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

Inclusion criteria

• 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:

• Hematology

• HB≥100 g/L;
• ANC≥1.5×109/L;
• PLT≥90×109/L;
• Blood biochemistry:

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

Exclusion criteria

• Primary liver cancer; gastric cancer;
• Active brain metastasis (medically uncontrolled), carcinomatous meningitis, spinal cord compression;
• Presence of clinically symptomatic third space fluid;
• Uncontrolled hypertension (SBP ≥ 140 mmHg and/or DBP ≥ 90 mmHg despite optimal pharmacological treatment);
• 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;
• Abnormal coagulation function;
• 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;
• History of psychotropic substance abuse, alcoholism or drug abuse;
• Use of study drugs in other clinical trials within 4 weeks prior to the first dose；
• Use of a potent CYP3A4 inhibitor or inducer within 2 weeks prior to the first dose;
• Use of any prescription or over-the-counter medication, vitamin products or herbs within 2 weeks before taking the investigational drug;
• Other factors that may lead to the termination of the participation in the study at the discretion of the investigators.