Cancer
Conditions
Brief summary
The purpose of this study is to determine the long term tolerability and safety of dalteparin in subjects with cancer.
Interventions
DRUGdalteparin
Daily subcutaneous injection 200IU/kg dalteparin
Sponsors
Pfizer
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male and female subjects, age greater than or equal to 18 years of age. 2. Females should be either of non-childbearing potential as a result of surgery, radiation therapy, menopause (one year post onset), or of childbearing potential and willing to adhere to an acceptable method of pregnancy prevention. 3. Subjects must be newly diagnosed, symptomatic proximal deep-vein thrombosis of the lower extremity, pulmonary embolism, or both. 4. Subjects must have active malignancy defined as a diagnosis of cancer (excluding basal cell or squamous cell carcinoma of the skin) within six months before enrollment, having received any treatment for cancer within the previous six months, or having documented recurrent or metastatic cancer. 5. Prior to enrollment, subjects must not have received therapeutic doses of anticoagulant therapy (including low molecular weight heparin \[LMWH\]) for \>48 hours (or \>4 doses within 48 hours). 6. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2. 7. Subjects must have a life expectancy of \>6 months. 8. Subjects must have a platelet count of \>75,000 mm\^3. 9. The subject must not be on any oral anticoagulant therapy for concomitant diseases. 10. Subjects must have no active or serious bleeding episodes within two weeks prior to study entry. 11. Subjects must be able to comply with scheduled follow-ups.
Exclusion criteria
1. Subjects who have a high risk of serious bleeding (e.g., recent neurosurgery within 30 days, history of intracranial hemorrhage, acute gastroduodenal ulcer, etc.). 2. Subjects who are on hemodialysis. 3. Subjects who have a prior placement of a Greenfield filter or other device to prevent embolization of deep vein thromboses. 4. Subjects with a known contraindication to the use of heparin (e.g., heparin-induced thrombocytopenia). 5. Subjects with a known hypersensitivity to heparin, dalteparin sodium, other LMWHs or pork products. 6. Subjects who are currently participating in another clinical trial involving anticoagulation therapy (with the exception of acetylsalicylic acid (ASA) in the 30 days prior to study entry, or who are actively using any investigational drugs/treatments 30 days prior to study entry involving anticoagulation therapy (with the exception of ASA , t.i.d). 7. Subject is pregnant or breast feeding. 8. Subjects with uncontrolled hypertension characterized by a sustained systolic pressure \>170 mmHg and/or diastolic pressure \>100 mmHg. 9. Subjects with a serious concomitant systemic disorder (for example, active infection including HIV or cardiac disease) that in the opinion of the investigator, would compromise the subject's ability to complete the study. 10. Any condition that makes the subject unsuitable in the opinion of the investigator. 11. Subjects with leukemia or myeloproliferative syndrome.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Major Bleeding Events Adjudicated by Central Adjudication Committee | Month 2 up to Month 6 | A bleeding event was considered as major if it was clinically overt and satisfies 1 or more of the following criteria: 1) bleeding accompanied by a decrease in hemoglobin of greater than or equal to (\>=) 2 gram per deciliter (g/dL), 2) bleeding occurred at a critical site (intraocular, spinal/epidural, intracranial, retroperitoneal, or pericardial bleeding), 3) bleeding leads to a transfusion of two or more units of packed red blood cells, 4) bleeding leads to death. In this outcome measure, number of participants with major bleeding events (adjudicated by Central Adjudication Committee) were reported. |
