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

NCT ID: NCT04322552

Last Updated: 2022-11-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-03-12
• Study Completion Date: 2021-05-03

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.

Conditions

Advanced Solid Tumor

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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；

Group Type: EXPERIMENTAL

Apatinib Mesylate

Intervention Type: DRUG

Apatinib at a dosage of will be administered daily from on D5 through D16

Digoxin tablet

Intervention Type: DRUG

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

Interventions

Apatinib Mesylate

Apatinib at a dosage of will be administered daily from on D5 through D16

Intervention Type: DRUG

Digoxin tablet

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

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Jiangsu HengRui Medicine Co., Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Hunan Cancer Hospital

Changsha, Hunan, China

Countries

China

Other Identifiers

HR-APTN-I-007

Identifier Type: -

Identifier Source: org_study_id