Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 2015-005703-83 | EudraCT Number |
Not provided
Not provided
Not provided
B2341002 was terminated on 26-OCT-2017 for strategic reasons. The decision to terminate the trial was not based on any safety concerns.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
This study employs a modified continual reassessment method (mCRM) design to estimate the maximum tolerated dose (MTD) of PF-05230907, defined as a target toxicity rate of 15% based on treatment emergent thromboembolic and/or ischemic events (TIEs). The mCRM design utilizes Bayesian methodology to continuously learn the dose-toxicity relationship, which is characterized by a parametric model.
Subjects with a diagnosis of ICH (determined by computed tomography) will be enrolled in cohorts of 3. The total length of time planned for study participation is approximately 3 months; 6.0 hours for screening, a single dose administration with a 4-day minimum hospital confinement period and follow-up visits through Day 91.
Severity of adverse events (AEs) and serious adverse events (SAEs) will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. All subjects who receive PF-05230907 are evaluable for TIEs. The determination of MTD using mCRM modeling will be based on TIEs which occur through 7 days post-dose (Day 8).
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| PF-05230907 (Cohort 1) | Experimental | PF-05230907 IV bolus injection |
|
| PF-05230907 (Cohort 2) | Experimental | PF-05230907 IV bolus injection |
|
| PF-05230907 (Cohort 3) | Experimental | PF-05230907 IV bolus injection |
|
| PF-05230907 (Cohort 4) | Experimental | PF-05230907 IV bolus injection |
|
| PF-05230907 (Cohort 5) | Experimental | PF-05230907 IV bolus injection |
|
| PF-05230907 (Cohort 6) | Experimental | PF-05230907 IV bolus injection |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| PF-05230907 | Biological | PF-05230907 IV bolus injection |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Treatment-Emergent Thromboembolic and/or Ischemic Events (TIEs) | Thromboembolic and/or ischemic events (TIEs) were defined as any of the following events: disseminated intravascular coagulation (Grade [Gr]>=3); acute coronary syndrome (Gr >=3); cardiac arrest (Gr >=4); myocardial infarction (Gr >=3); Cardiac troponin I increased (Gr 3); ischemia cerebrovascular (Gr >=1 and associated with lesion[s]); portal vein thrombosis (Gr >=2); ischemic stroke (Gr >=1 and associated with lesion[s]); transient ischemic attacks (Gr 2); purpura (Gr >=2); superior vena cava syndrome (Gr >=1); thromboembolic event (Gr >=2); visceral arterial ischemia (Gr >=2); peripheral arterial ischemia (Gr >=3). TIEs were graded based on Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. For the respective event to count as a treatment-emergent TIE, onset or worsening of the event must have occurred following treatment with PF-05230907 and during the interval between Day 1 dosing through Day 8. | Day 1 through day of discharge (Day 8) |
| Number of Participants With Treatment-Emergent Serious Adverse Events (SAEs) | A serious adverse event (SAE) was any untoward medical occurrence at any dose that: resulted in death; or was life threatening (immediate risk of death); or required inpatient hospitalization or prolongation of existing hospitalization; or resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); or resulted in congenital anomaly/birth defect. Any such events occurring following the start of treatment or increasing in severity were counted as treatment-emergent. | Day 1 through follow-up visit (Day 43) |
| Number of Participants With Treatment-Emergent Adverse Events (AEs) | An adverse event (AE) was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. For the respective event to count as a treatment-emergent AE, onset or worsening of the event must have occurred following treatment with PF-05230907 and during the interval between Day 1 dosing through Day 8. | Day 1 through day of discharge (Day 8) |
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Changes From Baseline for Activated Partial Thromboplastin Time (aPTT) | Maximum changes from baseline were calculated for activated partial thromboplastin time (aPTT) after dosing with PF-05230907 through Day 2. | Baseline (pre-dose), Day 2 |
| Maximum Changes From Baseline for Prothrombin Fragment 1+2 (PF1+2) |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Intracerebral Hemorrhage (ICH) Volume at 24 Hours | Change from baseline in intracerebral hemorrhage (ICH) volume was calculated at 24 hours. | Baseline (pre-dose), 24 hours |
| PF-05230907 Concentration in Plasma |
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Pfizer CT.gov Call Center | Pfizer | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Barnes Jewish Hospital | St Louis | Missouri | 63110 | United States | ||
| Washington University, |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33272131 | Derived | Silva Blas Y, Diringer MN, Lo B, Masjuan J, Perez de la Ossa N, Cardinal M, Yong F, Zhu T, Li G, Arkin S. Phase 1b Study to Evaluate Safety, Tolerability, and Maximum Tolerated Dose of PF-05230907 for Intracerebral Hemorrhage. Stroke. 2021 Jan;52(1):294-298. doi: 10.1161/STROKEAHA.120.029789. Epub 2020 Dec 4. |
| Label | URL |
|---|---|
| To obtain contact information for a study center near you, click here. | View source |
Not provided
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.
