Sickle Cell Disease
Conditions
Brief summary
TAK-755 (previously known as SHP655) is a medicine used to treat sickle cell disease (SCD). The main aim of the study is to measure the safety and tolerability of TAK-755 in SCD participants. Study participants will receive TAK-755 or placebo on Day 1. Their SCD will be treated by their doctor according to their doctor's usual clinical practice. During the study, participants will be asked to follow-up on 13 days following SHP655 or placebo administration for safety assessment. Maximum duration of participation is expected to be about 2 months.
Interventions
DRUGTAK-755
Participants will receive TAK-755 as a single IV infusion at one of the 3 dose levels of 40 IU/kg, 80 IU/kg, or 160 IU/kg.
OTHERPlacebo
Participants will receive placebo matched to TAK-755 of the 3 dose levels of 40 IU/kg, 80 IU/kg, and 160 IU/kg as single IV infusion.
Sponsors
Takeda Development Center Americas, Inc.
Shire
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Age 18 to 65 years at the time of signing the informed consent. * An understanding, ability, and willingness to fully comply with study procedures and requirements. * Ability to voluntarily provide written, signed, and dated (personally or via a legally authorized representative) informed consent to participate in the study. * Male or female with a documented history of HbSS or HbSβo thalassemia (based on clinical record of genetic, electrophoresis, or high-performance liquid chromatography testing). * Participant currently taking hydroxyurea must be on a stable dosing for 3 months at screening.
Exclusion criteria
* The participant was diagnosed with acute VOC in the 21 days before dosing on Day 1. * The participant has undergone blood transfusion within the last 30 days or blood transfusion on greater than or equal to (\>=) 2 occasions in the last 90 days, at Screening Visit. * The participant has a history of acquired or congenital thrombotic thrombocytopenic purpura. * The participant has serum creatinine level greater than (\>) 1.2 milligrams per deciliter (mg/dL). * The participant has alanine transaminase \>3\* upper limit of normal (based on clinical laboratory normal range), direct bilirubin level \>2 mg/dL, or indirect bilirubin level \>5 mg/dL at the Screening Visit. * The participant has a hemoglobin level \<5 grams per deciliter (g/dL) at the Screening Visit. * The participant has a platelet count of \<100 000/cubic millimeter (mm\^3) at the Screening Visit. * Signs or symptoms of infection requiring treatment with IV antibiotics during the Screening Period. * The participant has fever with body temperature of \>=38.5 degree Celsius (ºC) (101.3 degree Fahrenheit \[ºF\]) at the Screening Visit or before dosing on Day 1. * The participant has Acute Chest Syndrome (ACS), diagnosed or strongly suspected, as evidenced by a new infiltrate on chest radiograph, and one or more of the following criteria: 1. Fever with body temperature \>39°C (102.2°F) 2. Hypoxia (confirmed by arterial blood gases with partial pressure of arterial oxygen (PaO2) \<70 millimeter of mercury \[mmHg\]) 3. Chest pain 4. Suspicious findings on physical examination (tachypnea, intercostal retraction, wheezing, and/or rales) * The participant has recently (within the past 28 days, from Screening Visit) undergone major surgery, requires hospitalization, documented serious bacterial infection requiring antibiotic treatment, or significant bleeding. * The participant has had a recent (within the past 90 days, from Screening Visit) episode of stroke, transient ischemic attack, symptomatic pulmonary hypertension, or seizure. * Any history of hemorrhagic stroke or bleeding diathesis. * The participant has received any of the following protocol-restricted medicines: a) systemic steroid therapy within 48 hours before dosing, or there is the expectation that such therapy may be given during the study (inhaled or topical steroids are allowed); b) Anticoagulant or antiplatelet therapy within the past 3 weeks before dosing; c) crizanlizumab within the past 30 days before dosing; d) voxelotor within the past 14 days before dosing. * For participants receiving chronic or long-acting opioids, a change in dose or pain requiring medical attention in the past 14 days before dosing. * The participant has a medical or psychiatric condition that, in the opinion of the investigator, may pose a risk to the participant for participation or interfere with the conduct or results of the study. * The participant has received or plans to receive any other investigational agent within the 4 weeks prior to the study screening visit or during the course of the study. * There is the expectation that the participant will not be able to be followed for the duration of the study. * The participant is pregnant or lactating or a female of childbearing potential or male unable or unwilling to comply with birth control methods or abstinence until the end of study visit. * The participant with active use of illicit drugs (excluding marijuana) and/or alcohol dependence, as determined by the investigator. * The participant has been administered SHP655 previously. * Known life-threatening hypersensitivity reaction, including anaphylaxis, to the parent molecule ADAMTS-13, hamster protein, or other constituents of SHP655. * The participant has a positive test result for hepatitis B surface antigen, or hepatitis C antibody, or human immunodeficiency virus (HIV) antigen/antibody, at the Screening Visit. However, a participant with a hepatitis C antibody and a negative hepatitis C virus ribonucleic acid (RNA) polymerase chain reaction test is not excluded.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious (TEAEs) | From date of signing informed consent up to end of study visit (Day 28) | An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this investigational product (IP) or medicinal product. TEAEs were defined as AEs that started or worsened in severity on or after the infusion of IP. A serious TEAEs was any untoward clinical manifestation of signs, symptoms or outcomes (whether considered related to investigational product or not and at any dose) which resulted in death, was life-threatening, required inpatient hospitalization, prolongation of hospitalization, was an important medical event. TEAEs included both serious and non-serious AEs. |
| Number of Participants Who Developed Positive Binding Anti-ADAMTS13 and Inhibitory Anti-ADAMTS13 Antibodies to TAK-755 | From date of signing informed consent up to end of study visit (Day 28) | Measurement of Anti-ADAMTS13 antibodies can be used to assess whether the body's immune system has been stimulated to react to TAK-755. Binding Anti-ADAMTS13 antibodies measure antibodies that are able to bind to ADAMTS13, whether or not the antibodies have an effect on how well ADAMTS13 works. An inhibitory Anti-ADAMTS13 antibody is antibody that both binds to ADAMTS13 and able to affect how well ADAMTS13 works. Binding and Inhibitory anti-ADAMTS13 antibodies were categorized as pre-existing, treatment-induced, and treatment-boosted. Pre-existing: anti-ADAMTS13 antibodies were detected in the baseline sample prior to infusion with TAK-755. Treatment-induced: no anti-ADAMTS13 antibodies were detected in baseline sample but were detected in any sample drawn after TAK-755 infusion. Treatment-boosted: anti-ADAMTS13 antibodies were pre-existing and were detected at any time after TAK-755 infusion at titers that were at least 4 steps higher than the titers detected before TAK-755 infusion. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Reach Cmax (Tmax) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755 | Baseline (Pre-dose), 0.25, 1, 3, 8, 24, 72, 120, 168, 216, 288, and 648 hours post-dose | Tmax was a measure of the time to reach the maximum concentration in the plasma after the drug dose. Baseline was defined as the last non-missing measurement obtained prior to the date and time of the first dose of TAK-755. Baseline-adjusted values were used for this analysis. Baseline-adjusted values at each timepoint were calculated as the measured value minus the pre-infusion (baseline) value and results were summarized overall. |
| Terminal Half-Life (t1/2) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755 | Baseline (Pre-dose), 0.25, 1, 3, 8, 24, 72, 120, 168, 216, 288, and 648 hours post-dose | t1/2 was the time required for a given drug concentration in the plasma to decrease by 50%. Baseline was defined as the last non-missing measurement obtained prior to the date and time of the first dose of TAK-755. Baseline-adjusted values were used for this analysis. Baseline-adjusted values at each timepoint were calculated as the measured value minus the pre-infusion (baseline) value and results were summarized overall. |
| Mean Residence Time From Zero to Infinite (MRT0-Inf) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755 | Baseline (Pre-dose), 0.25, 1, 3, 8, 24, 72, 120, 168, 216, 288, and 648 hours post-dose | The MRT is the average time that the study product stays in the body (or plasma). The MRT0-Inf is defined as the average time from zero (pre-dose) extrapolated to infinite time (MRT0-inf). Baseline was defined as the last non-missing measurement obtained prior to the date and time of the first dose of TAK-755. Baseline-adjusted values were used for this analysis. Baseline-adjusted values at each timepoint were calculated as the measured value minus the pre-infusion (baseline) value and results were summarized overall. |
| Mean Residence Time From Zero to 72 Hours Post-dose (MRT0-72) of ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755 | Baseline (Pre-dose), 0.25, 1, 3, 8, 24, and 72 hours post-dose | The MRT is the average time that the study product stays in the body (or plasma) and The MRT0-72 is defined as the average time from zero (predose) to 72 hours post-dose (MRT0-72). Baseline was defined as the last non-missing measurement obtained prior to the date and time of the first dose of TAK-755. |
| Area Under the Curve From Zero to Time of Last Quantifiable Concentration (AUC0-Last) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755 | Baseline (Pre-dose), 0.25, 1, 3, 8, 24, 72, 120, 168, 216, 288, and 648 hours post-dose | AUC0-Last was an area under the concentration-time curve from zero (pre-dose) to time of last quantifiable concentration. Baseline was defined as the last non-missing measurement obtained prior to the date and time of the first dose of TAK-755. Baseline-adjusted values were used for this analysis. Baseline-adjusted values at each timepoint were calculated as the measured value minus the pre-infusion (baseline) value and results were summarized overall. |
| Area Under the Curve Time Curve From Zero to 72 Hours Post-dose (AUC0-72) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755 | Baseline (Pre-dose), 0.25, 1, 3, 8, 24, and 72 hours post-dose | AUC0-72 was an area under the concentration-time curve from zero (predose) to 72 hours post-dose (AUC0-72). Baseline was defined as the last non-missing measurement obtained prior to the date and time of the first dose of TAK-755. Baseline-adjusted values were used for this analysis. Baseline-adjusted values at each timepoint were calculated as the measured value minus the pre-infusion (baseline) value and results were summarized overall. |
| Area Under the Curve From Zero to Infinite Time (AUC0-Inf) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755 | Baseline (Pre-dose), 0.25, 1, 3, 8, 24, 72, 120, 168, 216, 288, and 648 hours post-dose | AUC0-inf was area under the concentration-time curve from zero (pre-dose) extrapolated to infinite time. Baseline was defined as the last non-missing measurement obtained prior to the date and time of the first dose of TAK-755. Baseline-adjusted values were used for this analysis. Baseline-adjusted values at each timepoint were calculated as the measured value minus the pre-infusion (baseline) value and results were summarized overall. |
| Incremental Recovery (IR) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755 | Baseline (Pre-dose), 0.25, 1, 3, 8, 24, 72, 120, 168, 216, 288, and 648 hours post-dose | IR was defined as the ratio of maximum increase in plasma ADAMTS13 antigen or activity level to TAK-755 dose per body weight. Baseline was defined as the last non-missing measurement obtained prior to the date and time of the first dose of TAK-755. Baseline-adjusted values were used for this analysis. Baseline-adjusted values at each timepoint were calculated as the measured value minus the pre-infusion (baseline) value and results were summarized overall. Here IU/mL/IU/kg refers to International units per milliliter per international units per kilogram. |
| Volume of Distribution at Steady State (Vss) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755 | Baseline (Pre-dose), 0.25, 1, 3, 8, 24, 72, 120, 168, 216, 288, and 648 hours post-dose | Vss is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Steady state volume of distribution (Vss) is the apparent volume of distribution at steady-state which is estimated by MRT(0-inf)\*CL. Baseline was defined as the last non-missing measurement obtained prior to the date and time of the first dose of TAK-755. Baseline-adjusted values were used for this analysis. Baseline-adjusted values at each timepoint were calculated as the measured value minus the pre-infusion (baseline) value and results were summarized overall. |
