Phase 2
N=23
Study to Evaluate the Safety, Tolerability, PK and PD of PB2452 in Healthy Younger, Older and Elderly Subjects
Healthy
Bottom Line
View on ClinicalTrials.gov: NCT03928353 ↗Enrolled (actual)
23
Serious AEs
4.4%
Results posted
May 2024
Primary outcome: Primary: Number Of Participants With Treatment-emergent Adverse Events (TEAEs) And Serious Adverse Events (SAEs) — 1; 2; 3; 3 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- PB2452 Infusion (Drug); Placebo - Sodium Chloride (Drug); Ticagrelor Oral Tablet - Pre-Treatment (Drug); Ticagrelor Oral Tablet - Pre-Treatment and Post-Treatment (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- SFJ Pharmaceuticals, Inc.
- Primary completion
- Oct 2019
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number Of Participants With Treatment-emergent Adverse Events (TEAEs) And Serious Adverse Events (SAEs) |
1; 2; 3; 3; 4; 1 | — |
| PRIMARY Number of Participants With Clinical Laboratory Abnormalities |
0; 0; 0; 0; 0 | — |
| PRIMARY Mean Diastolic Blood Pressure at Baseline |
74.17; 67.60; 71.18; 75.25; 63.83; 61.50 | — |
| PRIMARY Percent Change In Diastolic Blood Pressure From Baseline To Day 28 |
-2.50; -1.75; -2.13; -4.00; 4.00; 2.50 | — |
| PRIMARY Mean Systolic Blood Pressure at Baseline |
128.33; 115.40; 122.45; 119.00; 113.14; 108.50 | — |
| PRIMARY Percent Change In Systolic Blood Pressure From Baseline To Day 28 |
-6.75; 0.75; -3.00; -7.50; 5.83; 2.00 | — |
| PRIMARY Mean Oral Body Temperature at Baseline |
36.17; 35.88; 36.04; 36.25; 36.20; 36.35 | — |
| PRIMARY Percent Change In Oral Body Temperature From Baseline To Day 28 |
0.18; 0; 0.11; 0.15; 0.13; -0.10 | — |
| PRIMARY Mean Respiratory Rate at Baseline |
14.33; 13.60; 14.00; 12.50; 15.67; 17.00 | — |
| PRIMARY Percent Change In Respiratory Rate From Baseline To Day 28 |
-3.33; 0.50; -1.80; -0.50; -1.00; -3.00 | — |
| PRIMARY Mean Heart Rate at Baseline |
70.17; 60.20; 65.64; 63.00; 65.50; 78.00 | — |
| PRIMARY Percent Change In Heart Rate From Baseline To Day 28 |
-5.25; 0.50; -2.38; -4.00; -3.17; -16.00 | — |
| PRIMARY Incidence Of Clinically Significant 12-Lead Electrocardiogram (ECG) Findings |
0; 1; 0; 0; 0 | — |
| PRIMARY Participants Experiencing Anti-drug Antibodies (ADAs) |
2; 0; 2; 0; 0; 0 | — |
| PRIMARY Number of Participants With Adverse Events During Physical Examination |
0; 0; 1; 0; 0 | — |
Summary
This is a Phase 2A, randomized, double-blind, placebo-controlled, single dose, sequential group study to evaluate the safety, tolerability, PK, and PD of PB2452 vs matching placebo with ticagrelor (with or without acetylsalicylic acid (ASA)) pretreatment when various dose levels and administration regimens are administered to healthy younger (ages 18 to 50), older (ages 50 to 64 years) and elderly (ages 65 to 80 years) male and female subjects.
Up to 5 dose levels and/or administration regimens will be evaluated in up to 5 cohorts. Each cohort will include approximately 8 to 12 subjects randomized in a 3:1 ratio (PB2452:placebo).
Eligibility Criteria
Inclusion Criteria
- The subject provides written informed consent and agrees to comply with all protocol requirements.
- The subject is male or female between 18 and 80 years of age, inclusive (50 to 80 years for Cohorts 1-2, 18 to 50 years for Cohorts 3-5).
- The subject has a body mass index (BMI) between 18 and 35 kg/m2 and a weight of ≥50 kg but ≤120 kg, inclusive, at Screening.
- The subject is considered by the investigator to be in good general health, as determined by medical history, clinical laboratory test results, vital sign measurements, 12 lead ECG results, and physical examination findings at Screening. Older and elderly subjects with chronic, stable, and well-controlled medical conditions are eligible provided they meet all other inclusion/exclusion criteria. Some examples of stable and well-controlled medical conditions include but are not limited to:
- Hypertension (HTN) controlled with ≤2 antihypertensive drugs
- Diabetes controlled with diet/exercise or treated with up to 2 oral diabetes medications
- Subjects with diabetes must have a glycated hemoglobin HbA1c ≤8 mg/dL at Screening.
- Mild hepatic enzyme elevation (aspartate aminotransferase (AST) or alanine transaminase (ALT) 40 IU/mL) or amenorrhea for 24 consecutive months.
- Male subjects with partners of childbearing potential must agree to use appropriate and effective measures of contraception (e.g., condom plus diaphragm with spermicide, condom plus spermicide) during the study and for 30 days after the last dose of study drug, and refrain from donating sperm for ≥90 days following the last dose of study drug.
Exclusion Criteria
- Concern the subject may be unable to comply with study procedures and/or follow up, or, in the opinion of the investigator, the subject is not suitable for entry into the study
- History of any acute or chronic medical disorder expected to decrease the life expectancy of the subject
- History or presence of gastrointestinal (GI), hepatic (with the exception of Gilbert's syndrome), or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs
- Significant renal insufficiency, as indicated by estimated glomerular filtration rate (eGFR) 160 mm Hg
- Diastolic blood pressure (DBP) 95 mm Hg
- Resting heart rate (HR) 100 beats per minute (bpm)
Specific exclusionary criteria for ECG parameters at Screening or Check-in include any of the following:
- Prolonged Fridericia-corrected QT interval (QTcF) >450 milliseconds (msec)
- Shortened QTcF 3 seconds
- Family history of long QT syndrome
- Any specific contraindication to Brilinta® as described in the Brilinta® prescribing information and:
- History of intracranial hemorrhage, active bleeding, or hypersensitivity or allergic reaction to ticagrelor or any component of the product
- Any history of severe head trauma, intracranial neoplasm, arteriovenous malformation, aneurysm, or proliferative retinopathy
- Any history of intraocular, retroperitoneal, or spinal bleeding
- Have taken, within 30 days of Screening, any oral or parenteral anticoagulant, including low molecular-weight heparin
- Stool sample testing positive for occult blood within 3 months of Screening or at any time during the Screening Period
- Receiving chronic treatment with nonsteroidal anti-inflammatory drugs (NSAIDS; [including ASA >100 mg daily]), anticoagulants, or other antiplatelet agents that cannot be discontinued 14 days prior to randomization (including clopidogrel, prasugrel, ticlopidine, dipyridamole, or cilostazol)
- Positive test result for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, or human immunodeficiency virus (HIV) types 1 or 2 antibodies at Screening
- Concomitant oral or IV therapy with strong cytochrome P450 3A4 (CYP3A) inhibitors, CYP3A substrates with narrow therapeutic indices, or strong CYP3A inducers, which cannot be stopped within at least 5 half-lives, but not fewer than 10 days, before randomi
Data sourced from ClinicalTrials.gov (NCT03928353). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.