A Study of Ramucirumab (LY3009806) in Participants With Advanced Liver Cancer

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02069041
• Collaborator: (none)
• Enrollment: 8
• Locations: 3
• Arm: 1
• Duration (Months): 29
• Patients Per Site: 2.7
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The main purpose of this study is to determine if the advised dose of ramucirumab is safe to be taken with chemotherapy treatment in participants with advanced liver tumors.

Condition or Disease	Intervention/Treatment	Phase
Carcinoma, Hepatocellular	Biological: Ramucirumab; Drug: FOLFOX4	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 8 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase 1b Study of 5-FU/FA and Oxaliplatin (FOLFOX4) Plus Ramucirumab (LY3009806) in Patients With Advanced Hepatocellular Carcinoma
• Study Start Date: Apr 1, 2014
• Actual Primary Completion Date: Sep 1, 2016
• Actual Study Completion Date: Sep 1, 2016

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Ramucirumab + FOLFOX4 8 milligram/kilogram (mg/kg) ramucirumab given intravenously (IV) on Day 1 followed by FOLFOX4 (folinic acid + fluorouracil + oxaliplatin chemotherapy regimen) given IV on Day 1 of 2 week cycles: FOLFOX4 every 2 weeks: 85 milligram per square meter (mg/m²) oxaliplatin IV on Day 1 200 mg/m² folinic acid(FA) IV on days 1 and 2 400 mg/m² 5-FU bolus on days 1 and 2 600 mg/m2 5-FU 22-h continuous infusion on Days 1 and 2 Participants may continue to receive treatment until discontinuation criteria are met.

Biological: Ramucirumab; Administered IV.; Other Names: IMC-1121B LY3009806 ; Drug: FOLFOX4; Administered IV.; Other Names: FOLFOX4 (leucovorin + fluorouracil + oxaliplatin)

Outcome Measures

Primary Outcome Measures

1. Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration [Baseline through study completion (Up To 8 Months)]

   A summary of other non-serious Adverse Events (AEs), and all Serious Adverse Events (SAE's), regardless of causality, is located in the Reported Adverse Events section.

Secondary Outcome Measures

1. Pharmacokinetics (PK): Maximum Concentration (Cmax) of Ramucirumab [Cycle 1 and Cycle 3: 0,1.0,1.5,2.0,3.0,5.0,24.0,48.0,168.0,336.0 hours]

   Maximum Concentration (Cmax)

2. PK:Area Under the Concentration-Time Curve (AUC[0-∞]) of Ramucirumab [Cycle 1 and Cycle 3: 0,1.0,1.5,2.0,3.0,5.0,24.0,48.0,168.0,336.0 hours]

   Area under the concentration-time curve.

3. Number of Participants With Anti-Ramucirumab Antibodies [Baseline through 6.1 Months]

4. Percentage of Participants With Best Response of Complete Response (CR) or Partial Response (PR) (Overall Response Rate [ORR]) [Response to Disease Progression or Death (Up To 7 Months)]

   Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST, version[v] 1.1) criteria.CR was defined as the disappearance of all target and non-target lesions and all target and non-target lymph nodes were non-pathological or normal in size [<10 millimeter (mm) short axis]. PR is at least a 30% decrease in the sum of diameter of target lesions, taking as reference the baseline sum diameters. Progressive Disease(PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (including the baseline sum if that is the smallest).In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression. Percentage of participants with CR or PR= (number of participants whose best overall response was CR or PR)/(number of participants treated)*100.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Histological or cytological diagnosis of hepatocellular carcinoma (HCC) or imaging findings consistent with HCC in a participant with liver cirrhosis and alpha-fetoprotein > 200 nanogram per milliliter

• At least 1 measurable or non-measurable lesion

• Child-Pugh A

• Barcelona Clinic Liver Cancer (BCLC) stage C or BCLC stage B not amenable to locoregional therapy or refractory to locoregional therapy

• Eastern Cooperative Oncology Group Performance Status of 0 or 1

• Have not received previous systemic therapy for advanced HCC

• Have resolution to Grade ≤1 of all clinically significant toxic effects of prior locoregional therapy

