Study on Safety and Efficacy of an Oral Contraceptive in Long Cycles

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bayer
ClinicalTrials.gov Identifier:
NCT00266032
First received: December 14, 2005
Last updated: February 19, 2014
Last verified: February 2014
Results First Received: October 28, 2009  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Prevention
Condition: Contraception
Interventions: Drug: Flexible (extended) treatment of EE20/DRSP (YAZ, BAY86-5300)
Drug: Fixed extended treatment of EE20/DRSP (YAZ, BAY86-5300)
Drug: Standard 24+4 treatment of EE20/DRSP (YAZ, BAY86-5300)

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Randomization scheme in the subgroups was 1:1:1 for the 2 centers performing biopsies and measurements of Bone Mineral Density and metabolic parameters (82 subjects per treatment group). The remaining subjects were randomized according to the ratio 4:1:1.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
146 subjects failed screening, 96 of these 146 (65.8%) because inclusion or exclusion criteria were not met, 21 (14.4%) due to withdrawal of consent, 17 (11.6%) because of “other” reasons, 11 (7.5%) due to protocol deviations, 1 (0.7%) was lost to follow-up. 32 randomized subjects never took medication.

Reporting Groups
  Description
Flexible (Extended) Treatment of EE20/DRSP (YAZ, BAY86-5300) 3 cycles of treatment, each cycle comprising 120 days intended treatment with one tablet daily of 20µg ethinyl estradiol as betadex clathrate (EE20) plus 3 mg drospirenone (DRSP) followed by a 4 day tablet-free interval. If 3 consecutive days of bleeding and/or spotting occurred during the 120 day treatment period, a 4 day tablet free interval was advised. The minimum period between 2 tablet free intervals was 24 days. After each 4 day tablet free interval, a new 120 day intended treatment period was to be restarted, resulting in a minimum of 3 and maximum of 13 withdrawal bleeding episodes during one year of treatment.
Fixed Extended Treatment of EE20/DRSP (YAZ, BAY86-5300) 3 cycles of treatment, each cycle comprising 120 days uninterrupted treatment with one tablet daily of 20µg ethinyl estradiol as betadex clathrate plus 3 mg drospirenone followed by a 4 day tablet free interval, 3 withdrawal bleeding episodes during one year of treatment were expected.
Standard 24+4 Treatment of EE20/DRSP (YAZ, BAY86-5300) 13 cycles of treatment, each cycle comprising an intake of one tablet daily with 24 days of active tablets (20µg ethinyl estradiol as betadex clathrate plus 3 mg drospirenone) followed by 4 days of placebo tablets, 13 withdrawal bleeding episodes during one year of treatment were expected.

Participant Flow for 2 periods

Period 1:   Treatment
    Flexible (Extended) Treatment of EE20/DRSP (YAZ, BAY86-5300)     Fixed Extended Treatment of EE20/DRSP (YAZ, BAY86-5300)     Standard 24+4 Treatment of EE20/DRSP (YAZ, BAY86-5300)  
STARTED     691 [1]   236 [1]   239 [1]
Patients Treated     684     221     229  
Patients Treated and in FAS     642 [2]   209 [2]   216 [2]
COMPLETED     580 [3]   172 [3]   192 [3]
NOT COMPLETED     111     64     47  
Adverse Event                 42                 26                 10  
Lost to Follow-up                 19                 4                 2  
Pregnancy                 3                 2                 2  
Protocol Violation                 6                 14                 13  
Withdrawal by Subject                 28                 13                 12  
patient moved/wish for pregnancy/no need                 13                 5                 8  
[1] all randomized subjects, baseline data for full analysis set (FAS) only
[2] FAS
[3] not all entered period 2 (open-label safety extension)

Period 2:   Open-label Safety Extension
    Flexible (Extended) Treatment of EE20/DRSP (YAZ, BAY86-5300)     Fixed Extended Treatment of EE20/DRSP (YAZ, BAY86-5300)     Standard 24+4 Treatment of EE20/DRSP (YAZ, BAY86-5300)  
STARTED     489 [1]   129 [2]   165 [3]
COMPLETED     448     115     140  
NOT COMPLETED     41     14     25  
Adverse Event                 5                 0                 4  
Lost to Follow-up                 2                 5                 4  
Pregnancy                 4                 1                 2  
Protocol Violation                 1                 3                 2  
Withdrawal by Subject                 19                 3                 12  
patient moved/wish for pregnancy/no need                 10                 2                 1  
[1] treatment for subjects of all 3 treatment groups in 2nd period, except for 28 in subgroups
[2] 7 subjects continued their treatment in second period (safety extension)
[3] 21 subjects continued their treatment in second period (safety extension)



