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| Name | Class |
|---|---|
| Arvinas Estrogen Receptor, Inc. | INDUSTRY |
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The purpose of this clinical trial is to learn about the safety, tolerability, Pharmacokinetics (PK), and preliminary efficacy of ARV-471 as monotherapy in Japanese participants with ER+/HER2- locally advanced or metastatic breast cancer (mBC).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| vepdegestrant | Experimental | Daily oral dosages of vepdegestrant |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| vepdegestrant | Drug | ARV-471 will be administered orally QD with food, in continuous dosing over 28-day cycles. |
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| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Dose Limiting Toxicity (DLTs) During First Treatment Cycle | DLT was defined as any adverse event (AE) or abnormal laboratory value which were related to ARV-471 and assessed as unrelated to disease, disease progression, intercurrent illness or concomitant medications/therapies occurring during the first 28 days of treatment that met at least 1 of the study specified criteria. | Cycle 1 (28 days) |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With AEs and Serious AEs (SAEs)- All Causalities and Treatment Related | An AE is any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. Treatment-related AE was any untoward medical occurrence attributed to study treatment in a participant who received study treatment. Relatedness was judged by investigator. SAE was an AE resulted in any of the following outcomes: death, inpatient hospitalization or prolongation of existing hospitalization; was life-threatening experience (immediate risk of dying); resulted in persistent or significant disability/incapacity; congenital anomaly, a suspected transmission via a Pfizer product of an infectious agent, pathogenic or non-pathogenic. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Pfizer CT.gov Call Center | Pfizer | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Aichi Cancer Center Hospital | Nagoya | Aichi-ken | 464-8681 | Japan | ||
| National Cancer Center Hospital East |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39565495 | Derived | Iwata H, Naito Y, Hattori M, Yoshimura A, Yonemori K, Aizawa M, Mori Y, Yoshimitsu J, Umeyama Y, Mukohara T. Safety and pharmacokinetics of vepdegestrant in Japanese patients with ER+ advanced breast cancer: a phase 1 study. Int J Clin Oncol. 2025 Jan;30(1):72-82. doi: 10.1007/s10147-024-02648-3. Epub 2024 Nov 20. |
| Label | URL |
|---|---|
| To obtain contact information for a study center near you, click here. | View source |
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Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical\_trials/trial\_data\_and\_results/data\_requests.
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Results are reported at primary completion date. Remaining results would be reported on completion of analysis at study completion date later.
Japanese participants with estrogen receptor (ER+) or human epidermal growth factor receptor 2 (HER-2) locally advanced or metastatic breast cancer (mBC) were treated with ARV-471 (PF-07850327) as monotherapy. A total of 6 participants were enrolled.
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| ID | Title | Description |
|---|---|---|
| FG000 | ARV-471 200 mg | Participants received ARV-471 200 milligrams (mg) orally once daily (QD) with food, in continuous dosing over 28-day cycle (1 cycle = 28 days). Participants continued treatment at the discretion of the investigator until a treatment discontinuation criterion was met (disease progression; global deterioration of health status requiring discontinuation; unacceptable toxicity; pregnancy; significant protocol violation; lost to follow-up; participant refused further treatment; study terminated by sponsor; death). |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Treatment |
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| Follow-up |
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Full analysis set included all participants who have been assigned to ARV-471.
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| ID | Title | Description |
|---|---|---|
| BG000 | ARV-471 200 mg | Participants received ARV-471 200 mg orally QD, in continuous dosing over 28-day cycle. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With Dose Limiting Toxicity (DLTs) During First Treatment Cycle | DLT was defined as any adverse event (AE) or abnormal laboratory value which were related to ARV-471 and assessed as unrelated to disease, disease progression, intercurrent illness or concomitant medications/therapies occurring during the first 28 days of treatment that met at least 1 of the study specified criteria. | DLT evaluable analysis set included all enrolled participants who received at least 75% of the planned dose intensity of study treatment and either experienced DLT or did not have major protocol deviations during the DLT observation period. | Posted | Count of Participants | Participants | Cycle 1 (28 days) |
|
Day 1 of study treatment up to 35 days last dose of study treatment (maximum up to 33 weeks as maximum treatment exposure was 28 weeks)
