Gemcitabine Plus Bevacizumab in Locally Recurrent or Metastatic Breast Cancer

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00623233
• Collaborator: Genentech, Inc. (Industry)
• Enrollment: 52
• Locations: 16
• Arm: 1
• Duration (Months): 34
• Patients Per Site: 3.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

To determine how long Gemcitabine and Bevacizumab will stop the cancer from growing in patients with advanced breast cancer.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Breast Cancer; Locally Advanced Breast Cancer	Drug: Gemcitabine; Drug: Bevacizumab	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 52 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2 Study of Gemcitabine and Bevacizumab as First-Line Treatment in HER2 Negative, Locally Recurrent or Metastatic Breast Cancer Previously Treated With Taxanes
• Study Start Date: Mar 1, 2008
• Actual Primary Completion Date: Jan 1, 2011
• Actual Study Completion Date: Jan 1, 2011

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Gemcitabine + Bevacizumab Gemcitabine 2500 milligrams per square meter (mg/m^2) intravenous (IV) over 30 minutes given on Day 1 every 14 days (q 14 days) until disease progression (PD) or unacceptable toxicity. Bevacizumab 10 milligrams per kilogram (mg/kg) initially over 90 minutes given on Day 1 q 14 days until PD or unacceptable toxicity.

Drug: Gemcitabine; Gemcitabine 2500 mg/m^2 IV over 30 minutes given on Day 1 q 14 days prior to bevacizumab until PD or unacceptable toxicity.; Other Names: Gemzar LLY188011 ; Drug: Bevacizumab; Bevacizumab 10 mg/kg IV over 90 minutes at Cycle 1; infusion time may have been decreased for subsequent cycles. (For example, if the first infusion was tolerated without an infusion-associated adverse event [AE], the second infusion was delivered over 60 minutes. If the 60-minute infusion was well tolerated, all subsequent infusions were delivered over 30 minutes.) Bevacizumab 10 mg/kg initially over 90 minutes given on Day 1 q 14 days until PD or unacceptable toxicity.

Outcome Measures

Primary Outcome Measures

1. Progression Free Survival (PFS) Time [Baseline to measured PD or death from any cause. Tumor assessments were performed every 8 weeks during therapy and every 2 months during post-therapy until documented PD (up to 34 months).]

   PFS was measured from date of first dose to first date of progressive disease (PD) or death from any cause. For each participant who was not known to have died or to have had PD as of the data inclusion cut-off date for a particular analysis, PFS duration was censored for that analysis at the date of the participant's last progression-free tumor assessment before that cut-off date.

Secondary Outcome Measures

1. Overall Tumor Response Rate (ORR) [Baseline to measured PD. Tumor assessments were performed every 8 weeks (q 8 weeks) during therapy and q 2 months during post-therapy until documented PD (up to 34 months).]

   Response defined per Response Evaluation Criteria In Solid Tumors (RECIST) criteria: complete response (CR)=disappearance of all target lesions; partial response (PR)=30% decrease in sum of longest diameter of target lesions; progressive disease (PD)=20% increase in sum of longest diameter of target lesions; stable disease=small changes that do not meet above criteria. ORR=proportion of participants who achieved a confirmed best response of CR or PR (responders). ORR=number of participants with CR or PR /number of participants qualified for tumor response analysis (per protocol population).

2. Number of Participants With Adverse Events (AEs); Pharmacology Toxicities [Baseline, every cycle (every 14 days) up to 34 months]

   A listing of serious adverse events (SAEs) and other non-serious AEs is located in the Reported Adverse Event module.

3. 1-Year Overall Survival (OS) Rate [Baseline to death from any cause, 1 year]

   OS was measured from the date of first dose to the date of death from any cause. For each participant who was not known to have died as of the data inclusion cut-off date for a particular analysis, OS duration was censored for that analysis at the date of participant's last study contact prior to that cut-off date. The 1-year survival rate (percentage of participants who were alive at 1 year) was estimated from OS data.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Must be female and greater than or equal to 18 yrs of age

• Participants must have confirmed cancer with measurable or evaluable, locally recurrent or metastatic disease.

