily (QD), 5 mg twice daily (BID), 10 mg QD, 25 mg QD, 25 mg BID and 50 mg BID. Within each dose group, two women were randomized to placebo and eight to asoprisnil. Progesterone concentrations indicative of luteinization were defined as at least one progesterone measurement during the luteal phase exceeding 3.5 ng/ml.


RESULTS
Asoprisnil consistently prolonged the menstrual cycle at doses > or = 10 mg QD. However, the effects on luteal phase progesterone indicative of luteinization were inconsistent and lacked dose dependency. Asoprisnil suppressed periovulatory estradiol but not below follicular phase levels. No significant changes were observed in cortisol and prolactin. Asoprisnil was well tolerated.


CONCLUSIONS
Asoprisnil reversibly suppressed menstruation at doses > or = 10 mg QD irrespective of the effect on luteal phase progesterone concentrations indicative of luteinization. It induces amenorrhea primarily by targeting the endometrium in the absence of estrogen deprivation.
Chwalisz
Kristof
K
TAP Pharmaceutical Products Inc., Lake Forest, IL 60045, USA. Kristof.Chwalisz@TAP.com
Elger
Walter
W
Stickler
Therese
T
Mattia-Goldberg
Cynthia
C
Larsen
Lois
L
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood; D004311:Double-Blind Method; D004717:Endometrium / Q000166:cytology / Q000187:drug effects; D004958:Estradiol / Q000097:blood; D004963:Estrenes; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008183:Luteal Phase / Q000187:drug effects*; D034461:Luteinization / Q000187:drug effects; D007986:Luteinizing Hormone / Q000097:blood; D008875:Middle Aged; D009842:Oligopeptides; D010091:Oximes / Q000008:administration & dosage* / Q000009:adverse effects; D010120:Oxytocics / Q000008:administration & dosage* / Q000009:adverse effects; D017697:Premenopause; D011374:Progesterone / Q000097:blood; D011980:Receptors, Progesterone / Q000378:metabolism*; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism
D004963:Estrenes; D009842:Oligopeptides; D010091:Oximes; D010120:Oxytocics; D011980:Receptors, Progesterone; D012738:Sex Hormone-Binding Globulin; D011374:Progesterone; D004958:Estradiol; D019314:Dehydroepiandrosterone Sulfate; C118154:BIO 1211; C488516:asoprisnil; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D006854:Hydrocortisone