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

• Sponsor: Ferring Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01280981
• Collaborator: Xanodyne Pharmaceuticals (Industry)
• Enrollment: 288
• Locations: 92
• Arm: 1
• Duration (Months): 25
• Patients Per Site: 3.1
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Menorrhagia	Drug: Tranexamic acid	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 288 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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 Start Date: Apr 1, 2007
• Actual Primary Completion Date: May 1, 2009
• Actual Study Completion Date: May 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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).	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.; Other Names: XP12B Lysteda

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

2. Mean Blood Pressure Measurements at Week 36 [approximately week 36]

   Mean systolic and diastolic blood pressure measurements taken at week 36

3. 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.

4. Mean Intraocular Pressure at Month 9 [Day 1 up to Month 9]

   Mean intraocular pressure at month 9 or the early termination visit.

5. 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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 49 Years
• Sexes Eligible for Study: Female
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Radiant Research	Birmingham	Alabama	United States
2	Women's Health Research	Phoenix	Arizona	United States
3	Genova Clinical Research	Tucson	Arizona	United States
4	Quality of Life Medical and Research Center	Tucson	Arizona	United States
5	Radiant Research	Tucson	Arizona	United States
6	Visions Clinical Research	Tucson	Arizona	United States
7	Lynn Institute of the Ozarks	Little Rock	Arkansas	United States
8	Searcy Medical Center	Searcy	Arkansas	United States
9	Northern California Research Corp	Carmichael	California	United States
10	Physicians' Research Options, LC	Lakewood	California	United States
11	Sklar Center for Women's Wellness	Los Alamitos	California	United States
12	Medical Center for Clinical Research	San Diego	California	United States
13	INC Clinical Trials	Upland	California	United States
14	Advanced Women's Health Institute	Denver	Colorado	United States
15	Downtown Women's Health Care	Denver	Colorado	United States
16	Nature Coast Clinical Research	Crystal River	Florida	United States
17	University of Florida	Gainesville	Florida	United States
18	Jacksonville Center for Clinical Research	Jacksonville	Florida	United States
19	New Age Medical Research Corp	Miami	Florida	United States
20	University of Miami Cedars Medical Center	Miami	Florida	United States
21	Advanced Research Institute	New Port Richey	Florida	United States
22	Segal Institute for Clinical Research	North Miami	Florida	United States
23	Medical Network for Education & Research, Inc.	Decatur	Georgia	United States
24	The Women's Clinic	Boise	Idaho	United States
25	Rosemark Womencare Specialists	Idaho Falls	Idaho	United States
26	Provident Clinical Research	Bloomington	Indiana	United States
27	Wichita Clinic, P.A.	Newton	Kansas	United States
28	Radiant Research	Overland Park	Kansas	United States
29	York Clinical Consulting	Marrero	Louisiana	United States
30	The Gynecology Center	Baltimore	Maryland	United States
31	ClinSite, LLC	Ann Arbor	Michigan	United States
32	Quest Research Institute	Bingham Farms	Michigan	United States
33	Grand Valley Gynecologists PC	Grand Rapids	Michigan	United States
34	Women's Health Care Specialist	Paw Paw	Michigan	United States
35	KMED Research	St. Clair Shores	Michigan	United States
36	Center for Pharmaceutical Research	Kansas City	Missouri	United States
37	Montana Medical Research, Inc	Missoula	Montana	United States
38	The Women's Center of Western Nebraska	Scottsbluff	Nebraska	United States
39	Office of R Garn Mabey, MD	Las Vegas	Nevada	United States
40	Women's Health Research Center, LLC	Lawrenceville	New Jersey	United States
41	Phoenix OB-GYN Assoc, LLC	Moorestown	New Jersey	United States
42	American Clinical Trials	New York	New York	United States
43	Duke Fertility Center	Durham	North Carolina	United States
44	Women's Wellness Center	Durham	North Carolina	United States
45	Lyndhurst Gynecologic Associates	Winston-Salem	North Carolina	United States
46	Piedmont Medical Research Associates	Winston-Salem	North Carolina	United States
47	Mid Dakota Clinic	Bismarck	North Dakota	United States
48	Triphase Research Ltd	Centerville	Ohio	United States
49	Rapid Medical Research, Inc	Cleveland	Ohio	United States
50	University Suburban Health Center	Cleveland	Ohio	United States
51	Holzer Clinic	Gallipolis	Ohio	United States
52	Physicians Research, Inc.	Zanesville	Ohio	United States
53	LION Research	Norman	Oklahoma	United States
54	Lynn Health Science Institute	Oklahoma City	Oklahoma	United States
55	Clinical Trials of America	Eugene	Oregon	United States
56	PMG/OB-GYN Health Center	Medford	Oregon	United States
57	The Portland Clinic	Portland	Oregon	United States
58	Abington Reproductive Medicine, PC	Abington	Pennsylvania	United States
59	The Clinical Trial Center	Jenkintown	Pennsylvania	United States
60	Family Medical Associates Research Dept	Levittown	Pennsylvania	United States
61	Philadelphia Clinical Research, LLC	Philadelphia	Pennsylvania	United States
62	University of Pennsylvania, Dept. OB/GYN	Philadelphia	Pennsylvania	United States
63	Valley Forge OB/GYN	Phoenixville	Pennsylvania	United States
64	Research Across America	Reading	Pennsylvania	United States
65	Main Line OB/GYN	Strafford	Pennsylvania	United States
66	Wexford Professional Bldg II	Wexford	Pennsylvania	United States
67	SC Clinical Research Center	Columbia	South Carolina	United States
68	Greenville Hospital System-Univ Med Group Dept	Greenville	South Carolina	United States
69	Greenville Pharmaceutical Research	Greenville	South Carolina	United States
70	Radiant Research	Greer	South Carolina	United States
71	Seasons	Bristol	Tennessee	United States
72	Southeastern Clinical Research	Chattanooga	Tennessee	United States
73	Alpha Clinical Research, LLC	Clarksville	Tennessee	United States
74	Volunteer Research Group	Knoxville	Tennessee	United States
75	Research Memphis Associates	Memphis	Tennessee	United States
76	Tennessee Women's Care, PC	Nashville	Tennessee	United States
77	J&S Studies, Inc	College Station	Texas	United States
78	OB/GYN Infertility & Preventive Medicine	Dallas	Texas	United States
79	Phyllis Gee, MD	Plano	Texas	United States
80	King's Daughters Clinic	Temple	Texas	United States
81	Center of Reproductive Medicine	Webster	Texas	United States
82	Women's Healthcare	Woodlands	Texas	United States
83	Mt. Timpanogos Women's Health Center	Pleasant Grove	Utah	United States
84	Jean Brown Research	Salt Lake City	Utah	United States
85	Physician's Research Options	Sandy	Utah	United States
86	Granger Medical OB/GYN	West Valley City	Utah	United States
87	FAHC, Womens Health Research	Burlington	Vermont	United States
88	Clinical Trials of Virginia, INC	Richmond	Virginia	United States
89	Tidewater Clinical Research, Inc.	Virginia Beach	Virginia	United States
90	Valley Women's Clinic	Renton	Washington	United States
91	North Spokane Women's Center	Spokane	Washington	United States
92	Medical Associates Health Centers	Menomonee Falls	Wisconsin	United States

Sponsors and Collaborators

• Ferring Pharmaceuticals
• Xanodyne Pharmaceuticals

Investigators

• Study Director: Clinical Development Support, Ferring Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT01280981
• Other Study ID Numbers: XP12B-MR-304
• First Posted: Jan 21, 2011
• Last Update Posted: Jul 26, 2011
• Last Verified: Jun 1, 2011

• Keywords provided by , ,: Menorrhagia; Heavy Menstrual Bleeding; Lysteda
• Additional relevant MeSH terms: Menorrhagia; Tranexamic Acid

Study Results

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.

