This is a Phase 1b, multicenter, open-label, pharmacokinetic (PK), and safety study of multiple oral doses of oral decitabine and cedazuridine (formerly known as ASTX727) as a fixed-dose combination of decitabine 35 milligrams (mg) and cedazuridine 100 mg in cancer participants with moderate and severe hepatic impairment and cancer participants with normal hepatic function as control participants. Participants with severe hepatic impairment will be enrolled only after the safety evaluation of at least 6 participants with moderate hepatic impairment has been determined and supports the enrollment of participants with severe hepatic impairment. Adult participants with acute myeloid lymphoma (AML), myelodysplastic syndrome (MDS), or solid tumors who are candidates to receive oral decitabine and cedazuridine will be enrolled in this study. Study duration is per participant approximately up to 8 weeks.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
27
Multiple-dose oral administration of once-daily decitabine (35 mg) and cedazuridine (100 mg)
MD Anderson
Houston, Texas, United States
NOT_YET_RECRUITINGErebuni Medical Center
Yerevan, Armenia
RECRUITINGHematology Center After Prof. R. Yeolyan (Adult Blood Disorders)
Yerevan, Armenia
RECRUITINGHematology Center After Prof. R. Yeolyan (Clinic of Adults Oncology)
Yerevan, Armenia
RECRUITINGNational Center of Oncology Named After V.A. Fanarjyan
Yerevan, Armenia
RECRUITINGComplex Oncology Center - Plovdiv - Base II
Plovdiv, Bulgaria
WITHDRAWNBIO1
Vilnius, Lithuania
WITHDRAWNCentrum Badań Klinicznych Piotr Napora Lekarze Sp. p.
Wroclaw, Poland
RECRUITINGInstitutul Oncologic Bucuresti - Prof. Dr. Alexandru Trestioreanu
Bucharest, Romania
RECRUITINGInstitutul Oncologic Prof. Dr. Ion Chiricuta
Cluj-Napoca, Romania
RECRUITING...and 12 more locations
Pharmacokinetic Parameter: 5-day Cumulative Area Under the Concentration-time Curve Within 1 Dosing Interval (AUCtau)
AUCtau from Day 1 to Day 5 for decitabine.
Time frame: Predose and at multiple timepoints post-dose from Day 1 to Day 5
Pharmacokinetic Parameter: Apparent Clearance (CL/F)
CL/F of decitabine and cedazuridine.
Time frame: Predose from Day 1 to Day 5 and at multiple timepoints post-dose from Day 1 to Day 8
Pharmacokinetic Parameter: Renal Clearance (CLR)
CLR of decitabine, cedazuridine, and cedazuridine-epimer.
Time frame: Predose from Day 1 to Day 5 and at multiple timepoints post-dose from Day 1 to Day 8
Pharmacokinetic Parameter: Apparent Nonrenal Clearance (CLNR/F)
CLNR/F of decitabine and cedazuridine.
Time frame: Predose from Day 1 to Day 5 and at multiple timepoints post-dose from Day 1 to Day 8
Pharmacokinetic Parameter: Time to Maximum Observed Plasma Concentration (Tmax)
Tmax of decitabine, cedazuridine, and cedazuridine-epimer.
Time frame: Predose from Day 1 to Day 5 and at multiple timepoints post-dose from Day 1 to Day 8
Pharmacokinetic Parameter: Maximum Observed Plasma Concentration (Cmax)
Cmax of decitabine, cedazuridine, and cedazuridine-epimer.
Time frame: Predose and at multiple time points post-dose on Days 1, 2 and 5
Pharmacokinetic Parameter: Plasma Concentration Prior to Dosing (Ctrough)
Ctrough of decitabine, cedazuridine, and cedazuridine-epimer.
Time frame: Predose on Days 2, 3, 4, and 5
Pharmacokinetic Parameter: Area Under the Concentration-time Curve from Time 0 (Time of Dosing) to Time t (AUCt)
AUCt of decitabine, cedazuridine, and cedazuridine-epimer, where t is the last time point with concentrations above the lower limit of quantitation.
Time frame: Predose from Day 1 to Day 5 and at multiple timepoints post-dose from Day 1 to Day 8
Pharmacokinetic Parameter: Pharmacokinetic Parameter: AUC Within 1 Dosing Interval (AUCtau)
AUCtau of decitabine, cedazuridine, and cedazuridine-epimer.
Time frame: Predose from Day 1 to Day 2, Day 2 to Day 3, and Day 5 to Day 6 and at multiple timepoints on Day 1 to Day 2, Day 2 to Day 3, and Day 5 to Day 6
Pharmacokinetic Parameter: AUC From Time 0 Extrapolated to Infinity (AUC0-inf)
AUC0-inf of decitabine, cedazuridine, and cedazuridine-epimer.
Time frame: Predose and at multiple time points post-dose on Days 1, 2 and 5
Pharmacokinetic Parameter: Terminal Elimination Phase Rate Constant (λz)
λz of decitabine, cedazuridine, and cedazuridine-epimer.
Time frame: Predose from Day 1 to Day 5 and at multiple timepoints post-dose from Day 1 to Day 8]
Pharmacokinetic Parameter: Terminal Elimination Half-life (t1/2)
t1/2 of decitabine, cedazuridine, and cedazuridine-epimer.
Time frame: Predose from Day 1 to Day 5 and at multiple timepoints post-dose from Day 1 to Day 8
Pharmacokinetic Parameter: Apparent Volume of Distribution During Terminal Phase (Vz/F)
Vz/F of decitabine and cedazuridine.
Time frame: Predose from Day 1 to Day 5 and at multiple timepoints post-dose from Day 1 to Day 8
Pharmacokinetic Parameter: Fraction of Administered Drug Excreted into Urine (Fe/F))
Fe/F of decitabine and cedazuridine.
Time frame: Predose and at multiple timepoints post-dose up to 24 hours
Pharmacokinetic Parameter: Cumulative Amount Excreted from Time 0 to the Time of the Last Quantifiable Sample (Aelast)
Aelast of decitabine, cedazuridine, and cedazuridine-epimer.
Time frame: Predose and at multiple timepoints post-dose up to 24 hours
Safety Parameter: Number of Participants with Adverse Events (AEs)
Adverse events included any untoward medical occurrence in a participant administered a drug; it does not necessarily have to have a causal relationship with this treatment also including clinically meaningful findings in laboratory safety tests, vital signs, physical examinations, and electrocardiogram (ECG) findings.
Time frame: Up to 8 weeks
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