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

• Sponsor: Bayer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00185380
• Collaborator: (none)
• Enrollment: 742
• Locations: 35
• Arms: 3
• Duration (Months): 44
• Patients Per Site: 21.2
• Patients Per Site Per Month: 0.5

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Contraception	Drug: Levonorgestrel IUS (BAY86-5028, G04209B); Drug: Levonorgestrel IUS (BAY86-5028, G04209C); Drug: Levonorgestrel IUS (Mirena, BAY86-5028)	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 742 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Prevention
• Official Title: 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.
• Study Start Date: Apr 1, 2005
• Actual Primary Completion Date: Dec 1, 2008
• Actual Study Completion Date: Dec 1, 2008

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

6. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years to 40 Years
• Sexes Eligible for Study: 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:

• 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Espoo		Finland	02100
2		Helsinki		Finland	00100
3		Joensuu		Finland	80100
4		Jyväskylä		Finland	40620
5		Kotka		Finland	48100
6		Kuopio		Finland	70110
7		Lahti		Finland	15110
8		Oulu		Finland	90100
9		Oulu		Finland	90220
10		Oulu		Finland	90570
11		Tampere		Finland	33100
12		Turku		Finland	20100
13		Turku		Finland	20520
14		Turku		Finland	20540
15		Bekescsaba		Hungary	5600
16		Eger		Hungary	3300
17		Nyiregyhaza		Hungary	4400
18		Szeged		Hungary	6725
19		Drammen		Norway	3001
20		Elverum		Norway	2403
21		Kolbotn		Norway	1411
22		Larvik		Norway	3264
23		Oslo		Norway	0309
24		Trondheim		Norway	7014
25		Göteborg		Sweden	411 35
26		Huddinge		Sweden	14186
27		Kalmar		Sweden	39231
28		Luleå		Sweden	972 33
29		Norrköping		Sweden	602 22
30		Stockholm		Sweden	S-171 76
31		Umeå		Sweden	90185
32		Örebro		Sweden	701 46
33		Chesterfield	Derbyshire	United Kingdom	S40 4TF
34		Sheffield	South Yorkshire	United Kingdom	S1 2PJ
35		Chesterfield		United Kingdom	S40 1SX

Sponsors and Collaborators

• Bayer

Investigators

• Study Director: Bayer Study Director, Bayer

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Bayer
• ClinicalTrials.gov Identifier: NCT00185380
• Other Study ID Numbers: 91412; 2004-002291-42; 308901
• First Posted: Sep 16, 2005
• Last Update Posted: Jun 10, 2015
• Last Verified: May 1, 2015

• Additional relevant MeSH terms: Levonorgestrel

Study Results

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 Detail	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).

Arm/Group Title	LCS12	LCS16	IUS20 (Mirena)
Arm/Group Description	Levonorgestrel intrauterine contraceptive system (LCS) releasing 12 microg/24h in vitro	Levonorgestrel intrauterine contraceptive system (LCS) releasing 16 microg/24h in vitro	Levonorgestrel intrauterine system (IUS) releasing 20 microg/24h in vitro
Period Title: Overall Study
STARTED	240	246	256
Subjects Received Treatment	239	245	254
COMPLETED	174	174	182
NOT COMPLETED	66	72	74

Baseline Characteristics

Arm/Group Title	LCS12	LCS16	IUS20 (Mirena)	Total
Arm/Group Description	Levonorgestrel intrauterine contraceptive system (LCS) releasing 12 microg/24h in vitro	Levonorgestrel intrauterine contraceptive system (LCS) releasing 16 microg/24h in vitro	Levonorgestrel intrauterine system (IUS) releasing 20 microg/24h in vitro	Total of all reporting groups
Overall Participants	239	245	254	738
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	32.2 (5.44)	32.1 (5.31)	32.0 (5.21)	32.1 (5.31)
Sex: Female, Male (Count of Participants)
Female	239 100%	245 100%	254 100%	738 100%
Male	0 0%	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Pearl Index
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	LCS12	LCS16	IUS20 (Mirena)
Arm/Group Description	Levonorgestrel intrauterine contraceptive system (LCS) releasing 12 microg/24h in vitro	Levonorgestrel intrauterine contraceptive system (LCS) releasing 16 microg/24h in vitro	Levonorgestrel intrauterine system (IUS) releasing 20 microg/24h in vitro
Measure Participants	239	245	254
Median (95% Confidence Interval) [Number per 100 women years]	0.17	0.82	0.00

