Levonorgestrel Contraceptive Intrauterine Systems (LCS) Pearl Index Study

• ClinicalTrials.gov Identifier: NCT00528112
• Recruitment Status: Completed
• First Posted: September 12, 2007
• Results First Posted: September 24, 2012
• Last Update Posted: January 25, 2017
• Sponsor: Bayer
• Information provided by (Responsible Party): Bayer

Tracking Information

• First Submitted Date: September 11, 2007
• First Posted Date: September 12, 2007
• Results First Submitted Date: July 11, 2012
• Results First Posted Date: September 24, 2012
• Last Update Posted Date: January 25, 2017
• Study Start Date: August 2007
• Actual Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 1, 2016)

• Pearl Index up to 3 Years [ Time Frame: Up to 3 years ]
  The unadjusted Pearl Index (PI) is defined as the number of pregnancies per 100 woman years. The 3-year PI was obtained by dividing the number of pregnancies that occurred during the first three years of treatment by the time (in 100 women years) that the women were at risk of getting pregnant.
• Pearl Index for LCS16 up to 5 Years [ Time Frame: Up to 5 years ]
  The unadjusted Pearl Index (PI) is defined as the number of pregnancies per 100 woman years.

• Original Primary Outcome Measures (submitted: September 11, 2007): Pregnancy rate [ Time Frame: 3 year treatment ]

Current Secondary Outcome Measures (submitted: December 1, 2016)

