PEARLIV: PGL4001 Efficacy Assessment in Reduction of Symptoms Due to Uterine Leiomyomata

• Sponsor: PregLem SA (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01629563
• Collaborator: (none)
• Enrollment: 451
• Locations: 49
• Arms: 2
• Duration (Months): 31
• Patients Per Site: 9.2
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

Phase III, multicentre, randomized, double-blind, parallel group, long-term study investigating the efficacy and safety of the 5mg and 10mg doses of PGL4001 for the treatment of uterine myoma.

Condition or Disease	Intervention/Treatment	Phase
Uterine Fibroids	Drug: PGL4001 5 mg; Drug: PGL4001 10 mg	Phase 3

Detailed Description

The target population is composed of pre-menopausal women with symptomatic uterine myoma(s) characterised by heavy bleeding.The main objective of this study is to assess the sustained efficacy and safety of long term on-off treatment with PGL4001 5 or 10mg doses on uterine bleeding, myoma size, pain and quality of life.

Study Design

• Study Type: Interventional
• Actual Enrollment: 451 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase III, Multicentre, Randomized, Double-blind Clinical Study, Investigating the Efficacy and Safety of Repeated 12-week Courses of Daily 5mg or 10mg Doses of PGL4001 for the Long-term Management of Symptomatic Uterine Fibroids
• Study Start Date: Jun 1, 2012
• Actual Primary Completion Date: Jan 1, 2015
• Actual Study Completion Date: Jan 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ulipristal acetate (PGL4001) 5mg All subjects will be asked to take a 150mg size tablet (PGL4001 5mg or matching placebo: placebo 5) orally daily for repeated periods 84 days. The first treatment course will start on the first 4 days of menstruation and will be orally administered, once daily (1 tablet of 150mg size), for 84 days. The following three treatment courses should be started in the first two days of a menstrual period.	Drug: PGL4001 5 mg; PGL4001 5 mg daily administration; Other Names: Ulipristal Acetate, Esmya
Experimental: Ulipristal acetate (PGL4001) 10mg All subjects will be asked to take a 300mg size tablet (PGL4001 10mg or matching placebo: placebo 10 ) orally daily for repeated periods 84 days. The first treatment course will start on the first 4 days of menstruation and will be orally administered, once daily (1 tablet of 300mg size), for 84 days. The following three treatment courses should be started in the first two days of a menstrual period.	Drug: PGL4001 10 mg; PGL4001 10mg daily administration; Other Names: Ulipristal Acetate

Outcome Measures

Primary Outcome Measures

1. Percentage of Subjects Who Are in Amenorrhea at the End of All Four Treatment Courses [18 months study duration per subject (4 3-month intermittent treatment courses)]

   Amenorrhoea was defined as no more than 1 day of spotting within a 35 day interval. Subjects need to be in amenorrhoea at the end of all four treatment courses, i.e for at least 4x35 days.

Secondary Outcome Measures

1. Percentage of Subjects Who Were in Amenorrhea at the End of Treatment Course 4 [After 18 months]

   Amenorrhoea was defined as no more than 1 day of spotting within a 35 day interval.

2. Percentage of Subjects With Controlled Bleeding at the End of All 4 Treatment Courses [After 18 months]

   Controlled bleeding was defined as no episodes of heavy bleeding and a maximum of 8 days of bleeding during the last 56 days of a treatment course. Subjects need to be in controlled bleeding at the end of all 4 treatment courses i.e. for at least 4x56 days.

3. Percentage of Change From Baseline to End of Treatment Course 4 in the Total Volume of the 3 Largest Fibroids [After 18 months]

   For the 3 largest myomas at baseline and the 3 largest myomas at the end of treatment course 4 identified by transvaginal ultrasound, length, height and depth were measured and the volume was estimated by applying the equation for the voulme of an ellipsoid (length x height x depht x π/6). Subjects were exposed to 4 3-month intermittent courses.

4. Percentage of Change From Baseline to End of Treatment Course 4 in Quality of Life (Uterine Fibroid Symptom Severity (UFSQoL) [After 18 months]

   Quality of Life was assessed using a validated questionnaire measuring uterine fibroid symptom severity (UFSQoL) where lower scores indicate fewer symtoms and where a level of 23 has been reported for healthy subject (scale 0-100). Subjects were exposed to 4 3-month intermittent courses.