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | ARV-471 200 mg | Participants received ARV-471 200 mg orally QD, in continuous dosing over 28-day cycle. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA v26.0 | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Pfizer ClinicalTrials.gov Call Center | Pfizer Inc. | 1-800-718-1021 | ClinicalTrials.gov_Inquires@pfizer.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Oct 21, 2022 | May 9, 2024 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | May 25, 2023 | May 9, 2024 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
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| Day 1 of study treatment up to 35 days after last dose of study treatment (approximately 1.5 years) |
| Number of Participants With Laboratory Hematology Results by Maximum National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade | The following hematology parameters were assessed: hemoglobin, platelets, white blood cell (WBC), absolute neutrophils, absolute lymphocytes, absolute monocytes, absolute eosinophils and absolute basophils. Laboratory abnormality events were graded according to NCI CTCAE v 5.0 (grade 0=no change from normal or reference range, grade 1=mild, grade 2= moderate, grade 3= severe, grade 4= life-threatening and grade 5= death related). | During study treatment, approximately 1.5 years |
| Number of Participants With Laboratory Chemistry Results by Maximum NCI-CTCAE Grade | The following chemistry parameters were assessed: aspartate transaminase (AST), alkaline phosphatase (ALP), sodium, potassium, magnesium, chloride, total calcium, total bilirubin, blood urea nitrogen (BUN) or urea, creatinine, uric acid, glucose (non-fasted), albumin, phosphorus or phosphate, creatinine kinase (CK), amylase and lipase. Laboratory abnormality events were graded according to NCI CTCAE v 5.0 (grade 0=no change from normal or reference range, grade 1=mild, grade 2= moderate, grade 3= severe, grade 4= life-threatening and grade 5= death related). | During study treatment, approximately 1.5 years |
| Area Under the Plasma Concentration-Time Curve From Time Zero to Time Tau (AUCtau) of ARV 471 and ARV-473 | Through the end of the study treatment (approximately 1.5 years) |
| Area Under the Plasma Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of ARV-471 and ARV-473 | Through the end of the study treatment (approximately 1.5 years) |
| Maximum Observed Plasma Concentration (Cmax) of ARV-471 and ARV-473 | Through the end of the study treatment (approximately 1.5 years) |
| Time to Reach Maximum Concentration (Tmax) of ARV-471 and ARV-473 | Through the end of the study treatment (approximately 1.5 years) |
| Terminal Elimination Half-Life (t1/2) of ARV-471 and ARV-473 | Through the end of the study treatment (approximately 1.5 years) |
| Metabolite Ratio for Cmax (MRCmax) | Through the end of the study treatment (approximately 1.5 years) |
| Metabolite Ratio for AUCtau (MRAUCtau) | Through the end of the study treatment (approximately 1.5 years) |
| Lowest Concentration Observed During the Dosing Interval (Cmin) of ARV-471 and ARV-473 | Through the end of the study treatment (approximately 1.5 years) |
| Pre-dose Plasma Concentration (Ctrough) of ARV-471 and ARV-473 | Through the end of the study treatment (approximately 1.5 years) |
| Apparent Total Clearance (CL/F) of ARV-471 | Through the end of the study treatment (approximately 1.5 years) |
| Apparent Volume of Distribution (Vz/F) of ARV-471 | Through the end of the study treatment (approximately 1.5 years) |
| Effective Half-Life Based on Accumulation Ratio (t½Eff) of ARV-471 and ARV-473 | Through the end of the study treatment (approximately 1.5 years) |
| Accumulation Ratio (Rac) Based on AUC of ARV-471 and ARV-473 | Through the end of the study treatment (approximately 1.5 years) |
| Objective Response Rate (ORR) | ORR is defined as the percentage of participants with best overall response (BOR) of complete response (CR) and partial response (PR) as per Response Evaluation Criteria in Solid Tumours (RECIST version [v] 1.1). BOR: best response was recorded from start of study treatment until disease progression or death due to any cause. CR: complete disappearance of all target lesions with exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis less than [<]10 millimeter [mm]). PR: greater than or equal to (>=) 30 percent (%) decrease under baseline of sum of diameters of all targets measurable lesions. Short axis was used in sum for target nodes, while longest diameter was used in sum for all other target lesions. All target lesions were assessed. | From start of study treatment until disease progression or death due to any cause (approximately 1.5 years) |
| Clinical Benefit Response (CBR) | CBR is defined as the percentage of participants with BOR of CR, PR and stable disease (SD) of 24 weeks duration or longer. As per RECIST v1.1. SD: Does not qualify for CR, PR or Progression. All target lesions must be assessed. Stable could follow PR only in the rare case that the sum increased by <20% from the nadir, but enough that a previously documented 30% decrease no longer held. CR: complete disappearance of all target lesions and non-target disease, with exception of nodal disease. All nodes, both target and non-target, must decrease to normal short axis <10 mm). No new lesions. PR: >= 30% decrease under baseline of sum of diameters of all targets measurable lesions. Short diameter was used in sum for target nodes, while longest diameter was used in sum for all other target lesions. | From start of study treatment until disease progression or death due to any cause (approximately 1.5 years) |