• Bleeding Patterns in Days by 90-day Reference Periods - Reference Period 1 [ Time Frame: Day 1 to Day 90 ]
  The occurrence of genital bleeding was to be recorded by study subjects every day in a diary. Bleeding was to be recorded as light, normal or heavy, no bleeding, or spotting only. Spotting was defined as slight genital bleeding relative to the participant's experience.
• Bleeding Patterns in Days by 90-day Reference Periods - Reference Period 2 [ Time Frame: Day 91 to Day 180 ]
  The occurrence of genital bleeding was to be recorded by study subjects every day in a diary. Bleeding was to be recorded as light, normal or heavy, no bleeding, or spotting only. Spotting was defined as slight genital bleeding relative to the participant's experience.
• Bleeding Patterns in Days by 90-day Reference Periods - Reference Period 3 [ Time Frame: Day 181 to Day 270 ]
  The occurrence of genital bleeding was to be recorded by study subjects every day in a diary. Bleeding was to be recorded as light, normal or heavy, no bleeding, or spotting only. Spotting was defined as slight genital bleeding relative to the participant's experience.
• Bleeding Patterns in Days by 90-day Reference Periods - Reference Period 4 [ Time Frame: Day 271 to Day 360 ]
  The occurrence of genital bleeding was to be recorded by study subjects every day in a diary. Bleeding was to be recorded as light, normal or heavy, no bleeding, or spotting only. Spotting was defined as slight genital bleeding relative to the participant's experience.
• Bleeding Patterns in Days by 90-day Reference Periods - Reference Period 12 [ Time Frame: Day 991 to Day 1080 ]
  The occurrence of genital bleeding was to be recorded by study subjects every day in a diary. Bleeding was to be recorded as light, normal or heavy, no bleeding, or spotting only. Spotting was defined as slight genital bleeding relative to the participant's experience.
• Bleeding Patterns in Days by 30-day Reference Periods - Reference Period 1 [ Time Frame: Day 1 to Day 30 ]
  The occurrence of genital bleeding was to be recorded by study subjects every day in a diary. Bleeding was to be recorded as light, normal or heavy, no bleeding, or spotting only. Spotting was defined as slight genital bleeding relative to the participant's experience.
• Bleeding Patterns in Days by 30-day Reference Periods - Reference Period 2 [ Time Frame: Day 31 to Day 60 ]
  The occurrence of genital bleeding was to be recorded by study subjects every day in a diary. Bleeding was to be recorded as light, normal or heavy, no bleeding, or spotting only. Spotting was defined as slight genital bleeding relative to the participant's experience.
• Bleeding Patterns in Days by 30-day Reference Periods - Reference Period 3 [ Time Frame: Day 61 to Day 90 ]
  The occurrence of genital bleeding was to be recorded by study subjects every day in a diary. Bleeding was to be recorded as light, normal or heavy, no bleeding, or spotting only. Spotting was defined as slight genital bleeding relative to the participant's experience.
• Bleeding Patterns in Days by 30-day Reference Periods - Reference Period 4 [ Time Frame: Day 91 to Day 120 ]
  The occurrence of genital bleeding was to be recorded by study subjects every day in a diary. Bleeding was to be recorded as light, normal or heavy, no bleeding, or spotting only. Spotting was defined as slight genital bleeding relative to the participant's experience.
• Bleeding Patterns in Days by 30-day Reference Periods - Reference Period 12 [ Time Frame: Day 331 to Day 360 ]
  The occurrence of genital bleeding was to be recorded by study subjects every day in a diary. Bleeding was to be recorded as light, normal or heavy, no bleeding, or spotting only. Spotting was defined as slight genital bleeding relative to the participant's experience.
• Number of Participants With/Without Ovulation - Year 1 [ Time Frame: For six weeks in the second half of Year 1 ]
  Serum concentrations of progesterone were analyzed. All subjects with progesterone values equal to or greater than 2.5 ng/ml were assessed as having an ovulation.
• Number of Participants With/Without Ovulation - Year 2 [ Time Frame: For six weeks in the second half of Year 2 ]
  Serum concentrations of progesterone were analyzed. All subjects with progesterone values equal to or greater than 2.5 ng/ml were assessed as having an ovulation.
• Number of Participants With/Without Ovulation - Year 3 [ Time Frame: For six weeks in the second half of Year 3 ]
  Serum concentrations of progesterone were analyzed. All subjects with progesterone values equal to or greater than 2.5 ng/ml were assessed as having an ovulation.
• Average Total Cervical Score - Year 1 [ Time Frame: For six weeks in the second half of Year 1 ]
  Cervical mucus samples were analyzed to determine any effects of progesterone on the cervical mucus. Range of score: 0 (high contraceptive efficacy) to 12 (low contraceptive efficacy)
• Average Total Cervical Score - Year 2 [ Time Frame: For six weeks in the second half of Year 2 ]
  Cervical mucus samples were analyzed to determine any effects of progesterone on the cervical mucus. Range of score: 0 (high contraceptive efficacy) to 12 (low contraceptive efficacy)
• Average Total Cervical Score - Year 3 [ Time Frame: For six weeks in the second half of Year 3 ]
  Cervical mucus samples were analyzed to determine any effects of progesterone on the cervical mucus. Range of score: 0 (high contraceptive efficacy) to 12 (low contraceptive efficacy)
• Classification of Endometrium - Year 1 [ Time Frame: At Year 1 ]
  The histological evaluation of the endometrium examined the effects of progesterone on the endometrium
• Classification of Endometrium - Year 2 [ Time Frame: At Year 2 ]
  The histological evaluation of the endometrium examined the effects of progesterone on the endometrium
• Classification of Endometrium - Year 3 / End of Study [ Time Frame: At Year 3 / End of study ]
  The histological evaluation of the endometrium examined the effects of progesterone on the endometrium
• Degree of User Overall Satisfaction With Study Treatment [ Time Frame: At the end of study/Year 3 ]
  Overall user satisfaction was assessed by a questionnaire given to participants at the end of the study. The questionnaire was only given to participants whose end-of-study visit occurred after implementation of Protocol Amendment 3.
• Number of Participants With Partial or Total Expulsion [ Time Frame: Up to 3 years ]
  If LCS was displaced, but still in the cervical canal, it was assessed as being partially displaced. If LCS was expelled from the uterus, it was assessed as a total expulsion.
• Bleeding Patterns in Days by 90-day Reference Periods - Reference Period 13 [ Time Frame: Day 1081 to Day 1170 ]
  The occurrence of genital bleeding was to be recorded by study subjects every day in a diary. Bleeding was to be recorded as light, normal or heavy, no bleeding, or spotting only. Spotting was defined as slight genital bleeding relative to the participant's experience.
• Bleeding Patterns in Days by 90-day Reference Periods - Reference Period 20 [ Time Frame: Day 1711 to Day 1800 ]
  The occurrence of genital bleeding was to be recorded by study subjects every day in a diary. Bleeding was to be recorded as light, normal or heavy, no bleeding, or spotting only. Spotting was defined as slight genital bleeding relative to the participant's experience.
• Degree of User Overall Satisfaction With Study Treatment up to 5 Years [ Time Frame: At the end of study/Year 5 ]
  Overall user satisfaction was assessed by a questionnaire given to participants at the end of the study. The questionnaire was only given to participants whose end-of-study visit occurred after implementation of Protocol Amendment 3.
• Number of Participants With Partial or Total Expulsion up to 5 Years [ Time Frame: Up to 5 years ]
  If LCS was displaced, but still in the cervical canal, it was assessed as being partially displaced. If LCS was expelled from the uterus, it was assessed as a total expulsion.