5. Percentage of Change From Baseline to End of Treatment Course 4 in Quality of Life -Uterine Fibroid Health Related Quality of Life (HRQL) [18 months]

   Quality of Life was measured using a validated uterine fibroid symptom questionnaire. Total score for health related quality of Life (HRQL) range from 0 to 100 with higher scores indicating better Quality of Life. Subjects were exposed to 4 3-month intermittent courses.

6. Percentage of Change From Baseline to End of Treatment Course 4 in Pain Using a Visual Analogue Scale (VAS) [After 18 months]

   Pain was assessed using a Visual Analogue Scale (VAS) ranging from 0 to 100 with higher score indicating more severe pain. Subjects were exposed to 4 3-month intermittent courses.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 50 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Be a pre-menopausal woman between 18 and 50 years inclusive.

• Have a Body Mass Index (BMI) ≥ 18 and ≤ 40.

• Have FSH levels ≤ 20 mIU/mL

• Have excessive uterine bleeding due to myoma.

• Have regular menstrual cycles

• Have a myomatous uterus < 16 weeks with at least one myoma ≥ 3 cm in diameter.

• If of childbearing potential the subject must be practicing a non-hormonal method of contraception.

Exclusion Criteria:

• Has a history of or current uterine, cervical, ovarian or breast cancer.

• Has a history of or current endometrium atypical hyperplasia or adenocarcinoma.

• Has a known severe coagulation disorder.

• Has a history of or current treatment for myoma with a Selective Progesterone Receptor Modulator (SPRM).

• Has abnormal hepatic function at study entry.

• Has a positive pregnancy test, is nursing or planning a pregnancy during the course of the study.

• Has a current (within twelve months) problem with alcohol or drug abuse.

• Is currently enrolled in an investigational drug or device study or has participated in such a study within the last 30 days.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cliniques Universitaires Saint-Luc Gynécologie-Obstétrique	Brussels		Belgium	1200
2	UZ Leuven Campus Gasthuisberg	Leuven		Belgium	3000
3	CHU de Liège, CHR de la Citadelle Gynécologie-Obstétrique	Liège		Belgium	4000
4	CHU Mont-Godinne	Yvoir		Belgium	5530
5	Centrum ambulantni gynekologie a primarni pece	Brno		Czechia	60200
6	FN Brno Gynekologicko - porodnická klinika	Brno		Czechia	62500
7	Sanatorium SANUS	Hradec Kralove		Czechia	50002
8	Nemocnice Jihlava Gynekologicko - porodnicke oddeleni	Jihlava		Czechia	58633
9	G-CENTRUM Olomouc s.r.o.	Olomouc		Czechia	77200
10	FN Olomouc, Porodnicko-Gynekologicka klinika	Olomouc		Czechia	77220
11	Femina Sana, s.r.o.	Praha 3		Czechia	13000
12	Hôpital Bicêtre - APHP	Le Kremlin Bicêtre		France	94275
13	Hôpital Bichat, Service de Gynécologie Obstétrique	Paris		France	75018
14	CHU Bretonneau Service de Gynécologie Obstétrique	Tours		France	37044
15	Private practice	Hamburg		Germany	22159
16	Private practice	Hamburg		Germany	22359
17	Medizinische Hochschule Hannover Klinik für Frauenheilkunde und Geburtshilfe	Hannover		Germany	30625
18	Frauenarztpraxis	Hessen		Germany	60322
19	Praxis für Frauenheilkunde, Klinische Forschung und Weiterbildung	Magdeburg		Germany	39112
20	Technische Universität München	München		Germany	81675
21	Rethy Pal Korhaz és Rendelointezet Szuleszeti es Nogyogyaszati Osztaly	Bekescsaba		Hungary	5600
22	Institution Robert Karoly Maganklinika	Budapest		Hungary	1135
23	Szent Anna Szuleszeti, Nogyogyaszati es Ultrahang Maganrendelo	Debrecen		Hungary	4024
24	Josa Andras Oktatokorhaz	Nyiregyhaza		Hungary	4400
25	Fejer Megyei Szent Gyorgy Korhaz Szuleszeti es Nogyogyaszati Osztaly	Szekesfehervar		Hungary	8000
26	Szuleszeti es Nogyogyaszati Osztaly	Szentes		Hungary	6600
27	Sandor Dent Bt.	Szolnok		Hungary	5000
28	Dipartimento di Ostetricia e Ginecologia, Università degli Studi di Catanzaro "Magna Graecia"	Catanzaro		Italy	88100
29	Policlinico Universitario "Agostino Gemelli"	Roma		Italy	00168
30	Riga 1. hospital	Riga		Latvia	1001
31	Latvian Medical Marine Center	Riga		Latvia	LV-1005
32	Medical Company "ARS"	Riga		Latvia	LV-1010
33	Saules Family Medicine Center	Kaunas		Lithuania	49449
34	Family Medicine Centre"Seimos Gydytojas"	Vilnius		Lithuania	01118
35	Private Clinic "Maxmeda"	Vilnius		Lithuania	03225
36	Private Clinic "Kardiolita"	Vilnius		Lithuania	05263
37	Centrul Medical SANA SRL	Bucuresti		Romania	011025
38	Quantum Medical Center SRL Obstetrica-Ginecologie	Bucuresti		Romania	011426
39	Fortis Medical Center SRL Obstetrica Ginecologie	Bucuresti		Romania	012064
40	Spitalul Clinic Dr. I.Cantacuzino sectia Obstetrica-Ginecologie	Bucuresti		Romania	020475
41	Centrul Medical EUROMED SRL, Departamentul de Obtetrica/Ginecologie	Bucuresti		Romania	020762
42	Spitalul Clinic de Obstetrica	Iasi		Romania	700398
43	Kharkiv City Perinatal Center Gynaecological Department #1	Kharkiv		Ukraine	61176
44	Municipal Institution "Maternity Hospital #1" City Center of family planning	Odessa		Ukraine	65039
45	Maternity Hospital#4 Department of Gynaecology	Zaporizhzhya		Ukraine	69065
46	MRC Centre for Reproductive Health University of Edinburgh	Edinburgh		United Kingdom	EH16 4TJ
47	North Middlesex University Hospital NHS Trust	London		United Kingdom	N18 1QX
48	Women's Health, Royal Victoria Infirmary	Newcastle upon Tyne		United Kingdom	NE1 4LP
49	Norfolk & Norwich University Hospital	Norwich		United Kingdom	NR47UY

