Treatment of Post-Punch Biopsy Bleeding in Anticoagulated Patients Using Self-Administered BXP154

Study Overview
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Brief Summary
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The goal of this clinical trial is to test if the study drug, BXP154 works to stop bleeding from a minor wound in patients that are on anticoagulant therapy. The main questions it aims to answer are: How long does it take to stop bleeding after BXP154 is applied to a wound? How many people require the use of a rescue treatment to stop bleeding? Does BXP154 reduce instances of re-bleeding after the bleeding has stopped initially? Is BXP154 safe and well-tolerated?

Detailed Description
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Oral anticoagulant-related clinically relevant nonmajor bleeding (CRNMB; i.e., non-major bleeding that requires medical intervention, increased level of care, or face-to-face evaluation) and minor bleeding, often referred to as 'nuisance' bleeding, carries a high burden in terms of patient discomfort, anxiety, temporary disability, and reduced quality of life, and strain on medical and socioeconomic resources. Prolonged bleeding following minor injuries (falls, scrapes, cuts) can be life-interrupting and frequently leads patients to seek medical care, often times in an urgent care or emergency department (ED) setting. Prolonged bleeding from minor injuries is a significant challenge to daily life for people on anticoagulants, and is anything but 'minor' to the patient. Bio 54, LLC, is developing BXP154, a topical agent intended for self-administration (in or outside the home) to treat external bleeding from minor wounds in patients on anticoagulants. The development of BXP154 will offer patients on anticoagulants a much-needed treatment for self-management of external bleeding from minor wounds at home. BXP154-PIL is a randomized, double-blind, placebo-controlled, 2-way crossover-design study to evaluate the efficacy, safety, and pharmacokinetics of BXP154 (1500 mg/6 mL) compared with volume-matched placebo in the treatment of bleeding following punch biopsy in anticoagulated subjects. Subjects will be enrolled in this clinical trial for a total of nine days, following a screening period of up to 28 days. The study commences on Day 1 with a skin punch biopsy and administration of the investigational drug or placebo. Subsequently, follow-up assessments will be conducted on Days 2, 3, and 4. A second skin punch biopsy will be performed on Day 4, followed by additional follow-up assessments on Days 5, 6, 7,and 9. Upon completion of the Day 9 assessments, subjects will have fulfilled their involvement in the study.

Official Title
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Treatment of Post-Punch Biopsy Bleeding in Anticoagulated Patients Using Self-Administered BXP154

Conditions
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Wound Bleeding

Intervention / Treatment
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* Drug: BXP154
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female ≥18 years of age on the day of signed informed consent. At least 8 subjects of each sex will be enrolled. Currently receiving anticoagulant therapy at the permitted therapeutic dose as described below, and who have been on the same anticoagulant for ≥30 days prior to Screening Permitted anticoagulants and doses include: Warfarin, any dose as prescribed as long as the International Normalized Ratio (INR) criteria are met; apixaban (Eliquis®), 10 mg total daily dose; or rivaroxaban (Xarelto®), ≥15 mg total daily dose Subjects on Warfarin must meet INR therapeutic range: INR 2-3.5 Willing and able to provide informed consent prior to any study procedures and to comply with all aspects of the protocol Exclusion Criteria: Allergy or sensitization to any components of BXP154 Known genetic/familial hypercoagulable disorder Thrombocytopenia (platelets <75,000/mm3) Subjects using any prescribed chronic drug therapies that impact platelet function including clopidogrel (Plavix®), prasugrel (Effient®), ticagrelor (Brillinta®), dipyridamole (Aggrenox®), cilostazol (Pletal®), aspirin, or any non-steroidal anti-inflammatory drugs (NSAIDs; e.g., ibuprofen, naproxen, diclofenac, indomethacin, ketorolac, etc.) are excluded from participation in the study. NSAIDs or aspirin taken on an as needed (PRN) basis must be discontinued according to the following required windows prior to Day 1 (aspirin, 7 days; ibuprofen, 24 hours; all other NSAIDs, 4 days) and may not be taken for the duration of the study. Hypersensitivity to any local anesthetic being used by the site Pregnant, breastfeeding, or planning to become pregnant Use of any hormonal contraceptive methods (e.g., oral, injectable, vaginal ring, transdermal patch, or hormonal intrauterine device [IUD]), or any oral treatment containing estrogen or synthetic estrogen within 30 days prior to Screening or during study participation. Women of childbearing potential must agree to use effective non-hormonal contraception during study participation. Participation in another clinical trial for an investigational product within 30 days prior to Screening