Arm/Group Title	Tranexamic Acid
Arm/Group Description	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).
Period Title: Overall Study
STARTED	288
Intent to Treat (ITT) Population	260
COMPLETED	196
NOT COMPLETED	92

Baseline Characteristics

Arm/Group Title	Tranexamic Acid
Arm/Group Description	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).
Overall Participants	288
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	288 100%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	288 100%
Male	0 0%

Outcome Measures

1. Primary Outcome

Title	Participants With Treatment-Emergent Adverse Events (AEs)
Description	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

Outcome Measure Data

Analysis Population Description

Intent to treat population (ITT)

Arm/Group Title	Tranexamic Acid
Arm/Group Description	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).
Measure Participants	260
Any treatment-emergent AE	218 75.7%
Definitely related AE	1 0.3%
Probably related AE	3 1%
Possibly related AE	60 20.8%
Serious AE	5 1.7%
Life-threatening AE	2 0.7%
Died	0 0%
AE led to withdrawal from study	6 2.1%
Thrombotic or thromboembolic AE	0 0%

2. Secondary Outcome

Title	Participants With Abnormal Gynecological Examinations
Description	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

Outcome Measure Data

Analysis Population Description

Intent to treat population

Arm/Group Title	Tranexamic Acid
Arm/Group Description	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).
Measure Participants	260
Significant results from endometrial biopsies	0 0%
Abnormalities noted on TVU	3 1%
Discontinued due to failed physical exam	0 0%

3. Secondary Outcome

Title	Mean Blood Pressure Measurements at Week 36
Description	Mean systolic and diastolic blood pressure measurements taken at week 36
Time Frame	approximately week 36

Outcome Measure Data

Analysis Population Description

Intent to treat population of participants with week 36 blood pressure data.

Arm/Group Title	Tranexamic Acid
Arm/Group Description	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).
Measure Participants	200
Systolic blood pressure	118.94 (14.272)
Diastolic blood pressure	75.09 (10.167)

4. Secondary Outcome

Title	Participants With Treatment Emergent Adverse Experiences (TEAE) of Laboratory Values Related to Treatment
Description	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

Outcome Measure Data

Analysis Population Description

Intent to treat population

Arm/Group Title	Tranexamic Acid
Arm/Group Description	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).
Measure Participants	260
Hematology TEAE related to study drug	1 0.3%
Discontinued due to hematology TEAE	1 0.3%
Blood chemistry TEAE related to study drug	1 0.3%
Discontinued due to blood chemistry TEAE	0 0%
Urinalysis TEAE related to study drug	2 0.7%
Discontinued due to urinalysis TEAE	0 0%

5. Secondary Outcome

Title	Mean Intraocular Pressure at Month 9
Description	Mean intraocular pressure at month 9 or the early termination visit.
Time Frame	Day 1 up to Month 9

Outcome Measure Data

Analysis Population Description

Intent to treat participants who had ophthalmic exams.

Arm/Group Title	Tranexamic Acid
Arm/Group Description	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).
Measure Participants	199
Right eye	15.4 (2.866)
Left eye	15.3 (2.797)

6. Secondary Outcome

Title	Mean Fridericia-corrected QT Interval (QTcFRI) at Month 9
Description	The QT interval is the period that extends from the beginning of ventricular depolarization until the end of ventricular repolarization
Time Frame	Month 9

Outcome Measure Data

Analysis Population Description

Intent to treat participants who had an electrocardiogram (ECG) at month 9

Arm/Group Title	Tranexamic Acid
Arm/Group Description	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).
Measure Participants	193
Mean (Standard Deviation) [milliseconds]	412.3 (15.896)

