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

NCT01190150 | Completed Phase 4 Results

• 1 other identifier: FE999304 CS01
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Menorrhagia

Keywords

Cyclic Heavy Menstrual Bleed; Menorraghia

Outcome Measures

Primary Outcomes (9)

• 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 Outcomes (1)

• Participants With Treatment-emergent Adverse Events (TEAEs)

  Day 1 up to week 4

Study Arms (2)

0.65 g / 1.3 g tranexamic acid

EXPERIMENTAL

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

1.3 g / 0.65 g tranexamic acid

EXPERIMENTAL

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

Interventions

tranexamic acid DRUG

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.

Also known as: Lysteda, modified-immediate release tranexamic acid

0.65 g / 1.3 g tranexamic acid; 1.3 g / 0.65 g tranexamic acid

Eligibility Criteria

• Age: 12 Years - 16 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Ferring Pharmaceuticals: lead

Study Sites (1)

West Coast Clinical Trials

Cypress, California, United States

Location

MeSH Terms

Conditions

Menorrhagia

Interventions

Tranexamic Acid

Condition Hierarchy (Ancestors)

Uterine Hemorrhage; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Menstruation Disturbances

Intervention Hierarchy (Ancestors)

Cyclohexanecarboxylic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals

Results Point of Contact

• Title: Clinical Development Support
• Organization: Ferring Pharmaceuticals

DK0-Disclosure@ferring.com

Study Officials

• Clinical Development Support

  Ferring Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 26, 2010
• First Posted: August 27, 2010
• Study Start: August 1, 2010
• Primary Completion: April 1, 2011
• Study Completion: April 1, 2011
• Last Updated: July 16, 2012
• Results First Posted: July 3, 2012

Record last verified: 2012-07

Locations

US (1)