A Study to Investigate the Pharmacokinetics, Safety, and Tolerability of Emicizumab in Healthy Chinese Volunteers

Study Overview
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Brief Summary
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This single-center, open-label study will evaluate the pharmacokinetics, safety, and tolerability of emicizumab following a single subcutaneous (SC) administration to healthy Chinese subjects.

Official Title
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A Single-Center, Open-Label, Single Dose Study to Investigate the Pharmacokinetics, Safety, and Tolerability of Emicizumab in Healthy Chinese Volunteers

Conditions
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Healthy Volunteers, Hemophilia A

Intervention / Treatment
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* Drug: Emicizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy Chinese male subjects, aged 20-45 years inclusive at the time of screening Chinese subjects must have Chinese parents and grandparents, all of whom were born in China A body mass index (BMI) between 19 and 24 kilograms per height in meters squared (kg/m^2), inclusive Able to participate and willing to give written informed consent and to comply with the study requirements Exclusion Criteria: Any history or presence of a clinically significant disorder, or any other condition or disease which in the judgement of the investigator would place the subject at undue risk; interfere with absorption, distribution, metabolism, and excretion of emicizumab; or interfere with the ability of the subject to complete the study Major illness within 1 month prior to dosing, and/or any condition which could relapse during or immediately after the study Use of any prescribed or over-the-counter (OTC) medication or herbal medicine taken within 14 days prior to dosing or within 5 times the elimination half-life of the medication prior to dosing (whichever is longer), with some exceptions Any significant donation/loss of blood or plasma (greater than 450 milliliters) within the 3 months prior to dosing Regular smoker with consumption of more than 10 cigarettes per day or the equivalent amount of tobacco Participation within a clinical study with an investigational drug or device within the last 3 months prior to dosing Any clinically relevant history of hypersensitivity or allergic reactions, either spontaneous or following drug administration or exposure to foods or environmental agents Previous or concomitant thromboembolic disease such as deep vein thrombosis (DVT) or signs of thromboembolic disease, or family history of thromboembolic disorder such as serious DVT At high risk for thrombotic microangiopathy (e.g., have a previous medical or family history of thrombotic microangiopathy), in the investigator's judgment Previous or concomitant autoimmune or connective tissue disease History of tuberculosis or active tuberculosis with positive test result at screening Any other reason that, in the judgment of the investigator, would render the subject unsuitable for study participation

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Emicizumab<br> | Drug: Emicizumab<br>* Participants will receive a single 1 milligram per kilogram of body weight (mg/kg) subcutaneous dose of emicizumab on Day 1.<br>* Other names: RO5534262;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Plasma Concentration (Cmax) of Emicizumab | Plasma concentrations of emicizumab were analyzed using a validated enzyme-linked immunosorbent assay (ELISA). Pharmacokinetics (PK) parameters were estimated using standard non-compartmental methods. | Predose on Day 1 and postdose on Days 2, 4, 6, 8, 11, 15, 22, 29, 36, 43, 50, 57, 71, 85, and 113 | 
| Area Under the Plasma Concentration Versus Time Curve (AUC) Between Time Zero Extrapolated to Infinity (AUC0-inf) of Emicizumab | Plasma concentrations of emicizumab were analyzed using a validated enzyme-linked immunosorbent assay (ELISA). Pharmacokinetics (PK) parameters were estimated using standard non-compartmental methods. | Predose on Day 1 and postdose on Days 2, 4, 6, 8, 11, 15, 22, 29, 36, 43, 50, 57, 71, 85, and 113 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC Between Time Zero and the Time of Last Quantifiable Concentration (AUC0-last) of Emicizumab | Plasma concentrations of emicizumab were analyzed using a validated enzyme-linked immunosorbent assay (ELISA). Pharmacokinetics (PK) parameters were estimated using standard non-compartmental methods. | Predose on Day 1 and postdose on Days 2, 4, 6, 8, 11, 15, 22, 29, 36, 43, 50, 57, 71, 85, and 113 | 
| Time to Cmax (Tmax) of Emicizumab | Plasma concentrations of emicizumab were analyzed using a validated enzyme-linked immunosorbent assay (ELISA). Pharmacokinetics (PK) parameters were estimated using standard non-compartmental methods. | Predose on Day 1 and postdose on Days 2, 4, 6, 8, 11, 15, 22, 29, 36, 43, 50, 57, 71, 85, and 113 | 
| Apparent Terminal Half-Life (t1/2) of Emicizumab | Plasma concentrations of emicizumab were analyzed using a validated enzyme-linked immunosorbent assay (ELISA). Pharmacokinetics (PK) parameters were estimated using standard non-compartmental methods. | Predose on Day 1 and postdose on Days 2, 4, 6, 8, 11, 15, 22, 29, 36, 43, 50, 57, 71, 85, and 113 | 
