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The purpose of the study is to assess the efficacy and safety of Octafibrin for on-demand treatment of acute bleeding in subjects with congenital fibrinogen deficiency.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Octafibrin | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Octafibrin | Drug |
|
| Measure | Description | Time Frame |
|---|---|---|
| Overall Clinical Assessment of the Haemostatic Efficacy of Octafibrin in Treating the First Documented Bleeding Episode of Each Patient. | The first bleeding episode covers the time period from the first Octafibrin infusion until 24 hours (i.e., 1 day) after the last infusion. The investigator's overall clinical assessment of haemostatic efficacy for bleeding was based on a 4 point haemostatic efficacy scale. The final efficacy assessment of each patient was adjudicated by the Independent Data Monitoring & Endpoint Adjudication Committee (IDMEAC). | 24 hours after last infusion for each bleeding episode |
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Clot Firmness (MCF) After Fibrinogen Infusion in Each Documented Bleeding Episode (BE), Measured in Frozen Plasma in a Central Laboratory. | MCF (mm) was determined using ROTEM and was used as a surrogate marker for haemostatic efficacy. ROTEM is a method for the continuous measurement of clot formation and clot firmness. It utilises a mechanical detection system which is based on the ability of the blood or plasma clot to form a mechanical coupling over a distance of 1 mm. |
| Measure | Description | Time Frame |
|---|---|---|
| Analysis of Safety: Immunogenicity Testing for Anti-fibrinogen Antibodies | Immunogenicity testing for the presence of anti-fibrinogen antibodies at Day 14 and Day 30 after the administration of Octafibrin for bleeding. An experimental non-standard ELISA was developed for this study for evaluating anti-fibrinogen antibodies. No specific test was performed to discern for neutralizing antibodies. The clinical implications of the assay results are not known. |
Inclusion Criteria:
Exclusion Criteria:
Treatment with:
Presence or history of:
Pregnant women within the first 20 weeks of gestation.
Currently breast-feeding.
Known positive HIV infection with a viral load >200 particles/μL or >400,000 copies/mL.
Polytrauma 1 year prior to start of treatment for the bleeding episode or surgery.
Diagnosis or suspicion of a neutralizing anti-fibrinogen inhibitor currently or any time in the past.
Acute or chronic medical condition which may, in the opinion of investigator, affect the conduct of the study, including
Participation in another interventional clinical study currently or during the past 4 weeks.
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| Name | Affiliation | Role |
|---|---|---|
| Cristina Solomon, MD | Octapharma | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Miami Children's Hospital | Miami | Florida | 33155 | United States | ||
| Dept of Clinical Hematology for Hemorrhagic Diatheses and Anaemia, SHAT "Joan Pavel" |
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| ID | Title | Description |
|---|---|---|
| FG000 | Octafibrin | Thirty-three patients were screened and 25 patients received at least one administration of Octafibrin for treatment of bleeding or as surgical prophylaxis. Eight patients received Octafibrin for both bleeding and a surgical procedure. One patient was treated for a surgical procedure only. Octafibrin was individually dosed to achieve a recommended target plasma fibrinogen level of 100 mg/dL for minor bleeds/surgery or 150 mg/dL for major bleeds/surgery |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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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 | Oct 31, 2014 | Dec 21, 2020 |
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| Before first infusion and 1 hour after end of first and last infusion of each documented bleeding episode |
| Fibrinogen Plasma Level | Fibrinogen plasma level was assessed using the Clauss fibrinogen assay | Before (pre-infusion), 1 hour and 3 hours after the end of each subsequent infusion as well as at the time of the overall clinical assessment of haemostatic efficacy (i.e., 24 hours after the last infusion of each documented bleeding episode) |
| Response as Indicated by Incremental in Vivo Recovery (IVR) | Incremental IVR (response): calculated as the maximum increase in plasma fibrinogen (i.e., Clauss data) between pre-infusion and 1 and 3 hours post-infusion, divided by the exact dose of Octafibrin. | Pre-infusion and 1 and 3 hours post-infusion |
| Efficacy of Octafibrin for All Bleeding Episodes Collected in the Study | The investigator's overall clinical assessment of haemostatic efficacy for bleeding will be based on a 4-point haemostatic efficacy scale. The final efficacy assessment of each patient will be adjudicated by the Independent Data Monitoring & Endpoint Adjudication Committee (IDMEAC) | 24 hours after last infusion for each bleeding episode |
| Efficacy of Octafibrin in Preventing Bleeding During and After Surgery | The efficacy of Octafibrin will be assessed at the end of surgery by the surgeon and post-operatively by the haematologist using two 4-point haemostatic efficacy scales. An overall efficacy assessment taking both the intra- and post-operative assessment into account will be adjudicated by the IDMEAC | First dose of Octafibrin administered prior to elective surgery to at least 3 post-operative days for minor and 7 post-operative days for major surgeries or last post-operative infusion, whichever comes last |
| Up to 30 days (start of the first Octafibrin infusion until the end of each 30-day observation and follow-up period for on-demand treatment or until the Last Post-Operative Day in surgeries) |
| Sofia |
| Bulgaria |
| St. John's Medical College Hospital | Bangalore | India |
| Sahyadri Specialty Hospital | Pune | India |
| Dept of Hematology, Christian Medical College | Vellore | India |
| Seyed Al Shohada Hospital | Isfahan | Iran |
| Dastgheib Hospital | Shīrāz | Iran |
| Hotel-Dieu de France | Beirut | Lebanon |
| Haematological Scientific Center of Ministry of Healthcare of the Russian Federation | Moscow | Russia |
| Centre of Excellence in Thrombosis & Hemostasis, King Saud University | Riyadh | Saudi Arabia |
| Dept of Haematology, Ege University Children's Hospital | Izmir | Turkey (Türkiye) |
| Centre for Haemostasis & Thrombosis, St Thomas' Hospital | London | United Kingdom |
| SAFETY Population | 25 patients received at least one administration of Octafibrin. |
|
| FAS-Bleeding Population | Patients received Octafibrin for treatment of bleeding. |
|
| Surgical Prophylaxis Population | Patients received Octafibrin for surgical procedures. |
|
| COMPLETED |
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| NOT COMPLETED |
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All patients who received at least one Octafibrin administration during the study.
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| ID | Title | Description |
|---|---|---|
| BG000 | SAFETY Population | All patients who received at least one Octafibrin administration during the study. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
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| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
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| 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 | Overall Clinical Assessment of the Haemostatic Efficacy of Octafibrin in Treating the First Documented Bleeding Episode of Each Patient. | The first bleeding episode covers the time period from the first Octafibrin infusion until 24 hours (i.e., 1 day) after the last infusion. The investigator's overall clinical assessment of haemostatic efficacy for bleeding was based on a 4 point haemostatic efficacy scale. The final efficacy assessment of each patient was adjudicated by the Independent Data Monitoring & Endpoint Adjudication Committee (IDMEAC). | Posted | Count of Participants | Participants | 24 hours after last infusion for each bleeding episode |
|
|
| |||||||||||||||||||||||||||||||||||||
| Secondary | Maximum Clot Firmness (MCF) After Fibrinogen Infusion in Each Documented Bleeding Episode (BE), Measured in Frozen Plasma in a Central Laboratory. | MCF (mm) was determined using ROTEM and was used as a surrogate marker for haemostatic efficacy. ROTEM is a method for the continuous measurement of clot formation and clot firmness. It utilises a mechanical detection system which is based on the ability of the blood or plasma clot to form a mechanical coupling over a distance of 1 mm. | Posted | Mean | Standard Deviation | mm | Before first infusion and 1 hour after end of first and last infusion of each documented bleeding episode | Bleeding Episodes (BEs) | Bleeding Episodes (BEs) |
|
| |||||||||||||||||||||||||||||||||||
| Secondary | Fibrinogen Plasma Level | Fibrinogen plasma level was assessed using the Clauss fibrinogen assay | Posted | Mean | Standard Deviation | mg/dL | Before (pre-infusion), 1 hour and 3 hours after the end of each subsequent infusion as well as at the time of the overall clinical assessment of haemostatic efficacy (i.e., 24 hours after the last infusion of each documented bleeding episode) | BEs | BEs |
|
| |||||||||||||||||||||||||||||||||||
| Secondary | Response as Indicated by Incremental in Vivo Recovery (IVR) | Incremental IVR (response): calculated as the maximum increase in plasma fibrinogen (i.e., Clauss data) between pre-infusion and 1 and 3 hours post-infusion, divided by the exact dose of Octafibrin. | Posted | Mean | Standard Deviation | mg/dL/(mg/kg) | Pre-infusion and 1 and 3 hours post-infusion | BEs | BEs |
|
| |||||||||||||||||||||||||||||||||||
| Secondary | Efficacy of Octafibrin for All Bleeding Episodes Collected in the Study | The investigator's overall clinical assessment of haemostatic efficacy for bleeding will be based on a 4-point haemostatic efficacy scale. The final efficacy assessment of each patient will be adjudicated by the Independent Data Monitoring & Endpoint Adjudication Committee (IDMEAC) | Posted | Count of Units | BEs | 24 hours after last infusion for each bleeding episode | BEs | BEs |
|
| ||||||||||||||||||||||||||||||||||||
| Secondary | Efficacy of Octafibrin in Preventing Bleeding During and After Surgery | The efficacy of Octafibrin will be assessed at the end of surgery by the surgeon and post-operatively by the haematologist using two 4-point haemostatic efficacy scales. An overall efficacy assessment taking both the intra- and post-operative assessment into account will be adjudicated by the IDMEAC | Posted | Count of Units | Surgeries | First dose of Octafibrin administered prior to elective surgery to at least 3 post-operative days for minor and 7 post-operative days for major surgeries or last post-operative infusion, whichever comes last | Surgeries | Surgeries |
| |||||||||||||||||||||||||||||||||||||
| Other Pre-specified | Analysis of Safety: Immunogenicity Testing for Anti-fibrinogen Antibodies | Immunogenicity testing for the presence of anti-fibrinogen antibodies at Day 14 and Day 30 after the administration of Octafibrin for bleeding. An experimental non-standard ELISA was developed for this study for evaluating anti-fibrinogen antibodies. No specific test was performed to discern for neutralizing antibodies. The clinical implications of the assay results are not known. | Posted | Count of Participants | Participants | Up to 30 days (start of the first Octafibrin infusion until the end of each 30-day observation and follow-up period for on-demand treatment or until the Last Post-Operative Day in surgeries) |
|
|
Up to 30 days (start of the first Octafibrin infusion until the end of each 30-day observation and follow-up period for on-demand treatment or until the Last Post-Operative Day in surgeries).