| Number of Participants With New or Recurrent Venous Thromboembolism (VTE) Adjudicated by Central Adjudication Committee | Month 7 up to Month 12 | VTEs included both deep vein thrombosis (DVT) and pulmonary embolism (PE). DVT is a blood clot in the deep veins of the leg. If a DVT clot breaks off (embolizes) from a vein wall and flows towards the lungs and blocks some or all of the blood supply, it becomes pulmonary embolism (PE). When a blood clot (thrombus) breaks, loose and travels in the blood, this is called a venous thromboembolism. DVT was diagnosed using either computed tomography scan or contrast venography. PE was diagnosed by either radionuclide ventilation-perfusion studies, contrast CT scan or an angiogram. In this outcome measure, number of participants with new or recurrent VTE (adjudicated by Central Adjudication Committee) were reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to First Occurrence of Major Bleeding Event Adjudicated by Central Adjudication Committee | Month 1 up to Month 12 | Time to first occurrence of major bleeding event was defined as the time interval (in days) between the date of first study treatment and the date of documentation of first major bleeding event. A bleeding event was considered as major if it was clinically overt and satisfies 1 or more of the following criteria: 1) bleeding accompanied by a decrease in hemoglobin of \>=2 g/dL, 2) bleeding occurred at a critical site (intraocular, spinal/epidural, intracranial, retroperitoneal, or pericardial bleeding), 3) bleeding leads to a transfusion of two or more units of packed red blood cells, 4) bleeding leads to death. |
| Number of Participants With Investigator Identified New or Recurrent Venous Thromboembolism (VTEs) | Month 1 up to Month 6; Month 7 up to Month 12; Month 1 up to Month 12; Month 2 up to Month 6; Month 2 up to Month 12 | VTEs included both DVT and PE. DVT is a blood clot in the deep veins of the leg. If a DVT clot breaks off (embolizes) from a vein wall and flows towards the lungs and blocks some or all of the blood supply, it becomes PE. When a blood clot (thrombus) breaks, loose and travels in the blood, this is called a venous thromboembolism. DVT was diagnosed using either computed tomography scan or contrast venography. PE was diagnosed by either radionuclide ventilation-perfusion studies, contrast CT scan or an angiogram. In this outcome measure, number of participants with new or recurrent VTE (identified by investigator) were reported. |
| Number of Participants With New or Recurrent Venous Thromboembolism (VTE) or Central Venous Thrombosis (CVT) Adjudicated by Central Adjudication Committee | Month 1 up to Month 6; Month 7 up to Month 12; Month 1 up to Month 12; Month 2 up to Month 6; Month 2 up to Month 12 | VTEs included both DVT and PE. DVT is a blood clot in the deep veins of the leg. If a DVT clot breaks off (embolizes) from a vein wall and flows towards the lungs and blocks some or all of the blood supply, it becomes PE. When a blood clot (thrombus) breaks, loose and travels in the blood, this is called a venous thromboembolism. DVT was diagnosed using either computed tomography scan or contrast venography. PE was diagnosed by either radionuclide ventilation-perfusion studies, contrast CT scan or an angiogram. CVT is blood clot of the venous channels in the brain. CVT was diagnosed by contrast venography or ultrasonography. In this outcome measure, number of participants with new or recurrent VTE or CVT (adjudicated by Central Adjudication Committee) were reported. |
| Number of Participants With Investigator Identified New or Recurrent Venous Thromboembolism (VTE) or Central Venous Thrombosis (CVT) | Month 1 up to Month 6; Month 7 up to Month 12; Month 1 up to Month 12; Month 2 up to Month 6; Month 2 up to Month 12 | VTEs included both DVT and PE. DVT is a blood clot in the deep veins of the leg. If a DVT clot breaks off (embolizes) from a vein wall and flows towards the lungs and blocks some or all of the blood supply, it becomes PE. When a blood clot (thrombus) breaks, loose and travels in the blood, this is called a venous thromboembolism. DVT was diagnosed using either computed tomography scan or contrast venography. PE was diagnosed by either radionuclide ventilation-perfusion studies, contrast CT scan or an angiogram. CVT is blood clot of the venous channels in the brain. CVT was diagnosed by contrast venography or ultrasonography. In this outcome measure, number of participants with new or recurrent VTE or CVT (identified by investigator) were reported. |
| Time to First Occurrence of New or Recurrent Venous Thromboembolism (VTE) Adjudicated by Central Adjudication Committee | Month 1 up to Month 12 | Time to first occurrence of new or recurrent VTE was defined as the time interval (in days) between the date of first study treatment and the date of documentation of first VTE. VTEs included both DVT and PE. DVT is a blood clot in the deep veins of the leg. If a DVT clot breaks off (embolizes) from a vein wall and flows towards the lungs and blocks some or all of the blood supply, it becomes PE. When a blood clot (thrombus) breaks, loose and travels in the blood, this is called a venous thromboembolism. DVT was diagnosed using either computed tomography scan or contrast venography. PE was diagnosed by either radionuclide ventilation-perfusion studies, contrast CT scan or an angiogram. |
| Time to First Occurrence of New or Recurrent VTE or CVT Adjudicated by Central Adjudication Committee | Month 1 up to Month 12 | Time to first occurrence of new or recurrent VTE or CVT was defined as the time interval (in days) between the date of first study treatment and the date of documentation of first VTE or CVT. VTEs included both deep vein thrombosis (DVT) and pulmonary embolism (PE) .DVT is a blood clot in the deep veins of the leg. If a DVT clot that breaks off (embolizes) from a vein wall and flows towards the lungs and blocks some or all of the blood supply, it becomes pulmonary embolism (PE). When a blood clot (thrombus) breaks, loose and travels in the blood, this is called a venous thromboembolism. DVT was diagnosed using either computed tomography scan, contrast venography or contrast venography. PE was diagnosed by either radionuclide ventilation-perfusion studies, contrast CT scan or an angiogram. CVT is blood clot of the venous channels in the brain. CVT was diagnosed by contrast venography or ultrasonography. |
| Number of Participants With Investigator Identified Major Bleeding Events | Month 1 up to Month 6; Month 7 up to Month 12; Month 1 up to Month 12; Month 2 up to Month 6; Month 2 up to Month 12 | A bleeding event was considered as major if it was clinically overt and satisfies 1 or more of the following criteria: 1) bleeding accompanied by a decrease in hemoglobin of \>=2 g/dL, 2) bleeding occurred at a critical site (intraocular, spinal/epidural, intracranial, retroperitoneal, or pericardial bleeding), 3) bleeding leads to a transfusion of two or more units of packed red blood cells, 4) bleeding leads to death. In this outcome measure, number of participants with major bleeding events (identified by investigator) were reported. |
| Number of Participants With Any Bleeding Event (Major or Minor) Adjudicated by Central Adjudication Committee | Month 1 up to Month 6, Month 7 up to Month 12, Month 1 up to Month 12, Month 2 up to Month 6, and Month 2 up to Month 12 | A bleeding event was considered as major if it was clinically overt and satisfies 1 or more of the following criteria: 1) bleeding accompanied by a decrease in hemoglobin of \>=2 g/dL, 2) bleeding occurred at a critical site (intraocular, spinal/epidural, intracranial, retroperitoneal, or pericardial bleeding), 3) bleeding leads to a transfusion of two or more units of packed red blood cells, 4) bleeding leads to death. A bleeding event was considered as minor if it was clinically overt but not meeting the criteria for major bleeding. In this outcome measure, number of participants with any (major or minor) bleeding events (adjudicated by Central Adjudication Committee) were reported. |
| Number of Participants With Fatal Bleeding Events | Month 1 up to Month 6; Month 7 up to Month 12; Month 1 up to Month 12; Month 2 up to Month 6; Month 2 up to Month 12 | Fatal bleeding events refers to those bleeding events which leads to death of participant. In this outcome measure, number of participants with fatal bleeding events were reported. |
| Time to First Occurrence of Any Bleeding Event (Major or Minor) Adjudicated by Central Adjudication Committee | Month 1 up to Month 12 | Time to first occurrence of any bleeding event was defined as the time interval (in days) between the date of first study treatment and the date of documentation of first bleeding event (major or minor). A bleeding event was considered as major if it was clinically overt and satisfies 1 or more of the following criteria: 1) bleeding accompanied by a decrease in hemoglobin of \>=2 g/dL, 2) bleeding occurred at a critical site (intraocular, spinal/epidural, intracranial, retroperitoneal, or pericardial bleeding), 3) bleeding leads to a transfusion of two or more units of packed red blood cells, 4) bleeding leads to death. A bleeding event was considered as minor if it was clinically overt but not meeting the criteria for major bleeding. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Other Pre-specified: Number of Participants With Clinically Significant Electrocardiogram Findings | Baseline up to Week 52 | Clinically significant ECG findings included: corrected QT (QTc) \> 450 ms, QTc \>500 ms, change in QTc between 30 and 60 ms, change in QTc greater than or equal to 60 ms. |
