Trial Outcomes & Findings for A Clinical Study to Evaluate the Effects of Estrogen in Healthy Postmenopausal Women (NCT NCT00820664)

NCT ID: NCT00820664

Last Updated: 2016-01-22

Results Overview

Ratio of the total number of positively stained cell nuclei to the total number of cell nuclei. Proliferating endometrial cells express the Ki-67 antigen. The ratio was converted to a percent proliferating cells by taking the number of Ki-67 positive stained nuclei in a given field and dividing by the total number of nuclei in that field and multiplying by 100. At least 5 high power fields were scored in this manner and an aggregate percent Ki-67 positive cells was reported. Square root transformation was taken to make it approximately normally distributed for an ANOVA model to apply.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

29 participants

Primary outcome timeframe

4 weeks

Results posted on

2016-01-22

Participant Flow

Patients were recruited through advertisement and review of patient databases at Comprehensive Phase I, USA, between December 2008 and April 2009.

Major entry criteria - healthy postmenopausal women within 10 years of attaining menopause as determined by follicle-stimulating hormone (FSH) and estradiol levels within range of postmenopause, and other criteria. Normal transvaginal ultrasound at screening with endometrial thickening at \< 5.0 mm.

Participant milestones

Participant milestones
Measure	17β-estradiol 2.0 Milligrams Estrace 2.0 mg tablet	17β-estradiol 0.5 Milligrams Estrace 0.5 mg tablet	Placebo
Overall Study STARTED	9	11	9
Overall Study COMPLETED	9	11	9
Overall Study NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Clinical Study to Evaluate the Effects of Estrogen in Healthy Postmenopausal Women

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	17β-estradiol 2.0 Milligrams n=9 Participants Estrace 2.0 mg tablet	17β-estradiol 0.5 Milligrams n=11 Participants Estrace 0.5 mg tablet	Placebo n=9 Participants	Total n=29 Participants Total of all reporting groups
Age, Continuous	54.11 years STANDARD_DEVIATION 3.76 • n=5 Participants	53.91 years STANDARD_DEVIATION 5.65 • n=7 Participants	55.33 years STANDARD_DEVIATION 3.04 • n=5 Participants	54.41 years STANDARD_DEVIATION 4.30 • n=4 Participants
Sex: Female, Male Female	9 Participants n=5 Participants	11 Participants n=7 Participants	9 Participants n=5 Participants	29 Participants n=4 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race/Ethnicity, Customized Black	1 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	1 participants n=4 Participants
Race/Ethnicity, Customized White	8 participants n=5 Participants	11 participants n=7 Participants	9 participants n=5 Participants	28 participants n=4 Participants
Body Mass Index (BMI)	27.87 kg/m^2 STANDARD_DEVIATION 3.95 • n=5 Participants	28.69 kg/m^2 STANDARD_DEVIATION 2.74 • n=7 Participants	27.43 kg/m^2 STANDARD_DEVIATION 1.98 • n=5 Participants	28.05 kg/m^2 STANDARD_DEVIATION 2.92 • n=4 Participants

PRIMARY outcome

Timeframe: 4 weeks

Population: Though 29 subjects were enrolled, only 20 subjects had biopsy samples that were deemed adequate for Ki-67 immunohistochemical analysis at Week 4.

Outcome measures

Outcome measures
Measure	17β-estradiol 2.0 Milligrams n=6 Participants Estrace 2.0 mg tablet	17β-estradiol 0.5 Milligrams n=8 Participants Estrace 0.5 mg tablet	Placebo n=6 Participants
Immunohistochemistry (IHC) Proliferative Effects Measurement	0.73 Square root of % positive stained cells Interval 0.61 to 0.86	0.43 Square root of % positive stained cells Interval 0.32 to 0.54	0.25 Square root of % positive stained cells Interval 0.12 to 0.37

SECONDARY outcome

Timeframe: 4 weeks

Outcome measures

Outcome data not reported

Adverse Events

17β-estradiol 2.0 Milligrams

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

17β-estradiol 0.5 Milligrams

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Executive Vice President, Clinical and Quantitative Sciences

