Pharmacokinetics Profiles of HQP1351 Under Fasting and High-fat Meals in Patients With Chronic Myeloid Leukemia (CML)

January 19, 2020 updated by: Ascentage Pharma Group Inc.

A Randomized, Open, Double-crossing Trial to Evaluate the Effect of Fasting or High-fat Meals on the Pharmacokinetics of Single Oral Administration of HQP1351 Tablets on an Empty Stomach or a High-fat Meal in Patients With Chronic Myeloid Leukemia

The purpose of this study is to characterize the pharmacokinetics of HQP1351 in participants with resistant chronic myeloid leukemia (CML) in chronic phase (CP) after high-fat and fasting meals separately（Selection of high-fat meal spectrum：《The Food - Effect Bioavailability and Fed Bioequivalence Studies》high fat diet should be 800-1000 kcal heat.).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

The drug being test in this study is HQP1351，the study will characterize the pharmacokinetics of HQP1351 in participants with resistant chronic myeloid leukemia（CML）in chronic phase（CP）after high-fat meal and fasting meal separately at a dose of 30mg，single-dose. The study will enroll 12 subjects totally and be randomly divided into 2 groups（A group and B group）. Every group will have 6 subjects. The experiment is divided into two periods，in period 1, subjects in the group A will be given HQP1351 30mg after fasting meal，and the group B will be given HQP1351 30mg after 30 minutes of high-fat meal. Then after a seven-day of cleaning time the two groups of subjects took the drug interchangeably in the period 2.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
12

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Beijing
      • Beijing, Beijing, China, 100044
        • Peking University People's Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years to 51 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Male or non-pregnant, non-lactating female patients age 18-55 years old.
  2. CML Patients in CP with Ph-positive or BCR/ABL-positive.
  3. Previously treated with and or developed resistance / intolerance to second generation tyrosine kinase inhibitors (TKIs) (dasatinib，nilotinib）or，been identified to have the T315I mutation at any time during treatment.
  4. Ability to understand and willingness to sign a written informed consent form. The consent form must be signed by the patient prior to any study-specific procedures.
  5. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2.
  6. Predicted life expectancy of ≥3 months.

  7. Organ function as indicated by the following laboratory indicators must be met:

    • Hemoglobin ≥8.0g/dL.
    • White blood cell count ≥ 3.0×10^9/L, neutrophil count≥ 1.5 x 10^9/L.
    • Platelet count ≥ 75×10^9/L.
    • Serum creatinine ≤ 1.5×upper limit of normal (ULN) or 24 hours calculated creatinine clearance ≥ 50ml/min when serum creatinine >1.5×ULN.
    • Serum albumin≥ 3.0 g/dL.
    • Total bilirubin ≤ 1.5 x ULN.
    • Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤ 2.5 x ULN of institution's normal range.
    • Lipase≤1.5×ULN, Amylase≤1.5×ULN.
    • Prothrombin time (PT), activated partial thromboplastin time (APTT), INR≤1.5×ULN.
  8. Cardiac function index: ejection fraction (EF) > 50%.
  9. Corrected QT interval (QTc) interval on electrocardiogram (ECG) evaluation: QTc≤450ms in males or ≤470ms in females.
  10. Willingness to use contraception by a method that is deemed effective by the investigator by both males and female patients of child bearing potential and their partners throughout the treatment period and for at least 120 days following the last dose of study drug.
  11. Willingness and ability to comply with study procedures and follow-up examination.

Exclusion Criteria:

  1. Received cytotoxic chemotherapy or radiotherapy within 28 days, interferon or cytarabine within 14 days, any investigational therapy within 14 days prior to the first dose of study drug, or have not recovered (> grade 1 by NCI CTCAE v 4.03) from adverse events (AEs ) (except alopecia) due to agents previously administered.
  2. Require concurrent treatment with drugs that may have interactions with the study drug.
  3. Have previously been treated with ponatinib (or drugs of similar composition).
  4. Absorption disorder syndrome or other diseases affecting oral drug absorption.
  5. Have any history of heart or vascular disease, such as hypertension (systolic blood pressure > 140 mmHg and/or diastolic blood pressure > 90mmHg), or take medications that are known to cause prolonged ECG QT interval.
  6. Mean pulmonary artery pressure >25 mmHg.
  7. Have a history of serious cardiovascular diseases during the previous treatment of chronic myeloid leukemia with TKI.
  8. Underwent autologous or allogeneic stem cell transplant.
  9. Abnormal coagulation function，or have a bleeding disorder within 3 months before first administration.
  10. Underwent major surgery (with the exception of minor surgical procedures, such as placement or bone marrow biopsy) with 14 days prior to first dose of study drug.
  11. Require concurrent treatment with immunosuppressive agents, other than corticosteroids prescribed for a short course of therapy.
  12. Have active nervous system (CNS) disease as evidence by cytology or pathology. In the absence of clinical CNS disease, lumbar puncture is not required.
  13. History of primary malignancy (cured for more than 5 years, completely resected superficial skin cancer other than melanoma, adequately treated in-situ cancer, or controlled prostate cancer will not be considered exclusionary).
  14. Active symptomatic infection.
  15. Known to be allergic to study drug ingredients or their analogues.
  16. Are pregnant or lactating or expecting pregnancy during the study program.
  17. Suffer from any condition or illness that, in the opinion of the Investigator or the sponsor, would compromise patient safety or interfere with the evaluation of the safety of the study drug.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: A group
Subjects in the group A will be given HQP1351 after fasting meal on Day 1. Then after a seven-day of cleaning time, subjects in the group A will be given HQP1351 after 30 minutes of high-fat meal on Day 8.
Drug: HQP1351
Orally, single dose of 30mg on day 1 and day 8.
Experimental: B group
Subjects in the group B will be given HQP1351 after 30 minutes of high-fat meal on Day 1. Then after a seven-day of cleaning time, subjects in the group B will be given HQP1351 after fasting meal on Day 8.
Drug: HQP1351
Orally, single dose of 30mg on day 1 and day 8.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Area under the curve from the time of dosing to infinity [AUC(0-inf)]
Time Frame: 1-5 days after every drug administration
Area under the plasma concentration-time curve from time zero extrapolated to infinity time of HQP1351.
1-5 days after every drug administration
Area under the curve from the time of dosing to the last measurable concentration [AUC(0-last)]
Time Frame: 1-5 days after every drug administration
Area under the plasma concentration-time curve from time zero to the last measurable time point of HQP1351.
1-5 days after every drug administration
Percentage of AUC(0-inf)_obs due to extrapolation from the last measurable time point to infinity (AUC_%Extrap)
Time Frame: 1-5 days after every drug administration
Percentage of area under the concentration time curve from time zero extrapolated to infinite time obtained by extrapolation of HQP1351.
1-5 days after every drug administration
Maximum observed concentration (Cmax)
Time Frame: 1-5 days after every drug administration
Maximum observed plasma concentration of HQP1351.
1-5 days after every drug administration
Time of maximum observed concentration (Tmax)
Time Frame: 1-5 days after every drug administration
Time to maximum observed plasma concentration of HQP1351.
1-5 days after every drug administration
Terminal elimination half life (T1/2)
Time Frame: 1-5 days after every drug administration
Terminal elimination half life (T1/2) is defined as the duration until observation of half of the maximum concentration of HQP1351.
1-5 days after every drug administration
Total body clearance for extravascular administration (CL/F)
Time Frame: 1-5 days after every drug administration
Apparent clearance of HQP1351 following oral dosing. Clearance of a drug is a measure of rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose of HQP1351 (apparent oral clearance) is influenced by the fraction of dose absorbed.
1-5 days after every drug administration
Volume of distribution based on the terminal phase for extravascular administration (Vz/F)
Time Frame: 1-5 days after every drug administration
Apparent volume of distribution of HQP1351. Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution of HQP1351 after oral dose (Vz/F) is influenced by the fraction absorbed.
1-5 days after every drug administration

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Incidence of toxicity
Time Frame: up to 12 days
Incidence of toxicity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03
up to 12 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Ascentage Pharma Group Inc.

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
HealthQuest Pharma Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 25, 2019

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 16, 2019

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 16, 2019

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 12, 2019

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 17, 2019

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 20, 2019

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 22, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 19, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • HQP1351LC104

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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