• Participants must have received a taxane as neo-adjuvant and/or adjuvant therapy

• Participants may have received prior hormone therapy for locally recurrent or metastatic disease

Exclusion Criteria:

• Participants with breast cancer overexpressing Human Epidermal growth factor Receptor 2 (HER2) gene amplification

• Prior chemotherapy or targeted therapy for metastatic breast cancer

• Prior treatment with gemcitabine, trastuzumab, lapatinib or bevacizumab in any setting

• History of, or active brain mets

• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to treatment, or anticipation of need for major surgical procedure during course of study

• Prior history of high blood pressure crisis

• Have a serious, nonhealing wound, ulcer, or bone fracture

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Fayetteville	Arkansas	United States	72703
2	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Fresno	California	United States	93720
3	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	San Diego	California	United States	92121
4	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Longmont	Colorado	United States	80501
5	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Fairfield	Connecticut	United States	06824
6	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Augusta	Georgia	United States	30901
7	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Lambertville	Michigan	United States	48144
8	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	St Louis	Missouri	United States	63141
9	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Great Falls	Montana	United States	59405
10	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	New York	New York	United States	10003
11	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Oklahoma City	Oklahoma	United States	73112
12	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Columbia	South Carolina	United States	29210
13	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Germantown	Tennessee	United States	38138
14	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Nashville	Tennessee	United States	37203
15	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Salt Lake City	Utah	United States	84106
16	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Newport News	Virginia	United States	23601

Sponsors and Collaborators

• Eli Lilly and Company
• Genentech, Inc.

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern Time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Lilly Clinical Trial Registry

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT00623233
• Other Study ID Numbers: 11649; B9E-US-S379
• First Posted: Feb 25, 2008
• Last Update Posted: Jan 9, 2012
• Last Verified: Dec 1, 2011

• Keywords provided by Eli Lilly and Company: Breast Neoplasm
• Additional relevant MeSH terms: Breast Neoplasms; Gemcitabine; Bevacizumab

Study Results

Participant Flow

Arm/Group Title	Gemcitabine 2500 mg/m^2 + Bevacizumab 10 mg/kg
Arm/Group Description	Gemcitabine 2500 milligrams per square meter (mg/m^2) intravenous (IV) over 30 minutes given on Day 1 every 14 days (q 14 days) until disease progression (PD) or unacceptable toxicity. Bevacizumab 10 milligrams per kilogram (mg/kg) initially over 90 minutes given on Day 1 q 14 days until PD or unacceptable toxicity.
Period Title: Overall Study
STARTED	52
COMPLETED	28
NOT COMPLETED	24

Baseline Characteristics

Arm/Group Title	Gemcitabine 2500 mg/m^2 + Bevacizumab 10 mg/kg
Arm/Group Description	Gemcitabine 2500 milligrams per square meter (mg/m^2) intravenous (IV) over 30 minutes given on Day 1 every 14 days (q 14 days) until disease progression (PD) or unacceptable toxicity. Bevacizumab 10 milligrams per kilogram (mg/kg) initially over 90 minutes given on Day 1 q 14 days until PD or unacceptable toxicity.
Overall Participants	52
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	55.2 (11.66)
Sex: Female, Male (Count of Participants)
Female	52 100%
Male	0 0%
Race/Ethnicity, Customized (participants) [Number]
African descent	11 21.2%
Caucasian	41 78.8%
Region of Enrollment (participants) [Number]
United States	52 100%
Estrogen Receptor (ER) Status (participants) [Number]
ER+	33 63.5%
ER-	19 36.5%
Progesterone Receptor (PR) Status (participants) [Number]
PR+	30 57.7%
PR-	22 42.3%
Human Epidermal Growth Factor Receptor 2 (HER2/neu) (participants) [Number]
HER2/neu+	0 0%
HER2/neu-	52 100%
Eastern Cooperative Oncology Group (ECOG) Performance Status (participants) [Number]
0	28 53.8%
1	24 46.2%

