Clinical trial NCT01280981: A Study of Tranexamic Acid (XP12B) in Women With Heavy Menstrual Bleeding
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Menorrhagia
Keywords: Menorrhagia
Heavy Menstrual Bleeding
Lysteda
Lead sponsor: Ferring Pharmaceuticals
Sponsor class: INDUSTRY
Collaborators: name: Xanodyne Pharmaceuticals
First posted: 2011-01-21
Enrollment: 288
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 49
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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 β-Hydroxy β-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.

Primary outcomes:
measure: Participants With Treatment-Emergent Adverse Events (AEs)
timeFrame: Day 1 to up to Month 9
Secondary outcomes:
measure: Participants With Abnormal Gynecological Examinations
timeFrame: Day 1 to up to Month 9
measure: Mean Blood Pressure Measurements at Week 36
timeFrame: approximately week 36
measure: Participants With Treatment Emergent Adverse Experiences (TEAE) of Laboratory Values Related to Treatment
timeFrame: Day 1 to up to Month 9
measure: Mean Intraocular Pressure at Month 9
timeFrame: Day 1 up to Month 9
measure: Mean Fridericia-corrected QT Interval (QTcFRI) at Month 9
timeFrame: Month 9
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Radiant Research
state: Alabama
city: Phoenix
country: United States
facility: Women's Health Research
state: Arizona
city: Tucson
country: United States
facility: Genova Clinical Research
state: Arizona
city: Tucson
country: United States
facility: Quality of Life Medical and Research Center
state: Arizona
city: Tucson
country: United States
facility: Radiant Research
state: Arizona
city: Tucson
country: United States
facility: Visions Clinical Research
state: Arizona
city: Little Rock
country: United States
facility: Lynn Institute of the Ozarks
state: Arkansas
city: Searcy
country: United States
facility: Searcy Medical Center
state: Arkansas
city: Carmichael
country: United States
facility: Northern California Research Corp
state: California
city: Lakewood
country: United States
facility: Physicians' Research Options, LC
state: California
city: Los Alamitos
country: United States
facility: Sklar Center for Women's Wellness
state: California
city: San Diego
country: United States
facility: Medical Center for Clinical Research
state: California
city: Upland
country: United States
facility: INC Clinical Trials
state: California
city: Denver
country: United States
facility: Advanced Women's Health Institute
state: Colorado
city: Denver
country: United States
facility: Downtown Women's Health Care
state: Colorado
city: Crystal River
country: United States
facility: Nature Coast Clinical Research
state: Florida
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Jacksonville
country: United States
facility: Jacksonville Center for Clinical Research
state: Florida
city: Miami
country: United States
facility: New Age Medical Research Corp
state: Florida
city: Miami
country: United States
facility: University of Miami Cedars Medical Center
state: Florida
city: New Port Richey
country: United States
facility: Advanced Research Institute
state: Florida
city: North Miami
country: United States
facility: Segal Institute for Clinical Research
state: Florida
city: Decatur
country: United States
facility: Medical Network for Education & Research, Inc.
state: Georgia
city: Boise
country: United States
facility: The Women's Clinic
state: Idaho
city: Idaho Falls
country: United States
facility: Rosemark Womencare Specialists
state: Idaho
city: Bloomington
country: United States
facility: Provident Clinical Research
state: Indiana
city: Newton
country: United States
facility: Wichita Clinic, P.A.
state: Kansas
city: Overland Park
country: United States
facility: Radiant Research
state: Kansas
city: Marrero
country: United States
facility: York Clinical Consulting
state: Louisiana
city: Baltimore
country: United States
facility: The Gynecology Center
state: Maryland
city: Ann Arbor
country: United States
facility: ClinSite, LLC
state: Michigan
city: Bingham Farms
country: United States
facility: Quest Research Institute
state: Michigan
city: Grand Rapids
country: United States
facility: Grand Valley Gynecologists PC
state: Michigan
city: Paw Paw
country: United States
facility: Women's Health Care Specialist
state: Michigan
city: St. Clair Shores
country: United States
facility: KMED Research
state: Michigan
city: Kansas City
country: United States
facility: Center for Pharmaceutical Research
state: Missouri
city: Missoula
country: United States
facility: Montana Medical Research, Inc
state: Montana
city: Scottsbluff
country: United States
facility: The Women's Center of Western Nebraska
state: Nebraska
city: Las Vegas
country: United States
facility: Office of R Garn Mabey, MD
state: Nevada
city: Lawrenceville
country: United States
facility: Women's Health Research Center, LLC
state: New Jersey
city: Moorestown
country: United States
facility: Phoenix OB-GYN Assoc, LLC
state: New Jersey
city: New York
country: United States
facility: American Clinical Trials
state: New York
city: Durham
country: United States
facility: Duke Fertility Center
state: North Carolina
city: Durham
country: United States
facility: Women's Wellness Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Lyndhurst Gynecologic Associates
state: North Carolina
city: Winston-Salem
country: United States
facility: Piedmont Medical Research Associates
state: North Carolina
city: Bismarck
country: United States
facility: Mid Dakota Clinic
state: North Dakota
city: Centerville
country: United States
facility: Triphase Research Ltd
state: Ohio
city: Cleveland
country: United States
facility: Rapid Medical Research, Inc
state: Ohio
city: Cleveland
country: United States
facility: University Suburban Health Center
state: Ohio
city: Gallipolis
country: United States
facility: Holzer Clinic
state: Ohio
city: Zanesville
country: United States
facility: Physicians Research, Inc.
