Cytochrome P450 InteractionPhase 1NCT03245307
A Study To Test The Effect Of Apatinib On P450 Enzymes
A Phase 1 study testing Apatinib, Nifedipine GTIS and Warfarin Potassium in people with Cytochrome P450 Interaction, run by Jiangsu HengRui Medicine Co., Ltd. at 1 site in China.
Trial summary
Apatinib, an oral inhibitor of vascular endothelial growth factor receptor 2（VEGFR-2）, inhibits multiple cytochrome P450 (CYP450) enzymes in vitro. This study in patients with advanced cancer evaluated the effect of Apatinib on CYP450 function by comparing the pharmacokinetics of CYP-specific probe drugs in the… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Cytochrome P450 Interaction
- What is being tested?
- Apatinib, Nifedipine GTIS and Warfarin Potassium
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteChina
- Study dates
- 22 Aug 2017to 30 Sep 2018
- 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
- Histologically or cytologically confirmed diagnosis of advanced solid tumors.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Adequate bone marrow, renal, lung, and liver function.
- A female subject must not be pregnant and will agree not to become pregnant during the trial
Who cannot join
- Primary carcinoma of liver
- Any major surgery, chemotherapy, hormone therapy, investigational drugs, or radiotherapy within the last 28 days.
- Poorly controlled hypertension.
- A prior history of cardiovascular disease, arrhythmias, or significant ECG abnormalities, and corrected QT (QTc) prolongation defined as a QTc interval greater than or equal to 450 msec(male) or 470 msec(female).
- Arterial or venous thrombi (including cerebrovascular accident).
- Current use of therapeutic anticoagulation (low molecular weight heparin, oral anticoagulant agents).
- Active brain metastases.
- A history of bleeding problems.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Chinese Medical University First Hospital
Shenyang, Liaoning
Yunpeng Liu, 86024-83282802, cmu_trial@163.com
About this study
Official title: A Single-center, Open-Label, Drug Interaction Study to Determine the Effects of Apatinib on the Metabolism of CYP3A4/5 and CYP2C9 Probe Drugs in Patients With Solid Tumors
Apatinib, an oral inhibitor of vascular endothelial growth factor receptor 2（VEGFR-2）, inhibits multiple cytochrome P450 (CYP450) enzymes in vitro. This study in patients with advanced cancer evaluated the effect of Apatinib on CYP450 function by comparing the pharmacokinetics of CYP-specific probe drugs in the presence and absence of Apatinib. The probes used included Nifedipine (CYP3A specific), warfarin (CYP2C9 specific).
Read the detailed description
This open-label study consists of a drug interaction phase that (part A) and a drug-continuation phase (part B). Patients will receive CYP450-probe drugs, and PK assessments will be performed before apatinib-administration and aſter once-daily administration of apatinib for 5 days (the predicted time point when steady-state plasma apatinib concentrations will have been achieved).
- Conditions
- Cytochrome P450 Interaction
- Being tested
- Apatinib, Nifedipine GTIS, Warfarin Potassium
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ApatinibDrug
Apatinib at a dosage of 750mg will be administered daily from day 9 of phase A
Nifedipine GTISDrug
Also called Nifedipine
Nifedipine at a dosage of 30mg will be administered at day 1 and day 14 of phase A
Warfarin PotassiumDrug
Also called warfarin
Nifedipine at a dosage of 3mg will be administered at day 3 and day 16 of phase A
| Study group | Role | What they receive |
|---|---|---|
| Treament | Experimental | In phase A, subjects receiving a single 30 mg oral dose of Nifedipine controlled-release tablets and wash-out for 2 days,a single 3 mg oral dose of warfarin tablets and wash-out for 12 days, then apatinib 750 mg once daily with a single 30 mg oral dose of Nifedipine controlled-release tablets co-administered on day 6 ,a a single 3 mg oral dose of warfarin tablets co-administered on day 9. Receives: Drug: Apatinib; Drug: Nifedipine GTIS; Drug: Warfarin Potassium |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area under the plasma concentration versus time curve (AUC) of warfarin or nifedipine
AUC0~t of warfarin and nifedipine in the absence or in presence of apatinib will be defined
Measured: 1 year
Secondary outcomes (1)
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
to assess safety and tolerability of apatinib combined with warfarin or nifedipine in patients with advanced solid tumors. The vital signs, ECG, laboratory values and adverse events (AE and SAE) were judged according to NCI-CTCAE V4.0 criteria
Measured: Day 1 to 21 ( Phase A）
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Aug 2017
- Study start22 Aug 2017
- Primary completion30 Apr 2018 (estimated)
- Study completion30 Sep 2018 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cytochrome P450 InteractionStudies 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
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Jiangsu HengRui Medicine Co., Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03245307
- Sponsor's protocol ID
- HR-APTN-DDI-01
- Status last verified
- Jul 2017
- First submitted
- 17 Jul 2017
- Last updated
- 7 Feb 2018
- 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 7 Feb 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single-center, Open-Label, Drug Interaction Study to Determine the Effects of Apatinib on the Metabolism of CYP3A4/5 and CYP2C9 Probe Drugs in Patients With Solid Tumors
- ClinicalTrials.gov ID
- NCT03245307
- Acronym / sponsor ID
- HR-APTN-DDI-01
- Conditions
- Cytochrome P450 Interaction
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Jiangsu HengRui Medicine Co., Ltd.Industry (pharma, biotech, devices)
- Study start
- 22 Aug 2017 (actual)
- Primary completion
- 30 Apr 2018 (estimated)
- Study completion
- 30 Sep 2018 (estimated)
- First posted
- 10 Aug 2017 (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.
