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CompletedNCT00185380Updated Jun 10, 2015Results posted

Dose-finding Study for the Ultralow-dose Levonorgestrel Intrauterine Contraceptive System (LCS)

A Phase 2 interventional study of Levonorgestrel IUS (BAY86-5028, G04209B) and Levonorgestrel IUS (BAY86-5028, G04209C) in Contraception, sponsored by Bayer. Completed at 35 sites in 5 countries. Open to female participants aged 21 Years to 40 Years. Per ClinicalTrials.gov, last updated 2015-06-10.

Sponsored by Bayer · Phase 2, Interventional, and Prevention

Phase
Phase 2
Study type
Interventional
Enrollment
742
Allocation
Randomized
Ages
21 Years to 40 Years
Sex
Female
01

Study summary

The purpose of this study is to investigate if drug doses lower than the one released from Mirena® would be as effective for contraception as Mirena®. Subjects participating in the study will be randomly assigned to be inserted with any of the three different intrauterine systems (IUSs). The IUSs are nearly alike except that the amount of hormone released from them is different.

Read the detailed description

The study has previously been posted by Schering AG, Germany. Schering AG, Germany has been renamed to Bayer Schering Pharma AG, Germany.

Bayer Schering Pharma AG, Germany is the sponsor of the trial.

Although the title of the study describes "open", it was in fact single-blinded.

Issues on side effects are addressed in the Adverse Event section.

02

Conditions studied

  • Contraception
03

In context

Lead sponsor

Bayer is the lead sponsor of 1,643 studies on the registry; 57 are open to participants now.

Of its 209 completed or terminated interventional studies of FDA-regulated products, 129 (62%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
21 Years to 40 Years
Sexes eligible
Female
Accepts healthy volunteers
No

Inclusion criteria

  • Women with or without children and good general health and in need of contraception.
  • Regular menstrual cycle without hormonal contraceptives.

Exclusion criteria

Exclusion Criteria:

  • Pregnant or lactating.
  • Last delivery or abortion less than 12 weeks ago.
  • Previous pregnancies outside the womb.
  • Previous pelvic infections.
  • Abnormal bleeding.
  • Abnormal uterine cavity.
  • Climacteric signs.
  • Genital cancer.
  • Liver diseases.
  • Alcoholism or drug abuse.
05

Study design

Phase
Phase 2
Primary purpose
Prevention
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Single (Participant)
Enrollment
742 participants (actual)

Study arms

  • Experimental
    LCS12

    Levonorgestrel intrauterine contraceptive system (LCS) releasing 12 microg/24h in vitro

    Drug: Levonorgestrel IUS (BAY86-5028, G04209B)

  • Experimental
    LCS16

    Levonorgestrel intrauterine contraceptive system (LCS) releasing 16 microg/24h in vitro

    Drug: Levonorgestrel IUS (BAY86-5028, G04209C)

  • Active comparator
    IUS20 (Mirena)

    Levonorgestrel intrauterine system (IUS) releasing 20 microg/24h in vitro

    Drug: Levonorgestrel IUS (Mirena, BAY86-5028)

Interventions

  • DrugLevonorgestrel IUS (BAY86-5028, G04209B)

    Levonorgestrel intrauterine contraception system (IUS) releasing 12 microg/24 h in vitro, to be used for three years

  • DrugLevonorgestrel IUS (BAY86-5028, G04209C)

    Levonorgestrel intrauterine contraception system (IUS) releasing 16 microg/24 h in vitro, to be used for three years

  • DrugLevonorgestrel IUS (Mirena, BAY86-5028)

    Levonorgestrel Intrauterine contraception system (IUS) releasing 20 microg/24 h to be used for three years

06

What researchers measure

Primary outcomes

  1. Pearl Index

    The 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 under risk of getting pregnant.

    Time frame: Up to 3 years

Secondary outcomes

  1. Number of Subjects With Total or Partial Expulsions

    The numbers of subjects with partial or total IUS expulsions (device displaced from its correct position within the uterus) were to be given by treatment.

    Time frame: Up to 3 years

  2. Bleeding Pattern by 90-day Reference Periods - Reference Period 1

    Subjects kept a bleeding diary and recorded any bleeding every day by category: none, spotting, light, normal or heavy. Any missing data were obtained by direct questioning.

    Time frame: day 1 to day 90

  3. Bleeding Pattern by 90-day Reference Periods - Reference Period 2

    Subjects kept a bleeding diary and recorded any bleeding every day by category: none, spotting, light, normal or heavy. Any missing data were obtained by direct questioning.

    Time frame: day 91 to day 180

  4. Bleeding Pattern by 90-day Reference Periods - Reference Period 3

    Subjects kept a bleeding diary and recorded any bleeding every day by category: none, spotting, light, normal or heavy. Any missing data were obtained by direct questioning.

    Time frame: day 181 to day 270

  5. Bleeding Pattern by 90-day Reference Periods - Reference Period 4

    Subjects kept a bleeding diary and recorded any bleeding every day by category: none, spotting, light, normal or heavy. Any missing data were obtained by direct questioning.

