Pharmacokinetic, Safety, Tolerability and Immunogenicity Study of SB4 in Healthy Male Subjects

• Sponsor: Samsung Bioepis Co., Ltd. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01865552
• Collaborator: (none)
• Enrollment: 138
• Location: 1
• Arms: 6
• Duration (Months): 3
• Patients Per Site Per Month: 45.7

Study Details

Study Description

Brief Summary

The purpose of this study is to compare the pharmacokinetics, safety and immunogenicity of SB4 and Enbrel (EU sourced Enbrel and US sourced Enbrel) in healthy male subjects.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Biological: SB4; Biological: EU sourced Enbrel; Biological: US sourced Enbrel	Phase 1

Detailed Description

• Part A: Comparison between SB4 and EU sourced Enbrel

• Part B: Comparison between SB4 and US sourced Enbrel

• Part C: Comparison between EU sourced Enbrel and US sourced Enbrel

Study Design

• Study Type: Interventional
• Actual Enrollment: 138 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Single (Participant)
• Primary Purpose: Other
• Official Title: A Randomised, Single-blind, Three-part, Two-period, Two-sequence, Single-dose, Cross-over Study to Compare the Pharmacokinetics, Safety, Tolerability and Immunogenicity of Three Formulations of Etanercept (SB4, EU Sourced Enbrel® and US Sourced Enbrel®) in Healthy Male Subjects
• Study Start Date: May 1, 2013
• Actual Primary Completion Date: Aug 1, 2013
• Actual Study Completion Date: Aug 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: SB4 and EU sourced Enbrel in Part A SB4 followed by EU sourced Enbrel	Biological: SB4; SC administration; Biological: EU sourced Enbrel; SC administration
Experimental: EU sourced Enbrel and SB4 in Part A EU sourced Enbrel followed by SB4	Biological: SB4; SC administration; Biological: EU sourced Enbrel; SC administration
Experimental: SB4 and US sourced Enbrel in Part B SB4 followed by US sourced Enbrel	Biological: SB4; SC administration; Biological: US sourced Enbrel; SC administration
Experimental: US sourced Enbrel and SB4 in Part B US sourced Enbrel followed by SB4	Biological: SB4; SC administration; Biological: US sourced Enbrel; SC administration
Other: EU and US sourced Enbrel in Part C EU sourced Enbrel followed by US sourced Enbrel	Biological: EU sourced Enbrel; SC administration; Biological: US sourced Enbrel; SC administration
Other: US and EU sourced Enbrel in Part C US sourced Enbrel followed by EU sourced Enbrel	Biological: EU sourced Enbrel; SC administration; Biological: US sourced Enbrel; SC administration

Outcome Measures

Primary Outcome Measures

1. Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) [0 to 480 hours post-dose]

   pre-dose and at 6, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 216, 312 and 480 h post-dose

2. Maximum Serum Concentration (Cmax) [0 to 480 hours post-dose]

   pre-dose (0 h) and at 6, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 216, 312 and 480 h post-dose.

Secondary Outcome Measures

1. Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) [0 to 480 hours post-dose]

   pre-dose and at 6, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 216, 312 and 480 h post-dose

2. Time to Cmax (Tmax) [0 to 480 hours post-dose]

   pre-dose and at 6, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 216, 312 and 480 h post-dose

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Healthy male subjects

• Have a body weight between 60 and 94.9 kg and a body mass index between 20.0 and 29.9 kg/m², inclusive.

Exclusion Criteria:

• history and/or current presence of clinical significant atopic allergy, hypersensitivity or allergic reactions, also including known or suspected clinically relevant drug hypersensitivity to any components of the test and reference IP formulation or comparable drugs.

• active or latent Tuberculosis or who have a history of TB.

• history of invasive systemic fungal infections or other opportunistic infections

• systemic or local infection, a known risk for developing sepsis and/or known active inflammatory process

• serious infection associated with hospitalisation and/or which required intravenous antibiotics

• history of and/or current cardiac disease

• have received live vaccine(s) within 30 days prior to Screening or who will require live vaccine(s) between Screening and the final study visit.