Not provided
Not provided
Not provided
Not provided
Not all the 15 pre-specified dose groups (possible doses based on Bayesian modified continual reassessment method [mCRM]) were expected to be studied. The actual doses were determined by mCRM and safety review. Study results were reported for the 6 actual dose groups allocated with participants.
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | PF-05230907 5 Microgram Per Kilogram (mcg/kg) | PF-05230907 5 mcg/kg was administered as a single intravenous (IV) bolus on Day 1. |
| FG001 | PF-05230907 8 mcg/kg | PF-05230907 8 mcg/kg was administered as a single IV bolus on Day 1. |
| FG002 | PF-05230907 12 mcg/kg | PF-05230907 12 mcg/kg was administered as a single IV bolus on Day 1. |
| FG003 | PF-05230907 19 mcg/kg | PF-05230907 19 mcg/kg was administered as a single IV bolus on Day 1. |
| FG004 | PF-05230907 24 mcg/kg | PF-05230907 24 mcg/kg was administered as a single IV bolus on Day 1. |
| FG005 | PF-05230907 30 mcg/kg | PF-05230907 30 mcg/kg was administered as a single IV bolus on Day 1. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
All participants who received the treatment of PF-05230907.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | PF-05230907 5 Microgram Per Kilogram (mcg/kg) | PF-05230907 5 mcg/kg was administered as a single intravenous (IV) bolus on Day 1. |
| BG001 | PF-05230907 8 mcg/kg | PF-05230907 8 mcg/kg was administered as a single IV bolus on Day 1. |
| 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 Treatment-Emergent Thromboembolic and/or Ischemic Events (TIEs) | Thromboembolic and/or ischemic events (TIEs) were defined as any of the following events: disseminated intravascular coagulation (Grade [Gr]>=3); acute coronary syndrome (Gr >=3); cardiac arrest (Gr >=4); myocardial infarction (Gr >=3); Cardiac troponin I increased (Gr 3); ischemia cerebrovascular (Gr >=1 and associated with lesion[s]); portal vein thrombosis (Gr >=2); ischemic stroke (Gr >=1 and associated with lesion[s]); transient ischemic attacks (Gr 2); purpura (Gr >=2); superior vena cava syndrome (Gr >=1); thromboembolic event (Gr >=2); visceral arterial ischemia (Gr >=2); peripheral arterial ischemia (Gr >=3). TIEs were graded based on Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. For the respective event to count as a treatment-emergent TIE, onset or worsening of the event must have occurred following treatment with PF-05230907 and during the interval between Day 1 dosing through Day 8. | All participants who received the treatment of PF-05230907. | Posted | Count of Participants | Participants | Day 1 through day of discharge (Day 8) |
For each participant, Adverse Events (AEs) were collected up to Day 43/follow-up visit. All-Cause Mortality table presents all deaths up to 3.4 months.
An AE may be categorized as serious in 1 participant and as non-serious in another participant; 1 participant may have experienced both a serious and non-serious AE.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | PF-05230907 5 Microgram Per Kilogram (mcg/kg) | PF-05230907 5 mcg/kg was administered as a single intravenous (IV) bolus on Day 1. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pneumonia | Infections and infestations | MedDRA 20.1 | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 20.1 | Non-systematic Assessment |
The study was terminated after 21 participants were enrolled for a strategic reason, not for safety nor efficacy reasons.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Pfizer ClinicalTrials.gov Call Center | Pfizer, Inc. | 1-800-718-1021 | ClinicalTrials.gov_Inquiries@pfizer.com |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jan 17, 2017 | Oct 25, 2018 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jan 8, 2018 | Oct 25, 2018 | SAP_001.pdf |
| ID | Term |
|---|---|
| D002543 | Cerebral Hemorrhage |
| D006470 | Hemorrhage |
| D006406 | Hematoma |
| ID | Term |
|---|---|
| D020300 | Intracranial Hemorrhages |
| D002561 | Cerebrovascular Disorders |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C000717013 | PF-05230907 |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| PF-05230907 (Cohort 7) | Experimental | PF-05230907 IV bolus injection |
|
| PF-05230907 (Cohort 8) | Experimental | PF-05230907 IV bolus injection |
|
| PF-05230907 (Cohort 9) | Experimental | PF-05230907 IV bolus injection |
|
| PF-05230907 (Cohort 10) | Experimental | PF-05230907 IV bolus injection |
|
| PF-05230907 (Cohort 11) | Experimental | PF-05230907 IV bolus injection |
|
| PF-05230907 (Cohort 12) | Experimental | PF-05230907 IV bolus injection |
|
| PF-05230907 (Cohort 13) | Experimental | PF-05230907 IV bolus injection |
|
| PF-05230907 (Cohort 14) | Experimental | PF-05230907 IV bolus injection |
|
| PF-05230907 (Cohort 15) | Experimental | PF-05230907 IV bolus injection |
|