2. Secondary Outcome

Title	Number of Subjects With Total or Partial Expulsions
Description	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

Outcome Measure Data

Analysis Population Description

The analysis was performed on the FAS (all subjects who had an IUS inserted).

Arm/Group Title	LCS12	LCS16	IUS20 (Mirena)
Arm/Group Description	Levonorgestrel intrauterine contraceptive system (LCS) releasing 12 microg/24h in vitro	Levonorgestrel intrauterine contraceptive system (LCS) releasing 16 microg/24h in vitro	Levonorgestrel intrauterine system (IUS) releasing 20 microg/24h in vitro
Measure Participants	239	245	254
total expulsion	0 0%	3 1.2%	0 0%
partial expulsion	1 0.4%	2 0.8%	4 1.6%

3. Secondary Outcome

Title	Bleeding Pattern by 90-day Reference Periods - Reference Period 1
Description	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

Outcome Measure Data

Analysis Population Description

The analysis was performed on the FAS (all subjects with an insertion) and included subjects with bleeding or spotting or both.

Arm/Group Title	LCS12	LCS16	IUS20 (Mirena)
Arm/Group Description	Levonorgestrel intrauterine contraceptive system (LCS) releasing 12 microg/24h in vitro	Levonorgestrel intrauterine contraceptive system (LCS) releasing 16 microg/24h in vitro	Levonorgestrel intrauterine system (IUS) releasing 20 microg/24h in vitro
Measure Participants	228	241	244
Number of bleeding days (light, normal or heavy)	15.1 (10.1)	15.4 (12.2)	14.3 (12.9)
Number of bleeding/spotting days	39.9 (18.7)	39.2 (19.7)	36.6 (19.8)
Number of spotting only days	24.8 (14.1)	23.8 (12.9)	22.2 (13.5)

4. Secondary Outcome

Title	Bleeding Pattern by 90-day Reference Periods - Reference Period 2
Description	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

Outcome Measure Data

Analysis Population Description

The analysis was performed on the FAS (all subjects with an insertion) and included subjects with bleeding or spotting or both.

Arm/Group Title	LCS12	LCS16	IUS20 (Mirena)
Arm/Group Description	Levonorgestrel intrauterine contraceptive system (LCS) releasing 12 microg/24h in vitro	Levonorgestrel intrauterine contraceptive system (LCS) releasing 16 microg/24h in vitro	Levonorgestrel intrauterine system (IUS) releasing 20 microg/24h in vitro
Measure Participants	225	230	239
Number of bleeding days (light, normal or heavy)	8.2 (8.0)	7.7 (8.0)	7.6 (9.1)
Number of bleeding/spotting days	22.6 (14.3)	21.8 (14.3)	21.8 (16.8)
Number of spotting only days	14.4 (10.3)	14.1 (9.8)	14.2 (11.5)

5. Secondary Outcome

Title	Bleeding Pattern by 90-day Reference Periods - Reference Period 3
Description	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

Outcome Measure Data

Analysis Population Description

The analysis was performed on the FAS (all subjects with an insertion) and included subjects with bleeding or spotting or both.

