Clinical trial NCT04322552: A Pharmacokinetic Interaction Study Between Apatinib Mesylate and Transporter Pgp Substrate Digoxin in Advanced Solid Tumor Subjects
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Solid Tumor
Lead sponsor: Jiangsu HengRui Medicine Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2020-03-26
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Pharmacokinetics parameter: Cmax of digoxin
timeFrame: through study completion, an average of 16 days
measure: Pharmacokinetics parameter: AUC of digoxin
timeFrame: through study completion, an average of 16 days
Secondary outcomes:
measure: Pharmacokinetics parameter: Tmax of digoxin
timeFrame: through study completion, an average of 16 days
measure: Pharmacokinetics parameter: T1/2 of digoxin
timeFrame: through study completion, an average of 16 days
measure: Pharmacokinetic parameters CL/F of digoxin
timeFrame: through study completion, an average of 16 days
measure: Pharmacokinetics parameter: Vz/F of digoxin
timeFrame: through study completion, an average of 16 days
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
timeFrame: through study completion, an average of 16 days
Other outcomes:
Locations:
city: Changsha
country: China
facility: Hunan Cancer Hospital
state: Hunan
Study officials:
References: