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

NCT04322552 | Completed Phase 1

• 1 other identifier: HR-APTN-I-007
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (2)

• Pharmacokinetics parameter: Cmax of digoxin

  Peak Plasma Concentration (Cmax) of digoxin

  through study completion, an average of 16 days

• 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 Outcomes (5)

• Pharmacokinetics parameter: Tmax of digoxin

  through study completion, an average of 16 days

• Pharmacokinetics parameter: T1/2 of digoxin

  through study completion, an average of 16 days

• Pharmacokinetic parameters CL/F of digoxin

  through study completion, an average of 16 days

• Pharmacokinetics parameter: Vz/F of digoxin

  through study completion, an average of 16 days

• Number of participants with treatment-related adverse events as assessed by CTCAE v5.0

  through study completion, an average of 16 days

Study Arms (1)

Treament

EXPERIMENTAL

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; Drug: Digoxin tablet

Interventions

Apatinib Mesylate DRUG

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

Treament

Digoxin tablet DRUG

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

Treament

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Jiangsu HengRui Medicine Co., Ltd.: lead

Study Sites (1)

Hunan Cancer Hospital

Changsha, Hunan, 410013, China

Location

MeSH Terms

Interventions

apatinib; Digoxin

Intervention Hierarchy (Ancestors)

Digitalis Glycosides; Cardenolides; Cardiac Glycosides; Cardanolides; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Glycosides; Carbohydrates

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 17, 2020
• First Posted: March 26, 2020
• Study Start: March 12, 2020
• Primary Completion: April 3, 2021
• Study Completion: May 3, 2021
• Last Updated: November 7, 2022

Record last verified: 2020-03

Locations

CN (1)