Clinical trial NCT00307801: Efficacy and Safety Study for the Treatment of Dysfunctional Uterine Bleeding
Official title: A Multicenter, Double-Blind, Randomized, Parallel-Group, Placebo-Controlled, 7 Cycle Duration (196 Days), Phase 3 Study of Oral Estradiol Valerate/Dienogest Tablets for the Treatment of Dysfunctional Uterine Bleeding.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Metrorrhagia
Keywords: Dysfunctional uterine bleeding
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2006-03-28
Enrollment: 231
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether the study drug is safe and effective in the treatment of dysfunctional uterine bleeding.

Detailed description: The study has previously been posted by Schering AG, Germany. Schering AG, Germany has been renamed to Bayer HealthCare AG, Germany. Bayer HealthCare AG, Germany is the sponsor of the trial.

Eligibility criteria: Inclusion Criteria:

* Women 18 years or older
* And with a diagnosis of dysfunctional uterine bleeding without organic pathology
* And with at least one of the following symptoms: prolonged, frequent or excessive bleeding.

Exclusion Criteria:

* The use of steroidal oral contraceptives, or any drug that could alter oral contraception metabolism will be prohibited during the study.
* Women with a history of endometrial ablation or dilatation and curettage within 2 months prior to study start will be excluded.

Primary outcomes:
measure: Proportion of Participants With no Dysfunctional Uterine Bleeding (DUB) Symptoms
timeFrame: Efficacy phase was defined as a 90-day period under treatment. For patients who completed up to day 6 of treatment cycle 7, the efficacy phase started on the first day of treatment cycle 4, and continued through day 6 of treatment cycle 7
Secondary outcomes:
measure: Proportion of Participants Cured From Prolonged Bleeding
timeFrame: Efficacy phase was defined as a 90-day period under treatment. For patients who completed up to day 6 of treatment cycle 7, the efficacy phase started on the first day of treatment cycle 4, and continued through day 6 of treatment cycle 7
measure: Proportion of Participants Cured From Excessive Bleeding
timeFrame: Efficacy phase was defined as a 90-day period under treatment. For patients who completed up to day 6 of treatment cycle 7, the efficacy phase started on the first day of treatment cycle 4, and continued through day 6 of treatment cycle 7
measure: Proportion of Participants Cured From Frequent Bleeding
timeFrame: Efficacy phase was defined as a 90-day period under treatment. For patients who completed up to day 6 of treatment cycle 7, the efficacy phase started on the first day of treatment cycle 4, and continued through day 6 of treatment cycle 7
measure: Proportion of Participants With Improvement in the Investigator's Global Assessment Scale at Treatment Day 84
timeFrame: From baseline (visit 5, day 1) up to treatment day 84
measure: Proportion of Participants With Improvement in the Investigator's Global Assessment Scale at Treatment Day 196
timeFrame: From baseline (visit 5, day 1) up to treatment day 196
measure: Proportion of Participants With Improvement in the Patient's Overall Assessment Scale at Treatment Day 84
timeFrame: From baseline (visit 5, day 1) up to treatment day 84
measure: Proportion of Participants With Improvement in the Patient's Overall Assessment Scale at Treatment Day 196
timeFrame: From baseline (visit 5, day 1) up to treatment day 196
measure: Change From Baseline in Blood Loss Volume for All Participants to the Reference Period of 90 Days Under Treatment
timeFrame: Baseline and reference period of 90 days under treatment. For patients who completed up to day 6 of treatment cycle 7, the efficacy phase started on the first day of treatment cycle 4, and continued through day 6 of treatment cycle 7
measure: Menstrual Blood Loss Volume for All Participants at Cycle 1
timeFrame: Cycle 1 = 28 days (one cycle)
measure: Menstrual Blood Loss Volume for All Participants at Cycle 3
timeFrame: Cycle 3 = 28 days (one cycle)
measure: Menstrual Blood Loss Volume for All Participants at Cycle 7
timeFrame: Cycle 7 = 28 days (one cycle)
measure: Change From Baseline in Blood Loss Volume for Participants With Excessive Bleeding to the Reference Period of 90 Days Under Treatment.
timeFrame: Baseline and reference period of 90 days under treatment. For patients who completed up to day 6 of treatment cycle 7, the efficacy phase started on the first day of treatment cycle 4, and continued through day 6 of treatment cycle 7
measure: Menstrual Blood Loss Volume for Participants With Excessive Bleeding at Cycle 1.
timeFrame: Cycle 1 = 28 days (one cycle)
measure: Menstrual Blood Loss Volume for Participants With Excessive Bleeding at Cycle 3.
timeFrame: Cycle 3 = 28 days (one cycle)
measure: Menstrual Blood Loss Volume for Participants With Excessive Bleeding at Cycle 7.
timeFrame: Cycle 7 = 28 days (one cycle)
measure: Change From Baseline in Number of Bleeding Episodes to the Reference Period of 90 Days Under Treatment
timeFrame: Baseline and reference period of 90 days under treatment. For patients who completed up to day 6 of treatment cycle 7, the efficacy phase started on the first day of treatment cycle 4, and continued through day 6 of treatment cycle 7
measure: Change From Baseline in Number of Bleeding Days to the Reference Period of 90 Days Under Treatment
timeFrame: Baseline and reference period of 90 days under treatment. For patients who completed up to day 6 of treatment cycle 7, the efficacy phase started on the first day of treatment cycle 4, and continued through day 6 of treatment cycle 7
measure: Change From Baseline in Number of Sanitary Protection Used at 90 Days of Treatment
timeFrame: Baseline and reference period of 90 days under treatment. For patients who completed up to day 6 of treatment cycle 7, the efficacy phase started on the first day of treatment cycle 4, and continued through day 6 of treatment cycle 7
measure: Change From Baseline in Hemoglobin Concentration at Treatment Day 84
timeFrame: Baseline (visit 5) and treatment day 84
measure: Change From Baseline in Hemoglobin Concentration at Treatment Day 196
timeFrame: Baseline (visit 5) and treatment day 196
measure: Change From Baseline in Hematocrit at Treatment Day 196.
timeFrame: Baseline (visit 5) and treatment day 196
measure: Change From Baseline in Ferritin Concentration at Treatment Day 84
timeFrame: Baseline (visit 5, day 1) and treatment day 84
measure: Change From Baseline in Ferritin Concentration at Treatment Day 196
timeFrame: Baseline (visit 5, day 1) and treatment day 196
measure: Change From Baseline in Psychological General Well-Being Index (PGWBI) Score at Treatment Day 84.
timeFrame: Baseline (visit 5, day 1) and treatment day 84
measure: Change From Baseline in Psychological General Well-Being Index (PGWBI) Score at Treatment Day 196.
timeFrame: Baseline (visit 5, day 1) and treatment day 196
measure: Change From Baseline in McCoy Female Sexuality Questionnaire (MFSQ) Score at Treatment Day 84
timeFrame: Baseline (visit 5, day 1) and treatment day 84
measure: Change From Baseline in McCoy Female Sexuality Questionnaire (MFSQ) Score at Treatment Day 196
timeFrame: Baseline (visit 5, day 1) and treatment day 196
measure: Change From Baseline in EuroQol 5 Dimensional (EQ-5D) Score at Treatment Day 84
timeFrame: Baseline (visit 5, day 1) and treatment day 84
measure: Change From Baseline in EuroQol 5 Dimensional (EQ-5D) Score at Treatment Day 196
timeFrame: Baseline (visit 5, day 1) and treatment day 196
measure: Change From Baseline in Visual Analogue Scale (VAS) of the EQ-5D Score at Treatment Day 84.
timeFrame: Baseline (visit 5, day 1) and treatment day 84
measure: Change From Baseline in Visual Analogue Scale (VAS) of the EQ-5D Score at Treatment Day 196.
timeFrame: Baseline (visit 5, day 1) and treatment day 196
measure: Resource Use Assessment by Use of a Self Administered Questionnaire （Change in the Employment Status） at Treatment Day 84.
timeFrame: Treatment day 84
measure: Resource Use Assessment by Use of a Self Administered Questionnaire （Change in the Employment Status） at Treatment Day 196.
timeFrame: Treatment day 196
measure: Resource Use Assessment by Use of a Self Administered Questionnaire （Days Missed From Work） at Treatment Day 84
timeFrame: Treatment day 84
measure: Resource Use Assessment by Use of a Self Administered Questionnaire （Days Missed From Work） at Treatment Day 196
timeFrame: Treatment day 196
measure: Resource Use Assessment by Use of a Self Administered Questionnaire （Productivity While Working） at Treatment Day 84.
timeFrame: Treatment day 84
measure: Resource Use Assessment by Use of a Self Administered Questionnaire （Productivity While Working） at Treatment Day 196.
timeFrame: Treatment day 196
measure: Resource Use Assessment by Use of a Self Administered Questionnaire （Regular Daily Activities） at Treatment Day 84
timeFrame: Treatment day 84
measure: Resource Use Assessment by Use of a Self Administered Questionnaire （Regular Daily Activities） at Treatment Day 196.
timeFrame: Treatment day 196
measure: Resource Use Assessment by Use of a Self Administered Questionnaire （Unscheduled Outpatient Visit at Hospital） at Treatment Day 84
timeFrame: Treatment day 84
measure: Resource Use Assessment by Use of a Self Administered Questionnaire （Unscheduled Outpatient Visit at Hospital） at Treatment Day 196
timeFrame: Treatment day 196
measure: Resource Use Assessment by Use of a Self Administered Questionnaire （Unscheduled Outpatient Visit to Physician） at Treatment Day 84
timeFrame: Treatment day 84
measure: Resource Use Assessment by Use of a Self Administered Questionnaire （Unscheduled Outpatient Visit to Physician） at Treatment Day 196
timeFrame: Treatment day 196
measure: Resource Use Assessment by Use of a Self Administered Questionnaire （Additional Unscheduled Procedures） at Treatment Day 84
timeFrame: Treatment day 84
measure: Resource Use Assessment by Use of a Self Administered Questionnaire （Additional Unscheduled Procedures） at Treatment Day 196
timeFrame: Treatment day 196
measure: Resource Use Assessment by Use of a Self Administered Questionnaire （Received Ambulatory Services） at Treatment Day 84
timeFrame: Treatment day 84
measure: Resource Use Assessment by Use of a Self Administered Questionnaire （Received Ambulatory Services） at Treatment Day 196
timeFrame: Treatment day 196
measure: Resource Use Assessment by Use of a Self Administered Questionnaire （no Out-of-pocket Expenses） at Treatment Day 84
timeFrame: Treatment day 84
measure: Resource Use Assessment by Use of a Self Administered Questionnaire （no Out-of-pocket Expenses） at Treatment Day 196
timeFrame: Treatment day 196
measure: Resource Use Assessment by Use of a Self Administered Questionnaire （Not Have Any Medical Treatment） at Treatment Day 84
timeFrame: Treatment day 84
measure: Resource Use Assessment by Use of a Self Administered Questionnaire （Not Have Any Medical Treatment） at Treatment Day 196
timeFrame: Treatment day 196
Other outcomes:
Locations:
city: Ashfield
country: Australia
facility: Private Practice Dr. Ian Fraser
state: New South Wales
city: Subiaco
country: Australia
facility: King Edward Memorial Hospital
state: Western Australia
city: Ceske Budejovice
country: Czech Republic
facility: Gynekologicka ambulance Vanda Horejsi, MD
city: Pardubice
country: Czech Republic
facility: Center for Clinical& Basic Research
city: Pisek
country: Czech Republic
facility: Gynekologicko-poradnicka ambulance Dr. Hlavackova
city: Praha 7
country: Czech Republic
facility: Lekarsky dum Praha 7 a.s.Gynekologicka ambulance Dr. Jenicek
city: Espoo
country: Finland
facility: Adenova Lääkärikeskus Oy
city: Lahti
country: Finland
facility: Terveystalo Lahti
city: Tampere
country: Finland
facility: Koskiklinikka
city: Turku
country: Finland
facility: Ylioppilaiden terveydenhoitosäätiö, Turku
city: Karlsruhe
country: Germany
facility: Praxis Hr. Dr. U. Kohoutek
state: Baden-Württemberg
city: Rheinstetten
country: Germany
facility: Praxis Hr. Dr. S. Schönian
state: Baden-Württemberg
city: Hannover
country: Germany
facility: Praxis Hr. Dr. K. Greven
state: Niedersachsen
city: Dresden
country: Germany
facility: ClinPharm International GmbH
state: Sachsen
city: Berlin
country: Germany
facility: emovis GmbH
city: Budapest
country: Hungary
facility: University of Semmelweis
city: Komarom
country: Hungary
facility: Selya Janos Hospital
city: Miskolc
country: Hungary
facility: Borsod-Abauj-Zemplen County Hospital
city: Enschede
country: Netherlands
facility: Medisch Spectrum Twente, Locatie Ariensplein
city: Geleen
country: Netherlands
facility: PreCare Trial & Recruitment
city: Nijmegen
country: Netherlands
facility: Menox BV
city: Bialystok
country: Poland
facility: Poliklinika Ginekologiczna- Poloznicza
city: Lodz
country: Poland
facility: Instytut Centrum Zdrowia Matki Polki
city: Lublin
country: Poland
facility: SPSK nr 1
city: Poznan
country: Poland
facility: Szpital Kliniczny nr 3
city: Warszawa
country: Poland
facility: CSK MSWiA
city: Lund
country: Sweden
facility: Skånes Universitetssjukhus
city: Stockholm
country: Sweden
facility: Karolinska Universitetssjukhuset Huddinge
city: Uppsala
country: Sweden
facility: Akademiska Sjukhuset
city: Kiev
country: Ukraine
facility: Dept. of obstetrics and gynaecology
city: Kiev
country: Ukraine
facility: Instr. of Pediatrics, Obstetrics & Gynecology
city: Kiev
country: Ukraine
facility: Kyiv Medical Academy of Postdyploma Education
city: Lviv
country: Ukraine
facility: Lviv Regional Center Perinatal Center
city: Cheadle
country: United Kingdom
facility: Bridge House Medical Centre
state: Cheshire
city: Luton
country: United Kingdom
facility: Luton & Dunstable Hospital
city: Northwood
country: United Kingdom
facility: MeDiNova Research
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References:
citation: Fraser IS, Jensen J, Schaefers M, Mellinger U, Parke S, Serrani M. Normalization of blood loss in women with heavy menstrual bleeding treated with an oral contraceptive containing estradiol valerate/dienogest. Contraception. 2012 Aug;86(2):96-101. doi: 10.1016/j.contraception.2011.11.011. Epub 2012 Jan 10.
citation: Fraser IS, Parke S, Mellinger U, Machlitt A, Serrani M, Jensen J. Effective treatment of heavy and/or prolonged menstrual bleeding without organic cause: pooled analysis of two multinational, randomised, double-blind, placebo-controlled trials of oestradiol valerate and dienogest. Eur J Contracept Reprod Health Care. 2011 Aug;16(4):258-69. doi: 10.3109/13625187.2011.591456.
citation: Fraser IS, Romer T, Parke S, Zeun S, Mellinger U, Machlitt A, Jensen JT. Effective treatment of heavy and/or prolonged menstrual bleeding with an oral contraceptive containing estradiol valerate and dienogest: a randomized, double-blind Phase III trial. Hum Reprod. 2011 Oct;26(10):2698-708. doi: 10.1093/humrep/der224. Epub 2011 Jul 21.
citation: Wasiak R, Filonenko A, Vanness DJ, Wittrup-Jensen KU, Stull DE, Siak S, Fraser I. Impact of estradiol-valerate/dienogest on work productivity and activities of daily living in European and Australian women with heavy menstrual bleeding. Int J Womens Health. 2012;4:271-8. doi: 10.2147/IJWH.S31740. Epub 2012 Jul 12.
citation: Fraser IS, Zeun S, Parke S, Wilke B, Junge W, Serrani M. Improving the objective quality of large-scale clinical trials for women with heavy menstrual bleeding: experience from 2 multi-center, randomized trials. Reprod Sci. 2013 Jul;20(7):745-54. doi: 10.1177/1933719113477492. Epub 2013 Feb 25.