A Phase 1b, Open-label, Parallel Group, Multiple-dose Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Oral Decitabine and Cedazuridine (ASTX727) in Cancer Patients With Severe Renal Impairment and Cancer Patients With Normal Renal Function

Taiho Oncology, Inc.26 sites in 8 countries18 target enrollmentDecember 15, 2021

ConditionsAcute Myeloid Leukemia Myelodysplastic Syndromes

InterventionsASTX727

DrugsASTX727

Overview

Phase: Phase 1
Intervention: ASTX727
Conditions: Acute Myeloid Leukemia
Sponsor: Taiho Oncology, Inc.
Enrollment: 18
Locations: 26
Primary Endpoint: Pharmacokinetic Parameter: 5-day Cumulative Area Under the Concentration-time Curve Within 1 Dosing Interval (AUCtau)
Status: Recruiting
Last Updated: last month

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This is a Phase 1b, multicenter, open-label, 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 severe renal impairment and cancer participants with normal renal function as matched control participants. 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 per participant is approximately up to 8 weeks.

Registry

clinicaltrials.gov

Start Date

December 15, 2021

End Date

December 1, 2026

Last Updated

last month

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Taiho Oncology, Inc.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Able to understand and comply with the study procedures, understand the risks involved in the study, and provide legally effective informed consent before the first study-specific procedure; specifically able to comply with the PK assessment schedule during the first treatment cycle.
•Participants must have a histologically or cytologically confirmed malignancy as follows:
•A solid tumor that is metastatic or unresectable and for which standard life-prolonging measures are not available.
•AML or MDS. or
•A hematologic malignancy other than AML or MDS for which standard life-prolonging measures are not available.
•For participants with AML/MDS only:
•Cytologically or histologically confirmed diagnosis of AML (except M3 acute promyelocytic leukemia) or MDS according to the 2008 World Health Organization (WHO) classification or
•Participants with frontline MDS or treatment naïve AML not suitable for induction therapy (e.g., age \>75 years, Eastern Cooperative Oncology Group \[ECOG\] performance ≥2, severe pulmonary disorder, total bilirubin 1.5 × upper limit of normal \[ULN\]); or
•Platelet count ≥25,000/per microliter (μL); or
•Absolute neutrophil count (ANC) ≥100 cells/μL.

Exclusion Criteria

•Treatment with azacitidine or decitabine within 4 weeks before Screening. Prior cytotoxic chemotherapy for AML except for hydroxyurea to control high white blood cell (WBC) counts.
•Hospitalization for more than 2 days for documented febrile neutropenia, pneumonia, sepsis, or systemic infection 30 days prior to first dose.
•Treatment with any investigational medicinal product (IMP), investigational therapy, chemotherapy, immunotherapy, or targeted therapy within 2 weeks or 5 half-lives, whichever is longer, before the first dose of study treatment, or ongoing clinically significant adverse events from previous treatment.
•Concurrent MDS therapies, including lenalidomide, cyclosporine/tacrolimus, granulocyte-colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor, etc. Prior treatment with these agents is permitted, provided that completion is at least 1 week before the first dose of study treatment. Short-term use of G-CSF for febrile neutropenia is permitted at the discretion of the treating physician and should be guided by accepted practice or institutional guidelines. Hematopoietic growth factors will not be routinely used unless cleared by Taiho medical expert.
•Administration of live (attenuated) vaccines within 4 weeks before the first administration of oral decitabine and cedazuridine until after the follow-up visit. Other vaccines, e.g., inactivated or ribonucleic acid (RNA)-based, may be administered but should not occur from 7 days before first administration of oral decitabine and cedazuridine until after the follow-up visit.
•High medical risk because of other conditions such as uncontrolled systemic diseases, active uncontrolled infections, or comorbidities that may put the participants at risk of not being able to complete 1 cycle of treatment.
•Conditions which likely promote delayed ventricular repolarization (QT prolongation):
•Corrected QT interval (QTc) using Fridericia's correction (QTcF) at Screening or Day -1 \>470 milliseconds (ms) for males and \>480 ms for females or
•History or disposition for torsades des pointes (TdP) (e.g., heart failure, hypokalemia, family history of long QT Syndrome) or
•Concomitant medications that prolong the QT/QTc interval

Arms & Interventions

Group A: Severe Renal Impairment

Cancer participants with severe renal impairment not requiring dialysis (creatinine clearance \[CLcr\] \<30 mL/min/1.73m\^2)

Intervention: ASTX727

Group B: Normal Renal Function

Cancer participants with normal renal function (CLcr ≥80 mL/min/1.73m\^2)

Intervention: ASTX727

Outcomes

Primary Outcomes

Pharmacokinetic Parameter: 5-day Cumulative Area Under the Concentration-time Curve Within 1 Dosing Interval (AUCtau)

Time Frame: Predose and at multiple timepoints post-dose from Day 1 to Day 5

AUCtau from Day 1 to Day 5 for decitabine.

Secondary Outcomes

Pharmacokinetic Parameter: Renal Clearance (CLR)(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)(Predose from Day 1 to Day 5 and at multiple timepoints post-dose from Day 1 to Day 8)
Pharmacokinetic Parameter: Area Under the Concentration-time Curve from Time 0 (Time of Dosing) to Time t(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)(Predose from Day 1 to Day 5 and at multiple timepoints post-dose from Day 1 to Day 8)
Pharmacokinetic Parameter: Cumulative Amount Excreted from Time 0 to the Time of the Last Quantifiable Sample (Aelast)(Predose on Day 1 and at multiple timepoints post-dose from Day 1 to Day 6)
Safety Parameter: Number of Participants with Adverse Events (AEs)(Up to 8 weeks)
Pharmacokinetic Parameter: Apparent Clearance (CL/F)(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)(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)(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)(Predose on Day 1 and at multiple timepoints post-dose from Day 1 to Day 6)
Pharmacokinetic Parameter: Maximum Observed Plasma Concentration (Cmax)(Predose and at multiple timepoints post-dose on Days 1, 2, and 5)
Pharmacokinetic Parameter: Plasma Concentration Prior to Dosing (Ctrough)(Predose on Days 2, 3, 4 and 5)
Pharmacokinetic Parameter: AUC Within 1 Dosing Interval (AUCtau)(Predose on 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)(Predose and at multiple timepoints post-dose on Days 1, 2, and 5)
Pharmacokinetic Parameter: Terminal Elimination Phase Rate Constant (λz)(Predose from Day 1 to Day 5 and at multiple timepoints post-dose from Day 1 to Day 8)