Sponsors and Collaborators

• PregLem SA

Investigators

• Study Director: Pablo Arrigada, MD, PregLem SA

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: PregLem SA
• ClinicalTrials.gov Identifier: NCT01629563
• Other Study ID Numbers: PGL11-006
• First Posted: Jun 27, 2012
• Last Update Posted: Sep 4, 2019
• Last Verified: Aug 1, 2019

• Additional relevant MeSH terms: Leiomyoma; Myofibroma; Ulipristal acetate

Study Results

Participant Flow

Arm/Group Title	Ulipristal Acetate (PGL4001) 5mg	Ulipristal Acetate (PGL4001) 10mg
Arm/Group Description	PGL4001 5 mg: PGL4001 5 mg daily administration	PGL4001 10 mg: PGL4001 10mg daily administration
Period Title: Overall Study
STARTED	228	223
Safety Population	230	221
Started Treatment Course 2	213	207
Started Treatment Course 3	191	190
Started Treatment Course 4	178	176
COMPLETED	167	170
NOT COMPLETED	61	53

Baseline Characteristics

Arm/Group Title	Ulipristal Acetate (PGL4001) 5mg	Ulipristal Acetate (PGL4001) 10mg	Total
Arm/Group Description	PGL4001 5 mg: PGL4001 5 mg daily administration	PGL4001 10 mg: PGL4001 10mg daily administration	Total of all reporting groups
Overall Participants	228	223	451
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	228 100%	223 100%	451 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	41.6 (5.4)	41.4 (5.1)	41.5 (5.2)
Sex: Female, Male (Count of Participants)
Female	228 100%	223 100%	451 100%
Male	0 0%	0 0%	0 0%
Total volume of the 3 largest myoma (cm3) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [cm3]	42.6	43.6	43.3
Pain Assessment (Visual Analogue Scale) (units on a scale) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [units on a scale]	39.0	43.0	40.5
Uterine Fibroid Symptom Quality of Life Questionnaire (units on a scale) [Median (Inter-Quartile Range) ]
Symptom Severity (UFSQoL)	50.0	50.0	50.0
Health related Quality of Life (HRQL)	56.9	55.2	56.0

