A Study of Tranexamic Acid (XP12B) in Women With Heavy Menstrual Bleeding

Menorrhagia Clinical Trial

Official title:

A Multi-center, Open Label Extension Study to Evaluate the Safety of an Oral Dose of Tranexamic Acid (XP12B) Administered Three Times Daily During Menstruation for the Treatment of Menorrhagia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01280981
• Other study ID #: XP12B-MR-304
• Status: Completed
• Phase: Phase 3
• First received: January 19, 2011
• Last updated: June 28, 2011
• Start date: April 2007
• Est. completion date: May 2009

Study information

• Verified date: June 2011
• Source: Ferring Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This was a multicenter, open-label extension study for subjects completing either of 2 pivotal efficacy studies (NCT00401193 or NCT00386308). The study consisted of a treatment phase of 9 menstrual periods to assess the safety of tranexamic acid at an oral dose of 1.3 g administered 3 times per day for up to 5 days (maximum of 15 doses) during menstruation. After the last treatment period, a follow-up phone call occurred approximately 30 days (range 25 to 35 days) after the last dose of study drug.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 288
• Est. completion date: May 2009
• Est. primary completion date: May 2009
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 49 Years

Eligibility

Inclusion Criteria:

• The study enrolled subjects who had completed the double-blind therapy in either the XP12B-MR-301 or XP12B-MR-303 study, including scheduled evaluations, with no major protocol violations and no study events that, in the opinion of the investigator, would preclude the subject's entry into the open-label safety study.

• A negative urine pregnancy test was required immediately before entry into this study.

• Women must have been surgically sterile or, if of childbearing potential, must have been in a monogamous relationship with a sterile partner or a partner of the same sex.

• Women must have used an acceptable barrier contraception method with spermicide for the duration of the study or must have been using a copper intrauterine device (IUD).

• In the opinion of the investigator, the subject must be able to understand this study, cooperate with all study procedures, be able to return to the study site for visits within the required visit windows and be deemed likely to complete the study.

• Subject will provide voluntary, written consent to participate in the study by signing and dating an institutional review board (IRB)-approved informed consent before any procedures are performed or study drug is dispensed.

Exclusion Criteria:

• History or presence of clinically significant hepatic or renal disease or other medical disease that might confound the study or be detrimental to the subject (e.g., clinically significant cardiac arrhythmia, uncontrolled diabetes or uncontrolled hypertension) as determined by the investigator.

• Normal gynecological examination and breast examination.

• Clinically significant abnormalities on screening physical examination that might confound the study or be detrimental to the subject as assessed by the investigator. Abnormal clinically significant electrocardiograms (ECG) as determined by the centralized cardiologist, or laboratory tests suggestive of a potential pituitary-prolactin stimulating tumor (prolactin >=30 µg/L), thrombocytopenia (platelet count <100,000/mm3), uncontrolled hypothyroidism (TSH >=10 mU/L) or severe anemia (hemoglobin <8 g/dL]).

• Anovulatory dysfunctional uterine bleeding, metrorrhagia (irregular or frequent noncyclic flow), menometrorrhagia (irregular or frequent excessive noncyclic flow) or polymenorrhea (frequent flow, cycles of less than 21 days).

• History or presence of endometrial polyps, endometrial hyperplasia, endometrial carcinoma or cervical carcinoma (includes cervical carcinoma in situ).

• History of bilateral oophorectomy or hysterectomy.

• Women who are pregnant, breastfeeding, planning to become pregnant during the study or become pregnant during the study.

• History or active presence of myocardial infarction or ischemic disease. History or active presence of cerebrovascular accident, stroke, or transient ischemic attack.

• History or presence of thrombosis, thromboembolic disease or coagulopathy including, but not limited to, pulmonary embolism, deep venous thrombosis, phlebitis and any intravascular clotting disorder.

• History or known presence of acquired or inherited thrombophilia, including, but not limited to, antithrombin deficiency, Protein C and/or S deficiency, antiphospholipid deficiency, Factor V Leiden mutation and prothrombin mutation. Thalassemia or sickle cell disease (sickle cell trait individuals are not excluded).

• History or presence of subarachnoid hemorrhage.

• Use or anticipated use of medications taken to relieve ß-Hydroxy ß-methylbutyric acid (HMB) including the use of vaginal [rings, creams, gels] and transdermal hormone products; use of oral estrogen-, progestin- or SERM-containing drug products, or intrauterine progestins containing drug products. Use or anticipated use of Lupron (1 or 3 month) depot injection or estrogen pellet or long-acting progestin injectables.

• Use or anticipated use of meclofenamate sodium, mefenamic acid, danazol, or desmopressin acetate or herbal remedies. Herbal remedies include, but are not limited to, Capsella bursa pastoris (i.e. Sheperd's Purse), Agnus castus (i.e. Chasteberry, Vitex), Cimicifuga racemosa (i.e. Black Cohosh), Symphytum officionale (i.e. Comfrey), and/or Angelica sinensis (i.e. Dong Quai).