Merck Sharp & Dohme Corp

Phone: 1-800-672-6372

Results disclosure agreements

Principal investigator is a sponsor employee Merck agreements may vary with individual investigators, but will not prohibit any investigator from publishing. Merck supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Publication restrictions are in place

Restriction type: OTHER

Other adverse events
Measure	17β-estradiol 2.0 Milligrams n=9 participants at risk Estrace 2.0 mg tablet	17β-estradiol 0.5 Milligrams n=11 participants at risk Estrace 0.5 mg tablet	Placebo n=9 participants at risk
Nervous system disorders Dizziness	11.1% 1/9 • Reported AE data were collected during the period of the study from date of informed consent to the 14 day follow up period following completion of treatment. Clinical staff telephoned subjects daily during the study, in between clinic visits and asked the subjects if they had experienced any adverse experiences.	18.2% 2/11 • Reported AE data were collected during the period of the study from date of informed consent to the 14 day follow up period following completion of treatment. Clinical staff telephoned subjects daily during the study, in between clinic visits and asked the subjects if they had experienced any adverse experiences.	11.1% 1/9 • Reported AE data were collected during the period of the study from date of informed consent to the 14 day follow up period following completion of treatment. Clinical staff telephoned subjects daily during the study, in between clinic visits and asked the subjects if they had experienced any adverse experiences.
Nervous system disorders Headache	22.2% 2/9 • Reported AE data were collected during the period of the study from date of informed consent to the 14 day follow up period following completion of treatment. Clinical staff telephoned subjects daily during the study, in between clinic visits and asked the subjects if they had experienced any adverse experiences.	9.1% 1/11 • Reported AE data were collected during the period of the study from date of informed consent to the 14 day follow up period following completion of treatment. Clinical staff telephoned subjects daily during the study, in between clinic visits and asked the subjects if they had experienced any adverse experiences.	11.1% 1/9 • Reported AE data were collected during the period of the study from date of informed consent to the 14 day follow up period following completion of treatment. Clinical staff telephoned subjects daily during the study, in between clinic visits and asked the subjects if they had experienced any adverse experiences.
Nervous system disorders Somnolence	11.1% 1/9 • Reported AE data were collected during the period of the study from date of informed consent to the 14 day follow up period following completion of treatment. Clinical staff telephoned subjects daily during the study, in between clinic visits and asked the subjects if they had experienced any adverse experiences.	0.00% 0/11 • Reported AE data were collected during the period of the study from date of informed consent to the 14 day follow up period following completion of treatment. Clinical staff telephoned subjects daily during the study, in between clinic visits and asked the subjects if they had experienced any adverse experiences.	0.00% 0/9 • Reported AE data were collected during the period of the study from date of informed consent to the 14 day follow up period following completion of treatment. Clinical staff telephoned subjects daily during the study, in between clinic visits and asked the subjects if they had experienced any adverse experiences.
Psychiatric disorders Insomnia	0.00% 0/9 • Reported AE data were collected during the period of the study from date of informed consent to the 14 day follow up period following completion of treatment. Clinical staff telephoned subjects daily during the study, in between clinic visits and asked the subjects if they had experienced any adverse experiences.	9.1% 1/11 • Reported AE data were collected during the period of the study from date of informed consent to the 14 day follow up period following completion of treatment. Clinical staff telephoned subjects daily during the study, in between clinic visits and asked the subjects if they had experienced any adverse experiences.	0.00% 0/9 • Reported AE data were collected during the period of the study from date of informed consent to the 14 day follow up period following completion of treatment. Clinical staff telephoned subjects daily during the study, in between clinic visits and asked the subjects if they had experienced any adverse experiences.
Renal and urinary disorders Pollakiuria	0.00% 0/9 • Reported AE data were collected during the period of the study from date of informed consent to the 14 day follow up period following completion of treatment. Clinical staff telephoned subjects daily during the study, in between clinic visits and asked the subjects if they had experienced any adverse experiences.	0.00% 0/11 • Reported AE data were collected during the period of the study from date of informed consent to the 14 day follow up period following completion of treatment. Clinical staff telephoned subjects daily during the study, in between clinic visits and asked the subjects if they had experienced any adverse experiences.	11.1% 1/9 • Reported AE data were collected during the period of the study from date of informed consent to the 14 day follow up period following completion of treatment. Clinical staff telephoned subjects daily during the study, in between clinic visits and asked the subjects if they had experienced any adverse experiences.