Outcome Measures

1. Primary Outcome

Title	Percentage of Subjects Who Are in Amenorrhea at the End of All Four Treatment Courses
Description	Amenorrhoea was defined as no more than 1 day of spotting within a 35 day interval. Subjects need to be in amenorrhoea at the end of all four treatment courses, i.e for at least 4x35 days.
Time Frame	18 months study duration per subject (4 3-month intermittent treatment courses)

Outcome Measure Data

Analysis Population Description

Full Analysis Set 1 (subjects who received study treatment at least once for treatment course 1) (subjects with missing values were excluded from analysis)

Arm/Group Title	Ulipristal Acetate (PGL4001) 5mg	Ulipristal Acetate (PGL4001) 10mg
Arm/Group Description	PGL4001 5 mg: PGL4001 5 mg daily administration	PGL4001 10 mg: PGL4001 10mg daily administration
Measure Participants	195	185
Number [percentage of subjects]	48.7	60.5

2. Secondary Outcome

Title	Percentage of Subjects Who Were in Amenorrhea at the End of Treatment Course 4
Description	Amenorrhoea was defined as no more than 1 day of spotting within a 35 day interval.
Time Frame	After 18 months

Outcome Measure Data

Analysis Population Description

Full Analysis Set 1 (all subjects who received study treatment once for treatment course 1) (subjects with missing values were excluded from analysis)

Arm/Group Title	Ulipristal Acetate (PGL4001) 5mg	Ulipristal Acetate (PGL4001) 10mg
Arm/Group Description	PGL4001 5 mg: PGL4001 5 mg daily administration	PGL4001 10 mg: PGL4001 10mg daily administration
Measure Participants	227	220
Number [percentage of participants]	69.6 30.5%	74.5 33.4%

3. Secondary Outcome

Title	Percentage of Subjects With Controlled Bleeding at the End of All 4 Treatment Courses
Description	Controlled bleeding was defined as no episodes of heavy bleeding and a maximum of 8 days of bleeding during the last 56 days of a treatment course. Subjects need to be in controlled bleeding at the end of all 4 treatment courses i.e. for at least 4x56 days.
Time Frame	After 18 months

Outcome Measure Data

Analysis Population Description

Full analysis set 1 (all subject who received study treatment at least once for treatment course 1) (subjects with missing values were excluded from analysis)

Arm/Group Title	Ulipristal Acetate (PGL4001) 5mg	Ulipristal Acetate (PGL4001) 10mg
Arm/Group Description	PGL4001 5 mg: PGL4001 5 mg daily administration	PGL4001 10 mg: PGL4001 10mg daily administration
Measure Participants	158	146
Number [percentage of participants]	67.1 29.4%	71.9 32.2%

4. Secondary Outcome

Title	Percentage of Change From Baseline to End of Treatment Course 4 in the Total Volume of the 3 Largest Fibroids
Description	For the 3 largest myomas at baseline and the 3 largest myomas at the end of treatment course 4 identified by transvaginal ultrasound, length, height and depth were measured and the volume was estimated by applying the equation for the voulme of an ellipsoid (length x height x depht x π/6). Subjects were exposed to 4 3-month intermittent courses.
Time Frame	After 18 months

Outcome Measure Data

Analysis Population Description

Full Analysis Set 1 (all subjects who received study treatment at least once for treatment course 1) (subjects with missing values were excluded from analysis)

Arm/Group Title	Ulipristal Acetate (PGL4001) 5mg	Ulipristal Acetate (PGL4001) 10mg
Arm/Group Description	PGL4001 5 mg: PGL4001 5 mg daily administration	PGL4001 10 mg: PGL4001 10mg daily administration
Measure Participants	160	159
Median (Inter-Quartile Range) [percentage of change from baseline]	-67.0	-70.4

