Trial Outcomes & Findings for Efficacy and Safety Study for the Treatment of Dysfunctional Uterine Bleeding (NCT NCT00307801)

NCT ID: NCT00307801

Last Updated: 2014-12-30

Results Overview

At least 6, up to 8 criteria to be met in complete response during 90-day period: no bleeding episodes(BE) \>7 days, no \>4 BE, no BE with blood loss (menstrual blood loss, MBL) ≥80 mL, no \>1 BE increase from baseline, no increase from baseline in individual patient's total number of bleeding days and total number of bleeding days not \>24 days. Additionally, for subjects included with prolonged bleeding: decrease between maximum duration during run-in and efficacy ≥2 days excessive bleeding: MBL associated with each episode decreased by ≥50% from average of qualifying episodes during run-in.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 231 participants
• Primary outcome 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
• Results posted on: 2014-12-30

Participant Flow

The date of first subject first visit was 16 Feb 2006. The date of last visit last subject was 27 May 2008.

A total of 575 subjects were screened for inclusion into the study. 344 failed screening. The remaining 231 were randomized.

Participant milestones

Measure	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 Matching placebo to be taken orally daily
Overall Study STARTED	149	82
Overall Study Subjects Received Treatment	145	81
Overall Study Cycle 1, Visit 5, Baseline	145	81
Overall Study Cycle 3, Visit 7, Treatment Day 84	130	71
Overall Study Cycle 7, Treatment Day 196	141	77
Overall Study COMPLETED	117	65
Overall Study NOT COMPLETED	32	17

Reasons for withdrawal

Measure	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 Matching placebo to be taken orally daily
Overall Study Adverse Event	12	4
Overall Study Withdrawal by Subject	9	4
Overall Study Non-compliance, not taken all tablets	1	2
Overall Study Adverse event (AE)/Withdrawal of consent	2	0
Overall Study Decreased Libido (AE at discontinuation)	0	1
Overall Study Wrong Randomization	1	0
Overall Study Lack of Efficacy	0	2
Overall Study Lost to Follow-up, moved abroad	1	1
Overall Study Frustration with e-diary	1	0
Overall Study Protocol Violation	3	2
Overall Study No reason specified	2	0
Overall Study Pregnancy	0	1

Baseline Characteristics

Efficacy and Safety Study for the Treatment of Dysfunctional Uterine Bleeding

Baseline characteristics by cohort

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=149 Participants 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 n=82 Participants Matching placebo to be taken orally daily.	Total n=231 Participants Total of all reporting groups
Age, Continuous	39.5 Years STANDARD_DEVIATION 6.6 • n=5 Participants	38.5 Years STANDARD_DEVIATION 7.5 • n=7 Participants	39.2 Years STANDARD_DEVIATION 6.9 • n=5 Participants
Sex: Female, Male Female	149 Participants n=5 Participants	82 Participants n=7 Participants	231 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Body Mass Index (BMI)	24.5 kg/m² STANDARD_DEVIATION 3.5 • n=5 Participants	25.7 kg/m² STANDARD_DEVIATION 3.0 • n=7 Participants	24.9 kg/m² STANDARD_DEVIATION 3.4 • n=5 Participants
excessive bleeding	136 participants n=5 Participants	76 participants n=7 Participants	212 participants n=5 Participants
prolonged bleeding	20 participants n=5 Participants	10 participants n=7 Participants	30 participants n=5 Participants
frequent bleeding	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants
prolonged and frequent bleeding	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants
prolonged and excessive bleeding	15 participants n=5 Participants	9 participants n=7 Participants	24 participants n=5 Participants
frequent and excessive bleeding	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants
prolonged, frequent and excessive bleeding	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants

PRIMARY outcome

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

Population: Intent-To-Treat (ITT): all randomized subjects with ≥1 of the DUB symptoms in 90-day run-in phase: Prolonged bleeding: ≥2 bleeding episodes, each lasting ≥8 days Frequent bleeding: \>5 bleeding episodes, with minimum of 20 bleeding days overall. Excessive bleeding: ≥2 bleeding episodes each with blood loss volume (=MBL) of ≥80 mL

At least 6, up to 8 criteria to be met in complete response during 90-day period: no bleeding episodes(BE) >7 days, no >4 BE, no BE with blood loss (menstrual blood loss, MBL) ≥80 mL, no >1 BE increase from baseline, no increase from baseline in individual patient's total number of bleeding days and total number of bleeding days not >24 days. Additionally, for subjects included with prolonged bleeding: decrease between maximum duration during run-in and efficacy ≥2 days excessive bleeding: MBL associated with each episode decreased by ≥50% from average of qualifying episodes during run-in.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=149 Participants 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 n=82 Participants Matching placebo to be taken orally daily.
Proportion of Participants With no Dysfunctional Uterine Bleeding (DUB) Symptoms	0.295 Proportion of participants	0.012 Proportion of participants

SECONDARY outcome

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

Population: The ITT population consisted of all randomized subjects with prolonged bleeding: 2 or more bleeding episodes, each lasting 8 or more days

Prolonged bleeding: 2 or more bleeding episodes, each lasting 8 or more days. Cure from prolonged bleeding: no bleeding episodes lasting more than 7 days and the decrease between maximum duration during run-in and maximum duration during the efficacy phase was at least 2 days.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=20 Participants 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 n=10 Participants Matching placebo to be taken orally daily.
Proportion of Participants Cured From Prolonged Bleeding	0.350 Proportion of participants	0.100 Proportion of participants

