Menorrhagia
Conditions
Keywords
Menorrhagia, Heavy Menstrual Bleeding, Lysteda
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.
Interventions
DRUGTranexamic 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.
Sponsors
Xanodyne Pharmaceuticals
Ferring Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 49 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Participants With Treatment-Emergent Adverse Events (AEs) | Day 1 to up to Month 9 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Participants With Abnormal Gynecological Examinations | Day 1 to up to Month 9 | 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. |
| Mean Blood Pressure Measurements at Week 36 | approximately week 36 | Mean systolic and diastolic blood pressure measurements taken at week 36 |
| Participants With Treatment Emergent Adverse Experiences (TEAE) of Laboratory Values Related to Treatment | Day 1 to up to Month 9 | 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. |
| Mean Intraocular Pressure at Month 9 | Day 1 up to Month 9 | Mean intraocular pressure at month 9 or the early termination visit. |
| Mean Fridericia-corrected QT Interval (QTcFRI) at Month 9 | Month 9 | The QT interval is the period that extends from the beginning of ventricular depolarization until the end of ventricular repolarization |
Countries
United States
Participant flow
Recruitment details
Participants who completed double-blind therapy in either study XP12B-MR-301 (NCT00401193) or XP12B-MR-303 (NCT00386308) could participate in this trial.
Participants by arm
| Arm | Count |
|---|---|
| Tranexamic Acid Two 650 mg tablets orally 3 times per day with liquids for up to 5 days (not to exceed 3 doses in 1 day or 15 doses during the menstrual period). | 288 |
| Total | 288 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 6 |
| Overall Study | Elective surgery | 2 |
| Overall Study | Failed to return | 45 |
| Overall Study | Irregular or discontinued menses | 3 |
| Overall Study | Lack of Efficacy | 13 |
| Overall Study | Lost to Follow-up | 3 |
| Overall Study | Non-compliance with protocol | 3 |
| Overall Study | Protocol Violation | 2 |
| Overall Study | Study site closure | 1 |
| Overall Study | Withdrawal by Subject | 11 |
| Overall Study | Withdrawal of consent | 3 |
Baseline characteristics
| Characteristic | Tranexamic Acid |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 288 Participants |
| Sex: Female, Male Female | 288 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 218 / 260 |
| serious Total, serious adverse events | 5 / 260 |
Outcome results
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.
Time frame: Day 1 to up to Month 9
Population: Intent to treat population (ITT)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tranexamic Acid | Participants With Treatment-Emergent Adverse Events (AEs) | Probably related AE | 3 participants |
| Tranexamic Acid | Participants With Treatment-Emergent Adverse Events (AEs) | Any treatment-emergent AE | 218 participants |
| Tranexamic Acid | Participants With Treatment-Emergent Adverse Events (AEs) | Definitely related AE | 1 participants |
| Tranexamic Acid | Participants With Treatment-Emergent Adverse Events (AEs) | Possibly related AE | 60 participants |
| Tranexamic Acid | Participants With Treatment-Emergent Adverse Events (AEs) | Serious AE | 5 participants |
| Tranexamic Acid | Participants With Treatment-Emergent Adverse Events (AEs) | Life-threatening AE | 2 participants |
| Tranexamic Acid | Participants With Treatment-Emergent Adverse Events (AEs) | Died | 0 participants |
| Tranexamic Acid | Participants With Treatment-Emergent Adverse Events (AEs) | AE led to withdrawal from study | 6 participants |
| Tranexamic Acid | Participants With Treatment-Emergent Adverse Events (AEs) | Thrombotic or thromboembolic AE | 0 participants |
Secondary
Mean Blood Pressure Measurements at Week 36
Mean systolic and diastolic blood pressure measurements taken at week 36
Time frame: approximately week 36
Population: Intent to treat population of participants with week 36 blood pressure data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tranexamic Acid | Mean Blood Pressure Measurements at Week 36 | Systolic blood pressure | 118.94 mmHg | Standard Deviation 14.272 |
| Tranexamic Acid | Mean Blood Pressure Measurements at Week 36 | Diastolic blood pressure | 75.09 mmHg | Standard Deviation 10.167 |
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
Time frame: Month 9
Population: Intent to treat participants who had an electrocardiogram (ECG) at month 9
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tranexamic Acid | Mean Fridericia-corrected QT Interval (QTcFRI) at Month 9 | 412.3 milliseconds | Standard Deviation 15.896 |
Secondary
Mean Intraocular Pressure at Month 9
Mean intraocular pressure at month 9 or the early termination visit.
Time frame: Day 1 up to Month 9
Population: Intent to treat participants who had ophthalmic exams.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tranexamic Acid | Mean Intraocular Pressure at Month 9 | Right eye | 15.4 mmHg | Standard Deviation 2.866 |
| Tranexamic Acid | Mean Intraocular Pressure at Month 9 | Left eye | 15.3 mmHg | Standard Deviation 2.797 |
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.
Time frame: Day 1 to up to Month 9
Population: Intent to treat population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tranexamic Acid | Participants With Abnormal Gynecological Examinations | Significant results from endometrial biopsies | 0 participants |
| Tranexamic Acid | Participants With Abnormal Gynecological Examinations | Abnormalities noted on TVU | 3 participants |
| Tranexamic Acid | Participants With Abnormal Gynecological Examinations | Discontinued due to failed physical exam | 0 participants |
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.
Time frame: Day 1 to up to Month 9
Population: Intent to treat population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tranexamic Acid | Participants With Treatment Emergent Adverse Experiences (TEAE) of Laboratory Values Related to Treatment | Hematology TEAE related to study drug | 1 participants |
| Tranexamic Acid | Participants With Treatment Emergent Adverse Experiences (TEAE) of Laboratory Values Related to Treatment | Discontinued due to hematology TEAE | 1 participants |
| Tranexamic Acid | Participants With Treatment Emergent Adverse Experiences (TEAE) of Laboratory Values Related to Treatment | Blood chemistry TEAE related to study drug | 1 participants |
| Tranexamic Acid | Participants With Treatment Emergent Adverse Experiences (TEAE) of Laboratory Values Related to Treatment | Discontinued due to blood chemistry TEAE | 0 participants |
| Tranexamic Acid | Participants With Treatment Emergent Adverse Experiences (TEAE) of Laboratory Values Related to Treatment | Urinalysis TEAE related to study drug | 2 participants |
| Tranexamic Acid | Participants With Treatment Emergent Adverse Experiences (TEAE) of Laboratory Values Related to Treatment | Discontinued due to urinalysis TEAE | 0 participants |