Adverse Events

Time Frame	Treatment-emergent AEs: day 1 up to month 9
Arm/Group Title	Tranexamic Acid
Arm/Group Description	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).
All Cause Mortality
	Tranexamic Acid
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Tranexamic Acid
	Affected / at Risk (%)	# Events
Total	5/260 (1.9%)
Investigations
Blood glucose decreased	1/260 (0.4%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Carcinoid tumour of the stomach	1/260 (0.4%)
Nervous system disorders
Brain stem infarction	1/260 (0.4%)
Intracranial aneurysm	1/260 (0.4%)
Trigeminal neuralgia	1/260 (0.4%)
Reproductive system and breast disorders
Menorrhagia	2/260 (0.8%)
Other (Not Including Serious) Adverse Events
	Tranexamic Acid
	Affected / at Risk (%)	# Events
Total	218/260 (83.8%)
Blood and lymphatic system disorders
Anaemia	10/260 (3.8%)
Ear and labyrinth disorders
Ear congestion	1/260 (0.4%)
Ear discomfort	1/260 (0.4%)
Ear pain	4/260 (1.5%)
Ear pruritus	1/260 (0.4%)
Tympanic membrane disorder	1/260 (0.4%)
Vertigo	3/260 (1.2%)
Endocrine disorders
Hypothyroidism	1/260 (0.4%)
Eye disorders
Chalazion	1/260 (0.4%)
Conjunctivitis	1/260 (0.4%)
Corneal pigmentation	1/260 (0.4%)
Dry eye	1/260 (0.4%)
Eye discharge	1/260 (0.4%)
Eye irritation	1/260 (0.4%)
Ocular hypertension	1/260 (0.4%)
Retinal artery stenosis	1/260 (0.4%)
Retinal pigmentation	1/260 (0.4%)
Vision blurred	2/260 (0.8%)
Gastrointestinal disorders
Abdominal discomfort	15/260 (5.8%)
Abdominal pain	12/260 (4.6%)
Abdominal pain lower	1/260 (0.4%)
Abdominal pain upper	15/260 (5.8%)
Anal polyp	3/260 (1.2%)
Chapped lips	1/260 (0.4%)
Constipation	9/260 (3.5%)
Diarrhoea	19/260 (7.3%)
Dry mouth	1/260 (0.4%)
Dyspepsia	9/260 (3.5%)
Flatulence	2/260 (0.8%)
Food poisoning	1/260 (0.4%)
Gastritis	1/260 (0.4%)
Gastrooesophageal reflux disease	4/260 (1.5%)
Gingival pain	1/260 (0.4%)
Gingival swelling	1/260 (0.4%)
Lip blister	1/260 (0.4%)
Loose stools	1/260 (0.4%)
Nausea	17/260 (6.5%)
Oesophagitis	1/260 (0.4%)
Tongue disorder	1/260 (0.4%)
Toothache	11/260 (4.2%)
Vomiting	6/260 (2.3%)
General disorders
Chest discomfort	1/260 (0.4%)
Chest pain	1/260 (0.4%)
Chills	4/260 (1.5%)
Cyst	1/260 (0.4%)
Fatigue	14/260 (5.4%)
Influenza like illness	15/260 (5.8%)
Localized oedema	1/260 (0.4%)
Oedema	2/260 (0.8%)
Pyrexia	4/260 (1.5%)
Swelling	2/260 (0.8%)
Hepatobiliary disorders
Cholecystitis	1/260 (0.4%)
Immune system disorders
Multiple allergies	13/260 (5%)
Seasonal allergies	9/260 (3.5%)
Infections and infestations
Acute sinusitis	1/260 (0.4%)
Bronchitis	5/260 (1.9%)
Cystitis	3/260 (1.2%)
Ear infection	1/260 (0.4%)
Herpes simplex	1/260 (0.4%)
Herpes zoster	1/260 (0.4%)
Influenza	4/260 (1.5%)
