Trial Outcomes & Findings for A Study of TAK-662 for Japanese Patients With Congenital Protein C Deficiency (NCT NCT04984889)
NCT ID: NCT04984889
Last Updated: 2025-05-07
Results Overview
Protein C is a vitamin K-dependent plasma protein and is an important component of the coagulation system. Protein C activity level was measured by chromogenic assays. Protein C activity level of TAK-662 was reported.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
5 participants
Primary outcome timeframe
Pre-infusion, 0.5, 1, 2, 4, 8, 12, 24, and 36 hours post-infusion
Results posted on
2025-05-07
Participant Flow
This study was conducted at 4 centers in Japan from 7 September 2021 to 31 October 2024.
A total of 5 Japanese participants were enrolled in this 2-part study to receive TAK-662 in Pharmacokinetic (PK) part (Part 1) followed by 3 treatment options in the Extension part (Part 2) (on-demand, short-term, or long-term prophylaxis). As per planned analysis, the Extension Part data was collected, analyzed and reported as per On-demand and Short-term Prophylaxis treatments and per dose level wise data was not collected in this study.
Participant milestones
| Measure |
PK Part: TAK-662
Participants received a single 80 international unit per kilogram (IU/kg) dose of TAK-662, intravenous infusion on Day 1 in PK part.
|
Extension Part, On-demand Treatment (TAK-662)
Participants with purpura fulminans (PF), coumarin-induced skin necrosis/warfarin-induced skin necrosis (CISN/WISN), and/or other acute thromboembolic episode received a single dose of TAK-662 (100-120 IU/kg), followed by three subsequent infusions, every 6 hours at a dose of 60-80 IU/kg, and followed by subsequent infusions (45-60 IU/kg) continued every 6 or 12 hours until resolution of all non-necrotic lesions and/or stabilization of thrombi. Treatment could be terminated when an acute episode improved.
|
Extension Part, Short-term Prophylaxis Treatment (TAK-662)
Participants who required short-term prophylaxis of acute thrombotic episodes during surgery received TAK-662 at a dose of 100-120 IU/kg, intravenous infusion once daily, until anticoagulation therapy was successfully switched to TAK-662 prior to surgery. Fifteen minutes prior to surgery, a dose of 60-80 IU/kg was administered and continued once every 6 hours for the first 24 hours after surgery began. The frequency of infusions was reduced to 3 times daily between 24 and 48 hours, and twice daily after 48 hours at the same dose (45-60 IU/kg). Treatment with TAK-662 continued twice daily until anticoagulation therapy was initiated (if applicable) and the investigator determined that adequate level of the anticoagulation was achieved.
|
Extension Part, Long-term Prophylaxis Treatment (TAK-662)
Participants who required long-term prophylaxis were planned to receive TAK-662 at a dose of 45-60 IU/kg, intravenous infusion, twice daily. The dose was to be adjusted by referring to the latest protein C activity at the investigator's discretion. No participants received TAK-662 for long-term prophylaxis during the study.
|
|---|---|---|---|---|
|
PK Part: Up to 7 Days
STARTED
|
5
|
0
|
0
|
0
|
|
PK Part: Up to 7 Days
COMPLETED
|
5
|
0
|
0
|
0
|
|
PK Part: Up to 7 Days
NOT COMPLETED
|
0
|
0
|
0
|
0
|
|
Extension Part: Up to 35 Months
STARTED
|
0
|
4
|
1
|
0
|
|
Extension Part: Up to 35 Months
COMPLETED
|
0
|
4
|
1
|
0
|
|
Extension Part: Up to 35 Months
NOT COMPLETED
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
A Study of TAK-662 for Japanese Patients With Congenital Protein C Deficiency
Baseline characteristics by cohort
| Measure |
PK Part: TAK-662
n=5 Participants
Participants received a single 80 IU/kg dose of TAK-662, intravenous infusion on Day 1 in PK part.
|
|---|---|
|
Age, Continuous
|
15.2 years
STANDARD_DEVIATION 8.87 • n=93 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=93 Participants
|
|
Sex: Female, Male
Male
|
4 Participants
n=93 Participants
|
|
Race/Ethnicity, Customized
Japanese
|
5 Participants
n=93 Participants
|
PRIMARY outcome
Timeframe: Pre-infusion, 0.5, 1, 2, 4, 8, 12, 24, and 36 hours post-infusionPopulation: The PK population included all study participants who took at least 1 dose of TAK-662 and had enough number of quantifiable blood levels for TAK-662 collected post-dose without important protocol deviations (PDs)/violations or events thought to substantially affect the PK.
Protein C is a vitamin K-dependent plasma protein and is an important component of the coagulation system. Protein C activity level was measured by chromogenic assays. Protein C activity level of TAK-662 was reported.
Outcome measures
| Measure |
PK Part: TAK-662
n=5 Participants
Participants received a single 80 IU/kg dose of TAK-662, intravenous infusion on Day 1 in PK part.
|
Extension Part, On-demand Treatment (TAK-662)
Participants with PF, CISN/WISN, and/or other acute thromboembolic episode received a single dose of TAK-662 (100-120 IU/kg), followed by three subsequent infusions, every 6 hours at a dose of 60-80 IU/kg, and followed by subsequent infusions (45-60 IU/kg) continued every 6 or 12 hours until resolution of all non-necrotic lesions and/or stabilization of thrombi. Treatment could be terminated when an acute episode improved.
|
Extension Part, Short-term Prophylaxis Treatment (TAK-662)
Participants who required short-term prophylaxis of acute thrombotic episodes during surgery received TAK-662 at a dose of 100-120 IU/kg, intravenous infusion once daily, until anticoagulation therapy was successfully switched to TAK-662 prior to surgery. Fifteen minutes prior to surgery, a dose of 60-80 IU/kg was administered and continued once every 6 hours for the first 24 hours after surgery began. The frequency of infusions was reduced to 3 times daily between 24 and 48 hours, and twice daily after 48 hours at the same dose (45-60 IU/kg). Treatment with TAK-662 continued twice daily until anticoagulation therapy was initiated (if applicable) and the investigator determined that adequate level of the anticoagulation was achieved.
|
Extension Part, Long-term Prophylaxis Treatment (TAK-662)
Participants who required long-term prophylaxis were planned to receive TAK-662 at a dose of 45-60 IU/kg, intravenous infusion, twice daily. The dose was to be adjusted by referring to the latest protein C activity at the investigator's discretion. No participants received TAK-662 for long-term prophylaxis during the study.
|
|---|---|---|---|---|
|
PK Part: Protein C Activity Level of TAK-662
Pre-infusion
|
0.000 international unit per milliliter(IU/ml)
Standard Deviation 0.000
|
—
|
—
|
—
|
|
PK Part: Protein C Activity Level of TAK-662
0.5 hour
|
1.746 international unit per milliliter(IU/ml)
Standard Deviation 0.557
|
—
|
—
|
—
|
|
PK Part: Protein C Activity Level of TAK-662
1 hour
|
1.616 international unit per milliliter(IU/ml)
Standard Deviation 0.523
|
—
|
—
|
—
|
|
PK Part: Protein C Activity Level of TAK-662
2 hours
|
1.458 international unit per milliliter(IU/ml)
Standard Deviation 0.519
|
—
|
—
|
—
|
|
PK Part: Protein C Activity Level of TAK-662
4 hours
|
1.168 international unit per milliliter(IU/ml)
Standard Deviation 0.441
|
—
|
—
|
—
|
|
PK Part: Protein C Activity Level of TAK-662
8 hours
|
0.844 international unit per milliliter(IU/ml)
Standard Deviation 0.295
|
—
|
—
|
—
|
|
PK Part: Protein C Activity Level of TAK-662
12 hours
|
0.632 international unit per milliliter(IU/ml)
Standard Deviation 0.257
|
—
|
—
|
—
|
|
PK Part: Protein C Activity Level of TAK-662
24 hours
|
0.304 international unit per milliliter(IU/ml)
Standard Deviation 0.150
|
—
|
—
|
—
|
|
PK Part: Protein C Activity Level of TAK-662
36 hours
|
0.148 international unit per milliliter(IU/ml)
Standard Deviation 0.095
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Pre-infusion, 0.5, 1, 2, 4, 8, 12, 24, and 36 hours post-infusionPopulation: The PK population included all study participants who took at least 1 dose of TAK-662 and had enough number of quantifiable blood levels for TAK-662 collected post-dose without important PDs/violations or events thought to substantially affect the PK.
t1/2 of TAK-662 was reported.
Outcome measures
| Measure |
PK Part: TAK-662
n=5 Participants
Participants received a single 80 IU/kg dose of TAK-662, intravenous infusion on Day 1 in PK part.
|
Extension Part, On-demand Treatment (TAK-662)
Participants with PF, CISN/WISN, and/or other acute thromboembolic episode received a single dose of TAK-662 (100-120 IU/kg), followed by three subsequent infusions, every 6 hours at a dose of 60-80 IU/kg, and followed by subsequent infusions (45-60 IU/kg) continued every 6 or 12 hours until resolution of all non-necrotic lesions and/or stabilization of thrombi. Treatment could be terminated when an acute episode improved.
|
Extension Part, Short-term Prophylaxis Treatment (TAK-662)
Participants who required short-term prophylaxis of acute thrombotic episodes during surgery received TAK-662 at a dose of 100-120 IU/kg, intravenous infusion once daily, until anticoagulation therapy was successfully switched to TAK-662 prior to surgery. Fifteen minutes prior to surgery, a dose of 60-80 IU/kg was administered and continued once every 6 hours for the first 24 hours after surgery began. The frequency of infusions was reduced to 3 times daily between 24 and 48 hours, and twice daily after 48 hours at the same dose (45-60 IU/kg). Treatment with TAK-662 continued twice daily until anticoagulation therapy was initiated (if applicable) and the investigator determined that adequate level of the anticoagulation was achieved.
|
Extension Part, Long-term Prophylaxis Treatment (TAK-662)
Participants who required long-term prophylaxis were planned to receive TAK-662 at a dose of 45-60 IU/kg, intravenous infusion, twice daily. The dose was to be adjusted by referring to the latest protein C activity at the investigator's discretion. No participants received TAK-662 for long-term prophylaxis during the study.
|
|---|---|---|---|---|
|
PK Part: Terminal Phase Elimination Half-life (t1/2) of TAK-662
|
11.6 hour
Interval 7.68 to 13.0
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Pre-infusion, 0.5, 1, 2, 4, 8, 12, 24, and 36 hours post-infusionPopulation: The PK population included all study participants who took at least 1 dose of TAK-662 and had enough number of quantifiable blood levels for TAK-662 collected post-dose without important PDs/violations or events thought to substantially affect the PK.
IR of TAK-662 was reported measured in terms of international unit per milliliter/ international unit per kilogram (IU/mL)/(IU/kg).
