Brief Summary
Niraparib (Zejula®)is extensively metabolized and eliminated primarily by hepatic and renal pathways. The purpose of this study is to evaluate pharmacokinetics and safety of niraparib in patients with moderate hepatic impairment, for the purpose of providing recommendations to guide the initial dose and dose titration in this patient population.
Brief Title
Pharmacokinetic and Safety Study of Niraparib With Normal or Moderate Hepatic Impairment Patients
Categories
Completion Date
Completion Date Type
Actual
Conditions
Ovarian Neoplasms
Neoplasms
Solid Tumor
Hepatic Impairment
Eligibility Criteria
Inclusion Criteria:
Diagnosis and Criteria for Inclusion:
All patients:
To be considered eligible to participate in this study, all of the following requirements must be met:
1. Patient, male or female, is at least 18 years of age.
2. Patient has a diagnosis of advanced solid malignancy that has failed standard therapy or for which standard therapy is not likely to provide meaningful benefit, or patient has refused standard therapy.
3. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
4. Patient is able to take oral medications.
5. Female patient, if of childbearing potential, has a negative serum pregnancy test within 72 hours prior to taking study drug and agrees to abstain from activities that could result in pregnancy from enrollment through 120 days after the last dose of study treatment, or be of non-childbearing potential. Non-childbearing potential is defined as (by other than medical reasons):
* ≥45 years of age and has not had menses for \> 1 year.
* Amenorrheic for \< 2 years without a hysterectomy Post hysterectomy, bilateral oophorectomy, or tubal ligation..
Note: Abstinence is acceptable if this is the established and preferred contraception for the patient.
6. Male patient agrees to use an adequate method of contraception starting with the first dose of study treatment through 120 days after the last dose of study treatment..
7. Patient is able to understand the study procedures and agrees to participate in the study by providing written informed consent.
Patients with normal hepatic function (Group 1):
Patients screened for the normal hepatic function group must meet the following additional criteria to be eligible for enrollment:
1. Patient has no history of hepatic impairment.
2. Patient has liver function test (LFT) results within normal range:
* Total bilirubin ≤ ULN
* Aspartate aminotransferase (AST) ≤ ULN.
* INR ≤1.5 X ULN unless the patient is receiving anticoagulant therapy and the INR is within therapeutic range of intended use of anticoagulants.
3. Patient has adequate hematologic and renal function as defined below:
* Absolute neutrophil count ≥1500/µL
* Platelets ≥100,000/µL
* Hemoglobin ≥9 g/dL
* Serum creatinine ≤1.5 × ULN or a calculated creatinine clearance ≥60 mL/min using the Cockcroft-Gault equation.
Patients with moderate hepatic impairment (Group 2):
Patients screened for the moderate hepatic impairment group must meet the following additional criteria to be eligible for enrollment:
1. Patient has stable, moderate hepatic impairment, defined as:
* BILI: \>1.5 × to 3 × ULN, for at least 2 weeks prior to Day 1
* AST: Any value
* INR less than 1.8 unless the patient is receiving anticoagulant therapy and the INR is within therapeutic range of intended use of anticoagulants.
2. Patient has hematologic and renal function as defined below:
* Absolute neutrophil count ≥1000/µL
* Platelets ≥75,000/µL
* Hemoglobin ≥8 g/dL
* Serum creatinine ≤1.5 × ULN or a calculated creatinine clearance ≥60 mL/min using the Cockcroft-Gault equation.
3. Patient's hepatic disease is deemed stable by the Investigator
Criteria for Exclusion:
Patients will not be eligible for study entry if any of the following criteria are met:
All patients:
1. Patient has undergone palliative radiotherapy within 1 week of study drug administration, encompassing \>20% of the bone marrow.
2. Patient is starting chemotherapy within 3 weeks of study drug administration.
3. Patient has a known hypersensitivity to the components of niraparib or excipients
4. Patients who received colony-stimulating factors within 2 weeks prior to the first dose of study treatment are not eligible.
5. Patient has persistent chemotherapy associated Grade 2 or greater toxicity except for neuropathy, alopecia or fatigue.
6. Patient has symptomatic uncontrolled brain or leptomeningeal metastases.
7. Patient has undergone major surgery within 3 weeks of starting the study or patient has not recovered from any effects of any major surgery.
8. Patient is considered a poor medical risk due to a serious, uncontrolled medical disorder (other than hepatic impairment) or active, uncontrolled infection.