| Change From Baseline in Von Willebrand Factor: Antigen (VWF:Ag) at Specified Timepoints | Baseline (Pre-dose), 0.25, 1, 3, 8, 24, 72, 120, 168, 216, 288, and 648 hours post-dose | Von Willebrand factor (vWF or VWF) is a protein that is one of several components of the coagulation system that work together to stop bleeding within the body. VWF:Ag measures the level of von Willebrand factor protein in the blood. The change from baseline in VWF:Ag concentration was measured at different time points. Baseline was defined as the last non-missing measurement obtained prior to the date and time of the dose of IP. Change from baseline was calculated by subtracting the baseline value from the post-dose value. |
| Change From Baseline in Von Willebrand Factor:Ristocetin Cofactor Activity (VWF:RCo) At Specified Timepoints | Baseline (Pre-dose), 0.25, 1, 3, 8, 24, 72, 120, 168, 216, 288, and 648 hours post-dose | Von Willebrand factor (vWF or VWF) is a protein that is one of several components of the coagulation system that work together, to stop bleeding within the body. VWF:RCo assay is a test that measures the activity of the VWF in a plasma sample in terms of how well it is able to clump platelets together in the presence of the antibiotic ristocetin. Change from baseline in vWF:RCo concentration was measured at different timepoints. Baseline was defined as the last non-missing measurement obtained prior to the date and time of the dose of IP. Change from baseline was calculated by subtracting the baseline value from the post-dose value. |
| Change From Baseline in Platelet Count at Specified Timepoints | Baseline (Pre-dose), 3, 8, 24, 72, 120, 168, 216, 288, and 648 hours post-dose | Blood samples were collected to analyze platelet count. Baseline was defined as the last non-missing measurement obtained prior to the date and time of the dose of IP. Thechange from baseline was calculated by subtracting the baseline value from the post-dose value. |
| Change From Baseline in Plasma Free Hemoglobin at Specified Timepoints | Baseline (Pre-dose), 3, 8, 24, 72, 120, 168, 216, 288, and 648 hours post-dose | The plasma free hemoglobin test measures the level of hemoglobin in the plasma (that is, not contained within the red blood cells). Baseline was defined as the last non-missing measurement obtained prior to the date and time of the dose of IP. Change from baseline was calculated by subtracting the baseline value from the post-dose value. |
| Change From Baseline in Plasma Thrombospondin Levels at Specified Timepoints | Baseline (Pre-dose), 3, 8, 24, 72, 120, 168, 288, and 648 hours post-dose | Change from baseline in plasma thrombospondin levels over time was reported. Baseline was defined as the last non-missing measurement obtained prior to the date and time of the dose of IP. Change from baseline was calculated by subtracting the baseline value from the post-dose value. |
| Systemic Clearance (CL) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755 | Baseline (Pre-dose), 0.25, 1, 3, 8, 24, 72, 120, 168, 216, 288, and 648 hours post-dose | CL is a quantitative measure of the rate at which a drug substance is removed from the body. The total systemic clearance after intravenous dose was estimated by dividing the total administered dose by the plasma Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC\[0-infinity\]). Baseline was defined as the last non-missing measurement obtained prior to the date and time of the first dose of TAK-755. Baseline-adjusted values were used for this analysis. Baseline-adjusted values at each timepoint were calculated as the measured value minus the pre-infusion (baseline) value and results were summarized overall. |
| Observed Maximum Concentration (Cmax) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755 | Baseline (Pre-dose), 0.25, 1, 3, 8, 24, 72, 120, 168, 216, 288, and 648 hours post-dose | Cmax was a measure of the maximum amount of drug in the plasma after the dose was given. Baseline was defined as the last non-missing measurement obtained prior to the date and time of the first dose of TAK-755. Baseline-adjusted values were used for this analysis. Baseline-adjusted values at each timepoint were calculated as the measured value minus the pre-infusion (baseline) value and results were summarized overall. |
Countries
United States
Participant flow
Recruitment details
This study was conducted at 9 active sites in the United States from 21 October 2019 to 26 October 2022.
Pre-assignment details
A total of 19 participants were enrolled and treated in this study.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants with SCD at their baseline health received a single IV infusion of placebo matched to TAK-755 at 3 dose levels of 40 IU/kg, 80 IU/kg, and 160 IU/kg on Day 1 and followed for up to 28 days. | 5 |
| TAK-755: 40 IU/kg Participants with SCD at their baseline health received a single IV infusion of TAK-755 at a dose level of 40 IU/kg on Day 1 and followed for up to 28 days. | 4 |
| TAK-755: 80 IU/kg Participants with SCD at their baseline health received a single IV infusion of TAK-755 at a dose level of 80 IU/kg on Day 1 and followed for up to 28 days. | 6 |
| TAK-755: 160 IU/kg Participants with SCD at their baseline health received a single IV infusion of TAK-755 at a dose level of 160 IU/kg on Day 1 and followed for up to 28 days. | 4 |
| Total | 19 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Protocol Deviation | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Placebo | TAK-755: 40 IU/kg | TAK-755: 80 IU/kg | TAK-755: 160 IU/kg | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants | 4 Participants | 6 Participants | 4 Participants | 19 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 4 Participants | 6 Participants | 4 Participants | 19 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 4 Participants | 6 Participants | 4 Participants | 19 Participants |
| Race (NIH/OMB) More than one race | 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 |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 3 Participants | 1 Participants | 3 Participants | 1 Participants | 8 Participants |
| Sex: Female, Male Male | 2 Participants | 3 Participants | 3 Participants | 3 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 0 / 4 | 0 / 6 | 0 / 4 |
| other Total, other adverse events | 2 / 5 | 2 / 4 | 4 / 6 | 2 / 4 |
| serious Total, serious adverse events | 0 / 5 | 1 / 4 | 0 / 6 | 0 / 4 |
Outcome results
Primary
Number of Participants Who Developed Positive Binding Anti-ADAMTS13 and Inhibitory Anti-ADAMTS13 Antibodies to TAK-755
Measurement of Anti-ADAMTS13 antibodies can be used to assess whether the body's immune system has been stimulated to react to TAK-755. Binding Anti-ADAMTS13 antibodies measure antibodies that are able to bind to ADAMTS13, whether or not the antibodies have an effect on how well ADAMTS13 works. An inhibitory Anti-ADAMTS13 antibody is antibody that both binds to ADAMTS13 and able to affect how well ADAMTS13 works. Binding and Inhibitory anti-ADAMTS13 antibodies were categorized as pre-existing, treatment-induced, and treatment-boosted. Pre-existing: anti-ADAMTS13 antibodies were detected in the baseline sample prior to infusion with TAK-755. Treatment-induced: no anti-ADAMTS13 antibodies were detected in baseline sample but were detected in any sample drawn after TAK-755 infusion. Treatment-boosted: anti-ADAMTS13 antibodies were pre-existing and were detected at any time after TAK-755 infusion at titers that were at least 4 steps higher than the titers detected before TAK-755 infusion.
Time frame: From date of signing informed consent up to end of study visit (Day 28)
Population: The SAS included all participants randomized and who received any dose of IP.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants Who Developed Positive Binding Anti-ADAMTS13 and Inhibitory Anti-ADAMTS13 Antibodies to TAK-755 | Pre-Existing Inhibitory Anti-ADAMTS13 Antibodies | 0 Participants |
| Placebo | Number of Participants Who Developed Positive Binding Anti-ADAMTS13 and Inhibitory Anti-ADAMTS13 Antibodies to TAK-755 | Treatment-Induced Inhibitory Anti-ADAMTS13 Antibodies | 0 Participants |
| Placebo | Number of Participants Who Developed Positive Binding Anti-ADAMTS13 and Inhibitory Anti-ADAMTS13 Antibodies to TAK-755 | Treatment-Boosted Inhibitory Anti-ADAMTS13 Antibodies | 0 Participants |
| Placebo | Number of Participants Who Developed Positive Binding Anti-ADAMTS13 and Inhibitory Anti-ADAMTS13 Antibodies to TAK-755 | Pre-Existing Binding Anti-ADAMTS13 Antibodies | 1 Participants |
| Placebo | Number of Participants Who Developed Positive Binding Anti-ADAMTS13 and Inhibitory Anti-ADAMTS13 Antibodies to TAK-755 | Treatment-Induced Binding Anti-ADAMTS13 Antibodies | 1 Participants |
| Placebo | Number of Participants Who Developed Positive Binding Anti-ADAMTS13 and Inhibitory Anti-ADAMTS13 Antibodies to TAK-755 | Treatment-Boosted Binding Anti-ADAMTS13 Antibodies | 0 Participants |
| TAK-755: 40 IU/kg | Number of Participants Who Developed Positive Binding Anti-ADAMTS13 and Inhibitory Anti-ADAMTS13 Antibodies to TAK-755 | Treatment-Boosted Binding Anti-ADAMTS13 Antibodies | 0 Participants |
| TAK-755: 40 IU/kg | Number of Participants Who Developed Positive Binding Anti-ADAMTS13 and Inhibitory Anti-ADAMTS13 Antibodies to TAK-755 | Pre-Existing Binding Anti-ADAMTS13 Antibodies | 1 Participants |
| TAK-755: 40 IU/kg | Number of Participants Who Developed Positive Binding Anti-ADAMTS13 and Inhibitory Anti-ADAMTS13 Antibodies to TAK-755 | Pre-Existing Inhibitory Anti-ADAMTS13 Antibodies | 0 Participants |
| TAK-755: 40 IU/kg | Number of Participants Who Developed Positive Binding Anti-ADAMTS13 and Inhibitory Anti-ADAMTS13 Antibodies to TAK-755 | Treatment-Boosted Inhibitory Anti-ADAMTS13 Antibodies | 0 Participants |
| TAK-755: 40 IU/kg | Number of Participants Who Developed Positive Binding Anti-ADAMTS13 and Inhibitory Anti-ADAMTS13 Antibodies to TAK-755 | Treatment-Induced Inhibitory Anti-ADAMTS13 Antibodies | 0 Participants |
| TAK-755: 40 IU/kg | Number of Participants Who Developed Positive Binding Anti-ADAMTS13 and Inhibitory Anti-ADAMTS13 Antibodies to TAK-755 | Treatment-Induced Binding Anti-ADAMTS13 Antibodies | 1 Participants |
| TAK-755: 80 IU/kg | Number of Participants Who Developed Positive Binding Anti-ADAMTS13 and Inhibitory Anti-ADAMTS13 Antibodies to TAK-755 | Treatment-Induced Inhibitory Anti-ADAMTS13 Antibodies | 0 Participants |
| TAK-755: 80 IU/kg | Number of Participants Who Developed Positive Binding Anti-ADAMTS13 and Inhibitory Anti-ADAMTS13 Antibodies to TAK-755 | Treatment-Boosted Inhibitory Anti-ADAMTS13 Antibodies | 0 Participants |
| TAK-755: 80 IU/kg | Number of Participants Who Developed Positive Binding Anti-ADAMTS13 and Inhibitory Anti-ADAMTS13 Antibodies to TAK-755 | Pre-Existing Binding Anti-ADAMTS13 Antibodies | 2 Participants |
| TAK-755: 80 IU/kg | Number of Participants Who Developed Positive Binding Anti-ADAMTS13 and Inhibitory Anti-ADAMTS13 Antibodies to TAK-755 | Treatment-Boosted Binding Anti-ADAMTS13 Antibodies | 0 Participants |
| TAK-755: 80 IU/kg | Number of Participants Who Developed Positive Binding Anti-ADAMTS13 and Inhibitory Anti-ADAMTS13 Antibodies to TAK-755 | Treatment-Induced Binding Anti-ADAMTS13 Antibodies | 1 Participants |
| TAK-755: 80 IU/kg | Number of Participants Who Developed Positive Binding Anti-ADAMTS13 and Inhibitory Anti-ADAMTS13 Antibodies to TAK-755 | Pre-Existing Inhibitory Anti-ADAMTS13 Antibodies | 0 Participants |
| TAK-755: 160 IU/kg | Number of Participants Who Developed Positive Binding Anti-ADAMTS13 and Inhibitory Anti-ADAMTS13 Antibodies to TAK-755 | Treatment-Induced Binding Anti-ADAMTS13 Antibodies | 0 Participants |
| TAK-755: 160 IU/kg | Number of Participants Who Developed Positive Binding Anti-ADAMTS13 and Inhibitory Anti-ADAMTS13 Antibodies to TAK-755 | Treatment-Boosted Binding Anti-ADAMTS13 Antibodies | 0 Participants |
| TAK-755: 160 IU/kg | Number of Participants Who Developed Positive Binding Anti-ADAMTS13 and Inhibitory Anti-ADAMTS13 Antibodies to TAK-755 | Treatment-Induced Inhibitory Anti-ADAMTS13 Antibodies | 0 Participants |
| TAK-755: 160 IU/kg | Number of Participants Who Developed Positive Binding Anti-ADAMTS13 and Inhibitory Anti-ADAMTS13 Antibodies to TAK-755 | Pre-Existing Binding Anti-ADAMTS13 Antibodies | 2 Participants |
| TAK-755: 160 IU/kg | Number of Participants Who Developed Positive Binding Anti-ADAMTS13 and Inhibitory Anti-ADAMTS13 Antibodies to TAK-755 | Pre-Existing Inhibitory Anti-ADAMTS13 Antibodies | 0 Participants |
| TAK-755: 160 IU/kg | Number of Participants Who Developed Positive Binding Anti-ADAMTS13 and Inhibitory Anti-ADAMTS13 Antibodies to TAK-755 | Treatment-Boosted Inhibitory Anti-ADAMTS13 Antibodies | 0 Participants |
Primary
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious (TEAEs)
An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this investigational product (IP) or medicinal product. TEAEs were defined as AEs that started or worsened in severity on or after the infusion of IP. A serious TEAEs was any untoward clinical manifestation of signs, symptoms or outcomes (whether considered related to investigational product or not and at any dose) which resulted in death, was life-threatening, required inpatient hospitalization, prolongation of hospitalization, was an important medical event. TEAEs included both serious and non-serious AEs.