• Use of or anticipated use of the following drugs: oral, transdermal, injectable and vaginal ring (NuvaRing®) hormonal contraceptives; anticoagulants (warfarin [Coumadin®], heparin, low-molecular-weight heparin (LMWH), etc.), aminocaproic acid (Amicar®) or Plaquenil®.

• Current use of an intrauterine device (IUD) other than copper IUDs.

• History or presence of hypersensitivity or idiosyncratic reaction to antifibrinolytics (tranexamic acid or aminocaproic acid).

• Use of any investigational drug except XP12B-MR during the current study.

• Presence of untreated malabsorption disorder or malnutrition including, but not limited to, chronic diarrhea, celiac disease, short bowl syndrome, Whipple's disease or history of gastric bypass procedure.

• Presence of defective color vision as determined by the optometrist or ophthalmologist. Inability of the subject to correctly identify symbols on plate 7 of the HRR eye test is not considered defective color vision provided the subject correctly identifies the symbols on plates 11-20.

• History or presence of glaucoma, ocular hypertension, macular degeneration or retinopathies.

• History or presence of alcoholism or drug abuse within the past year.

• Malignancy, or treatment for malignancy, within the previous 2 years, with the exception of basal cell carcinomas of the skin or squamous cell carcinoma of the skin.

• Does not read or understand English.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Menorrhagia

Intervention

Drug:
• Tranexamic acid
Tranexamic acid at an oral dose of 1.3 g administered 3 times per day for up to 5 days (maximum of 15 doses) during menstruation for 9 menstrual periods.