Arm/Group Title	LCS12	LCS16	IUS20 (Mirena)
Arm/Group Description	Levonorgestrel intrauterine contraceptive system (LCS) releasing 12 microg/24h in vitro	Levonorgestrel intrauterine contraceptive system (LCS) releasing 16 microg/24h in vitro	Levonorgestrel intrauterine system (IUS) releasing 20 microg/24h in vitro
Measure Participants	220	224	230
Number of bleeding days (light, normal or heavy)	6.4 (7.3)	5.4 (6.9)	5.3 (7.3)
Number of bleeding/spotting days	18.3 (12.9)	16.7 (12.6)	16.8 (14.2)
Number of spotting only days	12.0 (9.3)	11.3 (8.4)	11.5 (9.5)

6. Secondary Outcome

Title	Bleeding Pattern by 90-day Reference Periods - Reference Period 4
Description	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

Outcome Measure Data

Analysis Population Description

The analysis was performed on the FAS (all subjects with an insertion) and included subjects with bleeding or spotting or both.

Arm/Group Title	LCS12	LCS16	IUS20 (Mirena)
Arm/Group Description	Levonorgestrel intrauterine contraceptive system (LCS) releasing 12 microg/24h in vitro	Levonorgestrel intrauterine contraceptive system (LCS) releasing 16 microg/24h in vitro	Levonorgestrel intrauterine system (IUS) releasing 20 microg/24h in vitro
Measure Participants	217	218	225
Number of bleeding days (light, normal or heavy)	5.5 (6.7)	4.7 (6.4)	4.2 (6.3)
Number of bleeding/spotting days	16.7 (11.4)	15.0 (11.6)	15.2 (12.3)
Number of spotting only days	11.2 (8.5)	10.2 (7.9)	11.0 (9.2)

7. Secondary Outcome

Title	Bleeding Pattern by 90-day Reference Periods - Reference Period 12
Description	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

Outcome Measure Data

Analysis Population Description

The analysis was performed on the FAS (all subjects with an insertion) and included subjects with bleeding or spotting or both.

Arm/Group Title	LCS12	LCS16	IUS20 (Mirena)
Arm/Group Description	Levonorgestrel intrauterine contraceptive system (LCS) releasing 12 microg/24h in vitro	Levonorgestrel intrauterine contraceptive system (LCS) releasing 16 microg/24h in vitro	Levonorgestrel intrauterine system (IUS) releasing 20 microg/24h in vitro
Measure Participants	165	169	178
Number of bleeding days (light, normal or heavy)	3.6 (6.0)	3.0 (4.5)	1.9 (3.6)
Number of bleeding/spotting days	12.8 (10.7)	10.6 (9.3)	8.8 (8.6)
Number of spotting only days	9.2 (8.4)	7.7 (6.9)	6.9 (6.7)

