Trial Outcomes & Findings for A Clinical Study to Evaluate the Safety of Ospemifene (NCT NCT00566982)

NCT ID: NCT00566982

Last Updated: 2018-05-18

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

426 participants

Primary outcome timeframe

12 weeks

Results posted on

2018-05-18

Participant Flow

This was a multicenter study conducted at 23 centers in Belgium, Denmark, Finland, and Sweden. First subject was screened on Nov. 26, 2007 and last subjected completed the study on June 26, 2009

Participant milestones

Participant milestones
Measure	Subjects on Placebo (Baseline) Placebo was taken orally, once daily, in the morning, with food for 52 weeks.	Subjects on Ospemifene 60 mg/Day (Baseline) Ospemifene was taken orally, once daily, in the morning, with food for 52 weeks.
Overall Study STARTED	63	363
Overall Study COMPLETED	55	294
Overall Study NOT COMPLETED	8	69

Reasons for withdrawal

Reasons for withdrawal
Measure	Subjects on Placebo (Baseline) Placebo was taken orally, once daily, in the morning, with food for 52 weeks.	Subjects on Ospemifene 60 mg/Day (Baseline) Ospemifene was taken orally, once daily, in the morning, with food for 52 weeks.
Overall Study Adverse Event	6	48
Overall Study Withdrawal by Subject	1	14
Overall Study Protocol Violation	1	4
Overall Study Lost to Follow-up	0	1
Overall Study Other-family problems & doctor's request	0	2

Baseline Characteristics

A Clinical Study to Evaluate the Safety of Ospemifene

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Subjects on Ospemifene 60 mg/Day (Baseline) n=363 Participants Ospemifene was taken orally, once daily, in the morning, with food for 52 weeks.	Subjects on Placebo (Baseline) n=63 Participants Placebo was taken orally, once daily, in the morning, with food for 52 weeks.	Total n=426 Participants Total of all reporting groups
Age, Continuous	61.7 years n=99 Participants	62.9 years n=107 Participants	62.3 years n=206 Participants
Sex: Female, Male Female	363 Participants n=99 Participants	63 Participants n=107 Participants	426 Participants n=206 Participants
Sex: Female, Male Male	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race/Ethnicity, Customized Caucasian	361 participants n=99 Participants	63 participants n=107 Participants	424 participants n=206 Participants
Race/Ethnicity, Customized Black	1 participants n=99 Participants	0 participants n=107 Participants	1 participants n=206 Participants
Race/Ethnicity, Customized Asian	1 participants n=99 Participants	0 participants n=107 Participants	1 participants n=206 Participants
Region of Enrollment Belgium	101 Participants n=99 Participants	18 Participants n=107 Participants	119 Participants n=206 Participants
Region of Enrollment Denmark	56 Participants n=99 Participants	9 Participants n=107 Participants	65 Participants n=206 Participants
Region of Enrollment Finland	177 Participants n=99 Participants	31 Participants n=107 Participants	208 Participants n=206 Participants
Region of Enrollment Sweden	29 Participants n=99 Participants	5 Participants n=107 Participants	34 Participants n=206 Participants
Alcohol	2.4 drinks/week n=99 Participants	2.3 drinks/week n=107 Participants	2.35 drinks/week n=206 Participants
BMI	24.65 kg/m^2 n=99 Participants	24.11 kg/m^2 n=107 Participants	24.38 kg/m^2 n=206 Participants

PRIMARY outcome

Timeframe: 12 weeks

Population: ITT

Outcome measures

Outcome measures
Measure	Subjects on Placebo (Baseline) n=63 Participants Placebo was taken orally, once daily, in the morning, with food for 52 weeks.	Subjects on Ospemifene 60 mg/Day (Baseline) n=363 Participants Ospemifene was taken orally, once daily, in the morning, with food for 52 weeks.	Subjects on Ospemifene 60 mg/Day (Baseline) Ospemifene was taken orally, once daily, in the morning, with food for 52 weeks.	Subjects on Ospemifene 60 mg/Day (Week 52) Ospemifene was taken orally, once daily, in the morning, with food for 52 weeks.
Mean Change From Baseline in Percentage of Parabasal Cells in Maturation Index of Vaginal Smear	5.0 percentage of parabasal cells Standard Deviation 27.86 • Interval -90.0 to 98.0	-46.0 percentage of parabasal cells Standard Deviation 41.96 • Interval -100.0 to 75.0	—	—