Time frame: From date of signing informed consent up to end of study visit (Day 28)
Population: SAS included all participants randomized and who received any dose of IP.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious (TEAEs) | Participants with TEAEs | 2 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious (TEAEs) | Participants with Serious TEAEs | 0 Participants |
| TAK-755: 40 IU/kg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious (TEAEs) | Participants with Serious TEAEs | 1 Participants |
| TAK-755: 40 IU/kg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious (TEAEs) | Participants with TEAEs | 2 Participants |
| TAK-755: 80 IU/kg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious (TEAEs) | Participants with Serious TEAEs | 0 Participants |
| TAK-755: 80 IU/kg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious (TEAEs) | Participants with TEAEs | 4 Participants |
| TAK-755: 160 IU/kg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious (TEAEs) | Participants with Serious TEAEs | 0 Participants |
| TAK-755: 160 IU/kg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious (TEAEs) | Participants with TEAEs | 2 Participants |
Secondary
Area Under the Curve From Zero to Infinite Time (AUC0-Inf) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755
AUC0-inf was area under the concentration-time curve from zero (pre-dose) extrapolated to infinite time. Baseline was defined as the last non-missing measurement obtained prior to the date and time of the first dose of TAK-755. Baseline-adjusted values were used for this analysis. Baseline-adjusted values at each timepoint were calculated as the measured value minus the pre-infusion (baseline) value and results were summarized overall.
Time frame: Baseline (Pre-dose), 0.25, 1, 3, 8, 24, 72, 120, 168, 216, 288, and 648 hours post-dose
Population: The PK Analysis Set included all participants who received at least 1 complete dose of TAK-755 or placebo and provided at least 1 concentration measured at a scheduled time post start of infusion for at least 1 of the PK analytes and had no major protocol deviations or events that may affect the integrity of the PK data. Data was not analyzed for PK parameters in the placebo arm where participants did not receive TAK-755.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Area Under the Curve From Zero to Infinite Time (AUC0-Inf) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755 | Baseline-adjusted ADAMTS13 Activity | NA hour* International unit per milliliter | — |
| Placebo | Area Under the Curve From Zero to Infinite Time (AUC0-Inf) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755 | Baseline-adjusted ADAMTS13 Antigen | NA hour* International unit per milliliter | — |
| TAK-755: 40 IU/kg | Area Under the Curve From Zero to Infinite Time (AUC0-Inf) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755 | Baseline-adjusted ADAMTS13 Activity | 190.1 hour* International unit per milliliter | Geometric Coefficient of Variation 45.3 |
| TAK-755: 40 IU/kg | Area Under the Curve From Zero to Infinite Time (AUC0-Inf) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755 | Baseline-adjusted ADAMTS13 Antigen | 88.34 hour* International unit per milliliter | Geometric Coefficient of Variation 34.6 |
| TAK-755: 80 IU/kg | Area Under the Curve From Zero to Infinite Time (AUC0-Inf) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755 | Baseline-adjusted ADAMTS13 Activity | 152.5 hour* International unit per milliliter | Geometric Coefficient of Variation 46.6 |
| TAK-755: 80 IU/kg | Area Under the Curve From Zero to Infinite Time (AUC0-Inf) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755 | Baseline-adjusted ADAMTS13 Antigen | 114.0 hour* International unit per milliliter | Geometric Coefficient of Variation 27.5 |
Secondary
Area Under the Curve From Zero to Time of Last Quantifiable Concentration (AUC0-Last) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755
AUC0-Last was an area under the concentration-time curve from zero (pre-dose) to time of last quantifiable concentration. Baseline was defined as the last non-missing measurement obtained prior to the date and time of the first dose of TAK-755. Baseline-adjusted values were used for this analysis. Baseline-adjusted values at each timepoint were calculated as the measured value minus the pre-infusion (baseline) value and results were summarized overall.
Time frame: Baseline (Pre-dose), 0.25, 1, 3, 8, 24, 72, 120, 168, 216, 288, and 648 hours post-dose
Population: The PK Analysis Set included all participants who received at least 1 complete dose of TAK-755 or placebo and provided at least 1 concentration measured at a scheduled time post start of infusion for at least 1 of the PK analytes and had no major protocol deviations or events that may affect the integrity of the PK data. Data was not analyzed for PK parameters in the placebo arm where participants did not receive TAK-755.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Area Under the Curve From Zero to Time of Last Quantifiable Concentration (AUC0-Last) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755 | Baseline-adjusted ADAMTS13 Activity | NA hour* International unit per milliliter | — |
| Placebo | Area Under the Curve From Zero to Time of Last Quantifiable Concentration (AUC0-Last) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755 | Baseline-adjusted ADAMTS13 Antigen | 25.96 hour* International unit per milliliter | Geometric Coefficient of Variation 32.9 |
| TAK-755: 40 IU/kg | Area Under the Curve From Zero to Time of Last Quantifiable Concentration (AUC0-Last) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755 | Baseline-adjusted ADAMTS13 Activity | 161.5 hour* International unit per milliliter | Geometric Coefficient of Variation 28.1 |
| TAK-755: 40 IU/kg | Area Under the Curve From Zero to Time of Last Quantifiable Concentration (AUC0-Last) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755 | Baseline-adjusted ADAMTS13 Antigen | 79.05 hour* International unit per milliliter | Geometric Coefficient of Variation 22 |
| TAK-755: 80 IU/kg | Area Under the Curve From Zero to Time of Last Quantifiable Concentration (AUC0-Last) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755 | Baseline-adjusted ADAMTS13 Activity | 137.2 hour* International unit per milliliter | Geometric Coefficient of Variation 36.1 |
| TAK-755: 80 IU/kg | Area Under the Curve From Zero to Time of Last Quantifiable Concentration (AUC0-Last) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755 | Baseline-adjusted ADAMTS13 Antigen | 105.7 hour* International unit per milliliter | Geometric Coefficient of Variation 27.7 |
Secondary
Area Under the Curve Time Curve From Zero to 72 Hours Post-dose (AUC0-72) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755
AUC0-72 was an area under the concentration-time curve from zero (predose) to 72 hours post-dose (AUC0-72). Baseline was defined as the last non-missing measurement obtained prior to the date and time of the first dose of TAK-755. Baseline-adjusted values were used for this analysis. Baseline-adjusted values at each timepoint were calculated as the measured value minus the pre-infusion (baseline) value and results were summarized overall.
Time frame: Baseline (Pre-dose), 0.25, 1, 3, 8, 24, and 72 hours post-dose
Population: The PK Analysis Set included all participants who received at least 1 complete dose of TAK-775 or placebo and provided at least 1 concentration measured at a scheduled time post start of infusion for at least 1 of the PK analytes and had no major protocol deviations or events that may affect the integrity of the PK data. Data was not analyzed for PK parameters in the placebo arm where participants did not receive TAK-755.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Area Under the Curve Time Curve From Zero to 72 Hours Post-dose (AUC0-72) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755 | Baseline-adjusted ADAMTS13 Activity | 19.77 hour* International unit per milliliter | Geometric Coefficient of Variation 122.3 |
| Placebo | Area Under the Curve Time Curve From Zero to 72 Hours Post-dose (AUC0-72) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755 | Baseline-adjusted ADAMTS13 Antigen | 17.91 hour* International unit per milliliter | Geometric Coefficient of Variation 22.7 |
| TAK-755: 40 IU/kg | Area Under the Curve Time Curve From Zero to 72 Hours Post-dose (AUC0-72) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755 | Baseline-adjusted ADAMTS13 Activity | 78.44 hour* International unit per milliliter | Geometric Coefficient of Variation 36.8 |
| TAK-755: 40 IU/kg | Area Under the Curve Time Curve From Zero to 72 Hours Post-dose (AUC0-72) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755 | Baseline-adjusted ADAMTS13 Antigen | 42.86 hour* International unit per milliliter | Geometric Coefficient of Variation 9.5 |
| TAK-755: 80 IU/kg | Area Under the Curve Time Curve From Zero to 72 Hours Post-dose (AUC0-72) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755 | Baseline-adjusted ADAMTS13 Activity | 92.41 hour* International unit per milliliter | Geometric Coefficient of Variation 27.1 |
| TAK-755: 80 IU/kg | Area Under the Curve Time Curve From Zero to 72 Hours Post-dose (AUC0-72) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755 | Baseline-adjusted ADAMTS13 Antigen | 73.20 hour* International unit per milliliter | Geometric Coefficient of Variation 22 |
Secondary
Change From Baseline in Plasma Free Hemoglobin at Specified Timepoints
The plasma free hemoglobin test measures the level of hemoglobin in the plasma (that is, not contained within the red blood cells). Baseline was defined as the last non-missing measurement obtained prior to the date and time of the dose of IP. Change from baseline was calculated by subtracting the baseline value from the post-dose value.