AEs occurring between the start of the first Octafibrin infusion and the end of each 30-day observation and follow-up period and during the surgical follow-up were recorded as treatment-emergent adverse events (TEAEs). Non-TEAEs were all AEs not falling into the follow-up periods
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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 | Safety Population | All patients who received at least one administration of Octafibrin during the study | 0 | 25 | 5 | 25 | 19 | 25 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Upper gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA V18.1 | Systematic Assessment |
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| Ligament rupture | Injury, poisoning and procedural complications | MedDRA V18.1 | Systematic Assessment |
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| Ligament sprain | Injury, poisoning and procedural complications | MedDRA V18.1 | Systematic Assessment |
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| Patella fracture | Injury, poisoning and procedural complications | MedDRA V18.1 | Systematic Assessment |
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| Transfusion reaction | Injury, poisoning and procedural complications | MedDRA V18.1 | Systematic Assessment |
| |
| Accelerated hypertension | Vascular disorders | MedDRA V18.1 | Systematic Assessment |
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| Thrombosis | Vascular disorders | MedDRA V18.1 | Systematic Assessment |
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| Peripheral ischaemia | Vascular disorders | MedDRA V18.1 | Systematic Assessment |
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| Dengue fever | Infections and infestations | MedDRA V18.1 | Systematic Assessment |
| |
| Hepatitis C | Infections and infestations | MedDRA V18.1 | Systematic Assessment |
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| Haemorrhage intracranial | Nervous system disorders | MedDRA V18.1 | Systematic Assessment |
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| Iron deficiency anaemia | Blood and lymphatic system disorders | MedDRA V18.1 | Systematic Assessment |
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| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA V18.1 | Systematic Assessment |
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| Abortion spontaneous | Pregnancy, puerperium and perinatal conditions | MedDRA V18.1 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Gingival bleeding | Gastrointestinal disorders | MedDRA V18.1 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA V18.1 | Systematic Assessment | Of these, 3 AEs in 2 patients were deemed to be TEAEs. |
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| Abdominal pain upper | Gastrointestinal disorders | MedDRA V18.1 | Systematic Assessment | This/these were deemed to be a TEAE. |
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| Constipation | Gastrointestinal disorders | MedDRA V18.1 | Systematic Assessment | This/these were deemed to be a TEAE. |
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| Gastritis | Gastrointestinal disorders | MedDRA V18.1 | Systematic Assessment |
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| Lip haemorrhage | Gastrointestinal disorders | MedDRA V18.1 | Systematic Assessment |
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| Rectal haemorrhage | Gastrointestinal disorders | MedDRA V18.1 | Systematic Assessment | This/these were deemed to be a TEAE. |
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| Toothache | Gastrointestinal disorders | MedDRA V18.1 | Systematic Assessment |
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| Limb injury | Injury, poisoning and procedural complications | MedDRA V18.1 | Systematic Assessment | This/these were deemed to be a TEAE. |
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| Procedural pain | Injury, poisoning and procedural complications | MedDRA V18.1 | Systematic Assessment | This/these were deemed to be a TEAE. |
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| Arthropod sting | Injury, poisoning and procedural complications | MedDRA V18.1 | Systematic Assessment | This/these were deemed to be a TEAE. |
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| Contusion | Injury, poisoning and procedural complications | MedDRA V18.1 | Systematic Assessment | This/these were deemed to be a TEAE. |
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| Epicondylitis | Injury, poisoning and procedural complications | MedDRA V18.1 | Systematic Assessment | This/these were deemed to be a TEAE. |
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| Incision site pain | Injury, poisoning and procedural complications | MedDRA V18.1 | Systematic Assessment | This/these were deemed to be a TEAE. |
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| Skin wound | Injury, poisoning and procedural complications | MedDRA V18.1 | Systematic Assessment | This/these were deemed to be a TEAE. |
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| Traumatic haemorrhage | Injury, poisoning and procedural complications | MedDRA V18.1 | Systematic Assessment | This/these were deemed to be a TEAE. |
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| Haemorrhage | Vascular disorders | MedDRA V18.1 | Systematic Assessment | Of these, 1 AE was deemed to be a TEAE. |
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| Hypertension | Vascular disorders | MedDRA V18.1 | Systematic Assessment | Of these, 1 AE was deemed to be a TEAE. |