Outcome measures
| Measure |
PK Part: TAK-662
n=5 Participants
Participants received a single 80 IU/kg dose of TAK-662, intravenous infusion on Day 1 in PK part.
|
Extension Part, On-demand Treatment (TAK-662)
Participants with PF, CISN/WISN, and/or other acute thromboembolic episode received a single dose of TAK-662 (100-120 IU/kg), followed by three subsequent infusions, every 6 hours at a dose of 60-80 IU/kg, and followed by subsequent infusions (45-60 IU/kg) continued every 6 or 12 hours until resolution of all non-necrotic lesions and/or stabilization of thrombi. Treatment could be terminated when an acute episode improved.
|
Extension Part, Short-term Prophylaxis Treatment (TAK-662)
Participants who required short-term prophylaxis of acute thrombotic episodes during surgery received TAK-662 at a dose of 100-120 IU/kg, intravenous infusion once daily, until anticoagulation therapy was successfully switched to TAK-662 prior to surgery. Fifteen minutes prior to surgery, a dose of 60-80 IU/kg was administered and continued once every 6 hours for the first 24 hours after surgery began. The frequency of infusions was reduced to 3 times daily between 24 and 48 hours, and twice daily after 48 hours at the same dose (45-60 IU/kg). Treatment with TAK-662 continued twice daily until anticoagulation therapy was initiated (if applicable) and the investigator determined that adequate level of the anticoagulation was achieved.
|
Extension Part, Long-term Prophylaxis Treatment (TAK-662)
Participants who required long-term prophylaxis were planned to receive TAK-662 at a dose of 45-60 IU/kg, intravenous infusion, twice daily. The dose was to be adjusted by referring to the latest protein C activity at the investigator's discretion. No participants received TAK-662 for long-term prophylaxis during the study.
|
|---|---|---|---|---|
|
PK Part: Incremental Recovery (IR) of TAK-662
|
0.02063 (IU/mL)/(IU/kg)
Standard Deviation 0.006588
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Pre-infusion, 0.5, 1, 2, 4, 8, 12, 24, and 36 hours post-infusionPopulation: The PK population included all study participants who took at least 1 dose of TAK-662 and had enough number of quantifiable blood levels for TAK-662 collected post-dose without important PDs/violations or events thought to substantially affect the PK.
IVR corrected for plasma was determined using the formula: IVR (percentage \[%\])= (Maximum observed plasma concentration (Cmax) \[IU/mL\] - Concentration (C) pre-infusion \[IU/mL\]) \* Plasma volume pre-infusion (PV) milliliter (mL)/ Dose (international unit \[IU\])\*100 where Cmax was the observed Cmax value before baseline correction. IVR of TAK-662 measured in terms of percentage was reported.
Outcome measures
| Measure |
PK Part: TAK-662
n=5 Participants
Participants received a single 80 IU/kg dose of TAK-662, intravenous infusion on Day 1 in PK part.
|
Extension Part, On-demand Treatment (TAK-662)
Participants with PF, CISN/WISN, and/or other acute thromboembolic episode received a single dose of TAK-662 (100-120 IU/kg), followed by three subsequent infusions, every 6 hours at a dose of 60-80 IU/kg, and followed by subsequent infusions (45-60 IU/kg) continued every 6 or 12 hours until resolution of all non-necrotic lesions and/or stabilization of thrombi. Treatment could be terminated when an acute episode improved.
|
Extension Part, Short-term Prophylaxis Treatment (TAK-662)
Participants who required short-term prophylaxis of acute thrombotic episodes during surgery received TAK-662 at a dose of 100-120 IU/kg, intravenous infusion once daily, until anticoagulation therapy was successfully switched to TAK-662 prior to surgery. Fifteen minutes prior to surgery, a dose of 60-80 IU/kg was administered and continued once every 6 hours for the first 24 hours after surgery began. The frequency of infusions was reduced to 3 times daily between 24 and 48 hours, and twice daily after 48 hours at the same dose (45-60 IU/kg). Treatment with TAK-662 continued twice daily until anticoagulation therapy was initiated (if applicable) and the investigator determined that adequate level of the anticoagulation was achieved.
|
Extension Part, Long-term Prophylaxis Treatment (TAK-662)
Participants who required long-term prophylaxis were planned to receive TAK-662 at a dose of 45-60 IU/kg, intravenous infusion, twice daily. The dose was to be adjusted by referring to the latest protein C activity at the investigator's discretion. No participants received TAK-662 for long-term prophylaxis during the study.
|
|---|---|---|---|---|
|
PK Part: Percentage of In-vivo Recovery (IVR) of TAK-662
|
95.71 percentage of IVR
Standard Deviation 31.22
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Pre-infusion, 0.5, 1, 2, 4, 8, 12, 24, and 36 hours post-infusionPopulation: The PK population included all study participants who took at least 1 dose of TAK-662 and had enough number of quantifiable blood levels for TAK-662 collected post-dose without important PDs/violations or events thought to substantially affect the PK.
AUClast of TAK-662 was reported measured in terms of international unit\*hour per milliliter (IU\*h/ml).
Outcome measures
| Measure |
PK Part: TAK-662
n=5 Participants
Participants received a single 80 IU/kg dose of TAK-662, intravenous infusion on Day 1 in PK part.
|
Extension Part, On-demand Treatment (TAK-662)
Participants with PF, CISN/WISN, and/or other acute thromboembolic episode received a single dose of TAK-662 (100-120 IU/kg), followed by three subsequent infusions, every 6 hours at a dose of 60-80 IU/kg, and followed by subsequent infusions (45-60 IU/kg) continued every 6 or 12 hours until resolution of all non-necrotic lesions and/or stabilization of thrombi. Treatment could be terminated when an acute episode improved.
|
Extension Part, Short-term Prophylaxis Treatment (TAK-662)
Participants who required short-term prophylaxis of acute thrombotic episodes during surgery received TAK-662 at a dose of 100-120 IU/kg, intravenous infusion once daily, until anticoagulation therapy was successfully switched to TAK-662 prior to surgery. Fifteen minutes prior to surgery, a dose of 60-80 IU/kg was administered and continued once every 6 hours for the first 24 hours after surgery began. The frequency of infusions was reduced to 3 times daily between 24 and 48 hours, and twice daily after 48 hours at the same dose (45-60 IU/kg). Treatment with TAK-662 continued twice daily until anticoagulation therapy was initiated (if applicable) and the investigator determined that adequate level of the anticoagulation was achieved.
