Bioequivalence of Azacitidine 300 mg Film-Coated Tablets in Adult Patients With Acute Myeloid Leukaemia (AML)

A Randomized, Single Oral Dose, Open Label, Two Sequence, Two Treatment, Four Periods, Full Replicate Crossover Study to Determine the Bioequivalence of Azacitidine 300 mg Film- Coated Tablets Versus Onureg® 300 mg Film-Coated Tablets for Adult Patients With Acute Myeloid Leukaemia (AML) Under Fasting Conditions

A Randomized, Single Oral Dose, Open Label, Two Treatment, Crossover study to investigate the bioequivalence of the Test Product Azacitidine 300 mg Film coated tablets relative to Reference Product Onureg® 300 mg Film Coated Tablets in adult patients with AML under fasting conditions

Study Overview

• Status: Not yet recruiting
• Conditions: Acute Myeloid Leukaemia
• Intervention / Treatment: Drug: Azacitidine; Drug: Onureg

• Study Type: Interventional
• Enrollment (Estimated): 32
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Ruba Jaber; Phone Number: 11663 00962797486999; Email: rjaber@hikma.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients age ≥ 18 years of age at the time of signing the informed consent document.
2. Patients with documented diagnosis of AML according to the 2022 updates of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukaemia.

3. Patients who achieved complete remission (CR) or complete remission with incomplete blood count recovery (CRi) following induction therapy with or without consolidation treatment and who are not candidates for, including those who choose not to proceed to, hematopoietic stem cell transplantation (HSCT). The definitions of response criteria for CR or CRi are primarily those defined by the 2022 report from the European LeukemiaNet (ELN) on AML as below:

   CR defined as bone marrow blasts <5%; absence of circulating blasts; absence of extramedullary disease; ANC ≥ 1.0 × 10^9/L (1,000/µL); platelet count ≥ 100 × 10^9/L(100 000/µL).

   CRi defined as all CR criteria, except for residual neutropenia < 1.0 × 10^9/L (1,000/µL) or thrombocytopenia < 100 × 10^9/L (100 000/µL).

4. Patients who don't have a known or suspected hypersensitivity to Azacitidine or any other ingredient used in the manufacturing of Azacitidine.
5. Patients who are physically able for appropriate pharmacokinetics sampling according to principal investigator evaluation.
6. Patients who have a haematological profile appropriate for receiving Azacitidine 300 mg dose for 4 consecutive days as per the principal investigator assessment.
7. Patients who understand and voluntarily sign a written informed consent document prior to any study related assessments/procedures are conducted.
8. Patient is capable of consent.
9. Females of childbearing potential may participate, providing the subject meets the following conditions: Negative serum pregnancy test at screening (sensitivity of at least 25 mIU/mL), and willing to use effective contraception during and up to 6 months after study.
10. Male patients must be willing to use effective contraception during and up to 3 months after the study.

Exclusion Criteria:

1. Patients with history of drug or alcohol abuse.
2. Female patients who are pregnant or nursing (lactating).
3. Patients with medical condition, laboratory abnormality, or psychiatric illness that, in the opinion of the investigator, might interfere with subject safety, compliance or evaluation of the condition of the study.
4. Patients with positive blood screen for HIV, Hepatitis B (HbsAG) or Hepatitis C (HCV) virus.
5. Patients with experience in any investigational drug in a clinical study within 6 months prior to study Day 1.
6. Patients has a difficulty fasting or consuming standard meals.
7. Patients has history of difficulties in swallowing or any gastrointestinal disease which could affect the drug absorption.
8. Patients does not agree to not be engaged in strenuous exercise at least one day prior to study drug administration until donating the last sample of the study.
9. Patients does not agree to not consuming any beverages or food containing grapefruit for at least two weeks prior to first study drug administration until donating the last sample of the study.
10. Patients does not agree to not consuming any beverages or food containing methyl-xanthines e.g., caffeine (coffee, tea, cola, energy drinks, chocolate etc.) at least 48 hours prior to first study drug administration until donating the last sample of the study.
11. Patients does not agree to not consuming any alcohol containing beverages and food at least 48 hours prior to first study drug administration until donating the last sample of the study

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Test Product: Azacitidine 300 mg Film coated tablets; Single oral dose of Azacitidine 300 mg Film coated tablets	Drug: Azacitidine; Azacitidine 300 mg Film coated tablets
Active Comparator: Reference Product: Onureg® 300 mg Film Coated Tablets; Single oral dose of Onureg® 300 mg Film Coated Tablets	Drug: Onureg; Azacitidine 300 mg Film coated tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax	Maximum measured plasma concentration over the time span specified	5 hours
AUC0-t	The area under the plasma concentration versus time curve, from time (0) to the last measurable concentration (t), as calculated by the linear trapezoidal method.	5 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC0-∞	The area under the plasma concentration versus time curve from time (0) to infinity.	5 hours
Kel	Apparent first-order elimination or terminal rate constant	5 hours
Tmax	Time of the maximum measured plasma concentration.	5 hours
T1/2el	The elimination or terminal half-life.	5 hours
Adverse Events (AEs)	Adverse Events (AEs)	Day 4
Change in clinical safety labs	Descriptive Change in clinical safety labs	Day 4

Collaborators and Investigators

• Sponsor: Hikma Pharmaceuticals LLC

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2024
• Primary Completion (Estimated): January 1, 2025
• Study Completion (Estimated): March 1, 2025

Study Registration Dates

• First Submitted: March 11, 2024
• First Submitted That Met QC Criteria: March 17, 2024
• First Posted (Actual): March 22, 2024

Study Record Updates

• Last Update Posted (Actual): March 22, 2024
• Last Update Submitted That Met QC Criteria: March 17, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Azacitidine
• Other Study ID Numbers: HIK-AZA-2023-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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