Clinical Trials List
Protocol NumberH3B-6527-G000-101
NCT Number(ClinicalTrials.gov Identfier)NCT02834780
2017-03-24 - 2020-02-29
Phase I
Terminated3
ICD-10C22
Malignant neoplasm of liver and intrahepatic bile ducts
An Open-Label Multicenter Phase 1 Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of H3B-6527 in Subjects With Advanced Hepatocelluar Carcinoma or Intrahepatic Cholangiocarcinoma
-
Sponsor
Eisai Co., Ltd., H3 Biomedicine Inc. (United States Research Subsidiary of Eisai Co., Ltd.)
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- 葉宏仁 Digestive System Department
- CHUNG-HSIN CHANG Digestive System Department
- 張碧倚 Division of Radiology
- 呂宜達 Digestive System Department
- 劉嘯天 Division of General Surgery
- 李少武 Digestive System Department
- 王俊元 Division of Ophthalmology
- TENG-YU LEE Digestive System Department
- 鄭紹彬 Division of General Surgery
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
Audit
None
Co-Principal Investigator
- Shinn-Cherng Chen Digestive System Department
- Chia-Yen Dai Digestive System Department
- Ming-Lung Yu Digestive System Department
- Wan-Long Chuang Digestive System Department
- Ming-Lun Yeh Digestive System Department
- Zu-Yau Lin Digestive System Department
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Nai-Jung Chiang Division of Hematology & Oncology
- Kwang-Yu Chang Division of Hematology & Oncology
- 姜乃榕 Division of Hematology & Oncology
- Shang-Hung Chen Division of Hematology & Oncology
- Chia-Jui Yen Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Audit
None
Condition/Disease
Advanced hepatocellular carcinoma
Objectives
Primary objectives
Determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of H3B-6527 in subjects with advanced hepatocellular carcinoma (HCC) or intrahepatic cholangiocarcinoma (JCC)
•Assess the safety and tolerability of H3B-6527 as a single agent administered orally
Secondary objectives
Evaluate the pharmacokinetic (PK) profile of H3B-6527
•Evaluate the preliminary antitumor activity of H3B-6527 at the RP2D and schedule in subjects with advanced HCC or ICC who are FGF19-positive as determined by the Sponsor-designated laboratory
Exploratory objectives
•Explore biomarkers and their correlation with safety and efficacy endpoints
•Assess the pharmacodynamic effects of H3B-6527 on FGF19，Ki67，pERK，bile acids and CYP7A1 and other FGFR4-related biomarkers in blood and tumor samples
•Explore the relationship between PK and pharmacodynamics
•Exposure to H3B-6527 in tumor samples may be assessed
•Explore the metabolite profile ofH3B-6527 in plasma and urine
Test Drug
H3B-6527
Active Ingredient
H3B-6527
Dosage Form
capsule
Dosage
50 mg, 100 mg and 200 mg
Endpoints
Primary objectives
Determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of H3B-6527 in subjects with advanced hepatocellular carcinoma (HCC) or intrahepatic cholangiocarcinoma (JCC)
•Assess the safety and tolerability of H3B-6527 as a single agent administered orally
Secondary objectives
Evaluate the pharmacokinetic (PK) profile of H3B-6527
•Evaluate the preliminary antitumor activity of H3B-6527 at the RP2D and schedule in subjects with advanced HCC or ICC who are FGF19-positive as determined by the Sponsor-designated laboratory
Exploratory objectives
•Explore biomarkers and their correlation with safety and efficacy endpoints
•Assess the pharmacodynamic effects of H3B-6527 on FGF19，Ki67，pERK，bile acids and CYP7A1 and other FGFR4-related biomarkers in blood and tumor samples
•Explore the relationship between PK and pharmacodynamics
•Exposure to H3B-6527 in tumor samples may be assessed
•Explore the metabolite profile ofH3B-6527 in plasma and urine
Determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of H3B-6527 in subjects with advanced hepatocellular carcinoma (HCC) or intrahepatic cholangiocarcinoma (JCC)
•Assess the safety and tolerability of H3B-6527 as a single agent administered orally
Secondary objectives
Evaluate the pharmacokinetic (PK) profile of H3B-6527
•Evaluate the preliminary antitumor activity of H3B-6527 at the RP2D and schedule in subjects with advanced HCC or ICC who are FGF19-positive as determined by the Sponsor-designated laboratory
Exploratory objectives
•Explore biomarkers and their correlation with safety and efficacy endpoints
•Assess the pharmacodynamic effects of H3B-6527 on FGF19，Ki67，pERK，bile acids and CYP7A1 and other FGFR4-related biomarkers in blood and tumor samples