• Intake medication with a half-life > 24 h within 1 month or 10 half-lives of the medication prior to the first administration of IP.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Parexel International GmbH	Berlin		Germany

Sponsors and Collaborators

• Samsung Bioepis Co., Ltd.

Investigators

• Principal Investigator: Rainard Fuhr, M.D., Ph.D., Parexel

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Samsung Bioepis Co., Ltd.
• ClinicalTrials.gov Identifier: NCT01865552
• Other Study ID Numbers: SB4-G11-NHV; 2012-004371-39
• First Posted: May 31, 2013
• Last Update Posted: Jun 4, 2019
• Last Verified: Jun 1, 2019

• Keywords provided by Samsung Bioepis Co., Ltd.: Pharmacokinetics
• Additional relevant MeSH terms: Etanercept

Study Results

Participant Flow

Arm/Group Title	SB4 and EU Sourced Enbrel in Part A	EU Sourced Enbrel and SB4 in Part A	SB4 and US Sourced Enbrel in Part B	US Sourced Enbrel and SB4 in Part B	EU and US Sourced Enbrel in Part C	US and EU Sourced Enbrel in Part C
Arm/Group Description	SB4 (Period 1) followed by EU sourced Enbrel (Period 2) SB4: SC administration EU sourced Enbrel: SC administration	EU sourced Enbrel (Period 1) followed by SB4 (Period 2) SB4: SC administration EU sourced Enbrel: SC administration	SB4 (Period 1) followed by US sourced Enbrel (Period 2) SB4: SC administration US sourced Enbrel: SC administration	US sourced Enbrel (Period 1) followed by SB4 (Period 2) SB4: SC administration US sourced Enbrel: SC administration	EU sourced Enbrel (Period 1) followed by US sourced Enbrel (Period 2) EU sourced Enbrel: SC administration US sourced Enbrel: SC administration	US sourced Enbrel (Period 1) followed by EU sourced Enbrel (Period 2) EU sourced Enbrel: SC administration US sourced Enbrel: SC administration
Period Title: Period 1
STARTED	23	23	23	23	23	23
Discontinued From Period 1	1	0	0	1	3	1
COMPLETED	22	23	23	22	20	22
NOT COMPLETED	1	0	0	1	3	1
Period Title: Period 1
STARTED	22	23	23	22	20	22
COMPLETED	22	23	23	22	20	22
NOT COMPLETED	0	0	0	0	0	0

Baseline Characteristics

Arm/Group Title	SB4 and EU Sourced Enbrel in Part A	EU Sourced Enbrel and SB4 in Part A	SB4 and US Sourced Enbrel in Part B	US Sourced Enbrel and SB4 in Part B	EU and US Sourced Enbrel in Part C	US and EU Sourced Enbrel in Part C	Total
Arm/Group Description	SB4 followed by EU sourced Enbrel SB4: SC administration EU sourced Enbrel: SC administration	EU sourced Enbrel followed by SB4 SB4: SC administration EU sourced Enbrel: SC administration	SB4 followed by US sourced Enbrel SB4: SC administration US sourced Enbrel: SC administration	US sourced Enbrel followed by SB4 SB4: SC administration US sourced Enbrel: SC administration	EU sourced Enbrel followed by US sourced Enbrel EU sourced Enbrel: SC administration US sourced Enbrel: SC administration	US sourced Enbrel followed by EU sourced Enbrel EU sourced Enbrel: SC administration US sourced Enbrel: SC administration	Total of all reporting groups
Overall Participants	23	23	23	23	23	23	138
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	38 (9.4)	41 (10.9)	38 (9.7)	43 (8.9)	40 (10.5)	41 (9.4)	40 (9.8)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Male	23 100%	23 100%	23 100%	23 100%	23 100%	23 100%	138 100%

Outcome Measures

1. Primary Outcome

Title	Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf)
Description	pre-dose and at 6, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 216, 312 and 480 h post-dose
Time Frame	0 to 480 hours post-dose

Outcome Measure Data

Analysis Population Description

Overall number of participans Analyzed equals to number of subjects who contributed to summary statistics.