Time frame: Baseline (Pre-dose), 3, 8, 24, 72, 120, 168, 216, 288, and 648 hours post-dose
Population: Pharmacodynamic analysis set: All participants who received at least 1 complete dose of TAK-755 or placebo and provided at least 1 valid data point post-dose of the respective infusion for at least 1 PD measurement for any of the PD outcome and had no major protocol deviations or events that may have affected the integrity of the PD data. Overall Number of Participants Analyzed refers participants evaluable for this outcome and number analyzed refers participants at the specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Plasma Free Hemoglobin at Specified Timepoints | Change at 72 hours | -9.23 milligrams per deciliter (mg/dL) | Standard Deviation 22.105 |
| Placebo | Change From Baseline in Plasma Free Hemoglobin at Specified Timepoints | Change at 3 hours | -5.23 milligrams per deciliter (mg/dL) | Standard Deviation 21.732 |
| Placebo | Change From Baseline in Plasma Free Hemoglobin at Specified Timepoints | Change at 8 hours | -11.28 milligrams per deciliter (mg/dL) | Standard Deviation 18.671 |
| Placebo | Change From Baseline in Plasma Free Hemoglobin at Specified Timepoints | Change at 24 hours | -3.88 milligrams per deciliter (mg/dL) | Standard Deviation 21.39 |
| Placebo | Change From Baseline in Plasma Free Hemoglobin at Specified Timepoints | Change at 120 hours | -14.70 milligrams per deciliter (mg/dL) | Standard Deviation 27.12 |
| Placebo | Change From Baseline in Plasma Free Hemoglobin at Specified Timepoints | Change at 168 hours | -10.60 milligrams per deciliter (mg/dL) | Standard Deviation 23.047 |
| Placebo | Change From Baseline in Plasma Free Hemoglobin at Specified Timepoints | Change at 288 hours | -8.05 milligrams per deciliter (mg/dL) | Standard Deviation 25.683 |
| Placebo | Change From Baseline in Plasma Free Hemoglobin at Specified Timepoints | Change at 648 hours | 13.30 milligrams per deciliter (mg/dL) | Standard Deviation 53.656 |
| TAK-755: 40 IU/kg | Change From Baseline in Plasma Free Hemoglobin at Specified Timepoints | Change at 168 hours | -44.37 milligrams per deciliter (mg/dL) | Standard Deviation 50.024 |
| TAK-755: 40 IU/kg | Change From Baseline in Plasma Free Hemoglobin at Specified Timepoints | Change at 120 hours | NA milligrams per deciliter (mg/dL) | — |
| TAK-755: 40 IU/kg | Change From Baseline in Plasma Free Hemoglobin at Specified Timepoints | Change at 8 hours | -30.58 milligrams per deciliter (mg/dL) | Standard Deviation 34.219 |
| TAK-755: 40 IU/kg | Change From Baseline in Plasma Free Hemoglobin at Specified Timepoints | Change at 648 hours | -26.43 milligrams per deciliter (mg/dL) | Standard Deviation 45.465 |
| TAK-755: 40 IU/kg | Change From Baseline in Plasma Free Hemoglobin at Specified Timepoints | Change at 3 hours | -8.98 milligrams per deciliter (mg/dL) | Standard Deviation 23.93 |
| TAK-755: 40 IU/kg | Change From Baseline in Plasma Free Hemoglobin at Specified Timepoints | Change at 72 hours | -44.93 milligrams per deciliter (mg/dL) | Standard Deviation 35.4 |
| TAK-755: 40 IU/kg | Change From Baseline in Plasma Free Hemoglobin at Specified Timepoints | Change at 24 hours | -34.28 milligrams per deciliter (mg/dL) | Standard Deviation 36.621 |
| TAK-755: 40 IU/kg | Change From Baseline in Plasma Free Hemoglobin at Specified Timepoints | Change at 288 hours | -46.47 milligrams per deciliter (mg/dL) | Standard Deviation 43.714 |
| TAK-755: 80 IU/kg | Change From Baseline in Plasma Free Hemoglobin at Specified Timepoints | Change at 8 hours | NA milligrams per deciliter (mg/dL) | — |
| TAK-755: 80 IU/kg | Change From Baseline in Plasma Free Hemoglobin at Specified Timepoints | Change at 24 hours | -44.77 milligrams per deciliter (mg/dL) | Standard Deviation 47.417 |
| TAK-755: 80 IU/kg | Change From Baseline in Plasma Free Hemoglobin at Specified Timepoints | Change at 72 hours | -49.27 milligrams per deciliter (mg/dL) | Standard Deviation 47.55 |
| TAK-755: 80 IU/kg | Change From Baseline in Plasma Free Hemoglobin at Specified Timepoints | Change at 120 hours | -47.47 milligrams per deciliter (mg/dL) | Standard Deviation 48.187 |
| TAK-755: 80 IU/kg | Change From Baseline in Plasma Free Hemoglobin at Specified Timepoints | Change at 168 hours | -41.37 milligrams per deciliter (mg/dL) | Standard Deviation 47.933 |
| TAK-755: 80 IU/kg | Change From Baseline in Plasma Free Hemoglobin at Specified Timepoints | Change at 648 hours | -43.83 milligrams per deciliter (mg/dL) | Standard Deviation 50.519 |
| TAK-755: 80 IU/kg | Change From Baseline in Plasma Free Hemoglobin at Specified Timepoints | Change at 3 hours | NA milligrams per deciliter (mg/dL) | — |
| TAK-755: 80 IU/kg | Change From Baseline in Plasma Free Hemoglobin at Specified Timepoints | Change at 288 hours | -46.67 milligrams per deciliter (mg/dL) | Standard Deviation 47.013 |
| TAK-755: 160 IU/kg | Change From Baseline in Plasma Free Hemoglobin at Specified Timepoints | Change at 8 hours | -147.80 milligrams per deciliter (mg/dL) | Standard Deviation 251.263 |
| TAK-755: 160 IU/kg | Change From Baseline in Plasma Free Hemoglobin at Specified Timepoints | Change at 72 hours | -108.30 milligrams per deciliter (mg/dL) | Standard Deviation 218.455 |
| TAK-755: 160 IU/kg | Change From Baseline in Plasma Free Hemoglobin at Specified Timepoints | Change at 24 hours | -105.95 milligrams per deciliter (mg/dL) | Standard Deviation 214.072 |
| TAK-755: 160 IU/kg | Change From Baseline in Plasma Free Hemoglobin at Specified Timepoints | Change at 288 hours | 5.17 milligrams per deciliter (mg/dL) | Standard Deviation 4.319 |
| TAK-755: 160 IU/kg | Change From Baseline in Plasma Free Hemoglobin at Specified Timepoints | Change at 120 hours | -98.18 milligrams per deciliter (mg/dL) | Standard Deviation 226.371 |
| TAK-755: 160 IU/kg | Change From Baseline in Plasma Free Hemoglobin at Specified Timepoints | Change at 648 hours | -130.87 milligrams per deciliter (mg/dL) | Standard Deviation 265.316 |
| TAK-755: 160 IU/kg | Change From Baseline in Plasma Free Hemoglobin at Specified Timepoints | Change at 3 hours | -106.15 milligrams per deciliter (mg/dL) | Standard Deviation 216.38 |
| TAK-755: 160 IU/kg | Change From Baseline in Plasma Free Hemoglobin at Specified Timepoints | Change at 168 hours | -123.83 milligrams per deciliter (mg/dL) | Standard Deviation 274.097 |
Secondary
Change From Baseline in Plasma Thrombospondin Levels at Specified Timepoints
Change from baseline in plasma thrombospondin levels over time was reported. Baseline was defined as the last non-missing measurement obtained prior to the date and time of the dose of IP. Change from baseline was calculated by subtracting the baseline value from the post-dose value.
Time frame: Baseline (Pre-dose), 3, 8, 24, 72, 120, 168, 288, and 648 hours post-dose
Population: Pharmacodynamic analysis set: All participants who received at least 1 complete dose of TAK-755 or placebo and provided at least 1 valid data point post-dose of the respective infusion for at least 1 PD measurement for any of the PD outcome and had no major protocol deviations or events that may have affected the integrity of the PD data. Overall Number of Participants Analyzed refers participants evaluable for this outcome and number analyzed refers participants at the specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Plasma Thrombospondin Levels at Specified Timepoints | Change at 8 hours | -1892.8 nanograms per milliliter (ng/mL) | Standard Deviation 3500.43 |
| Placebo | Change From Baseline in Plasma Thrombospondin Levels at Specified Timepoints | Change at 648 hours | -2857.0 nanograms per milliliter (ng/mL) | Standard Deviation 4236.96 |
| Placebo | Change From Baseline in Plasma Thrombospondin Levels at Specified Timepoints | Change at 24 hours | -934.0 nanograms per milliliter (ng/mL) | Standard Deviation 1815.42 |
| Placebo | Change From Baseline in Plasma Thrombospondin Levels at Specified Timepoints | Change at 72 hours | -701.4 nanograms per milliliter (ng/mL) | Standard Deviation 2560.18 |
| Placebo | Change From Baseline in Plasma Thrombospondin Levels at Specified Timepoints | Change at 120 hours | -1075.0 nanograms per milliliter (ng/mL) | Standard Deviation 1357.88 |
| Placebo | Change From Baseline in Plasma Thrombospondin Levels at Specified Timepoints | Change at 3 hours | 840.4 nanograms per milliliter (ng/mL) | Standard Deviation 3979.24 |
| Placebo | Change From Baseline in Plasma Thrombospondin Levels at Specified Timepoints | Change at 168 hours | -3886.0 nanograms per milliliter (ng/mL) | Standard Deviation 3999.22 |
| Placebo | Change From Baseline in Plasma Thrombospondin Levels at Specified Timepoints | Change at 288 hours | -103.0 nanograms per milliliter (ng/mL) | Standard Deviation 1974.37 |
| TAK-755: 40 IU/kg | Change From Baseline in Plasma Thrombospondin Levels at Specified Timepoints | Change at 72 hours | -651.8 nanograms per milliliter (ng/mL) | Standard Deviation 1208.59 |
| TAK-755: 40 IU/kg | Change From Baseline in Plasma Thrombospondin Levels at Specified Timepoints | Change at 288 hours | -482.0 nanograms per milliliter (ng/mL) | Standard Deviation 1150.09 |
| TAK-755: 40 IU/kg | Change From Baseline in Plasma Thrombospondin Levels at Specified Timepoints | Change at 24 hours | -408.0 nanograms per milliliter (ng/mL) | Standard Deviation 1140.98 |
| TAK-755: 40 IU/kg | Change From Baseline in Plasma Thrombospondin Levels at Specified Timepoints | Change at 8 hours | -604.5 nanograms per milliliter (ng/mL) | Standard Deviation 1763.64 |
| TAK-755: 40 IU/kg | Change From Baseline in Plasma Thrombospondin Levels at Specified Timepoints | Change at 120 hours | -1428.7 nanograms per milliliter (ng/mL) | Standard Deviation 1892.45 |
| TAK-755: 40 IU/kg | Change From Baseline in Plasma Thrombospondin Levels at Specified Timepoints | Change at 648 hours | -766.0 nanograms per milliliter (ng/mL) | Standard Deviation 1948.34 |
| TAK-755: 40 IU/kg | Change From Baseline in Plasma Thrombospondin Levels at Specified Timepoints | Change at 168 hours | -847.0 nanograms per milliliter (ng/mL) | Standard Deviation 1728.41 |
| TAK-755: 40 IU/kg | Change From Baseline in Plasma Thrombospondin Levels at Specified Timepoints | Change at 3 hours | -628.5 nanograms per milliliter (ng/mL) | Standard Deviation 1420.49 |
| TAK-755: 80 IU/kg | Change From Baseline in Plasma Thrombospondin Levels at Specified Timepoints | Change at 8 hours | -1471.8 nanograms per milliliter (ng/mL) | Standard Deviation 1274.07 |
| TAK-755: 80 IU/kg | Change From Baseline in Plasma Thrombospondin Levels at Specified Timepoints | Change at 120 hours | -331.8 nanograms per milliliter (ng/mL) | Standard Deviation 3735.24 |
| TAK-755: 80 IU/kg | Change From Baseline in Plasma Thrombospondin Levels at Specified Timepoints | Change at 24 hours | -1077.0 nanograms per milliliter (ng/mL) | Standard Deviation 1699.6 |
| TAK-755: 80 IU/kg | Change From Baseline in Plasma Thrombospondin Levels at Specified Timepoints | Change at 72 hours | -1080.0 nanograms per milliliter (ng/mL) | Standard Deviation 1945.58 |
| TAK-755: 80 IU/kg | Change From Baseline in Plasma Thrombospondin Levels at Specified Timepoints | Change at 3 hours | -1177.2 nanograms per milliliter (ng/mL) | Standard Deviation 1730.05 |
| TAK-755: 80 IU/kg | Change From Baseline in Plasma Thrombospondin Levels at Specified Timepoints | Change at 168 hours | -1623.7 nanograms per milliliter (ng/mL) | Standard Deviation 1569.6 |
| TAK-755: 80 IU/kg | Change From Baseline in Plasma Thrombospondin Levels at Specified Timepoints | Change at 288 hours | -1290.7 nanograms per milliliter (ng/mL) | Standard Deviation 1723.6 |
| TAK-755: 80 IU/kg | Change From Baseline in Plasma Thrombospondin Levels at Specified Timepoints | Change at 648 hours | -909.7 nanograms per milliliter (ng/mL) | Standard Deviation 1082.66 |
| TAK-755: 160 IU/kg | Change From Baseline in Plasma Thrombospondin Levels at Specified Timepoints | Change at 648 hours | 525.5 nanograms per milliliter (ng/mL) | Standard Deviation 3358.11 |
| TAK-755: 160 IU/kg | Change From Baseline in Plasma Thrombospondin Levels at Specified Timepoints | Change at 3 hours | -736.3 nanograms per milliliter (ng/mL) | Standard Deviation 860.29 |
| TAK-755: 160 IU/kg | Change From Baseline in Plasma Thrombospondin Levels at Specified Timepoints | Change at 8 hours | -1290.0 nanograms per milliliter (ng/mL) | Standard Deviation 1060.98 |
| TAK-755: 160 IU/kg | Change From Baseline in Plasma Thrombospondin Levels at Specified Timepoints | Change at 72 hours | -1406.0 nanograms per milliliter (ng/mL) | Standard Deviation 843.31 |
| TAK-755: 160 IU/kg | Change From Baseline in Plasma Thrombospondin Levels at Specified Timepoints | Change at 120 hours | 1351.8 nanograms per milliliter (ng/mL) | Standard Deviation 5880.93 |
| TAK-755: 160 IU/kg | Change From Baseline in Plasma Thrombospondin Levels at Specified Timepoints | Change at 168 hours | -687.5 nanograms per milliliter (ng/mL) | Standard Deviation 1373.36 |
| TAK-755: 160 IU/kg | Change From Baseline in Plasma Thrombospondin Levels at Specified Timepoints | Change at 288 hours | -903.5 nanograms per milliliter (ng/mL) | Standard Deviation 1232.02 |
| TAK-755: 160 IU/kg | Change From Baseline in Plasma Thrombospondin Levels at Specified Timepoints | Change at 24 hours | -1567.8 nanograms per milliliter (ng/mL) | Standard Deviation 957.61 |
Secondary
Change From Baseline in Platelet Count at Specified Timepoints
Blood samples were collected to analyze platelet count. Baseline was defined as the last non-missing measurement obtained prior to the date and time of the dose of IP. Thechange from baseline was calculated by subtracting the baseline value from the post-dose value.
