An Adaptive, Open-Label Study to Evaluate the Biodistribution of 89Zirconium-labelled GSK2398852 in the Heart and Other Organs of Patients With Transthyretin Cardiomyopathy (ATTR-CM) Using Positron Emission Tomography (PET) Imaging
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 2
- 试验地点
- 1
- 主要终点
- Part A- Session 1: Peak Standardized Uptake Values (SUV) in Focal Anatomical Regions of the Heart Following 80-200 mg Dose of Anti-SAP mAb
研究概览
简要总结
The principal aim of this study is to investigate the cardiac uptake of 89Zr-GSK2398852 in subjects with transthyretin cardiomyopathy amyloidosis (ATTR-CM), and its biodistribution to other organs. Low doses of GSK2398852 will be co-administered at levels not high enough for therapeutic benefit. This study will be conducted in two parts: Part A and Part B. Subjects in Part A will participate in up to two dosing sessions and subjects in Part B will participate in one dosing session. Subjects will undergo up to 3 PET scans at varying intervals after 89Zr-GSK2398852 administration. The total duration of study will be approximately 3 to 4 months for subjects in Part A and approximately 2 months for subjects in Part B. Part B of the study will be triggered based on data obtained in Part A and other emerging data.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 65 Years 至 80 Years（Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subject must be 65 to 80 years of age inclusive, at the time of signing the informed consent.
- •Subjects with a diagnosis of ATTR-CM: a) Wild-type ATTR status must be confirmed by genotyping and have one of the following: i) Definite histochemical identification of amyloid by Congo red staining and green birefringence in crossed polarized light in cardiac or other tissue biopsy and identification of Transthyretin amyloidosis (TTR) as the amyloid fibril protein either by immunohistochemistry or proteomic analysis OR ii) Scintigraphy Technetium-99m-labeled 3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) with confirmed myocardial uptake. b) Hereditary ATTR amyloidosis (example, TTR Val30Met) should have a known amyloidogenic TTR mutation demonstrated by genotyping and is recognized to be primarily associated with cardiomyopathy and one of the following: i) Definite histochemical identification of amyloid by Congo red staining and green birefringence in crossed polarized light in cardiac or other tissue biopsy and identification of TTR as the amyloid fibril protein either by immunohistochemistry or proteomic analysis. ii) Scintigraphy: 99mTc-DPD with confirmed myocardial uptake.
- •Both male and female subjects are eligible to participate. a) Male subjects: A male subject must agree to use contraception during the treatment period and for at least 3 months after the last scan and refrain from donating sperm during this period. b) Female subjects: A female subject is eligible to participate if she is not of childbearing potential.
- •Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and protocol.
- •New York Heart Association (NYHA) up to class 3; subjects should be clinically stable for at least 3 months preceding to Screening.
排除标准
- •Cardiomyopathy primarily caused by non-amyloid diseases (example, ischemic heart disease; valvular heart disease).
- •Interval from the Q wave on the ECG to point T using Fredericia's formula (QTcF) >500 milliseconds (msec).
- •Sustained (at a rate of >=120 beats per minute for >=30 seconds), or symptomatic monomorphic ventricular tachycardia (VT), or rapid polymorphic VT, at Screening/Baseline cardiac monitoring.
- •Systolic blood pressure <=100 millimeters of mercury (mm/Hg) based on triplicate readings at Screening.
- •Unstable heart failure defined as emergency hospitalization for worsening, or decompensated heart failure, or syncopal episode within 1 month of screening.
- •Implantable cardiac defibrillator (ICD) or permanent pacemaker (PPM) at Screening.
- •Estimated Glomerular filtration rate (eGFR) at Screening <50 milliliters per minute (mL/min) calculated using modification of diet in renal disease (MDRD).
- •Any active and persistent dermatological condition, which in the opinion of the Investigator and Medical Monitor would preclude safe participation.
- •History of allogeneic stem cell transplantation, prior solid organ transplant, or anticipated to undergo solid organ transplantation, or left ventricular assist device (LVAD) implantation.
- •Malignancy within last 5 years, except for basal or squamous cell carcinoma of the skin, or carcinoma in situ of the cervix that has been successfully treated.
- •Acute coronary syndrome, or any form of coronary revascularization procedure (including coronary artery bypass grafting [CABG]), within 6 months of screening.
- •Symptomatic, clinically significant autonomic neuropathy which the Principal Investigator (PI) feels will preclude administration of study treatment.
- •Uncontrolled hypertension during Screening.
- •ALT >3 times upper limit of normal (ULN) OR bilirubin >1.5 times ULN (isolated bilirubin >1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
- •Peripheral edema at Screening that in the opinion of the PI or designee might prevent adequate absorption of subcutaneously administered CPHPC.
- •Presence of any co-morbid (example, steroid refractory rheumatoid arthritis), or an uncontrolled medical condition (example, diabetes mellitus), which in the opinion of the investigator would increase the potential risk to the subject. Investigator should liaise with the Medical Monitor where there is uncertainty as to the eligibility of a subject.
- •Positive test for hepatitis B, hepatitis C and/or human immunodeficiency virus (HIV) during Screening, or within 3 months prior to first dose of study treatment.
- •Clinically significant multiple or severe drug allergies, intolerance to topical corticosteroids, or severe post-treatment hypersensitivity reactions (including, but not limited to, erythema multiforme major, linear immunoglobulin A [IgA] dermatosis, toxic epidermal necrolysis and exfoliative dermatitis).
- •Inability to comprehend and/or understand the study patient information sheet, and/or unwillingness or inability to follow the procedures outlined in the protocol.
- •Has any of the following: a) Fulfillment of diagnostic criteria for Amyloid Light-chain (AL) amyloidosis. b) Fulfillment of diagnostic criteria for amyloid A (AA) or non-TTR hereditary amyloidosis.
- •ATTR Disease Load: c) Histologically proven or clinically suspected gastrointestinal TTR amyloidosis; d) Diffuse skeletal muscle uptake of 99m(Tc)-DPD on Single-photon emission computed tomography (SPECT) imaging (where available); e) Peripheral neuropathy causing more than mild morbidity (example, walking disability; neuropathic pain affecting activities of daily living); f) Proven or clinically suspected intracranial TTR involvement including ophthalmological disease.
- •Non-amyloidosis related chronic liver disease (with the exception of Gilbert's syndrome or clinically asymptomatic gallstones).
- •Participation in a separate clinical trial involving CPHPC within 3 months of Screening.
- •Any prohibited concomitant medication within referenced timeframe.
- •Treatment with another investigational drug, biological agent, or device within 6 months of screening, or 5 half-lives of the study agent, whichever is longer.
- •Orthopnea of sufficient severity to preclude supine scanning as determined at Screening.
- •Inability to fit inside scanner due to body size (girth).
- •History of claustrophobia.
- •Contraindication to magnetic resonance imaging (MRI) contrast agents.
- •Contraindication for MRI scanning (as assessed by local MRI safety questionnaire), which includes but is not limited to: a) Intracranial aneurysm clips (except Sugita) or other metallic objects; b) Intra-orbital metal fragments that have not been removed; c) Pacemakers or other implanted cardiac rhythm management/monitoring devices and non-magnetic resonance (MR) conditional heart valves; d) Inner ear implants.
- •Donation of blood or blood products in excess of 500 milliliters (mL) within 84 days of Screening.
- •Poor or unsuitable venous access.
研究组 & 干预措施
Subjects with ATTR-CM in Part A
Approximately 3 subjects with either wild type or inherited ATTR-CM will be included. Subjects in Part A will participate in two anti-SAP dosing sessions approximately 26 days in duration. The first two subjects in Part A will have up to three 89Zr PET scans, while the remaining subject will undergo up to two 89Zr PET scans.
干预措施: GSK2315698 (CPHPC) (Drug)
Subjects with ATTR-CM in Part A
Approximately 3 subjects with either wild type or inherited ATTR-CM will be included. Subjects in Part A will participate in two anti-SAP dosing sessions approximately 26 days in duration. The first two subjects in Part A will have up to three 89Zr PET scans, while the remaining subject will undergo up to two 89Zr PET scans.
干预措施: GSK2398852 (unlabeled anti-SAP mAb) (Drug)
Subjects with ATTR-CM in Part A
Approximately 3 subjects with either wild type or inherited ATTR-CM will be included. Subjects in Part A will participate in two anti-SAP dosing sessions approximately 26 days in duration. The first two subjects in Part A will have up to three 89Zr PET scans, while the remaining subject will undergo up to two 89Zr PET scans.
干预措施: 89Zr-GSK2398852 (89Zr-labeled anti-SAP mAb) (Drug)
Subjects with ATTR-CM in Part B
Approximately 3 subjects with either wild type or inherited ATTR-CM will be included. Subjects in Part B will participate in one anti-SAP dosing session. Subjects will undergo up to two 89Zr PET scans.
干预措施: GSK2315698 (CPHPC) (Drug)
Subjects with ATTR-CM in Part B
Approximately 3 subjects with either wild type or inherited ATTR-CM will be included. Subjects in Part B will participate in one anti-SAP dosing session. Subjects will undergo up to two 89Zr PET scans.
干预措施: GSK2398852 (unlabeled anti-SAP mAb) (Drug)
Subjects with ATTR-CM in Part B
Approximately 3 subjects with either wild type or inherited ATTR-CM will be included. Subjects in Part B will participate in one anti-SAP dosing session. Subjects will undergo up to two 89Zr PET scans.
干预措施: 89Zr-GSK2398852 (89Zr-labeled anti-SAP mAb) (Drug)
结局指标
主要结局
Part A- Session 1: Peak Standardized Uptake Values (SUV) in Focal Anatomical Regions of the Heart Following 80-200 mg Dose of Anti-SAP mAb
时间窗: Session 1: Days 4, 5, 6 and 8
SUV was measured radioactivity concentration corrected for radioactive decay and normalized for administered amount of radioactivity per body weight. SUV was analyzed for each region of interest such as blood pool left atrium, blood pool left ventricle, blood pool right ventricle, left ventricle wall - high uptake, left ventricle wall - low uptake, mid septum - high uptake and mid septum - low uptake. Peak SUV values derived from PET images has been presented. All treated population consisted of all participants who received at least one Anti-SAP treatment including 89Zr-GSK2398852.
Part A- Session 2: Peak SUV in Focal Anatomical Regions of the Heart Following Anti-SAP mAb Dose Between 200 mg and <=500 mg
时间窗: Session 2: Days 3, 4 and 5
SUV was measured radioactivity concentration corrected for radioactive decay and normalized for administered amount of radioactivity per body weight. SUV was analyzed for each region of interest such as blood pool left atrium, blood pool left ventricle, blood pool right ventricle, left ventricle wall - high uptake, left ventricle wall - low uptake, mid septum - high uptake and mid septum - low uptake. Peak SUV values derived from PET images has been presented.
Part B: Peak SUV in Focal Anatomical Regions of the Heart Following 80-200 mg Dose of Anti-SAP mAb
时间窗: Days 3, 4 and 6
SUV in focal anatomical regions of the heart was planned to be measured.
Part B: Peak SUV in Focal Anatomical Regions of the Heart Following Anti-SAP mAb Dose Between 200 mg and <=500 mg
时间窗: Days 3, 4 and 6
SUV in focal anatomical regions of the heart was planned to be measured.
Part A- Session 1: Mean SUV of Whole Heart Following 80-200 mg Dose of Anti-SAP mAb
时间窗: Session 1: Days 4, 5, 6 and 8
SUV was measured radioactivity concentration corrected for radioactive decay and normalized for administered amount of radioactivity per body weight.
Part A- Session 2: Mean SUV of Whole Heart Following Anti-SAP mAb Dose Between 200 mg and <=500 mg
时间窗: Session 2: Days 3, 4 and 5
SUV was measured radioactivity concentration corrected for radioactive decay and normalized for administered amount of radioactivity per body weight.
Part B: Mean SUV of Whole Heart Following 80-200 mg Dose of Anti-SAP mAb
时间窗: Days 3, 4 and 6
SUV of whole heart was planned to be measured.
Part B: Mean SUV of Whole Heart Following Anti-SAP mAb Dose Between 200 mg and <=500 mg
时间窗: Days 3, 4 and 6
SUV of whole heart was planned to be measured.
次要结局
- Part A- Session 1: Mean SUV of Focal Radioactivity Uptake After 80-200 mg Dose of Anti-SAP mAb(Session 1: Days 4, 5, 6 and 8)
- Part A- Session 1: Mean SUV of Focal Radioactivity Uptake After 80-200 mg Dose of Anti-SAP mAb: Thyriod Gland-goitre Hotspot(Session 1: Days 4 and 6)
- Part A- Session 2: Mean SUV of Focal Radioactivity Uptake After Anti-SAP mAb Dose Between 200 mg and <=500 mg(Session 2: Days 3, 4 and 5)
- Part B: Mean SUV of Focal Radioactivity Uptake After 80-200 mg Dose of Anti-SAP mAb(Days 3, 4 and 6)
- Part B: Mean SUV of Focal Radioactivity Uptake After Anti-SAP mAb Dose Between 200 mg and <=500 mg(Days 3, 4 and 6)
- Part A- Session 1: Mean SUV of Total Radioactivity Uptake After 80-200 mg Dose of Anti-SAP mAb(Session 1: Days 4, 5, 6 and 8)
- Part A- Session 1: Mean SUV of Total Radioactivity Uptake After 80-200 mg Dose of Anti-SAP mAb: Thyroid Gland-goitre(Session 1: Days 4 and 6)
- Part A- Session 1: Mean SUV of Total Radioactivity Uptake After 80-200 mg Dose of Anti-SAP mAb: Testes(Session 1: Days 4, 5 and 8)
- Part A- Session 2: Mean SUV of Total Radioactivity Uptake After Anti-SAP mAb Dose Between 200 mg and <=500 mg(Session 2: Days 3, 4, and 5)
- Part B: Mean SUV of Total Radioactivity Uptake After 80-200 mg Dose of Anti-SAP mAb(Days 3, 4 and 6)
- Part B: Mean SUV of Total Radioactivity Uptake After an Anti-SAP mAb Dose Between 200 mg and <=500 mg(Days 3, 4 and 6)
- Part A: Maximum Concentration in Plasma (Cmax) of Total mAb(Sessions 1 and 2: Day 3 (pre-dose, halfway infusion, end of infusion, 4 and 7 hours after end of infusion), Days 4, 5, 6 and 7)
- Part B: Cmax of Total mAb(Day 3 (pre-dose, end of infusion, 4 and 7 hours post-infusion), Days 4, 5, 6, 7 and 8)
- Part A: Time Associated With Cmax (Tmax) of Total mAb(Sessions 1 and 2: Day 3 (pre-dose, halfway infusion, end of infusion, 4 and 7 hours after end of infusion), Days 4, 5, 6 and 7)
- Part B: Tmax of Total mAb(Day 3 (pre-dose, end of infusion, 4 and 7 hours post-infusion), Days 4, 5, 6, 7 and 8)
- Part A: Clearance of Total mAb(Sessions 1 and 2: Day 3 (pre-dose, halfway infusion, end of infusion, 4 and 7 hours after end of infusion), Days 4, 5, 6 and 7)
- Part B: Clearance of Total mAb(Day 3 (pre-dose, end of infusion, 4 and 7 hours post-infusion), Days 4, 5, 6, 7 and 8)
- Part A: Terminal Half-life (T1/2) of Total mAb(Sessions 1 and 2: Day 3 (pre-dose, halfway infusion, end of infusion, 4 and 7 hours after end of infusion), Days 4, 5, 6 and 7)
- Part B: T1/2 of Total mAb(Day 3 (pre-dose, end of infusion, 4 and 7 hours post-infusion), Days 4, 5, 6, 7 and 8)
- Part A:Area Under the Concentration Time Curve Till Last Observation (AUC[0 to t]) of Total mAb(Sessions 1 and 2: Day 3 (pre-dose, halfway infusion, end of infusion, 4 and 7 hours after end of infusion), Days 4, 5, 6 and 7)
- Part B: AUC(0 to t) of Total mAb(Day 3 (pre-dose, end of infusion, 4 and 7 hours post-infusion), Days 4, 5, 6, 7 and 8)
- Part A: Area Under the Concentration Time Curve Till Time Infinity (AUC[0 to Infinity]) of Total mAb(Sessions 1 and 2: Day 3 (pre-dose, halfway infusion, end of infusion, 4 and 7 hours after end of infusion), Days 4, 5, 6 and 7)
- Part B: AUC(0 to Infinity) of Total mAb(Day 3 (pre-dose, end of infusion, 4 and 7 hours post-infusion), Days 4, 5, 6, 7 and 8)
- Part A: Cmax of 89Zr-GSK2398852 PKs of Radioactivity (Radio-PK)(Sessions 1 and 2: Day 3 (10 minutes, 60 minutes, 4 hours, 7 hours post-dose), Days 4, 5 and 6)
- Part B: Cmax of 89Zr-GSK2398852 Radio-PK(Day 3 (10 minutes, 60 minutes, 4 hours, 7 hours post-dose), Days 4, 5 and 6)
- Part A: Tmax of 89Zr- GSK2398852 Radio-PK(Sessions 1 and 2: Day 3 (10 minutes, 60 minutes, 4 hours, 7 hours post-dose), Days 4, 5 and 6)
- Part B: Tmax of 89Zr-GSK2398852 Radio-PK(Day 3 (10 minutes, 60 minutes, 4 hours, 7 hours post-dose), Days 4, 5 and 6)
- Part A: T1/2 of 89Zr- GSK2398852 Radio-PK(Sessions 1 and 2: Day 3 (10 minutes, 60 minutes, 4 hours, 7 hours post-dose), Days 4, 5 and 6)
- Part B: T1/2 of 89Zr- GSK2398852 Radio-PK(Day 3 (10 minutes, 60 minutes, 4 hours, 7 hours post-dose), Days 4, 5 and 6)
- Part A: AUC(0 to t) of 89Zr- GSK2398852 Radio-PK(Sessions 1 and 2: Day 3 (10 minutes, 60 minutes, 4 hours, 7 hours post-dose), Days 4, 5 and 6)
- Part B: AUC(0 to t) of 89Zr- GSK2398852 Radio-PK(Day 3 (10 minutes, 60 minutes, 4 hours, 7 hours post-dose), Days 4, 5 and 6)
- Part A: AUC(0 to Infinity) of 89Zr- GSK2398852 Radio-PK(Sessions 1 and 2: Day 3 (10 minutes, 60 minutes, 4 hours, 7 hours post-dose), Days 4, 5 and 6)
- Part B: AUC(0 to Infinity) of 89Zr- GSK2398852 Radio-PK(Day 3 (10 minutes, 60 minutes, 4 hours, 7 hours post-dose), Days 4, 5 and 6)
- Part A: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)(Up to Day 26 of the last session)
- Part B: Number of Participants With AEs and SAEs(Up to Day 26)
- Part A: Number of Participants With Skin Rashes(Up to Day 26 of the last session)
- Part B: Number of Participants With Skin Rashes(Up to Day 26)
- Part A: Number of Participants With Cardiac Adverse Events(Up to Day 26 of the last session)
- Part B: Number of Participants With Cardiac Adverse Events(Up to Day 26)
- Part A: Number of Participants With Infusion Related Reactions(Up to Day 26 of the last session)
- Part B: Number of Participants With Infusion Related Reactions(Up to Day 26)
- Part A: Change From Baseline in Cardiac Troponin T and N-terminal Prohormone of Brain Natriuretic Peptide (NT-ProBNP)(Session 1: Baseline (Day 1 Pre-dose), Days 2, 3, 4, 5, 6, 7, 8, 9, 10 and 26; Session 2: Day 1- Pre-dose, Days 2, 3, 4, 5, 6, 7, 8, 9, 10 and 26)
- Part B: Change From Baseline in Cardiac Troponin T and NT-ProBNP(Baseline and up to Day 26)
- Part A: Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings(Up to Day 26 of the last session)
- Part B: Number of Participants With Abnormal 12-lead ECG Findings(Up to Day 26)
- Part A: Number of Participants With Abnormal Inpatient Cardiac Telemetry(Up to Day 26 of the last session)
- Part B: Number of Participants With Abnormal Inpatient Cardiac Telemetry(Up to Day 26)
- Part A: Number of Participants With Abnormal Outpatient Cardiac Telemetry(Up to Day 26 of the last session)
- Part B: Number of Participants With Abnormal Outpatient Cardiac Telemetry(Up to Day 26)
- Part A: Number of Participants With Abnormal Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)(Up to Day 26 of the last session)
- Part B: Number of Participants With Abnormal Respiratory Rate(Up to Day 26)
- Part A: Number of Participants With Abnormal Pulse Rate(Up to Day 26 of the last session)
- Part B: Number of Participants With Abnormal Pulse Rate(Up to Day 26)
- Part B: Number of Participants With Abnormal SBP and DBP(Up to Day 26)
- Part A: Number of Participants With Abnormal Temperature(Up to Day 26 of the last session)
- Part B: Number of Participants With Abnormal Temperature(Up to Day 26)
- Part A: Number of Participants With Abnormal Respiratory Rate(Up to Day 26 of the last session)
- Part A: Number of Participants With New Abnormal Physical Examination Findings(Session 1: At screening (within 35 days of Anti-SAP treatment of session 1), Day 1 Pre-dose, Day 3, Day 5, Day 8 and Day 11; Session 2: Day 1 Pre-dose, Day 3, Day 5, Day 8 and Day 11)
- Part B: Number of Participants With New Abnormal Physical Examination Findings(At screening (within 35 days of Anti-SAP treatment), Days 1, 3, 5, 8 and 11)
- Part A: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets(Session 1: Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26; Session 2: Day 1-Pre-dose, Days 3, 5, 7, 10 and 26)
- Part B: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets(Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26)
- Part A: Change From Baseline in Hematology Parameter: Hematocrit(Session 1: Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26; Session 2: Day 1-Pre-dose, Days 3, 5, 7, 10 and 26)
- Part B: Change From Baseline in Hematology Parameter: Hematocrit(Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26)
- Part A: Change From Baseline in Hematology Parameter: Hemoglobin(Session 1: Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26; Session 2: Day 1- Pre-dose, Days 3, 5, 7, 10 and 26)
- Part B: Change From Baseline in Hematology Parameter: Hemoglobin(Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26)
- Part A: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin(Session 1: Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26; Session 2: Day 1- Pre-dose, Days 3, 5, 7, 10 and 26)
- Part B: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin(Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26)
- Part A: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume(Session 1: Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26; Session 2: Day 1- Pre-dose, Days 3, 5, 7, 10 and 26)
- Part B: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume(Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26)
- Part A: Change From Baseline in Hematology Parameters: Erythrocytes, Reticulocytes(Session 1: Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26; Session 2: Day 1- Pre-dose, Days 3, 5, 7, 10 and 26)
- Part B: Change From Baseline in Hematology Parameters: Erythrocytes, Reticulocytes(Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26)
- Part A: Change From Baseline in Chemistry Parameters: Glucose, Calcium, Potassium, Sodium, Urea(Session 1: Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26; Session 2: Day 1- Pre-dose, Days 3, 5, 7, 10 and 26)
- Part B: Change From Baseline in Chemistry Parameters: Glucose, Calcium, Potassium, Sodium, Urea(Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26)
- Part A: Change From Baseline in Chemistry Parameters: Albumin, Protein(Session 1: Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26; Session 2: Day 1- Pre-dose, Days 3, 5, 7, 10 and 26)
- Part B: Change From Baseline in Chemistry Parameters: Albumin, Protein(Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26)
- Part A: Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST)(Session 1: Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26; Session 2: Day 1- Pre-dose, Days 3, 5, 7, 10 and 26)
- Part B: Change From Baseline in Chemistry Parameters: ALP, ALT, AST(Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26)
- Part A: Change From Baseline in Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine(Session 1: Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26; Session 2: Day 1- Pre-dose, Days 3, 5, 7, 10 and 26)
- Part B: Change From Baseline in Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine(Baseline (Day 1 Pre-dose), Days 3, 5, 7, 10 and 26)
- Part A: Number of Participants With Abnormal Urinalysis Parameters: Glucose, Protein, Blood, Ketones(Up to Day 26 of the last session)
- Part A: Number of Participants With Abnormal Urinalysis Parameters: Specific Gravity, Potential of Hydrogen(Up to Day 26 of the last session)
- Part B: Number of Participants With Abnormal Urinalysis Parameters: Glucose, Protein, Blood, Ketones(Up to Day 26)
- Part B: Number of Participants With Abnormal Urinalysis Parameters: Specific Gravity, Potential of Hydrogen(Up to Day 26)