• Original Secondary Outcome Measures (submitted: September 11, 2007): Drop out -rate, expulsion of the IUS, Vaginal bleeding patterns, dysmenorrhea [ Time Frame: 3 year treatment ]
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Levonorgestrel Contraceptive Intrauterine Systems (LCS) Pearl Index Study
• Official Title: Multi-Center, Open-Label, Randomized Study to Assess the Safety and Contraceptive Efficacy of Two Doses ( in vitro12 µg/24h and 16 µg/24h) of the Ultra Low Dose Levonorgestrel Contraceptive Intrauterine Systems (LCS) for a Maximum of 3 Years in Women 18 to 35 Years of Age and an Extension Phase of the 16µg/24h Dose Group (LCS16 Arm) up to 5 Years
• Brief Summary: This is a study on a new low dose levonorgestrel contraceptive intrauterine systems (LCS). The purpose of the study is to investigate which of the 2 administered doses is the lowest effective intrauterine dose of Levonorgestrel (LNG) administered via the LCS for contraception during 3 years. The study was amended: the LCS16 arm will be extended up to 5 years
• Detailed Description: Drop out-rate will be covered in Participant flow section.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Prevention
• Condition: Contraception

Intervention

• Drug: LCS12
  Intrauterine system (IUS) with Levonorgestrel, in vitro releasing rate 12 microg/24 h
• Drug: LCS16
  Intrauterine system (IUS) with Levonorgestrel, in vitro releasing rate 16 microg/24 h

Study Arms

• Experimental: LCS12
  Intrauterine levonorgestrel contraceptive system (LCS), releasing levonorgestrel (LNG) 12 microg/24 h in vitro
  Intervention: Drug: LCS12
• Experimental: LCS16
  Intrauterine levonorgestrel contraceptive system (LCS), releasing levonorgestrel (LNG) 16 microg/24 h in vitro
  Intervention: Drug: LCS16

Publications *

• Nahum GG, Kaunitz AM, Rosen K, Schmelter T, Lynen R. Ovarian cysts: presence and persistence with use of a 13.5mg levonorgestrel-releasing intrauterine system. Contraception. 2015 May;91(5):412-7. doi: 10.1016/j.contraception.2015.01.021. Epub 2015 Feb 7.
• Apter D, Gemzell-Danielsson K, Hauck B, Rosen K, Zurth C. Pharmacokinetics of two low-dose levonorgestrel-releasing intrauterine systems and effects on ovulation rate and cervical function: pooled analyses of phase II and III studies. Fertil Steril. 2014 Jun;101(6):1656-62.e1-4. doi: 10.1016/j.fertnstert.2014.03.004. Epub 2014 Apr 14.
• Nelson A, Apter D, Hauck B, Schmelter T, Rybowski S, Rosen K, Gemzell-Danielsson K. Two low-dose levonorgestrel intrauterine contraceptive systems: a randomized controlled trial. Obstet Gynecol. 2013 Dec;122(6):1205-13. doi: 10.1097/AOG.0000000000000019. Erratum in: Obstet Gynecol. 2014 May;123(5):1109.
• Gemzell-Danielsson K, Apter D, Hauck B, Schmelter T, Rybowski S, Rosen K, Nelson A. The Effect of Age, Parity and Body Mass Index on the Efficacy, Safety, Placement and User Satisfaction Associated With Two Low-Dose Levonorgestrel Intrauterine Contraceptive Systems: Subgroup Analyses of Data From a Phase III Trial. PLoS One. 2015 Sep 17;10(9):e0135309. doi: 10.1371/journal.pone.0135309. eCollection 2015.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: June 29, 2011): 2885
• Original Estimated Enrollment (submitted: September 11, 2007): 2820
• Actual Study Completion Date: June 2013
• Actual Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Age between 18 and 35 years (inclusive), in good general health and requesting contraception.
• Has regular menstrual cycles (length of cycle 21-35 days) (i.e., endogenous cyclicity without hormonal contraceptive use).

Exclusion Criteria:

• Known or suspected pregnancy or is lactating.
• History of ectopic pregnancies.
• Any genital infection (until successfully treated).
• Abnormal uterine bleeding of unknown origin.

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years to 35 Years (Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Canada, Chile, Finland, France, Hungary, Mexico, Netherlands, Norway, Sweden, United States
• Removed Location Countries: Brazil, Russian Federation

Administrative Information

• NCT Number: NCT00528112
• Other Study ID Numbers: 91665; 310442 ( Other Identifier: Company internal ); G04209F ( Other Identifier: Company internal ); G04209G ( Other Identifier: Company internal ); 2007-000420-40 ( EudraCT Number )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Bayer
• Study Sponsor: Bayer
• Collaborators: Not Provided

Investigators

• Study Director: Bayer Study Director; Bayer

• PRS Account: Bayer
• Verification Date: December 2016