PRIMARY outcome

Timeframe: 12 weeks

Population: ITT

Outcome measures

Outcome measures
Measure	Subjects on Placebo (Baseline) n=63 Participants Placebo was taken orally, once daily, in the morning, with food for 52 weeks.	Subjects on Ospemifene 60 mg/Day (Baseline) n=363 Participants Ospemifene was taken orally, once daily, in the morning, with food for 52 weeks.	Subjects on Ospemifene 60 mg/Day (Baseline) Ospemifene was taken orally, once daily, in the morning, with food for 52 weeks.	Subjects on Ospemifene 60 mg/Day (Week 52) Ospemifene was taken orally, once daily, in the morning, with food for 52 weeks.
Mean Change From Baseline in Percentage of Superficial Cells in Maturation Index of Vaginal Smear	1.0 percentage of superficial cells Standard Deviation 4.36 • Interval -5.0 to 28.0	10.3 percentage of superficial cells Standard Deviation 12.53 • Interval -5.0 to 60.0	—	—

PRIMARY outcome

Timeframe: 12 weeks

Population: ITT

Outcome measures

Outcome measures
Measure	Subjects on Placebo (Baseline) n=63 Participants Placebo was taken orally, once daily, in the morning, with food for 52 weeks.	Subjects on Ospemifene 60 mg/Day (Baseline) n=363 Participants Ospemifene was taken orally, once daily, in the morning, with food for 52 weeks.	Subjects on Ospemifene 60 mg/Day (Baseline) Ospemifene was taken orally, once daily, in the morning, with food for 52 weeks.	Subjects on Ospemifene 60 mg/Day (Week 52) Ospemifene was taken orally, once daily, in the morning, with food for 52 weeks.
Mean Change From Baseline in Vaginal pH	-0.16 pH Standard Deviation 0.945	-1.21 pH Standard Deviation 0.912	—	—

SECONDARY outcome

Timeframe: 52 weeks

Population: ITT

Outcome measures

Outcome measures
Measure	Subjects on Placebo (Baseline) n=63 Participants Placebo was taken orally, once daily, in the morning, with food for 52 weeks.	Subjects on Ospemifene 60 mg/Day (Baseline) n=363 Participants Ospemifene was taken orally, once daily, in the morning, with food for 52 weeks.	Subjects on Ospemifene 60 mg/Day (Baseline) Ospemifene was taken orally, once daily, in the morning, with food for 52 weeks.	Subjects on Ospemifene 60 mg/Day (Week 52) Ospemifene was taken orally, once daily, in the morning, with food for 52 weeks.
Change From Baseline in Estradiol Levels	0.004 nmol/L Standard Deviation 0.0120	0.004 nmol/L Standard Deviation 0.0145	—	—

SECONDARY outcome

Timeframe: 52 weeks

Population: ITT

Outcome measures

Outcome measures
Measure	Subjects on Placebo (Baseline) n=63 Participants Placebo was taken orally, once daily, in the morning, with food for 52 weeks.	Subjects on Ospemifene 60 mg/Day (Baseline) n=363 Participants Ospemifene was taken orally, once daily, in the morning, with food for 52 weeks.	Subjects on Ospemifene 60 mg/Day (Baseline) Ospemifene was taken orally, once daily, in the morning, with food for 52 weeks.	Subjects on Ospemifene 60 mg/Day (Week 52) Ospemifene was taken orally, once daily, in the morning, with food for 52 weeks.
Change From Baseline in Luteinizing Hormone Levels	-0.88 U/L Standard Deviation 7.738	-3.16 U/L Standard Deviation 8.127	—	—

SECONDARY outcome

Timeframe: 52 weeks

Population: ITT

Outcome measures

Outcome measures
Measure	Subjects on Placebo (Baseline) n=63 Participants Placebo was taken orally, once daily, in the morning, with food for 52 weeks.	Subjects on Ospemifene 60 mg/Day (Baseline) n=363 Participants Ospemifene was taken orally, once daily, in the morning, with food for 52 weeks.	Subjects on Ospemifene 60 mg/Day (Baseline) Ospemifene was taken orally, once daily, in the morning, with food for 52 weeks.	Subjects on Ospemifene 60 mg/Day (Week 52) Ospemifene was taken orally, once daily, in the morning, with food for 52 weeks.
Change From Baseline in Follicle Stimulating Hormone Levels	-7.63 U/L Standard Deviation 17.083	-19.69 U/L Standard Deviation 18.977	—	—