SECONDARY outcome

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

Population: The ITT population consisted of all randomized subjects who enrolled with excessive bleeding: 2 or more bleeding episodes each with blood loss volume of 80 mL or more in a 90-day run-in period, as assessed by the alkaline hematin method

Excessive bleeding:>=2 bleeding episodes each with blood loss volume (MBL) of >=80 mL in 90-day period, assessed by alkaline hematin method. This spectrophotometrical method measures hemoglobin (Hb) in fixed amount of alkaline solution, taken from pool of solution in which materials (used sanitary protection) to be tested have been macerated for Hb extraction. Cure from excessive bleeding: MBL in each episode <80 mL + blood loss volume associated with each bleeding episode is decrease of ≥50% from average of qualifying bleeding episodes (with blood loss volume ≥80 mL per episode during run-in)

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=136 Participants 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 n=76 Participants Matching placebo to be taken orally daily.
Proportion of Participants Cured From Excessive Bleeding	0.441 Proportion of participants	0.013 Proportion of participants

SECONDARY outcome

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

Population: The ITT population consisted of all randomized subjects who enrolled with frequent bleeding: greater than 5 bleeding episodes, with a minimum of 20 bleeding days overall

Frequent bleeding: greater than 5 bleeding episodes, with a minimum of 20 bleeding days overall. Cure from frequent bleeding: no more than 4 bleeding episodes and the total number of bleeding days did not exceed 24 days and no increase from baseline in an individual patient's total number of bleeding days occurred

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From baseline (visit 5, day 1) up to treatment day 84

Population: ITT, all participants with assessment at day 84 for this outcome measure

According to the investigator's global assessment scale "improved" was defined as being classified as 'very much improved', 'much improved', or 'improved' and "not improved" was defined as being classified as 'no change', 'worse', 'much worse', 'very much worse', or 'not assessed'. Central laboratory data, physical examination, e-diary data, and patient interview were used as sources for the assessment at day 84 compared with admission to study data.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=130 Participants 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 n=71 Participants Matching placebo to be taken orally daily.
Proportion of Participants With Improvement in the Investigator's Global Assessment Scale at Treatment Day 84	0.838 Proportion of participants	0.394 Proportion of participants

SECONDARY outcome

Timeframe: From baseline (visit 5, day 1) up to treatment day 196

Population: ITT, all participants with assessment at day 196 for this outcome measure

According to the investigator's global assessment scale "improved" was defined as being classified as 'very much improved', 'much improved', or 'improved' and "not improved" was defined as being classified as 'no change', 'worse', 'much worse', 'very much worse', or 'not assessed'. Central laboratory data, physical examination, e-diary data, and patient interview were used as sources for the assessment at day 196 compared with admission to study data.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=144 Participants 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 n=81 Participants Matching placebo to be taken orally daily.
Proportion of Participants With Improvement in the Investigator's Global Assessment Scale at Treatment Day 196	0.847 Proportion of participants	0.395 Proportion of participants

SECONDARY outcome

Timeframe: From baseline (visit 5, day 1) up to treatment day 84

Population: ITT, all participants with assessment at day 84 for this outcome measure

According to the patient's global assessment scale "improved" was defined as being classified as 'very much improved', 'much improved', or 'improved' and "not improved" was defined as being classified as 'no change', 'worse', 'much worse', 'very much worse', or 'not assessed'. Patients assessed the overall improvement at day 84 compared with admission to the study condition.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=127 Participants 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 n=68 Participants Matching placebo to be taken orally daily.
Proportion of Participants With Improvement in the Patient's Overall Assessment Scale at Treatment Day 84	0.724 Proportion of participants	0.529 Proportion of participants

SECONDARY outcome

Timeframe: From baseline (visit 5, day 1) up to treatment day 196

Population: ITT, all participants with assessment at day 196 for this outcome measure

According to the patient´s global assessment scale "improved" was defined as being classified as 'very much improved', 'much improved', or 'improved' and "not improved" was defined as being classified as 'no change', 'worse', 'much worse', 'very much worse', or 'not assessed'. Patients assessed the overall improvement at day 196 compared with admission to the study condition.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=136 Participants 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 n=71 Participants Matching placebo to be taken orally daily.
Proportion of Participants With Improvement in the Patient's Overall Assessment Scale at Treatment Day 196	0.779 Proportion of participants	0.451 Proportion of participants

SECONDARY outcome

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

Population: ITT, all participants with assessments at baseline and efficacy phase for this outcome measure

Menstrual blood loss volume as assessed by the alkaline hematin method for the 90 days before treatment (baseline) and for 90 days under treatment. This spectrophotometrical method measures hemoglobin (Hb) in fixed amount of alkaline solution, taken from pool of solution in which materials (used sanitary protection) to be tested have been macerated for Hb extraction. A negative value indicates a reduction in blood loss after treatment.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=108 Participants 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 n=60 Participants Matching placebo to be taken orally daily.
Change From Baseline in Blood Loss Volume for All Participants to the Reference Period of 90 Days Under Treatment	-458.4 ml Standard Deviation 409.6	-93.2 ml Standard Deviation 268.0

SECONDARY outcome

Timeframe: Cycle 1 = 28 days (one cycle)

Population: ITT, all participants with assessments for this outcome measure

Menstrual blood loss volume as assessed by the alkaline hematin method after patients were on treatment for one cycle. This spectrophotometrical method measures hemoglobin (Hb) in fixed amount of alkaline solution, taken from pool of solution in which materials (used sanitary protection) to be tested have been macerated for Hb extraction.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=144 Participants 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 n=81 Participants Matching placebo to be taken orally daily.
Menstrual Blood Loss Volume for All Participants at Cycle 1	175.6 ml Standard Deviation 188.3	194.3 ml Standard Deviation 171.1

