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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Ferring Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01190150
First received: August 26, 2010
Last updated: July 10, 2012
Last verified: July 2012
  Purpose

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.


Condition Intervention Phase
Menorrhagia
Drug: tranexamic acid
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Ferring Pharmaceuticals:

Primary Outcome Measures:
  • Maximum Concentrations Level (Cmax) [ Time Frame: 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) ] [ Designated as safety issue: No ]
    Cmax is the maximum measured plasma concentration over the time-span specified.

  • Dose-normalized Maximum Concentrations Level (Cmax) [ Time Frame: 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) ] [ Designated as safety issue: No ]
    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) [ Time Frame: 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) ] [ Designated as safety issue: No ]
    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) [ Time Frame: 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) ] [ Designated as safety issue: No ]
    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) [ Time Frame: 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) ] [ Designated as safety issue: No ]
    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) [ Time Frame: 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) ] [ Designated as safety issue: No ]
    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) [ Time Frame: 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) ] [ Designated as safety issue: No ]
    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 [ Time Frame: 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) ] [ Designated as safety issue: No ]
    Comparison of AUC0-t to AUCinf by creating a ratio.

  • Elimination Half-life (t ½) [ Time Frame: 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) ] [ Designated as safety issue: No ]
    Apparent first-order terminal elimination half life


Secondary Outcome Measures:
  • Participants With Treatment-emergent Adverse Events (TEAEs) [ Time Frame: Day 1 up to week 4 ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 20
Study Start Date: August 2010
Study Completion Date: April 2011
Primary Completion Date: April 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: tranexamic 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.
Other Names:
  • Lysteda
  • modified-immediate release tranexamic acid
Experimental: 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.
Drug: tranexamic 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.
Other Names:
  • Lysteda
  • modified-immediate release tranexamic acid

  Eligibility

Ages Eligible for Study:   12 Years to 16 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01190150

Locations
United States, California
West Coast Clinical Trials
Cypress, California, United States
Sponsors and Collaborators
Ferring Pharmaceuticals
Investigators
Study Director: Clinical Development Support Ferring Pharmaceuticals
  More Information

No publications provided

Responsible Party: Ferring Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01190150     History of Changes
Other Study ID Numbers: FE999304 CS01
Study First Received: August 26, 2010
Results First Received: May 30, 2012
Last Updated: July 10, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Ferring Pharmaceuticals:
Cyclic Heavy Menstrual Bleed
Menorraghia

Additional relevant MeSH terms:
Menstruation Disturbances
Hemorrhage
Menorrhagia
Pathologic Processes
Uterine Hemorrhage
Uterine Diseases
Genital Diseases, Female
Tranexamic Acid
Antifibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Hemostatics
Coagulants
Hematologic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 26, 2014