Outcome Measures

1. Primary Outcome

Title	Progression Free Survival (PFS) Time
Description	PFS was measured from date of first dose to first date of progressive disease (PD) or death from any cause. For each participant who was not known to have died or to have had PD as of the data inclusion cut-off date for a particular analysis, PFS duration was censored for that analysis at the date of the participant's last progression-free tumor assessment before that cut-off date.
Time Frame	Baseline to measured PD or death from any cause. Tumor assessments were performed every 8 weeks during therapy and every 2 months during post-therapy until documented PD (up to 34 months).

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) population included all enrolled participants who received at least 1 dose of study drug. Participants with events=41; censored participants=11.

Arm/Group Title	Gemcitabine 2500 mg/m^2 + Bevacizumab 10 mg/kg
Arm/Group Description	Gemcitabine 2500 milligrams per square meter (mg/m^2) intravenous (IV) over 30 minutes given on Day 1 every 14 days (q 14 days) until disease progression (PD) or unacceptable toxicity. Bevacizumab 10 milligrams per kilogram (mg/kg) initially over 90 minutes given on Day 1 q 14 days until PD or unacceptable toxicity.
Measure Participants	52
Median (95% Confidence Interval) [months]	4.80

2. Secondary Outcome

Title	Overall Tumor Response Rate (ORR)
Description	Response defined per Response Evaluation Criteria In Solid Tumors (RECIST) criteria: complete response (CR)=disappearance of all target lesions; partial response (PR)=30% decrease in sum of longest diameter of target lesions; progressive disease (PD)=20% increase in sum of longest diameter of target lesions; stable disease=small changes that do not meet above criteria. ORR=proportion of participants who achieved a confirmed best response of CR or PR (responders). ORR=number of participants with CR or PR /number of participants qualified for tumor response analysis (per protocol population).
Time Frame	Baseline to measured PD. Tumor assessments were performed every 8 weeks (q 8 weeks) during therapy and q 2 months during post-therapy until documented PD (up to 34 months).

Outcome Measure Data

Analysis Population Description

The per protocol (PP) population included all intent-to-treat (ITT) participants who met the following criteria: histological or cytological diagnosis of breast cancer; presence of measurable disease at baseline per RECIST criteria; had at least 1 dose of study drug; no current systemic anti-tumor treatment other than protocol-specified therapy.

Arm/Group Title	Gemcitabine 2500 mg/m^2 + Bevacizumab 10 mg/kg
Arm/Group Description	Gemcitabine 2500 milligrams per square meter (mg/m^2) intravenous (IV) over 30 minutes given on Day 1 every 14 days (q 14 days) until disease progression (PD) or unacceptable toxicity. Bevacizumab 10 milligrams per kilogram (mg/kg) initially over 90 minutes given on Day 1 q 14 days until PD or unacceptable toxicity.
Measure Participants	42
Number (95% Confidence Interval) [proportion of responders]	0.214

3. Secondary Outcome

Title	Number of Participants With Adverse Events (AEs); Pharmacology Toxicities
Description	A listing of serious adverse events (SAEs) and other non-serious AEs is located in the Reported Adverse Event module.
Time Frame	Baseline, every cycle (every 14 days) up to 34 months

Outcome Measure Data

Analysis Population Description

The safety population was the treated population and included all participants who received at least 1 dose of study therapy.

Arm/Group Title	Gemcitabine 2500 mg/m^2 + Bevacizumab 10 mg/kg
Arm/Group Description	Gemcitabine 2500 milligrams per square meter (mg/m^2) intravenous (IV) over 30 minutes given on Day 1 every 14 days (q 14 days) until disease progression (PD) or unacceptable toxicity. Bevacizumab 10 milligrams per kilogram (mg/kg) initially over 90 minutes given on Day 1 q 14 days until PD or unacceptable toxicity.
Measure Participants	52
SAEs	18 34.6%
Other non-serious AEs	51 98.1%

4. Secondary Outcome

Title	1-Year Overall Survival (OS) Rate
Description	OS was measured from the date of first dose to the date of death from any cause. For each participant who was not known to have died as of the data inclusion cut-off date for a particular analysis, OS duration was censored for that analysis at the date of participant's last study contact prior to that cut-off date. The 1-year survival rate (percentage of participants who were alive at 1 year) was estimated from OS data.
Time Frame	Baseline to death from any cause, 1 year

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) population included all enrolled participants who received at least 1 dose of study drug. Participants with events=25; censored participants=27.

