Clinical trial NCT03882281: Pharmacokinetics Profiles of HQP1351 Under Fasting and High-fat Meals in Patients With Chronic Myeloid Leukemia
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Chronic Myeloid Leukemia, Chronic Phase
Keywords: Chronic Myeloid Leukemia, Chronic Phase
HQP1351
Lead sponsor: Ascentage Pharma Group Inc.
Sponsor class: INDUSTRY
Collaborators: name: HealthQuest Pharma Inc.
First posted: 2019-03-20
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.).

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Area under the curve from the time of dosing to infinity [AUC(0-inf)]
timeFrame: 1-5 days after every drug administration
measure: Area under the curve from the time of dosing to the last measurable concentration [AUC(0-last)]
timeFrame: 1-5 days after every drug administration
measure: Percentage of AUC(0-inf)_obs due to extrapolation from the last measurable time point to infinity (AUC_%Extrap)
timeFrame: 1-5 days after every drug administration
measure: Maximum observed concentration (Cmax)
timeFrame: 1-5 days after every drug administration
measure: Time of maximum observed concentration (Tmax)
timeFrame: 1-5 days after every drug administration
measure: Terminal elimination half life (T1/2)
timeFrame: 1-5 days after every drug administration
measure: Total body clearance for extravascular administration (CL/F)
timeFrame: 1-5 days after every drug administration
measure: Volume of distribution based on the terminal phase for extravascular administration (Vz/F)
timeFrame: 1-5 days after every drug administration
Secondary outcomes:
measure: Incidence of toxicity
timeFrame: up to 12 days
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking University People's Hospital
state: Beijing
Study officials:
affiliation: Peking University People's Hospital
name: QIAN JIANG, Professor
role: PRINCIPAL_INVESTIGATOR
References: