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| ID | Type | Description | Link |
|---|---|---|---|
| U1111-1267-4412 | Other Identifier | WHO | |
| jRCT2031210209 | Registry Identifier | jRCT |
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Pharmacokinetic Part:
This study is for Japanese participants with congenital protein C deficiency. The main aim of this study is to check how much TAK-662 stays in their blood over time. This will help the study sponsor (Takeda) to work out the best dose to give patients in the future.
Participants will receive 1 single infusion of TAK-662.
They will stay at the clinic until 3 days after the infusion. Then, participants will return to their clinic 7 days after the infusion to check side effects from the study treatment.
Extension Part:
Participants who will complete the PK part will be given an opportunity to continue TAK-662 administration as 3 different treatment options (on-demand therapy, short-term prophylaxis, and long-term prophylaxis) in the Extension part, until the commercial protein C concentrate is available at each study site or study termination.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| TAK-662 80 IU/kg | Experimental | TAK-662 80 international unit (IU)/kg, single intravenous infusion over 15 minutes on Day 1. In the extension part, dose of TAK-662 will be modified per participants. TAK-662 is Protein C Concentrate, which is a lyophilized, sterile concentrate of human protein C. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| TAK-662 | Drug | Lyophilized, sterile concentrate of human protein C |
|
| Measure | Description | Time Frame |
|---|---|---|
| PK Part: Protein C Activity Level of TAK-662 | 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. | Pre-infusion, 0.5, 1, 2, 4, 8, 12, 24, and 36 hours post-infusion |
| PK Part: Terminal Phase Elimination Half-life (t1/2) of TAK-662 | t1/2 of TAK-662 was reported. | Pre-infusion, 0.5, 1, 2, 4, 8, 12, 24, and 36 hours post-infusion |
| PK Part: Incremental Recovery (IR) of TAK-662 | IR of TAK-662 was reported measured in terms of international unit per milliliter/ international unit per kilogram (IU/mL)/(IU/kg). | Pre-infusion, 0.5, 1, 2, 4, 8, 12, 24, and 36 hours post-infusion |
| PK Part: Percentage of In-vivo Recovery (IVR) of TAK-662 | 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. | Pre-infusion, 0.5, 1, 2, 4, 8, 12, 24, and 36 hours post-infusion |
| PK Part: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of TAK-662 | AUClast of TAK-662 was reported measured in terms of international unit*hour per milliliter (IU*h/ml). | Pre-infusion, 0.5, 1, 2, 4, 8, 12, 24, and 36 hours post-infusion |
| PK Part: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-infinity) of TAK-662 |
| Measure | Description | Time Frame |
|---|---|---|
| PK and Extension Parts: Number of Participants With Treatment-Related Adverse Experiences (AEs) | 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. |
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Inclusion Criteria:
PK Part:
Extension part:
Exclusion Criteria:
PK Part:
Extension Part:
1. New serious medical conditions which could affect participant's safety or treatment were observed during participation in the PK part of this study (TAK-662-1501).
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| Name | Affiliation | Role |
|---|---|---|
| Study Director | Takeda | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Nara Medical University Hospital | Kashihara | Nara | Japan | |||
| Chiba Children's Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 41859023 | Derived | Koh K, Nogami K, Kakuda H, Okimoto Y, Hino M, Tanigawara Y, Li Z, Suzuki C, Terashio S, Ueda H, Ohga S. A Phase 1/2, Open-Label, Single-Dose, Multicenter Study to Evaluate the Pharmacokinetics and Safety of Human Plasma-Derived Protein C Concentrate in Japanese Patients with Severe Congenital Protein C Deficiency (SCPCD). J Blood Med. 2026 Mar 13;17:535025. doi: 10.2147/JBM.S535025. eCollection 2026. |
| Label | URL |
|---|---|
| To obtain more information on the study, click here/on this link | View source |
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De-identified individual participant data from this particular study will not be shared as there is a reasonable likelihood that individual patients could be reidentified (due to the limited number of study participants/study sites).