5. Secondary Outcome

Title	Percentage of Change From Baseline to End of Treatment Course 4 in Quality of Life (Uterine Fibroid Symptom Severity (UFSQoL)
Description	Quality of Life was assessed using a validated questionnaire measuring uterine fibroid symptom severity (UFSQoL) where lower scores indicate fewer symtoms and where a level of 23 has been reported for healthy subject (scale 0-100). Subjects were exposed to 4 3-month intermittent courses.
Time Frame	After 18 months

Outcome Measure Data

Analysis Population Description

Full Analysis Set 1 (all subjects who received study treatment at least once for treatment course 1) (subjects with missing values were excluded from analysis)

Arm/Group Title	Ulipristal Acetate (PGL4001) 5mg	Ulipristal Acetate (PGL4001) 10mg
Arm/Group Description	PGL4001 5 mg: PGL4001 5 mg daily administration	PGL4001 10 mg: PGL4001 10mg daily administration
Measure Participants	137	137
Median (Inter-Quartile Range) [percentage of change from baseline]	-31.25	-28.13

6. Secondary Outcome

Title	Percentage of Change From Baseline to End of Treatment Course 4 in Quality of Life -Uterine Fibroid Health Related Quality of Life (HRQL)
Description	Quality of Life was measured using a validated uterine fibroid symptom questionnaire. Total score for health related quality of Life (HRQL) range from 0 to 100 with higher scores indicating better Quality of Life. Subjects were exposed to 4 3-month intermittent courses.
Time Frame	18 months

Outcome Measure Data

Analysis Population Description

Full Analysis Set 1 (all subjects who received study treatment at least once for treatment course 1) (subjects with missing values were excluded from analysis)

Arm/Group Title	Ulipristal Acetate (PGL4001) 5mg	Ulipristal Acetate (PGL4001) 10mg
Arm/Group Description	PGL4001 5 mg: PGL4001 5 mg daily administration	PGL4001 10 mg: PGL4001 10mg daily administration
Measure Participants	136	138
Median (Inter-Quartile Range) [percentage of change from baseline]	20.69	15.52

7. Secondary Outcome

Title	Percentage of Change From Baseline to End of Treatment Course 4 in Pain Using a Visual Analogue Scale (VAS)
Description	Pain was assessed using a Visual Analogue Scale (VAS) ranging from 0 to 100 with higher score indicating more severe pain. Subjects were exposed to 4 3-month intermittent courses.
Time Frame	After 18 months

Outcome Measure Data

Analysis Population Description

FAS1 (all subjects who received study treatment at least once for treatment course 1) (subjects with missing values were excluded from analysis)

Arm/Group Title	Ulipristal Acetate (PGL4001) 5mg	Ulipristal Acetate (PGL4001) 10mg
Arm/Group Description	PGL4001 5 mg: PGL4001 5 mg daily administration	PGL4001 10 mg: PGL4001 10mg daily administration
Measure Participants	136	138
Median (Inter-Quartile Range) [percentage of change from baseline]	-20.0	-23.0