| Progression Free Survival (PFS) | PFS was defined as the time from first dose of study treatment (ie, start date) to the date of progression of disease (PD) or death due to any cause, whichever occurred first. PFS data was censored on the date of the last adequate tumor assessment for participants without an event (PD or death), for participants who started new anti-cancer treatment prior to an event, or for participants with an event after two or more missing tumor assessments. PD as per RECIST v1.1 for target lesions was defined as 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy), with a minimum absolute increase of 5 mm. For non-target lesions- PD was defined as unequivocal progression of pre-existing lesions. Analysis was performed using Kaplan-Meier method. | From start of study treatment until disease progression or death due to any cause or censoring date (approximately 1.5 years) |
| Duration of Response (DOR) | Duration of response was defined as the time from the first documentation of objective tumor response to the first documentation of objective tumor progression or to death due to any cause, whichever occurred first in participants with confirmed objective response (CR or PR). 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 diameter was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. Analysis was performed using Kaplan-Meier method. | From the first documentation of objective tumor response to the first documentation of objective tumor progression or to death due to any cause (approximately 1.5 years) |
| Kashiwa |
| Chiba |
| 277-8577 |
| Japan |
| National Cancer Center Hospital | Chuo-ku | Tokyo | 104-0045 | Japan |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
|
|
| Secondary | Number of Participants With AEs and Serious AEs (SAEs)- All Causalities and Treatment Related | An AE is any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. Treatment-related AE was any untoward medical occurrence attributed to study treatment in a participant who received study treatment. Relatedness was judged by investigator. SAE was an AE resulted in any of the following outcomes: death, inpatient hospitalization or prolongation of existing hospitalization; was life-threatening experience (immediate risk of dying); resulted in persistent or significant disability/incapacity; congenital anomaly, a suspected transmission via a Pfizer product of an infectious agent, pathogenic or non-pathogenic. | Not Posted | Sep 2024 | Day 1 of study treatment up to 35 days after last dose of study treatment (approximately 1.5 years) | Participants |
| Secondary | Number of Participants With Laboratory Hematology Results by Maximum National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade | The following hematology parameters were assessed: hemoglobin, platelets, white blood cell (WBC), absolute neutrophils, absolute lymphocytes, absolute monocytes, absolute eosinophils and absolute basophils. Laboratory abnormality events were graded according to NCI CTCAE v 5.0 (grade 0=no change from normal or reference range, grade 1=mild, grade 2= moderate, grade 3= severe, grade 4= life-threatening and grade 5= death related). | Not Posted | Sep 2024 | During study treatment, approximately 1.5 years | Participants |
| Secondary | Number of Participants With Laboratory Chemistry Results by Maximum NCI-CTCAE Grade | The following chemistry parameters were assessed: aspartate transaminase (AST), alkaline phosphatase (ALP), sodium, potassium, magnesium, chloride, total calcium, total bilirubin, blood urea nitrogen (BUN) or urea, creatinine, uric acid, glucose (non-fasted), albumin, phosphorus or phosphate, creatinine kinase (CK), amylase and lipase. Laboratory abnormality events were graded according to NCI CTCAE v 5.0 (grade 0=no change from normal or reference range, grade 1=mild, grade 2= moderate, grade 3= severe, grade 4= life-threatening and grade 5= death related). | Not Posted | Sep 2024 | During study treatment, approximately 1.5 years | Participants |
| Secondary | Area Under the Plasma Concentration-Time Curve From Time Zero to Time Tau (AUCtau) of ARV 471 and ARV-473 | Not Posted | Sep 2024 | Through the end of the study treatment (approximately 1.5 years) | Participants |
| Secondary | Area Under the Plasma Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of ARV-471 and ARV-473 | Not Posted | Sep 2024 | Through the end of the study treatment (approximately 1.5 years) | Participants |
| Secondary | Maximum Observed Plasma Concentration (Cmax) of ARV-471 and ARV-473 | Not Posted | Sep 2024 | Through the end of the study treatment (approximately 1.5 years) | Participants |
| Secondary | Time to Reach Maximum Concentration (Tmax) of ARV-471 and ARV-473 | Not Posted | Sep 2024 | Through the end of the study treatment (approximately 1.5 years) | Participants |
| Secondary | Terminal Elimination Half-Life (t1/2) of ARV-471 and ARV-473 | Not Posted | Sep 2024 | Through the end of the study treatment (approximately 1.5 years) | Participants |
| Secondary | Metabolite Ratio for Cmax (MRCmax) | Not Posted | Sep 2024 | Through the end of the study treatment (approximately 1.5 years) | Participants |
| Secondary | Metabolite Ratio for AUCtau (MRAUCtau) | Not Posted | Sep 2024 | Through the end of the study treatment (approximately 1.5 years) | Participants |
| Secondary | Lowest Concentration Observed During the Dosing Interval (Cmin) of ARV-471 and ARV-473 | Not Posted | Sep 2024 | Through the end of the study treatment (approximately 1.5 years) | Participants |
| Secondary | Pre-dose Plasma Concentration (Ctrough) of ARV-471 and ARV-473 | Not Posted | Sep 2024 | Through the end of the study treatment (approximately 1.5 years) | Participants |