• Adequate organ function including: Absolute neutrophil coun t≥1.5×109/liter (L), hemoglobin ≥9 gram/deciliter, and platelets ≥90×109/L; Total bilirubin level ≤1.5 the upper limit of the normal range (ULN), aspartate transaminase and alanine transaminase ≤5 ULN, albumin >28 gram/L; Serum creatinine level ≤1.5 ULN; or calculated serum creatinine clearance ≥50 milliliter/minute; International Normalized Ratio≤1.5 and partial thromboplastin time ≤5 seconds above ULN

• The urinary protein is ≤ 1+. If ≥ 2+ proteinuria, the 24-hour urine protein is <1000 milligram

• An estimated life expectancy of at least 12 weeks

Exclusion Criteria:

• Received any investigational therapy or non-approved drug within 28 days prior to enrollment

• Undergone major surgery within 28 days prior to enrollment, or undergone central venous access device placement within 7 days prior to enrollment

• Undergone hepatic locoregional therapy within 28 days prior to enrollment

• Undergone radiation to any nonhepatic site within 14 days prior to enrollment

• Prior liver transplant

• Fibrolamellar carcinoma or cholangiocellular carcinoma

• Received any transfusion, blood component preparation, erythropoietin, albumin preparation, or granulocyte-colony stimulating factors within 14 days prior to enrollment

• Receiving therapeutic anticoagulation with warfarin, low-molecular weight heparin, or similar agents

• Receiving ongoing therapy with nonsteroidal anti-inflammatory agents or other antiplatelet agents.

• Known human immunodeficiency virus infection or acquired immunodeficiency syndrome-related illness

• Active or uncontrolled clinically serious infection

• Uncontrolled thrombotic or hemorrhagic disorder

• Serious or nonhealing wound, ulcer, or bone fracture within 28 days prior to enrollment

• History of gastrointestinal perforation or obstruction

• History of or current hepatic encephalopathy or current clinically meaningful ascites

• Known allergy to monoclonal antibody, fluorouracil, oxaliplatin or their excipients

• Interstitial pneumonia or interstitial fibrosis of the lung

• Central nervous system metastases or carcinomatous meningitis

• Known history of dihydropyrimidine dehydrogenase deficiency

• Symptomatic congestive heart failure, unstable angina pectoris, or symptomatic or poorly controlled cardiac arrhythmia

• Experienced any arterial thromboembolic event

• Uncontrolled arterial hypertension

• Grade 3-4 venous thromboembolic events occurring within 3 months prior to enrollment

• Experienced any grade 3-4 gastrointestinal bleeding or any variceal bleeding episode in the 3 months prior to enrollment requiring transfusion, endoscopic or operative intervention

• Esophageal or gastric varices that require immediate intervention or represent a high bleeding risk

• Pre-existing grade ≥ 2 motor or sensory neuropathy

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.	Tainan		Taiwan	70403
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.	Taipei		Taiwan	10048
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.	Taoyuan City		Taiwan	33305

Sponsors and Collaborators

• Eli Lilly and Company

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

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT02069041
• Other Study ID Numbers: 15233; I4T-CR-JVCQ
• First Posted: Feb 21, 2014
• Last Update Posted: Nov 21, 2018
• Last Verified: Sep 1, 2017

• Additional relevant MeSH terms: Carcinoma; Carcinoma, Hepatocellular; Leucovorin; Fluorouracil; Oxaliplatin; Ramucirumab

Study Results

Participant Flow

Pre-assignment Detail	Participants completed the study if they completed 3 cycles or discontinued due to a DLT during the DLT assessment period.

