Clinical Trials List
Protocol NumberI4T-MC-JVDE
NCT Number(ClinicalTrials.gov Identfier)NCT02435433
2015-07-01 - 2022-12-31
Phase III
Recruiting6
Terminated2
ICD-10C22.0
Liver cell carcinoma
ICD-10C22
Malignant neoplasm of liver and intrahepatic bile ducts
Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study of Ramucirumab and Best Supportive Care (BSC) Versus Placebo and BSC as Second-Line Treatment in Patients With Hepatocellular Carcinoma and Elevated Baseline Alpha-Fetoprotein (AFP) Following First-Line Therapy With Sorafenib
-
Trial Applicant
ELI LILLY AND COMPANY(TAIWAN), INC.
-
Sponsor
Eli Lilly and Company
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- 陳彥仰 Division of Hematology & Oncology
- Tai-Jan Chiu Division of Hematology & Oncology
- 饒坤銘 Division of Hematology & Oncology
- Meng-Jer Hsieh Division of Hematology & Oncology
- Yu-Li Su Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- Ming-Huang Chen Division of Hematology & Oncology
- Yee Chao Division of Hematology & Oncology
- Chien-Wei Su Digestive System Department
- Chung-Pin Li Digestive System Department
- Rheun-Chuan Lee Division of Radiology
The Actual Total Number of Participants Enrolled
2 Recruiting
Audit
None
Co-Principal Investigator
- 黃文聰 Division of Hematology & Oncology
- Shang-Wen Chen Division of Hematology & Oncology
- 曹朝榮 Division of Hematology & Oncology
- 林建良 Division of Hematology & Oncology
- 蕭聖諺 Division of Hematology & Oncology
- 陳昭勳 Division of Hematology & Oncology
- 陳彥勳 Division of Hematology & Oncology
- 陳威宇 Division of Hematology & Oncology
- Shang-Hung Chen Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Yu-Min Yeh Division of Hematology & Oncology
- Wei-Pang Chung Division of Hematology & Oncology
- Shang-Yin Wu Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
Audit
None
Co-Principal Investigator
- CHUNG-HSIN CHANG Digestive System Department
- 呂宜達 Digestive System Department
- 鄭友琦 Division of Radiology
- Sheng-Shun Yang Digestive System Department
- 張碧倚 Division of Radiology
- 葉宏仁 Digestive System Department
- 李少武 Digestive System Department
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Cheng-Lung Hsu Division of Hematology & Oncology
- Ming-Mo Hou Division of Hematology & Oncology
- Jen-Shi Chen Division of Hematology & Oncology
- Chia-Hsun Hsieh Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
3 Recruiting
Audit
None
Co-Principal Investigator
- 林宗哲 Division of Hematology & Oncology
- TSUNG-HAO LIU Division of Hematology & Oncology
- Chiun Hsu Division of Hematology & Oncology
- 呂理駿 Division of Hematology & Oncology
- Ann-Lii Cheng Division of Hematology & Oncology
- - - Division of Hematology & Oncology
- YU-YUN SHAO Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
Audit
None
Condition/Disease
Hepatocellular Carcinoma
Objectives
The primary objective of this study is to compare overall survival (OS) for ramucirumab versus
placebo in patients with advanced hepatocellular carcinoma (HCC) after intolerance or progression on prior
sorafenib treatment.
Test Drug
Ramucirumab (Cyramza)
Active Ingredient
Ramucirumab
Dosage Form
IV
Dosage
10
Endpoints
Efficacy: Overall survival will be measured from the date of randomization to the date of death from any cause.
For each patient who is not known to have died as of the data-inclusion cutoff date for OS analysis, OS will be
censored on the last date the patient is known to be alive.
Progression-free survival is defined as time from the date of randomization to the date of first observation of
objective progression or death from any cause.
Time to radiographic progression is defined as the time from the date of randomization to the date of first
observation of objective progression.
Objective response rate is defined as the percentage of patients who achieve a best overall response of complete
response or partial response. Best overall response will be classified based on the overall responses assessed by
study investigators according to Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1.
Safety: Adverse events will be coded using the Medical Dictionary for Regulatory Activities. Adverse events and
clinical laboratory values will be graded using the Common Terminology Criteria for Adverse Events
Version 4.0. Adverse events, drug exposure, hospitalizations due to adverse events, vital signs, and transfusions
will be summarized.