Renal and urinary disorders Urinary Retention	0.00% 0/9 • Reported AE data were collected during the period of the study from date of informed consent to the 14 day follow up period following completion of treatment. Clinical staff telephoned subjects daily during the study, in between clinic visits and asked the subjects if they had experienced any adverse experiences.	9.1% 1/11 • Reported AE data were collected during the period of the study from date of informed consent to the 14 day follow up period following completion of treatment. Clinical staff telephoned subjects daily during the study, in between clinic visits and asked the subjects if they had experienced any adverse experiences.	0.00% 0/9 • Reported AE data were collected during the period of the study from date of informed consent to the 14 day follow up period following completion of treatment. Clinical staff telephoned subjects daily during the study, in between clinic visits and asked the subjects if they had experienced any adverse experiences.
Reproductive system and breast disorders Endometrial Hyperplasia	0.00% 0/9 • Reported AE data were collected during the period of the study from date of informed consent to the 14 day follow up period following completion of treatment. Clinical staff telephoned subjects daily during the study, in between clinic visits and asked the subjects if they had experienced any adverse experiences.	9.1% 1/11 • Reported AE data were collected during the period of the study from date of informed consent to the 14 day follow up period following completion of treatment. Clinical staff telephoned subjects daily during the study, in between clinic visits and asked the subjects if they had experienced any adverse experiences.	0.00% 0/9 • Reported AE data were collected during the period of the study from date of informed consent to the 14 day follow up period following completion of treatment. Clinical staff telephoned subjects daily during the study, in between clinic visits and asked the subjects if they had experienced any adverse experiences.
Reproductive system and breast disorders Menorrhagia	0.00% 0/9 • Reported AE data were collected during the period of the study from date of informed consent to the 14 day follow up period following completion of treatment. Clinical staff telephoned subjects daily during the study, in between clinic visits and asked the subjects if they had experienced any adverse experiences.	9.1% 1/11 • Reported AE data were collected during the period of the study from date of informed consent to the 14 day follow up period following completion of treatment. Clinical staff telephoned subjects daily during the study, in between clinic visits and asked the subjects if they had experienced any adverse experiences.	0.00% 0/9 • Reported AE data were collected during the period of the study from date of informed consent to the 14 day follow up period following completion of treatment. Clinical staff telephoned subjects daily during the study, in between clinic visits and asked the subjects if they had experienced any adverse experiences.
Reproductive system and breast disorders Ovarian Cyst	0.00% 0/9 • Reported AE data were collected during the period of the study from date of informed consent to the 14 day follow up period following completion of treatment. Clinical staff telephoned subjects daily during the study, in between clinic visits and asked the subjects if they had experienced any adverse experiences.	9.1% 1/11 • Reported AE data were collected during the period of the study from date of informed consent to the 14 day follow up period following completion of treatment. Clinical staff telephoned subjects daily during the study, in between clinic visits and asked the subjects if they had experienced any adverse experiences.	0.00% 0/9 • Reported AE data were collected during the period of the study from date of informed consent to the 14 day follow up period following completion of treatment. Clinical staff telephoned subjects daily during the study, in between clinic visits and asked the subjects if they had experienced any adverse experiences.
Reproductive system and breast disorders Pelvic Pain	0.00% 0/9 • Reported AE data were collected during the period of the study from date of informed consent to the 14 day follow up period following completion of treatment. Clinical staff telephoned subjects daily during the study, in between clinic visits and asked the subjects if they had experienced any adverse experiences.	0.00% 0/11 • Reported AE data were collected during the period of the study from date of informed consent to the 14 day follow up period following completion of treatment. Clinical staff telephoned subjects daily during the study, in between clinic visits and asked the subjects if they had experienced any adverse experiences.	11.1% 1/9 • Reported AE data were collected during the period of the study from date of informed consent to the 14 day follow up period following completion of treatment. Clinical staff telephoned subjects daily during the study, in between clinic visits and asked the subjects if they had experienced any adverse experiences.