SECONDARY outcome

Timeframe: Cycle 3 = 28 days (one cycle)

Population: ITT, all participants with assessments for this outcome measure

Menstrual blood loss volume as assessed by the alkaline hematin method after patients were on treatment for 3 cycles. This spectrophotometrical method measures hemoglobin (Hb) in fixed amount of alkaline solution, taken from pool of solution in which materials (used sanitary protection) to be tested have been macerated for Hb extraction.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=136 Participants 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 n=73 Participants Matching placebo to be taken orally daily.
Menstrual Blood Loss Volume for All Participants at Cycle 3	68.3 ml Standard Deviation 111.6	195.1 ml Standard Deviation 161.8

SECONDARY outcome

Timeframe: Cycle 7 = 28 days (one cycle)

Population: ITT, all participants with assessments for this outcome measure

Menstrual blood loss volume as assessed by the alkaline hematin method after patients were on treatment for 7 cycles. This spectrophotometrical method measures hemoglobin (Hb) in fixed amount of alkaline solution, taken from pool of solution in which materials (used sanitary protection) to be tested have been macerated for Hb extraction.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=111 Participants 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 n=63 Participants Matching placebo to be taken orally daily.
Menstrual Blood Loss Volume for All Participants at Cycle 7	44.6 ml Standard Deviation 70.9	167.2 ml Standard Deviation 112.2

SECONDARY outcome

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

Population: ITT consisted of all randomized subjects enrolled with excessive bleeding. This spectrophotometrical method measures hemoglobin (Hb) in fixed amount of alkaline solution, taken from pool of solution in which materials (used sanitary protection) to be tested have been macerated for Hb extraction.

Blood loss volume as assessed by the alkaline hematin method for participants with excessive bleeding (2 or more bleeding episodes each with blood loss volume of 80 ml or more during the run-in phase) for the 90 days before treatment (ie, run-in phase) and for the 90 days under treatment. A negative value indicates a reduction in blood loss while under treatment compared to before treatment.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=102 Participants 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 n=59 Participants Matching placebo to be taken orally daily.
Change From Baseline in Blood Loss Volume for Participants With Excessive Bleeding to the Reference Period of 90 Days Under Treatment.	-480.6 ml Standard Deviation 410.6	-94.2 ml Standard Deviation 270.2

SECONDARY outcome

Timeframe: Cycle 1 = 28 days (one cycle)

Population: ITT consisted of all randomized subjects enrolled with excessive bleeding: 2 or more bleeding episodes each with blood loss volume of 80 mL or more, as assessed by the alkaline hematin method.

Blood loss volume as assessed by the alkaline hematin method for participants with excessive bleeding (2 or more bleeding episodes each with blood loss volume of 80 ml or more during the run-in phase) after participants were on treatment for one cycle. This spectrophotometrical method measures hemoglobin (Hb) in fixed amount of alkaline solution, taken from pool of solution in which materials (used sanitary protection) to be tested have been macerated for Hb extraction.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=133 Participants 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 n=75 Participants Matching placebo to be taken orally daily.
Menstrual Blood Loss Volume for Participants With Excessive Bleeding at Cycle 1.	207.8 ml Standard Deviation 186.1	238.9 ml Standard Deviation 196.0

SECONDARY outcome

Timeframe: Cycle 3 = 28 days (one cycle)

Population: ITT consisted of all randomized subjects enrolled with excessive bleeding: 2 or more bleeding episodes each with blood loss volume of 80 mL or more, as assessed by the alkaline hematin method.

Blood loss volume as assessed by the alkaline hematin method for participants with excessive bleeding (2 or more bleeding episodes each with blood loss volume of 80 ml or more during the run-in phase) after participants were on treatment for 3 cycles. This spectrophotometrical method measures hemoglobin (Hb) in fixed amount of alkaline solution, taken from pool of solution in which materials (used sanitary protection) to be tested have been macerated for Hb extraction.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=126 Participants 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 n=68 Participants Matching placebo to be taken orally daily.
Menstrual Blood Loss Volume for Participants With Excessive Bleeding at Cycle 3.	72.1 ml Standard Deviation 115.0	188.4 ml Standard Deviation 150.1

SECONDARY outcome

Timeframe: Cycle 7 = 28 days (one cycle)

Population: ITT consisted of all randomized subjects enrolled with excessive bleeding: 2 or more bleeding episodes each with blood loss volume of 80 mL or more, as assessed by the alkaline hematin method.