Kidney infection	1/260 (0.4%)
Laryngitis	2/260 (0.8%)
Onychomycosis	1/260 (0.4%)
Otitis media	1/260 (0.4%)
Pharyngitis streptococcal	2/260 (0.8%)
Pneumonia	1/260 (0.4%)
Recurring skin boils	1/260 (0.4%)
Rhinitis	4/260 (1.5%)
Salpingitis	1/260 (0.4%)
Sinusitis	22/260 (8.5%)
Tonsillitis	1/260 (0.4%)
Tooth abscess	1/260 (0.4%)
Tooth infection	3/260 (1.2%)
Upper respiratory tract infection	9/260 (3.5%)
Urinary tract infection	8/260 (3.1%)
Vaginal candidiasis	5/260 (1.9%)
Viral upper respiratory tract infection	31/260 (11.9%)
Vulvovaginitis trichomonal	2/260 (0.8%)
Injury, poisoning and procedural complications
Arthropod sting	1/260 (0.4%)
Back injury	1/260 (0.4%)
Foot fracture	1/260 (0.4%)
Joint injury	4/260 (1.5%)
Joint sprain	1/260 (0.4%)
Muscle strain	2/260 (0.8%)
Post procedural complication	1/260 (0.4%)
Post procedural discomfort	2/260 (0.8%)
Post procedural pain	7/260 (2.7%)
Investigations
Aspartate aminotransferase increased	1/260 (0.4%)
Biopsy breast	1/260 (0.4%)
Blood cholesterol increased	1/260 (0.4%)
Blood glucose increased	1/260 (0.4%)
Blood triglycerides increased	1/260 (0.4%)
Blood urine present	2/260 (0.8%)
Cardiac murmur	1/260 (0.4%)
Electrocardiogram T wave abnormal	1/260 (0.4%)
Faecal occult blood	1/260 (0.4%)
Gamma-glutamyltransferase increased	2/260 (0.8%)
Haematocrit decreased	3/260 (1.2%)
Haemoglobin decreased	4/260 (1.5%)
Human papilloma virus serology test negative	1/260 (0.4%)
Human papilloma virus serology test positive	1/260 (0.4%)
Lipids increased	2/260 (0.8%)
Lymph node palpable	1/260 (0.4%)
Mean cell haemoglobin decreased	1/260 (0.4%)
Monocyte count decreased	1/260 (0.4%)
Red blood cell count decreased	1/260 (0.4%)
Serum ferritin decreased	2/260 (0.8%)
Smear cervix abnormal	7/260 (2.7%)
Thyroxine increased	1/260 (0.4%)
Ultrasound uterus	2/260 (0.8%)
Urinary occult blood positive	2/260 (0.8%)
Weight increased	1/260 (0.4%)
Metabolism and nutrition disorders
Decreased appetite	1/260 (0.4%)
Insulin resistance	2/260 (0.8%)
Musculoskeletal and connective tissue disorders
Arthralgia	15/260 (5.8%)
Arthritis	1/260 (0.4%)
Back pain	60/260 (23.1%)
Buttock pain	1/260 (0.4%)
Flank pain	1/260 (0.4%)
Groin pain	1/260 (0.4%)
Joint stiffness	1/260 (0.4%)
Muscle cramp	11/260 (4.2%)
Muscular weakness	1/260 (0.4%)
Musculoskeletal discomfort	2/260 (0.8%)
Musculoskeletal pain	15/260 (5.8%)
Myalgia	7/260 (2.7%)
Neck pain	13/260 (5%)
Pain in extremity	20/260 (7.7%)
Pain in jaw	2/260 (0.8%)
Plantar fasciitis	2/260 (0.8%)
Tendonitis	1/260 (0.4%)
Nervous system disorders
Dizziness	3/260 (1.2%)
Headache	114/260 (43.8%)
Migraine	20/260 (7.7%)
Paraesthesia	3/260 (1.2%)
Restless leg syndrome	2/260 (0.8%)
Sedation	2/260 (0.8%)
Sinus headache	17/260 (6.5%)
Tension headache	2/260 (0.8%)
Psychiatric disorders
Anxiety	7/260 (2.7%)
Attention deficit/hyperactivity disorder	1/260 (0.4%)
Depressed mood	1/260 (0.4%)
Depression	9/260 (3.5%)
Insomnia	11/260 (4.2%)
Irritability	4/260 (1.5%)
Mood swings	4/260 (1.5%)
Stress symptoms	3/260 (1.2%)
Renal and urinary disorders
Bladder pain	1/260 (0.4%)
Cystitis interstitial	1/260 (0.4%)
Dysuria	1/260 (0.4%)
Polyuria	1/260 (0.4%)
Reproductive system and breast disorders
Adenomyosis	1/260 (0.4%)
Breast cyst	2/260 (0.8%)
Breast discharge	1/260 (0.4%)
Breast discomfort	1/260 (0.4%)
Breast mass	1/260 (0.4%)
Breast pain	1/260 (0.4%)
Breast tenderness	5/260 (1.9%)
Cervical polyp	1/260 (0.4%)
Dysmenorrhoea	5/260 (1.9%)
Fibrocystic breast disease	1/260 (0.4%)
Menometrorrhagia	1/260 (0.4%)
Menstrual discomfort	3/260 (1.2%)
Menstrual disorder	1/260 (0.4%)
Nipple pain	1/260 (0.4%)
Ovarian cyst	1/260 (0.4%)
Ovarian cyst ruptured	1/260 (0.4%)
Ovulation pain	1/260 (0.4%)
Paraesthesia of genital female	8/260 (3.1%)
Pelvic pain	2/260 (0.8%)
Premenstrual syndrome	2/260 (0.8%)
Pruritus genital	6/260 (2.3%)
Uterine enlargement	1/260 (0.4%)
Uterine leiomyoma	1/260 (0.4%)
Uterine pain	1/260 (0.4%)
Vaginal discharge	7/260 (2.7%)
Vaginal odour	1/260 (0.4%)
Respiratory, thoracic and mediastinal disorders
Allergic sinusitis	1/260 (0.4%)
Asthma	4/260 (1.5%)
Asthma exercise induced	1/260 (0.4%)
Cough	12/260 (4.6%)
Dry throat	2/260 (0.8%)
Dyspnoea	3/260 (1.2%)
Hoarseness	1/260 (0.4%)
Nasal congestion	9/260 (3.5%)
Postnasal drip	1/260 (0.4%)
Respiratory tract congestion	2/260 (0.8%)
Rhinitis allergic	1/260 (0.4%)
Rhinorrhoea	1/260 (0.4%)
Sinus congestion	16/260 (6.2%)
Sinus pain	3/260 (1.2%)
Sneezing	2/260 (0.8%)
Throat irritation	6/260 (2.3%)
Throat tightness	2/260 (0.8%)
Skin and subcutaneous tissue disorders
Acne	3/260 (1.2%)
Cold sweat	1/260 (0.4%)
Dermatitis contact	2/260 (0.8%)
Dry skin	2/260 (0.8%)
Ecchymosis	1/260 (0.4%)
Lichenification	1/260 (0.4%)
Rash	3/260 (1.2%)
Urticaria	1/260 (0.4%)
Surgical and medical procedures
Benign breast lump removal	1/260 (0.4%)
Meniscus operation	1/260 (0.4%)
Surgery	1/260 (0.4%)
Vascular disorders
Flushing	1/260 (0.4%)
Hypertension	3/260 (1.2%)
Hypotension	1/260 (0.4%)
Varicose vein	1/260 (0.4%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review the draft manuscript prior to publication and can request delay of publication where any contents are deemed patentable by the sponsor or confidential to the sponsor. Comments will be given within four weeks from receipt of the draft manuscript. Additional time may be required to allow Ferring to seek patent protection of the invention.