A Phase 2 Multicenter Study of Seliciclib (R-roscovitine) for Cushing Disease
This phase 2 multicenter, open-label clinical trial will evaluate safety and efficacy of 4 weeks of oral seliciclib in patients with newly diagnosed, persistent, or recurrent Cushing disease. Funding Source - FDA Office of Orphan Products Development (OOPD)
• Male and female patients at least 18 years old
• Patients with confirmed pituitary origin of excess adrenocorticotropic hormone (ACTH) production:
‣ Persistent hypercortisolemia established by two consecutive 24-hour UFC assessment ≥1.5× the upper limit of normal
⁃ Normal or elevated ACTH levels
⁃ Pituitary adenoma (\>1 cm) on MRI or inferior petrosal sinus sampling (IPSS) central to peripheral ACTH gradient \>2 at baseline and \>3 after CRH stimulation
⁃ Recurrent or persistent CD defined as pathologically confirmed resected pituitary ACTH-secreting tumor or IPSS central to peripheral ACTH gradient \>2 at baseline and \>3 after CRH stimulation, and 24h-UFC \>ULN beyond post-surgical week 6
• Patients on medical treatment for Cushing disease. The following washout periods must be completed before screening assessments are performed:
‣ Inhibitors of steroidogenesis: metyrapone, ketoconazole: 2 weeks; Levoketoconazole: 3 weeks; osilodrostat: 6 weeks
⁃ Somatostatin receptor ligand pasireotide: short-acting, 2 weeks; long-acting, 4 weeks
⁃ Progesterone receptor antagonist mifepristone: 2 weeks
⁃ Dopamine agonist cabergoline: 4 weeks
⁃ Patients treated with CYP3A or CYP2B6 strong inducers or inhibitors, including those listed below. Required washout time varies between drugs; minimum 5-6 times the half-life of the drug.
• Strong CYP3A inducers: apalutamide, carbamazepine, enzalutamide, mitotane, phenytoin, rifampin, St. John's wort
∙ Moderate CYP3A inducers: bosentan, efavirenz, etravirine, phenobarbital, primidone
∙ Weak CYP3A inducers: armodafinil, modafinil, rufinamide
∙ Strong CYP2B6 inducer: carbamazepine
∙ Moderate CYP2B6 inducers: efavirenz, rifampin
∙ Weak CYP2B6 inducers: nevirapine, ritonavir
∙ Strong CYP3A inhibitors: boceprevir, cobicistat, danoprevir and ritonavir, elvitegravir and ritonavir, grapefruit juice, indinavir and ritonavir, itraconazole, ketoconazole, lopinavir and ritonavir, paritaprevir and ritonavir and (ombitasvir and/or dasabuvir), posaconazole, ritonavir, saquinavir and ritonavir, telaprevir, tipranavir and ritonavir, telithromycin, troleandomycin, voriconazole, clarithromycin, idelalisib, nefazodone, nelfinavir.
∙ Moderate CYP3A inhibitors: aprepitant, ciprofloxacin, conivaptan, crizotinib, cyclosporine, diltiazem, dronedarone, erythromycin, fluconazole, fluvoxamine, imatinib, verapamil
∙ Strong CYP2B6 inhibitor: ticlopidine