Health Outcomes: Patient-reported outcomes, including disease-specific symptoms and health status, will be
assessed using the Functional Assessment of Cancer Therapy (FACT) Hepatobiliary Symptom Index-8 (FHSI-8)
and the EuroQol 5-Dimension 5 Level (EQ-5D-5L).
Immunogenicity: Blood samples will be collected at specified time points, and in the event of an infusion-related
reaction, to determine antibody production against ramucirumab or placebo.
Pharmacokinetics: Blood samples will be collected at specified time points, and in the event of an infusion-related
reaction, for assessment of ramucirumab serum concentrations.
Exploratory Biomarker Research: Tumor tissue, plasma, and whole blood will be collected and assayed for
biomarkers relevant to ramucirumab, angiogenesis, and the disease state, and to correlate these markers to
clinical outcome.
For each patient who is not known to have died as of the data-inclusion cutoff date for OS analysis, OS will be
censored on the last date the patient is known to be alive.
Progression-free survival is defined as time from the date of randomization to the date of first observation of
objective progression or death from any cause.
Time to radiographic progression is defined as the time from the date of randomization to the date of first
observation of objective progression.
Objective response rate is defined as the percentage of patients who achieve a best overall response of complete
response or partial response. Best overall response will be classified based on the overall responses assessed by
study investigators according to Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1.
Safety: Adverse events will be coded using the Medical Dictionary for Regulatory Activities. Adverse events and
clinical laboratory values will be graded using the Common Terminology Criteria for Adverse Events
Version 4.0. Adverse events, drug exposure, hospitalizations due to adverse events, vital signs, and transfusions
will be summarized.
Health Outcomes: Patient-reported outcomes, including disease-specific symptoms and health status, will be
assessed using the Functional Assessment of Cancer Therapy (FACT) Hepatobiliary Symptom Index-8 (FHSI-8)
and the EuroQol 5-Dimension 5 Level (EQ-5D-5L).
Immunogenicity: Blood samples will be collected at specified time points, and in the event of an infusion-related
reaction, to determine antibody production against ramucirumab or placebo.
Pharmacokinetics: Blood samples will be collected at specified time points, and in the event of an infusion-related
reaction, for assessment of ramucirumab serum concentrations.
Exploratory Biomarker Research: Tumor tissue, plasma, and whole blood will be collected and assayed for
biomarkers relevant to ramucirumab, angiogenesis, and the disease state, and to correlate these markers to
clinical outcome.
Inclution Criteria
Patients are eligible to be included in the study only if they meet all of the following criteria:
[1] The patient has a diagnosis of HCC based on either:
a. histopathologic or cytologic findings
b. in the absence of histologic confirmation, a diagnosis of cirrhosis and
HCC with classical imaging characteristics (that is, at least a 3-phase
liver protocol CT or MRI and a lesion that demonstrates arterial
hyperenhancement and washes out in the venous phase).
[2] The patient received sorafenib treatment for at least 14 days and discontinued
sorafenib treatment 14 days prior to randomization.
[3] The patient experienced radiographically confirmed disease progression
during or after discontinuation of sorafenib therapy or discontinued sorafenib
treatment because of intolerance despite appropriate sorafenib management
and supportive care.
[4] The patient received sorafenib as the only systemic therapeutic intervention
for advanced HCC.
[5] The patient has 1 measurable lesion per Response Evaluation Criteria In
Solid Tumors (RECIST) Version 1.1 (Eisenhauer et al. 2009) that has not
been previously treated with locoregional therapy.
[6] The patient is 18 years of age or of an age acceptable according to local
regulations, whichever is older.
[7] The patient has a Child-Pugh score of <7 (Child-Pugh Class A only) (Child
and Turcotte 1964; Pugh et al. 1973; Lucey et al. 1997).
[8] The patient has Barcelona Clinic Liver Cancer (BCLC) Stage C disease or
BCLC Stage B disease not amenable to locoregional therapy or refractory to
locoregional therapy.
[9] The patient has a baseline AFP 400 ng/mL, as determined by local
laboratory testing. See Section 10.4.1 for AFP testing requirements.
[10] The patient has an Eastern Cooperative Oncology Group (ECOG)
performance status (PS) of 0 or 1.
[11] The patient has resolution of all clinically significant toxic effects of prior
locoregional therapy, surgery, or other anticancer therapy to Grade 1
(National Cancer Institute Common Terminology Criteria for Adverse Events
[NCI-CTCAE; Version 4.0]).