Arm/Group Title	Gemcitabine 2500 mg/m^2 + Bevacizumab 10 mg/kg
Arm/Group Description	Gemcitabine 2500 milligrams per square meter (mg/m^2) intravenous (IV) over 30 minutes given on Day 1 every 14 days (q 14 days) until disease progression (PD) or unacceptable toxicity. Bevacizumab 10 milligrams per kilogram (mg/kg) initially over 90 minutes given on Day 1 q 14 days until PD or unacceptable toxicity.
Measure Participants	52
Number (95% Confidence Interval) [percentage of participants]	68.68 132.1%

Adverse Events

Arm/Group Title	Gemcitabine 2500 mg/m^2 + Bevacizumab 10 mg/kg
Arm/Group Description	Gemcitabine 2500 milligrams per square meter (mg/m^2) intravenous (IV) over 30 minutes given on Day 1 every 14 days (q 14 days) until disease progression (PD) or unacceptable toxicity. Bevacizumab 10 milligrams per kilogram (mg/kg) initially over 90 minutes given on Day 1 q 14 days until PD or unacceptable toxicity.
All Cause Mortality
	Gemcitabine 2500 mg/m^2 + Bevacizumab 10 mg/kg
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Gemcitabine 2500 mg/m^2 + Bevacizumab 10 mg/kg
	Affected / at Risk (%)	# Events
Total	18/52 (34.6%)
Blood and lymphatic system disorders
Anaemia	2/52 (3.8%)	3
Febrile Neutropenia	1/52 (1.9%)	1
Haemolytic Uraemic Syndrome	1/52 (1.9%)	1
Leukopenia	1/52 (1.9%)	1
Neutropenia	1/52 (1.9%)	1
Thrombocytopenia	1/52 (1.9%)	1
Cardiac disorders
Cardiac Failure Congestive	1/52 (1.9%)	1
Cardio-Respiratory Arrest	1/52 (1.9%)	1
Gastrointestinal disorders
Abdominal Pain	1/52 (1.9%)	1
Constipation	1/52 (1.9%)	1
Diarrhoea	1/52 (1.9%)	1
Duodenal Ulcer	1/52 (1.9%)	1
Dysphagia	1/52 (1.9%)	1
Gastritis Erosive	1/52 (1.9%)	1
Nausea	1/52 (1.9%)	1
Vomiting	2/52 (3.8%)	4
General disorders
Asthenia	1/52 (1.9%)	1
Infections and infestations
Bronchitis	1/52 (1.9%)	1
Cellulitis	1/52 (1.9%)	1
Gastroenteritis	1/52 (1.9%)	1
Sepsis	2/52 (3.8%)	2
Skin Infection	1/52 (1.9%)	1
Injury, poisoning and procedural complications
Overdose	1/52 (1.9%)	1
Investigations
Alanine Aminotransferase Increased	1/52 (1.9%)	1
Aspartate Aminotransferase Increased	1/52 (1.9%)	1
Oxygen Saturation Decreased	1/52 (1.9%)	1
Metabolism and nutrition disorders
Dehydration	1/52 (1.9%)	1
Fluid Retention	1/52 (1.9%)	1
Hypercalcaemia	1/52 (1.9%)	1
Hyponatraemia	1/52 (1.9%)	1
Hypovolaemia	2/52 (3.8%)	2
Nervous system disorders
Head Discomfort	1/52 (1.9%)	1
Loss Of Consciousness	1/52 (1.9%)	1
Reversible Posterior Leukoencephalopathy Syndrome	1/52 (1.9%)	1