Arm/Group Title	SB4 in Part A	EU Sourced Enbrel in Part A	SB4 in Part B	US Sourced Enbrel in Part B	EU Sourced Enbrel in Part C	US Sourced Enbrel in Part C
Arm/Group Description	SB4: SC administration	EU sourced Enbrel: SC administration	SB4: SC administration	US sourced Enbrel: SC administration	EU sourced Enbrel: SC administration	US sourced Enbrel: SC administration
Measure Participants	42	42	44	44	42	42
Mean (Standard Deviation) [µg·h/mL]	769.069 (243.9039)	771.680 (226.2874)	834.680 (242.7652)	810.054 (195.9770)	790.110 (274.2535)	768.228 (238.1251)

2. Primary Outcome

Title	Maximum Serum Concentration (Cmax)
Description	pre-dose (0 h) and at 6, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 216, 312 and 480 h post-dose.
Time Frame	0 to 480 hours post-dose

Outcome Measure Data

Analysis Population Description

Overall number of participans Analyzed equals to number of subjects who contributed to summary statistics.

Arm/Group Title	SB4 in Part A	EU Sourced Enbrel in Part A	SB4 in Part B	US Sourced Enbrel in Part B	EU Sourced Enbrel in Part C	US Sourced Enbrel in Part C
Arm/Group Description	SB4: SC administration	EU sourced Enbrel: SC administration	SB4: SC administration	US sourced Enbrel: SC administration	EU sourced Enbrel: SC administration	US sourced Enbrel: SC administration
Measure Participants	42	42	44	44	42	42
Mean (Standard Deviation) [μg/mL]	3.607 (1.4298)	3.435 (1.2390)	3.869 (1.3251)	3.613 (1.0252)	3.720 (1.5444)	3.575 (1.4833)

3. Secondary Outcome

Title	Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast)
Description	pre-dose and at 6, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 216, 312 and 480 h post-dose
Time Frame	0 to 480 hours post-dose

Outcome Measure Data

Analysis Population Description

Overall number of participans Analyzed equals to number of subjects who contributed to summary statistics.

Arm/Group Title	SB4 in Part A	EU Sourced Enbrel in Part A	SB4 in Part B	US Sourced Enbrel in Part B	EU Sourced Enbrel in Part C	US Sourced Enbrel in Part C
Arm/Group Description	SB4: SC administration	EU sourced Enbrel: SC administration	SB4: SC administration	US sourced Enbrel: SC administration	EU sourced Enbrel: SC administration	US sourced Enbrel: SC administration
Measure Participants	42	42	44	44	42	42
Mean (Standard Deviation) [µg·h/mL]	728.169 (234.7621)	734.015 (220.2722)	788.773 (232.4636)	765.187 (184.5046)	752.277 (259.2088)	727.820 (229.8597)

4. Secondary Outcome

Title	Time to Cmax (Tmax)
Description	pre-dose and at 6, 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 216, 312 and 480 h post-dose
Time Frame	0 to 480 hours post-dose

Outcome Measure Data

Analysis Population Description

Overall number of participans Analyzed equals to number of subjects who contributed to summary statistics.