Adverse Events

Adverse Event Reporting Description	An additional pregnancy was not recorded as an SAE.
Arm/Group Title	LCS12		LCS16		IUS20 (Mirena)
Arm/Group Description	Levonorgestrel intrauterine contraceptive system (LCS) releasing 12 microg/24h in vitro		Levonorgestrel intrauterine contraceptive system (LCS) releasing 16 microg/24h in vitro		Levonorgestrel intrauterine system (IUS) releasing 20 microg/24h in vitro
All Cause Mortality
	LCS12		LCS16		IUS20 (Mirena)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	LCS12		LCS16		IUS20 (Mirena)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/239 (5%)		12/245 (4.9%)		16/254 (6.3%)
Endocrine disorders
Goitre	1/239 (0.4%)		0/245 (0%)		0/254 (0%)
Eye disorders
Blindness unilateral	1/239 (0.4%)		0/245 (0%)		0/254 (0%)
Gastrointestinal disorders
Abdominal pain	0/239 (0%)		0/245 (0%)		1/254 (0.4%)
Gastroduodenal ulcer	0/239 (0%)		0/245 (0%)		1/254 (0.4%)
Gastrooesophageal reflux disease	0/239 (0%)		0/245 (0%)		1/254 (0.4%)
Vomiting	0/239 (0%)		0/245 (0%)		1/254 (0.4%)
General disorders
Chest pain	0/239 (0%)		1/245 (0.4%)		0/254 (0%)
Hernia obstructive	1/239 (0.4%)		0/245 (0%)		0/254 (0%)
Hepatobiliary disorders
Biliary dyskinesia	0/239 (0%)		1/245 (0.4%)		0/254 (0%)
Cholecystitis	0/239 (0%)		0/245 (0%)		1/254 (0.4%)
Cholecystitis chronic	0/239 (0%)		1/245 (0.4%)		0/254 (0%)
Infections and infestations
Appendicitis	0/239 (0%)		1/245 (0.4%)		2/254 (0.8%)
Cervicitis	0/239 (0%)		0/245 (0%)		1/254 (0.4%)
Clostridium difficile colitis	1/239 (0.4%)		0/245 (0%)		0/254 (0%)
Encephalitis herpes	0/239 (0%)		0/245 (0%)		1/254 (0.4%)
Pelvic inflammatory disease	0/239 (0%)		1/245 (0.4%)		1/254 (0.4%)
Pneumonia	1/239 (0.4%)		1/245 (0.4%)		0/254 (0%)
Post procedural infection	0/239 (0%)		0/245 (0%)		1/254 (0.4%)
Pyelonephritis	1/239 (0.4%)		0/245 (0%)		0/254 (0%)
Injury, poisoning and procedural complications
Brain contusion	0/239 (0%)		0/245 (0%)		1/254 (0.4%)
Post procedural haematoma	1/239 (0.4%)		0/245 (0%)		1/254 (0.4%)
Post procedural haemorrhage	0/239 (0%)		0/245 (0%)		1/254 (0.4%)
Road traffic accident	0/239 (0%)		0/245 (0%)		1/254 (0.4%)
Skull fractured base	0/239 (0%)		0/245 (0%)		1/254 (0.4%)
Subdural haematoma	0/239 (0%)		0/245 (0%)		1/254 (0.4%)
Traumatic intracranial haemorrhage	0/239 (0%)		0/245 (0%)		1/254 (0.4%)
Investigations
Body temperature increased	0/239 (0%)		0/245 (0%)		1/254 (0.4%)
Musculoskeletal and connective tissue disorders
Arthritis reactive	0/239 (0%)		1/245 (0.4%)		0/254 (0%)
Intervertebral disc protrusion	0/239 (0%)		1/245 (0.4%)		1/254 (0.4%)
Rotator cuff syndrome	0/239 (0%)		1/245 (0.4%)		0/254 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Benign breast neoplasm	1/239 (0.4%)		0/245 (0%)		0/254 (0%)
Leiomyoma	0/239 (0%)		1/245 (0.4%)		0/254 (0%)
Malignant melanoma	1/239 (0.4%)		0/245 (0%)		0/254 (0%)
Ovarian germ cell teratoma benign	1/239 (0.4%)		0/245 (0%)		0/254 (0%)
Phaeochromocytoma	1/239 (0.4%)		0/245 (0%)		0/254 (0%)
Nervous system disorders
Paraesthesia	1/239 (0.4%)		0/245 (0%)		0/254 (0%)
Post-traumatic epilepsy	0/239 (0%)		0/245 (0%)		1/254 (0.4%)