| Change From Baseline in Creatinine Clearance at Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 in Severely Renal Impaired Participants | Baseline, Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 | Creatinine clearance is an indicator of renal function. Creatinine clearance is the volume of blood plasma that is cleared of creatinine by the kidneys per unit time. Normal values for healthy, young males are in the range of 100-135 milliliters per minute (mL/min) and for females, 90-125 mL/min. Creatinine clearance decreases with age. |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Baseline (Day 1) up to Week 52 | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to Week 52 that were absent before treatment or that worsened relative to pretreatment state. AEs included both SAEs and non-SAEs. |
| Number of Participants With Abnormal Physical Examinations Findings | Baseline (Day 1), Week 1, 4, 8, 12, 24, 36, 48, 52 | Physical examinations included head, ears, nose, throat (ENT), neck, heart, chest, lungs, abdomen, extremities, neurological systems, skin, general appearance and others (thigh, abdomen unobtrusive scar, breast, cardio-vascular, constitutional, face, genitalia, genitourinary, gastrointestinal, hematologic, left ankle unobtrusive scar, lymph nodes, lymphatic, malaise/fatigue, mouth, musculoskeletal, musculoskeletal, peripherally inserted central catheters line site left arm, psychiatric, skeletal, urinary, weight, activity level, bladder irritation, dyspnea and eastern cooperative oncology group performance status \[used to assess how the disease affects the daily living abilities of the participant. It ranges on the scale from 0-5 (0= normal activity; 1= symptoms but ambulatory; 2= in bed for less than (\<) 50 percent (%) of the time; 3= in bed for greater than (\>) 50% of the time; 4= 100% bedridden; 5= dead\]). Abnormality in physical examinations was based on investigator's discretion. |
| Number of Participants With Clinically Significant Laboratory Abnormalities | Baseline (Day 1) up to Week 52 | Criteria for abnormality: Hemoglobin greater than or equal to(\>=)130\*lower limit of normal(LLN); less than or equal to(\<=)170\*upper limit of normal(ULN), hematocrit \>=0.39\*LLN;\<=0.51\*ULN, red blood cell \>=4.5\*LLN;\<=5.9\*ULN, platelet\>=150\*LLN;\<= 450\*ULN, white blood cells \>=4\*LLN;\<=11\*ULN; lymphocytes\>=0.09;\<=0.44, neutrophils=\>0.16\*LLN;\<=0.7\*ULN, eosinophils\<=0.04\*ULN, basophils\<=0.02\*ULN, monocytes\>0.08\*ULN; bilirubin \>=5.1\*LLN;\<=22.2\*ULN, aspartate aminotransferase \>=13\*LLN;\<=36\*ULN, alanine aminotransferase\>=11\*LLN;\<=54\*ULN, alkaline phosphatase\>=31\*LLN ;\<=104 \*ULN, total protein\>=60\*LLN; \<=76\*ULN, albumin=\>35\*LLN;\<=50\*ULN, glucose\>=3.77 ;\<=6.05;blood urea nitrogen\>=1.785\*LLN;\<=7.5\*ULN, creatinine\>=70.7\*LLN;\<=114.9\*ULN, creatinine kinase\>=30\*LLN ;\<=280\*ULN, lactate dehydrogenase\>=85\*LLN;\<=180\*ULN, sodium\>=137\*LLN ;\<=144\*ULN, potassium \>=3.5\*LLN;\<=5\*ULN, chloride\>=102\*LLN;\<=111\*ULN, calcium\>=2.22\*LLN ;\<=2.57\*ULN, phosphorus=\>0.81 ;\<=1.45); nitrogen cholesterol\>=1.78\*LLN ;\<=7.49\*ULN. |
Countries
Austria, Canada, Netherlands, Spain, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Dalteparin Sodium Participants received subcutaneous (SC) injection of dalteparin sodium 200 international units per kilogram (IU/kg) once daily (QD) from Week 1-4 followed by SC injection of dalteparin sodium 150 IU/kg QD from Week 5-52. | 334 |
| Total | 334 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 60 |
| Overall Study | Death | 76 |
| Overall Study | Deep vein thrombosis (DVT) | 2 |
| Overall Study | Inferior vena cava filter placement | 4 |
| Overall Study | Lost to Follow-up | 4 |
| Overall Study | Participant required pancreatic biopsy | 1 |
| Overall Study | Physician Decision | 11 |
| Overall Study | Progression of disease | 12 |
| Overall Study | Protocol Violation | 9 |
| Overall Study | Pulmonary embolism (PE) | 1 |