Time frame: Baseline (Pre-dose), 3, 8, 24, 72, 120, 168, 216, 288, and 648 hours post-dose
Population: Pharmacodynamic analysis set: All participants who received at least 1 complete dose of TAK-755 or placebo and provided at least 1 valid data point post-dose of the respective infusion for at least 1 PD measurement for any of the PD outcome and had no major protocol deviations or events that may have affected the integrity of the PD data. Overall Number of Participants Analyzed refers participants evaluable for this outcome and number analyzed refers participants at the specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Platelet Count at Specified Timepoints | Change at 3 hours | -39.40 10^9 cells per liter | Standard Deviation 35.795 |
| Placebo | Change From Baseline in Platelet Count at Specified Timepoints | Change at 8 hours | -33.96 10^9 cells per liter | Standard Deviation 29.535 |
| Placebo | Change From Baseline in Platelet Count at Specified Timepoints | Change at 24 hours | -1.60 10^9 cells per liter | Standard Deviation 38.946 |
| Placebo | Change From Baseline in Platelet Count at Specified Timepoints | Change at 72 hours | -20.80 10^9 cells per liter | Standard Deviation 61.378 |
| Placebo | Change From Baseline in Platelet Count at Specified Timepoints | Change at 120 hours | 4.50 10^9 cells per liter | Standard Deviation 100.018 |
| Placebo | Change From Baseline in Platelet Count at Specified Timepoints | Change at 168 hours | -38.40 10^9 cells per liter | Standard Deviation 94.648 |
| Placebo | Change From Baseline in Platelet Count at Specified Timepoints | Change at 288 hours | -42.00 10^9 cells per liter | Standard Deviation 97.06 |
| Placebo | Change From Baseline in Platelet Count at Specified Timepoints | Change at 648 hours | -116.40 10^9 cells per liter | Standard Deviation 232.119 |
| TAK-755: 40 IU/kg | Change From Baseline in Platelet Count at Specified Timepoints | Change at 168 hours | 22.33 10^9 cells per liter | Standard Deviation 58.046 |
| TAK-755: 40 IU/kg | Change From Baseline in Platelet Count at Specified Timepoints | Change at 120 hours | 40.83 10^9 cells per liter | Standard Deviation 35.617 |
| TAK-755: 40 IU/kg | Change From Baseline in Platelet Count at Specified Timepoints | Change at 8 hours | 11.40 10^9 cells per liter | Standard Deviation 24.309 |
| TAK-755: 40 IU/kg | Change From Baseline in Platelet Count at Specified Timepoints | Change at 648 hours | 29.00 10^9 cells per liter | Standard Deviation 27.313 |
| TAK-755: 40 IU/kg | Change From Baseline in Platelet Count at Specified Timepoints | Change at 288 hours | 17.67 10^9 cells per liter | Standard Deviation 10.408 |
| TAK-755: 40 IU/kg | Change From Baseline in Platelet Count at Specified Timepoints | Change at 72 hours | 36.35 10^9 cells per liter | Standard Deviation 19.025 |
| TAK-755: 40 IU/kg | Change From Baseline in Platelet Count at Specified Timepoints | Change at 24 hours | 22.88 10^9 cells per liter | Standard Deviation 36.779 |
| TAK-755: 40 IU/kg | Change From Baseline in Platelet Count at Specified Timepoints | Change at 3 hours | 3.50 10^9 cells per liter | Standard Deviation 27.111 |
| TAK-755: 80 IU/kg | Change From Baseline in Platelet Count at Specified Timepoints | Change at 288 hours | 6.17 10^9 cells per liter | Standard Deviation 105.447 |
| TAK-755: 80 IU/kg | Change From Baseline in Platelet Count at Specified Timepoints | Change at 24 hours | -11.83 10^9 cells per liter | Standard Deviation 55.654 |
| TAK-755: 80 IU/kg | Change From Baseline in Platelet Count at Specified Timepoints | Change at 72 hours | -7.10 10^9 cells per liter | Standard Deviation 81.77 |
| TAK-755: 80 IU/kg | Change From Baseline in Platelet Count at Specified Timepoints | Change at 120 hours | 18.94 10^9 cells per liter | Standard Deviation 104.933 |
| TAK-755: 80 IU/kg | Change From Baseline in Platelet Count at Specified Timepoints | Change at 168 hours | 20.35 10^9 cells per liter | Standard Deviation 122.803 |
| TAK-755: 80 IU/kg | Change From Baseline in Platelet Count at Specified Timepoints | Change at 648 hours | 6.93 10^9 cells per liter | Standard Deviation 77.027 |
| TAK-755: 80 IU/kg | Change From Baseline in Platelet Count at Specified Timepoints | Change at 3 hours | -42.80 10^9 cells per liter | Standard Deviation 27.151 |
| TAK-755: 80 IU/kg | Change From Baseline in Platelet Count at Specified Timepoints | Change at 8 hours | -38.42 10^9 cells per liter | Standard Deviation 33.679 |
| TAK-755: 160 IU/kg | Change From Baseline in Platelet Count at Specified Timepoints | Change at 24 hours | -18.50 10^9 cells per liter | Standard Deviation 25.265 |
| TAK-755: 160 IU/kg | Change From Baseline in Platelet Count at Specified Timepoints | Change at 72 hours | -40.75 10^9 cells per liter | Standard Deviation 64.691 |
| TAK-755: 160 IU/kg | Change From Baseline in Platelet Count at Specified Timepoints | Change at 8 hours | -23.77 10^9 cells per liter | Standard Deviation 25.325 |
| TAK-755: 160 IU/kg | Change From Baseline in Platelet Count at Specified Timepoints | Change at 3 hours | -32.00 10^9 cells per liter | Standard Deviation 19.511 |
| TAK-755: 160 IU/kg | Change From Baseline in Platelet Count at Specified Timepoints | Change at 120 hours | -47.25 10^9 cells per liter | Standard Deviation 61.927 |
| TAK-755: 160 IU/kg | Change From Baseline in Platelet Count at Specified Timepoints | Change at 648 hours | 3.75 10^9 cells per liter | Standard Deviation 51.344 |
| TAK-755: 160 IU/kg | Change From Baseline in Platelet Count at Specified Timepoints | Change at 288 hours | -50.75 10^9 cells per liter | Standard Deviation 70.296 |
| TAK-755: 160 IU/kg | Change From Baseline in Platelet Count at Specified Timepoints | Change at 168 hours | -73.33 10^9 cells per liter | Standard Deviation 97.007 |
Secondary
Change From Baseline in Von Willebrand Factor: Antigen (VWF:Ag) at Specified Timepoints
Von Willebrand factor (vWF or VWF) is a protein that is one of several components of the coagulation system that work together to stop bleeding within the body. VWF:Ag measures the level of von Willebrand factor protein in the blood. The change from baseline in VWF:Ag concentration was measured at different time points. Baseline was defined as the last non-missing measurement obtained prior to the date and time of the dose of IP. Change from baseline was calculated by subtracting the baseline value from the post-dose value.
