Safety and Tolerability of PF-05230907 in Intracerebral Hemorrhage

Study at a glance

From the registry record, last updated by the sponsor on 17 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title

A PHASE 1B MULTICENTER, OPEN-LABEL STUDY TO EVALUATE THE SAFETY AND TOLERABILITY AND DETERMINE THE MAXIMUM TOLERATED DOSE OF PF-05230907 IN SUBJECTS WITH INTRACEREBRAL HEMORRHAGE (ICH)

ClinicalTrials.gov ID

NCT02687191

Acronym / sponsor ID

B2341002

Conditions

Intracerebral Hemorrhage

Keywords

safety, maximum tolerated dose, modified continual reassessment method, intracerebral, hemorrhage, hematoma

Phase

Phase 1

Study type

Interventional

Recruitment status

TerminatedReason stopped: B2341002 was terminated on 26-OCT-2017 for strategic reasons. The decision to terminate the trial was not based on any safety concerns.

Enrolment

21 participants (actual)

Lead sponsor

PfizerIndustry (pharma, biotech, devices)

Study start

Nov 2016 (actual)

Primary completion

Jan 2018 (actual)

Study completion

Jan 2018 (actual)

First posted

22 Feb 2016 (estimated)

Results

Posted 17 Apr 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose

Treatment

Allocation

Non-randomised

Intervention model

Parallel groups

Masking

None (open label)

Number of arms

15

Who may qualify

Ages

18 to 79 years

Sex

All

Healthy volunteers

Not accepted

Age groups

Adult, Older adult

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Primary outcome

1. Number of Participants With Treatment-Emergent Thromboembolic and/or Ischemic Events (TIEs)

   Time frame: Day 1 through day of discharge (Day 8)

   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.

2. Number of Participants With Treatment-Emergent Serious Adverse Events (SAEs)

   Time frame: Day 1 through follow-up visit (Day 43)

   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.

3. Number of Participants With Treatment-Emergent Adverse Events (AEs)

   Time frame: Day 1 through day of discharge (Day 8)

   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.

4. Number of Participants With Treatment-Emergent Laboratory Abnormalities

   Time frame: Day 1 through Day 8 (or discharge) for D-dimer laboratory test and urinalysis; Day 1 through Day 4 for all other laboratory tests

   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.

5. Number of Participants With Changes From Baseline in Physical Examination

   Time frame: Baseline (pre-dose), Day 2, Day 3, Day 4, Day 8/discharge

   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.

6. Change From Baseline for Body Temperature

   Time frame: Baseline (pre-dose), Day 1 (5 and 45 minutes [min] post-dose), Day 2, Day 3, Day 4, Day 8/discharge

   Body temperature was measured by oral, tympanic, axillary or temporal method.

7. Change From Baseline for Supine Respiratory Rate

   Time frame: Baseline (pre-dose), Day 1 (5 and 45 minutes [min] post-dose), Day 2, Day 3, Day 4, Day 8/discharge

   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.

8. Change From Baseline for Supine Systolic and Diastolic Blood Pressure

   Time frame: Baseline (pre-dose), Day 1 (5 and 45 minutes [min] post-dose), Day 2, Day 3, Day 4, Day 8/discharge

   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.

9. Change From Baseline for Supine Pulse Rate

   Time frame: Baseline (pre-dose), Day 1 (5 and 45 minutes [min] post-dose), Day 2, Day 3, Day 4, Day 8/discharge

   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.

10. Number of Participants With Electrocardiogram (ECG) Qualitative Results

    Time frame: Baseline (pre-dose), Day 2, Day 4, Day 8/discharge

    The electrocardiogram (ECG) results over time were compared to baseline and assessed by the investigator as "less abnormal", "no significant change", or "more abnormal".

Results and safety

Loading the posted results from ClinicalTrials.gov…

Research links

• Official record on ClinicalTrials.govLast updated by the sponsor 17 Apr 2019.
• Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
• Derived from this study: PubMed 33272131Silva 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.
• To obtain contact information for a study center near you, click here.Link provided by the sponsor.
• To obtain contact information for a study center near you, click here.Link provided by the sponsor.
• Individual participant dataSharing planned: No. 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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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.

13 sites in 4 countries: see every site and its status.