Apatinib, an oral inhibitor of vascular endothelial growth factor receptor 2（VEGFR-2）, inhibits multiple cytochrome P450 (CYP450) enzymes in vitro. This study in patients with advanced cancer evaluated the effect of Apatinib on CYP450 function by comparing the pharmacokinetics of CYP-specific probe drugs in the presence and absence of Apatinib. The probes used included Nifedipine (CYP3A specific), warfarin (CYP2C9 specific).
Detailed description
This open-label study consists of a drug interaction phase that (part A) and a drug-continuation phase (part B). Patients will receive CYP450-probe drugs, and PK assessments will be performed before apatinib-administration and aſter once-daily administration of apatinib for 5 days (the predicted time point when steady-state plasma apatinib concentrations will have been achieved).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treament | Experimental | Drug: Apatinib, Drug: Nifedipine GTIS, Drug: Warfarin PotassiumIn phase A, subjects receiving a single 30 mg oral dose of Nifedipine controlled-release tablets and wash-out for 2 days,a single 3 mg oral dose of warfarin tablets and wash-out for 12 days, then apatinib 750 mg once daily with a single 30 mg oral dose of Nifedipine controlled-release tablets co-administered on day 6 ,a a single 3 mg oral dose of warfarin tablets co-administered on day 9. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Histologically or cytologically confirmed diagnosis of advanced solid tumors.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Adequate bone marrow, renal, lung, and liver function.
- A female subject must not be pregnant and will agree not to become pregnant during the trial
Key exclusion criteria (8 listed)
- Primary carcinoma of liver
- Any major surgery, chemotherapy, hormone therapy, investigational drugs, or radiotherapy within the last 28 days.
- Poorly controlled hypertension.
- A prior history of cardiovascular disease, arrhythmias, or significant ECG abnormalities, and corrected QT (QTc) prolongation defined as a QTc interval greater than or equal to 450 msec(male) or 470 msec(female).
- Arterial or venous thrombi (including cerebrovascular accident).
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 |
|---|---|---|
| ApatinibApatinib at a dosage of 750mg will be administered daily from day 9 of phase A | Drug | Treament |
| Nifedipine GTISAlso: NifedipineNifedipine at a dosage of 30mg will be administered at day 1 and day 14 of phase A | Drug | Treament |
| Warfarin PotassiumAlso: warfarinNifedipine at a dosage of 3mg will be administered at day 3 and day 16 of phase A | Drug | Treament |
Primary outcome
Area under the plasma concentration versus time curve (AUC) of warfarin or nifedipine
Time frame: 1 year
AUC0~t of warfarin and nifedipine in the absence or in presence of apatinib will be defined
1 secondary outcome
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time frame: Day 1 to 21 ( Phase A）
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Feb 2018.
- Individual participant dataSharing planned: Undecided
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Interaction
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.
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, Nifedipine GTIS and Warfarin Potassium in people with Cytochrome P450 Interaction, 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 4 inclusion and 8 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: status not confirmed, as of the sponsor's last update on 7 Feb 2018. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Area under the plasma concentration versus time curve (AUC) of warfarin or nifedipine (time frame: 1 year). 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 7 Feb 2018.