Blood loss volume as assessed by the alkaline hematin method for participants with excessive bleeding (2 or more bleeding episodes each with blood loss volume of 80 ml or more during the run-in phase) after participants were on treatment for 7 cycles. This spectrophotometrical method measures hemoglobin (Hb) in fixed amount of alkaline solution, taken from pool of solution in which materials (used sanitary protection) to be tested have been macerated for Hb extraction.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=104 Participants 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 n=60 Participants Matching placebo to be taken orally daily.
Menstrual Blood Loss Volume for Participants With Excessive Bleeding at Cycle 7.	46.7 ml Standard Deviation 72.7	168.6 ml Standard Deviation 112.6

SECONDARY outcome

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

Population: ITT, all participants with assessments at baseline and efficacy phase for this outcome measure

A bleeding episode is characterized by the following: • Bleeding for at least 2 days • Bleeding days can be separated by no more than 1 bleeding-free day • An episode stops with 2 consecutive bleeding-free days. The number of episodes was determined for the 90 days before treatment and for the 90 days under treatment. negative value indicates a reduction from baseline in the number of episodes while under treatment.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=108 Participants 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 n=60 Participants Matching placebo to be taken orally daily.
Change From Baseline in Number of Bleeding Episodes to the Reference Period of 90 Days Under Treatment	-0.35 Bleeding episodes Standard Deviation 1.09	-0.38 Bleeding episodes Standard Deviation 0.74

SECONDARY outcome

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

Population: ITT, all participants with assessments at baseline and efficacy phase for this outcome measure

A bleeding day is a day on which sanitary protection is required. The number of bleeding days was determined for the 90 days before treatment (baseline) and for 90 days while under treatment. A negative value indicates a reduction in the number of bleeding days while under treatment compared to baseline.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=108 Participants 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 n=60 Participants Matching placebo to be taken orally daily.
Change From Baseline in Number of Bleeding Days to the Reference Period of 90 Days Under Treatment	-5.13 Bleeding days Standard Deviation 9.72	-3.08 Bleeding days Standard Deviation 7.88

SECONDARY outcome

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

Population: ITT, all participants with assessments for baseline and efficacy phase for this outcome measure

The number of total sanitary protection items used during the 90 days before treatment (baseline) and those used during the 90 days while under treatment was determined. A negative value indicates a reduction in the number of sanitary protection items used while under treatment compared to baseline.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=108 Participants 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 n=60 Participants Matching placebo to be taken orally daily.
Change From Baseline in Number of Sanitary Protection Used at 90 Days of Treatment	-38.4 Sanitary protection products Standard Deviation 30.0	-16.5 Sanitary protection products Standard Deviation 32.2

SECONDARY outcome

Timeframe: Baseline (visit 5) and treatment day 84

Population: ITT, all participants with assessments at baseline and day 84 for this outcome measure

Hemoglobin was measured before treatment and after 84 days under treatment. A positive value indicates an increase in hemoglobin from baseline at treatment day 84.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=129 Participants 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 n=70 Participants Matching placebo to be taken orally daily.
Change From Baseline in Hemoglobin Concentration at Treatment Day 84	0.36 g/dL Standard Deviation 0.90	0.12 g/dL Standard Deviation 0.91

SECONDARY outcome

Timeframe: Baseline (visit 5) and treatment day 196

Population: ITT, all participants with assessments at baseline and day 196 for this outcome measure

Hemoglobin was measured before treatment and after 196 days under treatment. A positive value indicates an increase in hemoglobin from baseline at treatment day 196.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=137 Participants 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 n=76 Participants Matching placebo to be taken orally daily.
Change From Baseline in Hemoglobin Concentration at Treatment Day 196	0.70 g/dL Standard Deviation 1.19	0.06 g/dL Standard Deviation 0.90

SECONDARY outcome

Timeframe: Baseline (visit 5) and treatment day 196

Population: ITT, all participants with assessments at baseline and day 196 for this outcome measure

Hematocrit was measured before treatment and after 196 days under treatment. A positive value indicates an increase in hematocrit from baseline at treatment day 196.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=136 Participants 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 n=76 Participants Matching placebo to be taken orally daily.
Change From Baseline in Hematocrit at Treatment Day 196.	1.63 ng/mL Standard Deviation 4.25	0.08 ng/mL Standard Deviation 3.12

SECONDARY outcome

Timeframe: Baseline (visit 5, day 1) and treatment day 84

Population: ITT, all participants with assessments at baseline and treatment day 84 for this outcome measure

Ferritin was measured before treatment and after 84 days under treatment. A positive value indicates an increase in ferritin from baseline at treatment day 84.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=130 Participants 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 n=71 Participants Matching placebo to be taken orally daily.
Change From Baseline in Ferritin Concentration at Treatment Day 84	2.8 ng/mL Standard Deviation 10.7	0.0 ng/mL Standard Deviation 13.7

SECONDARY outcome

Timeframe: Baseline (visit 5, day 1) and treatment day 196

Population: ITT, all participants with assessments at baseline and treatment day 196 for this outcome measure

Ferritin was measured before treatment and after 196 days under treatment. A positive value indicates an increase in ferritin from baseline at treatment day 196.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=137 Participants 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 n=77 Participants Matching placebo to be taken orally daily.
Change From Baseline in Ferritin Concentration at Treatment Day 196	8.6 ng/mL Standard Deviation 18.5	0.5 ng/mL Standard Deviation 12.4

SECONDARY outcome

Timeframe: Baseline (visit 5, day 1) and treatment day 84

Population: ITT, all participants with assessments at baseline and treatment day 84 for this outcome measure

The PGWBI questionnaire consisted of 22 questions that were answered using a 6-grade Likert scale. The minimum overall score was 22 and the maximum 132. The higher the score, the better the well-being of the patient. The observation phase was the last 4 weeks. The following 6 dimensions were derived from the questionnaire: anxiety, depressed mood, positive well-being, self-control, health, and vitality and the highest possible scores were 30, 18, 24, 18, 18, and 24, respectively.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=121 Participants 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 n=65 Participants Matching placebo to be taken orally daily.
Change From Baseline in Psychological General Well-Being Index (PGWBI) Score at Treatment Day 84.	-1.2 Scores on a scale Standard Deviation 13.6	2.2 Scores on a scale Standard Deviation 12.1

