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

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

Status

Completed

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01190150

Acronym

PREA

Enrollment

Registered

2010-08-27

Start date

2010-08-31

Completion date

2011-04-30

Last updated

2012-07-16

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Menorrhagia

Keywords

Cyclic Heavy Menstrual Bleed, Menorraghia

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.

Interventions

DRUGtranexamic acid

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.

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Masking

NONE

Eligibility

Sex/Gender

FEMALE

Age

12 Years to 16 Years

Healthy volunteers

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)

Design outcomes

Primary

Measure	Time frame	Description
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
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.

Secondary

Measure	Time frame	Description
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.

Countries

United States

Participant flow

Participants by arm

Arm	Count
0.65 g / 1.3 g 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.	11
1.3 g / 0.65 g 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.	9
Total	20

Withdrawals & dropouts

Period	Reason	FG000	FG001
First Treatment	Withdrawal by Subject	1	0
Washout	Difficulty in adherence	0	1
Washout	Withdrawal by Subject	0	1

Baseline characteristics

Characteristic	1.3 g / 0.65 g Tranexamic Acid	Total	0.65 g / 1.3 g Tranexamic Acid
Age Continuous	14.3 years STANDARD_DEVIATION 1.32	14.4 years STANDARD_DEVIATION 1.19	14.5 years STANDARD_DEVIATION 1.13
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	1 Participants	1 Participants	0 Participants
Race (NIH/OMB) Black or African American	6 Participants	13 Participants	7 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	2 Participants	6 Participants	4 Participants
Sex: Female, Male Female	9 Participants	20 Participants	11 Participants
Sex: Female, Male Male	0 Participants	0 Participants	0 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	1 / 18	2 / 19
serious Total, serious adverse events	0 / 18	0 / 19

Outcome results

Primary

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.