Reproductive system and breast disorders Postmenopausal Haemorrhage	11.1% 1/9 • Reported AE data were collected during the period of the study from date of informed consent to the 14 day follow up period following completion of treatment. Clinical staff telephoned subjects daily during the study, in between clinic visits and asked the subjects if they had experienced any adverse experiences.	0.00% 0/11 • Reported AE data were collected during the period of the study from date of informed consent to the 14 day follow up period following completion of treatment. Clinical staff telephoned subjects daily during the study, in between clinic visits and asked the subjects if they had experienced any adverse experiences.	0.00% 0/9 • Reported AE data were collected during the period of the study from date of informed consent to the 14 day follow up period following completion of treatment. Clinical staff telephoned subjects daily during the study, in between clinic visits and asked the subjects if they had experienced any adverse experiences.
Reproductive system and breast disorders Vaginal Discharge	11.1% 1/9 • Reported AE data were collected during the period of the study from date of informed consent to the 14 day follow up period following completion of treatment. Clinical staff telephoned subjects daily during the study, in between clinic visits and asked the subjects if they had experienced any adverse experiences.	0.00% 0/11 • Reported AE data were collected during the period of the study from date of informed consent to the 14 day follow up period following completion of treatment. Clinical staff telephoned subjects daily during the study, in between clinic visits and asked the subjects if they had experienced any adverse experiences.	0.00% 0/9 • Reported AE data were collected during the period of the study from date of informed consent to the 14 day follow up period following completion of treatment. Clinical staff telephoned subjects daily during the study, in between clinic visits and asked the subjects if they had experienced any adverse experiences.
Reproductive system and breast disorders Vaginal Haemorrhage	44.4% 4/9 • Reported AE data were collected during the period of the study from date of informed consent to the 14 day follow up period following completion of treatment. Clinical staff telephoned subjects daily during the study, in between clinic visits and asked the subjects if they had experienced any adverse experiences.	9.1% 1/11 • Reported AE data were collected during the period of the study from date of informed consent to the 14 day follow up period following completion of treatment. Clinical staff telephoned subjects daily during the study, in between clinic visits and asked the subjects if they had experienced any adverse experiences.	0.00% 0/9 • Reported AE data were collected during the period of the study from date of informed consent to the 14 day follow up period following completion of treatment. Clinical staff telephoned subjects daily during the study, in between clinic visits and asked the subjects if they had experienced any adverse experiences.
Reproductive system and breast disorders Vulvovaginal Pruritus	22.2% 2/9 • Reported AE data were collected during the period of the study from date of informed consent to the 14 day follow up period following completion of treatment. Clinical staff telephoned subjects daily during the study, in between clinic visits and asked the subjects if they had experienced any adverse experiences.	0.00% 0/11 • Reported AE data were collected during the period of the study from date of informed consent to the 14 day follow up period following completion of treatment. Clinical staff telephoned subjects daily during the study, in between clinic visits and asked the subjects if they had experienced any adverse experiences.	0.00% 0/9 • Reported AE data were collected during the period of the study from date of informed consent to the 14 day follow up period following completion of treatment. Clinical staff telephoned subjects daily during the study, in between clinic visits and asked the subjects if they had experienced any adverse experiences.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/9 • Reported AE data were collected during the period of the study from date of informed consent to the 14 day follow up period following completion of treatment. Clinical staff telephoned subjects daily during the study, in between clinic visits and asked the subjects if they had experienced any adverse experiences.	0.00% 0/11 • Reported AE data were collected during the period of the study from date of informed consent to the 14 day follow up period following completion of treatment. Clinical staff telephoned subjects daily during the study, in between clinic visits and asked the subjects if they had experienced any adverse experiences.	33.3% 3/9 • Reported AE data were collected during the period of the study from date of informed consent to the 14 day follow up period following completion of treatment. Clinical staff telephoned subjects daily during the study, in between clinic visits and asked the subjects if they had experienced any adverse experiences.