| Number of Participants With Treatment-Emergent Laboratory Abnormalities | Laboratory safety parameters included hematology, blood chemistry, prothrombin time/international normalized ratio (PT/INR), fibrinogen, antithrombin III (ATIII), Protein S level, Protein C activity, cardiac troponin I, D-dimer, and urinalysis. The number of participants with laboratory test abnormalities meeting specified criteria without regard to baseline abnormality was assessed. Any abnormalities occurring after the administration of treatment and increasing in severity from baseline value were counted as treatment-emergent. | Day 1 through Day 8 (or discharge) for D-dimer laboratory test and urinalysis; Day 1 through Day 4 for all other laboratory tests |
| Number of Participants With Changes From Baseline in Physical Examination | Comprehensive and targeted physical examinations included general appearance, HEENT (head, eyes, ears, nose and throat), skin, heart (auscultation), lungs (auscultation), abdomen (palpitation and auscultation), and extremities with attention to swelling, general or localized tenderness, entire leg or calf swelling, edema, and collateral superficial veins. The results of the comprehensive and targeted physical examinations were combined to evaluate the changes from baseline through Day 8 (or discharge) for each site parameter according to the categories: positive change (abnormal to normal); no change (normal to normal or abnormal to abnormal); negative change (normal to abnormal). Parameters with at least 1 participant meeting the positive/negative change from baseline criteria are presented here. | Baseline (pre-dose), Day 2, Day 3, Day 4, Day 8/discharge |
| Change From Baseline for Body Temperature | Body temperature was measured by oral, tympanic, axillary or temporal method. | Baseline (pre-dose), Day 1 (5 and 45 minutes [min] post-dose), Day 2, Day 3, Day 4, Day 8/discharge |
| Change From Baseline for Supine Respiratory Rate | Respiratory rate was measured after 5 minutes rest in supine position by observing and counting the respirations of the participant for 30 seconds and multiplied by 2. The use of an automated device for measuring respiratory rate was acceptable. | Baseline (pre-dose), Day 1 (5 and 45 minutes [min] post-dose), Day 2, Day 3, Day 4, Day 8/discharge |
| Change From Baseline for Supine Systolic and Diastolic Blood Pressure | Supine blood pressure (BP, systolic and diastolic) was measured with the participant's arm supported at the level of the heart and recorded to the nearest milliliters of mercury (mmHg) after 5 minutes of rest whenever possible and as permitted by the participant's medical condition. | Baseline (pre-dose), Day 1 (5 and 45 minutes [min] post-dose), Day 2, Day 3, Day 4, Day 8/discharge |
| Change From Baseline for Supine Pulse Rate | The use of an automated device for measuring pulse rate was acceptable, although, when done manually, pulse rate was measured in the brachial/radial artery for at least 30 seconds. | Baseline (pre-dose), Day 1 (5 and 45 minutes [min] post-dose), Day 2, Day 3, Day 4, Day 8/discharge |
| Number of Participants With Electrocardiogram (ECG) Qualitative Results | The electrocardiogram (ECG) results over time were compared to baseline and assessed by the investigator as "less abnormal", "no significant change", or "more abnormal". | Baseline (pre-dose), Day 2, Day 4, Day 8/discharge |
Maximum changes from baseline were calculated for prothrombin fragment 1+2 (PF1+2) after dosing with PF-05230907 through Day 2. |
| Baseline (pre-dose), Day 2 |
| Number of Participants With Anti-Drug Antibody (ADA) Production | Participants with anti-drug antibody (ADA) production were those with at least 1 positive result from Day 1 through follow-up visit (Day 43 and/or Day 91). ADA positive: titer value >=1.88. | Day 1 up to follow-up visit (Day 43 and/or Day 91) |
| Number of Participants With Neutralizing Antibody (NAb) Production | ADA positive samples were planned to be further characterized for neutralizing antibody (NAb). Participants with NAb production were those with at least 1 positive result from Day 1 through follow-up visit (Day 43 and/or Day 91). As all ADA samples were negative (titer value <1.88), NAb analysis was not conducted. | Day 1 up to follow-up visit (Day 43 and/or Day 91) |
| Number of Participants With Depletion of Coagulation Factor X | Depletion of coagulation factor X was defined as >50% reduction relative to baseline (pre-dose). | Baseline (pre-dose), Day 43, Day 91 |
| Day 1 pre-dose, 5 and 45 minutes post-dose |
| Number of Participants With Anti-Chinese Hamster Ovary (CHO) Protein Antibody Production | Participants with anti-Chinese hamster ovary (CHO) antibody production were those with positive results. Positive: titer value >=2.00. | Day 1, Day 43 |