SECONDARY outcome

Timeframe: Baseline (visit 5, day 1) and treatment day 196

Population: ITT, all participants with assessments at baseline and treatment day 196 for this outcome measure

The PGWBI questionnaire consisted of 22 questions that were answered using a 6-grade Likert scale. The minimum overall score was 22 and the maximum 132. The higher the score, the better the well-being of the patient. The observation phase was the last 4 weeks. The following 6 dimensions were derived from the questionnaire: anxiety, depressed mood, positive well-being, self-control, health, and vitality and the highest possible scores were 30, 18, 24, 18, 18, and 24, respectively.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=127 Participants 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 n=68 Participants Matching placebo to be taken orally daily.
Change From Baseline in Psychological General Well-Being Index (PGWBI) Score at Treatment Day 196.	-2.3 Scores on a scale Standard Deviation 13.6	4.6 Scores on a scale Standard Deviation 11.0

SECONDARY outcome

Timeframe: Baseline (visit 5, day 1) and treatment day 84

Population: ITT, all participants with assessments at baseline and treatment day 84 for this outcome measure

The MFSQ was designed to measure aspects of female sexuality and asked about the patients´sexual experience during the last 4 weeks. Higher scores represent higher, more complete, or better integrated levels of female sexual function. Minimum and maximum values are 19 and 133.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=60 Participants 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 n=25 Participants Matching placebo to be taken orally daily.
Change From Baseline in McCoy Female Sexuality Questionnaire (MFSQ) Score at Treatment Day 84	-1.2 Scores on a scale Standard Deviation 9.1	0.4 Scores on a scale Standard Deviation 8.2

SECONDARY outcome

Timeframe: Baseline (visit 5, day 1) and treatment day 196

Population: ITT, all participants with assessments at baseline and treatment day 196 for this outcome measure

The MFSQ was designed to measure aspects of female sexuality and asked about the patients´sexual experience during the last 4 weeks. Higher scores represent higher, more complete, or better integrated levels of female sexual function. Minimum and maximum values are 19 and 133.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=67 Participants 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 n=28 Participants Matching placebo to be taken orally daily.
Change From Baseline in McCoy Female Sexuality Questionnaire (MFSQ) Score at Treatment Day 196	-4.9 Scores on a scale Standard Deviation 11.8	-2.4 Scores on a scale Standard Deviation 12.3

SECONDARY outcome

Timeframe: Baseline (visit 5, day 1) and treatment day 84

Population: ITT, all participants with assessments at baseline and treatment day 84 for this outcome measure

The health state classification of the EQ-5D comprises 5 questions addressing mobility, self-care, usual activity, pain/discomfort, and anxiety/depression. Patients were asked to indicate their current health state by ticking the most appropriate of 3 statements about each of the questions (ie, no problems, some problems, extreme problems). The best possible answers were (1,1,1,1,1), which equals a valuation score of 1.0. The worst possible answers were (3,3,3,3,3), which equals a score of .594.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=123 Participants 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 n=66 Participants Matching placebo to be taken orally daily.
Change From Baseline in EuroQol 5 Dimensional (EQ-5D) Score at Treatment Day 84	-0.0041 Scores on a scale Standard Deviation 0.1209	0.0082 Scores on a scale Standard Deviation 0.1400

SECONDARY outcome

Timeframe: Baseline (visit 5, day 1) and treatment day 196

Population: ITT, all participants with assessments at baseline and treatment day 196 for this outcome measure

The health state classification of the EQ-5D comprises 5 questions addressing mobility, self-care, usual activity, pain/discomfort, and anxiety/depression. Patients were asked to indicate their current health state by ticking the most appropriate of 3 statements about each of the questions (ie, no problems, some problems, extreme problems). The best possible answers were (1,1,1,1,1), which equals a valuation score of 1.0. The worst possible answers were (3,3,3,3,3), which equals a score of .594.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=133 Participants 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 n=70 Participants Matching placebo to be taken orally daily.
Change From Baseline in EuroQol 5 Dimensional (EQ-5D) Score at Treatment Day 196	-0.0191 Scores on a scale Standard Deviation 0.1612	0.0116 Scores on a scale Standard Deviation 0.1642

SECONDARY outcome

Timeframe: Baseline (visit 5, day 1) and treatment day 84

Population: ITT, all participants with assessments at baseline and treatment day 84 for this outcome measure

The visual analogue scale (ie, "thermometer") had endpoints of 100 (best imaginable health state) at the top, and 0 (worst imaginable health state) at the bottom. Patients rated their current health state by drawing a line from the box marked "your own health state today" to the appropriate point on the thermometer scale.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=123 Participants 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 n=66 Participants Matching placebo to be taken orally daily.
Change From Baseline in Visual Analogue Scale (VAS) of the EQ-5D Score at Treatment Day 84.	-1.63 Scores on a scale Standard Deviation 13.31	0.62 Scores on a scale Standard Deviation 12.95

SECONDARY outcome

Timeframe: Baseline (visit 5, day 1) and treatment day 196

Population: ITT, all participants with assessments at baseline and treatment day 196 for this outcome measure

The visual analogue scale (ie, "thermometer") had endpoints of 100 (best imaginable health state) at the top, and 0 (worst imaginable health state) at the bottom. Patients rated their current health state by drawing a line from the box marked "your own health state today" to the appropriate point on the thermometer scale.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=131 Participants 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 n=68 Participants Matching placebo to be taken orally daily.
Change From Baseline in Visual Analogue Scale (VAS) of the EQ-5D Score at Treatment Day 196.	-3.00 Scores on a scale Standard Deviation 15.02	2.69 Scores on a scale Standard Deviation 13.68

