- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05732428
A Study to Learn About the Study Medicine (Called ARV-471) in People With ER+/HER2- Advanced BC in China
A PHASE 1, OPEN LABEL STUDY EVALUATING THE PHARMACOKINETICS, SAFETY, AND TOLERABILITY OF ARV-471 (PF-07850327) AS A SINGLE AGENT IN CHINESE PARTICIPANTS WITH ER+/HER2- ADVANCED BREAST CANCER
The purpose of this clinical trial is to learn about the pharmacokinetics. safety and tolerability of the study medicine (called ARV-471) for the potential treatment of advanced estrogen receptor postive and human epidermal growth factor receptor 2 negative breast cancer.
This study is seeking participants have
- ER+/HER2- advanced breast cancer
- received at least 1 line of endocrine therapy with or without CDK4/6 inhibitor
- received up to 2 prior regimens of chemotherapy for advanced setting. All participants in this study will receive ARV-471. ARV-471 will be given by mouth at home once a day. The experiences of people receiving the study medicine will be examined. This will help determine if the study medicine is safe and effective.
Participants will take part in this study until their cancer is no longer responding. During this time, they will have visits at the study clinic about every 4 weeks.
Study Overview
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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Shanghai, China
- Cancer Hospital Chinese Academy of Medical Sciences
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Beijing
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Beijing, Beijing, China, 100021
- Cancer Hospital Chinese Academy of Medical Science
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Jilin
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Changchun, Jilin, China, 130000
- Jilin Cancer Hospital
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Shaanxi
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Xi'an, Shaanxi, China, 710061
- The First Affiliated Hospital of Xi'an Jiaotong University
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Zhejiang
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Hangzhou, Zhejiang, China, 310016
- Sir Run Run Shaw Hospital of Zhejiang University School of Medicine
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Histological or cytological diagnosis of breast cancer with evidence of ER+/HER2- locally advanced or metastatic disease, which is not amenable to surgical resection or radiation therapy with curative intent.
- Received at least 1 line of SOC of endocrine therapy with or without CDK4/6 inhibitor for locally advanced or metastatic disease.
- Up to 2 prior regimens of chemotherapy for advanced or metastatic disease setting are allowed.
Exclusion Criteria:
- Known active uncontrolled or symptomatic CNS metastases, carcinomatous meningitis, or leptomeningeal disease as indicated by clinical symptoms, cerebral edema, and/or progressive growth. Participants with a history of CNS metastases or cord compression are eligible if they have been definitively treated (eg, radiotherapy, stereotactic surgery) and clinically stable (including patients with residual CNS symptoms/deficits) off enzyme-inducing anticonvulsants and steroids for at least 28 days prior to first dose of study drug.
- Any of the following in the previous 6 months: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure (New York Heart Association Class III or IV), cerebrovascular accident, transient ischemic attack, or symptomatic pulmonary embolism or other clinically significant episode of thromboembolic disease, congenital long QT syndrome, Torsade de Pointes, serious conduction system abnormalities (eg, bifascicular block defined as right bundle branch and left anterior or posterior hemiblock, 3rd degree AV block), clinically important arrhythmias, left anterior hemiblock (bifascicular block), ongoing cardiac dysrhythmias of NCI CTCAE Grade ≥2, atrial fibrillation of any grade.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: ARV-471
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ARV-471 will be administered orally once daily with food (eg, a light meal of approximately 400 to 600 calories which includes a mixture of fat carbohydrates, and protein) at RP3D for monotherapy defined in study ARV-471-mBC-101, in continuous dosing over 28-day cycles
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Single dose Cmax (Maximum plasma concentration)
Time Frame: 0, 1, 2, 4, 6, 8, 12, 24 hours post-dose up to Day 2
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Maximum plasma concentration
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0, 1, 2, 4, 6, 8, 12, 24 hours post-dose up to Day 2
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Single dose AUCtau
Time Frame: 0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 2
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Area under the concentration-time profile from time zero to time tau (τ), the dosing interval, where tau = 24 hours (QD dosing)
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0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 2
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Multiple dose Cmax
Time Frame: 0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 71
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Maximum Observed Plasma Concentration (Cmax)
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0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 71
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Multiple dose AUCtau
Time Frame: 0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 71
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Area under the concentration curve from time 0 to end of dosing interval (AUCtau), where dosing interval was 24 hours.
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0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 71
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Objective Response Rate - Percentage of Participants With Objective Response
Time Frame: Baseline up to 24 weeks
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Percentage of participants with objective response based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). Confirmed responses are those that persist on repeat imaging study at least 4 weeks after initial documentation of response. Per RECIST v1.1: CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis <10 mm). No new lesions. PR was defined as >=30% decrease under baseline of Percentage of participants with objective response based assessment of complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). |
Baseline up to 24 weeks
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Percentage of Participants With Clinical Benefit
Time Frame: Baseline up to 24 weeks
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Percent of participants with confirmed complete response (CR), partial response (PR) or stable disease (SD) for at least 24 weeks on study according to RECIST. Per RECIST v1.1: CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis <10 mm). No new lesions. PR was defined as >=30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions. SD was defined as not qualifying for CR, PR, Progressive Disease (PD). |
Baseline up to 24 weeks
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Duration of Objective Response (DOR)
Time Frame: From the date of first documented response (CR or PR) until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 weeks
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DOR: time from date of first documented response (CR or PR) to first documented progression or death due to underlying cancer.