Arm/Group Title	Ramucirumab + FOLFOX4
Arm/Group Description	8 milligram/kilogram (mg/kg) ramucirumab given intravenously (IV) on Day 1 followed by FOLFOX4 (folinic acid + fluorouracil + oxaliplatin chemotherapy regimen) given IV on Day 1 of 2 week cycles: FOLFOX4 every 2 weeks: 85 milligram per square meter (mg/m²) oxaliplatin IV on Day 1 200 mg/m² folinic acid(FA) IV on days 1 and 2 400 mg/m² 5-FU bolus on days 1 and 2 600 mg/m2 5-FU 22-h continuous infusion on Days 1 and 2 Participants may continue to receive treatment until discontinuation criteria are met.
Period Title: Overall Study
STARTED	8
Received at Least One Dose of Study Drug	8
COMPLETED	8
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Ramucirumab + FOLFOX4
Arm/Group Description	8 milligram/kilogram (mg/kg) ramucirumab given intravenously (IV) on Day 1 followed by FOLFOX4 (folinic acid + fluorouracil + oxaliplatin chemotherapy regimen) given IV on Day 1 of 2 week cycles: FOLFOX4 every 2 weeks: 85 milligram per square meter (mg/m²) oxaliplatin IV on Day 1 200 mg/m² folinic acid(FA) IV on days 1 and 2 400 mg/m² 5-FU bolus on days 1 and 2 600 mg/m2 5-FU 22-h continuous infusion on Days 1 and 2 Participants may continue to receive treatment until discontinuation criteria are met.
Overall Participants	8
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	55.56 (11.06)
Sex: Female, Male (Count of Participants)
Female	2 25%
Male	6 75%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	8 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	8 100%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	0 0%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
Taiwan	8 100%
Basis of Initial Pathological Diagnosis (Count of Participants)
Histopathological	3 37.5%
Cytological	1 12.5%
Biochemical Assay and Imaging	2 25%
Disease Stage (Count of Participants)
Stage I	0 0%
Stage II	1 12.5%
Stage III	4 50%
Stage IV	1 12.5%
Unknown	0 0%
Duration of Disease (months) (months) [Median (Full Range) ]
Median (Full Range) [months]	0.345
Eastern Cooperative Oncology Group (ECOG) Performance Status (Count of Participants)
0	4 50%
1	4 50%
2	0 0%
>2	0 0%
Missing	0 0%
Barcelona Clinic Liver Cancer (BCLC) Classification (Count of Participants)
Stage A	0 0%
Stage B	1 12.5%
Stage C	7 87.5%
Stage D	0 0%
Missing	0 0%
Viral hepatitis B (Count of Participants)
Test Positive	8 100%
Test Negative	0 0%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration
Description	A summary of other non-serious Adverse Events (AEs), and all Serious Adverse Events (SAE's), regardless of causality, is located in the Reported Adverse Events section.
Time Frame	Baseline through study completion (Up To 8 Months)

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug.

Arm/Group Title	Ramucirumab + FOLFOX4
Arm/Group Description	8 milligram/kilogram (mg/kg) ramucirumab given intravenously (IV) on Day 1 followed by FOLFOX4 (folinic acid + fluorouracil + oxaliplatin chemotherapy regimen) given IV on Day 1 of 2 week cycles: FOLFOX4 every 2 weeks: 85 milligram per square meter (mg/m²) oxaliplatin IV on Day 1 200 mg/m² folinic acid(FA) IV on days 1 and 2 400 mg/m² 5-FU bolus on days 1 and 2 600 mg/m2 5-FU 22-h continuous infusion on Days 1 and 2 Participants may continue to receive treatment until discontinuation criteria are met.
Measure Participants	8
Count of Participants [Participants]	4 50%

2. Secondary Outcome

Title	Pharmacokinetics (PK): Maximum Concentration (Cmax) of Ramucirumab
Description	Maximum Concentration (Cmax)
Time Frame	Cycle 1 and Cycle 3: 0,1.0,1.5,2.0,3.0,5.0,24.0,48.0,168.0,336.0 hours

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug and had evaluable PK data.

Arm/Group Title	Ramucirumab + FOLFOX4
Arm/Group Description	8 milligram/kilogram (mg/kg) ramucirumab given intravenously (IV) on Day 1 followed by FOLFOX4 (folinic acid + fluorouracil + oxaliplatin chemotherapy regimen) given IV on Day 1 of 2 week cycles: FOLFOX4 every 2 weeks: 85 milligram per square meter (mg/m²) oxaliplatin IV on Day 1 200 mg/m² folinic acid(FA) IV on days 1 and 2 400 mg/m² 5-FU bolus on days 1 and 2 600 mg/m2 5-FU 22-h continuous infusion on Days 1 and 2 Participants may continue to receive treatment until discontinuation criteria are met.
Measure Participants	8
Cycle 1	155 (25)
Cycle 3	190 (29)

3. Secondary Outcome

Title	PK:Area Under the Concentration-Time Curve (AUC[0-∞]) of Ramucirumab
Description	Area under the concentration-time curve.
Time Frame	Cycle 1 and Cycle 3: 0,1.0,1.5,2.0,3.0,5.0,24.0,48.0,168.0,336.0 hours

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug and had evaluable PK data.

