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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00307801




Registration number
NCT00307801
Ethics application status
Date submitted
27/03/2006
Date registered
28/03/2006
Date last updated
30/12/2014

Titles & IDs
Public title
Efficacy and Safety Study for the Treatment of Dysfunctional Uterine Bleeding
Scientific 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.
Secondary ID [1] 0 0
2005-004340-32
Secondary ID [2] 0 0
91470
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metrorrhagia 0 0
Condition category
Condition code
Renal and Urogenital 0 0 0 0
Other renal and urogenital disorders
Reproductive Health and Childbirth 0 0 0 0
Menstruation and menopause

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Estradiol valerate/Dienogest (Natazia, Qlaira, BAY86-5027)
Treatment: Drugs - Placebo

Experimental: Estradiol valerate/Dienogest (Natazia, Qlaira, BAY86-5027) - A blister consists of 28 tablets taken orally once a day for 28 days (one cycle): 2 days of 3 mg estradiol valerate (EV); 5 days of 2 mg EV + 2 mg dienogest (DNG); 17 days of 2 mg EV + 3 mg DNG; 2 days of 1 mg EV; 2 days of placebo.

Placebo comparator: Placebo - Matching placebo to be taken orally daily.


Treatment: Drugs: Estradiol valerate/Dienogest (Natazia, Qlaira, BAY86-5027)
1 pill per day taken orally over 7 cycles of 28 pills per cycle

