This might be a treatment for ASIH much like a GnRH agonist.
MacLean DB, Matsui H, Suri A, Neuwirth R, Colombel M. Sustained Exposure to the Investigational Kisspeptin Analog, TAK-448, Downregulates Testosterone into the Castration Range in Healthy Males and in Patients with Prostate Cancer: Results From Two Phase 1 Studies. The Journal of Clinical Endocrinology & Metabolism. http://press.endocrine.org/doi/abs/10.1210/jc.2013-4236
Background/Objective: Kisspeptin-54, an endogenous naturally-occurring ligand of the G-protein coupled receptor-54 (GPR-54), stimulates GnRH-gonadotropin secretion and suppresses metastases in animal models of cancer but is subject to rapid degradation and inactivation.
TAK-448 is an investigational oligopeptide analog of the fully active 10-amino acid C-terminus of kisspeptin-54. This phase-1 study evaluated the safety, pharmacokinetics, and pharmacodynamics of TAK-448 in healthy subjects and patients with prostate cancer (PC).
Design: Healthy subjects aged ?50 years received TAK-448 subcutaneously (sc) as a single-bolus or 2h infusion (0.01–6 mg/day; Part A) and as a 14-day sc-administration (0.01–1 mg/day; Part B). In a subsequent, open-label, phase-1 study in PC patients aged 40–78 years, TAK-448 was given as a 1-month depot formulation.
Results: 82 healthy subjects received TAK-448; 30 received placebo. Grade 1–2 adverse events were reported in 26% of subjects during TAK-448 treatment. All dosing regimens resulted in dose-proportional exposures. Cmax occurred after 0.25–0.5h and t1/2 was 1.4–5.3h.
Testosterone increased approximately 1.3–2-fold by 48h following single-bolus or 2h injections whereas during the 14-day infusion, at doses above 0.1 mg/day, testosterone dropped to below-baseline values by 60h and reached a subsequently sustained below-castration level by day 8. In PC patients, testosterone decreased to <20 ng/dL in 4/5 patients dosed with 12 or 24 mg TAK-448 sc-depot injections. PSA decreased >50% in all patients dosed with 24 mg.
Conclusions: Continuous TAK-448 infusion was well-tolerated by healthy males and resulted in sustained testosterone suppression. Depot injection in patients with PC similarly reduced testosterone and resulted in PSA responses.
MacLean DB, Matsui H, Suri A, Neuwirth R, Colombel M. Sustained Exposure to the Investigational Kisspeptin Analog, TAK-448, Downregulates Testosterone into the Castration Range in Healthy Males and in Patients with Prostate Cancer: Results From Two Phase 1 Studies. The Journal of Clinical Endocrinology & Metabolism. http://press.endocrine.org/doi/abs/10.1210/jc.2013-4236
Background/Objective: Kisspeptin-54, an endogenous naturally-occurring ligand of the G-protein coupled receptor-54 (GPR-54), stimulates GnRH-gonadotropin secretion and suppresses metastases in animal models of cancer but is subject to rapid degradation and inactivation.
TAK-448 is an investigational oligopeptide analog of the fully active 10-amino acid C-terminus of kisspeptin-54. This phase-1 study evaluated the safety, pharmacokinetics, and pharmacodynamics of TAK-448 in healthy subjects and patients with prostate cancer (PC).
Design: Healthy subjects aged ?50 years received TAK-448 subcutaneously (sc) as a single-bolus or 2h infusion (0.01–6 mg/day; Part A) and as a 14-day sc-administration (0.01–1 mg/day; Part B). In a subsequent, open-label, phase-1 study in PC patients aged 40–78 years, TAK-448 was given as a 1-month depot formulation.
Results: 82 healthy subjects received TAK-448; 30 received placebo. Grade 1–2 adverse events were reported in 26% of subjects during TAK-448 treatment. All dosing regimens resulted in dose-proportional exposures. Cmax occurred after 0.25–0.5h and t1/2 was 1.4–5.3h.
Testosterone increased approximately 1.3–2-fold by 48h following single-bolus or 2h injections whereas during the 14-day infusion, at doses above 0.1 mg/day, testosterone dropped to below-baseline values by 60h and reached a subsequently sustained below-castration level by day 8. In PC patients, testosterone decreased to <20 ng/dL in 4/5 patients dosed with 12 or 24 mg TAK-448 sc-depot injections. PSA decreased >50% in all patients dosed with 24 mg.
Conclusions: Continuous TAK-448 infusion was well-tolerated by healthy males and resulted in sustained testosterone suppression. Depot injection in patients with PC similarly reduced testosterone and resulted in PSA responses.
