Lysteda Pediatric Research Equity Act (PREA) Pharmacokinetic Study in Adolescent Females With Heavy Menstrual Bleeding

Study Overview
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Brief Summary
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This is a Phase 4, randomized, 2-way crossover, pharmacokinetic study of Lysteda (tranexamic acid) tablets administered as single doses of 0.65 g and 1.3 g in fasting adolescent female subjects ages 12-16 years with heavy menstrual bleeding.

Official Title
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Randomized, 2-way Crossover, Pharmacokinetic Study of Lysteda (Xanodyne Modified-Immediate Release Tranexamic Acid) Tablets at 2 Doses in Fasting Adolescent Females With Evidence of Heavy Menstrual Bleeding

Conditions
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Menorrhagia

Intervention / Treatment
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* Drug: tranexamic acid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Generally healthy non-smoking (for at least 3 months) adolescent females 12-16 years of age with a history of at least 1 year of cyclic heavy menstrual bleeding (HMB) Subjects must report regularly occurring menstrual periods ≤10 days in duration, with 21-45 days from the start of one period to the start of the next menstrual period Diagnosis of HMB based on the medical judgment of the Principal Investigator and will include the following criteria: Laboratory (including a bleeding disorders work-up) and Physical Findings; Limitations in Activities of Daily Living (ADL); Soiling, Staining and Clotting; Sanitary product usage and extent of MBL using a patient reported pictorial blood assessment chart (PBAC). Subjects should either be sexually inactive (abstinent) or be using one of the following acceptable birth control methods and agree to continue its use throughout the study: copper intrauterine device (IUD) in place for at least 3 months; barrier methods (condom, diaphragm) with spermicide for at least 1 month prior to the first dose and throughout the study. Negative pregnancy test results Subject's legally authorized representative (e.g., parent, guardian) must voluntarily sign a parental permission/informed consent form (ICF), and the subject must sign an assent, before the conduct of any study procedure Exclusion Criteria: Breast-feeding, or a history of abortion in the last 6 months Known bleeding or coagulation disorders based on medical history and/or laboratory results Known systemic hematologic diseases (e.g., all types of sickle-cell disease, thalassemia of all types, multiple myeloma, hemolytic anemia) Clinical evidence of any significant chronic illness, including cardiovascular, renal, neurologic, hepatic, endocrine, gastric, central nervous system disease, any psychiatric illness which could affect the efficacy or safety of study medication Subjects treated with systemic steroids in the last 1 month or hormonal treatment in the last 3 months A history or presence of any drug abuse or alcohol abuse within the last 1 year History of subarachnoid hemorrhage. Active thromboembolic disease; history of thrombosis or thromboembolism, including retinal vein or artery occlusion; an intrinsic risk of thrombosis or thromboembolism Use of vaginal hormone products (rings, creams, and gels) within 4 weeks prior to screening. Use of oral estrogen-, progestin-, or selective estrogen receptor within 8 weeks prior to screening. Use of Lupron (3-month depot injection), estrogen pellet, or long-acting progestin injectables within 6 months prior to screening Subjects whose sitting blood pressure is less than 90/60 mmHg at screening Subjects whose pulse is lower than 50 b.p.m. at screening Subjects whose PR interval is >200 msec at screening and prior to dosing Subjects whose QTc interval >450 msec Subjects with positive tests for hepatitis B, C, or human immunodeficiency virus (HIV)

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 16 Years

Sexes Eligible for Study
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Female

