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

NCT03882281 | Completed Phase 1

• 1 other identifier: HQP1351LC104
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

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.).

Conditions

Chronic Myeloid Leukemia, Chronic Phase

Keywords

Chronic Myeloid Leukemia, Chronic Phase; HQP1351

Outcome Measures

Primary Outcomes (8)

• Area under the curve from the time of dosing to infinity [AUC(0-inf)]

  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)]

  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)

  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)

  Maximum observed plasma concentration of HQP1351.

  1-5 days after every drug administration

• Time of maximum observed concentration (Tmax)

  Time to maximum observed plasma concentration of HQP1351.

  1-5 days after every drug administration

• Terminal elimination half life (T1/2)

  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)

  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)

  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 Outcomes (1)

• Incidence of toxicity

  up to 12 days

Study Arms (2)

A group

EXPERIMENTAL

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

B group

EXPERIMENTAL

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

Interventions

HQP1351 DRUG

Orally, single dose of 30mg on day 1 and day 8.

A group; B group

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Male or non-pregnant, non-lactating female patients age 18-55 years old.
• CML Patients in CP with Ph-positive or BCR/ABL-positive.
• 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.
• 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.
• Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2.
• Predicted life expectancy of ≥3 months.
• 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.

You may not qualify if:

• 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.
• Require concurrent treatment with drugs that may have interactions with the study drug.
• Have previously been treated with ponatinib (or drugs of similar composition).
• Absorption disorder syndrome or other diseases affecting oral drug absorption.
• 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.
• Mean pulmonary artery pressure \>25 mmHg.
• Have a history of serious cardiovascular diseases during the previous treatment of chronic myeloid leukemia with TKI.
• Underwent autologous or allogeneic stem cell transplant.
• Abnormal coagulation function，or have a bleeding disorder within 3 months before first administration.
• 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.
• Require concurrent treatment with immunosuppressive agents, other than corticosteroids prescribed for a short course of therapy.
• Have active nervous system (CNS) disease as evidence by cytology or pathology. In the absence of clinical CNS disease, lumbar puncture is not required.
• Active symptomatic infection.
• Known to be allergic to study drug ingredients or their analogues.
• Are pregnant or lactating or expecting pregnancy during the study program.

Sponsors & Collaborators

• Ascentage Pharma Group Inc.: lead
• HealthQuest Pharma Inc.: collaborator

Study Sites (1)

Peking University People's Hospital

Beijing, Beijing Municipality, 100044, China

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Chronic-Phase

Interventions

olverembatinib

Condition Hierarchy (Ancestors)

Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• QIAN JIANG, Professor

  Peking University People's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 12, 2019
• First Posted: March 20, 2019
• Study Start: March 25, 2019
• Primary Completion: November 16, 2019
• Study Completion: November 16, 2019
• Last Updated: January 22, 2020

Record last verified: 2020-01

Locations

CN (1)