Time frame: Baseline (Pre-dose), 0.25, 1, 3, 8, 24, 72, 120, 168, 216, 288, and 648 hours post-dose
Population: Pharmacodynamic analysis set: All participants who received at least 1 complete dose of TAK-755 or placebo and provided at least 1 valid data point post-dose of the respective infusion for at least 1 PD measurement for any of the PD outcome and had no major protocol deviations or events that may have affected the integrity of the PD data. Overall Number of Participants Analyzed refers participants evaluable for this outcome and number analyzed refers participants at the specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Von Willebrand Factor: Antigen (VWF:Ag) at Specified Timepoints | Change at 288 hours | -38.40 Percentage of vWF Ag | Standard Deviation 33.032 |
| Placebo | Change From Baseline in Von Willebrand Factor: Antigen (VWF:Ag) at Specified Timepoints | Change at 72 hours | -25.20 Percentage of vWF Ag | Standard Deviation 27.695 |
| Placebo | Change From Baseline in Von Willebrand Factor: Antigen (VWF:Ag) at Specified Timepoints | Change at 8 hours | -8.20 Percentage of vWF Ag | Standard Deviation 14.245 |
| Placebo | Change From Baseline in Von Willebrand Factor: Antigen (VWF:Ag) at Specified Timepoints | Change at 216 hours | -44.10 Percentage of vWF Ag | Standard Deviation 35.056 |
| Placebo | Change From Baseline in Von Willebrand Factor: Antigen (VWF:Ag) at Specified Timepoints | Change at 24 hours | 0.10 Percentage of vWF Ag | Standard Deviation 17.116 |
| Placebo | Change From Baseline in Von Willebrand Factor: Antigen (VWF:Ag) at Specified Timepoints | Change at 1 hour | -9.90 Percentage of vWF Ag | Standard Deviation 27.518 |
| Placebo | Change From Baseline in Von Willebrand Factor: Antigen (VWF:Ag) at Specified Timepoints | Change at 0.25 hours | 5.20 Percentage of vWF Ag | Standard Deviation 23.774 |
| Placebo | Change From Baseline in Von Willebrand Factor: Antigen (VWF:Ag) at Specified Timepoints | Change at 168 hours | -46.80 Percentage of vWF Ag | Standard Deviation 23.708 |
| Placebo | Change From Baseline in Von Willebrand Factor: Antigen (VWF:Ag) at Specified Timepoints | Change at 120 hours | -14.40 Percentage of vWF Ag | Standard Deviation 37.183 |
| Placebo | Change From Baseline in Von Willebrand Factor: Antigen (VWF:Ag) at Specified Timepoints | Change at 3 hours | -7.80 Percentage of vWF Ag | Standard Deviation 12.301 |
| Placebo | Change From Baseline in Von Willebrand Factor: Antigen (VWF:Ag) at Specified Timepoints | Change at 648 hours | -34.30 Percentage of vWF Ag | Standard Deviation 45.276 |
| TAK-755: 40 IU/kg | Change From Baseline in Von Willebrand Factor: Antigen (VWF:Ag) at Specified Timepoints | Change at 72 hours | 8.93 Percentage of vWF Ag | Standard Deviation 43.275 |
| TAK-755: 40 IU/kg | Change From Baseline in Von Willebrand Factor: Antigen (VWF:Ag) at Specified Timepoints | Change at 0.25 hours | -29.47 Percentage of vWF Ag | Standard Deviation 17.719 |
| TAK-755: 40 IU/kg | Change From Baseline in Von Willebrand Factor: Antigen (VWF:Ag) at Specified Timepoints | Change at 1 hour | -19.47 Percentage of vWF Ag | Standard Deviation 10.161 |
| TAK-755: 40 IU/kg | Change From Baseline in Von Willebrand Factor: Antigen (VWF:Ag) at Specified Timepoints | Change at 3 hours | -18.27 Percentage of vWF Ag | Standard Deviation 4.67 |
| TAK-755: 40 IU/kg | Change From Baseline in Von Willebrand Factor: Antigen (VWF:Ag) at Specified Timepoints | Change at 8 hours | 13.07 Percentage of vWF Ag | Standard Deviation 20.433 |
| TAK-755: 40 IU/kg | Change From Baseline in Von Willebrand Factor: Antigen (VWF:Ag) at Specified Timepoints | Change at 24 hours | 16.00 Percentage of vWF Ag | Standard Deviation 34.113 |
| TAK-755: 40 IU/kg | Change From Baseline in Von Willebrand Factor: Antigen (VWF:Ag) at Specified Timepoints | Change at 120 hours | NA Percentage of vWF Ag | — |
| TAK-755: 40 IU/kg | Change From Baseline in Von Willebrand Factor: Antigen (VWF:Ag) at Specified Timepoints | Change at 168 hours | NA Percentage of vWF Ag | — |
| TAK-755: 40 IU/kg | Change From Baseline in Von Willebrand Factor: Antigen (VWF:Ag) at Specified Timepoints | Change at 216 hours | 13.87 Percentage of vWF Ag | Standard Deviation 15.597 |
| TAK-755: 40 IU/kg | Change From Baseline in Von Willebrand Factor: Antigen (VWF:Ag) at Specified Timepoints | Change at 288 hours | NA Percentage of vWF Ag | — |
| TAK-755: 40 IU/kg | Change From Baseline in Von Willebrand Factor: Antigen (VWF:Ag) at Specified Timepoints | Change at 648 hours | NA Percentage of vWF Ag | — |
| TAK-755: 80 IU/kg | Change From Baseline in Von Willebrand Factor: Antigen (VWF:Ag) at Specified Timepoints | Change at 72 hours | 20.32 Percentage of vWF Ag | Standard Deviation 25.345 |
| TAK-755: 80 IU/kg | Change From Baseline in Von Willebrand Factor: Antigen (VWF:Ag) at Specified Timepoints | Change at 1 hour | 9.50 Percentage of vWF Ag | Standard Deviation 20.168 |
| TAK-755: 80 IU/kg | Change From Baseline in Von Willebrand Factor: Antigen (VWF:Ag) at Specified Timepoints | Change at 216 hours | -4.90 Percentage of vWF Ag | Standard Deviation 43.425 |
| TAK-755: 80 IU/kg | Change From Baseline in Von Willebrand Factor: Antigen (VWF:Ag) at Specified Timepoints | Change at 0.25 hours | -0.96 Percentage of vWF Ag | Standard Deviation 32.87 |
| TAK-755: 80 IU/kg | Change From Baseline in Von Willebrand Factor: Antigen (VWF:Ag) at Specified Timepoints | Change at 648 hours | 25.17 Percentage of vWF Ag | Standard Deviation 30.641 |
| TAK-755: 80 IU/kg | Change From Baseline in Von Willebrand Factor: Antigen (VWF:Ag) at Specified Timepoints | Change at 168 hours | 6.82 Percentage of vWF Ag | Standard Deviation 29.703 |
| TAK-755: 80 IU/kg | Change From Baseline in Von Willebrand Factor: Antigen (VWF:Ag) at Specified Timepoints | Change at 8 hours | -0.24 Percentage of vWF Ag | Standard Deviation 15.028 |
| TAK-755: 80 IU/kg | Change From Baseline in Von Willebrand Factor: Antigen (VWF:Ag) at Specified Timepoints | Change at 288 hours | 2.58 Percentage of vWF Ag | Standard Deviation 32.591 |
| TAK-755: 80 IU/kg | Change From Baseline in Von Willebrand Factor: Antigen (VWF:Ag) at Specified Timepoints | Change at 24 hours | 20.42 Percentage of vWF Ag | Standard Deviation 18.756 |
| TAK-755: 80 IU/kg | Change From Baseline in Von Willebrand Factor: Antigen (VWF:Ag) at Specified Timepoints | Change at 120 hours | 0.67 Percentage of vWF Ag | Standard Deviation 29.733 |
| TAK-755: 80 IU/kg | Change From Baseline in Von Willebrand Factor: Antigen (VWF:Ag) at Specified Timepoints | Change at 3 hours | -0.30 Percentage of vWF Ag | Standard Deviation 22.744 |
| TAK-755: 160 IU/kg | Change From Baseline in Von Willebrand Factor: Antigen (VWF:Ag) at Specified Timepoints | Change at 3 hours | NA Percentage of vWF Ag | — |
| TAK-755: 160 IU/kg | Change From Baseline in Von Willebrand Factor: Antigen (VWF:Ag) at Specified Timepoints | Change at 72 hours | 9.47 Percentage of vWF Ag | Standard Deviation 25.026 |
| TAK-755: 160 IU/kg | Change From Baseline in Von Willebrand Factor: Antigen (VWF:Ag) at Specified Timepoints | Change at 1 hour | 4.00 Percentage of vWF Ag | Standard Deviation 12.139 |
| TAK-755: 160 IU/kg | Change From Baseline in Von Willebrand Factor: Antigen (VWF:Ag) at Specified Timepoints | Change at 288 hours | NA Percentage of vWF Ag | — |
| TAK-755: 160 IU/kg | Change From Baseline in Von Willebrand Factor: Antigen (VWF:Ag) at Specified Timepoints | Change at 120 hours | 9.60 Percentage of vWF Ag | Standard Deviation 47.411 |
| TAK-755: 160 IU/kg | Change From Baseline in Von Willebrand Factor: Antigen (VWF:Ag) at Specified Timepoints | Change at 168 hours | -20.40 Percentage of vWF Ag | Standard Deviation 24.212 |
| TAK-755: 160 IU/kg | Change From Baseline in Von Willebrand Factor: Antigen (VWF:Ag) at Specified Timepoints | Change at 0.25 hours | -16.27 Percentage of vWF Ag | Standard Deviation 9.341 |
| TAK-755: 160 IU/kg | Change From Baseline in Von Willebrand Factor: Antigen (VWF:Ag) at Specified Timepoints | Change at 648 hours | -26.93 Percentage of vWF Ag | Standard Deviation 45.377 |
| TAK-755: 160 IU/kg | Change From Baseline in Von Willebrand Factor: Antigen (VWF:Ag) at Specified Timepoints | Change at 216 hours | NA Percentage of vWF Ag | — |
| TAK-755: 160 IU/kg | Change From Baseline in Von Willebrand Factor: Antigen (VWF:Ag) at Specified Timepoints | Change at 8 hours | NA Percentage of vWF Ag | — |
| TAK-755: 160 IU/kg | Change From Baseline in Von Willebrand Factor: Antigen (VWF:Ag) at Specified Timepoints | Change at 24 hours | 2.93 Percentage of vWF Ag | Standard Deviation 24.981 |
Secondary
Change From Baseline in Von Willebrand Factor:Ristocetin Cofactor Activity (VWF:RCo) At Specified Timepoints
Von Willebrand factor (vWF or VWF) is a protein that is one of several components of the coagulation system that work together, to stop bleeding within the body. VWF:RCo assay is a test that measures the activity of the VWF in a plasma sample in terms of how well it is able to clump platelets together in the presence of the antibiotic ristocetin. Change from baseline in vWF:RCo concentration was measured at different timepoints. Baseline was defined as the last non-missing measurement obtained prior to the date and time of the dose of IP. Change from baseline was calculated by subtracting the baseline value from the post-dose value.