RECIST V1.1, a) CR: disappearance of all lesions; any pathological lymph nodes (TLs) or non-pathological (non-TLs) must have reduction in short axis to <10 mm; normalization of tumor marker level for non-TLs; b) PR: >=30% decrease in sum of diameter (dia) of all TLs, referring baseline sum of dia; c) PD: >=20% increase in sum of diameter of all measured target lesions taking as reference smallest sum of diameter of all target lesions recorded at or after baseline, sum must also be absolute increase of >=5 mm.
Unequivocal progression of existing non-target lesions.
Appearance of at least 1 new lesion.
If a participant with a CR or PR had no PD or death due to underlying cancer, participants was censored at date of last adequate tumor assessment.
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From the date of first documented response (CR or PR) until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 weeks
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Presence (rate) or absence of blood biomarkers
Time Frame: immediately after the end of treatment
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To identify biomarkers (ESR1 mutation) of complete response and progression if occurs
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immediately after the end of treatment
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Number of Participants With Notable Electrocardiogram (ECG) Values
Time Frame: From baseline up to 28 days after last dose of study drug
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Criteria for notable ECG values were as follow: QT interval (in millisecond [msec]) new (newly occurring post-baseline value) greater than (>) 450, 480, 500, increase from baseline >30, increase from baseline >60; corrected QT interval by Fredericia formula (QTcF) in msec new (newly occurring post-baseline value) > 450, 480, 500, increase from baseline >30, increase from baseline >60; corrected QT interval by Bazett's formula (QTcB) in msec new (newly occurring post-baseline value) > 450, 480, 500, increase from baseline >30, increase from baseline >60; heart rate in bpm new (newly occurring post-baseline value) <60 and >100.
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From baseline up to 28 days after last dose of study drug
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Number of Participants With Laboratory Abnormalities
Time Frame: Baseline (Day 1) up to at least 28 days after last dose of study drug
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Hemoglobin (HGB),hematocrit,erythrocytes (ery.),HDL
cholesterol (chl.)<0.8*lower
limit of normal(LLN);reticulocytes (ret.), ret./ery.
(%)<0.5*LLN,>1.5*upper
limit of normal (ULN);ery.
mean corpuscular (EMC) volume,EMC HGB,EMC HGB
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Baseline (Day 1) up to at least 28 days after last dose of study drug
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Number of Participants With Clinically Significant Change From Baseline in Vital Signs
Time Frame: Baseline up to 28 days after last dose of study drug
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Vital signs (temperature, respiratory rate, pulse, systolic and diastolic blood pressure) were obtained with participant in the seated position, after having sat calmly for at least 5 minutes.
Clinical significance of vital signs was determined at the investigator's discretion.
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Baseline up to 28 days after last dose of study drug
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Number of Participants With Adverse Events (AEs) by type, frequency, severity (as graded by NCI CTCAE verision 5.0), timing, seriousness and relationship to study treatment
Time Frame: Baseline up to 28 days after the last dose of study drug
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Counts of participants who had treatment-emergent adverse events (TEAEs), defined as newly occurring or worsening after first dose.
Relatedness to [study drug] was assessed by the investigator.
Participants with multiple occurrences of an AE within a category were counted once within the category.
An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.
As per CTCAE version 4, Grade 1= mild AE; Grade 2= moderate AE; Grade 3= severe AE; Grade 4= life-threatening or disabling AE; Grade 5= death related to an AE.
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Baseline up to 28 days after the last dose of study drug
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Single dose Tmax
Time Frame: 0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 2
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Time at which Cmax occurred
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0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 2
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Single dose AUClast
Time Frame: 0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 2
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Area under the concentration-time profile from time zero to the time of the last quantifiable concentration (Clast)
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0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 2
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Single dose MRCmax
Time Frame: 0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 2
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ARV-473 to ARV-471 ratio for Cmax
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0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 2
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Single dose AUCinf
Time Frame: 0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 2
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Area under the concentration-time profile from time zero extrapolated to infinite time
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0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 2
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Single dose CL/F
Time Frame: 0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 2
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Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.
Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed.
Clearance was estimated from population pharmacokinetic (PK) modeling.
Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
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0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 2
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Single dose Vz/F
Time Frame: 0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 2
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Apparent volume of distribution
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0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 2
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Single dose t½
Time Frame: 0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 2
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Terminal half-life
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0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 2
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Multiple dose Tmax
Time Frame: 0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 71
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Time to Reach Maximum Observed Plasma Concentration
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0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 71
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Multiple dose Vz/F
Time Frame: 0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 71
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0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 71
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Multiple dose MRCmax
Time Frame: 0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 71
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ARV-473 to ARV-471 ratio for Cmax
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0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 71
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Rac
Time Frame: 0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 71
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Accumulation ratio based on AUC (observed)
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0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 71
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t½eff
Time Frame: 0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 71
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Effective half-life (t½eff) based on accumulation ratio
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0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 71
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Multiple dose CL/F
Time Frame: 0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 71
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Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.
Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed.
Clearance was estimated from population pharmacokinetic (PK) modeling.
Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
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0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 71
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Multiple dose t½
Time Frame: 0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 71
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Terminal half-life
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0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 71
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Single dose MRAUCtau
Time Frame: 0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 2
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0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 2
|
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Multiple dose AUClast
Time Frame: 0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 71
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0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 71
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Multiple dose Cmin
Time Frame: 0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 71
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0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 71
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Multiple dose Ctrough
Time Frame: 0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 71
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0, 1, 2, 4, 6, 8, 12, 24 hours post-dose Up to Day 71
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Study Director: Pfizer CT.gov Call Center, Pfizer
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- C4891018
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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