Alzheimer's Disease
Conditions
Keywords
TB006, pharmacokinetics, pharmacodynamics, immunogenicity, mild to severe Alzheimer's Disease
Brief summary
Part 1 of this study will be conducted to determine the safety, tolerability, and pharmacokinetic (PK) profile of multiple doses of TB006, as well as the maximum tolerated dose of TB006, and to assess the immunogenicity of TB006 (production of anti-TB006 antibody). Part 2 of this study will be conducted to determine the clinical efficacy of TB006 in participants with mild to severe Alzheimer's Disease.
Interventions
DRUGTB006
intravenous infusion
DRUGPlacebo
intravenous infusion
Sponsors
TrueBinding, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Body weight of ≥ 50 kilograms (kg) and body mass index (BMI) between 18 and 35 kg/meters squared (m\^2), inclusive * Mini-Mental State Examination (MMSE) score of 24 or less * Must be ambulatory * Clinical diagnosis of Alzheimer's Disease (AD) consistent with the following: 1. Probable AD, according to National Institute of Neurological and Communicative Disorders and Stroke - Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) 2. Meets the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) - Criteria for Major Neurocognitive Disorder (previously dementia) * Participants or caregiver has the ability to understand the purpose and risks of the study and provide signed and dated informed consent which includes compliance with the requirements and restrictions listed in the inform consent form (ICF) and in this protocol. Participants whose caregiver signs the informed consent must provide their assent.
Exclusion criteria
* Any medical or neurological condition other than AD that in the opinion of the investigator could be a contributing cause of the participant's dementia (e.g., medication use, vitamin B12 deficiency, abnormal thyroid function, stroke or other cerebrovascular condition, diffuse Lewy body disease, head trauma) * History within the past 6 months or evidence of clinically significant psychiatric illness (e.g., major depression, schizophrenia, or bipolar affective disorder) * Diagnosis of a dementia-related central nervous system (CNS) disease other than AD (e.g., Parkinson's Disease, Huntington's Disease, frontotemporal dementia, multi-infarct dementia, dementia with Lewy bodies, normal pressure hydrocephalus) * Identification of other known cause of dementia or any other clinically significant contributing co-morbid pathologies at screening magnetic resonance imaging (MRI), in the opinion of the investigator * Participation in any other drug, biologic, device, or clinical study or treatment with any investigational drug or approved therapy for investigational use within 30 days (or 5 half lives, whichever is longer) prior to screening, and/or participation in any other clinical study involving experimental medications for AD within the 60 days (or 5 half lives, whichever is longer) prior to screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 2: Change From Baseline Through Day 104 on the Clinical Dementia Rating Scale - Sum of Boxes Total Score | Baseline through Day 104 | The Clinical Dementia Rating was obtained through semi-structured interviews of participants and informants, and cognitive functioning was rated in six domains of functioning: memory, orientation, judgement and problem solving, community affairs, home and hobbies, and personal care. Each domain was rated on a five-point scale of functioning as follows: 0: no impairment; 0.5: questionable impairment; 1: mild impairment; 2: moderate impairment; and 3: severe impairment. The Clinical Dementia Rating Scale - Sum of Boxes was based on summing each of the domain box scores with total scores ranging from 0-18, where lower total scores represent better outcomes, and higher total scores represent worse outcomes. Baseline was defined as the last available value prior to the subject receiving the first study drug infusion on Day 1. Change from Baseline value was obtained by subtracting Baseline value from post-dose visit value. |
| Part 1: Change From Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST) and Creatine Kinase (CK) | Baseline and up to Day 104 | Blood samples were collected for analysis of following clinical chemistry parameters including ALT, ALP, AST and CK. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value. |
| Part 1: Change From Baseline in Clinical Chemistry Parameters: Albumin and Protein | Baseline and up to Day 104 | Blood samples were collected for analysis of following clinical chemistry parameters including albumin and protein. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value. |
| Part 1: Change From Baseline in Chemistry Parameters: Calcium, Cholesterol, Creatinine, Direct Bilirubin, Glucose, HDL (High Density Lipoprotein) Cholesterol, LDL (Low Density Lipoprotein) Cholesterol, Total Bilirubin, Triglycerides and Urea Nitrogen | Baseline and up to Day 104 | Blood samples were collected for analysis of following clinical chemistry parameters including Calcium, Cholesterol, Creatinine, Direct Bilirubin, Glucose, HDL Cholesterol, LDL Cholesterol, Total Bilirubin, Triglycerides and Urea Nitrogen. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value. |
| Part 1: Change From Baseline in Clinical Chemistry Parameter: Hemoglobin A1C | Baseline and up to Day 104 | Blood samples were collected for analysis of following clinical chemistry parameters including Hemoglobin A1C. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value. |
| Part 1: Change From Baseline in Clinical Chemistry Parameters: Potassium and Sodium | Baseline and up to Day 104 | Blood samples were collected for analysis of following clinical chemistry parameters including Potassium and Sodium. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value. |
| Part 1: Change From Baseline in Clinical Chemistry Parameter: Thyrotropin | Baseline and up to Day 104 | Blood samples were collected for analysis of following clinical chemistry parameters including Thyrotropin. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value. |
| Part 1: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Platelets | Baseline and up to Day 104 | Blood samples were collected for analysis of following hematology parameters including Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Platelets. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value. |
| Part 1: Change From Baseline in Urine Specific Gravity | Baseline and up to Day 104 | Urine samples were collected for analysis of Urine specific gravity. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value. |
| Part 1: Change From Baseline in Hematology Parameter: Erythrocyte. Mean Corpuscular Hemoglobin (Ery. MCH) | Baseline and up to Day 104 | Blood samples were collected for analysis of following hematology parameter: Ery. MCH. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value. |
| Part 1: Change From Baseline in Hematology Parameter: Hematocrit | Baseline and up to Day 104 | Blood samples were collected for analysis of following hematology parameter: Hematocrit. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value. |
| Part 1: Change From Baseline in Hematology Parameter: Erythrocytes and Reticulocytes | Baseline and up to Day 104 | Blood samples were collected for analysis of following hematology parameter: Erythrocytes and Reticulocytes. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value. |
| Part 1: Change From Baseline in Hematology Parameter: Erythrocyte. Mean Corpuscular Volume (Ery. MCV) | Baseline and up to Day 104 | Blood samples were collected for analysis of following hematology parameter: Ery. MCV. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value. |
| Part 1: Change From Baseline in Hematology Parameter: Hemoglobin | Baseline and up to Day 104 | Blood samples were collected for analysis of following hematology parameter: Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value. |
| Part 1: Change From Baseline in Urine Potential of Hydrogen (pH) | Baseline and up to Day 104 | Urine samples were collected for analysis of Urine pH. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value. |
| Part 1: Change From Baseline in Urobilinogen | Baseline and up to Day 104 | Urine samples were collected for analysis of Urobilinogen. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value. |
| Part 1: Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | Baseline and Up to Day 104 | Vital signs including DBP and SBP was measured by at least 5 minutes of rest with the participant in a quiet setting without distractions (eg, television, cell phones). Blood pressure measurements were taken with the participant in the sitting position. Baseline was defined as the last available value prior to the participant receiving the first study drug infusion on Day 1. Change from Baseline was obtained by subtracting the Baseline value from post-dose visit value. |
| Part 1: Change From Baseline in Respiratory Rate | Baseline and Up to Day 104 | Vital signs including respiratory rate was measured by at least 5 minutes of rest with the participant in a quiet setting without distractions (eg, television, cell phones). Baseline was defined as the last available value prior to the participant receiving the first study drug infusion on Day 1. Change from Baseline was obtained by subtracting the Baseline value from post-dose visit value. |
| Part 1: Change From Baseline in Temperature | Baseline and Up to Day 104 | Vital signs including temperature was measured by at least 5 minutes of rest with the participant in a quiet setting without distractions (eg, television, cell phones). Baseline was defined as the last available value prior to the participant receiving the first study drug infusion on Day 1. Change from Baseline was obtained by subtracting the Baseline value from post-dose visit value. |
| Part 1: Change From Baseline in Heart Rate | Baseline and Up to Day 104 | Vital signs including heart rate was measured by at least 5 minutes of rest with the participant in a quiet setting without distractions (eg, television, cell phones). Baseline was defined as the last available value prior to the participant receiving the first study drug infusion on Day 1. Change from Baseline was obtained by subtracting the Baseline value from post-dose visit value. |
| Part 1: Change From Baseline in Electrocardiogram (ECG) Mean Heart Rate | Baseline and Up to Day 104 | 12-lead ECG measurements was obtained using an ECG machine that automatically calculates the heart rate. Baseline was defined as the last available value prior to the participant receiving the first study drug infusion on Day 1. Change from Baseline was obtained by subtracting the Baseline value from post-dose visit value value. |
| Part 1: Total Clearance (CL) of TB006 | At Day 29 | Blood samples were collected at indicated time points for PK analysis of TB006. PK parameters were analyzed using standard non-compartmental analysis. |
| Part 1: Volume of Distribution (Vd) of TB006 | At Day 29 | Blood samples were collected at indicated time points for PK analysis of TB006. PK parameters were analyzed using standard non-compartmental analysis. |
| Part 1: Change From Baseline in ECG Parameters | Baseline and Up to Day 104 | 12-lead ECG measurements was obtained using an ECG machine that automatically calculates the PR interval, QRS duration, QT interval and QT Corrected using Bazett's formula (QTcB). Baseline was defined as the last available value prior to the participant receiving the first study drug infusion on Day 1. Change from Baseline was obtained by subtracting the Baseline value from post-dose visit value. |
| Part 1: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) | Up to Day 104 | The C-SSRS is an interview-based instrument to systematically assess suicidal ideation and suicidal behavior. Number of participants that have an affirmative response to the 5 items for suicidal ideation (1. Wish to be dead, 2. Non-specific active suicidal thoughts, 3. Active suicidal ideation with any methods without intent to act, 4. Active suicidal ideation with some intent to act, without specific plan, 5. Active suicidal ideation with specific plan and intent) and/or to the 5 items for suicidal behavior (1. Preparatory acts or behavior, 2. Aborted attempt, 3. Interrupted attempt, 4. Actual attempt, 5. Completed suicide) were reported. The total score ranges from 0 (no ideation present) to 5 (active suicidal ideation with specific plan and intent); higher scores indicate worse symptoms. |
| Part 1: Number of Participants With Clinically Significant Physical Examination Findings | Up to Day 104 | A complete physical examination included, at a minimum, assessment of the Cardiovascular, Respiratory, Gastrointestinal and Neurological systems. This analysis was planned but data was not captured in the database. Abnormal changes were captured as adverse events if they were clinically significant. |
| Part 1: Number of Participants With Clinically Significant Neurological Examination Findings | Up to Day 104 | The neurological examination assessed mental status, motor and sensory skills, hearing and speech, vision, coordination, and balance. This analysis was planned but data was not captured in the database. Abnormal changes were captured as adverse events if they were clinically significant. |
| Part 1: Dose Normalized Area Under the Concentration Time Curve Over a Dosing Interval (AUCtau) of TB006 | Day 1 and Day 29 | Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of TB006. PK parameters were analyzed using standard non-compartmental analysis. AUCtau normalized to the actual administered dose is presented. The AUCtau was divided by the actual dose strength to get the normalized area under the concentration-time curve. |
| Part 1: Time at Which Maximum Plasma Concentration Occurs (Tmax) of TB006 | At Days 1, 8 and 29 | Blood samples were collected at indicated time points for PK analysis of TB006. PK parameters were analyzed using standard non-compartmental analysis. |
| Part 1: Dose Normalized Maximum Observed Plasma Concentration (Cmax) of TB006 | At Days 1, 8 and 29 | Blood samples were collected at indicated time points for PK analysis of TB006. PK parameters were analyzed using standard non-compartmental analysis. Cmax normalized to the actual administered dose is presented. The Cmax was divided by the actual dose strength to get the normalized maximum observed plasma concentration. |
| Part 1: Concentration at the End of a Dosing Interval (Ctrough) of TB006 | Day 8 and Day 29 | Blood samples were collected at indicated time points for PK analysis of TB006. PK parameters were analyzed using standard non-compartmental analysis. |
| Part 1: Terminal Elimination Phase Half-life (t1/2) of TB006 | At Day 29 | Blood samples were collected at indicated time points for PK analysis of TB006. PK parameters were analyzed using standard non-compartmental analysis. |
| Part 1: Number of Participants With Anti-TB006 Antibodies (Immunogenicity of TB006) | Day 1 (Predose), Day 8 (Predose), Day 36 and Day 104 | Plasma samples were collected at indicated time points for the determination of anti-TB006 antibodies. Plasma samples were screened for antibodies binding to TB006 and the titer of confirmed positive samples has been reported. |
| Part 1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Up to Day 104 | An adverse event is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An 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, associated with liver injury and impaired liver function or any other situations as per medical or scientific judgement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 2: Percentage of Responders on the Clinical Dementia Rating Scale - Sum of Boxes | At Days 36 and 104 | The Clinical Dementia Rating is obtained through semi-structured interviews of participants and informants, and cognitive functioning is rated in six domains of functioning: memory, orientation, judgement and problem solving, community affairs, home and hobbies, and personal care. Each domain is rated on a five-point scale of functioning as follows: 0, no impairment; 0.5, questionable impairment; 1, mild impairment; 2, moderate impairment; and 3, severe impairment. The Clinical Dementia Rating Scale - Sum of Boxes is based on summing each of the domain box scores with total scores ranging from 0-18, where lower total scores represent better outcomes, and higher total scores represent worse outcomes. A responder was defined as a participant with at least 1 point improvement from Baseline on the Sum of Boxes score. Percentage of responders on the Clinical Dementia Rating Scale - Sum of Boxes has been presented. |
| Part 2: Change From Baseline on Mini-Mental State Examination (MMSE) Score | Baseline and at Days 36 and 104 | The MMSE was used to measure cognitive impairment. The MMSE can evaluate overall cognitive function, and is widely used for the assessment of cognitive impairment in dementia participants. The questionnaire consists of 11 items, and each item aims to evaluate different cognitive domains such as orientation, memory, attention, and construction. The score ranged from 0 to 30, with a higher score indicating better function. A positive change score indicated improvement from Baseline. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value. |
| Part 2: Change From Baseline on the Neuropsychiatric Inventory (NPI) Score | Baseline and at Days 36 and 104 | The NPI was a questionnaire that quantified psychiatric symptoms and behavioral disorders in dementia. A total of 12 items (the original NPI-10 consisting of 10 behavioral domains: delusions, hallucinations, agitation/aggression, dysphoria, anxiety, euphoria, apathy, disinhibition, irritability/lability, and aberrant motor behavior, The NPI total score was calculated by adding the scores of the domains (each domain scores ranges from 0 to 12). The NPI total score ranges from 0 to 120 with higher scores indicating greater behavioral impairment. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value. |
