Effect of Food on Blood Levels of ASTX727

NCT03813186 | Completed Phase 1 FDA Drug

• 1 other identifier: ASTX727-04
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 4

Brief Summary

This study is designed to examine blood levels of ASTX727, a fixed-dose combination tablet containing the combination of cedazuridine (100 mg) and decitabine (35 mg), when given under fed versus fasted conditions to participants with myelodysplastic syndromes (MDS), including refractory anemia with excess blasts in transformation or chronic myelomonocytic leukemia (CMML), or acute myeloid leukemia (AML). This study will also assess the safety of ASTX727.

Conditions

Myelodysplastic Syndromes; Chronic Myelomonocytic Leukemia; Acute Myeloid Leukemia

Keywords

MDS; CMML; ASTX727; decitabine; AML

Outcome Measures

Primary Outcomes (5)

• AUC0-t (area under the concentration-time curve from time 0 to t hours).

  Area under the concentration-time curve from time 0 to t hours.

  6 months

• AUC0-8 (area under the concentration-time curve from time 0 to 8 hours).

  Area under the concentration-time curve from time 0 to 8 hours.

  6 months

• AUC0-24 (area under the concentration-time curve from time 0 to 24 hours).

  Area under the concentration-time curve from time 0 to 24 hours

  6 months

• AUC0-inf (area under the concentration-time curve from time 0 to infinity).

  Area under the concentration-time curve from time 0 to infinity.

  6 months

• Cmax (maximum plasma concentration).

  Maximum plasma concentration.

  6 months

Secondary Outcomes (5)

• hemoglobin level

  6 months

• platelet count

  6 months

• white blood cell count

  6 months

• neutrophils

  6 months

• Subject-reported and investigator-observed incidence and severity of adverse events.

  6 months

Study Arms (2)

ASTX727 + Day 2 Food

EXPERIMENTAL

Subjects will receive ASTX727 on Days 1-5 of Cycle 1 and a high-calorie, high-fat breakfast meal of 800-1000 calories pre-dose on Day 2 of Cycle 1.

Drug: ASTX727 + Day 2 Food

ASTX727 + Day 4 Food

EXPERIMENTAL

Subjects will receive ASTX727 on Days 1-5 of Cycle 1 and a high-calorie, high-fat breakfast meal of 800-1000 calories pre-dose on Day 4 of Cycle 1.

Drug: ASTX727 + Day 4 Food

Interventions

ASTX727 + Day 2 Food DRUG

ASTX727 is an oral drug product composed of a fixed-dose combination of cedazuridine (E7727), a CDA inhibitor, and decitabine. Food is a high-calorie, high-fat breakfast meal of 800-1000 calories given on Day 2.

Also known as: cedazuridine + decitabine + food on Day 2

ASTX727 + Day 2 Food

ASTX727 + Day 4 Food DRUG

ASTX727 is an oral drug product composed of a fixed-dose combination of cedazuridine (E7727), a CDA inhibitor, and decitabine. Food is a high-calorie, high-fat breakfast meal of 800-1000 calories given on Day 4.

Also known as: cedazuridine + decitabine + food on Day 4

ASTX727 + Day 4 Food

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able to understand and comply with the study procedures, including the ability to completely consume the breakfast meal in 20 minutes, understand the risks involved in the study, and provide written informed consent before the first study-specific procedure.
• Men or women ≥18 years with either:
• MDS, including all French-American-British subtypes (refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, CMML), and subjects with MDS IPSS int-1, -2, or high-risk MDS.
• AML, as diagnosed according to the 2016 WHO guidelines on acute leukemia, of any subtype except M3 (Acute Promyelocytic Leukemia), who are not candidates for intensive chemotherapy
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
• Adequate organ function defined as follows:
• Hepatic: Total or direct bilirubin ≤2 × upper limit of normal (ULN); aspartate aminotransferase/serum glutamic oxaloacetic transaminase (AST/SGOT) and alanine aminotransferase/serum glutamic pyruvic transaminase (ALT/SGPT) ≤5 × ULN.
• Renal: serum creatinine ≤1.5 × ULN or if serum creatinine is elevated; calculated creatinine clearance or glomerular filtration rate ≥50 mL/min.
• Women of child-bearing potential (according to recommendations of the Clinical Trial Facilitation Group) must not be pregnant or breastfeeding and must have a negative pregnancy test at screening.
• Subjects and their partners with reproductive potential must agree to use 2 highly effective contraceptive measures during the study and must agree not to become pregnant or father a child for 3 months after the last dose of study treatment.

You may not qualify if:

• Known or suspected hypersensitivity to decitabine, azacitidine, or cedazuridine.
• Treated with any investigational drug or therapy within 2 weeks of study treatment, or 5 half-lives, whichever is longer, before the protocol-defined first dose of study treatment, or ongoing clinically significant adverse events (AEs) from previous treatment with investigational drug or therapy.
• Poor medical risk because of other conditions such as uncontrolled systemic diseases or active uncontrolled infections.
• Life-threatening illness, medical condition or organ system dysfunction, or other reasons including laboratory abnormalities, which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of decitabine + cedazuridine or compromise the integrity of the study outcomes.
• Prior gastric surgery for ulcer disease, weight loss, etc., that would impair normal motility or absorption.
• Second malignancy currently requiring active chemotherapy. To clarify, patients with breast or prostate cancer stable on or responding to endocrine therapy, are eligible.
• Known history of human immunodeficiency virus or if known seropositive for hepatitis C virus or hepatitis B virus.
• Active uncontrolled gastric or duodenal ulcer.
• Subjects with Acute Promyelocytic Leukemia.

Sponsors & Collaborators

• Astex Pharmaceuticals, Inc.: lead

Study Sites (4)

Roswell Park

Buffalo, New York, 14263, United States

Location

Gabrail Cancer Center

Canton, Ohio, 44718, United States

Location

Vanderbilt

Nashville, Tennessee, 37232, United States

Location

Mays Cancer Center UT Health San Antonio MD Anderson Cancer Center

San Antonio, Texas, 78229, United States

Location

Related Publications (1)

• Cheson BD, Greenberg PL, Bennett JM, Lowenberg B, Wijermans PW, Nimer SD, Pinto A, Beran M, de Witte TM, Stone RM, Mittelman M, Sanz GF, Gore SD, Schiffer CA, Kantarjian H. Clinical application and proposal for modification of the International Working Group (IWG) response criteria in myelodysplasia. Blood. 2006 Jul 15;108(2):419-25. doi: 10.1182/blood-2005-10-4149. Epub 2006 Apr 11.

  PMID: 16609072 BACKGROUND

MeSH Terms

Conditions

Myelodysplastic Syndromes; Leukemia, Myelomonocytic, Chronic; Leukemia, Myeloid, Acute

Interventions

decitabine and cedazuridine drug combination; cedazuridine; Decitabine

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myelodysplastic-Myeloproliferative Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Azacitidine; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 11, 2019
• First Posted: January 23, 2019
• Study Start: November 8, 2018
• Primary Completion: June 14, 2019
• Study Completion: December 16, 2019
• Last Updated: August 2, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)