9. Patient has received a transfusion (platelets or red blood cells) within 3 weeks of receiving niraparib.
10. Patient is pregnant, breastfeeding, or expecting to conceive children while receiving study treatment or for 3 months after the last dose of study treatment.
11. Patient has a known history of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML).
NOTE: Exclusion Criteria 12-16 apply patients participating in the PK phase of the study.
12. Patient is currently receiving, or unable to refrain from taking from 4 days prior to dosing until the time of the last PK blood draw, any of the following cytochrome (CYP) 1A2 substrates: alosetron, duloxetine, melatonin, ramelteon, tacrine, tizanidine, and theophylline.
13. Patient is unable to refrain from any intake of grapefruit or grapefruit juice within 4 days of the first administration of niraparib until the final PK sample collection.
14. Patient is currently receiving, or unable to refrain from taking from 4 days prior to dosing until the last PK blood draw, any of the following P-glycoprotein (P-gp) inhibitors: amiodarone, azithromycin, captopril, carvedilol, clarithromycin, conivaptan, cyclosporine, diltiazem, dronedarone, erythromycin, felodipine, itraconazole, ketoconazole, lopinavir and ritonavir, quercetin, quinidine, ranolazine, ticagrelor and verapamil.
15. Patient is taking proton pump inhibitors, antacids, or histamine 2 (H2) blockers within 48 hours prior to niraparib administration, and/or within 6 hours after niraparib administration.
16. Patient has esophagogastrointestinal disease or resection that is likely to interfere with the absorption of niraparib.
Patients with moderate hepatic impairment (Group 2):
Patients screened for the moderate hepatic impairment group who meet any of the following additional criteria will be excluded from the study:
1. Patient has hepatic encephalopathy, severe portal hypertension and/or porto-systemic shunt.
2. Patient has fluctuating or rapidly deteriorating hepatic function as determined by the investigator within the screening period.
3. Patient has acute liver disease caused by drug toxicity or by an infection.
4. Patient has biliary obstruction or other causes of hepatic impairment not related to parenchymal disorder and/or disease of the liver.
5. Patient has esophageal variceal bleeding within the past 2 months.
6. Patient is receiving anticoagulant therapy with warfarin or related coumarins.
7. Patient has a history of hepatic transplant, systemic lupus erythematosus, or hepatic coma.
Diagnosis and Criteria for Inclusion:
All patients:
To be considered eligible to participate in this study, all of the following requirements must be met:
1. Patient, male or female, is at least 18 years of age.
2. Patient has a diagnosis of advanced solid malignancy that has failed standard therapy or for which standard therapy is not likely to provide meaningful benefit, or patient has refused standard therapy.
3. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
4. Patient is able to take oral medications.
5. Female patient, if of childbearing potential, has a negative serum pregnancy test within 72 hours prior to taking study drug and agrees to abstain from activities that could result in pregnancy from enrollment through 120 days after the last dose of study treatment, or be of non-childbearing potential. Non-childbearing potential is defined as (by other than medical reasons):
* ≥45 years of age and has not had menses for \> 1 year.
* Amenorrheic for \< 2 years without a hysterectomy Post hysterectomy, bilateral oophorectomy, or tubal ligation..
Note: Abstinence is acceptable if this is the established and preferred contraception for the patient.
6. Male patient agrees to use an adequate method of contraception starting with the first dose of study treatment through 120 days after the last dose of study treatment..
7. Patient is able to understand the study procedures and agrees to participate in the study by providing written informed consent.
Patients with normal hepatic function (Group 1):
Patients screened for the normal hepatic function group must meet the following additional criteria to be eligible for enrollment:
1. Patient has no history of hepatic impairment.
2. Patient has liver function test (LFT) results within normal range:
* Total bilirubin ≤ ULN
* Aspartate aminotransferase (AST) ≤ ULN.
* INR ≤1.5 X ULN unless the patient is receiving anticoagulant therapy and the INR is within therapeutic range of intended use of anticoagulants.
3. Patient has adequate hematologic and renal function as defined below:
* Absolute neutrophil count ≥1500/µL
* Platelets ≥100,000/µL
* Hemoglobin ≥9 g/dL
* Serum creatinine ≤1.5 × ULN or a calculated creatinine clearance ≥60 mL/min using the Cockcroft-Gault equation.
Patients with moderate hepatic impairment (Group 2):
Patients screened for the moderate hepatic impairment group must meet the following additional criteria to be eligible for enrollment:
1. Patient has stable, moderate hepatic impairment, defined as:
* BILI: \>1.5 × to 3 × ULN, for at least 2 weeks prior to Day 1
* AST: Any value
* INR less than 1.8 unless the patient is receiving anticoagulant therapy and the INR is within therapeutic range of intended use of anticoagulants.
2. Patient has hematologic and renal function as defined below:
* Absolute neutrophil count ≥1000/µL
* Platelets ≥75,000/µL
* Hemoglobin ≥8 g/dL
* Serum creatinine ≤1.5 × ULN or a calculated creatinine clearance ≥60 mL/min using the Cockcroft-Gault equation.
3. Patient's hepatic disease is deemed stable by the Investigator
Criteria for Exclusion:
Patients will not be eligible for study entry if any of the following criteria are met:
All patients:
1. Patient has undergone palliative radiotherapy within 1 week of study drug administration, encompassing \>20% of the bone marrow.
2. Patient is starting chemotherapy within 3 weeks of study drug administration.
3. Patient has a known hypersensitivity to the components of niraparib or excipients
4. Patients who received colony-stimulating factors within 2 weeks prior to the first dose of study treatment are not eligible.
5. Patient has persistent chemotherapy associated Grade 2 or greater toxicity except for neuropathy, alopecia or fatigue.
6. Patient has symptomatic uncontrolled brain or leptomeningeal metastases.
7. Patient has undergone major surgery within 3 weeks of starting the study or patient has not recovered from any effects of any major surgery.
8. Patient is considered a poor medical risk due to a serious, uncontrolled medical disorder (other than hepatic impairment) or active, uncontrolled infection.
9. Patient has received a transfusion (platelets or red blood cells) within 3 weeks of receiving niraparib.
10. Patient is pregnant, breastfeeding, or expecting to conceive children while receiving study treatment or for 3 months after the last dose of study treatment.
11. Patient has a known history of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML).
NOTE: Exclusion Criteria 12-16 apply patients participating in the PK phase of the study.
12. Patient is currently receiving, or unable to refrain from taking from 4 days prior to dosing until the time of the last PK blood draw, any of the following cytochrome (CYP) 1A2 substrates: alosetron, duloxetine, melatonin, ramelteon, tacrine, tizanidine, and theophylline.
13. Patient is unable to refrain from any intake of grapefruit or grapefruit juice within 4 days of the first administration of niraparib until the final PK sample collection.
14. Patient is currently receiving, or unable to refrain from taking from 4 days prior to dosing until the last PK blood draw, any of the following P-glycoprotein (P-gp) inhibitors: amiodarone, azithromycin, captopril, carvedilol, clarithromycin, conivaptan, cyclosporine, diltiazem, dronedarone, erythromycin, felodipine, itraconazole, ketoconazole, lopinavir and ritonavir, quercetin, quinidine, ranolazine, ticagrelor and verapamil.
15. Patient is taking proton pump inhibitors, antacids, or histamine 2 (H2) blockers within 48 hours prior to niraparib administration, and/or within 6 hours after niraparib administration.
16. Patient has esophagogastrointestinal disease or resection that is likely to interfere with the absorption of niraparib.
Patients with moderate hepatic impairment (Group 2):
Patients screened for the moderate hepatic impairment group who meet any of the following additional criteria will be excluded from the study:
1. Patient has hepatic encephalopathy, severe portal hypertension and/or porto-systemic shunt.
2. Patient has fluctuating or rapidly deteriorating hepatic function as determined by the investigator within the screening period.
3. Patient has acute liver disease caused by drug toxicity or by an infection.
4. Patient has biliary obstruction or other causes of hepatic impairment not related to parenchymal disorder and/or disease of the liver.
5. Patient has esophageal variceal bleeding within the past 2 months.
6. Patient is receiving anticoagulant therapy with warfarin or related coumarins.
7. Patient has a history of hepatic transplant, systemic lupus erythematosus, or hepatic coma.
Inclusion Criteria
Inclusion Criteria:
Diagnosis and Criteria for Inclusion:
All patients:
To be considered eligible to participate in this study, all of the following requirements must be met:
1. Patient, male or female, is at least 18 years of age.
2. Patient has a diagnosis of advanced solid malignancy that has failed standard therapy or for which standard therapy is not likely to provide meaningful benefit, or patient has refused standard therapy.
3. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
4. Patient is able to take oral medications.
5. Female patient, if of childbearing potential, has a negative serum pregnancy test within 72 hours prior to taking study drug and agrees to abstain from activities that could result in pregnancy from enrollment through 120 days after the last dose of study treatment, or be of non-childbearing potential. Non-childbearing potential is defined as (by other than medical reasons):
* ≥45 years of age and has not had menses for \> 1 year.
* Amenorrheic for \< 2 years without a hysterectomy Post hysterectomy, bilateral oophorectomy, or tubal ligation..
Note: Abstinence is acceptable if this is the established and preferred contraception for the patient.
6. Male patient agrees to use an adequate method of contraception starting with the first dose of study treatment through 120 days after the last dose of study treatment..
7. Patient is able to understand the study procedures and agrees to participate in the study by providing written informed consent.
Patients with normal hepatic function (Group 1):
Patients screened for the normal hepatic function group must meet the following additional criteria to be eligible for enrollment:
1. Patient has no history of hepatic impairment.
2. Patient has liver function test (LFT) results within normal range:
* Total bilirubin ≤ ULN
* Aspartate aminotransferase (AST) ≤ ULN.
* INR ≤1.5 X ULN unless the patient is receiving anticoagulant therapy and the INR is within therapeutic range of intended use of anticoagulants.
3. Patient has adequate hematologic and renal function as defined below:
* Absolute neutrophil count ≥1500/µL
* Platelets ≥100,000/µL
* Hemoglobin ≥9 g/dL
* Serum creatinine ≤1.5 × ULN or a calculated creatinine clearance ≥60 mL/min using the Cockcroft-Gault equation.
Patients with moderate hepatic impairment (Group 2):
Patients screened for the moderate hepatic impairment group must meet the following additional criteria to be eligible for enrollment:
1. Patient has stable, moderate hepatic impairment, defined as:
* BILI: \>1.5 × to 3 × ULN, for at least 2 weeks prior to Day 1
* AST: Any value
* INR less than 1.8 unless the patient is receiving anticoagulant therapy and the INR is within therapeutic range of intended use of anticoagulants.
2. Patient has hematologic and renal function as defined below:
* Absolute neutrophil count ≥1000/µL
* Platelets ≥75,000/µL
* Hemoglobin ≥8 g/dL
* Serum creatinine ≤1.5 × ULN or a calculated creatinine clearance ≥60 mL/min using the Cockcroft-Gault equation.
3. Patient's hepatic disease is deemed stable by the Investigator
Criteria for Exclusion:
Patients will not be eligible for study entry if any of the following criteria are met:
All patients:
1. Patient has undergone palliative radiotherapy within 1 week of study drug administration, encompassing \>20% of the bone marrow.
2. Patient is starting chemotherapy within 3 weeks of study drug administration.
3. Patient has a known hypersensitivity to the components of niraparib or excipients
4. Patients who received colony-stimulating factors within 2 weeks prior to the first dose of study treatment are not eligible.
5. Patient has persistent chemotherapy associated Grade 2 or greater toxicity except for neuropathy, alopecia or fatigue.
6. Patient has symptomatic uncontrolled brain or leptomeningeal metastases.
7. Patient has undergone major surgery within 3 weeks of starting the study or patient has not recovered from any effects of any major surgery.
8. Patient is considered a poor medical risk due to a serious, uncontrolled medical disorder (other than hepatic impairment) or active, uncontrolled infection.
9. Patient has received a transfusion (platelets or red blood cells) within 3 weeks of receiving niraparib.
10. Patient is pregnant, breastfeeding, or expecting to conceive children while receiving study treatment or for 3 months after the last dose of study treatment.
11. Patient has a known history of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML).
NOTE:
Diagnosis and Criteria for Inclusion:
All patients:
To be considered eligible to participate in this study, all of the following requirements must be met:
1. Patient, male or female, is at least 18 years of age.
2. Patient has a diagnosis of advanced solid malignancy that has failed standard therapy or for which standard therapy is not likely to provide meaningful benefit, or patient has refused standard therapy.
3. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
4. Patient is able to take oral medications.
5. Female patient, if of childbearing potential, has a negative serum pregnancy test within 72 hours prior to taking study drug and agrees to abstain from activities that could result in pregnancy from enrollment through 120 days after the last dose of study treatment, or be of non-childbearing potential. Non-childbearing potential is defined as (by other than medical reasons):
* ≥45 years of age and has not had menses for \> 1 year.
* Amenorrheic for \< 2 years without a hysterectomy Post hysterectomy, bilateral oophorectomy, or tubal ligation..
Note: Abstinence is acceptable if this is the established and preferred contraception for the patient.
6. Male patient agrees to use an adequate method of contraception starting with the first dose of study treatment through 120 days after the last dose of study treatment..
7. Patient is able to understand the study procedures and agrees to participate in the study by providing written informed consent.
Patients with normal hepatic function (Group 1):
Patients screened for the normal hepatic function group must meet the following additional criteria to be eligible for enrollment:
1. Patient has no history of hepatic impairment.
2. Patient has liver function test (LFT) results within normal range:
* Total bilirubin ≤ ULN
* Aspartate aminotransferase (AST) ≤ ULN.
* INR ≤1.5 X ULN unless the patient is receiving anticoagulant therapy and the INR is within therapeutic range of intended use of anticoagulants.
3. Patient has adequate hematologic and renal function as defined below:
* Absolute neutrophil count ≥1500/µL
* Platelets ≥100,000/µL
* Hemoglobin ≥9 g/dL
* Serum creatinine ≤1.5 × ULN or a calculated creatinine clearance ≥60 mL/min using the Cockcroft-Gault equation.
Patients with moderate hepatic impairment (Group 2):
Patients screened for the moderate hepatic impairment group must meet the following additional criteria to be eligible for enrollment:
1. Patient has stable, moderate hepatic impairment, defined as:
* BILI: \>1.5 × to 3 × ULN, for at least 2 weeks prior to Day 1
* AST: Any value
* INR less than 1.8 unless the patient is receiving anticoagulant therapy and the INR is within therapeutic range of intended use of anticoagulants.
2. Patient has hematologic and renal function as defined below:
* Absolute neutrophil count ≥1000/µL
* Platelets ≥75,000/µL
* Hemoglobin ≥8 g/dL
* Serum creatinine ≤1.5 × ULN or a calculated creatinine clearance ≥60 mL/min using the Cockcroft-Gault equation.
3. Patient's hepatic disease is deemed stable by the Investigator
Criteria for Exclusion:
Patients will not be eligible for study entry if any of the following criteria are met:
All patients:
1. Patient has undergone palliative radiotherapy within 1 week of study drug administration, encompassing \>20% of the bone marrow.
2. Patient is starting chemotherapy within 3 weeks of study drug administration.
3. Patient has a known hypersensitivity to the components of niraparib or excipients
4. Patients who received colony-stimulating factors within 2 weeks prior to the first dose of study treatment are not eligible.
5. Patient has persistent chemotherapy associated Grade 2 or greater toxicity except for neuropathy, alopecia or fatigue.
6. Patient has symptomatic uncontrolled brain or leptomeningeal metastases.
7. Patient has undergone major surgery within 3 weeks of starting the study or patient has not recovered from any effects of any major surgery.
8. Patient is considered a poor medical risk due to a serious, uncontrolled medical disorder (other than hepatic impairment) or active, uncontrolled infection.
9. Patient has received a transfusion (platelets or red blood cells) within 3 weeks of receiving niraparib.
10. Patient is pregnant, breastfeeding, or expecting to conceive children while receiving study treatment or for 3 months after the last dose of study treatment.
11. Patient has a known history of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML).
NOTE:
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT03359850
Org Class
Industry
Org Full Name
Tesaro, Inc.
Org Study Id
213354
Overall Status
Completed
Phases
Phase 1
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
An Open-Label, Non-Randomized, Multicenter Study to Determine the Pharmacokinetics and Safety of Niraparib Following a Single Oral Dose in Patients With Advanced Solid Tumors and Either Normal Hepatic Function or Moderate Hepatic Impairment
Primary Outcomes
Outcome Description
Blood samples were collected at indicated time points to evaluate AUC (last) of niraparib and M1. PK parameters were calculated by standard non-compartmental analysis.
Outcome Measure
Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of Niraparib and Its Major Metabolite (M1) During PK Phase
Outcome Time Frame
Pre-dose, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 120, 168 hours post dose Day 1
Outcome Description
Blood samples were collected at indicated time points to evaluate AUC (0-infinity) of niraparib and M1. PK parameters were calculated by standard non-compartmental analysis.
Outcome Measure
Area Under the Plasma Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC 0-infinity) of Niraparib and M1 During PK Phase
Outcome Time Frame
Pre-dose, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 120, 168 hours post dose Day 1
Outcome Description
Blood samples were collected at indicated time points to evaluate Cmax of niraparib and M1. PK parameters were calculated by standard non-compartmental analysis.
Outcome Measure
Observed Maximum Plasma Concentration (Cmax) of Niraparib and M1 During PK Phase
Outcome Time Frame
Pre-dose, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 120, 168 hours post dose Day 1
Outcome Description
Blood samples were collected at indicated time points to evaluate tmax of niraparib and M1. PK parameters were calculated by standard non-compartmental analysis.
Outcome Measure
Time to Maximum Concentration (Tmax) of Niraparib and M1 During PK Phase
Outcome Time Frame
Pre-dose, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 120, 168 hours post dose Day 1
Outcome Description
Blood samples were collected at indicated time points to evaluate t1/2 of niraparib and M1. PK parameters were calculated by standard non-compartmental analysis.
Outcome Measure
Terminal Half-life (t½) of Niraparib and M1 During PK Phase
Outcome Time Frame
Pre-dose, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 120, 168 hours post dose Day 1
Outcome Description
CL/F is calculated as Dose/(AUC 0-inf). Blood samples were collected at indicated time points to evaluate CL/F of niraparib and M1. PK parameters were calculated by standard non-compartmental analysis. Not applicable (NA) indicates that CL/F could not be measured for M1 since the dose of metabolite is unknown and only known dose is that of parent niraparib.
Outcome Measure
Apparent Total Body Clearance (CL/F) of Niraparib and M1 During PK Phase
Outcome Time Frame
Pre-dose, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 120, 168 hours post dose Day 1
Secondary Ids
Secondary Id
3000-01-003
Secondary Outcomes
Outcome Description
An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product, and which does not necessarily have to have a causal relationship with this treatment. SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; is a congenital anomaly/birth defect; or is an important medical event(s) requiring medical or scientific judgment. Treatment-emergent are any event that was not present prior to the initiation of study treatment or any event already present that worsens in either intensity or frequency following exposure to study treatment.
Outcome Time Frame
Up to Day 8
Outcome Measure
Number of Participants With Treatment-Emergent Adverse Events (TEAE) Including Non-serious Adverse Events (Non-SAEs), Serious Adverse Events (SAEs) and Discontinuations Due to AEs During PK Phase
Outcome Description
Blood samples were collected from participants for evaluation of Hb. Baseline is defined as the most recent measurement prior to the first administration of study drug in PK phase. Change from Baseline was calculated as post dose value minus Baseline value.
Outcome Time Frame
Baseline and at Day 8
Outcome Measure
Change From Baseline in Hemoglobin (Hb) During PK Phase
Outcome Description
Blood samples were collected to analyze hematology parameters:Leukocyte, Lymphocytes, Monocytes, Neutrophils and Platelets. Baseline is defined as the most recent measurement prior to the first administration of study drug in PK phase. Change from Baseline was calculated as post dose value minus Baseline value.
Outcome Time Frame
Baseline and Day 8
Outcome Measure
Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes and Leukocyte During PK Phase
Outcome Description
Blood samples were collected to analyze clinical chemistry parameters: protein and albumin. Baseline is defined as the most recent measurement prior to the first administration of study drug in PK phase. Change from Baseline was calculated as post dose value minus Baseline value.
Outcome Time Frame
Baseline and Day 8
Outcome Measure
Change From Baseline in Clinical Chemistry Parameter of Protein and Albumin During PK Phase
Outcome Description
Blood samples were collected at indicated time-points for analysis of clinical chemistry parameters: alkaline phosphatase, ALT, AST and LDH. Baseline is defined as the most recent measurement prior to the first administration of study drug in PK phase. Change from Baseline was calculated as post dose value minus Baseline value.
Outcome Time Frame
Baseline and Day 8
Outcome Measure
Change From Baseline in Clinical Chemistry Parameter of Alkaline Phosphatase, Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Lactate Dehydrogenase (LDH) During PK Phase
Outcome Description
Blood samples were collected at indicated time-points for analysis of clinical chemistry parameter: Amylase. Baseline is defined as the most recent measurement prior to the first administration of study drug in PK phase. Change from Baseline was calculated as post dose value minus Baseline value.
Outcome Time Frame
Baseline and Day 8
Outcome Measure
Change From Baseline in Clinical Chemistry Parameter of Amylase During PK Phase
Outcome Description
Blood samples were collected at indicated time-points for analysis of clinical chemistry parameters: Bilirubin and Creatinine. Baseline is defined as the most recent measurement prior to the first administration of study drug in PK phase. Change from Baseline was calculated as post dose value minus Baseline value.
Outcome Time Frame
Baseline and Day 8
Outcome Measure
Change From Baseline in Clinical Chemistry Parameter of Bilirubin and Creatinine During PK Phase
Outcome Description
Blood samples were collected at indicated time-points for analysis of clinical chemistry parameter:Glucose, Calcium, Chloride, Phosphate, Potassium, Sodium, Magnesium and BUN. Baseline is defined as the most recent measurement prior to the first administration of study drug in PK phase. Change from Baseline was calculated as post dose value minus Baseline value.
Outcome Time Frame
Baseline and Day 8
Outcome Measure
Change From Baseline in Chemistry Parameters: Glucose, Calcium, Chloride, Phosphate, Potassium, Sodium, Magnesium and Blood Urea Nitrogen (BUN) During PK Phase
Outcome Description
Weight was measured at indicated time-points. Baseline is defined as the most recent measurement prior to the first administration of study drug in PK phase. Change from Baseline was calculated as post dose value minus Baseline value.
Outcome Time Frame
Baseline, Day 2 and Day 8
Outcome Measure
Change From Baseline in Weight During PK Phase
Outcome Description
Vital signs including SBP and DBP were measured at indicated time-points. Baseline is defined as the most recent measurement prior to the first administration of study drug in PK phase. Change from Baseline was calculated as post dose value minus Baseline value.
Outcome Time Frame
Baseline, Day 2 and Day 8
Outcome Measure
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) During PK Phase
Outcome Description
Vital sign including pulse rate was measured at indicated time-points. Baseline is defined as the most recent measurement prior to the first administration of study drug in PK phase. Change from Baseline was calculated as post dose value minus Baseline value.
Outcome Time Frame
Baseline, Day 2 and Day 8
Outcome Measure
Change From Baseline in Pulse Rate During PK Phase
Outcome Description
Vital sign including body temperature was measured at indicated time-points. Baseline is defined as the most recent measurement prior to the first administration of study drug in PK phase. Change from Baseline was calculated as post dose value minus Baseline value.
Outcome Time Frame
Baseline, Day 2 and Day 8
Outcome Measure
Change From Baseline in Body Temperature During PK Phase
Outcome Description
An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product, and which does not necessarily have to have a causal relationship with this treatment. SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; is a congenital anomaly/birth defect; or is an important medical event(s) requiring medical or scientific judgment. Treatment-emergent are any event that was not present prior to the initiation of study treatment or any event already present that worsens in either intensity or frequency following exposure to study treatment.
Outcome Time Frame
Up to 28 months
Outcome Measure
Number of Participants With TEAE Including Non-SAEs, SAEs and Discontinuations Due to AEs During Extension Phase
Outcome Description
Blood samples were collected from participants for evaluation of Hb. Baseline is defined as the most recent measurement prior to the first administration of study drug in extension phase. Change from Baseline was calculated as post dose value minus Baseline value. NA indicates standard deviation could not be calculated as a single participant was analyzed.
Outcome Time Frame
Baseline and Cycle 1 (Days 8, 15, 21), Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1, and Cycle 6 Day 1 (each cycle was of 28 days)
Outcome Measure
Change From Baseline in Hb During Extension Phase
Outcome Description
Blood samples were collected to analyze hematology parameters: Lymphocytes, Leukocytes, Monocytes, Neutrophils and Platelets. Baseline is defined as the most recent measurement prior to the first administration of study drug in extension phase. Change from Baseline was calculated as post dose value minus Baseline value. NA indicates standard deviation could not be calculated as a single participant was analyzed.
Outcome Time Frame
Baseline and Cycle 1 (Days 8, 15, 21), Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1, and Cycle 6 Day 1 (each cycle was of 28 days)
Outcome Measure
Change From Baseline in Platelets, Neutrophils, Monocytes, Lymphocytes and Leukocytes During Extension Phase
Outcome Description
Blood samples were collected to analyze clinical chemistry parameters: protein and albumin. Baseline is defined as the most recent measurement prior to the first administration of study drug in extension phase. Change from Baseline was calculated as post dose value minus Baseline value. NA indicates standard deviation could not be calculated as a single participant was analyzed.