[12] The patient has adequate organ function as determined by:
a. Hepatic: Total bilirubin 1.5 times upper limit of institutional normal
value (ULN), aspartate transaminase (AST) and alanine transaminase
(ALT) 5 × ULN.
b. Renal:
i. Calculated creatinine clearance (per the Cockcroft-Gault formula
[Attachment 6] or measured using the appropriate radiolabeled method
[51-CrEDTA or Tc99m-DTPA]) to determine glomerular filtration rate
24-hour urine collection) 60 mL/min
ii. The patient’s urinary protein is ≤1+ on dipstick or routine urinalysis. If
urine dipstick or routine analysis indicates proteinuria 2+, then a 24-hour
urine must be collected and must demonstrate <1 g of protein in 24 hours
to allow participation in the study.
c. Hematologic: Absolute neutrophil count 1.0 × 109/L, hemoglobin
9 g/dL (5.58 mmol/L; packed red blood cell transfusions are not
allowed within 1 week prior to baseline hematology profile), and
platelets 75 × 109/L. Recent (<2 months prior to randomization) use of
growth factor support is not allowed.
d. Coagulation: The patient must have adequate coagulation function as
defined by International Normalized Ratio (INR) 1.5 and a partial
thromboplastin time (PTT) 5 seconds above the ULN. Patients
receiving low-dose anticoagulant therapy at prophylactic doses are
eligible provided that INR 1.5 and PTT 5 seconds above the ULN.
[13] The patient meets the more stringent of the following requirements:
a. local requirements regarding methods and duration of contraception.
b. if female, the patient is surgically sterile, postmenopausal, or compliant
with a highly effective contraceptive method (failure rate <1%) during
and for 12 weeks after the study treatment period. Oral hormonal
contraception alone is not considered highly effective and must be used
in combination with a barrier method.
if male, the patient is surgically sterile or compliant with a highly
effective contraceptive method (failure rate <1%) during and for
12 weeks after the study treatment period.
[14] The patient, if a woman of childbearing potential, has a negative serum
pregnancy test within 7 days prior to randomization.
[15] The patient has provided signed informed consent prior to any study specific
procedures and is amenable to compliance with protocol schedules and
testing.
[16] The patient is willing to provide blood/serum for research purposes.
Submission of blood/serum is mandatory for participation in this study, unless
restricted per local regulations.
[1] The patient has a diagnosis of HCC based on either:
a. histopathologic or cytologic findings
b. in the absence of histologic confirmation, a diagnosis of cirrhosis and
HCC with classical imaging characteristics (that is, at least a 3-phase
liver protocol CT or MRI and a lesion that demonstrates arterial
hyperenhancement and washes out in the venous phase).
[2] The patient received sorafenib treatment for at least 14 days and discontinued
sorafenib treatment 14 days prior to randomization.
[3] The patient experienced radiographically confirmed disease progression
during or after discontinuation of sorafenib therapy or discontinued sorafenib
treatment because of intolerance despite appropriate sorafenib management
and supportive care.
[4] The patient received sorafenib as the only systemic therapeutic intervention
for advanced HCC.
[5] The patient has 1 measurable lesion per Response Evaluation Criteria In
Solid Tumors (RECIST) Version 1.1 (Eisenhauer et al. 2009) that has not
been previously treated with locoregional therapy.
[6] The patient is 18 years of age or of an age acceptable according to local
regulations, whichever is older.
[7] The patient has a Child-Pugh score of <7 (Child-Pugh Class A only) (Child
and Turcotte 1964; Pugh et al. 1973; Lucey et al. 1997).
[8] The patient has Barcelona Clinic Liver Cancer (BCLC) Stage C disease or
BCLC Stage B disease not amenable to locoregional therapy or refractory to
locoregional therapy.
[9] The patient has a baseline AFP 400 ng/mL, as determined by local
laboratory testing. See Section 10.4.1 for AFP testing requirements.
[10] The patient has an Eastern Cooperative Oncology Group (ECOG)
performance status (PS) of 0 or 1.
[11] The patient has resolution of all clinically significant toxic effects of prior
locoregional therapy, surgery, or other anticancer therapy to Grade 1
(National Cancer Institute Common Terminology Criteria for Adverse Events
[NCI-CTCAE; Version 4.0]).