Respiratory, thoracic and mediastinal disorders Respiratory Tract Congestion	0.00% 0/9 • Reported AE data were collected during the period of the study from date of informed consent to the 14 day follow up period following completion of treatment. Clinical staff telephoned subjects daily during the study, in between clinic visits and asked the subjects if they had experienced any adverse experiences.	0.00% 0/11 • Reported AE data were collected during the period of the study from date of informed consent to the 14 day follow up period following completion of treatment. Clinical staff telephoned subjects daily during the study, in between clinic visits and asked the subjects if they had experienced any adverse experiences.	11.1% 1/9 • Reported AE data were collected during the period of the study from date of informed consent to the 14 day follow up period following completion of treatment. Clinical staff telephoned subjects daily during the study, in between clinic visits and asked the subjects if they had experienced any adverse experiences.
General disorders Feeling Cold	0.00% 0/9 • Reported AE data were collected during the period of the study from date of informed consent to the 14 day follow up period following completion of treatment. Clinical staff telephoned subjects daily during the study, in between clinic visits and asked the subjects if they had experienced any adverse experiences.	0.00% 0/11 • Reported AE data were collected during the period of the study from date of informed consent to the 14 day follow up period following completion of treatment. Clinical staff telephoned subjects daily during the study, in between clinic visits and asked the subjects if they had experienced any adverse experiences.	11.1% 1/9 • Reported AE data were collected during the period of the study from date of informed consent to the 14 day follow up period following completion of treatment. Clinical staff telephoned subjects daily during the study, in between clinic visits and asked the subjects if they had experienced any adverse experiences.
Infections and infestations Pharyngitis	0.00% 0/9 • Reported AE data were collected during the period of the study from date of informed consent to the 14 day follow up period following completion of treatment. Clinical staff telephoned subjects daily during the study, in between clinic visits and asked the subjects if they had experienced any adverse experiences.	0.00% 0/11 • Reported AE data were collected during the period of the study from date of informed consent to the 14 day follow up period following completion of treatment. Clinical staff telephoned subjects daily during the study, in between clinic visits and asked the subjects if they had experienced any adverse experiences.	11.1% 1/9 • Reported AE data were collected during the period of the study from date of informed consent to the 14 day follow up period following completion of treatment. Clinical staff telephoned subjects daily during the study, in between clinic visits and asked the subjects if they had experienced any adverse experiences.
Infections and infestations Viral Upper Respiratory Tract Infection	11.1% 1/9 • Reported AE data were collected during the period of the study from date of informed consent to the 14 day follow up period following completion of treatment. Clinical staff telephoned subjects daily during the study, in between clinic visits and asked the subjects if they had experienced any adverse experiences.	0.00% 0/11 • Reported AE data were collected during the period of the study from date of informed consent to the 14 day follow up period following completion of treatment. Clinical staff telephoned subjects daily during the study, in between clinic visits and asked the subjects if they had experienced any adverse experiences.	0.00% 0/9 • Reported AE data were collected during the period of the study from date of informed consent to the 14 day follow up period following completion of treatment. Clinical staff telephoned subjects daily during the study, in between clinic visits and asked the subjects if they had experienced any adverse experiences.
Investigations Blood Pressure Increased	0.00% 0/9 • Reported AE data were collected during the period of the study from date of informed consent to the 14 day follow up period following completion of treatment. Clinical staff telephoned subjects daily during the study, in between clinic visits and asked the subjects if they had experienced any adverse experiences.	0.00% 0/11 • Reported AE data were collected during the period of the study from date of informed consent to the 14 day follow up period following completion of treatment. Clinical staff telephoned subjects daily during the study, in between clinic visits and asked the subjects if they had experienced any adverse experiences.	22.2% 2/9 • Reported AE data were collected during the period of the study from date of informed consent to the 14 day follow up period following completion of treatment. Clinical staff telephoned subjects daily during the study, in between clinic visits and asked the subjects if they had experienced any adverse experiences.