| Number of Participants With Anti-Paired Basic Amino Acid Cleaving Enzyme (PACE) Furin Antibody Production | Participants with anti-paired basic amino acid cleaving enzyme (PACE) antibody production were those with positive results. Positive: titer value >=2.00. | Day 1, Day 43 |
| Neurological Function as Assessed by the National Institute of Health Stroke Scale (NIHSS) | The National Institute of Health Stroke Scale (NIHSS) is a 15-item neurologic examination stroke scale used to evaluate the effect of acute cerebral infarction on the levels of consciousness, language, neglect, visual-field loss, extraocular movement, motor strength, ataxia, dysarthria, and sensory loss. The total NIHSS score range is from 0 (normal) to 42 (severe impairment), with higher values indicating greater level of neurological impairment. | Screening, Day 1, Day 2, Day 4, Day 43, and Day 91 |
| Health Resource Utilization Surrogate Measures - Maximum Duration | Maximum duration for 4 types of hospital or health care unit: Intensive Care Unit (ICU), general ward, rehabilitation center, and other hospital units. This was an exploratory endpoint to evaluate information for designing future studies, which were no longer planned. | Day 1 up to Day 91 |
| St Louis |
| Missouri |
| 63110 |
| United States |
| James Cancer Hospital and Solove Research Institute | Columbus | Ohio | 43210 | United States |
| The Ohio State University Wexner Medical Center | Columbus | Ohio | 43210 | United States |
| Martha Morehouse Medical Plaza | Columbus | Ohio | 43221 | United States |
| The Ottawa Hospital | Ottawa | Ontario | K1Y4E9 | Canada |
| Montreal Neurological Institute and Hospital | Montreal | Quebec | H3A2B4 | Canada |
| Hospital Universitari Germans Trias i Pujol | Badalona | Barcelona | 08916 | Spain |
| Hospital Clínico Universitario de Santiago de Compostela, Area Neurovascular-Neurologia | Santiago de Compostela | LA Coruna | 15706 | Spain |
| Hospital Vall d'Hebron, Unidad de Ictus | Barcelona | 08035 | Spain |
| Hospital Universitari Dr. Josep Trueta IDIBGI, Department Neurology | Girona | 17007 | Spain |
| Hospital Universitario Ramon y Cajal | Madrid | 28034 | Spain |
| University College Hospital | London | NW1 2BU | United Kingdom |
| To obtain contact information for a study center near you, click here. | View source |
| Withdrawal by Subject |
|
| BG002 | PF-05230907 12 mcg/kg | PF-05230907 12 mcg/kg was administered as a single IV bolus on Day 1. |
| BG003 | PF-05230907 19 mcg/kg | PF-05230907 19 mcg/kg was administered as a single IV bolus on Day 1. |
| BG004 | PF-05230907 24 mcg/kg | PF-05230907 24 mcg/kg was administered as a single IV bolus on Day 1. |
| BG005 | PF-05230907 30 mcg/kg | PF-05230907 30 mcg/kg was administered as a single IV bolus on Day 1. |
| BG006 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| ID |
|---|
| Title |
|---|
| Description |
|---|
| OG000 | PF-05230907 5 Microgram Per Kilogram (mcg/kg) | PF-05230907 5 mcg/kg was administered as a single intravenous (IV) bolus on Day 1. |
| OG001 | PF-05230907 8 mcg/kg | PF-05230907 8 mcg/kg was administered as a single IV bolus on Day 1. |
| OG002 | PF-05230907 12 mcg/kg | PF-05230907 12 mcg/kg was administered as a single IV bolus on Day 1. |
| OG003 | PF-05230907 19 mcg/kg | PF-05230907 19 mcg/kg was administered as a single IV bolus on Day 1. |
| OG004 | PF-05230907 24 mcg/kg | PF-05230907 24 mcg/kg was administered as a single IV bolus on Day 1. |
| OG005 | PF-05230907 30 mcg/kg | PF-05230907 30 mcg/kg was administered as a single IV bolus on Day 1. |
|
|
| Primary | Number of Participants With Treatment-Emergent Serious Adverse Events (SAEs) | A serious adverse event (SAE) was any untoward medical occurrence at any dose that: resulted in death; or was life threatening (immediate risk of death); or required inpatient hospitalization or prolongation of existing hospitalization; or resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); or resulted in congenital anomaly/birth defect. Any such events occurring following the start of treatment or increasing in severity were counted as treatment-emergent. | All participants who received the treatment of PF-05230907. | Posted | Count of Participants | Participants | Day 1 through follow-up visit (Day 43) |
|
|
|
| Primary | Number of Participants With Treatment-Emergent Adverse Events (AEs) | An adverse event (AE) was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. For the respective event to count as a treatment-emergent AE, onset or worsening of the event must have occurred following treatment with PF-05230907 and during the interval between Day 1 dosing through Day 8. | All participants who received the treatment of PF-05230907. | Posted | Count of Participants | Participants | Day 1 through day of discharge (Day 8) |
|
|
|