|
Extension Part, Long-term Prophylaxis Treatment (TAK-662)
Participants who required long-term prophylaxis were planned to receive TAK-662 at a dose of 45-60 IU/kg, intravenous infusion, twice daily. The dose was to be adjusted by referring to the latest protein C activity at the investigator's discretion. No participants received TAK-662 for long-term prophylaxis during the study.
|
|---|---|---|---|---|
|
PK Part: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of TAK-662
|
19.24 IU*h/ml
Geometric Coefficient of Variation 47.0
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Pre-infusion, 0.5, 1, 2, 4, 8, 12, 24, and 36 hours post-infusionPopulation: The PK population included all study participants who took at least 1 dose of TAK-662 and had enough number of quantifiable blood levels for TAK-662 collected post-dose without important PDs/violations or events thought to substantially affect the PK.
AUC0-infinity of TAK-662 was reported.
Outcome measures
| Measure |
PK Part: TAK-662
n=5 Participants
Participants received a single 80 IU/kg dose of TAK-662, intravenous infusion on Day 1 in PK part.
|
Extension Part, On-demand Treatment (TAK-662)
Participants with PF, CISN/WISN, and/or other acute thromboembolic episode received a single dose of TAK-662 (100-120 IU/kg), followed by three subsequent infusions, every 6 hours at a dose of 60-80 IU/kg, and followed by subsequent infusions (45-60 IU/kg) continued every 6 or 12 hours until resolution of all non-necrotic lesions and/or stabilization of thrombi. Treatment could be terminated when an acute episode improved.
|
Extension Part, Short-term Prophylaxis Treatment (TAK-662)
Participants who required short-term prophylaxis of acute thrombotic episodes during surgery received TAK-662 at a dose of 100-120 IU/kg, intravenous infusion once daily, until anticoagulation therapy was successfully switched to TAK-662 prior to surgery. Fifteen minutes prior to surgery, a dose of 60-80 IU/kg was administered and continued once every 6 hours for the first 24 hours after surgery began. The frequency of infusions was reduced to 3 times daily between 24 and 48 hours, and twice daily after 48 hours at the same dose (45-60 IU/kg). Treatment with TAK-662 continued twice daily until anticoagulation therapy was initiated (if applicable) and the investigator determined that adequate level of the anticoagulation was achieved.
|
Extension Part, Long-term Prophylaxis Treatment (TAK-662)
Participants who required long-term prophylaxis were planned to receive TAK-662 at a dose of 45-60 IU/kg, intravenous infusion, twice daily. The dose was to be adjusted by referring to the latest protein C activity at the investigator's discretion. No participants received TAK-662 for long-term prophylaxis during the study.
|
|---|---|---|---|---|
|
PK Part: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-infinity) of TAK-662
|
21.88 IU*h/ml
Geometric Coefficient of Variation 47.1
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Pre-infusion, 0.5, 1, 2, 4, 8, 12, 24, and 36 hours post-infusionPopulation: The PK population included all study participants who took at least 1 dose of TAK-662 and had enough number of quantifiable blood levels for TAK-662 collected post-dose without important PDs/violations or events thought to substantially affect the PK.
Cmax of TAK-662 was reported.
Outcome measures
| Measure |
PK Part: TAK-662
n=5 Participants
Participants received a single 80 IU/kg dose of TAK-662, intravenous infusion on Day 1 in PK part.
|
Extension Part, On-demand Treatment (TAK-662)
Participants with PF, CISN/WISN, and/or other acute thromboembolic episode received a single dose of TAK-662 (100-120 IU/kg), followed by three subsequent infusions, every 6 hours at a dose of 60-80 IU/kg, and followed by subsequent infusions (45-60 IU/kg) continued every 6 or 12 hours until resolution of all non-necrotic lesions and/or stabilization of thrombi. Treatment could be terminated when an acute episode improved.
|
Extension Part, Short-term Prophylaxis Treatment (TAK-662)
Participants who required short-term prophylaxis of acute thrombotic episodes during surgery received TAK-662 at a dose of 100-120 IU/kg, intravenous infusion once daily, until anticoagulation therapy was successfully switched to TAK-662 prior to surgery. Fifteen minutes prior to surgery, a dose of 60-80 IU/kg was administered and continued once every 6 hours for the first 24 hours after surgery began. The frequency of infusions was reduced to 3 times daily between 24 and 48 hours, and twice daily after 48 hours at the same dose (45-60 IU/kg). Treatment with TAK-662 continued twice daily until anticoagulation therapy was initiated (if applicable) and the investigator determined that adequate level of the anticoagulation was achieved.
|
Extension Part, Long-term Prophylaxis Treatment (TAK-662)
Participants who required long-term prophylaxis were planned to receive TAK-662 at a dose of 45-60 IU/kg, intravenous infusion, twice daily. The dose was to be adjusted by referring to the latest protein C activity at the investigator's discretion. No participants received TAK-662 for long-term prophylaxis during the study.
|
|---|---|---|---|---|
|
PK Part: Maximum Observed Plasma Concentration (Cmax) of TAK-662
|
1.679 IU/ml
Geometric Coefficient of Variation 31.7
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Pre-infusion, 0.5, 1, 2, 4, 8, 12, 24, and 36 hours post-infusionPopulation: The PK population included all study participants who took at least 1 dose of TAK-662 and had enough number of quantifiable blood levels for TAK-662 collected post-dose without important PDs/violations or events thought to substantially affect the PK.
