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.

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00185380

Enrollment

742

Registered

2005-09-16

Start date

2005-04-30

Completion date

2008-12-31

Last updated

2015-06-10

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Contraception

Brief 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.

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.

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

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

PREVENTION

Masking

SINGLE (Subject)

Eligibility

Sex/Gender

FEMALE

Age

21 Years to 40 Years

Healthy volunteers

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.

Design outcomes

Primary

Measure	Time frame	Description
Pearl Index	Up to 3 years	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.

Secondary

Measure	Time frame	Description
Bleeding Pattern by 90-day Reference Periods - Reference Period 1	day 1 to day 90	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.
Bleeding Pattern by 90-day Reference Periods - Reference Period 2	day 91 to day 180	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.
Number of Subjects With Total or Partial Expulsions	Up to 3 years	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.
Bleeding Pattern by 90-day Reference Periods - Reference Period 4	day 271 to day 360	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.
Bleeding Pattern by 90-day Reference Periods - Reference Period 12	day 991 to day 1080	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.
Bleeding Pattern by 90-day Reference Periods - Reference Period 3	day 181 to day 270	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.

Countries

Finland, Hungary, Norway, Sweden, United Kingdom

Participant flow

Recruitment details

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

Pre-assignment details

Most screening failures were in-/exclusion criteria not met and over-screening. Randomized: 742 women, Treated: 738 women. Full analysis set (FAS), safety analysis set (SAF) and per protocol analysis set (PPS) were identical (738 subjects).

Participants by arm

Arm	Count
LCS12 Levonorgestrel intrauterine contraceptive system (LCS) releasing 12 microg/24h in vitro	239
LCS16 Levonorgestrel intrauterine contraceptive system (LCS) releasing 16 microg/24h in vitro	245
IUS20 (Mirena) Levonorgestrel intrauterine system (IUS) releasing 20 microg/24h in vitro	254
Total	738

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002
Overall Study	Adverse Event	41	43	48
Overall Study	Could not attend visits	2	0	4
Overall Study	Failed insertion	1	1	2
Overall Study	Lost to Follow-up	0	4	3
Overall Study	No need for contraception	3	3	3
Overall Study	personal reason	6	1	1
Overall Study	Planned pregnancy	9	12	12
Overall Study	Pregnancy	1	4	0
Overall Study	Protocol Violation	2	2	1
Overall Study	Withdrawal by Subject	1	2	0

Baseline characteristics

Characteristic	Total	LCS12	LCS16	IUS20 (Mirena)
Age, Continuous	32.1 years STANDARD_DEVIATION 5.31	32.2 years STANDARD_DEVIATION 5.44	32.1 years STANDARD_DEVIATION 5.31	32.0 years STANDARD_DEVIATION 5.21
Sex: Female, Male Female	738 Participants	239 Participants	245 Participants	254 Participants
Sex: Female, Male Male	0 Participants	0 Participants	0 Participants	0 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —
other Total, other adverse events	187 / 239	198 / 245	218 / 254
serious Total, serious adverse events	12 / 239	12 / 245	16 / 254

Outcome results

Primary

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

Population: All randomized women with a successful insertion were analyzed according to the treatment actually received and were included in the FAS, which was the set used for all safety and efficacy analyses. The PPS was identical to the FAS.

Arm	Measure	Value (MEDIAN)
LCS12	Pearl Index	0.17 Number per 100 women years
LCS16	Pearl Index	0.82 Number per 100 women years
IUS20 (Mirena)	Pearl Index	0.00 Number per 100 women years

Secondary

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