[12] The patient has adequate organ function as determined by:
a. Hepatic: Total bilirubin 1.5 times upper limit of institutional normal
value (ULN), aspartate transaminase (AST) and alanine transaminase
(ALT) 5 × ULN.
b. Renal:
i. Calculated creatinine clearance (per the Cockcroft-Gault formula
[Attachment 6] or measured using the appropriate radiolabeled method
[51-CrEDTA or Tc99m-DTPA]) to determine glomerular filtration rate
24-hour urine collection) 60 mL/min
ii. The patient’s urinary protein is ≤1+ on dipstick or routine urinalysis. If
urine dipstick or routine analysis indicates proteinuria 2+, then a 24-hour
urine must be collected and must demonstrate <1 g of protein in 24 hours
to allow participation in the study.
c. Hematologic: Absolute neutrophil count 1.0 × 109/L, hemoglobin
9 g/dL (5.58 mmol/L; packed red blood cell transfusions are not
allowed within 1 week prior to baseline hematology profile), and
platelets 75 × 109/L. Recent (<2 months prior to randomization) use of
growth factor support is not allowed.
d. Coagulation: The patient must have adequate coagulation function as
defined by International Normalized Ratio (INR) 1.5 and a partial
thromboplastin time (PTT) 5 seconds above the ULN. Patients
receiving low-dose anticoagulant therapy at prophylactic doses are
eligible provided that INR 1.5 and PTT 5 seconds above the ULN.
[13] The patient meets the more stringent of the following requirements:
a. local requirements regarding methods and duration of contraception.
b. if female, the patient is surgically sterile, postmenopausal, or compliant
with a highly effective contraceptive method (failure rate <1%) during
and for 12 weeks after the study treatment period. Oral hormonal
contraception alone is not considered highly effective and must be used
in combination with a barrier method.
if male, the patient is surgically sterile or compliant with a highly
effective contraceptive method (failure rate <1%) during and for
12 weeks after the study treatment period.
[14] The patient, if a woman of childbearing potential, has a negative serum
pregnancy test within 7 days prior to randomization.
[15] The patient has provided signed informed consent prior to any study specific
procedures and is amenable to compliance with protocol schedules and
testing.
[16] The patient is willing to provide blood/serum for research purposes.
Submission of blood/serum is mandatory for participation in this study, unless
restricted per local regulations.
Exclusion Criteria
Patients will be excluded from the study if they meet any of the following criteria:
[17] The patient has fibrolamellar carcinoma or mixed hepatocellular
cholangiocarcinoma.
[18] The patient had a previous or has concurrent malignancy. Patients with
carcinoma in situ of any origin and patients with prior malignancies who are
in remission and whose likelihood of recurrence is very low, as judged by the
investigator, may be eligible for this study in consultation with and approval
by the Lilly CRP.
[19] The patient has previously documented brain metastases, leptomeningeal
disease, or uncontrolled spinal cord compression.
[20] The patient has a history of or current hepatic encephalopathy (any grade) or
clinically meaningful ascites. Clinically meaningful ascites is defined as
CTCAE Grade >1 ascites resulting from cirrhosis. Patients who have been on
a stable medical regimen (for 3 months) to manage ascites are eligible if they
show no evidence of ascites on clinical exam that would require further
intervention.
[21] The patient has ongoing or recent (6 months prior to randomization)
hepatorenal syndrome.
[22] The patient had a prior liver transplant.
[23] The patient received any previous systemic therapy with VEGF inhibitors or
VEGF-Receptor inhibitors (including investigational agents) other than
sorafenib for treatment of HCC.
[24] The patient received any hepatic locoregional therapy (including radiation,
surgery, hepatic arterial embolization, chemoembolization, radiofrequency
ablation, cryoablation, or percutaneous ethanol injection) following sorafenib
or within 28 days prior to randomization. Use of locoregional therapy prior to
sorafenib is allowed.
[25] The patient received radiation to any nonhepatic (for example, bone) site
within 14 days prior to randomization. Prior radiation to >25% total bone
marrow is not allowed.
[26] The patient experienced either of the following:
a. a major surgical procedure, significant traumatic injury, non-healing
wound, peptic ulcer, or bone fracture 28 days prior to randomization, or
b. placement of a subcutaneous venous access device within 7 days prior to
the first dose of study treatment unless the procedure is of low risk of
bleeding in the judgment of the investigator (for example, introduction of
peripherally inserted central catheter line).
Study medications can be commenced only after complete wound healing.