| Part 2: Number of Participants With AEs and SAEs | Up to Day 104 | An adverse event is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An 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, associated with liver injury and impaired liver function or any other situations as per medical or scientific judgement. |
| Part 2: Change From Baseline in Clinical Chemistry Parameters: ALT, ALP, AST and CK | Baseline and up to Day 104 | Blood samples were collected for analysis of following clinical chemistry parameters including ALT, ALP, AST and CK. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value. |
| Part 2: Change From Baseline in Clinical Chemistry Parameters: Albumin and Protein | Baseline and up to Day 104 | Blood samples were collected for analysis of following clinical chemistry parameters including albumin and protein. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value. |
| Part 2: Change From Baseline in Chemistry Parameters: Calcium, Cholesterol, Creatinine, Direct Bilirubin, Glucose, HDL Cholesterol, LDL Cholesterol, Total Bilirubin, Triglycerides and Urea Nitrogen | Baseline and up to Day 104 | Blood samples were collected for analysis of following clinical chemistry parameters including Calcium, Cholesterol, Creatinine, Direct Bilirubin, Glucose, HDL Cholesterol, LDL Cholesterol, Total Bilirubin, Triglycerides and Urea Nitrogen. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value. |
| Part 2: Change From Baseline in Clinical Chemistry Parameter: Hemoglobin A1C | Baseline and up to Day 104 | Blood samples were collected for analysis of following clinical chemistry parameter including Hemoglobin A1C. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value. |
| Part 2: Change From Baseline in Clinical Chemistry Parameters: Potassium and Sodium | Baseline and up to Day 104 | Blood samples were collected for analysis of following clinical chemistry parameters including Potassium and Sodium. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value. |
| Part 2: Change From Baseline in Clinical Chemistry Parameter: Thyrotropin | Baseline and up to Day 104 | Blood samples were collected for analysis of following clinical chemistry parameter including Thyrotropin. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value. |
| Part 2: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Platelets | Baseline and up to Day 104 | Blood samples were collected for analysis of following hematology parameters including Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Platelets. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value. |
| Part 2: Change From Baseline in Hematology Parameter: Ery. MCH | Baseline and up to Day 104 | Blood samples were collected for analysis of following hematology parameter: Ery. MCH. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value. |
| Part 2: Change From Baseline in Hematology Parameter: Ery. MCV | Baseline and up to Day 104 | Blood samples were collected for analysis of following hematology parameter: Ery. MCV. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value. |
| Part 2: Change From Baseline in Hematology Parameter: Erythrocytes and Reticulocytes | Baseline and up to Day 104 | Blood samples were collected for analysis of following hematology parameter: Erythrocytes and Reticulocytes. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value. |
| Part 2: Change From Baseline in Hematology Parameter: Hematocrit | Baseline and up to Day 104 | Blood samples were collected for analysis of following hematology parameter: Hematocrit. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value. |
| Part 2: Change From Baseline in Hematology Parameter: Hemoglobin | Baseline and up to Day 104 | Blood samples were collected for analysis of following hematology parameter: Hemoglobin. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value. |
| Part 2: Change From Baseline in Urine pH | Baseline and up to Day 104 | Urine samples were collected for analysis of Urine pH. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value. |
| Part 2: Change From Baseline in Urine Specific Gravity | Baseline and up to Day 104 | Urine samples were collected for analysis of Urine specific gravity. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value. |
| Part 2: Change From Baseline in Urobilinogen | Baseline and up to Day 104 | Urine samples were collected for analysis of Urobilinogen. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value. |
| Part 2: Change From Baseline in DBP and SBP | Baseline and Up to Day 104 | Vital signs including DBP and SBP was measured by at least 5 minutes of rest with the participant in a quiet setting without distractions (eg, television, cell phones). Blood pressure measurements were taken with the participant in the sitting position. Baseline was defined as the last available value prior to the participant receiving the first study drug infusion on Day 1. Change from Baseline was obtained by subtracting the Baseline value from post-dose visit value. |
| Part 2: Change From Baseline in Respiratory Rate | Baseline and Up to Day 104 | Vital signs including respiratory rate was measured by at least 5 minutes of rest with the participant in a quiet setting without distractions (eg, television, cell phones). Blood pressure measurements were taken with the participant in the sitting position. Baseline was defined as the last available value prior to the participant receiving the first study drug infusion on Day 1. Change from Baseline was obtained by subtracting the Baseline value from post-dose visit value. |
| Part 2: Change From Baseline in Temperature | Baseline and Up to Day 104 | Vital signs including temperature was measured by at least 5 minutes of rest with the participant in a quiet setting without distractions (eg, television, cell phones). Blood pressure measurements were taken with the participant in the sitting position. Baseline was defined as the last available value prior to the participant receiving the first study drug infusion on Day 1. Change from Baseline was obtained by subtracting the Baseline value from post-dose visit value. |
| Part 2: Change From Baseline in Heart Rate | Baseline and Up to Day 104 | Vital signs including heart rate was measured by at least 5 minutes of rest with the participant in a quiet setting without distractions (eg, television, cell phones). Blood pressure measurements were taken with the participant in the sitting position. Baseline was defined as the last available value prior to the participant receiving the first study drug infusion on Day 1. Change from Baseline was obtained by subtracting the Baseline value from post-dose visit value. |
| Part 2: Change From Baseline in ECG Parameters | Baseline and Up to Day 104 | 12-lead ECG measurements was obtained using an ECG machine that automatically calculates the PR interval, QRS duration, QT interval and QTcB. Baseline was defined as the last available value prior to the participant receiving the first study drug infusion on Day 1. Change from Baseline was obtained by subtracting the Baseline value from post-dose visit value. |
| Part 2: Change From Baseline in ECG Mean Heart Rate | Baseline and Up to Day 104 | 12-lead ECG measurements was obtained using an ECG machine that automatically calculates the heart rate. Baseline was defined as the last available value prior to the participant receiving the first study drug infusion on Day 1. Change from Baseline was obtained by subtracting the Baseline value from post-dose visit value. |
| Part 2: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using C-SSRS | Up to Day 104 | The C-SSRS is an interview-based instrument to systematically assess suicidal ideation and suicidal behavior. Number of participants that have an affirmative response to the 5 items for suicidal ideation (1. Wish to be dead, 2. Non-specific active suicidal thoughts, 3. Active suicidal ideation with any methods without intent to act, 4. Active suicidal ideation with some intent to act, without specific plan, 5. Active suicidal ideation with specific plan and intent) and/or to the 5 items for suicidal behavior (1. Preparatory acts or behavior, 2. Aborted attempt, 3. Interrupted attempt, 4. Actual attempt, 5. Completed suicide) were reported. The total score ranges from 0 (no ideation present) to 5 (active suicidal ideation with specific plan and intent); higher scores indicate worse symptoms. |
| Part 2: Number of Participants With Clinically Significant Physical Examination Findings | Up to Day 104 | A complete physical examination included, at a minimum, assessment of the Cardiovascular, Respiratory, Gastrointestinal and Neurological systems. This analysis was planned but data was not captured in the database. Abnormal changes were captured as adverse events if they were clinically significant. |
| Part 2: Number of Participants With Clinically Significant Neurological Examination Findings | Up to Day 104 | The neurological examination assessed mental status, motor and sensory skills, hearing and speech, vision, coordination, and balance. This analysis was planned but data was not captured in the database. Abnormal changes were captured as adverse events if they were clinically significant. |
| Part 2: Ctrough of TB006 | Day 29 | Blood samples were collected at indicated time points for PK analysis of TB006. PK parameters were analyzed using standard non-compartmental analysis. |
| Part 2: t1/2 of TB006 | Day 29 | Blood samples were collected at indicated time points for PK analysis of TB006. PK parameters were analyzed using standard non-compartmental analysis. |
| Part 2: Cmax of TB006 | Day 1 and Day 29 | Blood samples were collected at indicated time points for PK analysis of TB006. PK parameters were analyzed using standard non-compartmental analysis. |
| Part 2: Change From Baseline Through Day 36 on the Clinical Dementia Rating Scale - Sum of Boxes Total Score | Baseline through Day 36 | The Clinical Dementia Rating was obtained through semi-structured interviews of participants and informants, and cognitive functioning was rated in six domains of functioning: memory, orientation, judgement and problem solving, community affairs, home and hobbies, and personal care. Each domain was rated on a five-point scale of functioning as follows: 0: no impairment; 0.5: questionable impairment; 1: mild impairment; 2: moderate impairment; and 3: severe impairment. The Clinical Dementia Rating Scale - Sum of Boxes was based on summing each of the domain box scores with total scores ranging from 0-18, where lower total scores represent better outcomes, and higher total scores represent worse outcomes. Baseline was defined as the last available value prior to the subject receiving the first study drug infusion on Day 1. Change from Baseline value was obtained by subtracting Baseline value from post-dose visit value. |
Countries
United States
Participant flow
Recruitment details
This was a multi-center study conducted at various centers across United States (US).
Pre-assignment details
This was a 2-part randomized, double-blind, placebo-controlled, multiple ascending dose (MAD) escalation study that evaluated the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and efficacy of TB006 in participants with Alzheimer's disease (AD).
Participants by arm
| Arm | Count |
|---|---|
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) Participants were randomized to receive intravenous infusions of TB006 140 mg weekly for over 1 hour. | 7 |
| Part 1: TB006 420 mg qw Participants were randomized to receive intravenous infusions of TB006 420 mg weekly for over 1 hour. | 6 |
| Part 1: TB006 1000 mg qw Participants were randomized to receive intravenous infusions of TB006 1000 mg weekly for over 1 hour. | 6 |
| Part 1: Placebo Participants were randomized to receive intravenous infusions of matching placebo weekly for over 1 hour. | 6 |
| Part 2: TB006 1000 mg qw Participants were randomized to receive intravenous infusions of TB006 1000 mg weekly for over 1 hour. | 63 |
| Part 2: Placebo Participants were randomized to receive intravenous infusions of matching placebo weekly for over 1 hour. | 66 |
| Total | 154 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Part 1 (Upto Day 104) | Lost to Follow-up | 0 | 0 | 0 | 1 | 0 | 0 |
| Part 1 (Upto Day 104) | Other | 1 | 0 | 0 | 0 | 0 | 0 |
| Part 2 (Upto Day 104) | Death | 0 | 0 | 0 | 0 | 1 | 0 |
| Part 2 (Upto Day 104) | Lost to Follow-up | 0 | 0 | 0 | 0 | 1 | 2 |
| Part 2 (Upto Day 104) | Other | 0 | 0 | 0 | 0 | 1 | 0 |
| Part 2 (Upto Day 104) | Withdrawal by Subject | 0 | 0 | 0 | 0 | 2 | 0 |
Baseline characteristics
| Characteristic | Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 1: TB006 420 mg qw | Part 1: TB006 1000 mg qw | Part 1: Placebo | Part 2: TB006 1000 mg qw | Part 2: Placebo | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 72.3 Years STANDARD_DEVIATION 3.25 | 73.0 Years STANDARD_DEVIATION 10.41 | 71.5 Years STANDARD_DEVIATION 6.77 | 72.2 Years STANDARD_DEVIATION 6.74 | 73.5 Years STANDARD_DEVIATION 9.3 | 71.5 Years STANDARD_DEVIATION 7.65 | 72.2 Years STANDARD_DEVIATION 7.35 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 5 Participants | 3 Participants | 27 Participants | 39 Participants | 75 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants | 5 Participants | 1 Participants | 3 Participants | 35 Participants | 26 Participants | 77 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 4 Participants | 6 Participants | 13 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 5 Participants | 5 Participants | 6 Participants | 5 Participants | 57 Participants | 60 Participants | 138 Participants |
| Sex: Female, Male Female | 6 Participants | 4 Participants | 2 Participants | 5 Participants | 33 Participants | 36 Participants | 86 Participants |
| Sex: Female, Male Male | 1 Participants | 2 Participants | 4 Participants | 1 Participants | 30 Participants | 30 Participants | 68 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 7 | 0 / 6 | 0 / 6 | 0 / 6 | 1 / 63 | 0 / 66 |
| other Total, other adverse events | 5 / 7 | 4 / 6 | 1 / 6 | 2 / 6 | 28 / 63 | 17 / 66 |
| serious Total, serious adverse events | 1 / 7 | 0 / 6 | 0 / 6 | 0 / 6 | 4 / 63 | 1 / 66 |
Outcome results
Primary
Part 1: Change From Baseline in Chemistry Parameters: Calcium, Cholesterol, Creatinine, Direct Bilirubin, Glucose, HDL (High Density Lipoprotein) Cholesterol, LDL (Low Density Lipoprotein) Cholesterol, Total Bilirubin, Triglycerides and Urea Nitrogen
Blood samples were collected for analysis of following clinical chemistry parameters including Calcium, Cholesterol, Creatinine, Direct Bilirubin, Glucose, HDL Cholesterol, LDL Cholesterol, Total Bilirubin, Triglycerides and Urea Nitrogen. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value.
Time frame: Baseline and up to Day 104
Population: Safety Analysis Set. Only those participants with data available at specified time points has been presented.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 1: Change From Baseline in Chemistry Parameters: Calcium, Cholesterol, Creatinine, Direct Bilirubin, Glucose, HDL (High Density Lipoprotein) Cholesterol, LDL (Low Density Lipoprotein) Cholesterol, Total Bilirubin, Triglycerides and Urea Nitrogen | Urea Nitrogen | -0.40 milligrams per deciliter | Standard Deviation 2.171 |
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 1: Change From Baseline in Chemistry Parameters: Calcium, Cholesterol, Creatinine, Direct Bilirubin, Glucose, HDL (High Density Lipoprotein) Cholesterol, LDL (Low Density Lipoprotein) Cholesterol, Total Bilirubin, Triglycerides and Urea Nitrogen | Calcium | -0.13 milligrams per deciliter | Standard Deviation 0.373 |
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 1: Change From Baseline in Chemistry Parameters: Calcium, Cholesterol, Creatinine, Direct Bilirubin, Glucose, HDL (High Density Lipoprotein) Cholesterol, LDL (Low Density Lipoprotein) Cholesterol, Total Bilirubin, Triglycerides and Urea Nitrogen | Cholesterol | -15.4 milligrams per deciliter | Standard Deviation 21.62 |
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 1: Change From Baseline in Chemistry Parameters: Calcium, Cholesterol, Creatinine, Direct Bilirubin, Glucose, HDL (High Density Lipoprotein) Cholesterol, LDL (Low Density Lipoprotein) Cholesterol, Total Bilirubin, Triglycerides and Urea Nitrogen | Direct Bilirubin | -0.007 milligrams per deciliter | Standard Deviation 0.032 |
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 1: Change From Baseline in Chemistry Parameters: Calcium, Cholesterol, Creatinine, Direct Bilirubin, Glucose, HDL (High Density Lipoprotein) Cholesterol, LDL (Low Density Lipoprotein) Cholesterol, Total Bilirubin, Triglycerides and Urea Nitrogen | Total Bilirubin | -0.036 milligrams per deciliter | Standard Deviation 0.093 |
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 1: Change From Baseline in Chemistry Parameters: Calcium, Cholesterol, Creatinine, Direct Bilirubin, Glucose, HDL (High Density Lipoprotein) Cholesterol, LDL (Low Density Lipoprotein) Cholesterol, Total Bilirubin, Triglycerides and Urea Nitrogen | LDL Cholesterol | -9.0 milligrams per deciliter | Standard Deviation 9.04 |
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 1: Change From Baseline in Chemistry Parameters: Calcium, Cholesterol, Creatinine, Direct Bilirubin, Glucose, HDL (High Density Lipoprotein) Cholesterol, LDL (Low Density Lipoprotein) Cholesterol, Total Bilirubin, Triglycerides and Urea Nitrogen | Triglycerides | -23.3 milligrams per deciliter | Standard Deviation 69.65 |
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 1: Change From Baseline in Chemistry Parameters: Calcium, Cholesterol, Creatinine, Direct Bilirubin, Glucose, HDL (High Density Lipoprotein) Cholesterol, LDL (Low Density Lipoprotein) Cholesterol, Total Bilirubin, Triglycerides and Urea Nitrogen | Glucose | 34.3 milligrams per deciliter | Standard Deviation 55.23 |
