Advanced Solid TumorPhase 1NCT04457180
A Pharmacokinetic Interaction Study Between Apatinib Mesylate and Repaglinide or Bupropion in Advanced Solid Tumor Subjects
A Phase 1 study testing Apatinib Mesylate, Repaglinide and Bupropion in people with Advanced Solid Tumor, run by Jiangsu HengRui Medicine Co., Ltd. at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Advanced Solid Tumor
- What is being tested?
- Apatinib Mesylate, Repaglinide and Bupropion
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteChina
- Study dates
- 16 Nov 2020to 19 Jun 2021
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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):
- 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.
Who cannot join
- 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);
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- 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;
- Use of study drugs in other clinical trials within 4 weeks prior to the first dose;
- Use of drugs affected gastric acid secretion or inhibitors of cytochrome enzyme CYP2C8、CYP2B6、CYP2D6、CYP3A or transporter OATP1B1, or traditional Chinese medicine within 2 weeks prior to the first dose; use of inducers of metabolic enzymes CYP2C8, CYP2B6, CYP2D6, or CYP3A within 4 weeks prior to the first dose;
- Unable to hold drugs that may prolong QT interval during the study (such as antiarrhythmics);
- Habitual alcohol consumption or smoking, tested positive for alcohol screening, and unable to abstain from smoking and alcohol during the trial;
- Other factors affecting drug absorption, distribution, metabolism, excretion within 48 hours；
- Active hepatitis B (positive HBsAg and HBV-DNA≥104 or 2000IU/ml) or C (Hepatitis C antibodies are positive and HCV-RNA is above the detection limit of the analytical method);
- Active infection requiring antimicrobial therapies (such as antibacterials, antivirals, or antifungals);
- Immunodeficiency, including positive results of HIV test or other acquired or congenital immunodeficiencies, or a history of organ transplantation;
- Allergic constitution, or known allergies to drug components used in this study;
- Pregnant or lactating women;
- Other factors that may affect the progress or the conclusion of the study, as determined by the investigator.
Trial locations and contacts
1 site in 1 country.
China1 site
The First Affiliated Hospital of University of Science and Technology of China
Hefei, Anhui, 201203
About this study
Official title: A Single Arm, Open and Fixed Sequence Study to Investigate the Pharmacokinetic Effects of Apatinib Mesylate on CYP2C8 Substrate Repaglinide or CYP2B6 Substrate in Advanced Solid Tumor Subjects
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
- Being tested
- Apatinib Mesylate, Repaglinide, Bupropion
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Apatinib MesylateDrug
Apatinib will be administered daily from on D5 through D16
RepaglinideDrug
Repaglinide will be administered daily on D1 and D12
BupropionDrug
Bupropion will be administered daily on D2 and D13
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Apatinib Mesylate; Drug: Repaglinide; Drug: Bupropion |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pharmacokinetics parameter: Cmax of digoxin
Peak Plasma Concentration (Cmax) of digoxin
Measured: through study completion, an average of 16 days
Pharmacokinetics parameter: AUC of digoxin
Area under the plasma concentration versus time curve (AUC) of digoxin
Measured: through study completion, an average of 16 days
Secondary outcomes (5)
Pharmacokinetics parameter: Tmax of digoxin
Time of maximum observed concentration (Tmax) of digoxin
Measured: through study completion, an average of 16 days
Pharmacokinetics parameter: T1/2 of digoxin
Half time (T1/2) of digoxin
Measured: through study completion, an average of 16 days
Pharmacokinetic parameters CL/F of digoxin
Total body clearance for extravascular administration (CL/F) of digoxin
Measured: through study completion, an average of 16 days
Pharmacokinetics parameter: Vz/F of digoxin
Volume of distribution (Vz/F) of digoxin
Measured: through study completion, an average of 16 days
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
Measured: through study completion, an average of 16 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jul 2020
- Study start16 Nov 2020
- Primary completion20 May 2021
- Study completion19 Jun 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Solid TumorStudies of the same condition, open and under way.
- More trials run by Jiangsu HengRui Medicine Co., Ltd.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jiangsu HengRui Medicine Co., Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- pan yueyin, Ph.D., Principal investigator, The First Affiliated Hospital of University of Science and Technology of China
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04457180
- Sponsor's protocol ID
- HR-APTN-I-008
- Status last verified
- Oct 2022
- First submitted
- 30 Jun 2020
- Last updated
- 26 Oct 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 26 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single Arm, Open and Fixed Sequence Study to Investigate the Pharmacokinetic Effects of Apatinib Mesylate on CYP2C8 Substrate Repaglinide or CYP2B6 Substrate in Advanced Solid Tumor Subjects
- ClinicalTrials.gov ID
- NCT04457180
- Acronym / sponsor ID
- HR-APTN-I-008
- Conditions
- Advanced Solid Tumor
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Jiangsu HengRui Medicine Co., Ltd.Industry (pharma, biotech, devices)
- Study start
- 16 Nov 2020 (actual)
- Primary completion
- 20 May 2021 (actual)
- Study completion
- 19 Jun 2021 (actual)
- First posted
- 7 Jul 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| treatment | Experimental | Drug: Apatinib Mesylate, Drug: Repaglinide, Drug: BupropionIn 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. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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.
Key exclusion criteria (26 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Apatinib MesylateApatinib will be administered daily from on D5 through D16 | Drug | treatment |
| RepaglinideRepaglinide will be administered daily on D1 and D12 | Drug | treatment |
| BupropionBupropion will be administered daily on D2 and D13 | Drug | treatment |
Primary outcome
Pharmacokinetics parameter: Cmax of digoxin
Time frame: through study completion, an average of 16 days
Peak Plasma Concentration (Cmax) of digoxin
Pharmacokinetics parameter: AUC of digoxin
Time frame: through study completion, an average of 16 days
Area under the plasma concentration versus time curve (AUC) of digoxin
5 secondary outcomes
Pharmacokinetics parameter: Tmax of digoxin
Time frame: through study completion, an average of 16 days
Pharmacokinetics parameter: T1/2 of digoxin
Time frame: through study completion, an average of 16 days
Pharmacokinetic parameters CL/F of digoxin
Time frame: through study completion, an average of 16 days
Pharmacokinetics parameter: Vz/F of digoxin
Time frame: through study completion, an average of 16 days
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
Time frame: through study completion, an average of 16 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Oct 2022.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
pan yueyin, Ph.D. principal investigator
The First Affiliated Hospital of University of Science and Technology of China
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Apatinib Mesylate, Repaglinide and Bupropion in people with Advanced Solid Tumor, run by Jiangsu HengRui Medicine Co., Ltd. at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pharmacokinetics parameter: Cmax of digoxin (time frame: through study completion, an average of 16 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Oct 2022.