| Primary | Number of Participants With Treatment-Emergent Laboratory Abnormalities | Laboratory safety parameters included hematology, blood chemistry, prothrombin time/international normalized ratio (PT/INR), fibrinogen, antithrombin III (ATIII), Protein S level, Protein C activity, cardiac troponin I, D-dimer, and urinalysis. The number of participants with laboratory test abnormalities meeting specified criteria without regard to baseline abnormality was assessed. Any abnormalities occurring after the administration of treatment and increasing in severity from baseline value were counted as treatment-emergent. | All participants who received the treatment of PF-05230907. | Posted | Count of Participants | Participants | Day 1 through Day 8 (or discharge) for D-dimer laboratory test and urinalysis; Day 1 through Day 4 for all other laboratory tests |
|
|
|
| Primary | Number of Participants With Changes From Baseline in Physical Examination | Comprehensive and targeted physical examinations included general appearance, HEENT (head, eyes, ears, nose and throat), skin, heart (auscultation), lungs (auscultation), abdomen (palpitation and auscultation), and extremities with attention to swelling, general or localized tenderness, entire leg or calf swelling, edema, and collateral superficial veins. The results of the comprehensive and targeted physical examinations were combined to evaluate the changes from baseline through Day 8 (or discharge) for each site parameter according to the categories: positive change (abnormal to normal); no change (normal to normal or abnormal to abnormal); negative change (normal to abnormal). Parameters with at least 1 participant meeting the positive/negative change from baseline criteria are presented here. | All participants who received the treatment of PF-05230907. | Posted | Count of Participants | Participants | Baseline (pre-dose), Day 2, Day 3, Day 4, Day 8/discharge |
|
|
|
| Primary | Change From Baseline for Body Temperature | Body temperature was measured by oral, tympanic, axillary or temporal method. | All participants who received the treatment of PF-05230907. "Number Analyzed" represents the number of participants evaluable for each specified time point. | Posted | Mean | Standard Deviation | Degree Celsius (°C) | Baseline (pre-dose), Day 1 (5 and 45 minutes [min] post-dose), Day 2, Day 3, Day 4, Day 8/discharge |
|
|
|
| Primary | Change From Baseline for Supine Respiratory Rate | Respiratory rate was measured after 5 minutes rest in supine position by observing and counting the respirations of the participant for 30 seconds and multiplied by 2. The use of an automated device for measuring respiratory rate was acceptable. | All participants who received the treatment of PF-05230907. "Number Analyzed" represents the number of participants evaluable for each specified time point. | Posted | Mean | Standard Deviation | respiration per minute | Baseline (pre-dose), Day 1 (5 and 45 minutes [min] post-dose), Day 2, Day 3, Day 4, Day 8/discharge |
|
|
|
| Primary | Change From Baseline for Supine Systolic and Diastolic Blood Pressure | Supine blood pressure (BP, systolic and diastolic) was measured with the participant's arm supported at the level of the heart and recorded to the nearest milliliters of mercury (mmHg) after 5 minutes of rest whenever possible and as permitted by the participant's medical condition. | All participants who received the treatment of PF-05230907. "Number Analyzed" represents the number of participants evaluable for each specified category. | Posted | Mean | Standard Deviation | milliliters of mercury (mmHg) | Baseline (pre-dose), Day 1 (5 and 45 minutes [min] post-dose), Day 2, Day 3, Day 4, Day 8/discharge |
|
|
|
| Primary | Change From Baseline for Supine Pulse Rate | The use of an automated device for measuring pulse rate was acceptable, although, when done manually, pulse rate was measured in the brachial/radial artery for at least 30 seconds. | All participants who received the treatment of PF-05230907. "Number Analyzed" represents the number of participants evaluable for each specified time point. | Posted | Mean | Standard Deviation | beats per minute (bpm) | Baseline (pre-dose), Day 1 (5 and 45 minutes [min] post-dose), Day 2, Day 3, Day 4, Day 8/discharge |
|
|
|
| Primary | Number of Participants With Electrocardiogram (ECG) Qualitative Results | The electrocardiogram (ECG) results over time were compared to baseline and assessed by the investigator as "less abnormal", "no significant change", or "more abnormal". | All participants who received the treatment of PF-05230907. "Number Analyzed" represents the number of participants evaluable for each specified category. | Posted | Count of Participants | Participants | Baseline (pre-dose), Day 2, Day 4, Day 8/discharge |
|
|
|
| Secondary | Maximum Changes From Baseline for Activated Partial Thromboplastin Time (aPTT) | Maximum changes from baseline were calculated for activated partial thromboplastin time (aPTT) after dosing with PF-05230907 through Day 2. | All treated participants who had at least 1 measurement of pharmacodynamic parameters of interest. | Posted | Mean | Standard Deviation | seconds (sec) | Baseline (pre-dose), Day 2 |
