A Pharmacokinetic Interaction Study Between Apatinib and Rosuvastatin or Metformin in Solid Tumor Subjects.

NCT04428086 | Completed Phase 1

• 1 other identifier: HR-APTN-I-010
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of the study was to assess investigate the pharmacokinetic effects of Apatinib on Rosuvastatin or Metformin. The secondary objective of the study was to assess the safety of Apatinib alone or Rosuvastatin/Metformin alone or concomitant medication.

Conditions

Solid Tumor, Adult

Outcome Measures

Primary Outcomes (3)

• Maximum Observed Plasma Concentration (Cmax)

  The Cmax is the maximum observed concentration

  Up to Day 10

• Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Time (AUC [0-last])

  The AUC (0-last) is the area under the plasma concentration-time curve from time zero to last quantifiable time.

  Up to Day 10

• Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC[0-infinity])

  The AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to infinite time

  Up to Day 10

Secondary Outcomes (1)

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

  through study completion, an average of 35 or 37 days in two groups.

Study Arms (2)

Assess PK effects of Apatinib on Rosuvastatin

EXPERIMENTAL

Participant will be administered a single oral dose of rosuvastatin 10 milligram (mg) on Day 1 and Day 7 and Apatinib at a dose of 250 mg once daily from Day 4 until Day 9.

Drug: Apatinib in arm1; Drug: Rosuvastatin

Assess PK effects of Apatinib on Metformin

EXPERIMENTAL

Participant will be administered a single oral dose of metformin 500 milligram (mg) on Day 1 and Day 6 and Apatinib at a dose of 250 mg once daily from Day 3 until Day 7.

Drug: Apatinib in arm2; Drug: Metformin

Interventions

Apatinib in arm1 DRUG

Apatinib will be administered at a dose of 250 mg once daily from Day 4 to Day 9.

Assess PK effects of Apatinib on Rosuvastatin

Rosuvastatin DRUG

Rosuvastatin will be administered as a single oral 10 milligram (mg) dose on Day 1 and Day 7.

Assess PK effects of Apatinib on Rosuvastatin

Apatinib in arm2 DRUG

Apatinib will be administered at a dose of 250 mg once daily from Day 3 to Day 7.

Assess PK effects of Apatinib on Metformin

Metformin DRUG

Metformin will be administered as a single oral 500 mg on Day 1 and Day 6.

Assess PK effects of Apatinib on Metformin

Eligibility Criteria

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

You may qualify if:

• Subjects must meet all of the following criteria to enter the study:
• Age: 18-70 years old (Include both values);
• Patients with histopathologically or cytologically confirmed advanced solid tumor(except primary gastrointestinal tumors or metastatic gastrointestinal tumors and primary hepatocellular tumors) , not necessary to have measurable lesions;
• The standard systemic treatment plan for tumors is ineffective, or intolerable, or there is no recurrence and metastasis after adjuvant chemotherapy and radiotherapy after surgery;
• ECOG PS score: 0-1;
• Expected survival ≥ 3 months;
• Adverse reactions caused by the subject receiving other treatments have recovered (recovered to ≤ grade 1 according to NCI-CTCAE 5.0, except for hair loss), more than 4 weeks after receiving radiotherapy or surgery or receiving other cytotoxic drugs or cell growth inhibitor.
• Major organs must function normally, meeting the following criteria:
• I. Haematology (no blood transfusion or blood products within the last 14 days, not corrected with G-CSF or other hematopoietic colony-stimulating factors):
• HB≥100 g/L;
• ANC≥1.5×109/L;
• PLT≥90×109/L;
• II. Blood biochemistry:
• TBIL≤ 1.25×ULN;
• ALT and AST≤2.5×ULN;

You may not qualify if:

• Subjects meeting any one of the followings will be excluded in this study:
• Patients with gastrointestinal diseases that affect the use or absorption of drugs, such as gastric cancer or intestinal cancer, unable to swallow, chronic diarrhea, intestinal obstruction, large stomach or total gastrectomy, or within 6 months before the first medication Patients with abdominal fistula, gastrointestinal perforation or abdominal abscess;
• Active (without medical control) brain metastases, cancerous meningitis, spinal cord compression patients, or imaging CT or MRI examination at screening to find diseases of the brain or pia mater
• Presence of clinically symptomatic third space fluid (e.g. large pleural fluid or ascites) that cannot be controlled by drainage or other methods;
• Patients with hypertension, or patients with a history of hypertension
• Patients with NYHA Class III-IV cardiac insufficiency or left ventricular ejection fraction (LVEF) \< 50% by echocardiography; uncontrolled arrhythmias (QTc interval ≥ 450 ms in males and ≥ 470 ms in females);
• During the study period, patients should be used drugs that may lead to prolonged QTc interval (such as antiarrhythmic drugs, quinidine, disopyramide, procainamide, sotalol, amiodarone, etc.)
• Patients with abnormal coagulation function (INR \> 1.5 or prothrombin time (PT) \> ULN + 4 s or APTT \> 1.5 ULN)
• Patients with clinically significant bleeding or clear bleeding tendency within 3 months prior to the first dose, such as coughing up blood, hemoptysis, GI bleeding, hemorrhagic gastric ulcer, or baseline fecal occult blood (FOB) ++ and above. Gastroscopy is required for patients with FOB (+) and no surgical resection of primary gastric tumor. In case of ulcerative gastric cancer, patients are not enrolled due to a risk of acute gastrointestinal hemorrhage;
• Events of arterial/venous thrombosis within 6 months prior to the first dose, such as cerebrovascular accidents (including transient ischemic attacks, cerebral hemorrhage, brain infarction), deep vein thrombosis, and pulmonary embolism;
• Known hereditary or acquired hemorrhage and thrombophilia (such as hemophilia, coagulopathy, thrombocytopenia, hypersplenism, etc.);
• Patients treated with anticoagulants or vitamin K antagonists such as warfarin, heparin or similar drugs;
• Have undergone major surgery or with severe traumatic injury, fracture, or ulcer within 4 weeks prior to the first dose; There is no previous wound healing.
• Use of study drugs in other clinical trials within 4 weeks prior to the first dose;
• Drugs that is CYP3A inhibitor, or the transporter BCRP or MATE1 inhibitor, or drugs that affect gastric acid secretion, or Chinese herbal medicines within 2 weeks before the first dose; use the drug that is metabolic enzyme CYP3A inducer within 4 weeks before the first dose

Sponsors & Collaborators

• Jiangsu HengRui Medicine Co., Ltd.: lead

Study Sites (1)

The Fourth Hospital of Hebei Medical University

Shijiazhuang, Hebei, 050035, China

Location

MeSH Terms

Interventions

apatinib; 26S proteasome non-ATPase regulatory subunit 13; Rosuvastatin Calcium; JPT1 protein, human; Metformin

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Biguanides; Guanidines; Amidines

Study Design

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

Model Details: Two arms Assignment

Study Record Dates

• First Submitted: May 27, 2020
• First Posted: June 11, 2020
• Study Start: July 27, 2020
• Primary Completion: August 22, 2021
• Study Completion: August 22, 2021
• Last Updated: July 26, 2022

Record last verified: 2022-07

Locations

CN (1)