Arm/Group Title	SB4 in Part A	EU Sourced Enbrel in Part A	SB4 in Part B	US Sourced Enbrel in Part B	EU Sourced Enbrel in Part C	US Sourced Enbrel in Part C
Arm/Group Description	SB4: SC administration	EU sourced Enbrel: SC administration	SB4: SC administration	US sourced Enbrel: SC administration	EU sourced Enbrel: SC administration	US sourced Enbrel: SC administration
Measure Participants	42	42	44	44	42	42
Mean (Standard Deviation) [h]	75.198 (29.1358)	71.711 (24.7538)	75.263 (30.8374)	70.385 (22.4972)	70.276 (30.3826)	71.150 (29.7904)

Adverse Events

Time Frame	7 weeks (49 days) after first dose administration of SB4, EU sourced Enbrel, or US sourced Enbrel
Arm/Group Title	SB4 in Part A		EU Sourced Enbrel in Part A		SB4 in Part B		US Sourced Enbrel in Part B		EU Sourced Enbrel in Part C		US Sourced Enbrel in Part C
Arm/Group Description	SB4: SC administration		EU sourced Enbrel: SC administration		SB4: SC administration		US sourced Enbrel: SC administration		EU sourced Enbrel: SC administration		US sourced Enbrel: SC administration
All Cause Mortality
	SB4 in Part A		EU Sourced Enbrel in Part A		SB4 in Part B		US Sourced Enbrel in Part B		EU Sourced Enbrel in Part C		US Sourced Enbrel in Part C
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/46 (0%)		0/46 (0%)		0/46 (0%)		0/46 (0%)		0/46 (0%)		0/46 (0%)
Serious Adverse Events
	SB4 in Part A		EU Sourced Enbrel in Part A		SB4 in Part B		US Sourced Enbrel in Part B		EU Sourced Enbrel in Part C		US Sourced Enbrel in Part C
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/46 (0%)		0/46 (0%)		0/46 (0%)		0/46 (0%)		0/46 (0%)		0/46 (0%)
Other (Not Including Serious) Adverse Events
	SB4 in Part A		EU Sourced Enbrel in Part A		SB4 in Part B		US Sourced Enbrel in Part B		EU Sourced Enbrel in Part C		US Sourced Enbrel in Part C
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	18/46 (39.1%)		16/46 (34.8%)		23/46 (50%)		20/46 (43.5%)		17/46 (37%)		14/46 (30.4%)
Cardiac disorders
Palpitations	0/46 (0%)		0/46 (0%)		1/46 (2.2%)		0/46 (0%)		1/46 (2.2%)		0/46 (0%)
Eye disorders
Conjunctivitis	0/46 (0%)		0/46 (0%)		0/46 (0%)		0/46 (0%)		1/46 (2.2%)		0/46 (0%)
Gastrointestinal disorders
Nausea	1/46 (2.2%)		2/46 (4.3%)		0/46 (0%)		0/46 (0%)		1/46 (2.2%)		0/46 (0%)
Abdominal distension	1/46 (2.2%)		0/46 (0%)		1/46 (2.2%)		0/46 (0%)		0/46 (0%)		0/46 (0%)
Diarrhoea	0/46 (0%)		2/46 (4.3%)		1/46 (2.2%)		1/46 (2.2%)		1/46 (2.2%)		0/46 (0%)
