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

Phase 4

Completed

Conditions: Menorrhagia

Interventions: Drug: tranexamic acid

Registration Number: NCT01190150

Lead Sponsor: Ferring Pharmaceuticals

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 20

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:
1. Laboratory (including a bleeding disorders work-up) and Physical Findings;
2. Limitations in Activities of Daily Living (ADL);
3. Soiling, Staining and Clotting;
4. 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)

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
1.3 g / 0.65 g tranexamic acid	tranexamic acid	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.
0.65 g / 1.3 g tranexamic acid	tranexamic acid	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.

Primary Outcome Measures

Name	Time	Method
Maximum Concentrations Level (Cmax)	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)	Cmax is the maximum measured plasma concentration over the time-span specified.
Dose-normalized Maximum Concentrations Level (Cmax)	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)	Cmax is the maximum measured plasma concentration over the time-span specified and normalized to the 1.3 g dose.
Time to Maximum Concentration Level (Tmax)	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 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.
Area Under the Concentration Versus Time Curve From 0 to the Last Time Point (AUC0-t)	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 area under the plasma concentration versus time curve, from time 0 to the last measurable concentration, as calculated by the linear trapezoidal method.
Dose Normalized Area Under the Concentration Versus Time Curve From 0 to the Last Time Point (AUC0-t)	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 area under the plasma concentration versus time curve, from time 0 to the last measurable concentration normalized to the 1.3 g dose.
Area Under the Concentration Versus Time Curve From 0 to Infinity (AUCinf)	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 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.
Dose Normalized Area Under the Concentration Versus Time Curve From 0 to Infinity (AUCinf)	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 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.
The Ratio of AUC0-t to AUCinf	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)	Comparison of AUC0-t to AUCinf by creating a ratio.
Elimination Half-life (t ½)	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)	Apparent first-order terminal elimination half life

Secondary Outcome Measures

Name	Time	Method
Participants With Treatment-emergent Adverse Events (TEAEs)	Day 1 up to week 4	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.