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 1: Change From Baseline in Chemistry Parameters: Calcium, Cholesterol, Creatinine, Direct Bilirubin, Glucose, HDL (High Density Lipoprotein) Cholesterol, LDL (Low Density Lipoprotein) Cholesterol, Total Bilirubin, Triglycerides and Urea Nitrogen | Creatinine | 0.047 milligrams per deciliter | Standard Deviation 0.081 |
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 1: Change From Baseline in Chemistry Parameters: Calcium, Cholesterol, Creatinine, Direct Bilirubin, Glucose, HDL (High Density Lipoprotein) Cholesterol, LDL (Low Density Lipoprotein) Cholesterol, Total Bilirubin, Triglycerides and Urea Nitrogen | HDL Cholesterol | -3.6 milligrams per deciliter | Standard Deviation 5.19 |
| Part 1: TB006 420 mg qw | Part 1: Change From Baseline in Chemistry Parameters: Calcium, Cholesterol, Creatinine, Direct Bilirubin, Glucose, HDL (High Density Lipoprotein) Cholesterol, LDL (Low Density Lipoprotein) Cholesterol, Total Bilirubin, Triglycerides and Urea Nitrogen | Total Bilirubin | -0.005 milligrams per deciliter | Standard Deviation 0.227 |
| Part 1: TB006 420 mg qw | Part 1: Change From Baseline in Chemistry Parameters: Calcium, Cholesterol, Creatinine, Direct Bilirubin, Glucose, HDL (High Density Lipoprotein) Cholesterol, LDL (Low Density Lipoprotein) Cholesterol, Total Bilirubin, Triglycerides and Urea Nitrogen | HDL Cholesterol | -3.0 milligrams per deciliter | Standard Deviation 4.65 |
| Part 1: TB006 420 mg qw | Part 1: Change From Baseline in Chemistry Parameters: Calcium, Cholesterol, Creatinine, Direct Bilirubin, Glucose, HDL (High Density Lipoprotein) Cholesterol, LDL (Low Density Lipoprotein) Cholesterol, Total Bilirubin, Triglycerides and Urea Nitrogen | LDL Cholesterol | -1.8 milligrams per deciliter | Standard Deviation 9.33 |
| Part 1: TB006 420 mg qw | Part 1: Change From Baseline in Chemistry Parameters: Calcium, Cholesterol, Creatinine, Direct Bilirubin, Glucose, HDL (High Density Lipoprotein) Cholesterol, LDL (Low Density Lipoprotein) Cholesterol, Total Bilirubin, Triglycerides and Urea Nitrogen | Cholesterol | -2.7 milligrams per deciliter | Standard Deviation 10.35 |
| Part 1: TB006 420 mg qw | Part 1: Change From Baseline in Chemistry Parameters: Calcium, Cholesterol, Creatinine, Direct Bilirubin, Glucose, HDL (High Density Lipoprotein) Cholesterol, LDL (Low Density Lipoprotein) Cholesterol, Total Bilirubin, Triglycerides and Urea Nitrogen | Urea Nitrogen | 6.95 milligrams per deciliter | Standard Deviation 8.277 |
| Part 1: TB006 420 mg qw | Part 1: Change From Baseline in Chemistry Parameters: Calcium, Cholesterol, Creatinine, Direct Bilirubin, Glucose, HDL (High Density Lipoprotein) Cholesterol, LDL (Low Density Lipoprotein) Cholesterol, Total Bilirubin, Triglycerides and Urea Nitrogen | Creatinine | 0.153 milligrams per deciliter | Standard Deviation 0.377 |
| Part 1: TB006 420 mg qw | Part 1: Change From Baseline in Chemistry Parameters: Calcium, Cholesterol, Creatinine, Direct Bilirubin, Glucose, HDL (High Density Lipoprotein) Cholesterol, LDL (Low Density Lipoprotein) Cholesterol, Total Bilirubin, Triglycerides and Urea Nitrogen | Triglycerides | 12.2 milligrams per deciliter | Standard Deviation 17.72 |
| Part 1: TB006 420 mg qw | Part 1: Change From Baseline in Chemistry Parameters: Calcium, Cholesterol, Creatinine, Direct Bilirubin, Glucose, HDL (High Density Lipoprotein) Cholesterol, LDL (Low Density Lipoprotein) Cholesterol, Total Bilirubin, Triglycerides and Urea Nitrogen | Direct Bilirubin | -0.003 milligrams per deciliter | Standard Deviation 0.033 |
| Part 1: TB006 420 mg qw | Part 1: Change From Baseline in Chemistry Parameters: Calcium, Cholesterol, Creatinine, Direct Bilirubin, Glucose, HDL (High Density Lipoprotein) Cholesterol, LDL (Low Density Lipoprotein) Cholesterol, Total Bilirubin, Triglycerides and Urea Nitrogen | Calcium | 0.17 milligrams per deciliter | Standard Deviation 0.28 |
| Part 1: TB006 420 mg qw | Part 1: Change From Baseline in Chemistry Parameters: Calcium, Cholesterol, Creatinine, Direct Bilirubin, Glucose, HDL (High Density Lipoprotein) Cholesterol, LDL (Low Density Lipoprotein) Cholesterol, Total Bilirubin, Triglycerides and Urea Nitrogen | Glucose | -15.0 milligrams per deciliter | Standard Deviation 18.51 |
| Part 1: TB006 1000 mg qw | Part 1: Change From Baseline in Chemistry Parameters: Calcium, Cholesterol, Creatinine, Direct Bilirubin, Glucose, HDL (High Density Lipoprotein) Cholesterol, LDL (Low Density Lipoprotein) Cholesterol, Total Bilirubin, Triglycerides and Urea Nitrogen | Calcium | -0.02 milligrams per deciliter | Standard Deviation 0.36 |
| Part 1: TB006 1000 mg qw | Part 1: Change From Baseline in Chemistry Parameters: Calcium, Cholesterol, Creatinine, Direct Bilirubin, Glucose, HDL (High Density Lipoprotein) Cholesterol, LDL (Low Density Lipoprotein) Cholesterol, Total Bilirubin, Triglycerides and Urea Nitrogen | Glucose | 21.3 milligrams per deciliter | Standard Deviation 45.45 |
| Part 1: TB006 1000 mg qw | Part 1: Change From Baseline in Chemistry Parameters: Calcium, Cholesterol, Creatinine, Direct Bilirubin, Glucose, HDL (High Density Lipoprotein) Cholesterol, LDL (Low Density Lipoprotein) Cholesterol, Total Bilirubin, Triglycerides and Urea Nitrogen | Cholesterol | 6.2 milligrams per deciliter | Standard Deviation 74.37 |
| Part 1: TB006 1000 mg qw | Part 1: Change From Baseline in Chemistry Parameters: Calcium, Cholesterol, Creatinine, Direct Bilirubin, Glucose, HDL (High Density Lipoprotein) Cholesterol, LDL (Low Density Lipoprotein) Cholesterol, Total Bilirubin, Triglycerides and Urea Nitrogen | Creatinine | 0.108 milligrams per deciliter | Standard Deviation 0.143 |
| Part 1: TB006 1000 mg qw | Part 1: Change From Baseline in Chemistry Parameters: Calcium, Cholesterol, Creatinine, Direct Bilirubin, Glucose, HDL (High Density Lipoprotein) Cholesterol, LDL (Low Density Lipoprotein) Cholesterol, Total Bilirubin, Triglycerides and Urea Nitrogen | Direct Bilirubin | 0.000 milligrams per deciliter | Standard Deviation 0.02 |
| Part 1: TB006 1000 mg qw | Part 1: Change From Baseline in Chemistry Parameters: Calcium, Cholesterol, Creatinine, Direct Bilirubin, Glucose, HDL (High Density Lipoprotein) Cholesterol, LDL (Low Density Lipoprotein) Cholesterol, Total Bilirubin, Triglycerides and Urea Nitrogen | HDL Cholesterol | 0.2 milligrams per deciliter | Standard Deviation 13.98 |
| Part 1: TB006 1000 mg qw | Part 1: Change From Baseline in Chemistry Parameters: Calcium, Cholesterol, Creatinine, Direct Bilirubin, Glucose, HDL (High Density Lipoprotein) Cholesterol, LDL (Low Density Lipoprotein) Cholesterol, Total Bilirubin, Triglycerides and Urea Nitrogen | LDL Cholesterol | -3.5 milligrams per deciliter | Standard Deviation 64.62 |
| Part 1: TB006 1000 mg qw | Part 1: Change From Baseline in Chemistry Parameters: Calcium, Cholesterol, Creatinine, Direct Bilirubin, Glucose, HDL (High Density Lipoprotein) Cholesterol, LDL (Low Density Lipoprotein) Cholesterol, Total Bilirubin, Triglycerides and Urea Nitrogen | Total Bilirubin | 0.032 milligrams per deciliter | Standard Deviation 0.132 |
| Part 1: TB006 1000 mg qw | Part 1: Change From Baseline in Chemistry Parameters: Calcium, Cholesterol, Creatinine, Direct Bilirubin, Glucose, HDL (High Density Lipoprotein) Cholesterol, LDL (Low Density Lipoprotein) Cholesterol, Total Bilirubin, Triglycerides and Urea Nitrogen | Triglycerides | 18.7 milligrams per deciliter | Standard Deviation 104.95 |
| Part 1: TB006 1000 mg qw | Part 1: Change From Baseline in Chemistry Parameters: Calcium, Cholesterol, Creatinine, Direct Bilirubin, Glucose, HDL (High Density Lipoprotein) Cholesterol, LDL (Low Density Lipoprotein) Cholesterol, Total Bilirubin, Triglycerides and Urea Nitrogen | Urea Nitrogen | 2.43 milligrams per deciliter | Standard Deviation 3.449 |
| Part 1: Placebo | Part 1: Change From Baseline in Chemistry Parameters: Calcium, Cholesterol, Creatinine, Direct Bilirubin, Glucose, HDL (High Density Lipoprotein) Cholesterol, LDL (Low Density Lipoprotein) Cholesterol, Total Bilirubin, Triglycerides and Urea Nitrogen | Cholesterol | -13.4 milligrams per deciliter | Standard Deviation 47.79 |
| Part 1: Placebo | Part 1: Change From Baseline in Chemistry Parameters: Calcium, Cholesterol, Creatinine, Direct Bilirubin, Glucose, HDL (High Density Lipoprotein) Cholesterol, LDL (Low Density Lipoprotein) Cholesterol, Total Bilirubin, Triglycerides and Urea Nitrogen | Total Bilirubin | -0.134 milligrams per deciliter | Standard Deviation 0.225 |
| Part 1: Placebo | Part 1: Change From Baseline in Chemistry Parameters: Calcium, Cholesterol, Creatinine, Direct Bilirubin, Glucose, HDL (High Density Lipoprotein) Cholesterol, LDL (Low Density Lipoprotein) Cholesterol, Total Bilirubin, Triglycerides and Urea Nitrogen | Direct Bilirubin | -0.022 milligrams per deciliter | Standard Deviation 0.03 |
| Part 1: Placebo | Part 1: Change From Baseline in Chemistry Parameters: Calcium, Cholesterol, Creatinine, Direct Bilirubin, Glucose, HDL (High Density Lipoprotein) Cholesterol, LDL (Low Density Lipoprotein) Cholesterol, Total Bilirubin, Triglycerides and Urea Nitrogen | Creatinine | -0.040 milligrams per deciliter | Standard Deviation 0.142 |
| Part 1: Placebo | Part 1: Change From Baseline in Chemistry Parameters: Calcium, Cholesterol, Creatinine, Direct Bilirubin, Glucose, HDL (High Density Lipoprotein) Cholesterol, LDL (Low Density Lipoprotein) Cholesterol, Total Bilirubin, Triglycerides and Urea Nitrogen | Urea Nitrogen | 1.30 milligrams per deciliter | Standard Deviation 4.266 |
| Part 1: Placebo | Part 1: Change From Baseline in Chemistry Parameters: Calcium, Cholesterol, Creatinine, Direct Bilirubin, Glucose, HDL (High Density Lipoprotein) Cholesterol, LDL (Low Density Lipoprotein) Cholesterol, Total Bilirubin, Triglycerides and Urea Nitrogen | Triglycerides | -23.8 milligrams per deciliter | Standard Deviation 39.06 |
| Part 1: Placebo | Part 1: Change From Baseline in Chemistry Parameters: Calcium, Cholesterol, Creatinine, Direct Bilirubin, Glucose, HDL (High Density Lipoprotein) Cholesterol, LDL (Low Density Lipoprotein) Cholesterol, Total Bilirubin, Triglycerides and Urea Nitrogen | Calcium | -0.18 milligrams per deciliter | Standard Deviation 0.356 |
| Part 1: Placebo | Part 1: Change From Baseline in Chemistry Parameters: Calcium, Cholesterol, Creatinine, Direct Bilirubin, Glucose, HDL (High Density Lipoprotein) Cholesterol, LDL (Low Density Lipoprotein) Cholesterol, Total Bilirubin, Triglycerides and Urea Nitrogen | LDL Cholesterol | -14.8 milligrams per deciliter | Standard Deviation 46.23 |
| Part 1: Placebo | Part 1: Change From Baseline in Chemistry Parameters: Calcium, Cholesterol, Creatinine, Direct Bilirubin, Glucose, HDL (High Density Lipoprotein) Cholesterol, LDL (Low Density Lipoprotein) Cholesterol, Total Bilirubin, Triglycerides and Urea Nitrogen | HDL Cholesterol | 4.0 milligrams per deciliter | Standard Deviation 17.13 |
| Part 1: Placebo | Part 1: Change From Baseline in Chemistry Parameters: Calcium, Cholesterol, Creatinine, Direct Bilirubin, Glucose, HDL (High Density Lipoprotein) Cholesterol, LDL (Low Density Lipoprotein) Cholesterol, Total Bilirubin, Triglycerides and Urea Nitrogen | Glucose | 8.2 milligrams per deciliter | Standard Deviation 49.94 |
Primary
Part 1: Change From Baseline in Clinical Chemistry Parameter: Hemoglobin A1C
Blood samples were collected for analysis of following clinical chemistry parameters including Hemoglobin A1C. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value.
Time frame: Baseline and up to Day 104
Population: Safety Analysis Set. Only those participants with data available at specified time points has been presented.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 1: Change From Baseline in Clinical Chemistry Parameter: Hemoglobin A1C | 0.06 percentage of glycosylated hemoglobin | Standard Deviation 0.162 |
| Part 1: TB006 420 mg qw | Part 1: Change From Baseline in Clinical Chemistry Parameter: Hemoglobin A1C | -0.02 percentage of glycosylated hemoglobin | Standard Deviation 0.567 |
| Part 1: TB006 1000 mg qw | Part 1: Change From Baseline in Clinical Chemistry Parameter: Hemoglobin A1C | -0.33 percentage of glycosylated hemoglobin | Standard Deviation 0.625 |
| Part 1: Placebo | Part 1: Change From Baseline in Clinical Chemistry Parameter: Hemoglobin A1C | -0.14 percentage of glycosylated hemoglobin | Standard Deviation 1.011 |
Primary
Part 1: Change From Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST) and Creatine Kinase (CK)
Blood samples were collected for analysis of following clinical chemistry parameters including ALT, ALP, AST and CK. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value.
Time frame: Baseline and up to Day 104
Population: Safety Analysis Set. Only those participants with data available at specified time points has been presented.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 1: Change From Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST) and Creatine Kinase (CK) | ALT | -1.7 International Units per Liter | Standard Deviation 2.21 |
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 1: Change From Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST) and Creatine Kinase (CK) | ALP | -0.6 International Units per Liter | Standard Deviation 9.11 |
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 1: Change From Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST) and Creatine Kinase (CK) | AST | -0.1 International Units per Liter | Standard Deviation 2.27 |
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 1: Change From Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST) and Creatine Kinase (CK) | CK | 22.0 International Units per Liter | Standard Deviation 39.27 |
| Part 1: TB006 420 mg qw | Part 1: Change From Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST) and Creatine Kinase (CK) | ALP | -4.0 International Units per Liter | Standard Deviation 5.59 |
| Part 1: TB006 420 mg qw | Part 1: Change From Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST) and Creatine Kinase (CK) | AST | -3.8 International Units per Liter | Standard Deviation 5.23 |
| Part 1: TB006 420 mg qw | Part 1: Change From Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST) and Creatine Kinase (CK) | CK | 0.5 International Units per Liter | Standard Deviation 44.37 |
| Part 1: TB006 420 mg qw | Part 1: Change From Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST) and Creatine Kinase (CK) | ALT | -5.5 International Units per Liter | Standard Deviation 5.32 |
| Part 1: TB006 1000 mg qw | Part 1: Change From Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST) and Creatine Kinase (CK) | AST | -1.3 International Units per Liter | Standard Deviation 7.61 |
| Part 1: TB006 1000 mg qw | Part 1: Change From Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST) and Creatine Kinase (CK) | ALP | -2.2 International Units per Liter | Standard Deviation 10.05 |
| Part 1: TB006 1000 mg qw | Part 1: Change From Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST) and Creatine Kinase (CK) | CK | 0.3 International Units per Liter | Standard Deviation 65.56 |
| Part 1: TB006 1000 mg qw | Part 1: Change From Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST) and Creatine Kinase (CK) | ALT | -0.7 International Units per Liter | Standard Deviation 10.33 |
| Part 1: Placebo | Part 1: Change From Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST) and Creatine Kinase (CK) | CK | -10.4 International Units per Liter | Standard Deviation 14.03 |
| Part 1: Placebo | Part 1: Change From Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST) and Creatine Kinase (CK) | ALP | 9.0 International Units per Liter | Standard Deviation 15.98 |
| Part 1: Placebo | Part 1: Change From Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST) and Creatine Kinase (CK) | ALT | 5.4 International Units per Liter | Standard Deviation 14.79 |
| Part 1: Placebo | Part 1: Change From Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST) and Creatine Kinase (CK) | AST | 3.2 International Units per Liter | Standard Deviation 13.65 |
Primary
Part 1: Change From Baseline in Clinical Chemistry Parameters: Albumin and Protein
Blood samples were collected for analysis of following clinical chemistry parameters including albumin and protein. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value.
Time frame: Baseline and up to Day 104
Population: Safety Analysis Set. Only those participants with data available at specified time points has been presented.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 1: Change From Baseline in Clinical Chemistry Parameters: Albumin and Protein | Albumin | -0.14 grams per deciliter | Standard Deviation 0.199 |
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 1: Change From Baseline in Clinical Chemistry Parameters: Albumin and Protein | Protein | -0.20 grams per deciliter | Standard Deviation 0.316 |
| Part 1: TB006 420 mg qw | Part 1: Change From Baseline in Clinical Chemistry Parameters: Albumin and Protein | Protein | 0.12 grams per deciliter | Standard Deviation 0.183 |
| Part 1: TB006 420 mg qw | Part 1: Change From Baseline in Clinical Chemistry Parameters: Albumin and Protein | Albumin | 0.02 grams per deciliter | Standard Deviation 0.098 |
| Part 1: TB006 1000 mg qw | Part 1: Change From Baseline in Clinical Chemistry Parameters: Albumin and Protein | Albumin | -0.03 grams per deciliter | Standard Deviation 0.367 |
| Part 1: TB006 1000 mg qw | Part 1: Change From Baseline in Clinical Chemistry Parameters: Albumin and Protein | Protein | -0.05 grams per deciliter | Standard Deviation 0.589 |
| Part 1: Placebo | Part 1: Change From Baseline in Clinical Chemistry Parameters: Albumin and Protein | Albumin | -0.04 grams per deciliter | Standard Deviation 0.167 |
| Part 1: Placebo | Part 1: Change From Baseline in Clinical Chemistry Parameters: Albumin and Protein | Protein | -0.08 grams per deciliter | Standard Deviation 0.363 |
Primary
Part 1: Change From Baseline in Clinical Chemistry Parameters: Potassium and Sodium
Blood samples were collected for analysis of following clinical chemistry parameters including Potassium and Sodium. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value.