Tmax of TAK-662 was reported.
Outcome measures
| Measure |
PK Part: TAK-662
n=5 Participants
Participants received a single 80 IU/kg dose of TAK-662, intravenous infusion on Day 1 in PK part.
|
Extension Part, On-demand Treatment (TAK-662)
Participants with PF, CISN/WISN, and/or other acute thromboembolic episode received a single dose of TAK-662 (100-120 IU/kg), followed by three subsequent infusions, every 6 hours at a dose of 60-80 IU/kg, and followed by subsequent infusions (45-60 IU/kg) continued every 6 or 12 hours until resolution of all non-necrotic lesions and/or stabilization of thrombi. Treatment could be terminated when an acute episode improved.
|
Extension Part, Short-term Prophylaxis Treatment (TAK-662)
Participants who required short-term prophylaxis of acute thrombotic episodes during surgery received TAK-662 at a dose of 100-120 IU/kg, intravenous infusion once daily, until anticoagulation therapy was successfully switched to TAK-662 prior to surgery. Fifteen minutes prior to surgery, a dose of 60-80 IU/kg was administered and continued once every 6 hours for the first 24 hours after surgery began. The frequency of infusions was reduced to 3 times daily between 24 and 48 hours, and twice daily after 48 hours at the same dose (45-60 IU/kg). Treatment with TAK-662 continued twice daily until anticoagulation therapy was initiated (if applicable) and the investigator determined that adequate level of the anticoagulation was achieved.
|
Extension Part, Long-term Prophylaxis Treatment (TAK-662)
Participants who required long-term prophylaxis were planned to receive TAK-662 at a dose of 45-60 IU/kg, intravenous infusion, twice daily. The dose was to be adjusted by referring to the latest protein C activity at the investigator's discretion. No participants received TAK-662 for long-term prophylaxis during the study.
|
|---|---|---|---|---|
|
PK Part: Time to Reach the Maximum Plasma Concentration (Tmax) of TAK-662
|
0.53 hour
Interval 0.43 to 0.6
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: PK Part: From the start of study drug administration up to Day 7; Extension Part: From the first dose of study drug administration in the Extension Part up to 35 monthsPopulation: The safety population included all enrolled participants in the study who took at least 1 dose of TAK-662.
A treatment-related AE was defined as an adverse event that followed a reasonable temporal sequence from administration of a drug (including the course after withdrawal of the drug), or for which possible involvement of the drug was not able to be ruled out, although factors other than the drug, such as underlying diseases, complications, concomitant medications and concurrent treatments, might also be responsible. Number of participants with treatment-related AEs as assessed by the Investigator were reported.
Outcome measures
| Measure |
PK Part: TAK-662
n=5 Participants
Participants received a single 80 IU/kg dose of TAK-662, intravenous infusion on Day 1 in PK part.
|
Extension Part, On-demand Treatment (TAK-662)
n=4 Participants
Participants with PF, CISN/WISN, and/or other acute thromboembolic episode received a single dose of TAK-662 (100-120 IU/kg), followed by three subsequent infusions, every 6 hours at a dose of 60-80 IU/kg, and followed by subsequent infusions (45-60 IU/kg) continued every 6 or 12 hours until resolution of all non-necrotic lesions and/or stabilization of thrombi. Treatment could be terminated when an acute episode improved.
|
Extension Part, Short-term Prophylaxis Treatment (TAK-662)
n=1 Participants
Participants who required short-term prophylaxis of acute thrombotic episodes during surgery received TAK-662 at a dose of 100-120 IU/kg, intravenous infusion once daily, until anticoagulation therapy was successfully switched to TAK-662 prior to surgery. Fifteen minutes prior to surgery, a dose of 60-80 IU/kg was administered and continued once every 6 hours for the first 24 hours after surgery began. The frequency of infusions was reduced to 3 times daily between 24 and 48 hours, and twice daily after 48 hours at the same dose (45-60 IU/kg). Treatment with TAK-662 continued twice daily until anticoagulation therapy was initiated (if applicable) and the investigator determined that adequate level of the anticoagulation was achieved.
|
Extension Part, Long-term Prophylaxis Treatment (TAK-662)
Participants who required long-term prophylaxis were planned to receive TAK-662 at a dose of 45-60 IU/kg, intravenous infusion, twice daily. The dose was to be adjusted by referring to the latest protein C activity at the investigator's discretion. No participants received TAK-662 for long-term prophylaxis during the study.
|
|---|---|---|---|---|
|
PK and Extension Parts: Number of Participants With Treatment-Related Adverse Experiences (AEs)
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Extension Part: From the first dose of TAK-662 on-demand treatment in the Extension Part up to 35 monthsPopulation: Efficacy Analysis Set in On-Demand Treatment included all participants who took at least 1 dose of TAK-662 on-demand in the extension part.
The treatment of episodes of PF, CISN/ WISN, and/or other vascular thromboembolic events were rated as "effective", "effective with complications", or "not effective" according to the efficacy rating scale, as judged by investigators on the basis of following criteria, Effective: stabilization and regression of skin lesions/stabilization of thrombi; Effective with complications: treatment was effective but caused an adverse drug reaction that interfered with the regimen (resulted in change of dose or frequency of dosing) or forcing discontinuation of treatment or introducing pathogenic viral infection; Not effective: all other cases.
