A Pharmacokinetic Interaction Study Between Apatinib Mesylate and Repaglinide or Bupropion in Advanced Solid Tumor Subjects

NCT04457180 | Completed Phase 1

• 1 other identifier: HR-APTN-I-008
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of the study was to assess investigate the pharmacokinetic effects of Apatinib Mesylate on CYP2C8 Substrate Repaglinide or CYP2B6 Substrate Bupropion and metabolite Hydroxy bupropion in Advanced solid tumor subjects. The secondary objective of the study was to assess the safety of Apatinib or/and Repaglinide and Bupropion.

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)

treatment

EXPERIMENTAL

In phase A, subjects receiving a single dose of Repaglinide orally on day 1 , a single dose of Bupropion orally on day 2 and wash-out for 10 days, then apatinib once daily will be conducted on D5 through D16 \# In addition, In phase B, subjects receiving a single dose of Repaglinide (in combination with apatinib) orally on day 12 , a single dose of Bupropion (in combination with apatinib) orally on day 13.

Drug: Apatinib Mesylate; Drug: Repaglinide; Drug: Bupropion

Interventions

Apatinib Mesylate DRUG

Apatinib will be administered daily from on D5 through D16

treatment

Repaglinide DRUG

Repaglinide will be administered daily on D1 and D12

treatment

Bupropion DRUG

Bupropion will be administered daily on D2 and D13

treatment

Eligibility Criteria

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

You may qualify if:

• Age: 18-70 years old (Include both values).
• Patients with histopathologically or cytologically confirmed advanced solid tumor (not necessary to have measurable lesions).
• Refractory or intolerant to standard treatment regimens, or no effective standard treatment regimens available, or the patients refused to use standard treatment plan.
• ECOG PS score: 0-1.
• Expected survival ≥ 3 months.
• Subjects have recovered from other treatments, at least 6 weeks since the last use of nitrosourea or mitomycin; at least 4 weeks since the last use of small molecule targeted therapy; at least 8 weeks since the last use of biological macromolecular therapy; at least 4 weeks since radiotherapy or surgery; at least 4 weeks since the last use of other cytotoxic or cytostatic drugs.
• Major organs must function normally, meeting the following criteria: (1) Hematology (no blood transfusion or blood products within the last 14 days, not corrected with G-CSF or other hematopoietic colony-stimulating factors):
• a. HB≥100 g/L; b. ANC≥1.5×109/L; c. PLT≥90×109/L; (2) Blood biochemistry: d. TBIL≤ 1.25×ULN; e. ALT and AST≤2.5×ULN; f. ALP≤2.5×ULN; g. Serum Cr ≤ 1.5 × ULN or endogenous CrCl \> 60 mL/min (Cockcroft-Gault formula); h. Albumin \> 30 g/L.
• Sign the ICF voluntarily, have good compliance, corporate with follow-up visits, and follow the study requirements.

You may not qualify if:

• Gastric cancer; tumors with risk of bleeding which researchers evaluated.
• Active brain metastasis (medically uncontrolled);
• Symptomatic third space fluid that cannot be controlled by drainage or other methods;
• Dysphagia, chronic diarrhea, or other factors affecting drug intake and absorption;
• Uncontrolled hypertension;
• Heart rate \< 60, Grade II or greater myocardial ischemia or myocardial infarction, uncontrolled arrhythmias (QTc interval ≥ 450 ms in males and ≥ 470 ms in females);
• Contraindications to Repaglinide and Bupropion;
• NYHA Class III-IV cardiac insufficiency or left ventricular ejection fraction (LVEF) \< 50% by echocardiography;
• Abnormal coagulation function (INR \> 1.5 or prothrombin time (PT) \> ULN + 4 s or APTT \> 1.5 ULN), bleeding tendency or who are currently receiving thrombolytics;
• Arterial/venous thrombosis within 6 months prior to the first dose;
• Hemorrhage and thrombophilia;
• Major surgery or with severe traumatic injury, fracture, or ulcer within 4 weeks prior to the first dose;
• Abdominal fistula, gastrointestinal perforation or abdominal abscess within 6 months prior to the first dose;
• Urine protein ≥ ++ and 24 h urine protein ≥ 1.0 g as indicated by urinalysis;
• Treatment with steroids for more than 50 days, or requires chronic steroid use;

Sponsors & Collaborators

• Jiangsu HengRui Medicine Co., Ltd.: lead

Study Sites (1)

The First Affiliated Hospital of University of Science and Technology of China

Hefei, Anhui, 201203, China

Location

MeSH Terms

Interventions

apatinib; repaglinide; Bupropion

Intervention Hierarchy (Ancestors)

Propiophenones; Ketones; Organic Chemicals

Study Officials

• pan yueyin, Ph.D.

  The First Affiliated Hospital of University of Science and Technology of China

  PRINCIPAL INVESTIGATOR

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: June 30, 2020
• First Posted: July 7, 2020
• Study Start: November 16, 2020
• Primary Completion: May 20, 2021
• Study Completion: June 19, 2021
• Last Updated: October 26, 2022

Record last verified: 2022-10

Locations

CN (1)