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Randomized, double-blind, placebo-controlled, 2-way crossover
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sequence A<br>Single topical application of BXP154 6ml (right leg), treatment period 1; single topical application of Placebo 6ml (left leg), treatment period 2 | Drug: BXP154<br>* BXP154 will be self-administered topically following wound induction<br>Drug: Placebo<br>* Placebo will be self-administered topically following wound induction<br>|
| Experimental: Sequence B<br>Single topical application of Placebo 6ml (right leg), treatment period 1; single topical application of BXP154 6ml (left leg), treatment period 2 | Drug: BXP154<br>* BXP154 will be self-administered topically following wound induction<br>Drug: Placebo<br>* Placebo will be self-administered topically following wound induction<br>|
| Experimental: Sequence C<br>Single topical application of BXP154 6ml (left leg), treatment period 1; single topical application of Placebo 6ml (right leg), treatment period 2 | Drug: BXP154<br>* BXP154 will be self-administered topically following wound induction<br>Drug: Placebo<br>* Placebo will be self-administered topically following wound induction<br>|
| Experimental: Sequence D<br>Single topical application of Placebo 6ml (left leg), treatment period 1; single topical application of BXP154 6ml (right leg), treatment period 2 | Drug: BXP154<br>* BXP154 will be self-administered topically following wound induction<br>Drug: Placebo<br>* Placebo will be self-administered topically following wound induction<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to achieve hemostasis (in minutes) following start of treatment | Time to achieve hemostasis (in minutes) will be compared between active treatment and control. | 60 minutes following start of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects who achieve hemostasis within 4mins, 8mins, 12mins, 16mins, 20mins, 25mins, 30mins, 50mins, 60mins | Summarized as the proportion of subjects that met criteria and compared between active treatment and control. | 60 minutes following start of treatment | 
| Proportion of subjects who require rescue treatment intervention to achieve hemostasis following biopsy | Summarized as the proportion of subjects that met criteria and compared between active treatment and control. | 60 minutes following start of treatment | 
| Time to achieve hemostasis (in minutes) with no rebleeding requiring self-managed or medical intervention within 72 hours after the start of treatment | Time (in minutes) to achieve hemostasis will be compared between active treatment and control. | 72 hours following start of treatment | 
| Proportion of subjects who experience rebleeding following initial hemostasis that requires self-managed or medical intervention to re-achieve hemostasis within 24, 48, and 72 hours after the start of treatment | Summarized as the proportion of subjects that met criteria and compared between active treatment and control. | 72 hours following start of treatment | 
| Proportion of subjects who experience rebleeding following initial hemostasis that requires subsequent self-managed intervention to re-achieve hemostasis within 24, 48, and 72 hours after the start of treatment | Summarized as the proportion of subjects that met criteria and compared between active treatment and control. | 72 hours following start of treatment | 
| Proportion of subjects who experience rebleeding following initial hemostasis that requires subsequent medical intervention to re-achieve hemostasis within 24, 48, and 72 hours after the start of treatment | Summarized as the proportion of subjects that met criteria and compared between active treatment and control. | 72 hours following start of treatment | 
| Number of rebleeding episodes following initial hemostasis that require subsequent medical intervention to re-achieve hemostasis within 24, 48, and 72 hours after the start of treatment | Summarized as the number of episodes per subject compared between active treatment and control. | 72 hours following start of treatment | 
| Proportion of subjects who experience adverse events including adverse skin reactions and other clinically significant findings on physical exam; clinically significant lab values; and clinically significant changes in vital signs. | Summarized as the proportion of subjects reporting adverse events compared between active treatment and control. | 9 days | 
| Systolic blood pressure | Summarized as observed values and change from baseline compared between active treatment and control. | 7 days | 
| Diastolic blood pressure | Summarized as observed values and change from baseline compared between active treatment and control. | 7 days | 
| Maximum plasma concentration (Cmax) | Cmax will be reported for individual subjects and summarized using descriptive statistics | 24 hours post dose | 
| Time to reach Cmax (Tmax) | Tmax will be reported for individual subjects and summarized using descriptive statistics | 24 hours post dose | 
| Area under the plasma concentration time curve (AUC) | AUC will be reported for individual subjects and summarized using descriptive statistics | 24 hours post dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Anticoagulant