Time frame: Baseline and up to Day 104
Population: Safety Analysis Set. Only those participants with data available at specified time points has been presented.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 1: Change From Baseline in Clinical Chemistry Parameters: Potassium and Sodium | Potassium | 0.10 Millimoles per liter | Standard Deviation 0.476 |
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 1: Change From Baseline in Clinical Chemistry Parameters: Potassium and Sodium | Sodium | -1.0 Millimoles per liter | Standard Deviation 2.24 |
| Part 1: TB006 420 mg qw | Part 1: Change From Baseline in Clinical Chemistry Parameters: Potassium and Sodium | Sodium | 0.8 Millimoles per liter | Standard Deviation 1.72 |
| Part 1: TB006 420 mg qw | Part 1: Change From Baseline in Clinical Chemistry Parameters: Potassium and Sodium | Potassium | -0.15 Millimoles per liter | Standard Deviation 0.288 |
| Part 1: TB006 1000 mg qw | Part 1: Change From Baseline in Clinical Chemistry Parameters: Potassium and Sodium | Potassium | 0.07 Millimoles per liter | Standard Deviation 0.378 |
| Part 1: TB006 1000 mg qw | Part 1: Change From Baseline in Clinical Chemistry Parameters: Potassium and Sodium | Sodium | -1.2 Millimoles per liter | Standard Deviation 2.56 |
| Part 1: Placebo | Part 1: Change From Baseline in Clinical Chemistry Parameters: Potassium and Sodium | Potassium | 0.02 Millimoles per liter | Standard Deviation 0.259 |
| Part 1: Placebo | Part 1: Change From Baseline in Clinical Chemistry Parameters: Potassium and Sodium | Sodium | -1.2 Millimoles per liter | Standard Deviation 2.39 |
Primary
Part 1: Change From Baseline in Clinical Chemistry Parameter: Thyrotropin
Blood samples were collected for analysis of following clinical chemistry parameters including Thyrotropin. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value.
Time frame: Baseline and up to Day 104
Population: Safety Analysis Set. Only those participants with data available at specified time points has been presented.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 1: Change From Baseline in Clinical Chemistry Parameter: Thyrotropin | 1.209 micro-international units per milliliter | Standard Deviation 3.114 |
| Part 1: TB006 420 mg qw | Part 1: Change From Baseline in Clinical Chemistry Parameter: Thyrotropin | -0.343 micro-international units per milliliter | Standard Deviation 0.298 |
| Part 1: TB006 1000 mg qw | Part 1: Change From Baseline in Clinical Chemistry Parameter: Thyrotropin | -0.370 micro-international units per milliliter | Standard Deviation 1.312 |
| Part 1: Placebo | Part 1: Change From Baseline in Clinical Chemistry Parameter: Thyrotropin | -0.246 micro-international units per milliliter | Standard Deviation 0.372 |
Primary
Part 1: Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
Vital signs including DBP and SBP was measured by at least 5 minutes of rest with the participant in a quiet setting without distractions (eg, television, cell phones). Blood pressure measurements were taken with the participant in the sitting position. Baseline was defined as the last available value prior to the participant receiving the first study drug infusion on Day 1. Change from Baseline was obtained by subtracting the Baseline value from post-dose visit value.
Time frame: Baseline and Up to Day 104
Population: Safety Analysis Set. Only those participants with data available at specified time points has been presented.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 1: Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | SBP | -10.4 Millimeters of mercury | Standard Deviation 13.39 |
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 1: Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | DBP | -2.1 Millimeters of mercury | Standard Deviation 12.06 |
| Part 1: TB006 420 mg qw | Part 1: Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | DBP | -2.3 Millimeters of mercury | Standard Deviation 10.37 |
| Part 1: TB006 420 mg qw | Part 1: Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | SBP | 3.5 Millimeters of mercury | Standard Deviation 9.61 |
| Part 1: TB006 1000 mg qw | Part 1: Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | DBP | -1.0 Millimeters of mercury | Standard Deviation 3.03 |
| Part 1: TB006 1000 mg qw | Part 1: Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | SBP | -6.2 Millimeters of mercury | Standard Deviation 13.17 |
| Part 1: Placebo | Part 1: Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | SBP | 2.2 Millimeters of mercury | Standard Deviation 17.74 |
| Part 1: Placebo | Part 1: Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | DBP | -7.2 Millimeters of mercury | Standard Deviation 9.09 |
Primary
Part 1: Change From Baseline in ECG Parameters
12-lead ECG measurements was obtained using an ECG machine that automatically calculates the PR interval, QRS duration, QT interval and QT Corrected using Bazett's formula (QTcB). Baseline was defined as the last available value prior to the participant receiving the first study drug infusion on Day 1. Change from Baseline was obtained by subtracting the Baseline value from post-dose visit value.
Time frame: Baseline and Up to Day 104
Population: Safety Analysis Set. Only those participants with data available at specified time points has been presented.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 1: Change From Baseline in ECG Parameters | QRS Duration | 0.3 milliseconds | Standard Deviation 3.07 |
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 1: Change From Baseline in ECG Parameters | QTcB Interval | 8.1 milliseconds | Standard Deviation 11.37 |
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 1: Change From Baseline in ECG Parameters | QT Interval | 21.9 milliseconds | Standard Deviation 12.72 |
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 1: Change From Baseline in ECG Parameters | PR Interval | 4.8 milliseconds | Standard Deviation 10.07 |
| Part 1: TB006 420 mg qw | Part 1: Change From Baseline in ECG Parameters | PR Interval | 0.7 milliseconds | Standard Deviation 5.9 |
| Part 1: TB006 420 mg qw | Part 1: Change From Baseline in ECG Parameters | QRS Duration | 1.1 milliseconds | Standard Deviation 5.27 |
| Part 1: TB006 420 mg qw | Part 1: Change From Baseline in ECG Parameters | QTcB Interval | -6.6 milliseconds | Standard Deviation 12.98 |
| Part 1: TB006 420 mg qw | Part 1: Change From Baseline in ECG Parameters | QT Interval | -2.9 milliseconds | Standard Deviation 10.48 |
| Part 1: TB006 1000 mg qw | Part 1: Change From Baseline in ECG Parameters | QT Interval | 0.3 milliseconds | Standard Deviation 9.36 |
| Part 1: TB006 1000 mg qw | Part 1: Change From Baseline in ECG Parameters | PR Interval | -11.0 milliseconds | Standard Deviation 14.74 |
| Part 1: TB006 1000 mg qw | Part 1: Change From Baseline in ECG Parameters | QTcB Interval | 9.9 milliseconds | Standard Deviation 11.5 |
| Part 1: TB006 1000 mg qw | Part 1: Change From Baseline in ECG Parameters | QRS Duration | 1.0 milliseconds | Standard Deviation 7.16 |
| Part 1: Placebo | Part 1: Change From Baseline in ECG Parameters | QTcB Interval | -15.2 milliseconds | Standard Deviation 4.15 |
| Part 1: Placebo | Part 1: Change From Baseline in ECG Parameters | PR Interval | 14.9 milliseconds | Standard Deviation 5.16 |
| Part 1: Placebo | Part 1: Change From Baseline in ECG Parameters | QRS Duration | -4.1 milliseconds | Standard Deviation 13.5 |
| Part 1: Placebo | Part 1: Change From Baseline in ECG Parameters | QT Interval | -5.0 milliseconds | Standard Deviation 11.47 |
Primary
Part 1: Change From Baseline in Electrocardiogram (ECG) Mean Heart Rate
12-lead ECG measurements was obtained using an ECG machine that automatically calculates the heart rate. Baseline was defined as the last available value prior to the participant receiving the first study drug infusion on Day 1. Change from Baseline was obtained by subtracting the Baseline value from post-dose visit value value.
Time frame: Baseline and Up to Day 104
Population: Safety Analysis Set. Only those participants with data available at specified time points has been presented.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 1: Change From Baseline in Electrocardiogram (ECG) Mean Heart Rate | -4.8 Beats per minute | Standard Deviation 5.78 |
| Part 1: TB006 420 mg qw | Part 1: Change From Baseline in Electrocardiogram (ECG) Mean Heart Rate | -0.9 Beats per minute | Standard Deviation 4 |
| Part 1: TB006 1000 mg qw | Part 1: Change From Baseline in Electrocardiogram (ECG) Mean Heart Rate | 3.0 Beats per minute | Standard Deviation 3.82 |
| Part 1: Placebo | Part 1: Change From Baseline in Electrocardiogram (ECG) Mean Heart Rate | -3.4 Beats per minute | Standard Deviation 4.87 |
Primary
Part 1: Change From Baseline in Heart Rate
Vital signs including heart rate was measured by at least 5 minutes of rest with the participant in a quiet setting without distractions (eg, television, cell phones). Baseline was defined as the last available value prior to the participant receiving the first study drug infusion on Day 1. Change from Baseline was obtained by subtracting the Baseline value from post-dose visit value.
Time frame: Baseline and Up to Day 104
Population: Safety Analysis Set. Only those participants with data available at specified time points has been presented.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 1: Change From Baseline in Heart Rate | -2.0 Beats per minute | Standard Deviation 8 |
| Part 1: TB006 420 mg qw | Part 1: Change From Baseline in Heart Rate | 3.3 Beats per minute | Standard Deviation 3.72 |
| Part 1: TB006 1000 mg qw | Part 1: Change From Baseline in Heart Rate | 4.0 Beats per minute | Standard Deviation 5.73 |
| Part 1: Placebo | Part 1: Change From Baseline in Heart Rate | -4.2 Beats per minute | Standard Deviation 9.5 |
Primary
Part 1: Change From Baseline in Hematology Parameter: Erythrocyte. Mean Corpuscular Hemoglobin (Ery. MCH)
Blood samples were collected for analysis of following hematology parameter: Ery. MCH. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value.
Time frame: Baseline and up to Day 104
Population: Safety Analysis Set. Only those participants with data available at specified time points has been presented.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 1: Change From Baseline in Hematology Parameter: Erythrocyte. Mean Corpuscular Hemoglobin (Ery. MCH) | -0.40 picograms | Standard Deviation 1.134 |
| Part 1: TB006 420 mg qw | Part 1: Change From Baseline in Hematology Parameter: Erythrocyte. Mean Corpuscular Hemoglobin (Ery. MCH) | -0.05 picograms | Standard Deviation 0.579 |
| Part 1: TB006 1000 mg qw | Part 1: Change From Baseline in Hematology Parameter: Erythrocyte. Mean Corpuscular Hemoglobin (Ery. MCH) | 1.02 picograms | Standard Deviation 3.511 |
| Part 1: Placebo | Part 1: Change From Baseline in Hematology Parameter: Erythrocyte. Mean Corpuscular Hemoglobin (Ery. MCH) | -0.34 picograms | Standard Deviation 0.631 |
Primary
Part 1: Change From Baseline in Hematology Parameter: Erythrocyte. Mean Corpuscular Volume (Ery. MCV)
Blood samples were collected for analysis of following hematology parameter: Ery. MCV. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value.
Time frame: Baseline and up to Day 104
Population: Safety Analysis Set. Only those participants with data available at specified time points has been presented.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 1: Change From Baseline in Hematology Parameter: Erythrocyte. Mean Corpuscular Volume (Ery. MCV) | 0.80 femtoliters | Standard Deviation 1.926 |
| Part 1: TB006 420 mg qw | Part 1: Change From Baseline in Hematology Parameter: Erythrocyte. Mean Corpuscular Volume (Ery. MCV) | 2.45 femtoliters | Standard Deviation 1.343 |
| Part 1: TB006 1000 mg qw | Part 1: Change From Baseline in Hematology Parameter: Erythrocyte. Mean Corpuscular Volume (Ery. MCV) | 5.42 femtoliters | Standard Deviation 5.724 |
| Part 1: Placebo | Part 1: Change From Baseline in Hematology Parameter: Erythrocyte. Mean Corpuscular Volume (Ery. MCV) | 0.20 femtoliters | Standard Deviation 2.699 |
Primary
Part 1: Change From Baseline in Hematology Parameter: Erythrocytes and Reticulocytes
Blood samples were collected for analysis of following hematology parameter: Erythrocytes and Reticulocytes. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value.
Time frame: Baseline and up to Day 104
Population: Safety Analysis Set. Only those participants with data available at specified time points has been presented.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 1: Change From Baseline in Hematology Parameter: Erythrocytes and Reticulocytes | Erythrocytes | 0.039 10^6 cells per microliter | Standard Deviation 0.401 |
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 1: Change From Baseline in Hematology Parameter: Erythrocytes and Reticulocytes | Reticulocytes | -0.011 10^6 cells per microliter | Standard Deviation 0.017 |
| Part 1: TB006 420 mg qw | Part 1: Change From Baseline in Hematology Parameter: Erythrocytes and Reticulocytes | Reticulocytes | -0.005 10^6 cells per microliter | Standard Deviation 0.004 |
| Part 1: TB006 420 mg qw | Part 1: Change From Baseline in Hematology Parameter: Erythrocytes and Reticulocytes | Erythrocytes | 0.012 10^6 cells per microliter | Standard Deviation 0.219 |
| Part 1: TB006 1000 mg qw | Part 1: Change From Baseline in Hematology Parameter: Erythrocytes and Reticulocytes | Erythrocytes | -0.108 10^6 cells per microliter | Standard Deviation 0.625 |
| Part 1: TB006 1000 mg qw | Part 1: Change From Baseline in Hematology Parameter: Erythrocytes and Reticulocytes | Reticulocytes | -0.008 10^6 cells per microliter | Standard Deviation 0.008 |
| Part 1: Placebo | Part 1: Change From Baseline in Hematology Parameter: Erythrocytes and Reticulocytes | Erythrocytes | 0.024 10^6 cells per microliter | Standard Deviation 0.211 |
| Part 1: Placebo | Part 1: Change From Baseline in Hematology Parameter: Erythrocytes and Reticulocytes | Reticulocytes | -0.005 10^6 cells per microliter | Standard Deviation 0.009 |
Primary
Part 1: Change From Baseline in Hematology Parameter: Hematocrit
Blood samples were collected for analysis of following hematology parameter: Hematocrit. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value.
Time frame: Baseline and up to Day 104
Population: Safety Analysis Set. Only those participants with data available at specified time points has been presented.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 1: Change From Baseline in Hematology Parameter: Hematocrit | 0.69 Percentage | Standard Deviation 2.563 |
| Part 1: TB006 420 mg qw | Part 1: Change From Baseline in Hematology Parameter: Hematocrit | 1.18 Percentage | Standard Deviation 2.105 |
| Part 1: TB006 1000 mg qw | Part 1: Change From Baseline in Hematology Parameter: Hematocrit | 1.18 Percentage | Standard Deviation 7.919 |
| Part 1: Placebo | Part 1: Change From Baseline in Hematology Parameter: Hematocrit | 0.32 Percentage | Standard Deviation 2.493 |
Primary
Part 1: Change From Baseline in Hematology Parameter: Hemoglobin
Blood samples were collected for analysis of following hematology parameter: Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value.
Time frame: Baseline and up to Day 104
Population: Safety Analysis Set. Only those participants with data available at specified time points has been presented.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 1: Change From Baseline in Hematology Parameter: Hemoglobin | -0.06 grams per deciliter | Standard Deviation 0.779 |
| Part 1: TB006 420 mg qw | Part 1: Change From Baseline in Hematology Parameter: Hemoglobin | 0.00 grams per deciliter | Standard Deviation 0.465 |
| Part 1: TB006 1000 mg qw | Part 1: Change From Baseline in Hematology Parameter: Hemoglobin | 0.08 grams per deciliter | Standard Deviation 3.26 |
| Part 1: Placebo | Part 1: Change From Baseline in Hematology Parameter: Hemoglobin | -0.10 grams per deciliter | Standard Deviation 0.877 |
Primary
Part 1: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Platelets
Blood samples were collected for analysis of following hematology parameters including Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Platelets. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value.