Time frame: Baseline (Pre-dose), 0.25, 1, 3, 8, 24, 72, 120, 168, 216, 288, and 648 hours post-dose
Population: Pharmacodynamic analysis set: All participants who received at least 1 complete dose of TAK-755 or placebo and provided at least 1 valid data point post-dose of the respective infusion for at least 1 PD measurement for any of the PD outcome and had no major protocol deviations or events that may have affected the integrity of the PD data. Overall Number of Participants Analyzed refers participants evaluable for this outcome and number analyzed refers participants at the specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Von Willebrand Factor:Ristocetin Cofactor Activity (VWF:RCo) At Specified Timepoints | Change at 0.25 hours | -6.78 Percentage of vWF RCo | Standard Deviation 8.107 |
| Placebo | Change From Baseline in Von Willebrand Factor:Ristocetin Cofactor Activity (VWF:RCo) At Specified Timepoints | Change at 8 hours | 0.28 Percentage of vWF RCo | Standard Deviation 34.209 |
| Placebo | Change From Baseline in Von Willebrand Factor:Ristocetin Cofactor Activity (VWF:RCo) At Specified Timepoints | Change at 168 hours | -9.87 Percentage of vWF RCo | Standard Deviation 6.217 |
| Placebo | Change From Baseline in Von Willebrand Factor:Ristocetin Cofactor Activity (VWF:RCo) At Specified Timepoints | Change at 1 hour | -10.08 Percentage of vWF RCo | Standard Deviation 11.346 |
| Placebo | Change From Baseline in Von Willebrand Factor:Ristocetin Cofactor Activity (VWF:RCo) At Specified Timepoints | Change at 120 hours | 4.33 Percentage of vWF RCo | Standard Deviation 15.284 |
| Placebo | Change From Baseline in Von Willebrand Factor:Ristocetin Cofactor Activity (VWF:RCo) At Specified Timepoints | Change at 24 hours | 8.30 Percentage of vWF RCo | Standard Deviation 5.582 |
| Placebo | Change From Baseline in Von Willebrand Factor:Ristocetin Cofactor Activity (VWF:RCo) At Specified Timepoints | Change at 3 hours | -9.75 Percentage of vWF RCo | Standard Deviation 5.047 |
| Placebo | Change From Baseline in Von Willebrand Factor:Ristocetin Cofactor Activity (VWF:RCo) At Specified Timepoints | Change at 648 hours | -17.03 Percentage of vWF RCo | Standard Deviation 10.801 |
| Placebo | Change From Baseline in Von Willebrand Factor:Ristocetin Cofactor Activity (VWF:RCo) At Specified Timepoints | Change at 288 hours | -22.33 Percentage of vWF RCo | Standard Deviation 11.712 |
| Placebo | Change From Baseline in Von Willebrand Factor:Ristocetin Cofactor Activity (VWF:RCo) At Specified Timepoints | Change at 72 hours | -8.03 Percentage of vWF RCo | Standard Deviation 8.176 |
| Placebo | Change From Baseline in Von Willebrand Factor:Ristocetin Cofactor Activity (VWF:RCo) At Specified Timepoints | Change at 216 hours | -15.90 Percentage of vWF RCo | Standard Deviation 20.132 |
| TAK-755: 40 IU/kg | Change From Baseline in Von Willebrand Factor:Ristocetin Cofactor Activity (VWF:RCo) At Specified Timepoints | Change at 72 hours | 20.17 Percentage of vWF RCo | Standard Deviation 22.167 |
| TAK-755: 40 IU/kg | Change From Baseline in Von Willebrand Factor:Ristocetin Cofactor Activity (VWF:RCo) At Specified Timepoints | Change at 216 hours | 13.20 Percentage of vWF RCo | Standard Deviation 37.091 |
| TAK-755: 40 IU/kg | Change From Baseline in Von Willebrand Factor:Ristocetin Cofactor Activity (VWF:RCo) At Specified Timepoints | Change at 120 hours | NA Percentage of vWF RCo | — |
| TAK-755: 40 IU/kg | Change From Baseline in Von Willebrand Factor:Ristocetin Cofactor Activity (VWF:RCo) At Specified Timepoints | Change at 168 hours | NA Percentage of vWF RCo | — |
| TAK-755: 40 IU/kg | Change From Baseline in Von Willebrand Factor:Ristocetin Cofactor Activity (VWF:RCo) At Specified Timepoints | Change at 3 hours | -20.80 Percentage of vWF RCo | Standard Deviation 72.904 |
| TAK-755: 40 IU/kg | Change From Baseline in Von Willebrand Factor:Ristocetin Cofactor Activity (VWF:RCo) At Specified Timepoints | Change at 648 hours | NA Percentage of vWF RCo | — |
| TAK-755: 40 IU/kg | Change From Baseline in Von Willebrand Factor:Ristocetin Cofactor Activity (VWF:RCo) At Specified Timepoints | Change at 8 hours | -34.80 Percentage of vWF RCo | Standard Deviation 63.461 |
| TAK-755: 40 IU/kg | Change From Baseline in Von Willebrand Factor:Ristocetin Cofactor Activity (VWF:RCo) At Specified Timepoints | Change at 288 hours | NA Percentage of vWF RCo | — |
| TAK-755: 40 IU/kg | Change From Baseline in Von Willebrand Factor:Ristocetin Cofactor Activity (VWF:RCo) At Specified Timepoints | Change at 24 hours | 20.07 Percentage of vWF RCo | Standard Deviation 36.049 |
| TAK-755: 40 IU/kg | Change From Baseline in Von Willebrand Factor:Ristocetin Cofactor Activity (VWF:RCo) At Specified Timepoints | Change at 1 hour | -7.80 Percentage of vWF RCo | Standard Deviation 9.242 |
| TAK-755: 40 IU/kg | Change From Baseline in Von Willebrand Factor:Ristocetin Cofactor Activity (VWF:RCo) At Specified Timepoints | Change at 0.25 hours | -7.40 Percentage of vWF RCo | Standard Deviation 10.802 |
| TAK-755: 80 IU/kg | Change From Baseline in Von Willebrand Factor:Ristocetin Cofactor Activity (VWF:RCo) At Specified Timepoints | Change at 288 hours | 8.58 Percentage of vWF RCo | Standard Deviation 3.812 |
| TAK-755: 80 IU/kg | Change From Baseline in Von Willebrand Factor:Ristocetin Cofactor Activity (VWF:RCo) At Specified Timepoints | Change at 0.25 hours | -6.06 Percentage of vWF RCo | Standard Deviation 14.134 |
| TAK-755: 80 IU/kg | Change From Baseline in Von Willebrand Factor:Ristocetin Cofactor Activity (VWF:RCo) At Specified Timepoints | Change at 1 hour | 6.63 Percentage of vWF RCo | Standard Deviation 31.637 |
| TAK-755: 80 IU/kg | Change From Baseline in Von Willebrand Factor:Ristocetin Cofactor Activity (VWF:RCo) At Specified Timepoints | Change at 3 hours | -10.10 Percentage of vWF RCo | Standard Deviation 7.833 |
| TAK-755: 80 IU/kg | Change From Baseline in Von Willebrand Factor:Ristocetin Cofactor Activity (VWF:RCo) At Specified Timepoints | Change at 8 hours | -17.36 Percentage of vWF RCo | Standard Deviation 34.424 |
| TAK-755: 80 IU/kg | Change From Baseline in Von Willebrand Factor:Ristocetin Cofactor Activity (VWF:RCo) At Specified Timepoints | Change at 24 hours | 9.32 Percentage of vWF RCo | Standard Deviation 18.59 |
| TAK-755: 80 IU/kg | Change From Baseline in Von Willebrand Factor:Ristocetin Cofactor Activity (VWF:RCo) At Specified Timepoints | Change at 72 hours | 8.60 Percentage of vWF RCo | Standard Deviation 9.908 |
| TAK-755: 80 IU/kg | Change From Baseline in Von Willebrand Factor:Ristocetin Cofactor Activity (VWF:RCo) At Specified Timepoints | Change at 120 hours | -32.33 Percentage of vWF RCo | Standard Deviation 50.707 |
| TAK-755: 80 IU/kg | Change From Baseline in Von Willebrand Factor:Ristocetin Cofactor Activity (VWF:RCo) At Specified Timepoints | Change at 168 hours | 0.97 Percentage of vWF RCo | Standard Deviation 7.227 |
| TAK-755: 80 IU/kg | Change From Baseline in Von Willebrand Factor:Ristocetin Cofactor Activity (VWF:RCo) At Specified Timepoints | Change at 216 hours | 9.35 Percentage of vWF RCo | Standard Deviation 8.005 |
| TAK-755: 80 IU/kg | Change From Baseline in Von Willebrand Factor:Ristocetin Cofactor Activity (VWF:RCo) At Specified Timepoints | Change at 648 hours | 9.43 Percentage of vWF RCo | Standard Deviation 10.112 |
| TAK-755: 160 IU/kg | Change From Baseline in Von Willebrand Factor:Ristocetin Cofactor Activity (VWF:RCo) At Specified Timepoints | Change at 72 hours | -11.30 Percentage of vWF RCo | Standard Deviation 11.895 |
| TAK-755: 160 IU/kg | Change From Baseline in Von Willebrand Factor:Ristocetin Cofactor Activity (VWF:RCo) At Specified Timepoints | Change at 648 hours | -12.83 Percentage of vWF RCo | Standard Deviation 83.921 |
| TAK-755: 160 IU/kg | Change From Baseline in Von Willebrand Factor:Ristocetin Cofactor Activity (VWF:RCo) At Specified Timepoints | Change at 216 hours | 7.08 Percentage of vWF RCo | Standard Deviation 22.733 |
| TAK-755: 160 IU/kg | Change From Baseline in Von Willebrand Factor:Ristocetin Cofactor Activity (VWF:RCo) At Specified Timepoints | Change at 24 hours | -1.20 Percentage of vWF RCo | Standard Deviation 26.771 |
| TAK-755: 160 IU/kg | Change From Baseline in Von Willebrand Factor:Ristocetin Cofactor Activity (VWF:RCo) At Specified Timepoints | Change at 8 hours | -8.00 Percentage of vWF RCo | Standard Deviation 14.178 |
| TAK-755: 160 IU/kg | Change From Baseline in Von Willebrand Factor:Ristocetin Cofactor Activity (VWF:RCo) At Specified Timepoints | Change at 3 hours | -7.00 Percentage of vWF RCo | Standard Deviation 10.835 |
| TAK-755: 160 IU/kg | Change From Baseline in Von Willebrand Factor:Ristocetin Cofactor Activity (VWF:RCo) At Specified Timepoints | Change at 288 hours | 7.83 Percentage of vWF RCo | Standard Deviation 36.533 |
| TAK-755: 160 IU/kg | Change From Baseline in Von Willebrand Factor:Ristocetin Cofactor Activity (VWF:RCo) At Specified Timepoints | Change at 1 hour | -4.60 Percentage of vWF RCo | Standard Deviation 8.285 |
| TAK-755: 160 IU/kg | Change From Baseline in Von Willebrand Factor:Ristocetin Cofactor Activity (VWF:RCo) At Specified Timepoints | Change at 0.25 hours | -3.50 Percentage of vWF RCo | Standard Deviation 13.365 |
| TAK-755: 160 IU/kg | Change From Baseline in Von Willebrand Factor:Ristocetin Cofactor Activity (VWF:RCo) At Specified Timepoints | Change at 168 hours | 15.00 Percentage of vWF RCo | Standard Deviation 9.367 |
| TAK-755: 160 IU/kg | Change From Baseline in Von Willebrand Factor:Ristocetin Cofactor Activity (VWF:RCo) At Specified Timepoints | Change at 120 hours | -0.55 Percentage of vWF RCo | Standard Deviation 11.301 |
Secondary
Incremental Recovery (IR) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755
IR was defined as the ratio of maximum increase in plasma ADAMTS13 antigen or activity level to TAK-755 dose per body weight. Baseline was defined as the last non-missing measurement obtained prior to the date and time of the first dose of TAK-755. Baseline-adjusted values were used for this analysis. Baseline-adjusted values at each timepoint were calculated as the measured value minus the pre-infusion (baseline) value and results were summarized overall. Here IU/mL/IU/kg refers to International units per milliliter per international units per kilogram.
Time frame: Baseline (Pre-dose), 0.25, 1, 3, 8, 24, 72, 120, 168, 216, 288, and 648 hours post-dose
Population: The Pharmacokinetic (PK) Analysis Set included all participants who received at least 1 complete dose of TAK-755 or placebo and provided at least 1 concentration measured at a scheduled time post start of infusion for at least 1 of the PK analytes and had no major protocol deviations or events that may affect the integrity of the PK data. Data was not analyzed for PK parameters in the placebo arm where participants did not receive TAK-755.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Incremental Recovery (IR) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755 | Baseline-adjusted ADAMTS13 Activity | 0.022440 IU/mL/IU/kg | Standard Deviation 32.3 |
| Placebo | Incremental Recovery (IR) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755 | Baseline-adjusted ADAMTS13 Antigen | 0.021809 IU/mL/IU/kg | Standard Deviation 25.8 |
| TAK-755: 40 IU/kg | Incremental Recovery (IR) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755 | Baseline-adjusted ADAMTS13 Activity | 0.025227 IU/mL/IU/kg | Standard Deviation 33.4 |
| TAK-755: 40 IU/kg | Incremental Recovery (IR) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755 | Baseline-adjusted ADAMTS13 Antigen | 0.021925 IU/mL/IU/kg | Standard Deviation 30.1 |
| TAK-755: 80 IU/kg | Incremental Recovery (IR) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755 | Baseline-adjusted ADAMTS13 Antigen | 0.022012 IU/mL/IU/kg | Standard Deviation 22.2 |
| TAK-755: 80 IU/kg | Incremental Recovery (IR) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755 | Baseline-adjusted ADAMTS13 Activity | 0.018423 IU/mL/IU/kg | Standard Deviation 33.6 |
Secondary
Mean Residence Time From Zero to 72 Hours Post-dose (MRT0-72) of ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755
The MRT is the average time that the study product stays in the body (or plasma) and The MRT0-72 is defined as the average time from zero (predose) to 72 hours post-dose (MRT0-72). Baseline was defined as the last non-missing measurement obtained prior to the date and time of the first dose of TAK-755.
Time frame: Baseline (Pre-dose), 0.25, 1, 3, 8, 24, and 72 hours post-dose
Population: Since MRT0-72 was considered irrelevant to the objective of the PK, therefore data for this outcome measure was not collected and reported.
Secondary
Mean Residence Time From Zero to Infinite (MRT0-Inf) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755
The MRT is the average time that the study product stays in the body (or plasma). The MRT0-Inf is defined as the average time from zero (pre-dose) extrapolated to infinite time (MRT0-inf). Baseline was defined as the last non-missing measurement obtained prior to the date and time of the first dose of TAK-755. Baseline-adjusted values were used for this analysis. Baseline-adjusted values at each timepoint were calculated as the measured value minus the pre-infusion (baseline) value and results were summarized overall.