Locations

Country	Name	City	State
United States	Abington Reproductive Medicine, PC	Abington	Pennsylvania
United States	ClinSite, LLC	Ann Arbor	Michigan
United States	The Gynecology Center	Baltimore	Maryland
United States	Quest Research Institute	Bingham Farms	Michigan
United States	Radiant Research	Birmingham	Alabama
United States	Mid Dakota Clinic	Bismarck	North Dakota
United States	Provident Clinical Research	Bloomington	Indiana
United States	The Women's Clinic	Boise	Idaho
United States	Seasons	Bristol	Tennessee
United States	FAHC, Womens Health Research	Burlington	Vermont
United States	Northern California Research Corp	Carmichael	California
United States	Triphase Research Ltd	Centerville	Ohio
United States	Southeastern Clinical Research	Chattanooga	Tennessee
United States	Alpha Clinical Research, LLC	Clarksville	Tennessee
United States	Rapid Medical Research, Inc	Cleveland	Ohio
United States	University Suburban Health Center	Cleveland	Ohio
United States	J&S Studies, Inc	College Station	Texas
United States	SC Clinical Research Center	Columbia	South Carolina
United States	Nature Coast Clinical Research	Crystal River	Florida
United States	OB/GYN Infertility & Preventive Medicine	Dallas	Texas
United States	Medical Network for Education & Research, Inc.	Decatur	Georgia
United States	Advanced Women's Health Institute	Denver	Colorado
United States	Downtown Women's Health Care	Denver	Colorado
United States	Duke Fertility Center	Durham	North Carolina
United States	Women's Wellness Center	Durham	North Carolina
United States	Clinical Trials of America	Eugene	Oregon
United States	University of Florida	Gainesville	Florida
United States	Holzer Clinic	Gallipolis	Ohio
United States	Grand Valley Gynecologists PC	Grand Rapids	Michigan
United States	Greenville Hospital System-Univ Med Group Dept	Greenville	South Carolina
United States	Greenville Pharmaceutical Research	Greenville	South Carolina
United States	Radiant Research	Greer	South Carolina
United States	Rosemark Womencare Specialists	Idaho Falls	Idaho
United States	Jacksonville Center for Clinical Research	Jacksonville	Florida
United States	The Clinical Trial Center	Jenkintown	Pennsylvania
United States	Center for Pharmaceutical Research	Kansas City	Missouri
United States	Volunteer Research Group	Knoxville	Tennessee
United States	Physicians' Research Options, LC	Lakewood	California
United States	Office of R Garn Mabey, MD	Las Vegas	Nevada
United States	Women's Health Research Center, LLC	Lawrenceville	New Jersey
United States	Family Medical Associates Research Dept	Levittown	Pennsylvania
United States	Lynn Institute of the Ozarks	Little Rock	Arkansas
United States	Sklar Center for Women's Wellness	Los Alamitos	California
United States	York Clinical Consulting	Marrero	Louisiana
United States	PMG/OB-GYN Health Center	Medford	Oregon
United States	Research Memphis Associates	Memphis	Tennessee
United States	Medical Associates Health Centers	Menomonee Falls	Wisconsin
United States	New Age Medical Research Corp	Miami	Florida
United States	University of Miami Cedars Medical Center	Miami	Florida
United States	Montana Medical Research, Inc	Missoula	Montana
United States	Phoenix OB-GYN Assoc, LLC	Moorestown	New Jersey
United States	Tennessee Women's Care, PC	Nashville	Tennessee
United States	Advanced Research Institute	New Port Richey	Florida
United States	American Clinical Trials	New York	New York
United States	Wichita Clinic, P.A.	Newton	Kansas
United States	LION Research	Norman	Oklahoma
United States	Segal Institute for Clinical Research	North Miami	Florida
United States	Lynn Health Science Institute	Oklahoma City	Oklahoma
United States	Radiant Research	Overland Park	Kansas
United States	Women's Health Care Specialist	Paw Paw	Michigan
United States	Philadelphia Clinical Research, LLC	Philadelphia	Pennsylvania
United States	University of Pennsylvania, Dept. OB/GYN	Philadelphia	Pennsylvania
United States	Women's Health Research	Phoenix	Arizona
United States	Valley Forge OB/GYN	Phoenixville	Pennsylvania
United States	Phyllis Gee, MD	Plano	Texas
United States	Mt. Timpanogos Women's Health Center	Pleasant Grove	Utah
United States	The Portland Clinic	Portland	Oregon
United States	Research Across America	Reading	Pennsylvania
United States	Valley Women's Clinic	Renton	Washington
United States	Clinical Trials of Virginia, INC	Richmond	Virginia
United States	Jean Brown Research	Salt Lake City	Utah
United States	Medical Center for Clinical Research	San Diego	California
United States	Physician's Research Options	Sandy	Utah
United States	The Women's Center of Western Nebraska	Scottsbluff	Nebraska
United States	Searcy Medical Center	Searcy	Arkansas
United States	North Spokane Women's Center	Spokane	Washington
United States	KMED Research	St. Clair Shores	Michigan
United States	Main Line OB/GYN	Strafford	Pennsylvania
United States	King's Daughters Clinic	Temple	Texas
United States	Genova Clinical Research	Tucson	Arizona
United States	Quality of Life Medical and Research Center	Tucson	Arizona
United States	Radiant Research	Tucson	Arizona
United States	Visions Clinical Research	Tucson	Arizona
United States	INC Clinical Trials	Upland	California
United States	Tidewater Clinical Research, Inc.	Virginia Beach	Virginia
United States	Center of Reproductive Medicine	Webster	Texas
United States	Granger Medical OB/GYN	West Valley City	Utah
United States	Wexford Professional Bldg II	Wexford	Pennsylvania
United States	Lyndhurst Gynecologic Associates	Winston-Salem	North Carolina
United States	Piedmont Medical Research Associates	Winston-Salem	North Carolina
United States	Women's Healthcare	Woodlands	Texas
United States	Physicians Research, Inc.	Zanesville	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
Ferring Pharmaceuticals	Xanodyne Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Participants With Treatment-Emergent Adverse Events (AEs)	Count of participants with treatment-emergent adverse events grouped in categories regarding relationship to study drug as assessed by the investigator, serious or life-threatening as assessed by the investigator, participants who died or their event led to withdrawal from study, and participants who experienced thrombotic or thromboembolic AEs.	Day 1 to up to Month 9	Yes
Secondary	Participants With Abnormal Gynecological Examinations	Participants with abnormal gynecological examination findings based on endometrial biopsies and transvaginal ultraonogrphy (TVU) are summarized. Clinically significant results from the endometrial biopsies are results that are not benign. Abnormalities found during transvaginal ultrasonography (TVU) are detailed in the AE listings. Please refer to AE listings.	Day 1 to up to Month 9	Yes
Secondary	Mean Blood Pressure Measurements at Week 36	Mean systolic and diastolic blood pressure measurements taken at week 36	approximately week 36	Yes
Secondary	Participants With Treatment Emergent Adverse Experiences (TEAE) of Laboratory Values Related to Treatment	Participants whose laboratory examinations (hematology, blood chemistry and urinalysis) were considered by the investigator to be treatment emergent adverse experiences (TEAE) and related to treatment. Also indicated is whether the TEAE lab parameter caused the participant to discontinue from the study.	Day 1 to up to Month 9	Yes
Secondary	Mean Intraocular Pressure at Month 9	Mean intraocular pressure at month 9 or the early termination visit.	Day 1 up to Month 9	Yes
Secondary	Mean Fridericia-corrected QT Interval (QTcFRI) at Month 9	The QT interval is the period that extends from the beginning of ventricular depolarization until the end of ventricular repolarization	Month 9	Yes