To Study the Oral Bioavailability of a New Combination Formation of Decitabine and Tetrahydrouridine in Healthy Males

An Open Label, Randomized, Single Dose, Two Way Crossover, Bioavailability Study of a Combination Formulation of Decitabine/Tetrahydrouridine (2.5 mg/100 mg) Modified Release Capsules in Healthy, Fasting, Male Adults

This is an open-label, randomized, single-dose per period, two-period, crossover study to evaluate the relative bioavailability of decitabine and tetrahydrouridine ingested as a modified-release combination formulation compared to THU and decitabine ingested as immediate-release capsules

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Decitabine; Drug: Tetrahydrouridine

Detailed Description

This study builds on previous bioavailability studies in healthy volunteers of a larger combination dosage form of decitabine and tetrahydrouridine (THU) (5 mg/250 mg). The smaller combination dosage form being evaluated in this study (2.5 mg/100 mg) is intended to allow more precise weight band dosing, to hopefully further decrease the inter-individual variability in pharmacokinetics and pharmacodynamics.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • San Antonio, Texas, United States, 78217
      • Worldwide Clinical Trails Early Phase Services

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Must understand and voluntarily sign a written informed consent form (ICF) prior to any study-related procedures being performed and be able to adhere to restrictions and examination schedules.
• Must be able to communicate with the Investigator and understand and comply with the requirements of the study.
• Healthy male volunteers from any race between 18 to 50 years of age (inclusive), and in good health as determined by past medical history, physical examination, vital signs, ECG, and laboratory tests at screening.
• Must have a body mass index (BMI) between 18 and 30 kg/m2 (inclusive) and a weight between 60 and 100 kg (~132 to 220 lb), inclusive, at screening.
• Subject's clinical laboratory test results have no clinically significant findings, in the opinion of the Investigator.
• Vital signs including systolic and diastolic blood pressure, heart rate, and temperature will be assessed in the supine position after the subject has rested for at least 5 minutes. At screening, the potential subject must have a body temperature of ≤37.7°C, with systolic blood pressure between 90 and 140 mmHg (inclusive), diastolic blood pressure between 60 and 90 mmHg (inclusive), and heart rate between 40 and 100 bpm (inclusive). Vital signs criteria at each check-in and predose measurements will be at the Investigator's discretion. Out-of-range vital signs may be repeated once at the discretion of the Investigator.
• Subjects must be free of any clinically significant disease that would interfere with the study evaluations.
• Males with female partners must use a highly effective form of contraception (i.e., double barrier method, which includes a condom plus diaphragm with spermicide or condom plus spermicide or has had a vasectomy) or have no female partners of childbearing potential at the time of screening and for 90 days after the last dose of study treatment. Subjects must also agree not to donate sperm for the duration of the study and until 90 days after the last dose of study treatment.

Exclusion Criteria:

• History or presence of clinically significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, oncologic, or psychiatric disease or any other condition, including the presence of laboratory abnormalities, that, in the opinion of the Investigator, would jeopardize the safety of the subject or the validity of the study results.
• Any serious medical condition, clinically significant laboratory abnormality, or psychiatric illness that would prevent the subject from signing the ICF.
• Tests positive for COVID-19 via polymerase chain reaction (PCR) test at check-in.
• Recent history within 3 years of any clinically significant neurological, gastrointestinal, renal, hepatic, cardiovascular, psychological, pulmonary, metabolic, endocrine, hematologic, or other major disorders.
• Used any prescribed systemic or topical medication within 14 days of the first dose administration.
• Used any non-prescribed systemic (including herbal medicines, e.g. St. John's Wort) or topical medication within 7 days of the first dose administration (with the exception of vitamin/mineral supplements)
• Subjects who have any surgical or medical conditions possibly affecting drug absorption, distribution, metabolism, and excretion (ADME).
• Exposed to an investigational drug (new chemical entity) within 30 days preceding the first dose administration or currently enrolled in any investigational trials.
• Donated blood or plasma within 8 weeks preceding the first dose administration.
• History of relevant drug and/or food allergies.
• Any clinically significant allergic disease (excluding nonactive hay fever).
• Self-reported history of drug abuse of at least 2 years prior to the first dose of study treatment, and/or positive drug screening test due to illicit drugs at screening or Day 1 of each period.
• Self-report of more than 21 units of alcohol per week (1 unit of alcohol equals approximately 12 ounces of 5% alcohol by volume [ABV] beer, 8 ounces of 7% ABV malt liquor, 5 ounces of 12% ABV wine, 1.5 ounces 40% ABV [80 proof] distilled spirits [e.g., gin, rum, vodka, whiskey, etc.]), and/or positive alcohol screen at screening or Day 1 of each period.
• Smokers or users of other tobacco products (e.g., chewing tobacco, or those using nicotine-containing products [i.e., patches, gum]) in the 3 months prior to screening, or positive urine cotinine test.
• Known to have serum hepatitis or known to be a carrier of the hepatitis B surface antigen (HBsAg) or hepatitis C antibody (HCVAb), or tests positive for human immunodeficiency virus (HIV) antibodies at screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Modified release formulation of decitabine and tetrahydrouridine; A modified-release combination formulation of decitabine/THU (2.5 mg/100 mg per capsule given as a single oral dose with approximately 240 mL (8 fluid ounces) of ambient temperature water.	Drug: Decitabine; Oral administration of decitabine as a single dose to healthy male subjects; Other Names: DEC; Drug: Tetrahydrouridine; Oral administration of Tetrahydrouridine as a single dose to healthy male subjects; Other Names: THU
Active Comparator: Immediate release capsules of decitabine and tetrahydrouridine; Capsules of THU are given as a single oral dose with approximately 240 mL (8 fluid ounces) of ambient temperature water, followed by a single oral dose of decitabine given 1 hour (± 5 min) later with approximately 240 mL (8 fluid ounces) of ambient temperature water.	Drug: Decitabine; Oral administration of decitabine as a single dose to healthy male subjects; Other Names: DEC; Drug: Tetrahydrouridine; Oral administration of Tetrahydrouridine as a single dose to healthy male subjects; Other Names: THU

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak decitabine and tetrahydrouridine concentration in plasma	Maximum levels of drug (decitabine and tetrahydrouridine) in plasma over 24 hr	0 to 24 hours
Decitabine and tetrahydrouridine drug level exposure over 24 hr	Area under the plasma concentration time profile for decitabine and tetrahydrouridine	0 to 24 hours

Collaborators and Investigators

• Sponsor: EpiDestiny, Inc.
• Collaborators: Worldwide Clinical Trials
• Investigators: Principal Investigator: Ingela Danielsson, MD, Worldwide Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): March 24, 2023
• Primary Completion (Actual): June 30, 2023
• Study Completion (Actual): October 10, 2023

Study Registration Dates

• First Submitted: March 31, 2023
• First Submitted That Met QC Criteria: April 14, 2023
• First Posted (Actual): April 18, 2023

Study Record Updates

• Last Update Posted (Actual): May 22, 2025
• Last Update Submitted That Met QC Criteria: May 20, 2025
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Decitabine; Tetrahydrouridine
• Other Study ID Numbers: EPI-01A-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data (IPD) will not be shared with researchers

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No