Endometriosis - TAK-013
Endometriosis is a painful, fertility threatening condition that is a result of tissue similar to that found in the womb lining growing elsewhere in the pelvis. The condition is sex hormone dependent, with gonadotropin releasing hormone (GnRH), a hypothalamic decapeptide amide that plays an important part in the regulation of reproductive processes, being implicated.
GnRH agonists improve the symptoms of endometriosis, but these agonists are associated with an initial hormone flare effect that can actually make symptoms worse. Peptide GnRH receptor antagonists suppress gonadotropin release from the outset, without causing the flare, but their oral availability is poor, so a small molecule alternative would be preferable.
Such a molecule is Takeda's TAK-013, which is highly specific for the human GnRH receptor.1 A randomised double-blind placebo-controlled ascending dose parallel group Phase I trial was carried out in 50 healthy premenopausal women to investigate its safety, tolerability, efficacy, pharmacokinetics and metabolism. Patients were given multiple oral doses of TAK-013 of 5, 10, 25, 50 or 100mg once a day for 14 days, which showed it was well tolerated and caused no adverse events.2
A second randomised double-blind placebo-controlled ascending dose parallel group Phase I trial looked at single and multiple doses of the drug.3 Patients were given single doses of 50, 100 or 200mg, or 25, 50 or 100mg twice a day for 14 days starting a week after single dosing. Again, no adverse events or significant changes in vital signs were seen. Phase II trials are now being carried out in both Europe and the US in patients with endometriosis and uterine fibrosis to establish its usefulness as a therapy.