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| Haematoma | Vascular disorders | MedDRA V18.1 | Systematic Assessment | This/these were deemed to be a TEAE. |
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| Brucellosis | Infections and infestations | MedDRA V18.1 | Systematic Assessment |
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| Pharyngitis | Infections and infestations | MedDRA V18.1 | Systematic Assessment | This/these were deemed to be a TEAE. |
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| Purulent discharge | Infections and infestations | MedDRA V18.1 | Systematic Assessment | This/these were deemed to be a TEAE. |
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| Rash pustular | Infections and infestations | MedDRA V18.1 | Systematic Assessment |
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| Rhinitis | Infections and infestations | MedDRA V18.1 | Systematic Assessment |
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| Tonsillitis | Infections and infestations | MedDRA V18.1 | Systematic Assessment | This/these were deemed to be a TEAE. |
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| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA V18.1 | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA V18.1 | Systematic Assessment | Of these, 1 AE was deemed to be a TEAE. |
|
| Groin pain | Musculoskeletal and connective tissue disorders | MedDRA V18.1 | Systematic Assessment |
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| Muscle haemorrhage | Musculoskeletal and connective tissue disorders | MedDRA V18.1 | Systematic Assessment | This/these were deemed to be a TEAE. |
|
| Ecchymosis | Skin and subcutaneous tissue disorders | MedDRA V18.1 | Systematic Assessment |
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| Drug eruption | Skin and subcutaneous tissue disorders | MedDRA V18.1 | Systematic Assessment | This/these were deemed to be a TEAE. |
|
| Skin fissures | Skin and subcutaneous tissue disorders | MedDRA V18.1 | Systematic Assessment | This/these were deemed to be a TEAE. |
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| Skin haemorrhage | Skin and subcutaneous tissue disorders | MedDRA V18.1 | Systematic Assessment |
| |
| Skin lesion | Skin and subcutaneous tissue disorders | MedDRA V18.1 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA V18.1 | Systematic Assessment |
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| Hypoaesthesia | Nervous system disorders | MedDRA V18.1 | Systematic Assessment |
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| Genital lesion | Reproductive system and breast disorders | MedDRA V18.1 | Systematic Assessment |
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| Menorrhagia | Reproductive system and breast disorders | MedDRA V18.1 | Systematic Assessment |
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| Pelvic congestion | Reproductive system and breast disorders | MedDRA V18.1 | Systematic Assessment |
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| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA V18.1 | Systematic Assessment | This/these were deemed to be a TEAE. |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA V18.1 | Systematic Assessment |
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| Upper respiratory tract infection | Respiratory, thoracic and mediastinal disorders | MedDRA V18.1 | Systematic Assessment | This/these were deemed to be a TEAE. |
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| Asthenia | General disorders | MedDRA V18.1 | Systematic Assessment | This/these were deemed to be a TEAE. |
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| Pain | General disorders | MedDRA V18.1 | Systematic Assessment | This/these were deemed to be a TEAE. |
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| Transaminases increased | Investigations | MedDRA V18.1 | Systematic Assessment | This/these were deemed to be a TEAE. |
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| Depression | Psychiatric disorders | MedDRA V18.1 | Systematic Assessment | This/these were deemed to be a TEAE. |
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| Dysuria | Renal and urinary disorders | MedDRA V18.1 | Systematic Assessment | This/these were deemed to be a TEAE. |
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| Reactive thrombocytosis | Blood and lymphatic system disorders | MedDRA V18.1 | Systematic Assessment | This/these were deemed to be a TEAE. |
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| Phlebitis | Vascular disorders | MedDRA V18.1 | Systematic Assessment | This/these were deemed to be a TEAE. |
|
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Director of Clinical Operations | Octapharma USA | 201 604-1149 | sylvia.werner@octapharma.com |
| Prot_002.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jul 11, 2016 | Dec 21, 2020 | SAP_003.pdf |
| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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| Moderate |
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| None |
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| Missing |
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| Overall treatment success |
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| Bleeding Episodes (BEs) |
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| Participants |
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| BEs |
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| BEs |
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