Time frame: Baseline (Pre-dose), 0.25, 1, 3, 8, 24, 72, 120, 168, 216, 288, and 648 hours post-dose
Population: The PK Analysis Set included all participants who received at least 1 complete dose of TAK-755 or placebo and provided at least 1 concentration measured at a scheduled time post start of infusion for at least 1 of the PK analytes and had no major protocol deviations or events that may affect the integrity of the PK data. Data was not analyzed for PK parameters in the placebo arm where participants did not receive TAK-755.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Residence Time From Zero to Infinite (MRT0-Inf) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755 | Baseline-adjusted ADAMTS13 Activity | NA hour | — |
| Placebo | Mean Residence Time From Zero to Infinite (MRT0-Inf) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755 | Baseline-adjusted ADAMTS13 Antigen | NA hour | — |
| TAK-755: 40 IU/kg | Mean Residence Time From Zero to Infinite (MRT0-Inf) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755 | Baseline-adjusted ADAMTS13 Activity | 118.6 hour | Standard Deviation 46.17 |
| TAK-755: 40 IU/kg | Mean Residence Time From Zero to Infinite (MRT0-Inf) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755 | Baseline-adjusted ADAMTS13 Antigen | 116.3 hour | Standard Deviation 57.699 |
| TAK-755: 80 IU/kg | Mean Residence Time From Zero to Infinite (MRT0-Inf) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755 | Baseline-adjusted ADAMTS13 Activity | 87.54 hour | Standard Deviation 37.734 |
| TAK-755: 80 IU/kg | Mean Residence Time From Zero to Infinite (MRT0-Inf) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755 | Baseline-adjusted ADAMTS13 Antigen | 69.48 hour | Standard Deviation 23.555 |
Secondary
Observed Maximum Concentration (Cmax) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755
Cmax was a measure of the maximum amount of drug in the plasma after the dose was given. Baseline was defined as the last non-missing measurement obtained prior to the date and time of the first dose of TAK-755. Baseline-adjusted values were used for this analysis. Baseline-adjusted values at each timepoint were calculated as the measured value minus the pre-infusion (baseline) value and results were summarized overall.
Time frame: Baseline (Pre-dose), 0.25, 1, 3, 8, 24, 72, 120, 168, 216, 288, and 648 hours post-dose
Population: The PK Analysis Set included all participants who received at least 1 complete dose of TAK-755 or placebo and provided at least 1 concentration measured at a scheduled time post start of infusion for at least 1 of the PK analytes and had no major protocol deviations or events that may affect the integrity of the PK data. Data was not analyzed for PK parameters in the placebo arm where participants did not receive TAK-755.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Observed Maximum Concentration (Cmax) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755 | Baseline-adjusted ADAMTS13 Activity | 0.90202 international units per milliliter | Geometric Coefficient of Variation 33.5 |
| Placebo | Observed Maximum Concentration (Cmax) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755 | Baseline-adjusted ADAMTS13 Antigen | 0.49848 international units per milliliter | Geometric Coefficient of Variation 27.9 |
| TAK-755: 40 IU/kg | Observed Maximum Concentration (Cmax) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755 | Baseline-adjusted ADAMTS13 Activity | 2.0080 international units per milliliter | Geometric Coefficient of Variation 33.2 |
| TAK-755: 40 IU/kg | Observed Maximum Concentration (Cmax) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755 | Baseline-adjusted ADAMTS13 Antigen | 1.0382 international units per milliliter | Geometric Coefficient of Variation 30.3 |
| TAK-755: 80 IU/kg | Observed Maximum Concentration (Cmax) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755 | Baseline-adjusted ADAMTS13 Activity | 2.9539 international units per milliliter | Geometric Coefficient of Variation 33.6 |
| TAK-755: 80 IU/kg | Observed Maximum Concentration (Cmax) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755 | Baseline-adjusted ADAMTS13 Antigen | 2.0392 international units per milliliter | Geometric Coefficient of Variation 22.2 |
Secondary
Systemic Clearance (CL) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755
CL is a quantitative measure of the rate at which a drug substance is removed from the body. The total systemic clearance after intravenous dose was estimated by dividing the total administered dose by the plasma Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC\[0-infinity\]). Baseline was defined as the last non-missing measurement obtained prior to the date and time of the first dose of TAK-755. Baseline-adjusted values were used for this analysis. Baseline-adjusted values at each timepoint were calculated as the measured value minus the pre-infusion (baseline) value and results were summarized overall.
Time frame: Baseline (Pre-dose), 0.25, 1, 3, 8, 24, 72, 120, 168, 216, 288, and 648 hours post-dose
Population: The PK Analysis Set included all participants who received at least 1 complete dose of TAK-755 or placebo and provided at least 1 concentration measured at a scheduled time post start of infusion for at least 1 of the PK analytes and had no major protocol deviations or events that may affect the integrity of the PK data. Data was not analyzed for PK parameters in the placebo arm where participants did not receive TAK-755.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Systemic Clearance (CL) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755 | Baseline-adjusted ADAMTS13 Activity | NA liters per hour (L/h) | — |
| Placebo | Systemic Clearance (CL) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755 | Baseline-adjusted ADAMTS13 Antigen | NA liters per hour (L/h) | — |
| TAK-755: 40 IU/kg | Systemic Clearance (CL) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755 | Baseline-adjusted ADAMTS13 Activity | 37.22 liters per hour (L/h) | Geometric Coefficient of Variation 64.3 |
| TAK-755: 40 IU/kg | Systemic Clearance (CL) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755 | Baseline-adjusted ADAMTS13 Antigen | 51.28 liters per hour (L/h) | Geometric Coefficient of Variation 66.1 |
| TAK-755: 80 IU/kg | Systemic Clearance (CL) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755 | Baseline-adjusted ADAMTS13 Activity | 74.35 liters per hour (L/h) | Geometric Coefficient of Variation 46.8 |
| TAK-755: 80 IU/kg | Systemic Clearance (CL) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755 | Baseline-adjusted ADAMTS13 Antigen | 54.47 liters per hour (L/h) | Geometric Coefficient of Variation 54.47 |
Secondary
Terminal Half-Life (t1/2) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755
t1/2 was the time required for a given drug concentration in the plasma to decrease by 50%. Baseline was defined as the last non-missing measurement obtained prior to the date and time of the first dose of TAK-755. Baseline-adjusted values were used for this analysis. Baseline-adjusted values at each timepoint were calculated as the measured value minus the pre-infusion (baseline) value and results were summarized overall.
Time frame: Baseline (Pre-dose), 0.25, 1, 3, 8, 24, 72, 120, 168, 216, 288, and 648 hours post-dose
Population: The PK Analysis Set included all participants who received at least 1 complete dose of TAK-755 or placebo and provided at least 1 concentration measured at a scheduled time post start of infusion for at least 1 of the PK analytes and had no major protocol deviations or events that may affect the integrity of the PK data. Data was not analyzed for PK parameters in the placebo arm where participants did not receive TAK-755.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Terminal Half-Life (t1/2) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755 | Baseline-adjusted ADAMTS13 Activity | NA hour | — |
| Placebo | Terminal Half-Life (t1/2) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755 | Baseline-adjusted ADAMTS13 Antigen | NA hour | — |
| TAK-755: 40 IU/kg | Terminal Half-Life (t1/2) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755 | Baseline-adjusted ADAMTS13 Activity | 54.56 hour | Standard Deviation 28.23 |
| TAK-755: 40 IU/kg | Terminal Half-Life (t1/2) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755 | Baseline-adjusted ADAMTS13 Antigen | 65.17 hour | Standard Deviation 41.728 |
| TAK-755: 80 IU/kg | Terminal Half-Life (t1/2) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755 | Baseline-adjusted ADAMTS13 Activity | 42.22 hour | Standard Deviation 9.7253 |
| TAK-755: 80 IU/kg | Terminal Half-Life (t1/2) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755 | Baseline-adjusted ADAMTS13 Antigen | 46.88 hour | Standard Deviation 16.821 |
Secondary
Time to Reach Cmax (Tmax) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755
Tmax was a measure of the time to reach the maximum concentration in the plasma after the drug dose. Baseline was defined as the last non-missing measurement obtained prior to the date and time of the first dose of TAK-755. Baseline-adjusted values were used for this analysis. Baseline-adjusted values at each timepoint were calculated as the measured value minus the pre-infusion (baseline) value and results were summarized overall.
Time frame: Baseline (Pre-dose), 0.25, 1, 3, 8, 24, 72, 120, 168, 216, 288, and 648 hours post-dose
Population: The PK Analysis Set included all participants who received at least 1 complete dose of TAK-755 or placebo and provided at least 1 concentration measured at a scheduled time post start of infusion for at least 1 of the PK analytes and had no major protocol deviations or events that may affect the integrity of the PK data. Data was not analyzed for PK parameters in the placebo arm where participants did not receive TAK-755.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Time to Reach Cmax (Tmax) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755 | Baseline-adjusted ADAMTS13 Activity | 2.16 hour |
| Placebo | Time to Reach Cmax (Tmax) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755 | Baseline-adjusted ADAMTS13 Antigen | 0.45 hour |
| TAK-755: 40 IU/kg | Time to Reach Cmax (Tmax) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755 | Baseline-adjusted ADAMTS13 Antigen | 1.10 hour |
| TAK-755: 40 IU/kg | Time to Reach Cmax (Tmax) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755 | Baseline-adjusted ADAMTS13 Activity | 1.08 hour |
| TAK-755: 80 IU/kg | Time to Reach Cmax (Tmax) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755 | Baseline-adjusted ADAMTS13 Antigen | 0.83 hour |
| TAK-755: 80 IU/kg | Time to Reach Cmax (Tmax) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755 | Baseline-adjusted ADAMTS13 Activity | 0.45 hour |
Secondary
Volume of Distribution at Steady State (Vss) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755
Vss is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Steady state volume of distribution (Vss) is the apparent volume of distribution at steady-state which is estimated by MRT(0-inf)\*CL. Baseline was defined as the last non-missing measurement obtained prior to the date and time of the first dose of TAK-755. Baseline-adjusted values were used for this analysis. Baseline-adjusted values at each timepoint were calculated as the measured value minus the pre-infusion (baseline) value and results were summarized overall.
Time frame: Baseline (Pre-dose), 0.25, 1, 3, 8, 24, 72, 120, 168, 216, 288, and 648 hours post-dose
Population: The PK Analysis Set included all participants who received at least 1 complete dose of TAK-755 or placebo and provided at least 1 concentration measured at a scheduled time post start of infusion for at least 1 of the PK analytes and had no major protocol deviations or events that may affect the integrity of the PK data. Data was not analyzed for PK parameters in the placebo arm where participants did not receive TAK-755.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Volume of Distribution at Steady State (Vss) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755 | Baseline-adjusted ADAMTS13 Activity | NA liters | — |
| Placebo | Volume of Distribution at Steady State (Vss) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755 | Baseline-adjusted ADAMTS13 Antigen | NA liters | — |
| TAK-755: 40 IU/kg | Volume of Distribution at Steady State (Vss) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755 | Baseline-adjusted ADAMTS13 Activity | 3993 liters | Geometric Coefficient of Variation 48.2 |
| TAK-755: 40 IU/kg | Volume of Distribution at Steady State (Vss) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755 | Baseline-adjusted ADAMTS13 Antigen | 4682 liters | Geometric Coefficient of Variation 8.4 |
| TAK-755: 80 IU/kg | Volume of Distribution at Steady State (Vss) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755 | Baseline-adjusted ADAMTS13 Activity | 5771 liters | Geometric Coefficient of Variation 17.2 |
| TAK-755: 80 IU/kg | Volume of Distribution at Steady State (Vss) for ADAMTS13 Activity and ADAMTS13 Antigen of TAK-755 | Baseline-adjusted ADAMTS13 Antigen | 3661 liters | Geometric Coefficient of Variation 21.7 |