| Apparent Clearance (CL/F) of Emicizumab | Plasma concentrations of emicizumab were analyzed using a validated enzyme-linked immunosorbent assay (ELISA). Pharmacokinetics (PK) parameters were estimated using standard non-compartmental methods. | Predose on Day 1 and postdose on Days 2, 4, 6, 8, 11, 15, 22, 29, 36, 43, 50, 57, 71, 85, and 113 | 
| Apparent Volume of Distribution (Vz/F) of Emicizumab | Plasma concentrations of emicizumab were analyzed using a validated enzyme-linked immunosorbent assay (ELISA). Pharmacokinetics (PK) parameters were estimated using standard non-compartmental methods. | Predose on Day 1 and postdose on Days 2, 4, 6, 8, 11, 15, 22, 29, 36, 43, 50, 57, 71, 85, and 113 | 
| Mean Residence Time (MRT) of Emicizumab | Plasma concentrations of emicizumab were analyzed using a validated enzyme-linked immunosorbent assay (ELISA). Pharmacokinetics (PK) parameters were estimated using standard non-compartmental methods. | Predose on Day 1 and postdose on Days 2, 4, 6, 8, 11, 15, 22, 29, 36, 43, 50, 57, 71, 85, and 113 | 
| Number of Participants With Adverse Events by Highest World Health Organization (WHO) Toxicity Grade | The WHO Toxicity Grading Scale was used for assessing adverse event severity. Any adverse event not specifically listed in the WHO Toxicity Grading Scale was assessed according to the following levels of severity: Grade 1 is mild; Grade 2 is moderate; Grade 3 is severe; and Grade 4 is life-threatening. Investigator text for adverse events were encoded using the Medical Dictionary for Regulatory Activities (MedDRA) version 21.1. After informed consent had been obtained but prior to initiation of study drug, only serious adverse events (SAEs) caused by a protocol-mandated intervention were to have been reported. After initiation of study drug, all adverse events, regardless of relationship to study drug, were to have been reported until the participant completed his last study visit. After this period, any SAEs believed to be related to prior study drug treatment were to be reported. | From screening to study completion (20 weeks) | 
| Number of Participants Testing Negative or Positive for the Presence of Anti-Drug Antibodies (ADA) Against Emicizumab by Timepoint and for the Overall Study | Participants were considered to be 'ADA Negative (Treatment Unaffected)' if baseline and all post-baseline samples were negative, or if they were ADA positive at baseline but did not have any post-baseline samples with a titer that was at least 4-fold greater than the titer of the baseline sample. 'Total ADA Positive' is the sum of all participants who tested positive for ADA in the 2 following categories: 'ADA Positive (Treatment Induced)', those who were ADA negative at baseline and tested positive for ADA following study drug administration; and 'ADA Positive (Treatment Boosted)', those who were pre-dose ADA positive and had post-baseline samples with a titer that was at least 4-fold greater compared to the baseline measurement. | Predose at Baseline (Day 1) and postdose on Days 57 and 113 | 
| Number of Participants With Laboratory Test Abnormalities | The number of participants with a laboratory abnormality during treatment (numerator) is reported among the 'number analyzed' in the table below (denominator), which represents the number of participants without that abnormality at baseline (last observation prior to initiation of study drug). Note that samples from all participants were analyzed for each laboratory parameter. Values falling above or below the Roche predefined standard reference range were laboratory abnormalities labelled accordingly as 'high' or 'low'. Not every laboratory abnormality qualified as an adverse event; only if it was accompanied by clinical symptoms, resulted in a change in study treatment or in a medical intervention, or was clinically significant in the investigator's judgment. SGOT/AST = serum glutamic-oxaloacetic transaminase/aspartate transaminase; SGPT/ALT = serum glutamic-pyruvic transaminase/alanine transaminase | Baseline and Days 2, 4, 8, 11, 15, 29, 43, 57, 71, 85, and 113 | 
| Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: Albumin Concentration | Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug. | Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113 | 
| Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: Alkaline Phosphatase Concentration | Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug. | Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113 | 
| Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: Bilirubin Concentration | Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug. | Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113 | 
| Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: Fasting Blood Glucose Concentration | Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug. | Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113 | 
| Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: Blood Urea Nitrogen Concentration | Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug. | Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113 | 
| Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: C-Reactive Protein Concentration | Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug. | Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113 | 
| Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: Chloride Concentration | Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug. | Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113 | 
| Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: Cholesterol Concentration | Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug. | Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113 | 
| Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: Creatine Kinase Concentration | Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug. | Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113 | 
| Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: Creatinine Concentration | Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug. | Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113 | 
| Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: Direct Bilirubin Concentration | Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug. | Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113 | 
| Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: Gamma Glutamyl Transferase Concentration | Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug. | Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113 | 
| Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: Lactate Dehydrogenase Concentration | Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug. | Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113 | 
| Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: Potassium Concentration | Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug. | Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113 | 
| Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: Total Protein Concentration | Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug. | Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113 | 
| Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: SGOT/AST Concentration | Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug. SGOT/AST = serum glutamic-oxaloacetic transaminase/aspartate transaminase | Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113 | 
| Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: SGPT/ALT Concentration | Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug. SGPT/ALT = serum glutamic-pyruvic transaminase/alanine transaminase | Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113 | 
| Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: Sodium Concentration | Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug. | Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113 | 
| Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: Fasting Triglycerides Concentration | Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug. | Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113 | 
| Change From Baseline in Clinical Chemistry Laboratory Test Results by Timepoint: Uric Acid Concentration | Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug. | Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113 | 
| Change From Baseline in Coagulation Laboratory Test Results by Timepoint: Activated Partial Thromboplastin Time | Blood samples were collected from participants at the indicated timepoints for evaluation of coagulation parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug. | Baseline and Days 2, 11, 29, 57, and 113 | 
| Change From Baseline in Coagulation Laboratory Test Results by Timepoint: Fibrinogen Concentration | Blood samples were collected from participants at the indicated timepoints for evaluation of coagulation parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug. | Baseline and Days 2, 11, 29, 57 and 113 | 
| Change From Baseline in Coagulation Laboratory Test Results by Timepoint: Prothrombin Time | Blood samples were collected from participants at the indicated timepoints for evaluation of coagulation parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug. | Baseline and Days 2, 11, 29, 57 and 113 | 
| Change From Baseline in Coagulation Laboratory Test Results by Timepoint: Prothrombin Time/International Normalized Ratio (INR) | The INR is a standardized measure of the prothrombin time. Blood samples were collected from participants at the indicated timepoints for evaluation of coagulation parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug. | Baseline and Days 2, 11, 29, 57 and 113 | 
| Change From Baseline in Hematology Laboratory Test Results by Timepoint: Basophils, Absolute Count | Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug. | Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113 | 
| Change From Baseline in Hematology Laboratory Test Results by Timepoint: Eosinophils, Absolute Count | Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug. | Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113 | 