SECONDARY outcome

Timeframe: 52 weeks

Population: ITT

Outcome measures

Outcome measures
Measure	Subjects on Placebo (Baseline) n=63 Participants Placebo was taken orally, once daily, in the morning, with food for 52 weeks.	Subjects on Ospemifene 60 mg/Day (Baseline) n=363 Participants Ospemifene was taken orally, once daily, in the morning, with food for 52 weeks.	Subjects on Ospemifene 60 mg/Day (Baseline) Ospemifene was taken orally, once daily, in the morning, with food for 52 weeks.	Subjects on Ospemifene 60 mg/Day (Week 52) Ospemifene was taken orally, once daily, in the morning, with food for 52 weeks.
Change From Baseline in Sex Hormone Binding Globulin Levels	-0.8 nmol/L Standard Deviation 15.41	31.0 nmol/L Standard Deviation 27.16	—	—

SECONDARY outcome

Timeframe: 52 weeks

Population: ITT

Outcome measures

Outcome measures
Measure	Subjects on Placebo (Baseline) n=63 Participants Placebo was taken orally, once daily, in the morning, with food for 52 weeks.	Subjects on Ospemifene 60 mg/Day (Baseline) n=63 Participants Ospemifene was taken orally, once daily, in the morning, with food for 52 weeks.	Subjects on Ospemifene 60 mg/Day (Baseline) n=363 Participants Ospemifene was taken orally, once daily, in the morning, with food for 52 weeks.	Subjects on Ospemifene 60 mg/Day (Week 52) n=363 Participants Ospemifene was taken orally, once daily, in the morning, with food for 52 weeks.
Visual Evaluation of the Vagina (Baseline & Week 52) Vaginal redness in the mucosa-None	13 participants	17 participants	76 participants	219 participants
Visual Evaluation of the Vagina (Baseline & Week 52) Friability-None	10 participants	20 participants	74 participants	241 participants
Visual Evaluation of the Vagina (Baseline & Week 52) Friability-Mild	28 participants	12 participants	118 participants	35 participants
Visual Evaluation of the Vagina (Baseline & Week 52) Friability-Moderate	14 participants	21 participants	125 participants	17 participants
Visual Evaluation of the Vagina (Baseline & Week 52) Friability-Severe	11 participants	3 participants	46 participants	4 participants
Visual Evaluation of the Vagina (Baseline & Week 52) Pallor-None	7 participants	13 participants	47 participants	232 participants
Visual Evaluation of the Vagina (Baseline & Week 52) Pallor-Mild	28 participants	21 participants	147 participants	53 participants
Visual Evaluation of the Vagina (Baseline & Week 52) Pallor-Moderate	23 participants	17 participants	146 participants	11 participants
Visual Evaluation of the Vagina (Baseline & Week 52) Pallor-Severe	5 participants	5 participants	23 participants	1 participants
Visual Evaluation of the Vagina (Baseline & Week 52) Petechiae-None	24 participants	22 participants	134 participants	243 participants
Visual Evaluation of the Vagina (Baseline & Week 52) Petechiae-Mild	18 participants	12 participants	110 participants	39 participants
Visual Evaluation of the Vagina (Baseline & Week 52) Petechiae-Moderate	19 participants	17 participants	95 participants	12 participants
Visual Evaluation of the Vagina (Baseline & Week 52) Petechiae-Severe	2 participants	5 participants	24 participants	3 participants
Visual Evaluation of the Vagina (Baseline & Week 52) Vaginal dryness in the mucosa-None	10 participants	18 participants	46 participants	242 participants
Visual Evaluation of the Vagina (Baseline & Week 52) Vaginal dryness in the mucosa-Mild	14 participants	17 participants	120 participants	39 participants
Visual Evaluation of the Vagina (Baseline & Week 52) Vaginal dryness in the mucosa-Moderate	32 participants	16 participants	150 participants	15 participants
Visual Evaluation of the Vagina (Baseline & Week 52) Vaginal dryness in the mucosa-Severe	7 participants	5 participants	47 participants	1 participants
Visual Evaluation of the Vagina (Baseline & Week 52) Vaginal redness in the mucosa-Mild	31 participants	21 participants	164 participants	52 participants
Visual Evaluation of the Vagina (Baseline & Week 52) Vaginal redness in the mucosa-Moderate	14 participants	15 participants	101 participants	22 participants
Visual Evaluation of the Vagina (Baseline & Week 52) Vaginal redness in the mucosa-Severe	5 participants	3 participants	21 participants	4 participants