SECONDARY outcome

Timeframe: Treatment day 84

Population: ITT, all participants with assessment at treatment day 84 for this outcome measure

The patient was asked if there was any change in her employment status in the last 12 weeks and was asked to specify the number of hours per week. The proportion of participants with such changes are displayed.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=126 Participants 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 n=66 Participants Matching placebo to be taken orally daily.
Resource Use Assessment by Use of a Self Administered Questionnaire （Change in the Employment Status） at Treatment Day 84.	0.095 Proportion of participants	0.152 Proportion of participants

SECONDARY outcome

Timeframe: Treatment day 196

Population: ITT, all participants with assessment at treatment day 196 for this outcome measure

The patient was asked if there was any change in her employment status in the last 12 weeks and was asked to specify the number of hours per week. The proportion of participants with such changes are displayed.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=133 Participants 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 n=69 Participants Matching placebo to be taken orally daily.
Resource Use Assessment by Use of a Self Administered Questionnaire （Change in the Employment Status） at Treatment Day 196.	0.098 Proportion of participants	0.087 Proportion of participants

SECONDARY outcome

Timeframe: Treatment day 84

Population: ITT, all participants with assessment at treatment day 84 for this outcome measure

The patient was asked how many days and hours she missed from work during the past 12 weeks because of her problems associated with her DUB, not including the time missed to participate in this study.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=96 Participants 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 n=52 Participants Matching placebo to be taken orally daily.
Resource Use Assessment by Use of a Self Administered Questionnaire （Days Missed From Work） at Treatment Day 84	0.14 days Standard Deviation 0.776	0.27 days Standard Deviation 1.140

SECONDARY outcome

Timeframe: Treatment day 196

Population: ITT, all participants with assessment at treatment day 196 for this outcome measure

The patient was asked how many days and hours she missed from work during the past 12 weeks because of her problems associated with her DUB, not including the time missed to participate in this study.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=112 Participants 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 n=52 Participants Matching placebo to be taken orally daily.
Resource Use Assessment by Use of a Self Administered Questionnaire （Days Missed From Work） at Treatment Day 196	0.13 days Standard Deviation 0.667	0.52 days Standard Deviation 1.904

SECONDARY outcome

Timeframe: Treatment day 84

Population: ITT, all participants with assessment at treatment day 84 for this outcome measure

The patient was asked to rate on a scale of 0 to 10, how much her DUB affected her productivity while she was working during the past 12 weeks, where 0 represented that her DUB had no effect on her work and 10 represented that her DUB completely prevented her from working.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=114 Participants 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 n=61 Participants Matching placebo to be taken orally daily.
Resource Use Assessment by Use of a Self Administered Questionnaire （Productivity While Working） at Treatment Day 84.	2.0 Scores on a scale Standard Deviation 1.71	3.1 Scores on a scale Standard Deviation 2.49

SECONDARY outcome

Timeframe: Treatment day 196

Population: ITT, all participants with assessment at treatment day 196 for this outcome measure

The patient was asked to rate on a scale of 0 to 10, how much her DUB affected her productivity while she was working during the past 12 weeks, where 0 represented that her DUB had no effect on her work and 10 represented that her DUB completely prevented her from working.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=125 Participants 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 n=60 Participants Matching placebo to be taken orally daily.
Resource Use Assessment by Use of a Self Administered Questionnaire （Productivity While Working） at Treatment Day 196.	1.8 Scores on a scale Standard Deviation 1.77	3.1 Scores on a scale Standard Deviation 2.51

SECONDARY outcome

Timeframe: Treatment day 84

Population: ITT, all participants with assessment at treatment day 84 for this outcome measure

The patient was asked to rate on a scale of 0 to 10, how much her DUB affected her ability to do her regular daily activities, other than work at a job, during the past 12 weeks, where 0 represented that her DUB had no effect on her daily activities and 10 represented that her DUB completely prevented her from doing her daily activities.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=118 Participants 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 n=63 Participants Matching placebo to be taken orally daily.
Resource Use Assessment by Use of a Self Administered Questionnaire （Regular Daily Activities） at Treatment Day 84	2.1 Scores on a scale Standard Deviation 1.75	3.2 Scores on a scale Standard Deviation 2.39

SECONDARY outcome

Timeframe: Treatment day 196

Population: ITT, all participants with assessment at treatment day 196 for this outcome measure

The patient was asked to rate on a scale of 0 to 10, how much her DUB affected her ability to do her regular daily activities, other than work at a job, during the past 12 weeks, where 0 represented that her DUB had no effect on her daily activities and 10 represented that her DUB completely prevented her from doing her daily activities.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=126 Participants 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 n=61 Participants Matching placebo to be taken orally daily.
Resource Use Assessment by Use of a Self Administered Questionnaire （Regular Daily Activities） at Treatment Day 196.	2.0 Scores on a scale Standard Deviation 1.79	3.2 Scores on a scale Standard Deviation 2.46

SECONDARY outcome

Timeframe: Treatment day 84

Population: ITT, all participants with assessment at treatment day 84 for this outcome measure

The patient was asked if she had any unscheduled outpatient visits to a hospital because of her DUB during the past 12 weeks, not including visits that were due to her participation in this study. She was also asked to indicate the number of visits. The proportion of participants with any unscheduled outpatient visits are displayed.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=121 Participants 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 n=66 Participants Matching placebo to be taken orally daily.
Resource Use Assessment by Use of a Self Administered Questionnaire （Unscheduled Outpatient Visit at Hospital） at Treatment Day 84	0.008 Proportion of participants	0.0 Proportion of participants