| Change From Baseline in Hematology Laboratory Test Results by Timepoint: Erythrocyte Mean Corpuscular Hemoglobin | Erythrocyte mean corpuscular hemoglobin (MCH) is a measure of the average amount of hemoglobin per red blood cell. Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug. | Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113 | 
| Change From Baseline in Hematology Laboratory Test Results by Timepoint: Erythrocyte Mean Corpuscular Volume | Erythrocyte mean corpuscular volume is a measure of the average volume of a red blood cell. Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug. | Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113 | 
| Change From Baseline in Hematology Laboratory Test Results by Timepoint: Erythrocyte Mean Corpuscular Hemoglobin Concentration | Erythrocyte mean corpuscular hemoglobin concentration (MCHC) is a measure of the average concentration of hemoglobin per red blood cell. Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug. | Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113 | 
| Change From Baseline in Hematology Laboratory Test Results by Timepoint: Hematocrit (as a Fraction of 1) | Hematocrit is a measure of the ratio of red blood cells (RBCs) in the blood by volume. Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug. | Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113 | 
| Change From Baseline in Hematology Laboratory Test Results by Timepoint: Hemoglobin Concentration | Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug. | Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113 | 
| Change From Baseline in Hematology Laboratory Test Results by Timepoint: Lymphocytes, Absolute Count | Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug. | Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113 | 
| Change From Baseline in Hematology Laboratory Test Results by Timepoint: Monocytes, Absolute Count | Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug. | Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113 | 
| Change From Baseline in Hematology Laboratory Test Results by Timepoint: Total Neutrophils, Absolute Count | Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug. | Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113 | 
| Change From Baseline in Hematology Laboratory Test Results by Timepoint: Platelet Count | Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug. | Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113 | 
| Change From Baseline in Hematology Laboratory Test Results by Timepoint: Red Blood Cell Count | Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug. | Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113 | 
| Change From Baseline in Hematology Laboratory Test Results by Timepoint: White Blood Cell Count | Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last sample prior to initiation of study drug. | Baseline and Days 2, 4, 8, 15, 29, 43, 57, 71, 85, and 113 | 
| Number of Participants by Test Results for Blood in Urine by Timepoint | Urine samples were collected from participants at the indicated timepoints for evaluation of urinalysis parameters. The number of participants with test results for blood in urine of 0 (Absent), +1 (Trace), +2 (Positive), and +3/+4 (Strong Positive) at baseline and each timepoint are reported. Baseline was defined as the participant's last sample prior to initiation of study drug. | Baseline and Days 2, 8, 29, 57, 85, and 113 | 
| Number of Participants by Test Results for Glucose in Urine by Timepoint | Urine samples were collected from participants at the indicated timepoints for evaluation of urinalysis parameters. The number of participants with test results for glucose in urine of 0 (Absent), +1 (Trace), +2 (Positive), and +3/+4 (Strong Positive) at baseline and each timepoint are reported. Baseline was defined as the participant's last sample prior to initiation of study drug. | Baseline and Days 2, 8, 29, 57, 85, and 113 | 
| Number of Participants by Test Results for Protein in Urine by Timepoint | Urine samples were collected from participants at the indicated timepoints for evaluation of urinalysis parameters. The number of participants with test results for protein in urine of 0 (Absent), +1 (Trace), +2 (Positive), and +3/+4 (Strong Positive) at baseline and each timepoint are reported. Baseline was defined as the participant's last sample prior to initiation of study drug. | Baseline and Days 2, 8, 29, 57, 85, and 113 | 
| Change From Baseline in Vital Signs by Timepoint: Diastolic Blood Pressure | Vital signs were measured prior to blood sampling while the participant was in a supine position after they had been resting for at least 5 minutes. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last value prior to initiation of study drug. | Baseline and Days 2, 4, 6, 8, 11, 15, 22, 29, 36, 43, 50, 57, 71, 85, and 113 | 
| Change From Baseline in Vital Signs by Timepoint: Pulse Rate | Vital signs were measured prior to blood sampling while the participant was in a supine position after they had been resting for at least 5 minutes. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last value prior to initiation of study drug. | Baseline and Days 2, 4, 6, 8, 11, 15, 22, 29, 36, 43, 50, 57, 71, 85, and 113 | 