Outcome measures
| Measure |
PK Part: TAK-662
n=19 Total Number of Episodes
Participants received a single 80 IU/kg dose of TAK-662, intravenous infusion on Day 1 in PK part.
|
Extension Part, On-demand Treatment (TAK-662)
Participants with PF, CISN/WISN, and/or other acute thromboembolic episode received a single dose of TAK-662 (100-120 IU/kg), followed by three subsequent infusions, every 6 hours at a dose of 60-80 IU/kg, and followed by subsequent infusions (45-60 IU/kg) continued every 6 or 12 hours until resolution of all non-necrotic lesions and/or stabilization of thrombi. Treatment could be terminated when an acute episode improved.
|
Extension Part, Short-term Prophylaxis Treatment (TAK-662)
Participants who required short-term prophylaxis of acute thrombotic episodes during surgery received TAK-662 at a dose of 100-120 IU/kg, intravenous infusion once daily, until anticoagulation therapy was successfully switched to TAK-662 prior to surgery. Fifteen minutes prior to surgery, a dose of 60-80 IU/kg was administered and continued once every 6 hours for the first 24 hours after surgery began. The frequency of infusions was reduced to 3 times daily between 24 and 48 hours, and twice daily after 48 hours at the same dose (45-60 IU/kg). Treatment with TAK-662 continued twice daily until anticoagulation therapy was initiated (if applicable) and the investigator determined that adequate level of the anticoagulation was achieved.
|
Extension Part, Long-term Prophylaxis Treatment (TAK-662)
Participants who required long-term prophylaxis were planned to receive TAK-662 at a dose of 45-60 IU/kg, intravenous infusion, twice daily. The dose was to be adjusted by referring to the latest protein C activity at the investigator's discretion. No participants received TAK-662 for long-term prophylaxis during the study.
|
|---|---|---|---|---|
|
Extension Part: Number of Episode Rated as Effective, Effective With Complications, or Not Effective on Efficacy Rating Scale During On-Demand Treatment
Effective
|
19 treatment episodes
|
—
|
—
|
—
|
|
Extension Part: Number of Episode Rated as Effective, Effective With Complications, or Not Effective on Efficacy Rating Scale During On-Demand Treatment
Effective With Complications
|
0 treatment episodes
|
—
|
—
|
—
|
|
Extension Part: Number of Episode Rated as Effective, Effective With Complications, or Not Effective on Efficacy Rating Scale During On-Demand Treatment
Not Effective
|
0 treatment episodes
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Extension Part: From the first dose of TAK-662 short-term prophylaxis treatment in the Extension Part up to 35 monthsPopulation: Efficacy Analysis Set in Short-term Prophylaxis included all participants who took at least 1 dose of TAK-662 during short-term prophylaxis in the extension part.
Percentage of surgical episodes for which TAK-662 was utilized as short-term prophylaxis that is free of presentations of PF or thromboembolic complications was reported.
Outcome measures
| Measure |
PK Part: TAK-662
n=1 Total Number of Surgical Episodes
Participants received a single 80 IU/kg dose of TAK-662, intravenous infusion on Day 1 in PK part.
|
Extension Part, On-demand Treatment (TAK-662)
Participants with PF, CISN/WISN, and/or other acute thromboembolic episode received a single dose of TAK-662 (100-120 IU/kg), followed by three subsequent infusions, every 6 hours at a dose of 60-80 IU/kg, and followed by subsequent infusions (45-60 IU/kg) continued every 6 or 12 hours until resolution of all non-necrotic lesions and/or stabilization of thrombi. Treatment could be terminated when an acute episode improved.
|
Extension Part, Short-term Prophylaxis Treatment (TAK-662)
Participants who required short-term prophylaxis of acute thrombotic episodes during surgery received TAK-662 at a dose of 100-120 IU/kg, intravenous infusion once daily, until anticoagulation therapy was successfully switched to TAK-662 prior to surgery. Fifteen minutes prior to surgery, a dose of 60-80 IU/kg was administered and continued once every 6 hours for the first 24 hours after surgery began. The frequency of infusions was reduced to 3 times daily between 24 and 48 hours, and twice daily after 48 hours at the same dose (45-60 IU/kg). Treatment with TAK-662 continued twice daily until anticoagulation therapy was initiated (if applicable) and the investigator determined that adequate level of the anticoagulation was achieved.
|
Extension Part, Long-term Prophylaxis Treatment (TAK-662)
Participants who required long-term prophylaxis were planned to receive TAK-662 at a dose of 45-60 IU/kg, intravenous infusion, twice daily. The dose was to be adjusted by referring to the latest protein C activity at the investigator's discretion. No participants received TAK-662 for long-term prophylaxis during the study.
|
|---|---|---|---|---|
|
Extension Part: Percentage of Surgical Episodes During Short-Term Prophylaxis That is Free of Presentations of PF or Thromboembolic Complications
|
100.0 percentage of episode
Interval 2.5 to 100.0
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Extension Part: From the first dose of TAK-662 long-term prophylaxis treatment in the Extension Part up to 35 monthsPopulation: Efficacy Analysis Set in Long-term Prophylaxis included all study participants who took at least 1 dose of TAK-662 during long-term prophylaxis in the extension part. The "Overall Number of Participants Analyzed" is zero because no participants received TAK-662 for long-term prophylaxis; therefore, no data was collected and reported.
Number of episodes of PF and/or thrombotic episodes during long-term prophylaxis was planned to be reported.