Arm/Group Title	Ramucirumab + FOLFOX4
Arm/Group Description	8 milligram/kilogram (mg/kg) ramucirumab given intravenously (IV) on Day 1 followed by FOLFOX4 (folinic acid + fluorouracil + oxaliplatin chemotherapy regimen) given IV on Day 1 of 2 week cycles: FOLFOX4 every 2 weeks: 85 milligram per square meter (mg/m²) oxaliplatin IV on Day 1 200 mg/m² folinic acid(FA) IV on days 1 and 2 400 mg/m² 5-FU bolus on days 1 and 2 600 mg/m2 5-FU 22-h continuous infusion on Days 1 and 2 Participants may continue to receive treatment until discontinuation criteria are met.
Measure Participants	8
Cycle 1	940 (24)
Cycle 3	1190 (25)

4. Secondary Outcome

Title	Number of Participants With Anti-Ramucirumab Antibodies
Time Frame	Baseline through 6.1 Months

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug.

Arm/Group Title	Ramucirumab + FOLFOX4
Arm/Group Description	8 milligram/kilogram (mg/kg) ramucirumab given intravenously (IV) on Day 1 followed by FOLFOX4 (folinic acid + fluorouracil + oxaliplatin chemotherapy regimen) given IV on Day 1 of 2 week cycles: FOLFOX4 every 2 weeks: 85 milligram per square meter (mg/m²) oxaliplatin IV on Day 1 200 mg/m² folinic acid(FA) IV on days 1 and 2 400 mg/m² 5-FU bolus on days 1 and 2 600 mg/m2 5-FU 22-h continuous infusion on Days 1 and 2 Participants may continue to receive treatment until discontinuation criteria are met.
Measure Participants	8
Count of Participants [Participants]	0 0%

5. Secondary Outcome

Title	Percentage of Participants With Best Response of Complete Response (CR) or Partial Response (PR) (Overall Response Rate [ORR])
Description	Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST, version[v] 1.1) criteria.CR was defined as the disappearance of all target and non-target lesions and all target and non-target lymph nodes were non-pathological or normal in size [<10 millimeter (mm) short axis]. PR is at least a 30% decrease in the sum of diameter of target lesions, taking as reference the baseline sum diameters. Progressive Disease(PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (including the baseline sum if that is the smallest).In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression. Percentage of participants with CR or PR= (number of participants whose best overall response was CR or PR)/(number of participants treated)*100.
Time Frame	Response to Disease Progression or Death (Up To 7 Months)

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug.

Arm/Group Title	Ramucirumab + FOLFOX4
Arm/Group Description	8 milligram/kilogram (mg/kg) ramucirumab given intravenously (IV) on Day 1 followed by FOLFOX4 (folinic acid + fluorouracil + oxaliplatin chemotherapy regimen) given IV on Day 1 of 2 week cycles: FOLFOX4 every 2 weeks: 85 milligram per square meter (mg/m²) oxaliplatin IV on Day 1 200 mg/m² folinic acid(FA) IV on days 1 and 2 400 mg/m² 5-FU bolus on days 1 and 2 600 mg/m2 5-FU 22-h continuous infusion on Days 1 and 2 Participants may continue to receive treatment until discontinuation criteria are met.
Measure Participants	8
Number [percentage of Participants]	25 312.5%