•Explore the relationship between PK and pharmacodynamics
•Exposure to H3B-6527 in tumor samples may be assessed
•Explore the metabolite profile ofH3B-6527 in plasma and urine
Inclution Criteria
1. Be ≥18 years of age.
2. Have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
3. Have an HCC or ICC diagnosis with the following criteria:
• Confirmed by available pathology records or current biopsy (For HCC subjects,
confirmed diagnosis may be made by histological examination or by noninvasive
criteria according to the European Association for the Study of the Liver or the
American Association for the Study of Liver Disease Guidelines)
• Advanced, unresectable, or recurrent
• Progressing since the last antitumor therapy
• Child-Pugh A classification
• No clinically significant ascites
• Must have received at least one prior standard-of-care therapy or declined such
therapy.
4. Have received prior platinum- based therapy (cisplatin or oxaliplatin) (ICC subjects only),
unless contraindicated.
5. Be tumor- FGF19-positive as determined by a Sponsor-designated laboratory prior to
enrollment in the Dose Expansion Phase of the trial.
6. Have completed any prior chemotherapy, monoclonal antibody or immunotherapy (eg, tumor
vaccine, cytokine, or growth factor given to control the cancer) at least 4 weeks or 5 half-lives
(whichever is shorter) before study drug administration, and all AEs must have either returned
to baseline or resolved to Grade 0 or 1.
7. Have completed any prior definitive radiation therapy at least 3 weeks before study drug
administration; any prior focal radiotherapy at least 2 weeks before study drug administration;
irradiated lesions should show evidence of size increase as defined in inclusion criterion #7 if
they are intended to be followed as target lesions. Radiopharmaceutical therapy (strontium,
samarium, yttrium) must have been completed 8 weeks before study drug administration.
8. Have available tumor tissue as follows:
a. Part 1, Dose Escalation: tumor tissue (screening acquisition or archival tissue if obtained)
is requested but not mandated.
b. Part 2, Expansion: Fresh tumor tissue (screening acquisition) must be available and the
subject must have accessible tumors for repeat biopsy and consent to acquisition of
tumor tissue during study treatment. Archival tissue if available is requested but not
mandated.
9. Have measurable disease as follows:
a. Part 1, Dose Escalation: Subjects may have measurable or nonmeasurable disease as
defined by RECIST 1.1/mRECIST (depending on tumor type).
b. Part 2, Expansion: Subjects must have measurable disease meeting the following
criteria:
i. Subjects with HCC: At least 1 measurable target lesion according to mRECIST
that meets the following criteria:
• Hepatic lesion
- The lesion can be accurately measured in at least one dimension as ≥1.0 cm
- The lesion is suitable for repeat measurement
- The lesion shows intratumoral arterial phase enhancement on
contrast-enhanced computed tomography (CT) or magnetic resonance
imaging (MRI)
• Nonhepatic lesion
- Lymph node (LN) lesion that measures at least one dimension as ≥1.5 cm in
the short axis, except for porta hepatis LN that measures ≥2.0 cm in the short
axis
- Non-nodal lesion that measures ≥1.0 cm in the longest diameter
Lesions previously treated with radiotherapy or locoregional therapy must show
radiographic evidence of disease progression by mRECIST to be deemed a target
lesion.
ii. Subjects with ICC:
• At least 1 lesion of ≥1.0 cm in the longest diameter for a non-lymph node or ≥1.5
cm in the short-axis diameter for a lymph node that is serially measurable
according to RECIST 1.1 using CT/MRI.
• Lesions that have had external beam radiotherapy (EBRT) or loco-regional
therapies such as radiofrequency (RF) ablation or chemoembolization must show
evidence of progressive disease based on RECIST 1.1 to be deemed a targetlesion.
10. Have left ventricular ejection fraction (LVEF) >50% on echocardiography or multiple-gate
acquisition (MUGA) scan.
11. Have adequate renal function defined as serum creatinine <1.5 × ULN (or calculated creatinine
clearance ≥50 mL/min per the Cockcroft and Gault formula).
12. Have adequate bone marrow function as follows:
a. Absolute neutrophil count (ANC) ≥1500/mm3 (≥1.5 × 109/L)
b. Platelet counts ≥75,000/mm3 (≥75 × 109/L)
c. Hemoglobin ≥9.0 g/dL (may have been transfused).
13. Have adequate liver function as follows:
a. Adequate blood coagulation as evidenced by an International Normalized Ratio (INR)
≤1.5.
b. Total bilirubin ≤1.5 × ULN.
c. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤5 × ULN.
d. No evidence of biliary duct obstruction unless obstruction controlled by local treatment
or, the biliary tree can be decompressed by endoscopic or percutaneous stenting with
subsequent reduction in bilirubin to ≤1.5 × ULN.
14. Females must not be lactating or pregnant at Screening or Baseline (as documented by a
negative beta-human chorionic gonadotropin [ß-hCG] test with a minimum sensitivity of
25 IU/L or equivalent units of ß-hCG). A separate baseline assessment is required if a
negative screening pregnancy test was obtained more than 72 hours before the first dose of
study drug.
NOTE: All females will be considered to be of childbearing potential unless they are
postmenopausal (amenorrheic for at least 12 consecutive months, in the appropriate age group
and without other known or suspected cause) or have been sterilized surgically (ie, bilateral
tubal ligation, total hysterectomy or bilateral oophorectomy, all with surgery at least 1 month
before dosing).
15. Females of childbearing potential should avoid becoming pregnant and use highly effective
contraception while on treatment and for at least 1 month after finishing treatment. Females
of childbearing potential must not have had unprotected sexual intercourse within 30 days
before study entry and must agree to use a highly effective method of contraception (eg, total abstinence, an intrauterine device, a contraceptive implant, an oral contraceptive, or have a
vasectomized partner with confirmed azoospermia) throughout the entire study period and for
30 days after study drug discontinuation. Females who are using hormonal contraceptives
must have been on a stable dose of the same hormonal contraceptive product for at least
4 weeks before dosing and must continue to use the same contraceptive during the study and
for 30 days after study drug discontinuation. Women using oral hormonal contraceptives
should add a barrier method.
16. Be willing and able to comply with all aspects of the protocol.
17. Provide written informed consent prior to any study-specific screening procedures.
2. Have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
3. Have an HCC or ICC diagnosis with the following criteria:
• Confirmed by available pathology records or current biopsy (For HCC subjects,
confirmed diagnosis may be made by histological examination or by noninvasive
criteria according to the European Association for the Study of the Liver or the
American Association for the Study of Liver Disease Guidelines)
• Advanced, unresectable, or recurrent
• Progressing since the last antitumor therapy
• Child-Pugh A classification
• No clinically significant ascites
• Must have received at least one prior standard-of-care therapy or declined such
therapy.
4. Have received prior platinum- based therapy (cisplatin or oxaliplatin) (ICC subjects only),
unless contraindicated.
5. Be tumor- FGF19-positive as determined by a Sponsor-designated laboratory prior to
enrollment in the Dose Expansion Phase of the trial.
6. Have completed any prior chemotherapy, monoclonal antibody or immunotherapy (eg, tumor
vaccine, cytokine, or growth factor given to control the cancer) at least 4 weeks or 5 half-lives
(whichever is shorter) before study drug administration, and all AEs must have either returned
to baseline or resolved to Grade 0 or 1.
7. Have completed any prior definitive radiation therapy at least 3 weeks before study drug
administration; any prior focal radiotherapy at least 2 weeks before study drug administration;
irradiated lesions should show evidence of size increase as defined in inclusion criterion #7 if
they are intended to be followed as target lesions. Radiopharmaceutical therapy (strontium,
samarium, yttrium) must have been completed 8 weeks before study drug administration.
8. Have available tumor tissue as follows:
a. Part 1, Dose Escalation: tumor tissue (screening acquisition or archival tissue if obtained)
is requested but not mandated.
b. Part 2, Expansion: Fresh tumor tissue (screening acquisition) must be available and the
subject must have accessible tumors for repeat biopsy and consent to acquisition of
tumor tissue during study treatment. Archival tissue if available is requested but not
mandated.
9. Have measurable disease as follows:
a. Part 1, Dose Escalation: Subjects may have measurable or nonmeasurable disease as
defined by RECIST 1.1/mRECIST (depending on tumor type).
b. Part 2, Expansion: Subjects must have measurable disease meeting the following
criteria:
i. Subjects with HCC: At least 1 measurable target lesion according to mRECIST
that meets the following criteria:
• Hepatic lesion
- The lesion can be accurately measured in at least one dimension as ≥1.0 cm
- The lesion is suitable for repeat measurement
- The lesion shows intratumoral arterial phase enhancement on
contrast-enhanced computed tomography (CT) or magnetic resonance
imaging (MRI)
• Nonhepatic lesion
- Lymph node (LN) lesion that measures at least one dimension as ≥1.5 cm in
the short axis, except for porta hepatis LN that measures ≥2.0 cm in the short
axis
- Non-nodal lesion that measures ≥1.0 cm in the longest diameter
Lesions previously treated with radiotherapy or locoregional therapy must show
radiographic evidence of disease progression by mRECIST to be deemed a target
lesion.
ii. Subjects with ICC:
• At least 1 lesion of ≥1.0 cm in the longest diameter for a non-lymph node or ≥1.5
cm in the short-axis diameter for a lymph node that is serially measurable
according to RECIST 1.1 using CT/MRI.
• Lesions that have had external beam radiotherapy (EBRT) or loco-regional
therapies such as radiofrequency (RF) ablation or chemoembolization must show
evidence of progressive disease based on RECIST 1.1 to be deemed a targetlesion.
10. Have left ventricular ejection fraction (LVEF) >50% on echocardiography or multiple-gate
acquisition (MUGA) scan.
11. Have adequate renal function defined as serum creatinine <1.5 × ULN (or calculated creatinine
clearance ≥50 mL/min per the Cockcroft and Gault formula).
12. Have adequate bone marrow function as follows:
a. Absolute neutrophil count (ANC) ≥1500/mm3 (≥1.5 × 109/L)
b. Platelet counts ≥75,000/mm3 (≥75 × 109/L)
c. Hemoglobin ≥9.0 g/dL (may have been transfused).
13. Have adequate liver function as follows:
a. Adequate blood coagulation as evidenced by an International Normalized Ratio (INR)
≤1.5.
b. Total bilirubin ≤1.5 × ULN.
c. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤5 × ULN.
d. No evidence of biliary duct obstruction unless obstruction controlled by local treatment
or, the biliary tree can be decompressed by endoscopic or percutaneous stenting with
subsequent reduction in bilirubin to ≤1.5 × ULN.
14. Females must not be lactating or pregnant at Screening or Baseline (as documented by a
negative beta-human chorionic gonadotropin [ß-hCG] test with a minimum sensitivity of
25 IU/L or equivalent units of ß-hCG). A separate baseline assessment is required if a
negative screening pregnancy test was obtained more than 72 hours before the first dose of
study drug.
NOTE: All females will be considered to be of childbearing potential unless they are
postmenopausal (amenorrheic for at least 12 consecutive months, in the appropriate age group
and without other known or suspected cause) or have been sterilized surgically (ie, bilateral
tubal ligation, total hysterectomy or bilateral oophorectomy, all with surgery at least 1 month
before dosing).
15. Females of childbearing potential should avoid becoming pregnant and use highly effective
contraception while on treatment and for at least 1 month after finishing treatment. Females
of childbearing potential must not have had unprotected sexual intercourse within 30 days
before study entry and must agree to use a highly effective method of contraception (eg, total abstinence, an intrauterine device, a contraceptive implant, an oral contraceptive, or have a
vasectomized partner with confirmed azoospermia) throughout the entire study period and for
30 days after study drug discontinuation. Females who are using hormonal contraceptives
must have been on a stable dose of the same hormonal contraceptive product for at least
4 weeks before dosing and must continue to use the same contraceptive during the study and
for 30 days after study drug discontinuation. Women using oral hormonal contraceptives
should add a barrier method.
16. Be willing and able to comply with all aspects of the protocol.
17. Provide written informed consent prior to any study-specific screening procedures.
Exclusion Criteria
1. Other malignancy active within the previous 2 years except for basal or squamous cell skin
cancer, stage 1 prostate cancer, superficial bladder cancer or carcinoma in situ of the cervix or
breast that has completed curative therapy.
2. Current evidence of corneal disorder/keratopathy including but not limited to corneal
epithelial thinning, bullous/band keratopathy, corneal abrasion, inflammation/ulceration, or
keratoconjunctivitis (to be confirmed by ophthalmological examination). Pre-existing
cataract is not a reason for exclusion.
3. Brain or subdural metastases are not eligible, unless they have completed local therapy and
have discontinued the use of corticosteroids for this indication for at least 4 weeks before
starting treatment in this study. Any signs (eg, radiologic) or symptoms of brain metastases
must be stable for at least 4 weeks before starting study treatment.
4. Genetic diseases of the liver that may complicate review of safety data.
5. Known human immunodeficiency virus (HIV) infection.
6. Uncontrolled significant active infections, except Hepatitis B (HBV) or Hepatitis C (HCV).
Subjects with HBV are eligible but should be taking an appropriate antiviral medication if
indicated. Subjects with HCV are eligible but must not be taking concomitant treatment for
HCV while receiving H3B-6527.
7. Major surgery or other locoregional treatment within 4 weeks before the first dose of study
drug or radionuclide treatment (eg, 90Yttrium intra-arterial treatment) 8 weeks before study
drug administration.
8. Inability to take oral medication, or presence of a malabsorption syndrome or any other
uncontrolled gastrointestinal condition (eg, nausea, diarrhea, or vomiting) that might impair the bioavailability of H3B-6527. Subjects with prior gastric resection are eligible.
9. Use of any drug that is a strong inhibitor or inducer of the CYP3A4 enzyme within at least 2
weeks before the start of study drug and during the conduct of the study unless there is an
emergent or life-threatening medical condition that requires it.
10. Use of any drug known to prolong QTc interval within at least 2 weeks before the start of the
study drug and during the conduct of the study.
11. Treatment with proton pump inhibitors that cannot be discontinued 3 days prior to the start of
study drug and during the course of the study; antacids are permitted except for calcium
carbonate antacids (eg, Tums® ).
12. Use of other investigational drugs within 28 days or at least 5 half-lives (whichever is shorter)
before study drug administration.
13. Previous treatment with a selective FGF19-FGFR4 targeted therapy.
14. Use of any live vaccines against infectious diseases (eg, influenza, varicella) within 4 weeks
(28 days) of initiation of study therapy.
15. Presence of gastric or esophageal varices requiring active treatment.
16. A clinically significant ECG abnormality, including a marked baseline prolonged QTc interval
(eg, a repeated demonstration of a QTc interval >500 ms).
17. Significant cardiovascular impairment: history of congestive heart failure greater than New
York Heart Association Class II, uncontrolled arterial hypertension, unstable angina,
myocardial infarction, or stroke within 6 months of the first dose of study drug; or cardiac
arrhythmia requiring medical treatment (including oral anticoagulation).
18. Any other major illness, medical condition or concomitant medication that, in the
investigator’s judgment, will substantially increase the risk associated with the subject’s
participation in this study or would compromise the subject’s ability to safely complete the
study.
19. Males who have not had a successful vasectomy (confirmed azoospermia) or they and their
female partners do not meet the criteria above (ie, not of childbearing potential or practicing
highly effective contraception throughout the study period or for 90 days after study drug
discontinuation). No sperm donation is allowed during the study period or for 90 days after
study drug discontinuation.
20. Hypersensitivity to the study drug or to any of the excipients.
21. Intolerance or hypersensitivity to both CT and MRI contrast material that would preclude the
ability to acquire the triphasic liver imaging required by the protocol.
22. An inorganic phosphorus > ULN for the institution. Note: Subjects may be on treatment for
hyperphosphatemia, but the levels must be normal at screening to participate in this study.
Subjects with high levels on screening may subsequently be treated and rescreened and,
should they have stable levels for 2 weeks prior to study, may enter the study.
23. A total or ionized serum calcium > ULN for the institution. Note: Subjects may be on
treatment for hypercalcemia, but the levels must be normal at screening to participate in this
study. Subjects with high levels on screening may subsequently be treated and rescreened
and, should they have stable levels for 2 weeks prior to study, may enter the study.
24. Endocrine changes that may result in increases in calcium or phosphate, including but not
limited to hyperparathyroidism and tumoral calcinosis.
25. Past medical history and/or current evidence of tumoral calcinosis or tissue calcification.
26. Use of calcium or vitamin D supplements or systemic corticosteroids. The duration between the last systemic corticosteroid administration and the first dose of study drug should be at least 2 weeks.
cancer, stage 1 prostate cancer, superficial bladder cancer or carcinoma in situ of the cervix or
breast that has completed curative therapy.
2. Current evidence of corneal disorder/keratopathy including but not limited to corneal
epithelial thinning, bullous/band keratopathy, corneal abrasion, inflammation/ulceration, or
keratoconjunctivitis (to be confirmed by ophthalmological examination). Pre-existing
cataract is not a reason for exclusion.