Outcome measures
Outcome data not reported
Adverse Events
PK Part: TAK-662
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Extension Part, On-demand Treatment (TAK-662)
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Extension Part, Short-term Prophylaxis Treatment (TAK-662)
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Extension Part, Long-term Prophylaxis Treatment (TAK-662)
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
PK Part: TAK-662
n=5 participants at risk
Participants received a single 80 international unit per kilogram (IU/kg) dose of TAK-662, intravenous infusion on Day 1 in PK part.
|
Extension Part, On-demand Treatment (TAK-662)
n=4 participants at risk
Participants with purpura fulminans (PF), coumarin-induced skin necrosis/warfarin-induced skin necrosis (CISN/WISN), and/or other acute thromboembolic episode received a single dose of TAK-662 (100-120 IU/kg), followed by three subsequent infusions, every 6 hours at a dose of 60-80 IU/kg, and followed by subsequent infusions (45-60 IU/kg) continued every 6 or 12 hours until resolution of all non-necrotic lesions and/or stabilization of thrombi. Treatment could be terminated when an acute episode improved.
|
Extension Part, Short-term Prophylaxis Treatment (TAK-662)
n=1 participants at risk
Participants who required short-term prophylaxis of acute thrombotic episodes during surgery received TAK-662 at a dose of 100-120 IU/kg, intravenous infusion once daily, until anticoagulation therapy was successfully switched to TAK-662 prior to surgery. Fifteen minutes prior to surgery, a dose of 60-80 IU/kg was administered and continued once every 6 hours for the first 24 hours after surgery began. The frequency of infusions was reduced to 3 times daily between 24 and 48 hours, and twice daily after 48 hours at the same dose (45-60 IU/kg). Treatment with TAK-662 continued twice daily until anticoagulation therapy was initiated (if applicable) and the investigator determined that adequate level of the anticoagulation was achieved.
|
Extension Part, Long-term Prophylaxis Treatment (TAK-662)
Participants who required long-term prophylaxis were planned to receive TAK-662 at a dose of 45-60 IU/kg, intravenous infusion, twice daily. The dose was to be adjusted by referring to the latest protein C activity at the investigator's discretion. No participants received TAK-662 for long-term prophylaxis during the study.
|
|---|---|---|---|---|
|
Injury, poisoning and procedural complications
Contusion
|
0.00%
0/5 • PK Part: From start of study drug administration up to Day 7; Extension part: From first dose of study drug administration in Extension Part up to up to 35 months
No participant received TAK-662 for long-term prophylaxis and therefore, no safety data could be collected and reported for 'Extension Part, Long-term Prophylaxis treatment (TAK-662) arm.
|
25.0%
1/4 • PK Part: From start of study drug administration up to Day 7; Extension part: From first dose of study drug administration in Extension Part up to up to 35 months
No participant received TAK-662 for long-term prophylaxis and therefore, no safety data could be collected and reported for 'Extension Part, Long-term Prophylaxis treatment (TAK-662) arm.
|
0.00%
0/1 • PK Part: From start of study drug administration up to Day 7; Extension part: From first dose of study drug administration in Extension Part up to up to 35 months
No participant received TAK-662 for long-term prophylaxis and therefore, no safety data could be collected and reported for 'Extension Part, Long-term Prophylaxis treatment (TAK-662) arm.
|
—
0/0 • PK Part: From start of study drug administration up to Day 7; Extension part: From first dose of study drug administration in Extension Part up to up to 35 months
No participant received TAK-662 for long-term prophylaxis and therefore, no safety data could be collected and reported for 'Extension Part, Long-term Prophylaxis treatment (TAK-662) arm.
|
|
Skin and subcutaneous tissue disorders
Decubitus ulcer
|
0.00%
0/5 • PK Part: From start of study drug administration up to Day 7; Extension part: From first dose of study drug administration in Extension Part up to up to 35 months
No participant received TAK-662 for long-term prophylaxis and therefore, no safety data could be collected and reported for 'Extension Part, Long-term Prophylaxis treatment (TAK-662) arm.
|
25.0%
1/4 • PK Part: From start of study drug administration up to Day 7; Extension part: From first dose of study drug administration in Extension Part up to up to 35 months
No participant received TAK-662 for long-term prophylaxis and therefore, no safety data could be collected and reported for 'Extension Part, Long-term Prophylaxis treatment (TAK-662) arm.
|
0.00%
0/1 • PK Part: From start of study drug administration up to Day 7; Extension part: From first dose of study drug administration in Extension Part up to up to 35 months
No participant received TAK-662 for long-term prophylaxis and therefore, no safety data could be collected and reported for 'Extension Part, Long-term Prophylaxis treatment (TAK-662) arm.
|
—
0/0 • PK Part: From start of study drug administration up to Day 7; Extension part: From first dose of study drug administration in Extension Part up to up to 35 months
No participant received TAK-662 for long-term prophylaxis and therefore, no safety data could be collected and reported for 'Extension Part, Long-term Prophylaxis treatment (TAK-662) arm.
|
|
Renal and urinary disorders
Haematuria
|
0.00%
0/5 • PK Part: From start of study drug administration up to Day 7; Extension part: From first dose of study drug administration in Extension Part up to up to 35 months
No participant received TAK-662 for long-term prophylaxis and therefore, no safety data could be collected and reported for 'Extension Part, Long-term Prophylaxis treatment (TAK-662) arm.
|
25.0%
1/4 • PK Part: From start of study drug administration up to Day 7; Extension part: From first dose of study drug administration in Extension Part up to up to 35 months
No participant received TAK-662 for long-term prophylaxis and therefore, no safety data could be collected and reported for 'Extension Part, Long-term Prophylaxis treatment (TAK-662) arm.
|
0.00%
0/1 • PK Part: From start of study drug administration up to Day 7; Extension part: From first dose of study drug administration in Extension Part up to up to 35 months
No participant received TAK-662 for long-term prophylaxis and therefore, no safety data could be collected and reported for 'Extension Part, Long-term Prophylaxis treatment (TAK-662) arm.
|
—
0/0 • PK Part: From start of study drug administration up to Day 7; Extension part: From first dose of study drug administration in Extension Part up to up to 35 months
No participant received TAK-662 for long-term prophylaxis and therefore, no safety data could be collected and reported for 'Extension Part, Long-term Prophylaxis treatment (TAK-662) arm.