Treatment: Drugs: Placebo
1 pill per day taken orally over 7 cycles of 28 pills per cycle
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Proportion of Participants With no Dysfunctional Uterine Bleeding (DUB) Symptoms
Timepoint [1] 0 0
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 outcome [1] 0 0
Proportion of Participants Cured From Prolonged Bleeding
Timepoint [1] 0 0
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 outcome [2] 0 0
Proportion of Participants Cured From Excessive Bleeding
Timepoint [2] 0 0
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 outcome [3] 0 0
Proportion of Participants Cured From Frequent Bleeding
Timepoint [3] 0 0
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 outcome [4] 0 0
Proportion of Participants With Improvement in the Investigator's Global Assessment Scale at Treatment Day 84
Timepoint [4] 0 0
From baseline (visit 5, day 1) up to treatment day 84
Secondary outcome [5] 0 0
Proportion of Participants With Improvement in the Investigator's Global Assessment Scale at Treatment Day 196
Timepoint [5] 0 0
From baseline (visit 5, day 1) up to treatment day 196
Secondary outcome [6] 0 0
Proportion of Participants With Improvement in the Patient's Overall Assessment Scale at Treatment Day 84
Timepoint [6] 0 0
From baseline (visit 5, day 1) up to treatment day 84
Secondary outcome [7] 0 0
Proportion of Participants With Improvement in the Patient's Overall Assessment Scale at Treatment Day 196
Timepoint [7] 0 0
From baseline (visit 5, day 1) up to treatment day 196
Secondary outcome [8] 0 0
Change From Baseline in Blood Loss Volume for All Participants to the Reference Period of 90 Days Under Treatment
Timepoint [8] 0 0
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
Secondary outcome [9] 0 0
Menstrual Blood Loss Volume for All Participants at Cycle 1
Timepoint [9] 0 0
Cycle 1 = 28 days (one cycle)
Secondary outcome [10] 0 0
Menstrual Blood Loss Volume for All Participants at Cycle 3
Timepoint [10] 0 0
Cycle 3 = 28 days (one cycle)
Secondary outcome [11] 0 0
Menstrual Blood Loss Volume for All Participants at Cycle 7
Timepoint [11] 0 0
Cycle 7 = 28 days (one cycle)
Secondary outcome [12] 0 0
Change From Baseline in Blood Loss Volume for Participants With Excessive Bleeding to the Reference Period of 90 Days Under Treatment.
Timepoint [12] 0 0
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
Secondary outcome [13] 0 0
Menstrual Blood Loss Volume for Participants With Excessive Bleeding at Cycle 1.
Timepoint [13] 0 0
Cycle 1 = 28 days (one cycle)
Secondary outcome [14] 0 0
Menstrual Blood Loss Volume for Participants With Excessive Bleeding at Cycle 3.
Timepoint [14] 0 0
Cycle 3 = 28 days (one cycle)
Secondary outcome [15] 0 0
Menstrual Blood Loss Volume for Participants With Excessive Bleeding at Cycle 7.
Timepoint [15] 0 0
Cycle 7 = 28 days (one cycle)
Secondary outcome [16] 0 0
Change From Baseline in Number of Bleeding Episodes to the Reference Period of 90 Days Under Treatment
Timepoint [16] 0 0
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
Secondary outcome [17] 0 0
Change From Baseline in Number of Bleeding Days to the Reference Period of 90 Days Under Treatment
Timepoint [17] 0 0
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
Secondary outcome [18] 0 0
Change From Baseline in Number of Sanitary Protection Used at 90 Days of Treatment
Timepoint [18] 0 0
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
Secondary outcome [19] 0 0
Change From Baseline in Hemoglobin Concentration at Treatment Day 84
Timepoint [19] 0 0
Baseline (visit 5) and treatment day 84
Secondary outcome [20] 0 0
Change From Baseline in Hemoglobin Concentration at Treatment Day 196
Timepoint [20] 0 0
Baseline (visit 5) and treatment day 196
Secondary outcome [21] 0 0
Change From Baseline in Hematocrit at Treatment Day 196.
Timepoint [21] 0 0
Baseline (visit 5) and treatment day 196
Secondary outcome [22] 0 0
Change From Baseline in Ferritin Concentration at Treatment Day 84
Timepoint [22] 0 0
Baseline (visit 5, day 1) and treatment day 84
Secondary outcome [23] 0 0
Change From Baseline in Ferritin Concentration at Treatment Day 196
Timepoint [23] 0 0
Baseline (visit 5, day 1) and treatment day 196
Secondary outcome [24] 0 0
Change From Baseline in Psychological General Well-Being Index (PGWBI) Score at Treatment Day 84.
Timepoint [24] 0 0
Baseline (visit 5, day 1) and treatment day 84
Secondary outcome [25] 0 0
Change From Baseline in Psychological General Well-Being Index (PGWBI) Score at Treatment Day 196.
Timepoint [25] 0 0
Baseline (visit 5, day 1) and treatment day 196
Secondary outcome [26] 0 0
Change From Baseline in McCoy Female Sexuality Questionnaire (MFSQ) Score at Treatment Day 84
Timepoint [26] 0 0
Baseline (visit 5, day 1) and treatment day 84
Secondary outcome [27] 0 0
Change From Baseline in McCoy Female Sexuality Questionnaire (MFSQ) Score at Treatment Day 196
Timepoint [27] 0 0
Baseline (visit 5, day 1) and treatment day 196
Secondary outcome [28] 0 0
Change From Baseline in EuroQol 5 Dimensional (EQ-5D) Score at Treatment Day 84
Timepoint [28] 0 0
Baseline (visit 5, day 1) and treatment day 84
Secondary outcome [29] 0 0
Change From Baseline in EuroQol 5 Dimensional (EQ-5D) Score at Treatment Day 196
Timepoint [29] 0 0
Baseline (visit 5, day 1) and treatment day 196
Secondary outcome [30] 0 0
Change From Baseline in Visual Analogue Scale (VAS) of the EQ-5D Score at Treatment Day 84.
Timepoint [30] 0 0
Baseline (visit 5, day 1) and treatment day 84
Secondary outcome [31] 0 0
Change From Baseline in Visual Analogue Scale (VAS) of the EQ-5D Score at Treatment Day 196.
Timepoint [31] 0 0
Baseline (visit 5, day 1) and treatment day 196
Secondary outcome [32] 0 0
Resource Use Assessment by Use of a Self Administered Questionnaire (Change in the Employment Status) at Treatment Day 84.
Timepoint [32] 0 0
Treatment day 84
Secondary outcome [33] 0 0
Resource Use Assessment by Use of a Self Administered Questionnaire (Change in the Employment Status) at Treatment Day 196.
Timepoint [33] 0 0
Treatment day 196
Secondary outcome [34] 0 0
Resource Use Assessment by Use of a Self Administered Questionnaire (Days Missed From Work) at Treatment Day 84
Timepoint [34] 0 0
Treatment day 84
Secondary outcome [35] 0 0
Resource Use Assessment by Use of a Self Administered Questionnaire (Days Missed From Work) at Treatment Day 196
Timepoint [35] 0 0
Treatment day 196
Secondary outcome [36] 0 0
Resource Use Assessment by Use of a Self Administered Questionnaire (Productivity While Working) at Treatment Day 84.
Timepoint [36] 0 0
Treatment day 84
Secondary outcome [37] 0 0
Resource Use Assessment by Use of a Self Administered Questionnaire (Productivity While Working) at Treatment Day 196.
Timepoint [37] 0 0
Treatment day 196
Secondary outcome [38] 0 0
Resource Use Assessment by Use of a Self Administered Questionnaire (Regular Daily Activities) at Treatment Day 84
Timepoint [38] 0 0
Treatment day 84
Secondary outcome [39] 0 0
Resource Use Assessment by Use of a Self Administered Questionnaire (Regular Daily Activities) at Treatment Day 196.
Timepoint [39] 0 0
Treatment day 196
Secondary outcome [40] 0 0
Resource Use Assessment by Use of a Self Administered Questionnaire (Unscheduled Outpatient Visit at Hospital) at Treatment Day 84
Timepoint [40] 0 0
Treatment day 84
Secondary outcome [41] 0 0
Resource Use Assessment by Use of a Self Administered Questionnaire (Unscheduled Outpatient Visit at Hospital) at Treatment Day 196
Timepoint [41] 0 0
Treatment day 196
Secondary outcome [42] 0 0
Resource Use Assessment by Use of a Self Administered Questionnaire (Unscheduled Outpatient Visit to Physician) at Treatment Day 84
Timepoint [42] 0 0
Treatment day 84
Secondary outcome [43] 0 0
Resource Use Assessment by Use of a Self Administered Questionnaire (Unscheduled Outpatient Visit to Physician) at Treatment Day 196
Timepoint [43] 0 0
Treatment day 196
Secondary outcome [44] 0 0
Resource Use Assessment by Use of a Self Administered Questionnaire (Additional Unscheduled Procedures) at Treatment Day 84
Timepoint [44] 0 0
Treatment day 84
Secondary outcome [45] 0 0
Resource Use Assessment by Use of a Self Administered Questionnaire (Additional Unscheduled Procedures) at Treatment Day 196
Timepoint [45] 0 0
Treatment day 196
Secondary outcome [46] 0 0
Resource Use Assessment by Use of a Self Administered Questionnaire (Received Ambulatory Services) at Treatment Day 84
Timepoint [46] 0 0
Treatment day 84
Secondary outcome [47] 0 0
Resource Use Assessment by Use of a Self Administered Questionnaire (Received Ambulatory Services) at Treatment Day 196
Timepoint [47] 0 0
Treatment day 196
Secondary outcome [48] 0 0
Resource Use Assessment by Use of a Self Administered Questionnaire (no Out-of-pocket Expenses) at Treatment Day 84
Timepoint [48] 0 0
Treatment day 84
Secondary outcome [49] 0 0
Resource Use Assessment by Use of a Self Administered Questionnaire (no Out-of-pocket Expenses) at Treatment Day 196
Timepoint [49] 0 0
Treatment day 196
Secondary outcome [50] 0 0
Resource Use Assessment by Use of a Self Administered Questionnaire (Not Have Any Medical Treatment) at Treatment Day 84
Timepoint [50] 0 0
Treatment day 84
Secondary outcome [51] 0 0
Resource Use Assessment by Use of a Self Administered Questionnaire (Not Have Any Medical Treatment) at Treatment Day 196
Timepoint [51] 0 0
Treatment day 196

