Clinical Trials /

Effect of Food on Blood Levels of ASTX727

NCT03813186

Description:

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.

Related Conditions:
  • Chronic Myelomonocytic Leukemia
  • Myelodysplastic Syndromes
  • Refractory Anemia
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Effect of Food on Blood Levels of ASTX727
  • Official Title: A Phase 1b Study to Evaluate the Effect of Food on Pharmacokinetics of ASTX727 (Cedazuridine and Decitabine) in Subjects With Myelodysplastic Syndromes

Clinical Trial IDs

  • ORG STUDY ID: ASTX727-04
  • NCT ID: NCT03813186

Conditions

  • Myelodysplastic Syndromes
  • Chronic Myelomonocytic Leukemia

Interventions

DrugSynonymsArms
ASTX727 + Day 2 Foodcedazuridine + decitabine + food on Day 2ASTX727 + Day 2 Food
ASTX727 + Day 4 Foodcedazuridine + decitabine + food on Day 4ASTX727 + Day 4 Food

Purpose

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). This study will also assess the safety of ASTX727.

Detailed Description

      This is a Phase 1b, multicenter, open-label, randomized, two-sequence, crossover study of
      ASTX727 in participants with MDS, including refractory anemia with excess blasts in
      transformation or CMML. Participants will continue to be enrolled until evaluable data is
      collected from 12 participants. It is expected that approximately 18 participants will be
      enrolled in total.

      This study will be conducted in 28-day cycles. All participants will take part in Cycle 1 and
      may continue into Cycles ≥2 at the investigator's discretion. Participants will receive one
      tablet of ASTX727 containing 100 mg cedazuridine and 35 mg decitabine once daily for 5 days
      in 28-day cycles starting from Cycle 1 Day 1.

      Participants will be randomized in a 1:1 ratio to receive high-calorie, high-fat breakfast
      meal pre-dose on either Day 2 or Day 4 of Cycle 1. Blood will be drawn at specified time
      points in Cycle 1 on Days 2 through 5 to assess the effect of food on the PK of cedazuridine
      and decitabine.

      After completion of the first treatment cycle, participants may continue to receive treatment
      with ASTX727 at the investigator's discretion for subsequent cycles (Days 1 through 5 of
      28-day cycles), until disease progression, unacceptable toxicity, investigator decision to
      discontinue treatment, or the participant decides to discontinue treatment or withdraw from
      the study. In Cycles ≥2, participants will fast for 2 hours before and 2 hours after taking
      the ASTX727 tablet on all dosing days.
    

Trial Arms

NameTypeDescriptionInterventions
ASTX727 + Day 2 FoodExperimentalSubjects 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.
  • ASTX727 + Day 2 Food
ASTX727 + Day 4 FoodExperimentalSubjects 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.
  • ASTX727 + Day 4 Food

Eligibility Criteria

        Inclusion Criteria:

          1. 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.

          2. Men or women ≥18 years with 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, and CMML), and
             subjects with MDS int-1, -2, or high-risk MDS.

          3. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.

          4. Adequate organ function defined as follows:

               1. 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.

               2. Renal: serum creatinine ≤1.5 × ULN or if serum creatinine is elevated; calculated
                  creatinine clearance or glomerular filtration rate ≥50 mL/min.

          5. 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.

          6. 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.

        Exclusion Criteria:

          1. Known or suspected hypersensitivity to decitabine, azacitidine, or cedazuridine.

          2. 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.

          3. Poor medical risk because of other conditions such as uncontrolled systemic diseases
             or active uncontrolled infections.

          4. 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.

          5. Prior gastric surgery for ulcer disease, weight loss, etc., that would impair normal
             motility or absorption.

          6. Prior malignancy, except for adequately treated basal cell or squamous cell skin
             cancer, in situ cervical cancer, non-metastatic prostate cancer with normal
             prostate-specific antigen, or other cancer from which the subject has been disease
             free for at least 3 years.

          7. Known history of human immunodeficiency virus or if known seropositive for hepatitis C
             virus or hepatitis B virus.

          8. Active uncontrolled gastric or duodenal ulcer.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:AUC0-t (area under the concentration-time curve from time 0 to t hours).
Time Frame:6 months
Safety Issue:
Description:Area under the concentration-time curve from time 0 to t hours.

Secondary Outcome Measures

Measure:hemoglobin level
Time Frame:6 months
Safety Issue:
Description:Assessed in g/dL
Measure:platelet count
Time Frame:6 months
Safety Issue:
Description:Assessed as 10^9/L
Measure:white blood cell count
Time Frame:6 months
Safety Issue:
Description:Assessed as fraction of 1
Measure:neutrophils
Time Frame:6 months
Safety Issue:
Description:Assessed as percent
Measure:Subject-reported and investigator-observed incidence and severity of adverse events.
Time Frame:6 months
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Astex Pharmaceuticals

Trial Keywords

  • MDS
  • CMML
  • ASTX727
  • decitabine

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