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Efficacy and Safety of 20 mg (2 Tablets of 10mg)VAC BNO 1095 FCT on Cyclic Mastodynia and PMS

This study has been terminated.
Information provided by (Responsible Party):
Bionorica SE Identifier:
First received: May 16, 2013
Last updated: September 12, 2016
Last verified: September 2016
The purpose of this study is to proof the efficacy and safety of 20 mg (2 tablets of 10 mg) VAC BNO 1095 film-coated tablets in patients suffering from cyclic mastodynia and PMS (pre menstrual syndrome).

Condition Intervention Phase
Premenstrual Syndrome
Drug: 20mg VAC BNO 1095 FCT
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Prospective, Double-blind, Placebo-controlled, Parallel-group, Multi-centre Randomized Clinical Trial to Proof Efficacy and Safety of 20 mg (2 Tablets of 10 mg) VAC BNO 1095 FCT in Patients Suffering From Cyclic Mastodynia and PMS

Resource links provided by NLM:

Further study details as provided by Bionorica SE:

Primary Outcome Measures:
  • Maximum severity of cyclic breast pain [ Time Frame: after 3 months treatment under Investigational Medicinal Product (IMP). ] [ Designated as safety issue: No ]
    Maximum severity of cyclic breast pain after 3 months treatment under Investigational Medicinal Product (IMP). The severity of cyclic breast pain will be self-assessed by the patient on a Visual Analogue Scale (VAS).

Secondary Outcome Measures:
  • Severity of cyclic breast pain and PMS symptoms [ Time Frame: After 1, 2 and 3 months of treatment ] [ Designated as safety issue: No ]
    • Maximum severity of cyclic breast pain after 1 and 2 months treatment, respectively. The severity of cyclic breast pain will be self-assessed by the patient on a VAS
    • Average severity of cyclic mastodynia, determined in the late luteal phase of each of the treatment cycles.
    • Intensity of PMS assessed by means of a PMS diary (COPE = calendar of premenstrual experiences) during each of the treatment cycles
    • Overall assessments of efficacy on cyclic mastodynia and PMS by patient and investigator at study end by a score ranging from 1 to 5
    • Subgroup analysis: A. Patients with the waist circumference ≤ 90 cm B. Patients with the waist circumference > 90 cm. For both subgroups A. and B.: Maximum severity of cyclic breast pain after 3 months treatment under IMP. The severity of cyclic breast pain will be self-assessed by the patient on a VAS.

Enrollment: 96
Study Start Date: June 2013
Study Completion Date: October 2014
Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: VAC BNO 1095 2x10 mg FCT
VAC BNO 1095 2x10 mg FCT 2 tablets of verum in the morning, oral, 3 months treatment
Drug: 20mg VAC BNO 1095 FCT
Placebo Comparator: Placebo
2 tablets in the morning, oral, 3 months treatment
Drug: Placebo

Detailed Description:

The study consists of a 2-cycle run-in period, followed by 3 cycles of treatment. After first screening at S-2 further visits are scheduled after the end of each of the first and second run-in cycle, and after the first, second and third treatment cycle, respectively.

At least 220 patients should be eligible for randomisation, 110 to each treatment group, of which 160 (80 per group) will be available for data evaluation.


Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Females 18 to 45 Y with a history of cyclic mastodynia and PMS
  • Stable cycle duration of 25 to 35 days.
  • Subject is reporting at least one moderate or severe physical PMS symptom moderate and one psychic symptom, using the COPE symptom list
  • Subject is reporting symptoms of a total score of at least 15 in the late luteal phase of the preceding cycle, using the COPE symptom list
  • In both run-in cycles: Confirmation of cyclic mastodynia based on daily recordings of patient diary (VAS and COPE data)
  • Subject provides a negative pregnancy test at study start and is willing to use a hormone-free medically acknowledged contraception methods with a PEARL-index < 1 % from enrolment
  • Unsuspicious breast USG/mammogram not older than 12 months ruling out signs of malignancy

Exclusion Criteria:

  • Hypersensitivity to the active substance or to the excipients of the IMP
  • Proof of PMDD according to DSM IV criteria as defined by APA
  • Intake of any of the following medications before treatment start and within 6 months prior to screening visit:

    • hypothalamic hormones
    • injectable contraceptives: 3-month injection
  • Intake of any of the following medications (including herbal or homeopathic drugs) before treatment start and within 3 months prior to screening visit:

    • any treatment for mastodynia or premenstrual complaints
    • sexual hormones, combinations and inhibitors
    • pituitary hormones and their inhibitors
    • dopamine-agonists and dopamine-antagonists
    • neuroleptics, antidepressants (including serotonin- and serotonin-norepinephrine-reuptake-inhibitors)
    • prolactin-inhibitors or prolactin stimulating preparations
    • drug abuse or continuous intake of NSAIDs or any other analgetics including antirheumatics (up to 2 tablets of paracetamol 500 mg or equivalent per week are allowed)
    • spironolactone
    • gonadotrophin inhibitors
    • diuretics
    • danazol
    • psychotropic agents
  • Any psychiatric treatment before treatment start and within 12 months prior to screening visit
  • Medical history or presence of any of the following medical conditions/ diseases before treatment start:

    • Uncontrolled diabetes mellitus: Patients with known diabetes mellitus, who have a glycosylated haemoglobin (HbA1c) ≥ 7% as assessed at visit S-1
    • Uncontrolled hypertension: Patients with a diastolic blood pressure >90mmHg at visit S-2
    • Known cardiac insufficiency, coronary heart disease, valvular heart disease, cardiac arrhythmia, QT interval prolongation or other severe cardiac disease at visit S-2
    • Known clinically significant organ or systemic diseases or any other relevant medical condition such that in the opinion of the investigator, the significance of the disease or condition will compromise the subject's participation in the study
    • Known hyperprolactinemia (serum prolactin basal > 50 ng/ml or > 1050 mlU/L)
    • Known hypo-/hyperthyreosis
    • Known hypo-/hyperparathyroidism
    • Known pituitary tumor including prolactinoma
    • Known chronic kidney disease
    • Known gastrointestinal, or liver diseases, such as:

      i. active peptic gastric ulcer ii. malabsorption iii. hepatitis

    • endometriosis
    • breast cancer, fibroadenoma, intraductal papilloma or other malignancy within the last 10 years
    • suspicious non-verified finding on any breast ultrasound or mammograms in the past
    • galactorrhea of degree II or III
    • purulent or bloody nipple discharge
    • refractory and/or unverified breast skin- or nipple/areola lesions
    • pregnancy, lactation
    • wish for pregnancy
    • any surgery planned to take place during the trial including breast cyst puncture
  • Values of safety laboratory parameters outside normal ranges and clinically relevant as assessed by the investigator at S-1
  • At screening:TSH > 2.5 mU/L
  • Patients who have difficulties in understanding the language in which the patient information is given
  • Patients who are members of the staff of the study centre, staff of the sponsor or CRO, the investigator herself or close relatives of the investigator
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01870687

Private Doctor's office - Dr. Hannes Herold
Munich, Bavaria, Germany, 80802
Sponsors and Collaborators
Bionorica SE
Study Chair: Andrzej Witek, MD PhD Prof.
Study Chair: Hannes Herold, Dr. med.
  More Information

Responsible Party: Bionorica SE Identifier: NCT01870687     History of Changes
Other Study ID Numbers: P-AG-E-4  2012-005042-37 
Study First Received: May 16, 2013
Last Updated: September 12, 2016
Health Authority: Germany: Federal Institute for Drugs and Medical Devices
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products

Keywords provided by Bionorica SE:
vitex agnus castus
clinical trial
cyclic mastodynia

Additional relevant MeSH terms:
Premenstrual Syndrome
Menstruation Disturbances
Pathologic Processes
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms processed this record on January 18, 2017