Adverse Events

Time Frame	Serious Adverse events were reported where the start date was on or after the first dose of study medication, up to the end of study follow-up (21 months on average).Other Adverse Events are summarised as on-treatment TEAEs.
Adverse Event Reporting Description	2 subjects randomised to Ulipristal acetate 10 mg received 5 mg by mistake. They are included in the safety set according to treatment received. On-treatment TEAEs are events where the start date was on or after the first dose of study medication, up to and including 7 days after the last dose of study medication within each treatment course.
Arm/Group Title	Ulipristal Acetate (PGL4001) 5mg		Ulipristal Acetate (PGL4001) 10mg
Arm/Group Description	PGL4001 5 mg: PGL4001 5 mg daily administration		PGL4001 10 mg: PGL4001 10mg daily administration
All Cause Mortality
	Ulipristal Acetate (PGL4001) 5mg		Ulipristal Acetate (PGL4001) 10mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Ulipristal Acetate (PGL4001) 5mg		Ulipristal Acetate (PGL4001) 10mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	16/230 (7%)		12/221 (5.4%)
Blood and lymphatic system disorders
Anaemia	1/230 (0.4%)		0/221 (0%)
Iron deficiency Anaemia	1/230 (0.4%)		0/221 (0%)
Cardiac disorders
arteriospam coronary	0/230 (0%)		1/221 (0.5%)
Ear and labyrinth disorders
tinnitus	0/230 (0%)		1/221 (0.5%)
Endocrine disorders
toxic nodular goitre	1/230 (0.4%)		0/221 (0%)
Gastrointestinal disorders
abdominal pain	1/230 (0.4%)		0/221 (0%)
small intestinal obstruction	0/230 (0%)		1/221 (0.5%)
General disorders
accidental death	1/230 (0.4%)		0/221 (0%)
homicide	1/230 (0.4%)		0/221 (0%)
Hepatobiliary disorders
cholelithiasis	0/230 (0%)		1/221 (0.5%)
Musculoskeletal and connective tissue disorders
back pain	1/230 (0.4%)		0/221 (0%)
periarthritis	1/230 (0.4%)		0/221 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Uterine Leiomyoma	1/230 (0.4%)		3/221 (1.4%)
breast cancer	0/230 (0%)		1/221 (0.5%)
endometrial cancer	1/230 (0.4%)		0/221 (0%)
castleman's disease	1/230 (0.4%)		0/221 (0%)
Nervous system disorders
carpal tunnel syndrome	0/230 (0%)		1/221 (0.5%)
Psychiatric disorders
bipolar disorder	1/230 (0.4%)		0/221 (0%)
Renal and urinary disorders
urethral stenesis	0/230 (0%)		1/221 (0.5%)
Reproductive system and breast disorders
Menorrhagia	4/230 (1.7%)		1/221 (0.5%)
breast hyperplasia	0/230 (0%)		1/221 (0.5%)
Endometriosis	0/230 (0%)		1/221 (0.5%)
Vascular disorders
deep vein thrombosis	1/230 (0.4%)		0/221 (0%)
Other (Not Including Serious) Adverse Events
	Ulipristal Acetate (PGL4001) 5mg		Ulipristal Acetate (PGL4001) 10mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	129/230 (56.1%)		131/221 (59.3%)
Blood and lymphatic system disorders
aneamia	5/230 (2.2%)		3/221 (1.4%)
Ear and labyrinth disorders
vertigo	6/230 (2.6%)		2/221 (0.9%)
Gastrointestinal disorders
nausea	8/230 (3.5%)		6/221 (2.7%)
abdominal pain	5/230 (2.2%)		5/221 (2.3%)
General disorders
fatigue	7/230 (3%)		8/221 (3.6%)
Infections and infestations
influenza	12/230 (5.2%)		10/221 (4.5%)
nasopharyngitis	7/230 (3%)		12/221 (5.4%)
tonsillitis	4/230 (1.7%)		5/221 (2.3%)
cystitis	3/230 (1.3%)		5/221 (2.3%)
Investigations
weight increased	5/230 (2.2%)		3/221 (1.4%)
blood creatine phosphokinase increased	5/230 (2.2%)		2/221 (0.9%)
Musculoskeletal and connective tissue disorders
back pain	5/230 (2.2%)		6/221 (2.7%)
Nervous system disorders
headache	31/230 (13.5%)		30/221 (13.6%)
Psychiatric disorders
anxiety	5/230 (2.2%)		4/221 (1.8%)
Reproductive system and breast disorders
hot flush	18/230 (7.8%)		23/221 (10.4%)
breast pain/breast tenderness/breast disconfort	10/230 (4.3%)		8/221 (3.6%)
pelvic pain	10/230 (4.3%)		5/221 (2.3%)
vaginal discharge	5/230 (2.2%)		7/221 (3.2%)
Respiratory, thoracic and mediastinal disorders
cough	2/230 (0.9%)		6/221 (2.7%)
oropharyngeal pain	0/230 (0%)		5/221 (2.3%)
Skin and subcutaneous tissue disorders
acne	5/230 (2.2%)		4/221 (1.8%)
Vascular disorders
hypertension	5/230 (2.2%)		4/221 (1.8%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

PI shall submit to sponsor results communication for review 60 days prior to publication submission. If in the sponsor judgement, publication at a given time would hinder the sponsor's IP development, PI shall consider modifying the publication schedule. PI agrees to delete information identified by sponsor as confidential or defer publication to permit filing of patent application by the sponsor. Publication based on 1 site results shall not be made before the first muti-centre publication.