[27] The patient is currently enrolled in a clinical trial involving an investigational
product or nonapproved use of a drug or device or is concurrently enrolled in
any other type of medical research judged not to be scientifically or medically
compatible with this study. Patients participating in surveys or observational
studies are eligible to participate in this study.
[28] The patient discontinued from study treatment from another clinical trial
within 28 days prior to randomization.
[29] The patient has a known allergy or hypersensitivity reaction to any of the
treatment components.
[30] The patient has uncontrolled hypertension, as defined in CTCAE Version 4.0,
prior to initiating study treatment, despite antihypertensive intervention.
CTCAE Version 4.0 defines uncontrolled hypertension as Grade >2
hypertension; clinically, the patient continues to experience elevated blood
pressure (systolic >160 mm Hg and/or diastolic >100 mm Hg) despite
medications).
[31] The patient experienced any arterial thrombotic event, including myocardial
infarction, unstable angina, cerebrovascular accident, or transient ischemic
attack, within 6 months prior to randomization.
[32] The patient experienced any bleeding episode considered life-threatening, or
any Grade 3 or 4 gastrointestinal/variceal bleeding episode in the 3 months
prior to randomization requiring transfusion or endoscopic or operative
intervention.
[33] The patient has esophageal or gastric varices that require immediate
intervention (for example, banding or sclerotherapy) or represent a high
bleeding risk in the opinion of the investigator or consulting gastroenterologist
or hepatologist. Patients with evidence of portal hypertension (including
splenomegaly detected radiographically) or any prior history of variceal
bleeding must have had endoscopic evaluation within the 3 months
immediately prior to randomization.
[34] The patient has a history of gastrointestinal perforation and/or fistulae within
6 months prior to randomization.
[35] The patient has symptomatic congestive heart failure (New York Heart
Association II-IV), unstable angina pectoris, or symptomatic or poorly
controlled cardiac arrhythmia.
[36] The patient is pregnant or breast-feeding.
[37] The patient has an acute or chronic medical or psychiatric condition or
laboratory abnormality that may increase the risk associated with study
participation or study drug administration, or may interfere with the
interpretation of study results, and in the judgment of the investigator would
make the patient ineligible for entry into this study. Such conditions or
abnormalities include but are not limited to:
a. Known human immunodeficiency virus infection or acquired
immunodeficiency syndrome-related illness.
b. Active or uncontrolled clinically serious infection. (Patients with chronic
viral hepatitis are eligible.)
c. Ongoing or recent history of drug abuse.
d. The patient has a history of uncontrolled hereditary or acquired
thrombotic or bleeding disorder.
[38] The patient has a bowel obstruction, history or presence of inflammatory
enteropathy or extensive intestinal resection (hemicolectomy or extensive
small intestine resection with chronic diarrhea), Crohn's disease, ulcerative
colitis, or chronic diarrhea.
[39] The patient is receiving therapeutic dose anticoagulation with warfarin,
low-molecular-weight heparin, or similar agents.
[40] The patient is receiving chronic therapy with nonsteroidal anti-inflammatory
agents (such as indomethacin, ibuprofen, naproxen or similar agents) or other
anti-platelet agents (such as clopidogrel, ticlopidine, dipyridamole, or
anagrelide). Aspirin at doses up to 100 mg/day is permitted.
[41] The patient plans to undergo elective major surgery during the course of the
trial.
[17] The patient has fibrolamellar carcinoma or mixed hepatocellular
cholangiocarcinoma.
[18] The patient had a previous or has concurrent malignancy. Patients with
carcinoma in situ of any origin and patients with prior malignancies who are
in remission and whose likelihood of recurrence is very low, as judged by the
investigator, may be eligible for this study in consultation with and approval
by the Lilly CRP.
[19] The patient has previously documented brain metastases, leptomeningeal
disease, or uncontrolled spinal cord compression.
[20] The patient has a history of or current hepatic encephalopathy (any grade) or
clinically meaningful ascites. Clinically meaningful ascites is defined as
CTCAE Grade >1 ascites resulting from cirrhosis. Patients who have been on
a stable medical regimen (for 3 months) to manage ascites are eligible if they
show no evidence of ascites on clinical exam that would require further
intervention.
[21] The patient has ongoing or recent (6 months prior to randomization)
hepatorenal syndrome.
[22] The patient had a prior liver transplant.
[23] The patient received any previous systemic therapy with VEGF inhibitors or
VEGF-Receptor inhibitors (including investigational agents) other than
sorafenib for treatment of HCC.