| Change From Baseline in Vital Signs by Timepoint: Respiratory Rate | Vital signs were measured prior to blood sampling while the participant was in a supine position after they had been resting for at least 5 minutes. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last value prior to initiation of study drug. | Baseline and Days 2, 4, 6, 8, 11, 15, 22, 29, 36, 43, 50, 57, 71, 85, and 113 | 
| Change From Baseline in Vital Signs by Timepoint: Systolic Blood Pressure | Vital signs were measured prior to blood sampling while the participant was in a supine position after they had been resting for at least 5 minutes. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last value prior to initiation of study drug. | Baseline and Days 2, 4, 6, 8, 11, 15, 22, 29, 36, 43, 50, 57, 71, 85, and 113 | 
| Change From Baseline in Vital Signs by Timepoint: Temperature (Axillary) | Vital signs were measured prior to blood sampling while the participant was in a supine position after they had been resting for at least 5 minutes. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last value prior to initiation of study drug. | Baseline and Days 2, 4, 6, 8, 11, 15, 22, 29, 36, 43, 50, 57, 71, 85, and 113 | 
| Change From Baseline in Electrocardiogram (ECG) Results by Timepoint: Heart Rate | The 12-lead electrocardiogram (ECG) measurements were collected in triplicate (three consecutive interpretable ECGs within 5 minutes) after the participant had been in a supine position for at least 10 minutes. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last value prior to initiation of study drug. | Baseline and Days 2, 4, 6, 8, 15, 29, 43, 57, 71, 85, and 113 | 
| Change From Baseline in ECG Results by Timepoint: PR Duration | The 12-lead electrocardiogram (ECG) measurements were collected in triplicate (three consecutive interpretable ECGs within 5 minutes) after the participant had been in a supine position for at least 10 minutes. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last value prior to initiation of study drug. | Baseline and Days 2, 4, 6, 8, 15, 29, 43, 57, 71, 85, and 113 | 
| Change From Baseline in ECG Results by Timepoint: QRS Duration | The 12-lead electrocardiogram (ECG) measurements were collected in triplicate (three consecutive interpretable ECGs within 5 minutes) after the participant had been in a supine position for at least 10 minutes. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last value prior to initiation of study drug. | Baseline and Days 2, 4, 6, 8, 15, 29, 43, 57, 71, 85, and 113 | 
| Change From Baseline in ECG Results by Timepoint: QT Duration | The 12-lead electrocardiogram (ECG) measurements were collected in triplicate (three consecutive interpretable ECGs within 5 minutes) after the participant had been in a supine position for at least 10 minutes. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last value prior to initiation of study drug. | Baseline and Days 2, 4, 6, 8, 15, 29, 43, 57, 71, 85, and 113 | 
| Change From Baseline in ECG Results by Timepoint: QTcB Duration (Bazett's Correction Formula) | The 12-lead electrocardiogram (ECG) measurements were collected in triplicate (three consecutive interpretable ECGs within 5 minutes) after the participant had been in a supine position for at least 10 minutes. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last value prior to initiation of study drug. | Baseline and Days 2, 4, 6, 8, 15, 29, 43, 57, 71, 85, and 113 | 
| Change From Baseline in ECG Results by Timepoint: QTcF Duration (Fridericia's Correction Formula) | The 12-lead electrocardiogram (ECG) measurements were collected in triplicate (three consecutive interpretable ECGs within 5 minutes) after the participant had been in a supine position for at least 10 minutes. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last value prior to initiation of study drug. | Baseline and Days 2, 4, 6, 8, 15, 29, 43, 57, 71, 85, and 113 | 
| Change From Baseline in ECG Results by Timepoint: RR Duration | The 12-lead electrocardiogram (ECG) measurements were collected in triplicate (three consecutive interpretable ECGs within 5 minutes) after the participant had been in a supine position for at least 10 minutes. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The post-baseline minimum and maximum change from baseline values are, respectively, the smallest and largest value changes obtained after baseline through the last study visit, including repeat and unscheduled tests. Baseline was defined as the participant's last value prior to initiation of study drug. | Baseline and Days 2, 4, 6, 8, 15, 29, 43, 57, 71, 85, and 113 | 
| Number of Participants With Concomitant Medications | The original terms recorded by the investigator for concomitant medications were standardized by the sponsor by assigning preferred terms. The duration of treatment with the concomitant medications ranged from 1 day to 5 days. Except for 1 participant who was treated during the in-clinic period (Days -1 to 4), all other concomitant medications were recorded during the ambulatory period (Days 6 to 113). | From screening to study completion (20 weeks) |