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Flexible (Extended) Treatment of EE20/DRSP (YAZ, BAY86-5300) 3 cycles of treatment, each cycle comprising 120 days intended treatment with one tablet daily of 20µg ethinyl estradiol as betadex clathrate (EE20) plus 3 mg drospirenone (DRSP) followed by a 4 day tablet-free interval. If 3 consecutive days of bleeding and/or spotting occurred during the 120 day treatment period, a 4 day tablet free interval was advised. The minimum period between 2 tablet free intervals was 24 days. After each 4 day tablet free interval, a new 120 day intended treatment period was to be restarted, resulting in a minimum of 3 and maximum of 13 withdrawal bleeding episodes during one year of treatment.
Fixed Extended Treatment of EE20/DRSP (YAZ, BAY86-5300) 3 cycles of treatment, each cycle comprising 120 days uninterrupted treatment with one tablet daily of 20µg ethinyl estradiol as betadex clathrate plus 3 mg drospirenone followed by a 4 day tablet free interval, 3 withdrawal bleeding episodes during one year of treatment were expected.
Standard 24+4 Treatment of EE20/DRSP (YAZ, BAY86-5300) 13 cycles of treatment, each cycle comprising an intake of one tablet daily with 24 days of active tablets (20µg ethinyl estradiol as betadex clathrate plus 3 mg drospirenone) followed by 4 days of placebo tablets, 13 withdrawal bleeding episodes during one year of treatment were expected.
Total Total of all reporting groups

Baseline Measures
    Flexible (Extended) Treatment of EE20/DRSP (YAZ, BAY86-5300)     Fixed Extended Treatment of EE20/DRSP (YAZ, BAY86-5300)     Standard 24+4 Treatment of EE20/DRSP (YAZ, BAY86-5300)     Total  
Number of Participants  
[units: participants]
  642     209     216     1067  
Age [1]
[units: years]
Mean ( Full Range )
  24.8  
  ( 18 to 35 )  
  24.8  
  ( 18 to 35 )  
  24.3  
  ( 18 to 35 )  
  24.7  
  ( 18 to 35 )  
Gender [1]
[units: participants]
       
Female     642     209     216     1067  
Male     0     0     0     0  
Body-Mass-Index (BMI) [2]
[units: kg/m²]
Mean ( Full Range )
  22.541  
  ( 17.95 to 30.50 )  
  22.541  
  ( 18.00 to 29.70 )  
  22.566  
  ( 17.90 to 29.80 )  
  22.546  
  ( 17.90 to 30.50 )  
[1] Number of Participants analyzed for baseline was Full Analysis Set (FAS=safety set)
[2]

Body mass index was calculated with body weight and height measured at screening (BMI = body weight in kg²/ body height in m³) and had to be 18 Years to 35 Years old (smokers ≤ 30 Years old) at inclusion.

Number of Participants analyzed for baseline was Full Analysis Set (FAS=safety set).




  Outcome Measures
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1.  Primary:   Number of Days With Bleeding Including Spotting   [ Time Frame: up to 1 year ]

2.  Primary:   Number of Unintended Pregnancies in Yaz Flexible Arm   [ Time Frame: up to 2 years ]

3.  Primary:   Pearl Index   [ Time Frame: Up to 2 years ]

4.  Primary:   Number of Unintended Pregnancies Due to Method Failure   [ Time Frame: Up to 2 years ]

5.  Primary:   Adjusted Pearl Index   [ Time Frame: Up to 2 years ]

6.  Secondary:   Number of Days With Bleeding Excluding Spotting   [ Time Frame: up to 1 year ]

7.  Secondary:   Number of Bleeding Days During One Year of Treatment in Subjects With at Least 248 Days of Exposure Normalized to 372 Days   [ Time Frame: up to 1 year ]

8.  Secondary:   Number of Bleeding / Spotting Days by 90-day Reference Period   [ Time Frame: up to 1 year ]

9.  Secondary:   Number of Bleeding / Spotting Episodes in 90 Day Reference Period   [ Time Frame: Up to one year ]

10.  Secondary:   Days With Scheduled Versus Unscheduled Bleeding   [ Time Frame: Up to one year ]

11.  Post-Hoc:   Number of Unintended Pregnancies Including Pregnancies Occuring Within 14 Days After End of Study Medication.   [ Time Frame: Up to one year ]

12.  Post-Hoc:   Pearl Index (FDA Criteria)   [ Time Frame: Up to one year ]


  Serious Adverse Events


  Other Adverse Events


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Limitations and Caveats
Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
Data for center no. 1148 was included in “all randomized” set of subjects, but not in FAS, as during medical monitoring of laboratory data a suspicion of potential misconduct was found. An audit was made, but the suspicion could not be resolved.  


Results Point of Contact:  
Name/Title: Therapeutic Area Head
Organization: BAYER
e-mail: clinical-trials-contact@bayerhealthcare.com


Publications of Results:

Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT00266032     History of Changes
Other Study ID Numbers: 91450, 2005-002125-32, 308683
Study First Received: December 14, 2005
Results First Received: October 28, 2009
Last Updated: February 19, 2014
Health Authority: Canada: Health Canada
Germany: Federal Institute for Drugs and Medical Devices
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)