[24] The patient received any hepatic locoregional therapy (including radiation,
surgery, hepatic arterial embolization, chemoembolization, radiofrequency
ablation, cryoablation, or percutaneous ethanol injection) following sorafenib
or within 28 days prior to randomization. Use of locoregional therapy prior to
sorafenib is allowed.
[25] The patient received radiation to any nonhepatic (for example, bone) site
within 14 days prior to randomization. Prior radiation to >25% total bone
marrow is not allowed.
[26] The patient experienced either of the following:
a. a major surgical procedure, significant traumatic injury, non-healing
wound, peptic ulcer, or bone fracture 28 days prior to randomization, or
b. placement of a subcutaneous venous access device within 7 days prior to
the first dose of study treatment unless the procedure is of low risk of
bleeding in the judgment of the investigator (for example, introduction of
peripherally inserted central catheter line).
Study medications can be commenced only after complete wound healing.
[27] The patient is currently enrolled in a clinical trial involving an investigational
product or nonapproved use of a drug or device or is concurrently enrolled in
any other type of medical research judged not to be scientifically or medically
compatible with this study. Patients participating in surveys or observational
studies are eligible to participate in this study.
[28] The patient discontinued from study treatment from another clinical trial
within 28 days prior to randomization.
[29] The patient has a known allergy or hypersensitivity reaction to any of the
treatment components.
[30] The patient has uncontrolled hypertension, as defined in CTCAE Version 4.0,
prior to initiating study treatment, despite antihypertensive intervention.
CTCAE Version 4.0 defines uncontrolled hypertension as Grade >2
hypertension; clinically, the patient continues to experience elevated blood
pressure (systolic >160 mm Hg and/or diastolic >100 mm Hg) despite
medications).
[31] The patient experienced any arterial thrombotic event, including myocardial
infarction, unstable angina, cerebrovascular accident, or transient ischemic
attack, within 6 months prior to randomization.
[32] The patient experienced any bleeding episode considered life-threatening, or
any Grade 3 or 4 gastrointestinal/variceal bleeding episode in the 3 months
prior to randomization requiring transfusion or endoscopic or operative
intervention.
[33] The patient has esophageal or gastric varices that require immediate
intervention (for example, banding or sclerotherapy) or represent a high
bleeding risk in the opinion of the investigator or consulting gastroenterologist
or hepatologist. Patients with evidence of portal hypertension (including
splenomegaly detected radiographically) or any prior history of variceal
bleeding must have had endoscopic evaluation within the 3 months
immediately prior to randomization.
[34] The patient has a history of gastrointestinal perforation and/or fistulae within
6 months prior to randomization.
[35] The patient has symptomatic congestive heart failure (New York Heart
Association II-IV), unstable angina pectoris, or symptomatic or poorly
controlled cardiac arrhythmia.
[36] The patient is pregnant or breast-feeding.
[37] The patient has an acute or chronic medical or psychiatric condition or
laboratory abnormality that may increase the risk associated with study
participation or study drug administration, or may interfere with the
interpretation of study results, and in the judgment of the investigator would
make the patient ineligible for entry into this study. Such conditions or
abnormalities include but are not limited to:
a. Known human immunodeficiency virus infection or acquired
immunodeficiency syndrome-related illness.
b. Active or uncontrolled clinically serious infection. (Patients with chronic
viral hepatitis are eligible.)
c. Ongoing or recent history of drug abuse.
d. The patient has a history of uncontrolled hereditary or acquired
thrombotic or bleeding disorder.
[38] The patient has a bowel obstruction, history or presence of inflammatory
enteropathy or extensive intestinal resection (hemicolectomy or extensive
small intestine resection with chronic diarrhea), Crohn's disease, ulcerative
colitis, or chronic diarrhea.
[39] The patient is receiving therapeutic dose anticoagulation with warfarin,
low-molecular-weight heparin, or similar agents.
[40] The patient is receiving chronic therapy with nonsteroidal anti-inflammatory
agents (such as indomethacin, ibuprofen, naproxen or similar agents) or other
anti-platelet agents (such as clopidogrel, ticlopidine, dipyridamole, or
anagrelide). Aspirin at doses up to 100 mg/day is permitted.
[41] The patient plans to undergo elective major surgery during the course of the
trial.
The Estimated Number of Participants
-
Taiwan
44-49 participants
-
Global
399 participants
