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

Multi-center, Open, Randomized, Dose Finding Phase II Study to Investigate Ultra Low Dose Levonorgestrel Contraceptive Intrauterine Systems (LCS) Releasing Different Amounts of Levonorgestrel Compared to MIRENA in Nulliparous and Parous Women in Need of Contraception.

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.

Study Overview

• Status: Completed
• Conditions: Contraception
• Intervention / Treatment: Drug: Levonorgestrel IUS (BAY86-5028, G04209B); Drug: Levonorgestrel IUS (BAY86-5028, G04209C); Drug: Levonorgestrel IUS (Mirena, BAY86-5028)

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.

• Study Type: Interventional
• Enrollment (Actual): 742
• Phase: Phase 2

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 40 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

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

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: LCS12; Levonorgestrel intrauterine contraceptive system (LCS) releasing 12 microg/24h in vitro	Drug: Levonorgestrel IUS (BAY86-5028, G04209B); Levonorgestrel intrauterine contraception system (IUS) releasing 12 microg/24 h in vitro, to be used for three years
EXPERIMENTAL: LCS16; Levonorgestrel intrauterine contraceptive system (LCS) releasing 16 microg/24h in vitro	Drug: Levonorgestrel IUS (BAY86-5028, G04209C); Levonorgestrel intrauterine contraception system (IUS) releasing 16 microg/24 h in vitro, to be used for three years
ACTIVE_COMPARATOR: IUS20 (Mirena); Levonorgestrel intrauterine system (IUS) releasing 20 microg/24h in vitro	Drug: Levonorgestrel IUS (Mirena, BAY86-5028); Levonorgestrel Intrauterine contraception system (IUS) releasing 20 microg/24 h to be used for three years

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to 3 years
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.	day 1 to day 90
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.	day 91 to day 180
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.	day 181 to day 270
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.	day 271 to day 360
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.	day 991 to day 1080

Collaborators and Investigators

• Sponsor: Bayer

Publications and helpful links

General 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.
• 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.

Study record dates

Study Major Dates

• Study Start: April 1, 2005
• Primary Completion (ACTUAL): December 1, 2008
• Study Completion (ACTUAL): December 1, 2008

Study Registration Dates

• First Submitted: September 13, 2005
• First Submitted That Met QC Criteria: September 13, 2005
• First Posted (ESTIMATE): September 16, 2005

Study Record Updates

• Last Update Posted (ESTIMATE): June 10, 2015
• Last Update Submitted That Met QC Criteria: May 15, 2015
• Last Verified: May 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptives, Oral; Contraceptive Agents, Female; Contraceptives, Oral, Synthetic; Levonorgestrel
• Other Study ID Numbers: 91412; 2004-002291-42 (EUDRACT_NUMBER); 308901 (OTHER: Company internal)