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A Pharmacokinetic Interaction Study Between Apatinib Mesylate and Transporter Pgp Substrate Digoxin in Advanced Solid Tumor Subjects

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04322552
Recruitment Status : Recruiting
First Posted : March 26, 2020
Last Update Posted : March 26, 2020
Sponsor:
Information provided by (Responsible Party):
Jiangsu HengRui Medicine Co., Ltd.

Brief Summary:
Apatinib, an oral inhibitor of vascular endothelial growth factor receptor 2#VEGFR-2#, Induces Transporter Pgp function in vitro. This study in patients with advanced cancer evaluated the effect of Apatinib on Transporter Pgp function by comparing the pharmacokinetics of Transporter Pgp-specific probe drugs in the presence and absence of Apatinib. The probes used Substrate Digoxin.

Condition or disease Intervention/treatment Phase
Advanced Solid Tumor Drug: Apatinib Mesylate Drug: Digoxin tablet Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 18 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Single Arm, Open and Fixed Sequence Study to Investigate the Pharmacokinetic Effects of Apatinib Mesylate on Transporter Pgp Substrate Digoxin in Advanced Solid Tumor Subjects
Actual Study Start Date : March 12, 2020
Estimated Primary Completion Date : March 12, 2021
Estimated Study Completion Date : September 12, 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Digoxin

Arm Intervention/treatment
Experimental: Treament
In phase A, subjects receiving a single 0.25 mg of digoxin orally and wash-out for 5 days, then apatinib once daily will be conducted on D5 through D16 ; In addition, a single dose of 0.25 mg digoxin (in combination with apatinib) will be orally administered in fasting conditions on D12;
Drug: Apatinib Mesylate
Apatinib at a dosage of will be administered daily from on D5 through D16

Drug: Digoxin tablet
Digoxin at a dosage of 0.25mg will be administered at day 1 and day 12




Primary Outcome Measures :
  1. Pharmacokinetics parameter: Cmax of digoxin [ Time Frame: through study completion, an average of 16 days ]
    Peak Plasma Concentration (Cmax) of digoxin

  2. Pharmacokinetics parameter: AUC of digoxin [ Time Frame: through study completion, an average of 16 days ]
    Area under the plasma concentration versus time curve (AUC) of digoxin


Secondary Outcome Measures :
  1. Pharmacokinetics parameter: Tmax of digoxin [ Time Frame: through study completion, an average of 16 days ]
    Time of maximum observed concentration (Tmax) of digoxin

  2. Pharmacokinetics parameter: T1/2 of digoxin [ Time Frame: through study completion, an average of 16 days ]
    Half time (T1/2) of digoxin

  3. Pharmacokinetic parameters CL/F of digoxin [ Time Frame: through study completion, an average of 16 days ]
    Total body clearance for extravascular administration (CL/F) of digoxin

  4. Pharmacokinetics parameter: Vz/F of digoxin [ Time Frame: through study completion, an average of 16 days ]
    Volume of distribution (Vz/F) of digoxin

  5. Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 [ Time Frame: through study completion, an average of 16 days ]
    An adverse event is any untoward medical occurrence in a patient or clinical study participant criteria



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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

1. Histologically or cytologically confirmed diagnosis of advanced solid tumors. 2. ECOG PS score: 0-1; 3. Expected survival ≥ 3 months; 4. Major organs must function normally, meeting the following criteria:

  1. Hematology

    1. HB≥100 g/L;
    2. ANC≥1.5×109/L;
    3. PLT≥90×109/L;
  2. Blood biochemistry:

    1. TBIL≤ 1.25×ULN;
    2. ALT and AST≤2.5×ULN;
    3. ALP≤2.5×ULN;
    4. Serum Cr ≤ 1.5 × ULN or endogenous CrCl ≥ 60 mL/min (Cockcroft-Gault formula);
    5. Albumin > 30 g/L;
    6. K+>3.0mmol/L; 5. Able to understand and sign an informed consent form (ICF).

Exclusion Criteria:

  1. Primary liver cancer; gastric cancer;
  2. Active brain metastasis (medically uncontrolled), carcinomatous meningitis, spinal cord compression;
  3. Presence of clinically symptomatic third space fluid;
  4. Uncontrolled hypertension (SBP ≥ 140 mmHg and/or DBP ≥ 90 mmHg despite optimal pharmacological treatment);
  5. Uncontrolled clinically significant heart disease, including but not limited to the following: (1) >2 NYHA 2 congestive heart failure; (2) left ventricular ejection fraction (LVEF) < 50% (3) heart rate <60 (4) Grade II or greater myocardial ischemia or myocardial infarction(5) QTc interval ≥ 450 ms in males and ≥ 470 ms in females;
  6. Abnormal coagulation function;
  7. Prior radiotherapy, systemic chemotherapy (< 6 weeks if chemotherapy including nitrosoureas or mitomycin), hormone therapy, surgery or target therapy within 4 weeks before the study drug administration, or any unresolved AEs > CTC-AE Grade 1;
  8. History of psychotropic substance abuse, alcoholism or drug abuse;
  9. Use of study drugs in other clinical trials within 4 weeks prior to the first dose;
  10. Use of a potent CYP3A4 inhibitor or inducer within 2 weeks prior to the first dose;
  11. Use of any prescription or over-the-counter medication, vitamin products or herbs within 2 weeks before taking the investigational drug;
  12. Other factors that may lead to the termination of the participation in the study at the discretion of the investigators.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04322552


Locations
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China, Hunan
HuNan Cancer Hospital Recruiting
Changsha, Hunan, China, 201203
Contact: LI Yan kun, Ph.D    13549680713 ext 86    Lkunyan@163.com   
Principal Investigator: LI Yan kun, Ph.D         
Principal Investigator: Wang Hui, M.D         
Sponsors and Collaborators
Jiangsu HengRui Medicine Co., Ltd.
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Responsible Party: Jiangsu HengRui Medicine Co., Ltd.
ClinicalTrials.gov Identifier: NCT04322552    
Other Study ID Numbers: HR-APTN-I-007
First Posted: March 26, 2020    Key Record Dates
Last Update Posted: March 26, 2020
Last Verified: March 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Neoplasms
Apatinib
Digoxin
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Arrhythmia Agents
Cardiotonic Agents
Protective Agents
Physiological Effects of Drugs