Time frame: Baseline and up to Day 104
Population: Safety Analysis Set. Only those participants with data available at specified time points has been presented.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 1: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Platelets | Lymphocytes | -0.264 10^3 cells per microliter | Standard Deviation 0.188 |
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 1: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Platelets | Neutrophils | -0.396 10^3 cells per microliter | Standard Deviation 0.719 |
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 1: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Platelets | Monocytes | -0.094 10^3 cells per microliter | Standard Deviation 0.118 |
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 1: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Platelets | Basophils | -0.023 10^3 cells per microliter | Standard Deviation 0.015 |
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 1: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Platelets | Platelets | -9.1 10^3 cells per microliter | Standard Deviation 37.53 |
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 1: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Platelets | Eosinophils | 0.014 10^3 cells per microliter | Standard Deviation 0.138 |
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 1: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Platelets | Leukocytes | -0.76 10^3 cells per microliter | Standard Deviation 0.65 |
| Part 1: TB006 420 mg qw | Part 1: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Platelets | Platelets | 5.0 10^3 cells per microliter | Standard Deviation 37.25 |
| Part 1: TB006 420 mg qw | Part 1: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Platelets | Eosinophils | 0.003 10^3 cells per microliter | Standard Deviation 0.068 |
| Part 1: TB006 420 mg qw | Part 1: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Platelets | Leukocytes | 0.00 10^3 cells per microliter | Standard Deviation 1.292 |
| Part 1: TB006 420 mg qw | Part 1: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Platelets | Monocytes | -0.017 10^3 cells per microliter | Standard Deviation 0.114 |
| Part 1: TB006 420 mg qw | Part 1: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Platelets | Neutrophils | 0.078 10^3 cells per microliter | Standard Deviation 1.171 |
| Part 1: TB006 420 mg qw | Part 1: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Platelets | Basophils | -0.005 10^3 cells per microliter | Standard Deviation 0.019 |
| Part 1: TB006 420 mg qw | Part 1: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Platelets | Lymphocytes | -0.025 10^3 cells per microliter | Standard Deviation 0.241 |
| Part 1: TB006 1000 mg qw | Part 1: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Platelets | Basophils | 0.005 10^3 cells per microliter | Standard Deviation 0.028 |
| Part 1: TB006 1000 mg qw | Part 1: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Platelets | Eosinophils | 0.038 10^3 cells per microliter | Standard Deviation 0.089 |
| Part 1: TB006 1000 mg qw | Part 1: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Platelets | Leukocytes | 0.40 10^3 cells per microliter | Standard Deviation 1.563 |
| Part 1: TB006 1000 mg qw | Part 1: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Platelets | Lymphocytes | -0.037 10^3 cells per microliter | Standard Deviation 1.265 |
| Part 1: TB006 1000 mg qw | Part 1: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Platelets | Monocytes | 0.032 10^3 cells per microliter | Standard Deviation 0.108 |
| Part 1: TB006 1000 mg qw | Part 1: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Platelets | Neutrophils | 0.368 10^3 cells per microliter | Standard Deviation 0.641 |
| Part 1: TB006 1000 mg qw | Part 1: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Platelets | Platelets | -9.6 10^3 cells per microliter | Standard Deviation 89.83 |
| Part 1: Placebo | Part 1: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Platelets | Eosinophils | 0.030 10^3 cells per microliter | Standard Deviation 0.173 |
| Part 1: Placebo | Part 1: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Platelets | Platelets | -4.5 10^3 cells per microliter | Standard Deviation 50.16 |
| Part 1: Placebo | Part 1: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Platelets | Neutrophils | -0.318 10^3 cells per microliter | Standard Deviation 1.145 |
| Part 1: Placebo | Part 1: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Platelets | Basophils | 0.006 10^3 cells per microliter | Standard Deviation 0.013 |
| Part 1: Placebo | Part 1: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Platelets | Leukocytes | -0.28 10^3 cells per microliter | Standard Deviation 1.092 |
| Part 1: Placebo | Part 1: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Platelets | Monocytes | 0.028 10^3 cells per microliter | Standard Deviation 0.062 |
| Part 1: Placebo | Part 1: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Platelets | Lymphocytes | -0.036 10^3 cells per microliter | Standard Deviation 0.25 |
Primary
Part 1: Change From Baseline in Respiratory Rate
Vital signs including respiratory rate was measured by at least 5 minutes of rest with the participant in a quiet setting without distractions (eg, television, cell phones). Baseline was defined as the last available value prior to the participant receiving the first study drug infusion on Day 1. Change from Baseline was obtained by subtracting the Baseline value from post-dose visit value.
Time frame: Baseline and Up to Day 104
Population: Safety Analysis Set. Only those participants with data available at specified time points has been presented.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 1: Change From Baseline in Respiratory Rate | 0.0 breaths per minute | Standard Deviation 0 |
| Part 1: TB006 420 mg qw | Part 1: Change From Baseline in Respiratory Rate | -0.7 breaths per minute | Standard Deviation 2.16 |
| Part 1: TB006 1000 mg qw | Part 1: Change From Baseline in Respiratory Rate | 0.3 breaths per minute | Standard Deviation 1.03 |
| Part 1: Placebo | Part 1: Change From Baseline in Respiratory Rate | -0.2 breaths per minute | Standard Deviation 1.3 |
Primary
Part 1: Change From Baseline in Temperature
Vital signs including temperature was measured by at least 5 minutes of rest with the participant in a quiet setting without distractions (eg, television, cell phones). Baseline was defined as the last available value prior to the participant receiving the first study drug infusion on Day 1. Change from Baseline was obtained by subtracting the Baseline value from post-dose visit value.
Time frame: Baseline and Up to Day 104
Population: Safety Analysis Set. Only those participants with data available at specified time points has been presented.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 1: Change From Baseline in Temperature | 0.26 degrees Celsius | Standard Deviation 0.351 |
| Part 1: TB006 420 mg qw | Part 1: Change From Baseline in Temperature | -0.37 degrees Celsius | Standard Deviation 0.35 |
| Part 1: TB006 1000 mg qw | Part 1: Change From Baseline in Temperature | -0.03 degrees Celsius | Standard Deviation 0.833 |
| Part 1: Placebo | Part 1: Change From Baseline in Temperature | -0.22 degrees Celsius | Standard Deviation 0.13 |
Primary
Part 1: Change From Baseline in Urine Potential of Hydrogen (pH)
Urine samples were collected for analysis of Urine pH. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value.
Time frame: Baseline and up to Day 104
Population: Safety Analysis Set. Only those participants with data available at specified time points has been presented.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 1: Change From Baseline in Urine Potential of Hydrogen (pH) | -0.36 potential of Hydrogen | Standard Deviation 1.215 |
| Part 1: TB006 420 mg qw | Part 1: Change From Baseline in Urine Potential of Hydrogen (pH) | 0.40 potential of Hydrogen | Standard Deviation 1.294 |
| Part 1: TB006 1000 mg qw | Part 1: Change From Baseline in Urine Potential of Hydrogen (pH) | -0.50 potential of Hydrogen | Standard Deviation 1.612 |
| Part 1: Placebo | Part 1: Change From Baseline in Urine Potential of Hydrogen (pH) | -0.80 potential of Hydrogen | Standard Deviation 0.975 |
Primary
Part 1: Change From Baseline in Urine Specific Gravity
Urine samples were collected for analysis of Urine specific gravity. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value.
Time frame: Baseline and up to Day 104
Population: Safety Analysis Set. Only those participants with data available at specified time points has been presented.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 1: Change From Baseline in Urine Specific Gravity | 0.003 Ratio | Standard Deviation 0.008 |
| Part 1: TB006 420 mg qw | Part 1: Change From Baseline in Urine Specific Gravity | 0.003 Ratio | Standard Deviation 0.006 |
| Part 1: TB006 1000 mg qw | Part 1: Change From Baseline in Urine Specific Gravity | 0.004 Ratio | Standard Deviation 0.011 |
| Part 1: Placebo | Part 1: Change From Baseline in Urine Specific Gravity | 0.007 Ratio | Standard Deviation 0.01 |
Primary
Part 1: Change From Baseline in Urobilinogen
Urine samples were collected for analysis of Urobilinogen. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value.
Time frame: Baseline and up to Day 104
Population: Safety Analysis Set. Only those participants with data available at specified time points has been presented.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 1: Change From Baseline in Urobilinogen | 0.00 milligrams per deciliter | Standard Deviation 0.462 |
| Part 1: TB006 420 mg qw | Part 1: Change From Baseline in Urobilinogen | -0.16 milligrams per deciliter | Standard Deviation 0.358 |
| Part 1: TB006 1000 mg qw | Part 1: Change From Baseline in Urobilinogen | -0.13 milligrams per deciliter | Standard Deviation 0.602 |
| Part 1: Placebo | Part 1: Change From Baseline in Urobilinogen | 0.00 milligrams per deciliter | Standard Deviation 0 |
Primary
Part 1: Concentration at the End of a Dosing Interval (Ctrough) of TB006
Blood samples were collected at indicated time points for PK analysis of TB006. PK parameters were analyzed using standard non-compartmental analysis.
Time frame: Day 8 and Day 29
Population: Pharmacokinetic Analysis Set. Only those participants with data available at specified timepoints has been presented.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 1: Concentration at the End of a Dosing Interval (Ctrough) of TB006 | Day 8 | 25.77 micrograms per milliliter | Geometric Coefficient of Variation 21.23 |
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 1: Concentration at the End of a Dosing Interval (Ctrough) of TB006 | Day 29 | 76.69 micrograms per milliliter | Geometric Coefficient of Variation 19.62 |
| Part 1: TB006 420 mg qw | Part 1: Concentration at the End of a Dosing Interval (Ctrough) of TB006 | Day 8 | 71.44 micrograms per milliliter | Geometric Coefficient of Variation 20.75 |
| Part 1: TB006 420 mg qw | Part 1: Concentration at the End of a Dosing Interval (Ctrough) of TB006 | Day 29 | 204.77 micrograms per milliliter | Geometric Coefficient of Variation 20.46 |
| Part 1: TB006 1000 mg qw | Part 1: Concentration at the End of a Dosing Interval (Ctrough) of TB006 | Day 8 | 68.62 micrograms per milliliter | Geometric Coefficient of Variation 70.91 |
| Part 1: TB006 1000 mg qw | Part 1: Concentration at the End of a Dosing Interval (Ctrough) of TB006 | Day 29 | 348.20 micrograms per milliliter | Geometric Coefficient of Variation 22.34 |
Primary
Part 1: Dose Normalized Area Under the Concentration Time Curve Over a Dosing Interval (AUCtau) of TB006
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of TB006. PK parameters were analyzed using standard non-compartmental analysis. AUCtau normalized to the actual administered dose is presented. The AUCtau was divided by the actual dose strength to get the normalized area under the concentration-time curve.
Time frame: Day 1 and Day 29
Population: Pharmacokinetic Analysis Set comprises of all participants who received at least 1 dose of TB006 and have at least 1 post-dose blood sample with measurable TB006 concentrations. Only those participants with data available at specified timepoints has been presented.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 1: Dose Normalized Area Under the Concentration Time Curve Over a Dosing Interval (AUCtau) of TB006 | Day 29 | 125.92 hours*micrograms/milliliter/milligram | Geometric Coefficient of Variation 18.01 |
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 1: Dose Normalized Area Under the Concentration Time Curve Over a Dosing Interval (AUCtau) of TB006 | Day 1 | 39.81 hours*micrograms/milliliter/milligram | Geometric Coefficient of Variation 23.17 |
| Part 1: TB006 420 mg qw | Part 1: Dose Normalized Area Under the Concentration Time Curve Over a Dosing Interval (AUCtau) of TB006 | Day 1 | 29.87 hours*micrograms/milliliter/milligram | Geometric Coefficient of Variation 38.15 |
| Part 1: TB006 420 mg qw | Part 1: Dose Normalized Area Under the Concentration Time Curve Over a Dosing Interval (AUCtau) of TB006 | Day 29 | 117.75 hours*micrograms/milliliter/milligram | Geometric Coefficient of Variation 24.52 |
| Part 1: TB006 1000 mg qw | Part 1: Dose Normalized Area Under the Concentration Time Curve Over a Dosing Interval (AUCtau) of TB006 | Day 1 | 11.93 hours*micrograms/milliliter/milligram | Geometric Coefficient of Variation 100.21 |
| Part 1: TB006 1000 mg qw | Part 1: Dose Normalized Area Under the Concentration Time Curve Over a Dosing Interval (AUCtau) of TB006 | Day 29 | 82.95 hours*micrograms/milliliter/milligram | Geometric Coefficient of Variation 18.18 |
Primary
Part 1: Dose Normalized Maximum Observed Plasma Concentration (Cmax) of TB006
Blood samples were collected at indicated time points for PK analysis of TB006. PK parameters were analyzed using standard non-compartmental analysis. Cmax normalized to the actual administered dose is presented. The Cmax was divided by the actual dose strength to get the normalized maximum observed plasma concentration.
Time frame: At Days 1, 8 and 29
Population: Pharmacokinetic Analysis Set. Only those participants with data available at specified timepoints has been presented.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 1: Dose Normalized Maximum Observed Plasma Concentration (Cmax) of TB006 | Day 29 | 0.95 micrograms/milliliter/milligram | Geometric Coefficient of Variation 18.15 |
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 1: Dose Normalized Maximum Observed Plasma Concentration (Cmax) of TB006 | Day 1 | 0.36 micrograms/milliliter/milligram | Geometric Coefficient of Variation 25.72 |
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 1: Dose Normalized Maximum Observed Plasma Concentration (Cmax) of TB006 | Day 8 | 0.58 micrograms/milliliter/milligram | Geometric Coefficient of Variation 27.57 |
| Part 1: TB006 420 mg qw | Part 1: Dose Normalized Maximum Observed Plasma Concentration (Cmax) of TB006 | Day 29 | 0.85 micrograms/milliliter/milligram | Geometric Coefficient of Variation 22.89 |
| Part 1: TB006 420 mg qw | Part 1: Dose Normalized Maximum Observed Plasma Concentration (Cmax) of TB006 | Day 1 | 0.29 micrograms/milliliter/milligram | Geometric Coefficient of Variation 36.97 |
| Part 1: TB006 420 mg qw | Part 1: Dose Normalized Maximum Observed Plasma Concentration (Cmax) of TB006 | Day 8 | 0.49 micrograms/milliliter/milligram | Geometric Coefficient of Variation 26.77 |
| Part 1: TB006 1000 mg qw | Part 1: Dose Normalized Maximum Observed Plasma Concentration (Cmax) of TB006 | Day 29 | 0.61 micrograms/milliliter/milligram | Geometric Coefficient of Variation 13.4 |
| Part 1: TB006 1000 mg qw | Part 1: Dose Normalized Maximum Observed Plasma Concentration (Cmax) of TB006 | Day 8 | 0.30 micrograms/milliliter/milligram | Geometric Coefficient of Variation 30.27 |
| Part 1: TB006 1000 mg qw | Part 1: Dose Normalized Maximum Observed Plasma Concentration (Cmax) of TB006 | Day 1 | 0.07 micrograms/milliliter/milligram | Geometric Coefficient of Variation 105.32 |
Primary
Part 1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
An adverse event is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An 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, associated with liver injury and impaired liver function or any other situations as per medical or scientific judgement.
Time frame: Up to Day 104
Population: Safety Population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any AE | 5 Participants |
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any SAE | 1 Participants |
| Part 1: TB006 420 mg qw | Part 1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any AE | 4 Participants |
| Part 1: TB006 420 mg qw | Part 1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any SAE | 0 Participants |
| Part 1: TB006 1000 mg qw | Part 1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any SAE | 0 Participants |
| Part 1: TB006 1000 mg qw | Part 1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any AE | 1 Participants |
| Part 1: Placebo | Part 1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any SAE | 0 Participants |
| Part 1: Placebo | Part 1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any AE | 2 Participants |
Primary
Part 1: Number of Participants With Anti-TB006 Antibodies (Immunogenicity of TB006)
Plasma samples were collected at indicated time points for the determination of anti-TB006 antibodies. Plasma samples were screened for antibodies binding to TB006 and the titer of confirmed positive samples has been reported.
Time frame: Day 1 (Predose), Day 8 (Predose), Day 36 and Day 104
Population: Safety Analysis Set.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 1: Number of Participants With Anti-TB006 Antibodies (Immunogenicity of TB006) | Day 1 (Predose) | 0 Participants |
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 1: Number of Participants With Anti-TB006 Antibodies (Immunogenicity of TB006) | Day 8 (Predose) | 0 Participants |
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 1: Number of Participants With Anti-TB006 Antibodies (Immunogenicity of TB006) | Day 36 | 0 Participants |
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 1: Number of Participants With Anti-TB006 Antibodies (Immunogenicity of TB006) | Day 104 | 1 Participants |
| Part 1: TB006 420 mg qw | Part 1: Number of Participants With Anti-TB006 Antibodies (Immunogenicity of TB006) | Day 104 | 0 Participants |
| Part 1: TB006 420 mg qw | Part 1: Number of Participants With Anti-TB006 Antibodies (Immunogenicity of TB006) | Day 36 | 0 Participants |
| Part 1: TB006 420 mg qw | Part 1: Number of Participants With Anti-TB006 Antibodies (Immunogenicity of TB006) | Day 8 (Predose) | 0 Participants |
| Part 1: TB006 420 mg qw | Part 1: Number of Participants With Anti-TB006 Antibodies (Immunogenicity of TB006) | Day 1 (Predose) | 0 Participants |
| Part 1: TB006 1000 mg qw | Part 1: Number of Participants With Anti-TB006 Antibodies (Immunogenicity of TB006) | Day 36 | 0 Participants |
| Part 1: TB006 1000 mg qw | Part 1: Number of Participants With Anti-TB006 Antibodies (Immunogenicity of TB006) | Day 104 | 0 Participants |
| Part 1: TB006 1000 mg qw | Part 1: Number of Participants With Anti-TB006 Antibodies (Immunogenicity of TB006) | Day 8 (Predose) | 0 Participants |
| Part 1: TB006 1000 mg qw | Part 1: Number of Participants With Anti-TB006 Antibodies (Immunogenicity of TB006) | Day 1 (Predose) | 0 Participants |
| Part 1: Placebo | Part 1: Number of Participants With Anti-TB006 Antibodies (Immunogenicity of TB006) | Day 8 (Predose) | 0 Participants |
| Part 1: Placebo | Part 1: Number of Participants With Anti-TB006 Antibodies (Immunogenicity of TB006) | Day 1 (Predose) | 0 Participants |
| Part 1: Placebo | Part 1: Number of Participants With Anti-TB006 Antibodies (Immunogenicity of TB006) | Day 104 | 0 Participants |
| Part 1: Placebo | Part 1: Number of Participants With Anti-TB006 Antibodies (Immunogenicity of TB006) | Day 36 | 0 Participants |
Primary
Part 1: Number of Participants With Clinically Significant Neurological Examination Findings
The neurological examination assessed mental status, motor and sensory skills, hearing and speech, vision, coordination, and balance. This analysis was planned but data was not captured in the database. Abnormal changes were captured as adverse events if they were clinically significant.