3. Brain or subdural metastases are not eligible, unless they have completed local therapy and
have discontinued the use of corticosteroids for this indication for at least 4 weeks before
starting treatment in this study. Any signs (eg, radiologic) or symptoms of brain metastases
must be stable for at least 4 weeks before starting study treatment.
4. Genetic diseases of the liver that may complicate review of safety data.
5. Known human immunodeficiency virus (HIV) infection.
6. Uncontrolled significant active infections, except Hepatitis B (HBV) or Hepatitis C (HCV).
Subjects with HBV are eligible but should be taking an appropriate antiviral medication if
indicated. Subjects with HCV are eligible but must not be taking concomitant treatment for
HCV while receiving H3B-6527.
7. Major surgery or other locoregional treatment within 4 weeks before the first dose of study
drug or radionuclide treatment (eg, 90Yttrium intra-arterial treatment) 8 weeks before study
drug administration.
8. Inability to take oral medication, or presence of a malabsorption syndrome or any other
uncontrolled gastrointestinal condition (eg, nausea, diarrhea, or vomiting) that might impair the bioavailability of H3B-6527. Subjects with prior gastric resection are eligible.
9. Use of any drug that is a strong inhibitor or inducer of the CYP3A4 enzyme within at least 2
weeks before the start of study drug and during the conduct of the study unless there is an
emergent or life-threatening medical condition that requires it.
10. Use of any drug known to prolong QTc interval within at least 2 weeks before the start of the
study drug and during the conduct of the study.
11. Treatment with proton pump inhibitors that cannot be discontinued 3 days prior to the start of
study drug and during the course of the study; antacids are permitted except for calcium
carbonate antacids (eg, Tums® ).
12. Use of other investigational drugs within 28 days or at least 5 half-lives (whichever is shorter)
before study drug administration.
13. Previous treatment with a selective FGF19-FGFR4 targeted therapy.
14. Use of any live vaccines against infectious diseases (eg, influenza, varicella) within 4 weeks
(28 days) of initiation of study therapy.
15. Presence of gastric or esophageal varices requiring active treatment.
16. A clinically significant ECG abnormality, including a marked baseline prolonged QTc interval
(eg, a repeated demonstration of a QTc interval >500 ms).
17. Significant cardiovascular impairment: history of congestive heart failure greater than New
York Heart Association Class II, uncontrolled arterial hypertension, unstable angina,
myocardial infarction, or stroke within 6 months of the first dose of study drug; or cardiac
arrhythmia requiring medical treatment (including oral anticoagulation).
18. Any other major illness, medical condition or concomitant medication that, in the
investigator’s judgment, will substantially increase the risk associated with the subject’s
participation in this study or would compromise the subject’s ability to safely complete the
study.
19. Males who have not had a successful vasectomy (confirmed azoospermia) or they and their
female partners do not meet the criteria above (ie, not of childbearing potential or practicing
highly effective contraception throughout the study period or for 90 days after study drug
discontinuation). No sperm donation is allowed during the study period or for 90 days after
study drug discontinuation.
20. Hypersensitivity to the study drug or to any of the excipients.
21. Intolerance or hypersensitivity to both CT and MRI contrast material that would preclude the
ability to acquire the triphasic liver imaging required by the protocol.
22. An inorganic phosphorus > ULN for the institution. Note: Subjects may be on treatment for
hyperphosphatemia, but the levels must be normal at screening to participate in this study.
Subjects with high levels on screening may subsequently be treated and rescreened and,
should they have stable levels for 2 weeks prior to study, may enter the study.
23. A total or ionized serum calcium > ULN for the institution. Note: Subjects may be on
treatment for hypercalcemia, but the levels must be normal at screening to participate in this
study. Subjects with high levels on screening may subsequently be treated and rescreened
and, should they have stable levels for 2 weeks prior to study, may enter the study.
24. Endocrine changes that may result in increases in calcium or phosphate, including but not
limited to hyperparathyroidism and tumoral calcinosis.
25. Past medical history and/or current evidence of tumoral calcinosis or tissue calcification.
26. Use of calcium or vitamin D supplements or systemic corticosteroids. The duration between the last systemic corticosteroid administration and the first dose of study drug should be at least 2 weeks.
The Estimated Number of Participants
-
Taiwan
28 participants
-
Global
128 participants