Eye disorders Vision Blurred	11.1% 1/9 • Reported AE data were collected during the period of the study from date of informed consent to the 14 day follow up period following completion of treatment. Clinical staff telephoned subjects daily during the study, in between clinic visits and asked the subjects if they had experienced any adverse experiences.	0.00% 0/11 • Reported AE data were collected during the period of the study from date of informed consent to the 14 day follow up period following completion of treatment. Clinical staff telephoned subjects daily during the study, in between clinic visits and asked the subjects if they had experienced any adverse experiences.	0.00% 0/9 • Reported AE data were collected during the period of the study from date of informed consent to the 14 day follow up period following completion of treatment. Clinical staff telephoned subjects daily during the study, in between clinic visits and asked the subjects if they had experienced any adverse experiences.
Gastrointestinal disorders Abdominal Discomfort	22.2% 2/9 • Reported AE data were collected during the period of the study from date of informed consent to the 14 day follow up period following completion of treatment. Clinical staff telephoned subjects daily during the study, in between clinic visits and asked the subjects if they had experienced any adverse experiences.	0.00% 0/11 • Reported AE data were collected during the period of the study from date of informed consent to the 14 day follow up period following completion of treatment. Clinical staff telephoned subjects daily during the study, in between clinic visits and asked the subjects if they had experienced any adverse experiences.	0.00% 0/9 • Reported AE data were collected during the period of the study from date of informed consent to the 14 day follow up period following completion of treatment. Clinical staff telephoned subjects daily during the study, in between clinic visits and asked the subjects if they had experienced any adverse experiences.
Gastrointestinal disorders Abdominal Distension	11.1% 1/9 • Reported AE data were collected during the period of the study from date of informed consent to the 14 day follow up period following completion of treatment. Clinical staff telephoned subjects daily during the study, in between clinic visits and asked the subjects if they had experienced any adverse experiences.	0.00% 0/11 • Reported AE data were collected during the period of the study from date of informed consent to the 14 day follow up period following completion of treatment. Clinical staff telephoned subjects daily during the study, in between clinic visits and asked the subjects if they had experienced any adverse experiences.	0.00% 0/9 • Reported AE data were collected during the period of the study from date of informed consent to the 14 day follow up period following completion of treatment. Clinical staff telephoned subjects daily during the study, in between clinic visits and asked the subjects if they had experienced any adverse experiences.
Gastrointestinal disorders Abdominal Pain	22.2% 2/9 • Reported AE data were collected during the period of the study from date of informed consent to the 14 day follow up period following completion of treatment. Clinical staff telephoned subjects daily during the study, in between clinic visits and asked the subjects if they had experienced any adverse experiences.	18.2% 2/11 • Reported AE data were collected during the period of the study from date of informed consent to the 14 day follow up period following completion of treatment. Clinical staff telephoned subjects daily during the study, in between clinic visits and asked the subjects if they had experienced any adverse experiences.	22.2% 2/9 • Reported AE data were collected during the period of the study from date of informed consent to the 14 day follow up period following completion of treatment. Clinical staff telephoned subjects daily during the study, in between clinic visits and asked the subjects if they had experienced any adverse experiences.
Gastrointestinal disorders Abdominal Pain Lower	11.1% 1/9 • Reported AE data were collected during the period of the study from date of informed consent to the 14 day follow up period following completion of treatment. Clinical staff telephoned subjects daily during the study, in between clinic visits and asked the subjects if they had experienced any adverse experiences.	9.1% 1/11 • Reported AE data were collected during the period of the study from date of informed consent to the 14 day follow up period following completion of treatment. Clinical staff telephoned subjects daily during the study, in between clinic visits and asked the subjects if they had experienced any adverse experiences.	11.1% 1/9 • Reported AE data were collected during the period of the study from date of informed consent to the 14 day follow up period following completion of treatment. Clinical staff telephoned subjects daily during the study, in between clinic visits and asked the subjects if they had experienced any adverse experiences.