Time frame: Up to Day 104
Population: Full Analysis Set. This analysis was planned but data was not captured in the database.
Primary
Part 1: Number of Participants With Clinically Significant Physical Examination Findings
A complete physical examination included, at a minimum, assessment of the Cardiovascular, Respiratory, Gastrointestinal and Neurological systems. This analysis was planned but data was not captured in the database. Abnormal changes were captured as adverse events if they were clinically significant.
Time frame: Up to Day 104
Population: Full analysis set comprised of all participants who are randomly assigned to study drug. This analysis was planned but data was not captured in the database.
Primary
Part 1: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS)
The C-SSRS is an interview-based instrument to systematically assess suicidal ideation and suicidal behavior. Number of participants that have an affirmative response to the 5 items for suicidal ideation (1. Wish to be dead, 2. Non-specific active suicidal thoughts, 3. Active suicidal ideation with any methods without intent to act, 4. Active suicidal ideation with some intent to act, without specific plan, 5. Active suicidal ideation with specific plan and intent) and/or to the 5 items for suicidal behavior (1. Preparatory acts or behavior, 2. Aborted attempt, 3. Interrupted attempt, 4. Actual attempt, 5. Completed suicide) were reported. The total score ranges from 0 (no ideation present) to 5 (active suicidal ideation with specific plan and intent); higher scores indicate worse symptoms.
Time frame: Up to Day 104
Population: Safety Analysis Set. Only those participants with data available at specified time points has been presented.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 1: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) | Non-specific active suicidal thoughts | 0 Participants |
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 1: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) | First attempt | 0 Participants |
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 1: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) | Aborted attempt | 0 Participants |
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 1: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) | Preparatory acts or behavior | 0 Participants |
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 1: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) | Most recent attempt | 0 Participants |
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 1: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) | Wish to be dead | 0 Participants |
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 1: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) | Active suicidal ideation with some intent to act, without specific plan | 0 Participants |
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 1: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) | Active suicidal ideation without any methods without intent to act | 0 Participants |
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 1: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) | Active suicidal ideation with specific plan and intent | 0 Participants |
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 1: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) | Any suicidal behavior | 0 Participants |
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 1: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) | Interrupted attempt | 0 Participants |
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 1: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) | Lethal attempt | 0 Participants |
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 1: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) | Actual attempt | 0 Participants |
| Part 1: TB006 420 mg qw | Part 1: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) | Actual attempt | 0 Participants |
| Part 1: TB006 420 mg qw | Part 1: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) | First attempt | 0 Participants |
| Part 1: TB006 420 mg qw | Part 1: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) | Active suicidal ideation with specific plan and intent | 0 Participants |
| Part 1: TB006 420 mg qw | Part 1: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) | Aborted attempt | 0 Participants |
| Part 1: TB006 420 mg qw | Part 1: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) | Most recent attempt | 0 Participants |
| Part 1: TB006 420 mg qw | Part 1: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) | Active suicidal ideation without any methods without intent to act | 0 Participants |
| Part 1: TB006 420 mg qw | Part 1: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) | Preparatory acts or behavior | 0 Participants |
| Part 1: TB006 420 mg qw | Part 1: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) | Non-specific active suicidal thoughts | 0 Participants |
| Part 1: TB006 420 mg qw | Part 1: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) | Lethal attempt | 0 Participants |
| Part 1: TB006 420 mg qw | Part 1: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) | Active suicidal ideation with some intent to act, without specific plan | 0 Participants |
| Part 1: TB006 420 mg qw | Part 1: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) | Interrupted attempt | 0 Participants |
| Part 1: TB006 420 mg qw | Part 1: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) | Wish to be dead | 0 Participants |
| Part 1: TB006 420 mg qw | Part 1: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) | Any suicidal behavior | 0 Participants |
| Part 1: TB006 1000 mg qw | Part 1: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) | Interrupted attempt | 0 Participants |
| Part 1: TB006 1000 mg qw | Part 1: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) | Non-specific active suicidal thoughts | 0 Participants |
| Part 1: TB006 1000 mg qw | Part 1: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) | Actual attempt | 0 Participants |
| Part 1: TB006 1000 mg qw | Part 1: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) | Wish to be dead | 0 Participants |
| Part 1: TB006 1000 mg qw | Part 1: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) | Active suicidal ideation with some intent to act, without specific plan | 0 Participants |
| Part 1: TB006 1000 mg qw | Part 1: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) | Active suicidal ideation with specific plan and intent | 0 Participants |
| Part 1: TB006 1000 mg qw | Part 1: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) | Any suicidal behavior | 0 Participants |
| Part 1: TB006 1000 mg qw | Part 1: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) | Aborted attempt | 0 Participants |
| Part 1: TB006 1000 mg qw | Part 1: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) | Preparatory acts or behavior | 0 Participants |
| Part 1: TB006 1000 mg qw | Part 1: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) | Most recent attempt | 0 Participants |
| Part 1: TB006 1000 mg qw | Part 1: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) | First attempt | 0 Participants |
| Part 1: TB006 1000 mg qw | Part 1: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) | Lethal attempt | 0 Participants |
| Part 1: TB006 1000 mg qw | Part 1: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) | Active suicidal ideation without any methods without intent to act | 0 Participants |
| Part 1: Placebo | Part 1: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) | Actual attempt | 0 Participants |
| Part 1: Placebo | Part 1: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) | Active suicidal ideation with some intent to act, without specific plan | 0 Participants |
| Part 1: Placebo | Part 1: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) | First attempt | 0 Participants |
| Part 1: Placebo | Part 1: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) | Any suicidal behavior | 0 Participants |
| Part 1: Placebo | Part 1: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) | Active suicidal ideation with specific plan and intent | 0 Participants |
| Part 1: Placebo | Part 1: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) | Active suicidal ideation without any methods without intent to act | 0 Participants |
| Part 1: Placebo | Part 1: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) | Lethal attempt | 0 Participants |
| Part 1: Placebo | Part 1: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) | Wish to be dead | 0 Participants |
| Part 1: Placebo | Part 1: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) | Most recent attempt | 0 Participants |
| Part 1: Placebo | Part 1: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) | Preparatory acts or behavior | 0 Participants |
| Part 1: Placebo | Part 1: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) | Aborted attempt | 0 Participants |
| Part 1: Placebo | Part 1: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) | Non-specific active suicidal thoughts | 0 Participants |
| Part 1: Placebo | Part 1: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia Suicide Severity Rating Scale (C-SSRS) | Interrupted attempt | 0 Participants |
Primary
Part 1: Terminal Elimination Phase Half-life (t1/2) of TB006
Blood samples were collected at indicated time points for PK analysis of TB006. PK parameters were analyzed using standard non-compartmental analysis.
Time frame: At Day 29
Population: Pharmacokinetic Analysis Set. Only those participants with data available at specified time points has been presented.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 1: Terminal Elimination Phase Half-life (t1/2) of TB006 | 711.49 hours | Geometric Coefficient of Variation 19.87 |
| Part 1: TB006 420 mg qw | Part 1: Terminal Elimination Phase Half-life (t1/2) of TB006 | 757.59 hours | Geometric Coefficient of Variation 22.8 |
| Part 1: TB006 1000 mg qw | Part 1: Terminal Elimination Phase Half-life (t1/2) of TB006 | 739.50 hours | Geometric Coefficient of Variation 14.9 |
Primary
Part 1: Time at Which Maximum Plasma Concentration Occurs (Tmax) of TB006
Blood samples were collected at indicated time points for PK analysis of TB006. PK parameters were analyzed using standard non-compartmental analysis.
Time frame: At Days 1, 8 and 29
Population: Pharmacokinetic Analysis Set. Only those participants with data available at specified time points has been presented.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 1: Time at Which Maximum Plasma Concentration Occurs (Tmax) of TB006 | Day 29 | 2.03 hours |
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 1: Time at Which Maximum Plasma Concentration Occurs (Tmax) of TB006 | Day 8 | 1.23 hours |
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 1: Time at Which Maximum Plasma Concentration Occurs (Tmax) of TB006 | Day 1 | 1.12 hours |
| Part 1: TB006 420 mg qw | Part 1: Time at Which Maximum Plasma Concentration Occurs (Tmax) of TB006 | Day 29 | 2.18 hours |
| Part 1: TB006 420 mg qw | Part 1: Time at Which Maximum Plasma Concentration Occurs (Tmax) of TB006 | Day 1 | 2.01 hours |
| Part 1: TB006 420 mg qw | Part 1: Time at Which Maximum Plasma Concentration Occurs (Tmax) of TB006 | Day 8 | 1.60 hours |
| Part 1: TB006 1000 mg qw | Part 1: Time at Which Maximum Plasma Concentration Occurs (Tmax) of TB006 | Day 8 | 2.50 hours |
| Part 1: TB006 1000 mg qw | Part 1: Time at Which Maximum Plasma Concentration Occurs (Tmax) of TB006 | Day 1 | 2.00 hours |
| Part 1: TB006 1000 mg qw | Part 1: Time at Which Maximum Plasma Concentration Occurs (Tmax) of TB006 | Day 29 | 2.00 hours |
Primary
Part 1: Total Clearance (CL) of TB006
Blood samples were collected at indicated time points for PK analysis of TB006. PK parameters were analyzed using standard non-compartmental analysis.
Time frame: At Day 29
Population: Pharmacokinetic Analysis Set. Only those participants with data available at specified time points has been presented.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 1: Total Clearance (CL) of TB006 | 7.94 milliliters per hour | Geometric Coefficient of Variation 17.06 |
| Part 1: TB006 420 mg qw | Part 1: Total Clearance (CL) of TB006 | 8.49 milliliters per hour | Geometric Coefficient of Variation 19.27 |
| Part 1: TB006 1000 mg qw | Part 1: Total Clearance (CL) of TB006 | 12.06 milliliters per hour | Geometric Coefficient of Variation 19.68 |
Primary
Part 1: Volume of Distribution (Vd) of TB006
Blood samples were collected at indicated time points for PK analysis of TB006. PK parameters were analyzed using standard non-compartmental analysis.
Time frame: At Day 29
Population: Pharmacokinetic Analysis Set. Only those participants with data available at specified time points has been presented.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 1: Volume of Distribution (Vd) of TB006 | 8151.47 milliliters | Geometric Coefficient of Variation 21.38 |
| Part 1: TB006 420 mg qw | Part 1: Volume of Distribution (Vd) of TB006 | 9282.51 milliliters | Geometric Coefficient of Variation 28.97 |
| Part 1: TB006 1000 mg qw | Part 1: Volume of Distribution (Vd) of TB006 | 13617.70 milliliters | Geometric Coefficient of Variation 30.63 |
Primary
Part 2: Change From Baseline Through Day 104 on the Clinical Dementia Rating Scale - Sum of Boxes Total Score
The Clinical Dementia Rating was obtained through semi-structured interviews of participants and informants, and cognitive functioning was rated in six domains of functioning: memory, orientation, judgement and problem solving, community affairs, home and hobbies, and personal care. Each domain was rated on a five-point scale of functioning as follows: 0: no impairment; 0.5: questionable impairment; 1: mild impairment; 2: moderate impairment; and 3: severe impairment. The Clinical Dementia Rating Scale - Sum of Boxes was based on summing each of the domain box scores with total scores ranging from 0-18, where lower total scores represent better outcomes, and higher total scores represent worse outcomes. Baseline was defined as the last available value prior to the subject receiving the first study drug infusion on Day 1. Change from Baseline value was obtained by subtracting Baseline value from post-dose visit value.
Time frame: Baseline through Day 104
Population: Efficacy Analysis Set comprised of all participants who received assigned dose of TB006 in Part 2 and the participants enrolled at the same TB006 dose level in Part 1, as well as all placebo participants were included and had at least one post-dose evaluable Pharmacodynamic assessment across participant.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 2: Change From Baseline Through Day 104 on the Clinical Dementia Rating Scale - Sum of Boxes Total Score | 0.01 Scores on a scale | Standard Error 0.147 |
| Part 1: TB006 420 mg qw | Part 2: Change From Baseline Through Day 104 on the Clinical Dementia Rating Scale - Sum of Boxes Total Score | 0.35 Scores on a scale | Standard Error 0.142 |
p-value: 0.083895% CI: [-0.741, 0.047]Mixed Models Analysis
Secondary
Part 2: Change From Baseline in Chemistry Parameters: Calcium, Cholesterol, Creatinine, Direct Bilirubin, Glucose, HDL Cholesterol, LDL Cholesterol, Total Bilirubin, Triglycerides and Urea Nitrogen
Blood samples were collected for analysis of following clinical chemistry parameters including Calcium, Cholesterol, Creatinine, Direct Bilirubin, Glucose, HDL Cholesterol, LDL Cholesterol, Total Bilirubin, Triglycerides and Urea Nitrogen. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value.
Time frame: Baseline and up to Day 104
Population: Safety Analysis Set. Only those participants with data available at specified time points has been presented.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 2: Change From Baseline in Chemistry Parameters: Calcium, Cholesterol, Creatinine, Direct Bilirubin, Glucose, HDL Cholesterol, LDL Cholesterol, Total Bilirubin, Triglycerides and Urea Nitrogen | Cholesterol | -5.8 milligrams per deciliter | Standard Deviation 32.3 |
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 2: Change From Baseline in Chemistry Parameters: Calcium, Cholesterol, Creatinine, Direct Bilirubin, Glucose, HDL Cholesterol, LDL Cholesterol, Total Bilirubin, Triglycerides and Urea Nitrogen | Creatinine | 0.014 milligrams per deciliter | Standard Deviation 0.098 |
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 2: Change From Baseline in Chemistry Parameters: Calcium, Cholesterol, Creatinine, Direct Bilirubin, Glucose, HDL Cholesterol, LDL Cholesterol, Total Bilirubin, Triglycerides and Urea Nitrogen | Direct Bilirubin | 0.005 milligrams per deciliter | Standard Deviation 0.037 |
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 2: Change From Baseline in Chemistry Parameters: Calcium, Cholesterol, Creatinine, Direct Bilirubin, Glucose, HDL Cholesterol, LDL Cholesterol, Total Bilirubin, Triglycerides and Urea Nitrogen | Glucose | -5.6 milligrams per deciliter | Standard Deviation 26.98 |
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 2: Change From Baseline in Chemistry Parameters: Calcium, Cholesterol, Creatinine, Direct Bilirubin, Glucose, HDL Cholesterol, LDL Cholesterol, Total Bilirubin, Triglycerides and Urea Nitrogen | HDL Cholesterol | -2.4 milligrams per deciliter | Standard Deviation 8.49 |
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 2: Change From Baseline in Chemistry Parameters: Calcium, Cholesterol, Creatinine, Direct Bilirubin, Glucose, HDL Cholesterol, LDL Cholesterol, Total Bilirubin, Triglycerides and Urea Nitrogen | LDL Cholesterol | -7.5 milligrams per deciliter | Standard Deviation 24.64 |
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 2: Change From Baseline in Chemistry Parameters: Calcium, Cholesterol, Creatinine, Direct Bilirubin, Glucose, HDL Cholesterol, LDL Cholesterol, Total Bilirubin, Triglycerides and Urea Nitrogen | Total Bilirubin | 0.023 milligrams per deciliter | Standard Deviation 0.157 |
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 2: Change From Baseline in Chemistry Parameters: Calcium, Cholesterol, Creatinine, Direct Bilirubin, Glucose, HDL Cholesterol, LDL Cholesterol, Total Bilirubin, Triglycerides and Urea Nitrogen | Triglycerides | -9.2 milligrams per deciliter | Standard Deviation 73.95 |
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 2: Change From Baseline in Chemistry Parameters: Calcium, Cholesterol, Creatinine, Direct Bilirubin, Glucose, HDL Cholesterol, LDL Cholesterol, Total Bilirubin, Triglycerides and Urea Nitrogen | Urea Nitrogen | 0.41 milligrams per deciliter | Standard Deviation 3.817 |
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 2: Change From Baseline in Chemistry Parameters: Calcium, Cholesterol, Creatinine, Direct Bilirubin, Glucose, HDL Cholesterol, LDL Cholesterol, Total Bilirubin, Triglycerides and Urea Nitrogen | Calcium | -0.09 milligrams per deciliter | Standard Deviation 0.437 |
| Part 1: TB006 420 mg qw | Part 2: Change From Baseline in Chemistry Parameters: Calcium, Cholesterol, Creatinine, Direct Bilirubin, Glucose, HDL Cholesterol, LDL Cholesterol, Total Bilirubin, Triglycerides and Urea Nitrogen | HDL Cholesterol | -0.3 milligrams per deciliter | Standard Deviation 8.26 |
| Part 1: TB006 420 mg qw | Part 2: Change From Baseline in Chemistry Parameters: Calcium, Cholesterol, Creatinine, Direct Bilirubin, Glucose, HDL Cholesterol, LDL Cholesterol, Total Bilirubin, Triglycerides and Urea Nitrogen | Cholesterol | 0.3 milligrams per deciliter | Standard Deviation 28.17 |
| Part 1: TB006 420 mg qw | Part 2: Change From Baseline in Chemistry Parameters: Calcium, Cholesterol, Creatinine, Direct Bilirubin, Glucose, HDL Cholesterol, LDL Cholesterol, Total Bilirubin, Triglycerides and Urea Nitrogen | Triglycerides | -0.4 milligrams per deciliter | Standard Deviation 46.29 |
| Part 1: TB006 420 mg qw | Part 2: Change From Baseline in Chemistry Parameters: Calcium, Cholesterol, Creatinine, Direct Bilirubin, Glucose, HDL Cholesterol, LDL Cholesterol, Total Bilirubin, Triglycerides and Urea Nitrogen | Creatinine | -0.017 milligrams per deciliter | Standard Deviation 0.124 |
| Part 1: TB006 420 mg qw | Part 2: Change From Baseline in Chemistry Parameters: Calcium, Cholesterol, Creatinine, Direct Bilirubin, Glucose, HDL Cholesterol, LDL Cholesterol, Total Bilirubin, Triglycerides and Urea Nitrogen | LDL Cholesterol | -4.6 milligrams per deciliter | Standard Deviation 23.63 |
| Part 1: TB006 420 mg qw | Part 2: Change From Baseline in Chemistry Parameters: Calcium, Cholesterol, Creatinine, Direct Bilirubin, Glucose, HDL Cholesterol, LDL Cholesterol, Total Bilirubin, Triglycerides and Urea Nitrogen | Urea Nitrogen | -1.03 milligrams per deciliter | Standard Deviation 4.777 |
| Part 1: TB006 420 mg qw | Part 2: Change From Baseline in Chemistry Parameters: Calcium, Cholesterol, Creatinine, Direct Bilirubin, Glucose, HDL Cholesterol, LDL Cholesterol, Total Bilirubin, Triglycerides and Urea Nitrogen | Glucose | -6.3 milligrams per deciliter | Standard Deviation 27.92 |
| Part 1: TB006 420 mg qw | Part 2: Change From Baseline in Chemistry Parameters: Calcium, Cholesterol, Creatinine, Direct Bilirubin, Glucose, HDL Cholesterol, LDL Cholesterol, Total Bilirubin, Triglycerides and Urea Nitrogen | Total Bilirubin | -0.014 milligrams per deciliter | Standard Deviation 0.128 |
| Part 1: TB006 420 mg qw | Part 2: Change From Baseline in Chemistry Parameters: Calcium, Cholesterol, Creatinine, Direct Bilirubin, Glucose, HDL Cholesterol, LDL Cholesterol, Total Bilirubin, Triglycerides and Urea Nitrogen | Calcium | -0.11 milligrams per deciliter | Standard Deviation 0.432 |
| Part 1: TB006 420 mg qw | Part 2: Change From Baseline in Chemistry Parameters: Calcium, Cholesterol, Creatinine, Direct Bilirubin, Glucose, HDL Cholesterol, LDL Cholesterol, Total Bilirubin, Triglycerides and Urea Nitrogen | Direct Bilirubin | -0.006 milligrams per deciliter | Standard Deviation 0.03 |
Secondary
Part 2: Change From Baseline in Clinical Chemistry Parameter: Hemoglobin A1C
Blood samples were collected for analysis of following clinical chemistry parameter including Hemoglobin A1C. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value.