SECONDARY outcome

Timeframe: Treatment day 196

Population: ITT, all participants with assessment at treatment day 196 for this outcome measure

The patient was asked if she had any unscheduled outpatient visits to a hospital because of her DUB during the past 12 weeks, not including visits that were due to her participation in this study. She was also asked to indicate the number of visits. The proportion of participants with any unscheduled outpatient visits are displayed.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=131 Participants 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 n=68 Participants Matching placebo to be taken orally daily.
Resource Use Assessment by Use of a Self Administered Questionnaire （Unscheduled Outpatient Visit at Hospital） at Treatment Day 196	0.008 Proportion of participants	0.0 Proportion of participants

SECONDARY outcome

Timeframe: Treatment day 84

Population: ITT, all participants with assessment at treatment day 84 for this outcome measure

The patient was asked if she had any unscheduled outpatient visits to a physician (non-hospital medical care) because of her DUB during the past 12 weeks, not including visits that were due to her participation in this study. She was also asked to indicate the number of visits. The proportion of participants with such visits are displayed.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=121 Participants 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 n=65 Participants Matching placebo to be taken orally daily.
Resource Use Assessment by Use of a Self Administered Questionnaire （Unscheduled Outpatient Visit to Physician） at Treatment Day 84	0.058 Proportion of participants	0.031 Proportion of participants

SECONDARY outcome

Timeframe: Treatment day 196

Population: ITT, all participants with assessment at treatment day 196 for this outcome measure

The patient was asked if she had any unscheduled outpatient visits to a physician (non-hospital medical care) because of her DUB during the past 12 weeks, not including visits that were due to her participation in this study. She was also asked to indicate the number of visits. The proportion of participants with such visits are displayed.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=130 Participants 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 n=66 Participants Matching placebo to be taken orally daily.
Resource Use Assessment by Use of a Self Administered Questionnaire （Unscheduled Outpatient Visit to Physician） at Treatment Day 196	0.031 Proportion of participants	0.015 Proportion of participants

SECONDARY outcome

Timeframe: Treatment day 84

Population: ITT, all participants with assessment at treatment day 84 for this outcome measure

The patient was asked if she had any unscheduled procedures (eg, laparoscopy, laboratory tests, ultrasound) because of her DUB during the past 12 weeks. The proportion of participants with such procedures are displayed.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=120 Participants 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 n=65 Participants Matching placebo to be taken orally daily.
Resource Use Assessment by Use of a Self Administered Questionnaire （Additional Unscheduled Procedures） at Treatment Day 84	0.0 Proportion of participants	0.0 Proportion of participants

SECONDARY outcome

Timeframe: Treatment day 196

Population: ITT, all participants with assessment at treatment day 196 for this outcome measure

The patient was asked if she had any unscheduled procedures (eg, laparoscopy, laboratory tests, ultrasound) because of her DUB during the past 12 weeks. The proportion of participants with such procedures are displayed.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=128 Participants 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 n=61 Participants Matching placebo to be taken orally daily.
Resource Use Assessment by Use of a Self Administered Questionnaire （Additional Unscheduled Procedures） at Treatment Day 196	0.0 Proportion of participants	0.0 Proportion of participants

SECONDARY outcome

Timeframe: Treatment day 84

Population: ITT, all participants with assessment at treatment day 84 for this outcome measure

The patient was asked if she received ambulatory services (eg, home help, child care) because of her DUB during the past 12 weeks, and if yes, how many hours per week. The proportion of participants with such services are displayed.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=117 Participants 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 n=65 Participants Matching placebo to be taken orally daily.
Resource Use Assessment by Use of a Self Administered Questionnaire （Received Ambulatory Services） at Treatment Day 84	0.0 Proportion of participants	0.0 Proportion of participants

SECONDARY outcome

Timeframe: Treatment day 196

Population: ITT, all participants with assessment at treatment day 196 for this outcome measure

The patient was asked if she received ambulatory services (eg, home help, child care) because of her DUB during the past 12 weeks, and if yes, how many hours per week. The proportion of participants with such services are displayed.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=130 Participants 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 n=63 Participants Matching placebo to be taken orally daily.
Resource Use Assessment by Use of a Self Administered Questionnaire （Received Ambulatory Services） at Treatment Day 196	0.0 Proportion of participants	0.0 Proportion of participants

SECONDARY outcome

Timeframe: Treatment day 84

Population: ITT, all participants with assessment at treatment day 84 for this outcome measure

The patient was asked to specify her out-of pocket expenses because of her DUB during the past 12 weeks, including over-the-counter medication (the name of the medication, the number of packages, and the cost per package), co-payments due to prescribed medication, and costs to travel to and from medical appointments. The proportion of participants with no out-of pocket expenses are displayed.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=124 Participants 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 n=67 Participants Matching placebo to be taken orally daily.
Resource Use Assessment by Use of a Self Administered Questionnaire （no Out-of-pocket Expenses） at Treatment Day 84	0.855 Proportion of participants	0.881 Proportion of participants

SECONDARY outcome

Timeframe: Treatment day 196

Population: ITT, all participants with assessment at treatment day 196 for this outcome measure

