Comparative Pharmacodynamic Effects of Abarelix Depot-F vs. Lupron Depot® in Women with Endometriosis-Associated Pain

Abstract

Objectives: Abarelix depot-F is a sustained release formulation of the potent, pure GnRH receptor antagonist, abarelix. Abarelix is devoid of any stimulatory activity at the GnRH receptor and therefore overcomes a significant drawback inherent to all GnRH agonists. The objectives of this study were to examine the dose-dependent pharmacodynamic effects of abarelix depot-F administered by SC injection and compare them to those of Lupron Depot® administered IM in women with endometriosis.Design: In a randomized, parallel arm, dose ranging study, 30, 60, 90, and 120 mg abarelix depot-F (SC) and 3.75 mg Lupron Depot® (IM) were compared by administering drug to women with endometriosis-associated pain.Materials and Methods: Blood samples were collected at frequent time intervals post-dose for determination of circulating abarelix, estradiol (E2), luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels.Results: Preliminary results indicate that all doses of abarelix depot-F were well tolerated. Administration of abarelix depot-F produced a decrease in serum E2 as early as 4 hours (−1% to −17%) with peak inhibitory effect at 7 days (−70%) for all abarelix depot-F doses. In contrast, injection of Lupron Depot® caused an E2 surge detectable as early as 4 hours (15%) with a peak at 7 days (+487%). An inhibitory effect of abarelix on LH (−39 to −60%) and FSH (−11 to −15%) levels was observed at 2 hours at all study doses. In contrast, Lupron Depot® injection caused an immediate surge of LH and FSH levels, peaking at 4 hours post-dose with mean concentrations 7 and 15 times higher, respectively, than pre-dose LH and FSH levels.Conclusions: These study results confirm that abarelix depot-F acts in women with a very rapid onset of action and effect. By providing rapid inhibition of LH, FSH and E2 production, avoidance of hormonal flare, and sustained activity, abarelix depot-F offers a potential therapeutic advance in clinical conditions where GnRH agonists are currently in common use. Objectives: Abarelix depot-F is a sustained release formulation of the potent, pure GnRH receptor antagonist, abarelix. Abarelix is devoid of any stimulatory activity at the GnRH receptor and therefore overcomes a significant drawback inherent to all GnRH agonists. The objectives of this study were to examine the dose-dependent pharmacodynamic effects of abarelix depot-F administered by SC injection and compare them to those of Lupron Depot® administered IM in women with endometriosis. Design: In a randomized, parallel arm, dose ranging study, 30, 60, 90, and 120 mg abarelix depot-F (SC) and 3.75 mg Lupron Depot® (IM) were compared by administering drug to women with endometriosis-associated pain. Materials and Methods: Blood samples were collected at frequent time intervals post-dose for determination of circulating abarelix, estradiol (E2), luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels. Results: Preliminary results indicate that all doses of abarelix depot-F were well tolerated. Administration of abarelix depot-F produced a decrease in serum E2 as early as 4 hours (−1% to −17%) with peak inhibitory effect at 7 days (−70%) for all abarelix depot-F doses. In contrast, injection of Lupron Depot® caused an E2 surge detectable as early as 4 hours (15%) with a peak at 7 days (+487%). An inhibitory effect of abarelix on LH (−39 to −60%) and FSH (−11 to −15%) levels was observed at 2 hours at all study doses. In contrast, Lupron Depot® injection caused an immediate surge of LH and FSH levels, peaking at 4 hours post-dose with mean concentrations 7 and 15 times higher, respectively, than pre-dose LH and FSH levels. Conclusions: These study results confirm that abarelix depot-F acts in women with a very rapid onset of action and effect. By providing rapid inhibition of LH, FSH and E2 production, avoidance of hormonal flare, and sustained activity, abarelix depot-F offers a potential therapeutic advance in clinical conditions where GnRH agonists are currently in common use.