Time frame: Baseline and up to Day 104
Population: Safety Analysis Set. Only those participants with data available at specified time points has been presented.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 2: Change From Baseline in Clinical Chemistry Parameter: Hemoglobin A1C | -0.06 percentage of glycosylated hemoglobin | Standard Deviation 0.638 |
| Part 1: TB006 420 mg qw | Part 2: Change From Baseline in Clinical Chemistry Parameter: Hemoglobin A1C | 0.07 percentage of glycosylated hemoglobin | Standard Deviation 0.555 |
Secondary
Part 2: Change From Baseline in Clinical Chemistry Parameters: Albumin and Protein
Blood samples were collected for analysis of following clinical chemistry parameters including albumin and protein. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value.
Time frame: Baseline and up to Day 104
Population: Safety Analysis Set. Only those participants with data available at specified time points has been presented.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 2: Change From Baseline in Clinical Chemistry Parameters: Albumin and Protein | Albumin | -0.10 grams per deciliter | Standard Deviation 0.3 |
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 2: Change From Baseline in Clinical Chemistry Parameters: Albumin and Protein | Protein | -0.10 grams per deciliter | Standard Deviation 0.47 |
| Part 1: TB006 420 mg qw | Part 2: Change From Baseline in Clinical Chemistry Parameters: Albumin and Protein | Albumin | -0.01 grams per deciliter | Standard Deviation 0.251 |
| Part 1: TB006 420 mg qw | Part 2: Change From Baseline in Clinical Chemistry Parameters: Albumin and Protein | Protein | 0.00 grams per deciliter | Standard Deviation 0.404 |
Secondary
Part 2: Change From Baseline in Clinical Chemistry Parameters: ALT, ALP, AST and CK
Blood samples were collected for analysis of following clinical chemistry parameters including ALT, ALP, AST and CK. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value.
Time frame: Baseline and up to Day 104
Population: Safety Analysis Set. Only those participants with data available at specified time points has been presented.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 2: Change From Baseline in Clinical Chemistry Parameters: ALT, ALP, AST and CK | ALT | -0.5 International Units per Liter | Standard Deviation 12.88 |
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 2: Change From Baseline in Clinical Chemistry Parameters: ALT, ALP, AST and CK | ALP | 1.0 International Units per Liter | Standard Deviation 12.01 |
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 2: Change From Baseline in Clinical Chemistry Parameters: ALT, ALP, AST and CK | AST | -0.4 International Units per Liter | Standard Deviation 10.44 |
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 2: Change From Baseline in Clinical Chemistry Parameters: ALT, ALP, AST and CK | CK | -14.3 International Units per Liter | Standard Deviation 77.24 |
| Part 1: TB006 420 mg qw | Part 2: Change From Baseline in Clinical Chemistry Parameters: ALT, ALP, AST and CK | CK | 6.3 International Units per Liter | Standard Deviation 52.07 |
| Part 1: TB006 420 mg qw | Part 2: Change From Baseline in Clinical Chemistry Parameters: ALT, ALP, AST and CK | ALT | -0.4 International Units per Liter | Standard Deviation 5.4 |
| Part 1: TB006 420 mg qw | Part 2: Change From Baseline in Clinical Chemistry Parameters: ALT, ALP, AST and CK | AST | -0.5 International Units per Liter | Standard Deviation 3.58 |
| Part 1: TB006 420 mg qw | Part 2: Change From Baseline in Clinical Chemistry Parameters: ALT, ALP, AST and CK | ALP | 0.0 International Units per Liter | Standard Deviation 11.92 |
Secondary
Part 2: Change From Baseline in Clinical Chemistry Parameters: Potassium and Sodium
Blood samples were collected for analysis of following clinical chemistry parameters including Potassium and Sodium. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value.
Time frame: Baseline and up to Day 104
Population: Safety Analysis Set. Only those participants with data available at specified time points has been presented.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 2: Change From Baseline in Clinical Chemistry Parameters: Potassium and Sodium | Potassium | -0.14 Millimoles per liter | Standard Deviation 0.469 |
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 2: Change From Baseline in Clinical Chemistry Parameters: Potassium and Sodium | Sodium | -0.7 Millimoles per liter | Standard Deviation 2.11 |
| Part 1: TB006 420 mg qw | Part 2: Change From Baseline in Clinical Chemistry Parameters: Potassium and Sodium | Potassium | -0.13 Millimoles per liter | Standard Deviation 0.521 |
| Part 1: TB006 420 mg qw | Part 2: Change From Baseline in Clinical Chemistry Parameters: Potassium and Sodium | Sodium | -0.7 Millimoles per liter | Standard Deviation 3.05 |
Secondary
Part 2: Change From Baseline in Clinical Chemistry Parameter: Thyrotropin
Blood samples were collected for analysis of following clinical chemistry parameter including Thyrotropin. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value.
Time frame: Baseline and up to Day 104
Population: Safety Analysis Set. Only those participants with data available at specified time points has been presented.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 2: Change From Baseline in Clinical Chemistry Parameter: Thyrotropin | -0.118 micro-international units per milliliter | Standard Deviation 0.619 |
| Part 1: TB006 420 mg qw | Part 2: Change From Baseline in Clinical Chemistry Parameter: Thyrotropin | 0.134 micro-international units per milliliter | Standard Deviation 1 |
Secondary
Part 2: Change From Baseline in DBP and SBP
Vital signs including DBP and SBP was measured by at least 5 minutes of rest with the participant in a quiet setting without distractions (eg, television, cell phones). Blood pressure measurements were taken with the participant in the sitting position. Baseline was defined as the last available value prior to the participant receiving the first study drug infusion on Day 1. Change from Baseline was obtained by subtracting the Baseline value from post-dose visit value.
Time frame: Baseline and Up to Day 104
Population: Safety Analysis Set. Only those participants with data available at specified time points has been presented.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 2: Change From Baseline in DBP and SBP | DBP | 0.8 Millimeters of mercury | Standard Deviation 6.42 |
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 2: Change From Baseline in DBP and SBP | SBP | 1.4 Millimeters of mercury | Standard Deviation 15.02 |
| Part 1: TB006 420 mg qw | Part 2: Change From Baseline in DBP and SBP | DBP | 0.7 Millimeters of mercury | Standard Deviation 9.48 |
| Part 1: TB006 420 mg qw | Part 2: Change From Baseline in DBP and SBP | SBP | 0.0 Millimeters of mercury | Standard Deviation 15.57 |
Secondary
Part 2: Change From Baseline in ECG Mean Heart Rate
12-lead ECG measurements was obtained using an ECG machine that automatically calculates the heart rate. Baseline was defined as the last available value prior to the participant receiving the first study drug infusion on Day 1. Change from Baseline was obtained by subtracting the Baseline value from post-dose visit value.
Time frame: Baseline and Up to Day 104
Population: Safety Analysis Set. Only those participants with data available at specified time points has been presented.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 2: Change From Baseline in ECG Mean Heart Rate | -1.8 Beats per minute | Standard Deviation 8.87 |
| Part 1: TB006 420 mg qw | Part 2: Change From Baseline in ECG Mean Heart Rate | -1.3 Beats per minute | Standard Deviation 7.4 |
Secondary
Part 2: Change From Baseline in ECG Parameters
12-lead ECG measurements was obtained using an ECG machine that automatically calculates the PR interval, QRS duration, QT interval and QTcB. Baseline was defined as the last available value prior to the participant receiving the first study drug infusion on Day 1. Change from Baseline was obtained by subtracting the Baseline value from post-dose visit value.
Time frame: Baseline and Up to Day 104
Population: Safety Analysis Set. Only those participants with data available at specified time points has been presented.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 2: Change From Baseline in ECG Parameters | QRS Duration | -2.2 milliseconds | Standard Deviation 13.31 |
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 2: Change From Baseline in ECG Parameters | PR Interval | -1.6 milliseconds | Standard Deviation 13.17 |
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 2: Change From Baseline in ECG Parameters | QTcB Interval | -2.0 milliseconds | Standard Deviation 18.01 |
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 2: Change From Baseline in ECG Parameters | QT Interval | 4.2 milliseconds | Standard Deviation 26.29 |
| Part 1: TB006 420 mg qw | Part 2: Change From Baseline in ECG Parameters | QTcB Interval | -1.7 milliseconds | Standard Deviation 15.99 |
| Part 1: TB006 420 mg qw | Part 2: Change From Baseline in ECG Parameters | PR Interval | 2.1 milliseconds | Standard Deviation 18.32 |
| Part 1: TB006 420 mg qw | Part 2: Change From Baseline in ECG Parameters | QT Interval | 3.9 milliseconds | Standard Deviation 20.28 |
| Part 1: TB006 420 mg qw | Part 2: Change From Baseline in ECG Parameters | QRS Duration | -1.4 milliseconds | Standard Deviation 7.71 |
Secondary
Part 2: Change From Baseline in Heart Rate
Vital signs including heart rate was measured by at least 5 minutes of rest with the participant in a quiet setting without distractions (eg, television, cell phones). Blood pressure measurements were taken with the participant in the sitting position. Baseline was defined as the last available value prior to the participant receiving the first study drug infusion on Day 1. Change from Baseline was obtained by subtracting the Baseline value from post-dose visit value.
Time frame: Baseline and Up to Day 104
Population: Safety Analysis Set. Only those participants with data available at specified time points has been presented.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 2: Change From Baseline in Heart Rate | -4.2 Beats per minute | Standard Deviation 8.59 |
| Part 1: TB006 420 mg qw | Part 2: Change From Baseline in Heart Rate | -2.1 Beats per minute | Standard Deviation 7.86 |
Secondary
Part 2: Change From Baseline in Hematology Parameter: Ery. MCH
Blood samples were collected for analysis of following hematology parameter: Ery. MCH. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value.
Time frame: Baseline and up to Day 104
Population: Safety Analysis Set. Only those participants with data available at specified time points has been presented.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 2: Change From Baseline in Hematology Parameter: Ery. MCH | 0.19 picograms | Standard Deviation 0.775 |
| Part 1: TB006 420 mg qw | Part 2: Change From Baseline in Hematology Parameter: Ery. MCH | 0.51 picograms | Standard Deviation 1.045 |
Secondary
Part 2: Change From Baseline in Hematology Parameter: Ery. MCV
Blood samples were collected for analysis of following hematology parameter: Ery. MCV. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value.
Time frame: Baseline and up to Day 104
Population: Safety Analysis Set. Only those participants with data available at specified time points has been presented.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 2: Change From Baseline in Hematology Parameter: Ery. MCV | 1.54 femtoliters | Standard Deviation 2.743 |
| Part 1: TB006 420 mg qw | Part 2: Change From Baseline in Hematology Parameter: Ery. MCV | 2.04 femtoliters | Standard Deviation 3.412 |
Secondary
Part 2: Change From Baseline in Hematology Parameter: Erythrocytes and Reticulocytes
Blood samples were collected for analysis of following hematology parameter: Erythrocytes and Reticulocytes. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value.
Time frame: Baseline and up to Day 104
Population: Safety Analysis Set. Only those participants with data available at specified time points has been presented.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 2: Change From Baseline in Hematology Parameter: Erythrocytes and Reticulocytes | Erythrocytes | -0.028 10^6 cells per microliter | Standard Deviation 0.269 |
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 2: Change From Baseline in Hematology Parameter: Erythrocytes and Reticulocytes | Reticulocytes | 0.001 10^6 cells per microliter | Standard Deviation 0.012 |
| Part 1: TB006 420 mg qw | Part 2: Change From Baseline in Hematology Parameter: Erythrocytes and Reticulocytes | Erythrocytes | 0.024 10^6 cells per microliter | Standard Deviation 0.228 |
| Part 1: TB006 420 mg qw | Part 2: Change From Baseline in Hematology Parameter: Erythrocytes and Reticulocytes | Reticulocytes | -0.003 10^6 cells per microliter | Standard Deviation 0.012 |
Secondary
Part 2: Change From Baseline in Hematology Parameter: Hematocrit
Blood samples were collected for analysis of following hematology parameter: Hematocrit. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value.
Time frame: Baseline and up to Day 104
Population: Safety Analysis Set. Only those participants with data available at specified time points has been presented.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 2: Change From Baseline in Hematology Parameter: Hematocrit | 0.41 Percentage | Standard Deviation 2.735 |
| Part 1: TB006 420 mg qw | Part 2: Change From Baseline in Hematology Parameter: Hematocrit | 1.11 Percentage | Standard Deviation 2.403 |
Secondary
Part 2: Change From Baseline in Hematology Parameter: Hemoglobin
Blood samples were collected for analysis of following hematology parameter: Hemoglobin. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value.
Time frame: Baseline and up to Day 104
Population: Safety Analysis Set. Only those participants with data available at specified time points has been presented.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 2: Change From Baseline in Hematology Parameter: Hemoglobin | 0.00 grams per deciliter | Standard Deviation 0.766 |
| Part 1: TB006 420 mg qw | Part 2: Change From Baseline in Hematology Parameter: Hemoglobin | 0.29 grams per deciliter | Standard Deviation 0.827 |
Secondary
Part 2: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Platelets
Blood samples were collected for analysis of following hematology parameters including Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Platelets. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value.