Lip erosion	0/46 (0%)		1/46 (2.2%)		0/46 (0%)		0/46 (0%)		0/46 (0%)		0/46 (0%)
Dyspepsia	0/46 (0%)		0/46 (0%)		2/46 (4.3%)		0/46 (0%)		0/46 (0%)		0/46 (0%)
Toothache	0/46 (0%)		0/46 (0%)		1/46 (2.2%)		1/46 (2.2%)		0/46 (0%)		1/46 (2.2%)
Flatulence	0/46 (0%)		0/46 (0%)		1/46 (2.2%)		1/46 (2.2%)		0/46 (0%)		0/46 (0%)
Aphthous stomatitis	0/46 (0%)		0/46 (0%)		0/46 (0%)		1/46 (2.2%)		1/46 (2.2%)		0/46 (0%)
Lip blister	0/46 (0%)		0/46 (0%)		0/46 (0%)		0/46 (0%)		1/46 (2.2%)		0/46 (0%)
Oral discomfort	0/46 (0%)		0/46 (0%)		0/46 (0%)		0/46 (0%)		0/46 (0%)		1/46 (2.2%)
General disorders
Injection site reaction	2/46 (4.3%)		3/46 (6.5%)		3/46 (6.5%)		3/46 (6.5%)		1/46 (2.2%)		3/46 (6.5%)
Chest discomfort	1/46 (2.2%)		0/46 (0%)		1/46 (2.2%)		0/46 (0%)		1/46 (2.2%)		0/46 (0%)
Asthenia	0/46 (0%)		0/46 (0%)		1/46 (2.2%)		0/46 (0%)		1/46 (2.2%)		0/46 (0%)
Fatigue	0/46 (0%)		0/46 (0%)		1/46 (2.2%)		0/46 (0%)		2/46 (4.3%)		2/46 (4.3%)
Influenza like illness	0/46 (0%)		0/46 (0%)		0/46 (0%)		1/46 (2.2%)		0/46 (0%)		0/46 (0%)
Infections and infestations
Nasopharyngitis	5/46 (10.9%)		2/46 (4.3%)		2/46 (4.3%)		2/46 (4.3%)		2/46 (4.3%)		1/46 (2.2%)
Rhinitis	2/46 (4.3%)		2/46 (4.3%)		1/46 (2.2%)		1/46 (2.2%)		0/46 (0%)		1/46 (2.2%)
Pharyngitis	1/46 (2.2%)		0/46 (0%)		2/46 (4.3%)		2/46 (4.3%)		0/46 (0%)		0/46 (0%)
Oral herpes	0/46 (0%)		1/46 (2.2%)		1/46 (2.2%)		0/46 (0%)		1/46 (2.2%)		0/46 (0%)
Gastroenteritis	0/46 (0%)		0/46 (0%)		1/46 (2.2%)		0/46 (0%)		0/46 (0%)		0/46 (0%)
Tooth abscess	0/46 (0%)		0/46 (0%)		0/46 (0%)		1/46 (2.2%)		0/46 (0%)		0/46 (0%)
Folliculitis	0/46 (0%)		0/46 (0%)		0/46 (0%)		0/46 (0%)		0/46 (0%)		1/46 (2.2%)
Injury, poisoning and procedural complications
Arthropod bite	1/46 (2.2%)		0/46 (0%)		0/46 (0%)		0/46 (0%)		0/46 (0%)		0/46 (0%)
Traumatic haematoma	0/46 (0%)		0/46 (0%)		1/46 (2.2%)		0/46 (0%)		0/46 (0%)		0/46 (0%)
Laceration	0/46 (0%)		0/46 (0%)		0/46 (0%)		1/46 (2.2%)		0/46 (0%)		0/46 (0%)
Limb injury	0/46 (0%)		0/46 (0%)		0/46 (0%)		0/46 (0%)		1/46 (2.2%)		0/46 (0%)
Injury	0/46 (0%)		0/46 (0%)		0/46 (0%)		0/46 (0%)		0/46 (0%)		1/46 (2.2%)
Ligament rupture	0/46 (0%)		0/46 (0%)		0/46 (0%)		0/46 (0%)		0/46 (0%)		1/46 (2.2%)
Investigations
Alanine aminotransferase increased	0/46 (0%)		0/46 (0%)		1/46 (2.2%)		0/46 (0%)		1/46 (2.2%)		0/46 (0%)
Metabolism and nutrition disorders