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

Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 0.65 g / 1.3 g tranexamic acid<br>Participants received a single dose of 0.65 g tranexamic acid on Day 1 and a single dose of 1.3 g tranexamic acid on Day 8. | Drug: tranexamic acid<br>* Either one or two modified-immediate release tranexamic acid tablets (0.65 g each) taken orally, administered with 240 mL of water, as a single dose, at approximately 8 AM.<br>* Other names: modified-immediate release tranexamic acid;|
| Experimental: 1.3 g / 0.65 g tranexamic acid<br>Participants received a single dose of 1.3 g tranexamic acid on Day 1 and a single dose of 0.65 g tranexamic acid on Day 8. | Drug: tranexamic acid<br>* Either one or two modified-immediate release tranexamic acid tablets (0.65 g each) taken orally, administered with 240 mL of water, as a single dose, at approximately 8 AM.<br>* Other names: modified-immediate release tranexamic acid;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Concentrations Level (Cmax) | Cmax is the maximum measured plasma concentration over the time-span specified. | Day 1 or Day 8 (before dosing and at the following times thereafter: 0.5, 0.75, 1, 2, 2.5, 3.0, 3.5, 4, 5, 6, 10, 14, and 24 hours post-dose) | 
| Dose-normalized Maximum Concentrations Level (Cmax) | Cmax is the maximum measured plasma concentration over the time-span specified and normalized to the 1.3 g dose. | Day 1 or Day 8 (before dosing and at the following times thereafter: 0.5, 0.75, 1, 2, 2.5, 3.0, 3.5, 4, 5, 6, 10, 14, and 24 hours post-dose) | 
| Time to Maximum Concentration Level (Tmax) | Time of the maximum measured plasma concentration. If the maximum value occurs at more than one time point, Tmax is defined as the first time point with this value. | Day 1 or Day 8 (before dosing and at the following times thereafter: 0.5, 0.75, 1, 2, 2.5, 3.0, 3.5, 4, 5, 6, 10, 14, and 24 hours post-dose) | 
| Area Under the Concentration Versus Time Curve From 0 to the Last Time Point (AUC0-t) | The area under the plasma concentration versus time curve, from time 0 to the last measurable concentration, as calculated by the linear trapezoidal method. | Day 1 or Day 8 (before dosing and at the following times thereafter: 0.5, 0.75, 1, 2, 2.5, 3.0, 3.5, 4, 5, 6, 10, 14, and 24 hours post-dose) | 
| Dose Normalized Area Under the Concentration Versus Time Curve From 0 to the Last Time Point (AUC0-t) | The area under the plasma concentration versus time curve, from time 0 to the last measurable concentration normalized to the 1.3 g dose. | Day 1 or Day 8 (before dosing and at the following times thereafter: 0.5, 0.75, 1, 2, 2.5, 3.0, 3.5, 4, 5, 6, 10, 14, and 24 hours post-dose) | 
| Area Under the Concentration Versus Time Curve From 0 to Infinity (AUCinf) | The area under the plasma concentration versus time curve from time 0 to infinity. AUCinf is calculated as the sum of AUC0-t plus the ratio of the last measurable plasma concentration to the elimination rate constant. | Day 1 or Day 8 (before dosing and at the following times thereafter: 0.5, 0.75, 1, 2, 2.5, 3.0, 3.5, 4, 5, 6, 10, 14, and 24 hours post-dose) | 
| Dose Normalized Area Under the Concentration Versus Time Curve From 0 to Infinity (AUCinf) | Dose-normalized AUCinf is calculated as the sum of AUC0-t plus the ratio of the last measurable plasma concentration to the elimination rate constant, normalized to the 1.3 g dose. | Day 1 or Day 8 (before dosing and at the following times thereafter: 0.5, 0.75, 1, 2, 2.5, 3.0, 3.5, 4, 5, 6, 10, 14, and 24 hours post-dose) | 
| The Ratio of AUC0-t to AUCinf | Comparison of AUC0-t to AUCinf by creating a ratio. | Day 1 or Day 8 (before dosing and at the following times thereafter: 0.5, 0.75, 1, 2, 2.5, 3.0, 3.5, 4, 5, 6, 10, 14, and 24 hours post-dose) | 
| Elimination Half-life (t ½) | Apparent first-order terminal elimination half life | Day 1 or Day 8 (before dosing and at the following times thereafter: 0.5, 0.75, 1, 2, 2.5, 3.0, 3.5, 4, 5, 6, 10, 14, and 24 hours post-dose) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Participants With Treatment-emergent Adverse Events (TEAEs) | Treatment-emergent AEs are summarized by total participants with TEAEs, participants with serious TEAEs, participants with TEAEs deemed by the investigator to be related to treatment, and participants who experienced TEAEs that caused permanent discontinuation from the study. | Day 1 up to week 4 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cyclic Heavy Menstrual Bleed, Menorraghia