Gastrointestinal disorders Diarrhoea	11.1% 1/9 • Reported AE data were collected during the period of the study from date of informed consent to the 14 day follow up period following completion of treatment. Clinical staff telephoned subjects daily during the study, in between clinic visits and asked the subjects if they had experienced any adverse experiences.	0.00% 0/11 • Reported AE data were collected during the period of the study from date of informed consent to the 14 day follow up period following completion of treatment. Clinical staff telephoned subjects daily during the study, in between clinic visits and asked the subjects if they had experienced any adverse experiences.	0.00% 0/9 • Reported AE data were collected during the period of the study from date of informed consent to the 14 day follow up period following completion of treatment. Clinical staff telephoned subjects daily during the study, in between clinic visits and asked the subjects if they had experienced any adverse experiences.
Gastrointestinal disorders Frequent Bowel Movements	0.00% 0/9 • Reported AE data were collected during the period of the study from date of informed consent to the 14 day follow up period following completion of treatment. Clinical staff telephoned subjects daily during the study, in between clinic visits and asked the subjects if they had experienced any adverse experiences.	9.1% 1/11 • Reported AE data were collected during the period of the study from date of informed consent to the 14 day follow up period following completion of treatment. Clinical staff telephoned subjects daily during the study, in between clinic visits and asked the subjects if they had experienced any adverse experiences.	0.00% 0/9 • Reported AE data were collected during the period of the study from date of informed consent to the 14 day follow up period following completion of treatment. Clinical staff telephoned subjects daily during the study, in between clinic visits and asked the subjects if they had experienced any adverse experiences.
Musculoskeletal and connective tissue disorders Back Pain	0.00% 0/9 • Reported AE data were collected during the period of the study from date of informed consent to the 14 day follow up period following completion of treatment. Clinical staff telephoned subjects daily during the study, in between clinic visits and asked the subjects if they had experienced any adverse experiences.	18.2% 2/11 • Reported AE data were collected during the period of the study from date of informed consent to the 14 day follow up period following completion of treatment. Clinical staff telephoned subjects daily during the study, in between clinic visits and asked the subjects if they had experienced any adverse experiences.	0.00% 0/9 • Reported AE data were collected during the period of the study from date of informed consent to the 14 day follow up period following completion of treatment. Clinical staff telephoned subjects daily during the study, in between clinic visits and asked the subjects if they had experienced any adverse experiences.
Musculoskeletal and connective tissue disorders Groin Pain	0.00% 0/9 • Reported AE data were collected during the period of the study from date of informed consent to the 14 day follow up period following completion of treatment. Clinical staff telephoned subjects daily during the study, in between clinic visits and asked the subjects if they had experienced any adverse experiences.	0.00% 0/11 • Reported AE data were collected during the period of the study from date of informed consent to the 14 day follow up period following completion of treatment. Clinical staff telephoned subjects daily during the study, in between clinic visits and asked the subjects if they had experienced any adverse experiences.	11.1% 1/9 • Reported AE data were collected during the period of the study from date of informed consent to the 14 day follow up period following completion of treatment. Clinical staff telephoned subjects daily during the study, in between clinic visits and asked the subjects if they had experienced any adverse experiences.
Musculoskeletal and connective tissue disorders Pain In Extremity	0.00% 0/9 • Reported AE data were collected during the period of the study from date of informed consent to the 14 day follow up period following completion of treatment. Clinical staff telephoned subjects daily during the study, in between clinic visits and asked the subjects if they had experienced any adverse experiences.	9.1% 1/11 • Reported AE data were collected during the period of the study from date of informed consent to the 14 day follow up period following completion of treatment. Clinical staff telephoned subjects daily during the study, in between clinic visits and asked the subjects if they had experienced any adverse experiences.	11.1% 1/9 • Reported AE data were collected during the period of the study from date of informed consent to the 14 day follow up period following completion of treatment. Clinical staff telephoned subjects daily during the study, in between clinic visits and asked the subjects if they had experienced any adverse experiences.