Outcome Time Frame
Baseline and Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1 and Cycle 6 Day 1 (each cycle was of 28 days)
Outcome Measure
Change From Baseline in Clinical Chemistry Parameter of Protein and Albumin During Extension Phase
Outcome Description
Blood samples were collected at indicated time-points for analysis of clinical chemistry parameters: alkaline phosphatase, ALT, AST and LDH. Baseline is defined as the most recent measurement prior to the first administration of study drug in extension phase. Change from Baseline was calculated as post dose value minus Baseline value. NA indicates standard deviation could not be calculated as a single participant was analyzed.
Outcome Time Frame
Baseline and Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1 and Cycle 6 Day 1 (each cycle was of 28 days)
Outcome Measure
Change From Baseline in Clinical Chemistry Parameter of Alkaline Phosphatase, ALT, AST and LDH During Extension Phase
Outcome Description
Blood samples were collected at indicated time-points for analysis of clinical chemistry parameter: Amylase. Baseline is defined as the most recent measurement prior to the first administration of study drug in extension phase. Change from Baseline was calculated as post dose value minus Baseline value. NA indicates standard deviation could not be calculated as a single participant was analyzed.
Outcome Time Frame
Baseline and Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1 and Cycle 6 Day 1 (each cycle was of 28 days)
Outcome Measure
Change From Baseline in Clinical Chemistry Parameter of Amylase During Extension Phase
Outcome Description
Blood samples were collected at indicated time-points for analysis of clinical chemistry parameter: Bilirubin and Creatinine. Baseline is defined as the most recent measurement prior to the first administration of study drug in extension phase. Change from Baseline was calculated as post dose value minus Baseline value. NA indicates standard deviation could not be calculated as a single participant was analyzed.
Outcome Time Frame
Baseline and Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1 and Cycle 6 Day 1 (each cycle was of 28 days)
Outcome Measure
Change From Baseline in Clinical Chemistry Parameter of Bilirubin and Creatinine During Extension Phase
Outcome Description
Blood samples were collected at indicated time-points for analysis of clinical chemistry parameter:Glucose, Calcium, Chloride, Phosphate, Potassium, Sodium, Magnesium and BUN. Baseline is defined as the most recent measurement prior to the first administration of study drug in extension phase. Change from Baseline was calculated as post dose value minus Baseline value. NA indicates standard deviation could not be calculated as a single participant was analyzed.
Outcome Time Frame
Baseline and Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1 and Cycle 6 Day 1 (each cycle was of 28 days)
Outcome Measure
Change From Baseline in Chemistry Parameters: Glucose, Calcium, Chloride, Phosphate, Potassium, Sodium, Magnesium and BUN During Extension Phase
Outcome Description
Weight was measured at indicated time-points. Baseline is defined as the most recent measurement prior to the first administration of study drug in extension phase. Change from Baseline was calculated as post dose value minus Baseline value. NA indicates standard deviation could not be calculated as a single participant was analyzed.
Outcome Time Frame
Baseline and Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1 and Cycle 6 Day 1 (each cycle was of 28 days)
Outcome Measure
Change From Baseline in Weight During Extension Phase
Outcome Description
Vital signs including SBP and DBP were measured at indicated time-points. Baseline is defined as the most recent measurement prior to the first administration of study drug in extension phase. Change from Baseline was calculated as post dose value minus Baseline value. NA indicates standard deviation could not be calculated as a single participant was analyzed.
Outcome Time Frame
Baseline and Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1 and Cycle 6 Day 1 (each cycle was of 28 days)
Outcome Measure
Change From Baseline in SBP and DBP During Extension Phase
Outcome Description
Vital sign including pulse rate was measured at indicated time-points. Baseline is defined as the most recent measurement prior to the first administration of study drug in extension phase. Change from Baseline was calculated as post dose value minus Baseline value. NA indicates standard deviation could not be calculated as a single participant was analyzed.
Outcome Time Frame
Baseline and Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1 and Cycle 6 Day 1 (each cycle was of 28 days)
Outcome Measure
Change From Baseline in Pulse Rate During Extension Phase
Outcome Description
Vital sign including temperature was measured at indicated time-points. Baseline is defined as the most recent measurement prior to the first administration of study drug in extension phase. Change from Baseline was calculated as post dose value minus Baseline value. NA indicates standard deviation could not be calculated as a single participant was analyzed.
Outcome Time Frame
Baseline and Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1 and Cycle 6 Day 1 (each cycle was of 28 days)
Outcome Measure
Change From Baseline in Temperature During Extension Phase
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Sanjay Goel
Investigator Email
sgoel@montefiore.org
Investigator Phone
718-405-8404