|
|
|
| Secondary | Maximum Changes From Baseline for Prothrombin Fragment 1+2 (PF1+2) | Maximum changes from baseline were calculated for prothrombin fragment 1+2 (PF1+2) after dosing with PF-05230907 through Day 2. | All treated participants who had at least 1 measurement of pharmacodynamic parameters of interest. | Posted | Mean | Standard Deviation | picomoles per liter (pmol/L) | Baseline (pre-dose), Day 2 |
|
|
|
| Secondary | Number of Participants With Anti-Drug Antibody (ADA) Production | Participants with anti-drug antibody (ADA) production were those with at least 1 positive result from Day 1 through follow-up visit (Day 43 and/or Day 91). ADA positive: titer value >=1.88. | All treated participants who had at least 1 measurement of post-treatment immunogenicity parameters of interest. | Posted | Count of Participants | Participants | Day 1 up to follow-up visit (Day 43 and/or Day 91) |
|
|
|
| Secondary | Number of Participants With Neutralizing Antibody (NAb) Production | ADA positive samples were planned to be further characterized for neutralizing antibody (NAb). Participants with NAb production were those with at least 1 positive result from Day 1 through follow-up visit (Day 43 and/or Day 91). As all ADA samples were negative (titer value <1.88), NAb analysis was not conducted. | All treated participants who had at least 1 measurement of post-treatment immunogenicity parameters of interest. | Posted | Day 1 up to follow-up visit (Day 43 and/or Day 91) |
|
|
| Secondary | Number of Participants With Depletion of Coagulation Factor X | Depletion of coagulation factor X was defined as >50% reduction relative to baseline (pre-dose). | All participants who received the treatment of PF-05230907. "Number Analyzed" represents the number of participants evaluable for each specified category. | Posted | Count of Participants | Participants | Baseline (pre-dose), Day 43, Day 91 |
|
|
|
| Other Pre-specified | Change From Baseline in Intracerebral Hemorrhage (ICH) Volume at 24 Hours | Change from baseline in intracerebral hemorrhage (ICH) volume was calculated at 24 hours. | All participants who received the treatment of PF-05230907. | Posted | Mean | Standard Deviation | centimeter (cm)^3 | Baseline (pre-dose), 24 hours |
|
|
|
| Other Pre-specified | PF-05230907 Concentration in Plasma | All treated participants who had at least 1 measurement of PF-05230907 concentration. "Number Analyzed" represents the number of participants evaluable for each specified category. | Posted | Mean | Standard Deviation | nanogram per milliliter (ng/mL) | Day 1 pre-dose, 5 and 45 minutes post-dose |
|
|
|
| Other Pre-specified | Number of Participants With Anti-Chinese Hamster Ovary (CHO) Protein Antibody Production | Participants with anti-Chinese hamster ovary (CHO) antibody production were those with positive results. Positive: titer value >=2.00. | All treated participants who had at least 1 measurement of post-treatment immunogenicity parameters of interest. "Number Analyzed" represents the number of participants evaluable for each specified category. | Posted | Count of Participants | Participants | Day 1, Day 43 |
|
|
|
| Other Pre-specified | Number of Participants With Anti-Paired Basic Amino Acid Cleaving Enzyme (PACE) Furin Antibody Production | Participants with anti-paired basic amino acid cleaving enzyme (PACE) antibody production were those with positive results. Positive: titer value >=2.00. | All treated participants who had at least 1 measurement of post-treatment immunogenicity parameters of interest. "Number Analyzed" represents the number of participants evaluable for each specified category. | Posted | Count of Participants | Participants | Day 1, Day 43 |
|
|
|
| Other Pre-specified | Neurological Function as Assessed by the National Institute of Health Stroke Scale (NIHSS) | The National Institute of Health Stroke Scale (NIHSS) is a 15-item neurologic examination stroke scale used to evaluate the effect of acute cerebral infarction on the levels of consciousness, language, neglect, visual-field loss, extraocular movement, motor strength, ataxia, dysarthria, and sensory loss. The total NIHSS score range is from 0 (normal) to 42 (severe impairment), with higher values indicating greater level of neurological impairment. | All participants who received the treatment of PF-05230907. "Number Analyzed" represents the number of participants evaluable for each specified category. | Posted | Mean | Standard Deviation | units on a scale | Screening, Day 1, Day 2, Day 4, Day 43, and Day 91 |
|
|
|
