Clinical Trials /

A Phase 1 Trial of ASTX030 in Patients With Myelodysplastic Syndrome

NCT04608110

Description:

The purpose of this study is to identify the doses of the azacitidine (AZA) tablets and cedazuridine (CED) tablets which achieve a total AUC for AZA comparable to that for AZA injection at 75 mg/m2

Related Conditions:
  • Myelodysplastic Syndromes
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Phase 1 Trial of ASTX030 in Patients With Myelodysplastic Syndrome
  • Official Title: A Phase 1, Multi-center, Open-label, Uncontrolled, Dose-escalation Study to Evaluate the Pharmacokinetics of ASTX030 in Patients With Myelodysplastic Syndrome (MDS)

Clinical Trial IDs

  • ORG STUDY ID: 418-102-00001
  • NCT ID: NCT04608110

Conditions

  • Myelodysplastic Syndrome (MDS)

Interventions

DrugSynonymsArms
ASTX030Azacitidine + Cedazuridine

Purpose

The purpose of this study is to identify the doses of the azacitidine (AZA) tablets and cedazuridine (CED) tablets which achieve a total AUC for AZA comparable to that for AZA injection at 75 mg/m2

Trial Arms

NameTypeDescriptionInterventions
Azacitidine + CedazuridineExperimentalDrug: Azacitidine Tablets for oral administration and powder for reconstitution to aqueous suspension for subcutaneous administration Drug: Cedazuridine Tablets for oral administration
  • ASTX030

Eligibility Criteria

        Inclusion Criteria:

          -  Patients aged 20 years or older

          -  Patients with a diagnosis of MDS (refractory anemia [RA], refractory anemia with
             ringed sideroblasts [RARS], refractory anemia with excess blasts [RAEB], refractory
             anemia with excess blasts in transformation [RAEB-T], or chronic myelomonocytic
             leukemia [CMML]) according to the French-American-British (FAB) classification
             Low-risk patients who fall under the risk category of low or intermediate-1 (Int-1)
             based on the International Prognostic Scoring System (IPSS) can be enrolled only if
             they are unlikely to respond to any other treatment or if they are currently being
             treated with azacytidine (AZA) injection

          -  Patients with an ECOG PS score of 0 or 1 or with an ECOG PS score of 2 due to primary
             disease-associated conditions

          -  Patients with adequate organ function as indicated below

               1. Hepatic function: All of the following criteria must be satisfied.

                    -  Total bilirubin ≤ 2.0 × upper limit of normal (ULN)

                    -  Aspartate aminotransferase (AST) ≤ 2.5 × ULN

                    -  Alanine aminotransferase (ALT) ≤ 2.5 × ULN

               2. Renal function: Either of the following criteria must be satisfied.

                    -  Serum creatinine ≤ 1.5 × ULN

                    -  Creatinine clearance or glomerular filtration rate ≥ 50 mL/min

               3. Respiratory function: percutaneous arterial oxygen saturation (SpO2) ≥ 90%

          -  Patients who are expected to survive for at least 3 months

          -  Patients who give written consent to participate in the trial using the informed
             consent form approved by the institutional review board

        Exclusion Criteria:

          -  Patients who are unlikely to respond to AZA

          -  Patients who have received chemotherapy, hormone therapy, antibody therapy,
             radiotherapy, or other exploratory anti-cancer treatments for the primary disease
             within 3 weeks prior to the first administration of the investigational medicinal
             product (IMP)

          -  Patients who have used any other IMP or any privately imported medicine within 4 weeks
             prior to the first administration of IMP

          -  Patients with heart disease of Class 3 or 4 according to the New York Heart
             Association classification

          -  Patients with uncontrolled systemic disease or active infection

          -  Patients with uncontrolled gastric or duodenal ulcer

          -  Patients with prior or current interstitial lung disease

          -  Patients with a history of surgical gastrectomy

          -  Patients with life-threatening conditions/symptoms, multiple organ failure, or other
             factors (including laboratory abnormalities) that, in the opinion of the investigator,
             are likely to affect their safety or the absorption and metabolism of AZA and
             cedazuridine (CED), or influence the trial evaluation

          -  Patients with other malignancies (except appropriately treated basal cell carcinoma,
             squamous cell carcinoma, or cervical carcinoma in situ; prostate or breast cancer
             stabilized by endocrine therapies; and malignancies that have not relapsed for at
             least 1 year since the last successful treatment)

          -  Patients who are positive for HIV antibody, HBV-DNA, or HCV antibody

          -  Patients with any ≥ Grade 2 AE (except alopecia) associated with prior treatment of
             the primary disease. However, the parameters defined in inclusion criterion above are
             excluded.

          -  Patients who have undergone a highly invasive and extensive surgical procedure within
             4 weeks prior to the first administration of IMP

          -  Patients who previously underwent or plan on undergoing hematopoietic stem cell
             transplantation

          -  Patients with a history of hypersensitivity to the active ingredient or any excipient
             of IMP

          -  Patients who are, in the opinion of the investigator, at high risk for being unable to
             comply with the trial protocol because of mental disorders or other medical conditions
             (alcohol/substance abuse or addiction)

          -  Pregnant or nursing female patients, or female patients with a positive pregnancy test
             at screening. Nursing patients cannot participate in the trial even if they
             discontinue breastfeeding. Female patients must undergo a pregnancy test to confirm
             that they are not pregnant at screening. However, a pregnancy test is not necessary
             for female patients without childbearing potential (ie, patients with a history of
             bilateral oophorectomy or hysterectomy or who have been postmenopausal for at least 12
             months except for cases where menopause could be due to the effect of antineoplastic
             treatment).

          -  Sexually active males (except those with a history of bilateral orchiectomy) or
             females of childbearing potential who do not agree to practice 2 different methods of
             birth control or remain abstinent during the trial and for 3 months (males) and 6
             months (females) after the last dose of IMP. If birth control is employed, 2 of the
             following precautions must be used: vasectomy, tubal ligation, intrauterine device,
             oral contraceptive, and condom (all methods approved or certified in Japan)

          -  Patients who, in the opinion of the investigator, are otherwise ineligible to
             participate in the trial
      
Maximum Eligible Age:N/A
Minimum Eligible Age:20 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:• AUC ratio of AZA after oral administration of AZA tablets in combination with CED tablets compared with subcutaneous (SC) administration of AZA injection
Time Frame:Up to 1 month
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Otsuka Pharmaceutical Co., Ltd.

Last Updated

October 23, 2020