Adverse Events

Adverse Event Reporting Description	All participants who received at least one dose of study drug.
Arm/Group Title	Ramucirumab + FOLFOX4
Arm/Group Description	8 milligram/kilogram (mg/kg) ramucirumab given intravenously (IV) on Day 1 followed by FOLFOX4 (folinic acid + fluorouracil + oxaliplatin chemotherapy regimen) given IV on Day 1 of 2 week cycles: FOLFOX4 every 2 weeks: 85 milligram per square meter (mg/m²) oxaliplatin IV on Day 1 200 mg/m² folinic acid(FA) IV on days 1 and 2 400 mg/m² 5-FU bolus on days 1 and 2 600 mg/m2 5-FU 22-h continuous infusion on Days 1 and 2 Participants may continue to receive treatment until discontinuation criteria are met.
All Cause Mortality
	Ramucirumab + FOLFOX4
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Ramucirumab + FOLFOX4
	Affected / at Risk (%)	# Events
Total	5/8 (62.5%)
Gastrointestinal disorders
Ascites	2/8 (25%)	2
General disorders
Pyrexia	3/8 (37.5%)	5
Hepatobiliary disorders
Hepatic haemorrhage	1/8 (12.5%)	1
Infections and infestations
Bacteraemia	1/8 (12.5%)	1
Peritonitis bacterial	1/8 (12.5%)	1
Investigations
Blood bilirubin increased	1/8 (12.5%)	2
Neutrophil count decreased	2/8 (25%)	2
Respiratory, thoracic and mediastinal disorders
Lung infiltration	1/8 (12.5%)	1
Other (Not Including Serious) Adverse Events
	Ramucirumab + FOLFOX4
	Affected / at Risk (%)	# Events
Total	8/8 (100%)
Blood and lymphatic system disorders
Anaemia	3/8 (37.5%)	4
Febrile neutropenia	1/8 (12.5%)	1
Leukocytosis	1/8 (12.5%)	1
Leukopenia	1/8 (12.5%)	1
Neutropenia	1/8 (12.5%)	2
Gastrointestinal disorders
Abdominal distension	2/8 (25%)	3
Abdominal pain	6/8 (75%)	10
Abdominal pain upper	3/8 (37.5%)	6
Ascites	1/8 (12.5%)	2
Constipation	3/8 (37.5%)	4
Diarrhoea	5/8 (62.5%)	9
Gingival bleeding	1/8 (12.5%)	1
Mouth haemorrhage	1/8 (12.5%)	2
Mouth ulceration	2/8 (25%)	3
Nausea	4/8 (50%)	7
Stomatitis	3/8 (37.5%)	4
Vomiting	2/8 (25%)	5
General disorders
Chest discomfort	1/8 (12.5%)	1
Chest pain	1/8 (12.5%)	1
Chills	1/8 (12.5%)	1
Fatigue	4/8 (50%)	7
Malaise	1/8 (12.5%)	1
Mucosal inflammation	1/8 (12.5%)	1
Oedema peripheral	3/8 (37.5%)	4
Pyrexia	2/8 (25%)	8
Infections and infestations
Influenza	1/8 (12.5%)	1
Periodontitis	1/8 (12.5%)	1
Injury, poisoning and procedural complications
Allergic transfusion reaction	1/8 (12.5%)	1
Wound complication	1/8 (12.5%)	2
Investigations
Alanine aminotransferase increased	2/8 (25%)	5
Aspartate aminotransferase increased	2/8 (25%)	6
Blood alkaline phosphatase increased	2/8 (25%)	2
Blood bilirubin increased	2/8 (25%)	3
Blood creatinine increased	2/8 (25%)	4
Gamma-glutamyltransferase increased	1/8 (12.5%)	2
Neutrophil count decreased	5/8 (62.5%)	7
Platelet count decreased	4/8 (50%)	12
Weight decreased	2/8 (25%)	2
Weight increased	1/8 (12.5%)	1
White blood cell count decreased	3/8 (37.5%)	9
Metabolism and nutrition disorders
Decreased appetite	5/8 (62.5%)	9
Hyperglycaemia	1/8 (12.5%)	1
Hyperkalaemia	2/8 (25%)	3
Hyperuricaemia	1/8 (12.5%)	1
Hypoalbuminaemia	4/8 (50%)	10
Hypocalcaemia	1/8 (12.5%)	1
Hypokalaemia	1/8 (12.5%)	1
Hyponatraemia	2/8 (25%)	5
Musculoskeletal and connective tissue disorders
Musculoskeletal pain	2/8 (25%)	2
Temporomandibular joint syndrome	1/8 (12.5%)	3
Nervous system disorders
Dizziness	3/8 (37.5%)	3
Headache	2/8 (25%)	3
Hypoaesthesia	1/8 (12.5%)	1
Neuropathy peripheral	1/8 (12.5%)	1
Psychiatric disorders
Insomnia	2/8 (25%)	3
Renal and urinary disorders
Proteinuria	2/8 (25%)	2
Respiratory, thoracic and mediastinal disorders
Cough	2/8 (25%)	2
Dyspnoea	2/8 (25%)	2
Epistaxis	2/8 (25%)	3
Oropharyngeal pain	1/8 (12.5%)	1
Skin and subcutaneous tissue disorders
Alopecia	1/8 (12.5%)	1
Pruritus	1/8 (12.5%)	1
Rash	1/8 (12.5%)	1
Urticaria	1/8 (12.5%)	1
Vascular disorders
Hypertension	2/8 (25%)	3
Hypotension	1/8 (12.5%)	1

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.