| Other Pre-specified | Health Resource Utilization Surrogate Measures - Maximum Duration | Maximum duration for 4 types of hospital or health care unit: Intensive Care Unit (ICU), general ward, rehabilitation center, and other hospital units. This was an exploratory endpoint to evaluate information for designing future studies, which were no longer planned. | All participants who received the treatment of PF-05230907. "Number Analyzed" represents the number of participants evaluable for each specified category. | Posted | Median | Full Range | days | Day 1 up to Day 91 |
|
|
|
| 0 |
| 3 |
| 0 |
| 3 |
| 2 |
| 3 |
| EG001 | PF-05230907 8 mcg/kg | PF-05230907 8 mcg/kg was administered as a single IV bolus on Day 1. | 1 | 3 | 1 | 3 | 3 | 3 |
| EG002 | PF-05230907 12 mcg/kg | PF-05230907 12 mcg/kg was administered as a single IV bolus on Day 1. | 1 | 3 | 1 | 3 | 3 | 3 |
| EG003 | PF-05230907 19 mcg/kg | PF-05230907 19 mcg/kg was administered as a single IV bolus on Day 1. | 0 | 6 | 0 | 6 | 5 | 6 |
| EG004 | PF-05230907 24 mcg/kg | PF-05230907 24 mcg/kg was administered as a single IV bolus on Day 1. | 2 | 3 | 2 | 3 | 3 | 3 |
| EG005 | PF-05230907 30 mcg/kg | PF-05230907 30 mcg/kg was administered as a single IV bolus on Day 1. | 1 | 3 | 2 | 3 | 3 | 3 |
| Brain oedema | Nervous system disorders | MedDRA 20.1 | Non-systematic Assessment |
|
| Cerebral haemorrhage | Nervous system disorders | MedDRA 20.1 | Non-systematic Assessment |
|
| Stroke in evolution | Nervous system disorders | MedDRA 20.1 | Non-systematic Assessment |
|
| Deep vein thrombosis | Vascular disorders | MedDRA 20.1 | Non-systematic Assessment |
|
| Thrombophlebitis | Vascular disorders | MedDRA 20.1 | Non-systematic Assessment |
|
| Atrial flutter | Cardiac disorders | MedDRA 20.1 | Non-systematic Assessment |
|
| Sinus tachycardia | Cardiac disorders | MedDRA 20.1 | Non-systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA 20.1 | Non-systematic Assessment |
|
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA 20.1 | Non-systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 20.1 | Non-systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 20.1 | Non-systematic Assessment |
|
| Chest pain | General disorders | MedDRA 20.1 | Non-systematic Assessment |
|
| Injection site phlebitis | General disorders | MedDRA 20.1 | Non-systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA 20.1 | Non-systematic Assessment |
|
| Pain | General disorders | MedDRA 20.1 | Non-systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 20.1 | Non-systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA 20.1 | Non-systematic Assessment |
|
| Fall | Injury, poisoning and procedural complications | MedDRA 20.1 | Non-systematic Assessment |
|
| Subcutaneous haematoma | Injury, poisoning and procedural complications | MedDRA 20.1 | Non-systematic Assessment |
|
| Bacterial test positive | Investigations | MedDRA 20.1 | Non-systematic Assessment |
|
| Blood triglycerides increased | Investigations | MedDRA 20.1 | Non-systematic Assessment |
|
| Fibrin D dimer increased | Investigations | MedDRA 20.1 | Non-systematic Assessment |
|
| Troponin I increased | Investigations | MedDRA 20.1 | Non-systematic Assessment |
|
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 20.1 | Non-systematic Assessment |
|
| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA 20.1 | Non-systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 20.1 | Non-systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 20.1 | Non-systematic Assessment |
|
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 20.1 | Non-systematic Assessment |
|
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA 20.1 | Non-systematic Assessment |
|
| Cerebral ischaemia | Nervous system disorders | MedDRA 20.1 | Non-systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 20.1 | Non-systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 20.1 | Non-systematic Assessment |
|
| Seizure | Nervous system disorders | MedDRA 20.1 | Non-systematic Assessment |
|
| Somnolence | Nervous system disorders | MedDRA 20.1 | Non-systematic Assessment |
|
| Syncope | Nervous system disorders | MedDRA 20.1 | Non-systematic Assessment |
|
| Agitation | Psychiatric disorders | MedDRA 20.1 | Non-systematic Assessment |
|
| Urinary retention | Renal and urinary disorders | MedDRA 20.1 | Non-systematic Assessment |
|
| Apnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Non-systematic Assessment |
|
| Hypoventilation | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Non-systematic Assessment |
|
| Pulmonary hypertension | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Non-systematic Assessment |
|
| Respiratory disorder | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Non-systematic Assessment |
|
| Skin ulcer | Skin and subcutaneous tissue disorders | MedDRA 20.1 | Non-systematic Assessment |
|
| Pain management | Surgical and medical procedures | MedDRA 20.1 | Non-systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA 20.1 | 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.