    Time frame: day 271 to day 360

  6. Bleeding Pattern by 90-day Reference Periods - Reference Period 12

    Subjects kept a bleeding diary and recorded any bleeding every day by category: none, spotting, light, normal or heavy. Any missing data were obtained by direct questioning.

    Time frame: day 991 to day 1080

07

Results

Posted Mar 10, 2010

Participant flow

Parous or nulliparous women in good general health and in need of contraception were recruited from medical clinics between April and Nov 2005.

Participant flow — Overall Study
MilestoneLCS12LCS16IUS20 (Mirena)
Started240246256
Subjects received treatment239245254
Completed174174182
Not completed667274
Withdrew: Adverse event414348
Withdrew: Lost to follow-up043
Withdrew: Pregnancy140
Withdrew: Protocol violation221
Withdrew: Withdrawal by subject120
Withdrew: Failed insertion112
Withdrew: Planned pregnancy91212
Withdrew: No need for contraception333
Withdrew: Could not attend visits204
Withdrew: Personal reason611

Outcome measures

PrimaryPearl Index

The 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 under risk of getting pregnant.

Time frame:
Up to 3 years
Reported as:
Median · Number per 100 women years
Pearl Index
Number per 100 women yearsLCS12LCS16IUS20 (Mirena)
Pearl Index0.17 (0.00 to 0.93)0.82 (0.27 to 1.92)0.00 (0.00 to 0.59)
SecondaryNumber of Subjects With Total or Partial Expulsions

The numbers of subjects with partial or total IUS expulsions (device displaced from its correct position within the uterus) were to be given by treatment.

Time frame:
Up to 3 years
Reported as:
Number · participants
Number of Subjects With Total or Partial Expulsions
participantsLCS12LCS16IUS20 (Mirena)
total expulsion030
partial expulsion124
SecondaryBleeding Pattern by 90-day Reference Periods - Reference Period 1

Subjects kept a bleeding diary and recorded any bleeding every day by category: none, spotting, light, normal or heavy. Any missing data were obtained by direct questioning.

Time frame:
day 1 to day 90
Reported as:
Mean · days
Bleeding Pattern by 90-day Reference Periods - Reference Period 1
daysLCS12LCS16IUS20 (Mirena)
Number of bleeding days (light, normal or heavy)15.1 ± 10.115.4 ± 12.214.3 ± 12.9
Number of bleeding/spotting days39.9 ± 18.739.2 ± 19.736.6 ± 19.8
Number of spotting only days24.8 ± 14.123.8 ± 12.922.2 ± 13.5
SecondaryBleeding Pattern by 90-day Reference Periods - Reference Period 2

Subjects kept a bleeding diary and recorded any bleeding every day by category: none, spotting, light, normal or heavy. Any missing data were obtained by direct questioning.

Time frame:
day 91 to day 180
Reported as:
Mean · days
Bleeding Pattern by 90-day Reference Periods - Reference Period 2
daysLCS12LCS16IUS20 (Mirena)
Number of bleeding days (light, normal or heavy)8.2 ± 8.07.7 ± 8.07.6 ± 9.1
Number of bleeding/spotting days22.6 ± 14.321.8 ± 14.321.8 ± 16.8
Number of spotting only days14.4 ± 10.314.1 ± 9.814.2 ± 11.5
SecondaryBleeding Pattern by 90-day Reference Periods - Reference Period 3

Subjects kept a bleeding diary and recorded any bleeding every day by category: none, spotting, light, normal or heavy. Any missing data were obtained by direct questioning.

Time frame:
day 181 to day 270
Reported as:
Mean · days
Bleeding Pattern by 90-day Reference Periods - Reference Period 3
daysLCS12LCS16IUS20 (Mirena)
Number of bleeding days (light, normal or heavy)6.4 ± 7.35.4 ± 6.95.3 ± 7.3
Number of bleeding/spotting days18.3 ± 12.916.7 ± 12.616.8 ± 14.2
Number of spotting only days12.0 ± 9.311.3 ± 8.411.5 ± 9.5
SecondaryBleeding Pattern by 90-day Reference Periods - Reference Period 4

Subjects kept a bleeding diary and recorded any bleeding every day by category: none, spotting, light, normal or heavy. Any missing data were obtained by direct questioning.

Time frame:
day 271 to day 360
Reported as:
Mean · days
Bleeding Pattern by 90-day Reference Periods - Reference Period 4
daysLCS12LCS16IUS20 (Mirena)
Number of bleeding days (light, normal or heavy)5.5 ± 6.74.7 ± 6.44.2 ± 6.3
Number of bleeding/spotting days16.7 ± 11.415.0 ± 11.615.2 ± 12.3
Number of spotting only days11.2 ± 8.510.2 ± 7.911.0 ± 9.2
SecondaryBleeding Pattern by 90-day Reference Periods - Reference Period 12

Subjects kept a bleeding diary and recorded any bleeding every day by category: none, spotting, light, normal or heavy. Any missing data were obtained by direct questioning.

