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

Advanced Solid Tumor Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04322552
• Other study ID #: HR-APTN-I-007
• Status: Completed
• Phase: Phase 1
• Start date: March 12, 2020
• Est. completion date: May 3, 2021

Study information

• Verified date: March 2020
• Source: Jiangsu HengRui Medicine Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: May 3, 2021
• Est. primary completion date: April 3, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Advanced Solid Tumor
• Neoplasms

Intervention

Drug:
• Apatinib Mesylate
Apatinib at a dosage of will be administered daily from on D5 through D16
• Digoxin tablet
Digoxin at a dosage of 0.25mg will be administered at day 1 and day 12

Locations

Country	Name	City	State
China	Hunan Cancer Hospital	Changsha	Hunan

Sponsors (1)

Lead Sponsor	Collaborator
Jiangsu HengRui Medicine Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pharmacokinetics parameter: Cmax of digoxin	Peak Plasma Concentration (Cmax) of digoxin	through study completion, an average of 16 days
Primary	Pharmacokinetics parameter: AUC of digoxin	Area under the plasma concentration versus time curve (AUC) of digoxin	through study completion, an average of 16 days
Secondary	Pharmacokinetics parameter: Tmax of digoxin	Time of maximum observed concentration (Tmax) of digoxin	through study completion, an average of 16 days
Secondary	Pharmacokinetics parameter: T1/2 of digoxin	Half time (T1/2) of digoxin	through study completion, an average of 16 days
Secondary	Pharmacokinetic parameters CL/F of digoxin	Total body clearance for extravascular administration (CL/F) of digoxin	through study completion, an average of 16 days
Secondary	Pharmacokinetics parameter: Vz/F of digoxin	Volume of distribution (Vz/F) of digoxin	through study completion, an average of 16 days
Secondary	Number of participants with treatment-related adverse events as assessed by CTCAE v5.0	An adverse event is any untoward medical occurrence in a patient or clinical study participant criteria	through study completion, an average of 16 days