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous	0/239 (0%)		1/245 (0.4%)		0/254 (0%)
Ectopic pregnancy	1/239 (0.4%)		2/245 (0.8%)		0/254 (0%)
Pregnancy	0/239 (0%)		1/245 (0.4%)		0/254 (0%)
Psychiatric disorders
Alcohol abuse	0/239 (0%)		0/245 (0%)		1/254 (0.4%)
Reproductive system and breast disorders
Cervical dysplasia	0/239 (0%)		0/245 (0%)		1/254 (0.4%)
Ovarian cyst	0/239 (0%)		0/245 (0%)		5/254 (2%)
Vaginal haemorrhage	0/239 (0%)		0/245 (0%)		1/254 (0.4%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	0/239 (0%)		1/245 (0.4%)		1/254 (0.4%)
Surgical and medical procedures
Abdominal hernia repair	1/239 (0.4%)		0/245 (0%)		0/254 (0%)
Adhesiolysis	1/239 (0.4%)		0/245 (0%)		0/254 (0%)
Knee arthroplasty	0/239 (0%)		0/245 (0%)		1/254 (0.4%)
Mammoplasty	0/239 (0%)		0/245 (0%)		1/254 (0.4%)
Other (Not Including Serious) Adverse Events
	LCS12		LCS16		IUS20 (Mirena)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	187/239 (78.2%)		198/245 (80.8%)		218/254 (85.8%)
Gastrointestinal disorders
Abdominal distension	40/239 (16.7%)		49/245 (20%)		50/254 (19.7%)
Abdominal pain	19/239 (7.9%)		19/245 (7.8%)		23/254 (9.1%)
Nausea	18/239 (7.5%)		20/245 (8.2%)		22/254 (8.7%)
Abdominal pain lower	16/239 (6.7%)		19/245 (7.8%)		21/254 (8.3%)
General disorders
Oedema	15/239 (6.3%)		21/245 (8.6%)		19/254 (7.5%)
Infections and infestations
Vulvovaginal candidiasis	23/239 (9.6%)		30/245 (12.2%)		21/254 (8.3%)
Sinusitis	16/239 (6.7%)		20/245 (8.2%)		22/254 (8.7%)
Influenza	14/239 (5.9%)		22/245 (9%)		20/254 (7.9%)
Urinary tract infection	22/239 (9.2%)		18/245 (7.3%)		13/254 (5.1%)
Vaginal infection	14/239 (5.9%)		11/245 (4.5%)		21/254 (8.3%)
Nasopharyngitis	14/239 (5.9%)		13/245 (5.3%)		18/254 (7.1%)
Bronchitis	8/239 (3.3%)		7/245 (2.9%)		16/254 (6.3%)
Vaginitis bacterial	12/239 (5%)		9/245 (3.7%)		8/254 (3.1%)
Injury, poisoning and procedural complications
Procedural pain	18/239 (7.5%)		21/245 (8.6%)		24/254 (9.4%)
Investigations
Weight increased	38/239 (15.9%)		39/245 (15.9%)		31/254 (12.2%)
Musculoskeletal and connective tissue disorders
Back pain	18/239 (7.5%)		14/245 (5.7%)		23/254 (9.1%)
Nervous system disorders
Headache	63/239 (26.4%)		63/245 (25.7%)		82/254 (32.3%)
Psychiatric disorders
Mood altered	43/239 (18%)		30/245 (12.2%)		38/254 (15%)
Depression	13/239 (5.4%)		6/245 (2.4%)		10/254 (3.9%)
Reproductive system and breast disorders
Breast discomfort	52/239 (21.8%)		51/245 (20.8%)		62/254 (24.4%)
Ovarian cyst	21/239 (8.8%)		24/245 (9.8%)		60/254 (23.6%)
Breast pain	20/239 (8.4%)		35/245 (14.3%)		27/254 (10.6%)
Dysmenorrhoea	14/239 (5.9%)		19/245 (7.8%)		18/254 (7.1%)
Skin and subcutaneous tissue disorders
Acne	64/239 (26.8%)		61/245 (24.9%)		73/254 (28.7%)
Seborrhoea	16/239 (6.7%)		18/245 (7.3%)		21/254 (8.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The sponsor is interested in the publication of the results of every study. As some of the information concerning the study drug and the sponsor's development activities may be strictly confidential, any publication manuscript (including conference contributions, etc.) must first be reviewed by the sponsor before its submission or presentation.