Adverse Events

Subjects on Placebo (Baseline)

Serious events: 4 serious events

Other events: 37 other events

Deaths: 0 deaths

Subjects on Ospemifene 60 mg/Day (Baseline)

Serious events: 18 serious events

Other events: 252 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Shionogi Clinical Trials Administrator

Shionogi Inc.

Phone: 800-849-9707

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The sponsor can embargo results from a PI's center until the combined results from the completed study have been published in full or the sponsor confirms there will be no multicenter study publication. Results communications must be provided to the sponsor for review at least 60 days before submission for publication. By written request, the sponsor can extend the embargo up to an additional 60 days. The sponsor cannot require changes to scientific content and cannot further extend the embargo.
Publication restrictions are in place

Restriction type: OTHER

Measure	Subjects on Placebo (Baseline) n=62 participants at risk Placebo was taken orally, once daily, in the morning, with food for 52 weeks.	Subjects on Ospemifene 60 mg/Day (Baseline) n=364 participants at risk Ospemifene was taken orally, once daily, in the morning, with food for 52 weeks.
Musculoskeletal and connective tissue disorders Seronegative Arthritis	1.6% 1/62 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.	0.00% 0/364 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.
Gastrointestinal disorders Nausea	1.6% 1/62 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.	0.00% 0/364 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.
Cardiac disorders Tachycardia	1.6% 1/62 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.	0.00% 0/364 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.
Nervous system disorders Dizziness	1.6% 1/62 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.	0.00% 0/364 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.
Renal and urinary disorders Calculus urinary	1.6% 1/62 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.	0.00% 0/364 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.
Infections and infestations Urinary tract infection	1.6% 1/62 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.	0.00% 0/364 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.
Injury, poisoning and procedural complications Patella fracture	1.6% 1/62 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.	0.00% 0/364 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.
Cardiac disorders Mitral valve incompetence	1.6% 1/62 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.	0.00% 0/364 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.
Nervous system disorders Cerebral haemorrhage	0.00% 0/62 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.	0.27% 1/364 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/62 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.	0.27% 1/364 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.
Surgical and medical procedures Cardiac ablation	0.00% 0/62 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.	0.27% 1/364 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.
Reproductive system and breast disorders Endometrial hyperplasia	0.00% 0/62 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.	0.27% 1/364 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.
Gastrointestinal disorders Diverticulitis	0.00% 0/62 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.	0.27% 1/364 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.
Surgical and medical procedures Breast cosmetic surgery	0.00% 0/62 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.	0.27% 1/364 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.
Surgical and medical procedures Carpel tunnel decompression	0.00% 0/62 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.	0.27% 1/364 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.
Surgical and medical procedures Blepharoplasty	0.00% 0/62 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.	0.27% 1/364 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.
Nervous system disorders Cerebrovascular accident	0.00% 0/62 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.	0.27% 1/364 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.
Gastrointestinal disorders Hiatus hernia	0.00% 0/62 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.	0.27% 1/364 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.
Hepatobiliary disorders Cholelithiasis	0.00% 0/62 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.	0.27% 1/364 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Ovarian cyst	0.00% 0/62 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.	0.27% 1/364 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.
Vascular disorders Deep vein thrombosis	0.00% 0/62 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.	0.27% 1/364 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.
Gastrointestinal disorders Gastrointestinal inflammation	0.00% 0/62 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.	0.27% 1/364 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.
Injury, poisoning and procedural complications Lower limb fracture	0.00% 0/62 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.	0.27% 1/364 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.
Injury, poisoning and procedural complications Road traffic accident	0.00% 0/62 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.	0.27% 1/364 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.
Injury, poisoning and procedural complications Burns third degree	0.00% 0/62 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.	0.27% 1/364 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.
Nervous system disorders Global amnesia	0.00% 0/62 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.	0.27% 1/364 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Mesothelioma malignant	0.00% 0/62 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.	0.27% 1/364 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.
Surgical and medical procedures Arthrodesis	0.00% 0/62 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.	0.27% 1/364 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.
Blood and lymphatic system disorders Multiple myeloma	0.00% 0/62 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.	0.27% 1/364 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.
Musculoskeletal and connective tissue disorders Spinal column stenosis	0.00% 0/62 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.	0.27% 1/364 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.