Time frame: Baseline and up to Day 104
Population: Safety Analysis Set. Only those participants with data available at specified time points has been presented.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 2: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Platelets | Lymphocytes | -0.118 10^3 cells per microliter | Standard Deviation 0.392 |
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 2: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Platelets | Basophils | -0.004 10^3 cells per microliter | Standard Deviation 0.027 |
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 2: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Platelets | Monocytes | -0.021 10^3 cells per microliter | Standard Deviation 0.109 |
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 2: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Platelets | Neutrophils | -0.109 10^3 cells per microliter | Standard Deviation 1.295 |
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 2: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Platelets | Leukocytes | -0.26 10^3 cells per microliter | Standard Deviation 1.383 |
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 2: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Platelets | Platelets | -1.9 10^3 cells per microliter | Standard Deviation 32.08 |
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 2: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Platelets | Eosinophils | -0.008 10^3 cells per microliter | Standard Deviation 0.113 |
| Part 1: TB006 420 mg qw | Part 2: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Platelets | Platelets | -12.1 10^3 cells per microliter | Standard Deviation 46.27 |
| Part 1: TB006 420 mg qw | Part 2: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Platelets | Basophils | -0.002 10^3 cells per microliter | Standard Deviation 0.022 |
| Part 1: TB006 420 mg qw | Part 2: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Platelets | Eosinophils | -0.040 10^3 cells per microliter | Standard Deviation 0.13 |
| Part 1: TB006 420 mg qw | Part 2: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Platelets | Leukocytes | -0.02 10^3 cells per microliter | Standard Deviation 1.244 |
| Part 1: TB006 420 mg qw | Part 2: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Platelets | Lymphocytes | -0.053 10^3 cells per microliter | Standard Deviation 0.411 |
| Part 1: TB006 420 mg qw | Part 2: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Platelets | Neutrophils | 0.067 10^3 cells per microliter | Standard Deviation 1.206 |
| Part 1: TB006 420 mg qw | Part 2: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Platelets | Monocytes | 0.003 10^3 cells per microliter | Standard Deviation 0.107 |
Secondary
Part 2: Change From Baseline in Respiratory Rate
Vital signs including respiratory rate was measured by at least 5 minutes of rest with the participant in a quiet setting without distractions (eg, television, cell phones). Blood pressure measurements were taken with the participant in the sitting position. Baseline was defined as the last available value prior to the participant receiving the first study drug infusion on Day 1. Change from Baseline was obtained by subtracting the Baseline value from post-dose visit value.
Time frame: Baseline and Up to Day 104
Population: Safety Analysis Set. Only those participants with data available at specified time points has been presented.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 2: Change From Baseline in Respiratory Rate | 0.1 breaths per minute | Standard Deviation 0.97 |
| Part 1: TB006 420 mg qw | Part 2: Change From Baseline in Respiratory Rate | 0.2 breaths per minute | Standard Deviation 0.97 |
Secondary
Part 2: Change From Baseline in Temperature
Vital signs including temperature was measured by at least 5 minutes of rest with the participant in a quiet setting without distractions (eg, television, cell phones). Blood pressure measurements were taken with the participant in the sitting position. Baseline was defined as the last available value prior to the participant receiving the first study drug infusion on Day 1. Change from Baseline was obtained by subtracting the Baseline value from post-dose visit value.
Time frame: Baseline and Up to Day 104
Population: Safety Analysis Set. Only those participants with data available at specified time points has been presented.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 2: Change From Baseline in Temperature | 0.01 degrees Celsius | Standard Deviation 0.489 |
| Part 1: TB006 420 mg qw | Part 2: Change From Baseline in Temperature | -0.03 degrees Celsius | Standard Deviation 0.461 |
Secondary
Part 2: Change From Baseline in Urine pH
Urine samples were collected for analysis of Urine pH. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value.
Time frame: Baseline and up to Day 104
Population: Safety Analysis Set. Only those participants with data available at specified time points has been presented.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 2: Change From Baseline in Urine pH | -0.13 potential of Hydrogen | Standard Deviation 0.788 |
| Part 1: TB006 420 mg qw | Part 2: Change From Baseline in Urine pH | 0.18 potential of Hydrogen | Standard Deviation 0.791 |
Secondary
Part 2: Change From Baseline in Urine Specific Gravity
Urine samples were collected for analysis of Urine specific gravity. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value.
Time frame: Baseline and up to Day 104
Population: Safety Analysis Set. Only those participants with data available at specified time points has been presented.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 2: Change From Baseline in Urine Specific Gravity | 0.002 Ratio | Standard Deviation 0.01 |
| Part 1: TB006 420 mg qw | Part 2: Change From Baseline in Urine Specific Gravity | 0.001 Ratio | Standard Deviation 0.008 |
Secondary
Part 2: Change From Baseline in Urobilinogen
Urine samples were collected for analysis of Urobilinogen. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value.
Time frame: Baseline and up to Day 104
Population: Safety Analysis Set. Only those participants with data available at specified time points has been presented.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 2: Change From Baseline in Urobilinogen | 0.07 milligrams per deciliter | Standard Deviation 0.313 |
| Part 1: TB006 420 mg qw | Part 2: Change From Baseline in Urobilinogen | 0.05 milligrams per deciliter | Standard Deviation 0.354 |
Secondary
Part 2: Change From Baseline on Mini-Mental State Examination (MMSE) Score
The MMSE was used to measure cognitive impairment. The MMSE can evaluate overall cognitive function, and is widely used for the assessment of cognitive impairment in dementia participants. The questionnaire consists of 11 items, and each item aims to evaluate different cognitive domains such as orientation, memory, attention, and construction. The score ranged from 0 to 30, with a higher score indicating better function. A positive change score indicated improvement from Baseline. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value.
Time frame: Baseline and at Days 36 and 104
Population: Efficacy Analysis Set. Only those participants with data available at specified timepoints has been presented.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 2: Change From Baseline on Mini-Mental State Examination (MMSE) Score | Day 36 | 1.2 Scores on a scale | Standard Deviation 2.59 |
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 2: Change From Baseline on Mini-Mental State Examination (MMSE) Score | Day 104 | 1.0 Scores on a scale | Standard Deviation 3.1 |
| Part 1: TB006 420 mg qw | Part 2: Change From Baseline on Mini-Mental State Examination (MMSE) Score | Day 36 | 0.2 Scores on a scale | Standard Deviation 2.52 |
| Part 1: TB006 420 mg qw | Part 2: Change From Baseline on Mini-Mental State Examination (MMSE) Score | Day 104 | 0.6 Scores on a scale | Standard Deviation 2.97 |
Secondary
Part 2: Change From Baseline on the Neuropsychiatric Inventory (NPI) Score
The NPI was a questionnaire that quantified psychiatric symptoms and behavioral disorders in dementia. A total of 12 items (the original NPI-10 consisting of 10 behavioral domains: delusions, hallucinations, agitation/aggression, dysphoria, anxiety, euphoria, apathy, disinhibition, irritability/lability, and aberrant motor behavior, The NPI total score was calculated by adding the scores of the domains (each domain scores ranges from 0 to 12). The NPI total score ranges from 0 to 120 with higher scores indicating greater behavioral impairment. Baseline was defined as Day 1. Change from Baseline was obtained by subtracting Baseline value from post-dose visit value.
Time frame: Baseline and at Days 36 and 104
Population: Efficacy Analysis Set. Only those participants with data available at specified time points has been presented.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 2: Change From Baseline on the Neuropsychiatric Inventory (NPI) Score | Day 104 | -3.5 Scores on a scale | Standard Deviation 11.47 |
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 2: Change From Baseline on the Neuropsychiatric Inventory (NPI) Score | Day 36 | -2.5 Scores on a scale | Standard Deviation 8.1 |
| Part 1: TB006 420 mg qw | Part 2: Change From Baseline on the Neuropsychiatric Inventory (NPI) Score | Day 36 | -0.8 Scores on a scale | Standard Deviation 9.12 |
| Part 1: TB006 420 mg qw | Part 2: Change From Baseline on the Neuropsychiatric Inventory (NPI) Score | Day 104 | -1.1 Scores on a scale | Standard Deviation 6.79 |
Secondary
Part 2: Change From Baseline Through Day 36 on the Clinical Dementia Rating Scale - Sum of Boxes Total Score
The Clinical Dementia Rating was obtained through semi-structured interviews of participants and informants, and cognitive functioning was rated in six domains of functioning: memory, orientation, judgement and problem solving, community affairs, home and hobbies, and personal care. Each domain was rated on a five-point scale of functioning as follows: 0: no impairment; 0.5: questionable impairment; 1: mild impairment; 2: moderate impairment; and 3: severe impairment. The Clinical Dementia Rating Scale - Sum of Boxes was based on summing each of the domain box scores with total scores ranging from 0-18, where lower total scores represent better outcomes, and higher total scores represent worse outcomes. Baseline was defined as the last available value prior to the subject receiving the first study drug infusion on Day 1. Change from Baseline value was obtained by subtracting Baseline value from post-dose visit value.
Time frame: Baseline through Day 36
Population: Efficacy Analysis Set.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 2: Change From Baseline Through Day 36 on the Clinical Dementia Rating Scale - Sum of Boxes Total Score | -0.16 Scores on a scale | Standard Error 0.162 |
| Part 1: TB006 420 mg qw | Part 2: Change From Baseline Through Day 36 on the Clinical Dementia Rating Scale - Sum of Boxes Total Score | 0.23 Scores on a scale | Standard Error 0.157 |
Secondary
Part 2: Cmax of TB006
Blood samples were collected at indicated time points for PK analysis of TB006. PK parameters were analyzed using standard non-compartmental analysis.
Time frame: Day 1 and Day 29
Population: Pharmacokinetic Analysis Set. Only those participants with data available at specified time points has been presented.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 2: Cmax of TB006 | Day 1 | 339.17 Micrograms per milliliter | Geometric Coefficient of Variation 23.82 |
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 2: Cmax of TB006 | Day 29 | 731.55 Micrograms per milliliter | Geometric Coefficient of Variation 25.13 |
Secondary
Part 2: Ctrough of TB006
Blood samples were collected at indicated time points for PK analysis of TB006. PK parameters were analyzed using standard non-compartmental analysis.
Time frame: Day 29
Population: Pharmacokinetic Analysis Set. Only those participants with data available at specified time points has been presented.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 2: Ctrough of TB006 | 395.82 micrograms per milliliter | Geometric Coefficient of Variation 35.88 |
Secondary
Part 2: Number of Participants With AEs and SAEs
An adverse event is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An 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, associated with liver injury and impaired liver function or any other situations as per medical or scientific judgement.
Time frame: Up to Day 104
Population: Safety Population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 2: Number of Participants With AEs and SAEs | Any AE | 28 Participants |
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 2: Number of Participants With AEs and SAEs | Any SAE | 4 Participants |
| Part 1: TB006 420 mg qw | Part 2: Number of Participants With AEs and SAEs | Any AE | 17 Participants |
| Part 1: TB006 420 mg qw | Part 2: Number of Participants With AEs and SAEs | Any SAE | 1 Participants |
Secondary
Part 2: Number of Participants With Clinically Significant Neurological Examination Findings
The neurological examination assessed mental status, motor and sensory skills, hearing and speech, vision, coordination, and balance. This analysis was planned but data was not captured in the database. Abnormal changes were captured as adverse events if they were clinically significant.
Time frame: Up to Day 104
Population: Full Analysis Set. This analysis was planned but data was not captured in the database.
Secondary
Part 2: Number of Participants With Clinically Significant Physical Examination Findings
A complete physical examination included, at a minimum, assessment of the Cardiovascular, Respiratory, Gastrointestinal and Neurological systems. This analysis was planned but data was not captured in the database. Abnormal changes were captured as adverse events if they were clinically significant.
Time frame: Up to Day 104
Population: Full Analysis Set. This analysis was planned but data was not captured in the database.
Secondary
Part 2: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using C-SSRS
The C-SSRS is an interview-based instrument to systematically assess suicidal ideation and suicidal behavior. Number of participants that have an affirmative response to the 5 items for suicidal ideation (1. Wish to be dead, 2. Non-specific active suicidal thoughts, 3. Active suicidal ideation with any methods without intent to act, 4. Active suicidal ideation with some intent to act, without specific plan, 5. Active suicidal ideation with specific plan and intent) and/or to the 5 items for suicidal behavior (1. Preparatory acts or behavior, 2. Aborted attempt, 3. Interrupted attempt, 4. Actual attempt, 5. Completed suicide) were reported. The total score ranges from 0 (no ideation present) to 5 (active suicidal ideation with specific plan and intent); higher scores indicate worse symptoms.
Time frame: Up to Day 104
Population: Safety Analysis Set. Only those participants with data available at specified time points has been presented.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 2: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using C-SSRS | Wish to be dead | 0 Participants |
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 2: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using C-SSRS | Active suicidal ideation without any methods without intent to act | 0 Participants |
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 2: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using C-SSRS | Any suicidal behavior | 0 Participants |
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 2: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using C-SSRS | First attempt | 0 Participants |
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 2: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using C-SSRS | Lethal attempt | 0 Participants |
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 2: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using C-SSRS | Non-specific active suicidal thoughts | 0 Participants |
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 2: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using C-SSRS | Active suicidal ideation with some intent to act, without specific plan | 0 Participants |
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 2: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using C-SSRS | Active suicidal ideation with specific plan and intent | 0 Participants |
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 2: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using C-SSRS | Actual attempt | 0 Participants |
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 2: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using C-SSRS | Interrupted attempt | 0 Participants |
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 2: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using C-SSRS | Aborted attempt | 0 Participants |
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 2: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using C-SSRS | Preparatory acts or behavior | 0 Participants |
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 2: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using C-SSRS | Most recent attempt | 0 Participants |
| Part 1: TB006 420 mg qw | Part 2: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using C-SSRS | Active suicidal ideation with some intent to act, without specific plan | 0 Participants |
| Part 1: TB006 420 mg qw | Part 2: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using C-SSRS | Interrupted attempt | 0 Participants |
| Part 1: TB006 420 mg qw | Part 2: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using C-SSRS | Active suicidal ideation with specific plan and intent | 0 Participants |
| Part 1: TB006 420 mg qw | Part 2: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using C-SSRS | Most recent attempt | 0 Participants |
| Part 1: TB006 420 mg qw | Part 2: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using C-SSRS | Any suicidal behavior | 0 Participants |
| Part 1: TB006 420 mg qw | Part 2: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using C-SSRS | First attempt | 0 Participants |
| Part 1: TB006 420 mg qw | Part 2: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using C-SSRS | Preparatory acts or behavior | 0 Participants |
| Part 1: TB006 420 mg qw | Part 2: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using C-SSRS | Lethal attempt | 0 Participants |
| Part 1: TB006 420 mg qw | Part 2: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using C-SSRS | Wish to be dead | 0 Participants |
| Part 1: TB006 420 mg qw | Part 2: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using C-SSRS | Actual attempt | 0 Participants |
| Part 1: TB006 420 mg qw | Part 2: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using C-SSRS | Non-specific active suicidal thoughts | 0 Participants |
| Part 1: TB006 420 mg qw | Part 2: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using C-SSRS | Active suicidal ideation without any methods without intent to act | 0 Participants |
| Part 1: TB006 420 mg qw | Part 2: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using C-SSRS | Aborted attempt | 0 Participants |
Secondary
Part 2: Percentage of Responders on the Clinical Dementia Rating Scale - Sum of Boxes
The Clinical Dementia Rating is obtained through semi-structured interviews of participants and informants, and cognitive functioning is rated in six domains of functioning: memory, orientation, judgement and problem solving, community affairs, home and hobbies, and personal care. Each domain is rated on a five-point scale of functioning as follows: 0, no impairment; 0.5, questionable impairment; 1, mild impairment; 2, moderate impairment; and 3, severe impairment. The Clinical Dementia Rating Scale - Sum of Boxes is based on summing each of the domain box scores with total scores ranging from 0-18, where lower total scores represent better outcomes, and higher total scores represent worse outcomes. A responder was defined as a participant with at least 1 point improvement from Baseline on the Sum of Boxes score. Percentage of responders on the Clinical Dementia Rating Scale - Sum of Boxes has been presented.
Time frame: At Days 36 and 104
Population: Efficacy Analysis Set.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 2: Percentage of Responders on the Clinical Dementia Rating Scale - Sum of Boxes | Day 36 | 25.4 Percentage of responders |
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 2: Percentage of Responders on the Clinical Dementia Rating Scale - Sum of Boxes | Day 104 | 22.4 Percentage of responders |
| Part 1: TB006 420 mg qw | Part 2: Percentage of Responders on the Clinical Dementia Rating Scale - Sum of Boxes | Day 36 | 9.7 Percentage of responders |
| Part 1: TB006 420 mg qw | Part 2: Percentage of Responders on the Clinical Dementia Rating Scale - Sum of Boxes | Day 104 | 15.3 Percentage of responders |
Secondary
Part 2: t1/2 of TB006
Blood samples were collected at indicated time points for PK analysis of TB006. PK parameters were analyzed using standard non-compartmental analysis.
Time frame: Day 29
Population: Pharmacokinetic Analysis Set. Only those participants with data available at specified time points has been presented.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: TB006 140 Milligrams (mg) Weekly (qw) | Part 2: t1/2 of TB006 | 756.78 hours | Geometric Coefficient of Variation 22.05 |