Time frame:
day 991 to day 1080
Reported as:
Mean · days
Bleeding Pattern by 90-day Reference Periods - Reference Period 12
daysLCS12LCS16IUS20 (Mirena)
Number of bleeding days (light, normal or heavy)3.6 ± 6.03.0 ± 4.51.9 ± 3.6
Number of bleeding/spotting days12.8 ± 10.710.6 ± 9.38.8 ± 8.6
Number of spotting only days9.2 ± 8.47.7 ± 6.96.9 ± 6.7

Adverse events

Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
LCS12—12/239 (5%)187/239 (78.2%)
LCS16—12/245 (4.9%)198/245 (80.8%)
IUS20 (Mirena)—16/254 (6.3%)218/254 (85.8%)
Most frequent serious events
Showing 10 of 49
Most frequent serious events
EventLCS12LCS16IUS20 (Mirena)
Ovarian cystReproductive system and breast disorders0/2390/2455/254
Ectopic pregnancyPregnancy, puerperium and perinatal conditions1/2392/2450/254
AppendicitisInfections and infestations0/2391/2452/254
GoitreEndocrine disorders1/2390/2450/254
Blindness unilateralEye disorders1/2390/2450/254
Hernia obstructiveGeneral disorders1/2390/2450/254
Clostridium difficile colitisInfections and infestations1/2390/2450/254
PneumoniaInfections and infestations1/2391/2450/254
PyelonephritisInfections and infestations1/2390/2450/254
Post procedural haematomaInjury, poisoning and procedural complications1/2390/2451/254
Most frequent other events
Showing 10 of 25
Most frequent other events
EventLCS12LCS16IUS20 (Mirena)
HeadacheNervous system disorders63/23963/24582/254
AcneSkin and subcutaneous tissue disorders64/23961/24573/254
Breast discomfortReproductive system and breast disorders52/23951/24562/254
Ovarian cystReproductive system and breast disorders21/23924/24560/254
Abdominal distensionGastrointestinal disorders40/23949/24550/254
Mood alteredPsychiatric disorders43/23930/24538/254
Weight increasedInvestigations38/23939/24531/254
Breast painReproductive system and breast disorders20/23935/24527/254
Vulvovaginal candidiasisInfections and infestations23/23930/24521/254
Procedural painInjury, poisoning and procedural complications18/23921/24524/254

Baseline characteristics

Age, Continuous
Age, Continuous(years)LCS12LCS16IUS20 (Mirena)Total
Mean32.2 ± 5.4432.1 ± 5.3132.0 ± 5.2132.1 ± 5.31
Sex: Female, Male
Sex: Female, Male(Participants)LCS12LCS16IUS20 (Mirena)Total
Female239245254738
Male0000
08

Study locations

35 sites
  • Espoo, 02100, Finland
  • Helsinki, 00100, Finland
  • Joensuu, 80100, Finland
  • Jyväskylä, 40620, Finland
  • Kotka, 48100, Finland
  • Kuopio, 70110, Finland
  • Lahti, 15110, Finland
  • Oulu, 90100, Finland
  • Oulu, 90220, Finland
  • Oulu, 90570, Finland
  • Tampere, 33100, Finland
  • Turku, 20100, Finland
  • Turku, 20520, Finland
  • Turku, 20540, Finland
  • Bekescsaba, 5600, Hungary
  • Eger, 3300, Hungary
  • Nyiregyhaza, 4400, Hungary
  • Szeged, 6725, Hungary
  • Drammen, 3001, Norway
  • Elverum, 2403, Norway
  • Kolbotn, 1411, Norway
  • Larvik, 3264, Norway
  • Oslo, 0309, Norway
  • Trondheim, 7014, Norway
  • Göteborg, 411 35, Sweden
  • Huddinge, 14186, Sweden
  • Kalmar, 39231, Sweden
  • Luleå, 972 33, Sweden
  • Norrköping, 602 22, Sweden
  • Stockholm, S-171 76, Sweden
  • Umeå, 90185, Sweden
  • Örebro, 701 46, Sweden
  • Chesterfield, Derbyshire S40 4TF, United Kingdom
  • Sheffield, South Yorkshire S1 2PJ, United Kingdom
  • Chesterfield, S40 1SX, United Kingdom
09

References and documents

Publications

  • Gemzell-Danielsson K, Schellschmidt I, Apter D. A randomized, phase II study describing the efficacy, bleeding profile, and safety of two low-dose levonorgestrel-releasing intrauterine contraceptive systems and Mirena. Fertil Steril. 2012 Mar;97(3):616-22.e1-3. doi: 10.1016/j.fertnstert.2011.12.003. Epub 2012 Jan 4. PubMed 22222193 ↗
  • 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. PubMed 24726226 ↗
10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jun 10, 2015, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT00185380
Lead sponsor
Bayer
Responsible party
Sponsor
First posted
Sep 16, 2005
Start date
Apr 2005
Primary completion
Dec 2008
Completion
Dec 2008
Results posted
Mar 10, 2010
Last update
Jun 10, 2015

Study contacts

Bayer Study Director
study director · Bayer

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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