| Secondary | Apparent Total Clearance (CL/F) of ARV-471 | Not Posted | Sep 2024 | Through the end of the study treatment (approximately 1.5 years) | Participants |
| Secondary | Apparent Volume of Distribution (Vz/F) of ARV-471 | Not Posted | Sep 2024 | Through the end of the study treatment (approximately 1.5 years) | Participants |
| Secondary | Effective Half-Life Based on Accumulation Ratio (t½Eff) of ARV-471 and ARV-473 | Not Posted | Sep 2024 | Through the end of the study treatment (approximately 1.5 years) | Participants |
| Secondary | Accumulation Ratio (Rac) Based on AUC of ARV-471 and ARV-473 | Not Posted | Sep 2024 | Through the end of the study treatment (approximately 1.5 years) | Participants |
| Secondary | Objective Response Rate (ORR) | ORR is defined as the percentage of participants with best overall response (BOR) of complete response (CR) and partial response (PR) as per Response Evaluation Criteria in Solid Tumours (RECIST version [v] 1.1). BOR: best response was recorded from start of study treatment until disease progression or death due to any cause. CR: complete disappearance of all target lesions with exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis less than [<]10 millimeter [mm]). PR: greater than or equal to (>=) 30 percent (%) decrease under baseline of sum of diameters of all targets measurable lesions. Short axis was used in sum for target nodes, while longest diameter was used in sum for all other target lesions. All target lesions were assessed. | Not Posted | Sep 2024 | From start of study treatment until disease progression or death due to any cause (approximately 1.5 years) | Participants |
| Secondary | Clinical Benefit Response (CBR) | CBR is defined as the percentage of participants with BOR of CR, PR and stable disease (SD) of 24 weeks duration or longer. As per RECIST v1.1. SD: Does not qualify for CR, PR or Progression. All target lesions must be assessed. Stable could follow PR only in the rare case that the sum increased by <20% from the nadir, but enough that a previously documented 30% decrease no longer held. CR: complete disappearance of all target lesions and non-target disease, with exception of nodal disease. All nodes, both target and non-target, must decrease to normal short axis <10 mm). No new lesions. PR: >= 30% decrease under baseline of sum of diameters of all targets measurable lesions. Short diameter was used in sum for target nodes, while longest diameter was used in sum for all other target lesions. | Not Posted | Sep 2024 | From start of study treatment until disease progression or death due to any cause (approximately 1.5 years) | Participants |
| Secondary | Progression Free Survival (PFS) | PFS was defined as the time from first dose of study treatment (ie, start date) to the date of progression of disease (PD) or death due to any cause, whichever occurred first. PFS data was censored on the date of the last adequate tumor assessment for participants without an event (PD or death), for participants who started new anti-cancer treatment prior to an event, or for participants with an event after two or more missing tumor assessments. PD as per RECIST v1.1 for target lesions was defined as 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy), with a minimum absolute increase of 5 mm. For non-target lesions- PD was defined as unequivocal progression of pre-existing lesions. Analysis was performed using Kaplan-Meier method. | Not Posted | Sep 2024 | From start of study treatment until disease progression or death due to any cause or censoring date (approximately 1.5 years) | Participants |
| Secondary | Duration of Response (DOR) | Duration of response was defined as the time from the first documentation of objective tumor response to the first documentation of objective tumor progression or to death due to any cause, whichever occurred first in participants with confirmed objective response (CR or PR). 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 diameter was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. Analysis was performed using Kaplan-Meier method. | Not Posted | Sep 2024 | From the first documentation of objective tumor response to the first documentation of objective tumor progression or to death due to any cause (approximately 1.5 years) | Participants |
| 0 |
| 6 |
| 0 |
| 6 |
| 4 |
| 6 |
| Abdominal discomfort | Gastrointestinal disorders | MedDRA v26.0 | Non-systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA v26.0 | Non-systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA v26.0 | Non-systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA v26.0 | Non-systematic Assessment |
|
| Pyrexia | General disorders | MedDRA v26.0 | Non-systematic Assessment |
|
| Seasonal allergy | Immune system disorders | MedDRA v26.0 | Non-systematic Assessment |
|
| COVID-19 | Infections and infestations | MedDRA v26.0 | Non-systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA v26.0 | Non-systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA v26.0 | Non-systematic Assessment |
|
| Hypercalcaemia | Metabolism and nutrition disorders | MedDRA v26.0 | Non-systematic Assessment |
|
| Tumour pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA v26.0 | Non-systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA v26.0 | Non-systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA v26.0 | Non-systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA v26.0 | Non-systematic Assessment |
|
Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
| D017437 |
| Skin and Connective Tissue Diseases |