state: Ohio
city: Norman
country: United States
facility: LION Research
state: Oklahoma
city: Oklahoma City
country: United States
facility: Lynn Health Science Institute
state: Oklahoma
city: Eugene
country: United States
facility: Clinical Trials of America
state: Oregon
city: Medford
country: United States
facility: PMG/OB-GYN Health Center
state: Oregon
city: Portland
country: United States
facility: The Portland Clinic
state: Oregon
city: Abington
country: United States
facility: Abington Reproductive Medicine, PC
state: Pennsylvania
city: Jenkintown
country: United States
facility: The Clinical Trial Center
state: Pennsylvania
city: Levittown
country: United States
facility: Family Medical Associates Research Dept
state: Pennsylvania
city: Philadelphia
country: United States
facility: Philadelphia Clinical Research, LLC
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania, Dept. OB/GYN
state: Pennsylvania
city: Phoenixville
country: United States
facility: Valley Forge OB/GYN
state: Pennsylvania
city: Reading
country: United States
facility: Research Across America
state: Pennsylvania
city: Strafford
country: United States
facility: Main Line OB/GYN
state: Pennsylvania
city: Wexford
country: United States
facility: Wexford Professional Bldg II
state: Pennsylvania
city: Columbia
country: United States
facility: SC Clinical Research Center
state: South Carolina
city: Greenville
country: United States
facility: Greenville Hospital System-Univ Med Group Dept
state: South Carolina
city: Greenville
country: United States
facility: Greenville Pharmaceutical Research
state: South Carolina
city: Greer
country: United States
facility: Radiant Research
state: South Carolina
city: Bristol
country: United States
facility: Seasons
state: Tennessee
city: Chattanooga
country: United States
facility: Southeastern Clinical Research
state: Tennessee
city: Clarksville
country: United States
facility: Alpha Clinical Research, LLC
state: Tennessee
city: Knoxville
country: United States
facility: Volunteer Research Group
state: Tennessee
city: Memphis
country: United States
facility: Research Memphis Associates
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Women's Care, PC
state: Tennessee
city: College Station
country: United States
facility: J&S Studies, Inc
state: Texas
city: Dallas
country: United States
facility: OB/GYN Infertility & Preventive Medicine
state: Texas
city: Plano
country: United States
facility: Phyllis Gee, MD
state: Texas
city: Temple
country: United States
facility: King's Daughters Clinic
state: Texas
city: Webster
country: United States
facility: Center of Reproductive Medicine
state: Texas
city: Woodlands
country: United States
facility: Women's Healthcare
state: Texas
city: Pleasant Grove
country: United States
facility: Mt. Timpanogos Women's Health Center
state: Utah
city: Salt Lake City
country: United States
facility: Jean Brown Research
state: Utah
city: Sandy
country: United States
facility: Physician's Research Options
state: Utah
city: West Valley City
country: United States
facility: Granger Medical OB/GYN
state: Utah
city: Burlington
country: United States
facility: FAHC, Womens Health Research
state: Vermont
city: Richmond
country: United States
facility: Clinical Trials of Virginia, INC
state: Virginia
city: Virginia Beach
country: United States
facility: Tidewater Clinical Research, Inc.
state: Virginia
city: Renton
country: United States
facility: Valley Women's Clinic
state: Washington
city: Spokane
country: United States
facility: North Spokane Women's Center
state: Washington
city: Menomonee Falls
country: United States
facility: Medical Associates Health Centers
state: Wisconsin
Study officials:
affiliation: Ferring Pharmaceuticals
name: Clinical Development Support
role: STUDY_DIRECTOR
References: