A Study of Tranexamic Acid (XP12B) in Women With Heavy Menstrual Bleeding
Condition: Menorrhagia
MeSH terms: Menorrhagia
Intervention: Tranexamic acid
Intervention description: 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.
Intervention MeSH terms: Tranexamic Acid
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 288.0
Sex: Female
Minimum age: 18 Years
Maximum age: 49 Years
Healthy volunteers: No
Keywords: Menorrhagia; Heavy Menstrual Bleeding; Lysteda

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.