The patient was asked to specify her out-of pocket expenses because of her DUB during the past 12 weeks, including over-the-counter medication (the name of the medication, the number of packages, and the cost per package), co-payments due to prescribed medication, and costs to travel to and from medical appointments. The proportion of participants with no out-of pocket expenses are displayed.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=137 Participants 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 n=66 Participants Matching placebo to be taken orally daily.
Resource Use Assessment by Use of a Self Administered Questionnaire （no Out-of-pocket Expenses） at Treatment Day 196	0.920 Proportion of participants	0.879 Proportion of participants

SECONDARY outcome

Timeframe: Treatment day 84

Population: ITT, all participants with assessment at treatment day 84 for this outcome measure

The patient was asked if she had any medical treatment (eg, prescribed medication, other treatment) because of her DUB during the past 12 weeks, and to specify the cost. The proportion of participants with such treatment are displayed.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=119 Participants 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 n=65 Participants Matching placebo to be taken orally daily.
Resource Use Assessment by Use of a Self Administered Questionnaire （Not Have Any Medical Treatment） at Treatment Day 84	0.966 Proportion of participants	0.954 Proportion of participants

SECONDARY outcome

Timeframe: Treatment day 196

Population: ITT, all participants with assessment at treatment day 196 for this outcome measure

The patient was asked if she had any medical treatment (eg, prescribed medication, other treatment) because of her DUB during the past 12 weeks, and to specify the cost. The proportion of participants with such treatment are displayed.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=130 Participants 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 n=66 Participants Matching placebo to be taken orally daily.
Resource Use Assessment by Use of a Self Administered Questionnaire （Not Have Any Medical Treatment） at Treatment Day 196	0.977 Proportion of participants	0.985 Proportion of participants

POST_HOC outcome

Timeframe: during a time period of 28 days under treatment

Population: Only participants with heavy menstrual bleeding were included in the analysis.

End of Study menstrual blood loss (MBL) ≤ 80 mL and a decrease to a value of ≤ 50% of the Baseline MBL was considered as treatment success.

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=132 Participants 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 n=75 Participants Matching placebo to be taken orally daily.
Proportion of Participants With Successful Treatment End of study MBL <=80 mL	0.758 Proportion of participants	0.133 Proportion of participants
Proportion of Participants With Successful Treatment Decrease MBL >=50% of baseline MBL	0.788 Proportion of participants	0.133 Proportion of participants
Proportion of Participants With Successful Treatment Successful treatment	0.720 Proportion of participants	0.107 Proportion of participants

POST_HOC outcome

Timeframe: during a time period of 28 days under treatment

Population: Only participants with heavy menstrual bleeding were included in the analysis.

The MBL for each cycle includes intermenstrual bleeding in addition to withdrawal bleeding. Baseline MBL was the mean MBL of measured MBL during three cycles in the run-in Phase. One cycle was defined as 28 days. For this analysis, the run-in Phase was defined by the days 1 to 84 (= 3 cycles each of 28 days). End of Study MBL was measured during Cycle 7 of the Treatment Phase (data imputation and Last Observation Carried Forward was applied).

Outcome measures

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=132 Participants 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 n=75 Participants Matching placebo to be taken orally daily.
Change in Absolute Value From Baseline Menstrual Blood Loss (MBL) to end-of Study MBL	-169.94 mL Standard Deviation 225.762	4.628 mL Standard Deviation 165.408

Adverse Events

Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027)

Serious events: 2 serious events

Other events: 44 other events

Deaths: 0 deaths

Placebo

Serious events: 2 serious events

Other events: 21 other events

Deaths: 0 deaths

Serious adverse events

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=145 participants at risk 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 n=81 participants at risk Matching placebo to be taken orally daily
Ear and labyrinth disorders Vertigo	0.00% 0/145	1.2% 1/81 • Number of events 1
Hepatobiliary disorders Cholecystitis chronic	0.69% 1/145 • Number of events 1	0.00% 0/81
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer in situ	0.69% 1/145 • Number of events 1	0.00% 0/81
Pregnancy, puerperium and perinatal conditions Abortion spontaneous	0.00% 0/145	1.2% 1/81 • Number of events 1
Pregnancy, puerperium and perinatal conditions Complication of pregnancy	0.00% 0/145	1.2% 1/81 • Number of events 1
Psychiatric disorders Panic attack	0.00% 0/145	1.2% 1/81 • Number of events 1

Other adverse events

Measure	Estradiol Valerate/Dienogest (Natazia, Qlaira, BAY86-5027) n=145 participants at risk 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 n=81 participants at risk Matching placebo to be taken orally daily
Infections and infestations Nasopharyngitis	8.3% 12/145 • Number of events 15	4.9% 4/81 • Number of events 4
Investigations Serum ferritin decreased	2.1% 3/145 • Number of events 3	7.4% 6/81 • Number of events 6
Nervous system disorders Headache	14.5% 21/145 • Number of events 46	14.8% 12/81 • Number of events 24
Reproductive system and breast disorders Breast pain	5.5% 8/145 • Number of events 10	0.00% 0/81
Reproductive system and breast disorders Metrorrhagia	5.5% 8/145 • Number of events 9	1.2% 1/81 • Number of events 1

Additional Information

Therapeutic Area Head

BAYER

Email: clinical-trials-contact@bayerhealthcare.com

Results disclosure agreements

• Principal investigator is a sponsor employee Schering AG is interested in the publication of the results of every study. As some of the information concerning the study drug and development activities at Schering AG may be of strictly confidential nature, any publication manuscript must first be reviewed by the sponsor before its submission or presentation.
• Publication restrictions are in place

Restriction type: OTHER