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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.
This study was conducted at 4 centers in Japan from 7 September 2021 to 31 October 2024.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| FG001 | 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. |
| FG002 | 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. |
| FG003 | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| PK Part: Up to 7 Days |
| |||||||||||||
| Extension Part: Up to 35 Months |
|
The safety population included all enrolled participants in the study who took at least 1 dose of TAK-662.
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| ID | Title | Description |
|---|---|---|
| BG000 | PK Part: TAK-662 | Participants received a single 80 IU/kg dose of TAK-662, intravenous infusion on Day 1 in PK part. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | PK Part: Protein C Activity Level of TAK-662 | 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. | 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. | Posted | Mean | Standard Deviation | international unit per milliliter(IU/ml) | Pre-infusion, 0.5, 1, 2, 4, 8, 12, 24, and 36 hours post-infusion |
|
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.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Contusion | Injury, poisoning and procedural complications | MedDRA 27.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Takeda | +1-877-825-3327 | TrialDisclosures@takeda.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Sep 8, 2022 | Mar 27, 2023 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Oct 28, 2022 | Mar 27, 2023 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D011486 | Protein C |
| ID | Term |
|---|---|
| D004792 | Enzyme Precursors |
| D045762 | Enzymes and Coenzymes |
| D006023 | Glycoproteins |
| D006001 | Glycoconjugates |
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AUC0-infinity of TAK-662 was reported. |
| Pre-infusion, 0.5, 1, 2, 4, 8, 12, 24, and 36 hours post-infusion |
| PK Part: Maximum Observed Plasma Concentration (Cmax) of TAK-662 | Cmax of TAK-662 was reported. | Pre-infusion, 0.5, 1, 2, 4, 8, 12, 24, and 36 hours post-infusion |
| PK Part: Time to Reach the Maximum Plasma Concentration (Tmax) of TAK-662 | Tmax of TAK-662 was reported. | Pre-infusion, 0.5, 1, 2, 4, 8, 12, 24, and 36 hours post-infusion |
| 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 months |
| Extension Part: Number of Episode Rated as Effective, Effective With Complications, or Not Effective on Efficacy Rating Scale During On-Demand Treatment | 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. | Extension Part: From the first dose of TAK-662 on-demand treatment in the Extension Part up to 35 months |
| Extension Part: Percentage of Surgical Episodes During Short-Term Prophylaxis That is Free of Presentations of PF or Thromboembolic Complications | 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. | Extension Part: From the first dose of TAK-662 short-term prophylaxis treatment in the Extension Part up to 35 months |
| Extension Part: Number of Episodes of PF and/or Thrombotic Episodes During Long-Term Prophylaxis | Number of episodes of PF and/or thrombotic episodes during long-term prophylaxis was planned to be reported. | Extension Part: From the first dose of TAK-662 long-term prophylaxis treatment in the Extension Part up to 35 months |
| Chiba |
| Japan |
| Chiba University Hospital | Chiba | Japan |
| Saitama Prefectural Children's Medical Center | Saitama | Japan |
| COMPLETED |
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| NOT COMPLETED |
|
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Units | Counts |
|---|---|
| Participants |
|
|
| Primary | PK Part: Terminal Phase Elimination Half-life (t1/2) of TAK-662 | t1/2 of TAK-662 was reported. | 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. | Posted | Median | Full Range | hour | Pre-infusion, 0.5, 1, 2, 4, 8, 12, 24, and 36 hours post-infusion |
|
|
|
| Primary | PK Part: Incremental Recovery (IR) of TAK-662 | IR of TAK-662 was reported measured in terms of international unit per milliliter/ international unit per kilogram (IU/mL)/(IU/kg). | 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. | Posted | Mean | Standard Deviation | (IU/mL)/(IU/kg) | Pre-infusion, 0.5, 1, 2, 4, 8, 12, 24, and 36 hours post-infusion |