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/02/2006
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/05/2008
Sample size
Target
Accrual to date
Final
231
Recruitment in Australia
Recruitment state(s)
NSW,WA
Recruitment hospital [1] 0 0
Private Practice Dr. Ian Fraser - Ashfield
Recruitment hospital [2] 0 0
King Edward Memorial Hospital - Subiaco
Recruitment postcode(s) [1] 0 0
NSW 2131 - Ashfield
Recruitment postcode(s) [2] 0 0
6008 - Subiaco
Recruitment outside Australia
Country [1] 0 0
Czech Republic
State/province [1] 0 0
Ceske Budejovice
Country [2] 0 0
Czech Republic
State/province [2] 0 0
Pardubice
Country [3] 0 0
Czech Republic
State/province [3] 0 0
Pisek
Country [4] 0 0
Czech Republic
State/province [4] 0 0
Praha 7
Country [5] 0 0
Finland
State/province [5] 0 0
Espoo
Country [6] 0 0
Finland
State/province [6] 0 0
Lahti
Country [7] 0 0
Finland
State/province [7] 0 0
Tampere
Country [8] 0 0
Finland
State/province [8] 0 0
Turku
Country [9] 0 0
Germany
State/province [9] 0 0
Baden-Württemberg
Country [10] 0 0
Germany
State/province [10] 0 0
Niedersachsen
Country [11] 0 0
Germany
State/province [11] 0 0
Sachsen
Country [12] 0 0
Germany
State/province [12] 0 0
Berlin
Country [13] 0 0
Hungary
State/province [13] 0 0
Budapest
Country [14] 0 0
Hungary
State/province [14] 0 0
Komarom
Country [15] 0 0
Hungary
State/province [15] 0 0
Miskolc
Country [16] 0 0
Netherlands
State/province [16] 0 0
Enschede
Country [17] 0 0
Netherlands
State/province [17] 0 0
Geleen
Country [18] 0 0
Netherlands
State/province [18] 0 0
Nijmegen
Country [19] 0 0
Poland
State/province [19] 0 0
Bialystok
Country [20] 0 0
Poland
State/province [20] 0 0
Lodz
Country [21] 0 0
Poland
State/province [21] 0 0
Lublin
Country [22] 0 0
Poland
State/province [22] 0 0
Poznan
Country [23] 0 0
Poland
State/province [23] 0 0
Warszawa
Country [24] 0 0
Sweden
State/province [24] 0 0
Lund
Country [25] 0 0
Sweden
State/province [25] 0 0
Stockholm
Country [26] 0 0
Sweden
State/province [26] 0 0
Uppsala
Country [27] 0 0
Ukraine
State/province [27] 0 0
Kiev
Country [28] 0 0
Ukraine
State/province [28] 0 0
Lviv
Country [29] 0 0
United Kingdom
State/province [29] 0 0
Cheshire
Country [30] 0 0
United Kingdom
State/province [30] 0 0
Luton
Country [31] 0 0
United Kingdom
State/province [31] 0 0
Northwood

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Bayer
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT00307801
Trial related presentations / publications
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.
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.
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.
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.
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.
Public notes

Contacts
Principal investigator
Name 0 0
Bayer Study Director
Address 0 0
Bayer
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00307801