Decreased appetite	0/46 (0%)		0/46 (0%)		0/46 (0%)		0/46 (0%)		1/46 (2.2%)		0/46 (0%)
Musculoskeletal and connective tissue disorders
Back pain	1/46 (2.2%)		0/46 (0%)		1/46 (2.2%)		3/46 (6.5%)		0/46 (0%)		0/46 (0%)
Neck pain	1/46 (2.2%)		0/46 (0%)		0/46 (0%)		0/46 (0%)		0/46 (0%)		0/46 (0%)
Myalgia	0/46 (0%)		1/46 (2.2%)		0/46 (0%)		0/46 (0%)		0/46 (0%)		1/46 (2.2%)
Musculoskeletal chest pain	0/46 (0%)		0/46 (0%)		1/46 (2.2%)		0/46 (0%)		0/46 (0%)		0/46 (0%)
Limb discomfort	0/46 (0%)		0/46 (0%)		0/46 (0%)		0/46 (0%)		1/46 (2.2%)		0/46 (0%)
Nervous system disorders
Headache	4/46 (8.7%)		2/46 (4.3%)		3/46 (6.5%)		4/46 (8.7%)		4/46 (8.7%)		3/46 (6.5%)
Dizziness	0/46 (0%)		0/46 (0%)		0/46 (0%)		3/46 (6.5%)		1/46 (2.2%)		0/46 (0%)
Dizziness postural	0/46 (0%)		0/46 (0%)		0/46 (0%)		1/46 (2.2%)		0/46 (0%)		0/46 (0%)
Paraesthesia	0/46 (0%)		0/46 (0%)		0/46 (0%)		1/46 (2.2%)		0/46 (0%)		0/46 (0%)
Somnolence	0/46 (0%)		0/46 (0%)		0/46 (0%)		0/46 (0%)		1/46 (2.2%)		1/46 (2.2%)
Renal and urinary disorders
Pollakiuria	0/46 (0%)		1/46 (2.2%)		0/46 (0%)		0/46 (0%)		0/46 (0%)		0/46 (0%)
Reproductive system and breast disorders
Erection increased	0/46 (0%)		0/46 (0%)		1/46 (2.2%)		0/46 (0%)		0/46 (0%)		0/46 (0%)
Respiratory, thoracic and mediastinal disorders
Epistaxis	1/46 (2.2%)		0/46 (0%)		1/46 (2.2%)		0/46 (0%)		0/46 (0%)		0/46 (0%)
Nasal congestion	1/46 (2.2%)		0/46 (0%)		1/46 (2.2%)		1/46 (2.2%)		0/46 (0%)		0/46 (0%)
Cough	0/46 (0%)		1/46 (2.2%)		0/46 (0%)		0/46 (0%)		0/46 (0%)		1/46 (2.2%)
Oropharyngeal pain	0/46 (0%)		0/46 (0%)		2/46 (4.3%)		1/46 (2.2%)		0/46 (0%)		0/46 (0%)
Sinus congestion	0/46 (0%)		0/46 (0%)		0/46 (0%)		1/46 (2.2%)		0/46 (0%)		0/46 (0%)
Skin and subcutaneous tissue disorders
Sunburn	1/46 (2.2%)		1/46 (2.2%)		1/46 (2.2%)		1/46 (2.2%)		0/46 (0%)		0/46 (0%)
Photosensitivity reaction	1/46 (2.2%)		0/46 (0%)		0/46 (0%)		0/46 (0%)		0/46 (0%)		0/46 (0%)
Skin fissures	0/46 (0%)		1/46 (2.2%)		0/46 (0%)		0/46 (0%)		1/46 (2.2%)		0/46 (0%)
Rash erythematous	0/46 (0%)		0/46 (0%)		1/46 (2.2%)		0/46 (0%)		0/46 (0%)		0/46 (0%)
Pruritus	0/46 (0%)		0/46 (0%)		0/46 (0%)		1/46 (2.2%)		1/46 (2.2%)		0/46 (0%)
Dermatitis	0/46 (0%)		0/46 (0%)		0/46 (0%)		0/46 (0%)		0/46 (0%)		1/46 (2.2%)
Eczema	0/46 (0%)		0/46 (0%)		0/46 (0%)		0/46 (0%)		0/46 (0%)		1/46 (2.2%)
Vascular disorders
Hot flush	0/46 (0%)		0/46 (0%)		0/46 (0%)		0/46 (0%)		1/46 (2.2%)		0/46 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.