| D009422 | Nervous System Diseases |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| Extremities: Negative change, Day 2 |
|
| Extremities: Negative change, Day 3 |
|
| Extremities: Negative change, Day 4 |
|
| Extremities: Negative change, Day 8/discharge |
|
| Extremities: Positive change, Day 3 |
|
| Extremities: Positive change, Day 4 |
|
| Extremities: Positive change, Day 8/discharge |
|
| Eyes: Negative change, Day 3 |
|
| Eyes: Negative change, Day 8/discharge |
|
| Eyes: Positive change, Day 2 |
|
| Eyes: Positive change, Day 8/discharge |
|
| Head: Negative change, Day 2 |
|
| Head: Negative change, Day 4 |
|
| Head: Positive change, Day 8/discharge |
|
| Heart: Negative change, Day 2 |
|
| Heart: Negative change, Day 3 |
|
| Heart: Negative change, Day 4 |
|
| Heart: Negative change, Day 8/discharge |
|
| Lungs: Negative change, Day 2 |
|
| Lungs: Negative change, Day 4 |
|
| Lungs: Negative change, Day 8/discharge |
|
| Lungs: Positive change, Day 2 |
|
| Lungs: Positive change, Day 8/discharge |
|
| Neurological: Negative change, Day 8/discharge |
|
| Neurological: Positive change, Day 2 |
|
| Neurological: Positive change, Day 3 |
|
| Neurological: Positive change, Day 4 |
|
| Skin: Positive change, Day 2 |
|
| Skin: Positive change, Day 4 |
|
| Skin: Positive change, Day 8/discharge |
|
| Throat: Negative change, Day 8/discharge |
|
|
| Day 1 (45 min) |
|
|
| Day 2 |
|
|
| Day 3 |
|
|
| Day 4 |
|
|
| Day 8/discharge |
|
|
|
| Day 1 (45 min) |
|
|
| Day 2 |
|
|
| Day 3 |
|
|
| Day 4 |
|
|
| Day 8/discharge |
|
|
|
| Supine Systolic BP, Day 1 (45 min) |
|
|
| Supine Systolic BP, Day 2 |
|
|
| Supine Systolic BP, Day 3 |
|
|
| Supine Systolic BP, Day 4 |
|
|
| Supine Systolic BP, Day 8/discharge |
|
|
| Supine Diastolic BP, Day 1 (5 min) |
|
|
| Supine Diastolic BP, Day 1 (45 min) |
|
|
| Supine Diastolic BP, Day 2 |
|
|
| Supine Diastolic BP, Day 3 |
|
|
| Supine Diastolic BP, Day 4 |
|
|
| Supine Diastolic BP, Day 8/discharge |
|
|
|
| Day 1 (45 min) |
|
|
| Day 2 |
|
|
| Day 3 |
|
|
| Day 4 |
|
|
| Day 8/discharge |
|
|
|
| Day 4 |
|
|
| Day 8/discharge |
|
|
|
| Day 91 |
|
|
|
| 5 minutes post-dose |
|
|
| 45 minutes post-dose |
|
|
|
| Day 43 |
|
|
|
| Day 43 |
|
|
|
| Day 1 |
|
|
| Day 2 |
|
|
| Day 4 |
|
|
| Day 43 |
|
|
| Day 91 |
|
|
|
| General ward |
|
|
| Rehabilitation center |
|
|
| Other hospital unit |
|
|
| No significant change |
|
| More abnormal |
|
| No significant change |
|
| More abnormal |
|