Syncope	1/52 (1.9%)	1
Psychiatric disorders
Delirium	1/52 (1.9%)	1
Depression	1/52 (1.9%)	1
Renal and urinary disorders
Hydronephrosis	1/52 (1.9%)	1
Renal Failure Acute	2/52 (3.8%)	2
Respiratory, thoracic and mediastinal disorders
Atelectasis	1/52 (1.9%)	1
Dyspnoea	1/52 (1.9%)	1
Hypoxia	1/52 (1.9%)	1
Pleural Effusion	2/52 (3.8%)	2
Pulmonary Embolism	1/52 (1.9%)	1
Other (Not Including Serious) Adverse Events
	Gemcitabine 2500 mg/m^2 + Bevacizumab 10 mg/kg
	Affected / at Risk (%)	# Events
Total	51/52 (98.1%)
Blood and lymphatic system disorders
Anaemia	16/52 (30.8%)	18
Leukopenia	10/52 (19.2%)	14
Neutropenia	14/52 (26.9%)	21
Thrombocytopenia	5/52 (9.6%)	12
Cardiac disorders
Sinus Tachycardia	3/52 (5.8%)	3
Tachycardia	6/52 (11.5%)	7
Gastrointestinal disorders
Abdominal Pain	6/52 (11.5%)	6
Abdominal Pain Lower	3/52 (5.8%)	4
Constipation	21/52 (40.4%)	22
Diarrhoea	12/52 (23.1%)	18
Dyspepsia	7/52 (13.5%)	10
Nausea	32/52 (61.5%)	51
Stomatitis	8/52 (15.4%)	9
Vomiting	14/52 (26.9%)	17
General disorders
Asthenia	4/52 (7.7%)	4
Chest Pain	3/52 (5.8%)	4
Fatigue	32/52 (61.5%)	38
Influenza Like Illness	3/52 (5.8%)	4
Oedema	4/52 (7.7%)	5
Oedema Peripheral	4/52 (7.7%)	4
Pain	3/52 (5.8%)	4
Pyrexia	7/52 (13.5%)	7
Infections and infestations
Upper Respiratory Tract Infection	4/52 (7.7%)	4
Urinary Tract Infection	7/52 (13.5%)	7
Investigations
Alanine Aminotransferase Increased	3/52 (5.8%)	3
Aspartate Aminotransferase Increased	3/52 (5.8%)	4
Blood Alkaline Phosphatase Increased	3/52 (5.8%)	3
Weight Decreased	5/52 (9.6%)	5
Metabolism and nutrition disorders
Decreased Appetite	15/52 (28.8%)	17
Musculoskeletal and connective tissue disorders
Arthralgia	7/52 (13.5%)	8
Back Pain	11/52 (21.2%)	11
Bone Pain	6/52 (11.5%)	9
Musculoskeletal Chest Pain	4/52 (7.7%)	4
Musculoskeletal Pain	3/52 (5.8%)	3
Myalgia	3/52 (5.8%)	4
Nervous system disorders
Dizziness	8/52 (15.4%)	8
Headache	11/52 (21.2%)	13
Neuropathy Peripheral	3/52 (5.8%)	3
Psychiatric disorders
Anxiety	4/52 (7.7%)	4
Depression	6/52 (11.5%)	7
Insomnia	4/52 (7.7%)	5
Renal and urinary disorders
Proteinuria	13/52 (25%)	19
Respiratory, thoracic and mediastinal disorders
Cough	8/52 (15.4%)	8
Dyspnoea	15/52 (28.8%)	17
Epistaxis	10/52 (19.2%)	10
Paranasal Sinus Hypersecretion	4/52 (7.7%)	4
Skin and subcutaneous tissue disorders
Alopecia	8/52 (15.4%)	8
Rash	5/52 (9.6%)	5
Vascular disorders
Hypertension	12/52 (23.1%)	16
Lymphoedema	3/52 (5.8%)	3

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.