|
|
Infections and infestations
Nasopharyngitis
|
0.00%
0/5 • PK Part: From start of study drug administration up to Day 7; Extension part: From first dose of study drug administration in Extension Part up to up to 35 months
No participant received TAK-662 for long-term prophylaxis and therefore, no safety data could be collected and reported for 'Extension Part, Long-term Prophylaxis treatment (TAK-662) arm.
|
25.0%
1/4 • PK Part: From start of study drug administration up to Day 7; Extension part: From first dose of study drug administration in Extension Part up to up to 35 months
No participant received TAK-662 for long-term prophylaxis and therefore, no safety data could be collected and reported for 'Extension Part, Long-term Prophylaxis treatment (TAK-662) arm.
|
0.00%
0/1 • PK Part: From start of study drug administration up to Day 7; Extension part: From first dose of study drug administration in Extension Part up to up to 35 months
No participant received TAK-662 for long-term prophylaxis and therefore, no safety data could be collected and reported for 'Extension Part, Long-term Prophylaxis treatment (TAK-662) arm.
|
—
0/0 • PK Part: From start of study drug administration up to Day 7; Extension part: From first dose of study drug administration in Extension Part up to up to 35 months
No participant received TAK-662 for long-term prophylaxis and therefore, no safety data could be collected and reported for 'Extension Part, Long-term Prophylaxis treatment (TAK-662) arm.
|
|
Infections and infestations
Oral herpes
|
0.00%
0/5 • PK Part: From start of study drug administration up to Day 7; Extension part: From first dose of study drug administration in Extension Part up to up to 35 months
No participant received TAK-662 for long-term prophylaxis and therefore, no safety data could be collected and reported for 'Extension Part, Long-term Prophylaxis treatment (TAK-662) arm.
|
25.0%
1/4 • PK Part: From start of study drug administration up to Day 7; Extension part: From first dose of study drug administration in Extension Part up to up to 35 months
No participant received TAK-662 for long-term prophylaxis and therefore, no safety data could be collected and reported for 'Extension Part, Long-term Prophylaxis treatment (TAK-662) arm.
|
0.00%
0/1 • PK Part: From start of study drug administration up to Day 7; Extension part: From first dose of study drug administration in Extension Part up to up to 35 months
No participant received TAK-662 for long-term prophylaxis and therefore, no safety data could be collected and reported for 'Extension Part, Long-term Prophylaxis treatment (TAK-662) arm.
|
—
0/0 • PK Part: From start of study drug administration up to Day 7; Extension part: From first dose of study drug administration in Extension Part up to up to 35 months
No participant received TAK-662 for long-term prophylaxis and therefore, no safety data could be collected and reported for 'Extension Part, Long-term Prophylaxis treatment (TAK-662) arm.
|
|
Skin and subcutaneous tissue disorders
Purpura
|
20.0%
1/5 • PK Part: From start of study drug administration up to Day 7; Extension part: From first dose of study drug administration in Extension Part up to up to 35 months
No participant received TAK-662 for long-term prophylaxis and therefore, no safety data could be collected and reported for 'Extension Part, Long-term Prophylaxis treatment (TAK-662) arm.
|
25.0%
1/4 • PK Part: From start of study drug administration up to Day 7; Extension part: From first dose of study drug administration in Extension Part up to up to 35 months
No participant received TAK-662 for long-term prophylaxis and therefore, no safety data could be collected and reported for 'Extension Part, Long-term Prophylaxis treatment (TAK-662) arm.
|
0.00%
0/1 • PK Part: From start of study drug administration up to Day 7; Extension part: From first dose of study drug administration in Extension Part up to up to 35 months
No participant received TAK-662 for long-term prophylaxis and therefore, no safety data could be collected and reported for 'Extension Part, Long-term Prophylaxis treatment (TAK-662) arm.
|
—
0/0 • PK Part: From start of study drug administration up to Day 7; Extension part: From first dose of study drug administration in Extension Part up to up to 35 months
No participant received TAK-662 for long-term prophylaxis and therefore, no safety data could be collected and reported for 'Extension Part, Long-term Prophylaxis treatment (TAK-662) arm.
|
|
General disorders
Pyrexia
|
20.0%
1/5 • PK Part: From start of study drug administration up to Day 7; Extension part: From first dose of study drug administration in Extension Part up to up to 35 months
No participant received TAK-662 for long-term prophylaxis and therefore, no safety data could be collected and reported for 'Extension Part, Long-term Prophylaxis treatment (TAK-662) arm.
|
0.00%
0/4 • PK Part: From start of study drug administration up to Day 7; Extension part: From first dose of study drug administration in Extension Part up to up to 35 months
No participant received TAK-662 for long-term prophylaxis and therefore, no safety data could be collected and reported for 'Extension Part, Long-term Prophylaxis treatment (TAK-662) arm.
|
0.00%
0/1 • PK Part: From start of study drug administration up to Day 7; Extension part: From first dose of study drug administration in Extension Part up to up to 35 months
No participant received TAK-662 for long-term prophylaxis and therefore, no safety data could be collected and reported for 'Extension Part, Long-term Prophylaxis treatment (TAK-662) arm.
|
—
0/0 • PK Part: From start of study drug administration up to Day 7; Extension part: From first dose of study drug administration in Extension Part up to up to 35 months
No participant received TAK-662 for long-term prophylaxis and therefore, no safety data could be collected and reported for 'Extension Part, Long-term Prophylaxis treatment (TAK-662) arm.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee If a multicenter publication is not submitted within twelve (12) months after conclusion, abandonment or termination of the Study at all sites, or after Sponsor confirms there shall be no multicenter Study publication, the Institution and/or such Principal Investigator may publish the results from the Institution site individually.
- Publication restrictions are in place
Restriction type: OTHER