Measure	Subjects on Placebo (Baseline) n=62 participants at risk Placebo was taken orally, once daily, in the morning, with food for 52 weeks.	Subjects on Ospemifene 60 mg/Day (Baseline) n=364 participants at risk Ospemifene was taken orally, once daily, in the morning, with food for 52 weeks.
Gastrointestinal disorders Diarrhoea	1.6% 1/62 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.	4.1% 15/364 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.
Gastrointestinal disorders Abdominal Pain Lower	3.2% 2/62 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.	2.7% 10/364 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.
Gastrointestinal disorders Nausea	3.2% 2/62 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.	2.7% 10/364 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.
Gastrointestinal disorders Abdominal Pain	3.2% 2/62 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.	1.4% 5/364 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.
Gastrointestinal disorders Abdominal Pain Upper	6.5% 4/62 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.	0.82% 3/364 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.
General disorders Influenza Like Illness	6.5% 4/62 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.	3.8% 14/364 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.
Infections and infestations Nasopharyngitis	6.5% 4/62 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.	9.9% 36/364 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.
Infections and infestations Vulvovaginal Candidiasis	1.6% 1/62 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.	7.4% 27/364 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.
Infections and infestations Urinary Tract Infection	11.3% 7/62 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.	5.5% 20/364 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.
Infections and infestations Cystitis	0.00% 0/62 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.	4.9% 18/364 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.
Infections and infestations Urinary Tract Infection Bacterial	9.7% 6/62 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.	4.4% 16/364 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.
Infections and infestations Bronchitis	1.6% 1/62 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.	4.1% 15/364 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.
Infections and infestations Sinusitis	0.00% 0/62 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.	3.8% 14/364 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.
Infections and infestations Gastroenteritis	3.2% 2/62 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.	2.2% 8/364 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.
Infections and infestations Urinary Tract Infection Staphylococcal	3.2% 2/62 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.	0.55% 2/364 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.
Infections and infestations Asymptomatic Bacteriuria	3.2% 2/62 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.	0.27% 1/364 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.
Metabolism and nutrition disorders Hypercholesterolaemia	6.5% 4/62 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.	1.6% 6/364 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.
Musculoskeletal and connective tissue disorders Muscle Spasms	6.5% 4/62 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.	8.5% 31/364 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.
Musculoskeletal and connective tissue disorders Back Pain	3.2% 2/62 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.	6.6% 24/364 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.
Musculoskeletal and connective tissue disorders Arthralgia	4.8% 3/62 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.	3.8% 14/364 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.
Musculoskeletal and connective tissue disorders Pain In Extremity	0.00% 0/62 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.	3.3% 12/364 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.
Musculoskeletal and connective tissue disorders Tendonitis	3.2% 2/62 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.	0.27% 1/364 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.
Nervous system disorders Headache	9.7% 6/62 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.	9.1% 33/364 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.
Psychiatric disorders Insomnia	0.00% 0/62 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.	5.2% 19/364 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.
Reproductive system and breast disorders Vaginal Discharge	0.00% 0/62 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.	5.5% 20/364 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.
Reproductive system and breast disorders Vulvovaginal Dryness	1.6% 1/62 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.	3.3% 12/364 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.
Reproductive system and breast disorders Genital Discharge	1.6% 1/62 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.	3.0% 11/364 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.
Skin and subcutaneous tissue disorders Hyperhidrosis	8.1% 5/62 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.	6.0% 22/364 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.
Vascular disorders Hot Flush	6.5% 4/62 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.	12.6% 46/364 • 16 Weeks; From the signing of the informed consent form to the last safety evaluation (Week 12) Safety data were reported in the safety population, which included all treated subjects according to the treatment they actually received.