|
|
|
| Primary | PK Part: Percentage of In-vivo Recovery (IVR) of TAK-662 | 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. | 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. | Posted | Mean | Standard Deviation | percentage of IVR | Pre-infusion, 0.5, 1, 2, 4, 8, 12, 24, and 36 hours post-infusion |
|
|
|
| Primary | PK Part: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of TAK-662 | AUClast of TAK-662 was reported measured in terms of international unit*hour per milliliter (IU*h/ml). | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | IU*h/ml | Pre-infusion, 0.5, 1, 2, 4, 8, 12, 24, and 36 hours post-infusion |
|
|
|
| Primary | PK Part: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-infinity) of TAK-662 | AUC0-infinity of TAK-662 was reported. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | IU*h/ml | Pre-infusion, 0.5, 1, 2, 4, 8, 12, 24, and 36 hours post-infusion |
|
|
|
| Primary | PK Part: Maximum Observed Plasma Concentration (Cmax) of TAK-662 | Cmax of TAK-662 was reported. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | IU/ml | Pre-infusion, 0.5, 1, 2, 4, 8, 12, 24, and 36 hours post-infusion |
|
|
|
| Primary | PK Part: Time to Reach the Maximum Plasma Concentration (Tmax) of TAK-662 | Tmax of TAK-662 was reported. | 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. | Posted | Median | Full Range | hour | Pre-infusion, 0.5, 1, 2, 4, 8, 12, 24, and 36 hours post-infusion |
|
|
|
| Secondary | PK and Extension Parts: Number of Participants With Treatment-Related Adverse Experiences (AEs) | 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. | The safety population included all enrolled participants in the study who took at least 1 dose of TAK-662. | Posted | Count of Participants | Participants | 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 months |
|
|
|
| Secondary | Extension Part: Number of Episode Rated as Effective, Effective With Complications, or Not Effective on Efficacy Rating Scale During On-Demand Treatment | 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. | 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. | Posted | Number | treatment episodes | Extension Part: From the first dose of TAK-662 on-demand treatment in the Extension Part up to 35 months | Total Number of Episodes | Total Number of Episodes |
|
|
|
| Secondary | Extension Part: Percentage of Surgical Episodes During Short-Term Prophylaxis That is Free of Presentations of PF or Thromboembolic Complications | 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. | 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. | Posted | Number | 95% Confidence Interval | percentage of episode | Extension Part: From the first dose of TAK-662 short-term prophylaxis treatment in the Extension Part up to 35 months | Total Number of Surgical Episodes | Total Number of Surgical Episodes |
|
|
|
| Secondary | Extension Part: Number of Episodes of PF and/or Thrombotic Episodes During Long-Term Prophylaxis | Number of episodes of PF and/or thrombotic episodes during long-term prophylaxis was planned to be reported. | 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. | Posted | Extension Part: From the first dose of TAK-662 long-term prophylaxis treatment in the Extension Part up to 35 months |
|
|
| 0 |
| 5 |
| 0 |
| 5 |
| 2 |
| 5 |
| EG001 | 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. | 0 | 4 | 0 | 4 | 3 | 4 |
| EG002 | 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. | 0 | 1 | 0 | 1 | 0 | 1 |
| EG003 | 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. | 0 | 0 | 0 | 0 | 0 | 0 |
| Decubitus ulcer | Skin and subcutaneous tissue disorders | MedDRA 27.1 | Systematic Assessment |
|
| Haematuria | Renal and urinary disorders | MedDRA 27.1 | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA 27.1 | Systematic Assessment |
|
| Oral herpes | Infections and infestations | MedDRA 27.1 | Systematic Assessment |
|
| Purpura | Skin and subcutaneous tissue disorders | MedDRA 27.1 | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 27.1 | Systematic Assessment |
|
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.
| D002241 |
| Carbohydrates |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D011498 | Protein Precursors |
| D019774 | Blood Coagulation Factor Inhibitors |
| D001685 | Biological Factors |
| Title | Measurements |
|---|---|
|