| Overall Study | Sponsor request | 5 |
| Overall Study | Withdrawal by Subject | 44 |
Baseline characteristics
| Characteristic | Dalteparin Sodium |
|---|---|
| Age, Continuous | 63.8 years STANDARD_DEVIATION 10.63 |
| Sex: Female, Male Female | 171 Participants |
| Sex: Female, Male Male | 163 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 328 / 334 |
| serious Total, serious adverse events | 213 / 334 |
Outcome results
Primary
Number of Participants With Major Bleeding Events Adjudicated by Central Adjudication Committee
A bleeding event was considered as major if it was clinically overt and satisfies 1 or more of the following criteria: 1) bleeding accompanied by a decrease in hemoglobin of greater than or equal to (\>=) 2 gram per deciliter (g/dL), 2) bleeding occurred at a critical site (intraocular, spinal/epidural, intracranial, retroperitoneal, or pericardial bleeding), 3) bleeding leads to a transfusion of two or more units of packed red blood cells, 4) bleeding leads to death. In this outcome measure, number of participants with major bleeding events (adjudicated by Central Adjudication Committee) were reported.
Time frame: Month 2 up to Month 6
Population: Safety population included all participants who received at least 1 treatment with dalteparin sodium.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dalteparin Sodium | Number of Participants With Major Bleeding Events Adjudicated by Central Adjudication Committee | 14 participants |
Primary
Number of Participants With Major Bleeding Events Adjudicated by Central Adjudication Committee
A bleeding event was considered as major if it was clinically overt and satisfies 1 or more of the following criteria: 1) bleeding accompanied by a decrease in hemoglobin of \>=2 g/dL, 2) bleeding occurred at a critical site (intraocular, spinal/epidural, intracranial, retroperitoneal, or pericardial bleeding), 3) bleeding leads to a transfusion of two or more units of packed red blood cells, 4) bleeding leads to death. In this outcome measure, number of participants with major bleeding events (adjudicated by Central Adjudication Committee) were reported.
Time frame: Month 7 up to Month 12
Population: Safety population included all participants who received at least one 1 treatment with dalteparin sodium.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dalteparin Sodium | Number of Participants With Major Bleeding Events Adjudicated by Central Adjudication Committee | 8 participants |
Primary
Number of Participants With New or Recurrent Venous Thromboembolism (VTE) Adjudicated by Central Adjudication Committee
VTEs included both deep vein thrombosis (DVT) and pulmonary embolism (PE). DVT is a blood clot in the deep veins of the leg. If a DVT clot breaks off (embolizes) from a vein wall and flows towards the lungs and blocks some or all of the blood supply, it becomes pulmonary embolism (PE). When a blood clot (thrombus) breaks, loose and travels in the blood, this is called a venous thromboembolism. DVT was diagnosed using either computed tomography scan or contrast venography. PE was diagnosed by either radionuclide ventilation-perfusion studies, contrast CT scan or an angiogram. In this outcome measure, number of participants with new or recurrent VTE (adjudicated by Central Adjudication Committee) were reported.
Time frame: Month 7 up to Month 12
Population: Efficacy analysis population included all participants who received at least 1 study treatment with dalteparin sodium. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dalteparin Sodium | Number of Participants With New or Recurrent Venous Thromboembolism (VTE) Adjudicated by Central Adjudication Committee | 8 participants |
Secondary
Number of Participants With Any Bleeding Event (Major or Minor) Adjudicated by Central Adjudication Committee
A bleeding event was considered as major if it was clinically overt and satisfies 1 or more of the following criteria: 1) bleeding accompanied by a decrease in hemoglobin of \>=2 g/dL, 2) bleeding occurred at a critical site (intraocular, spinal/epidural, intracranial, retroperitoneal, or pericardial bleeding), 3) bleeding leads to a transfusion of two or more units of packed red blood cells, 4) bleeding leads to death. A bleeding event was considered as minor if it was clinically overt but not meeting the criteria for major bleeding. In this outcome measure, number of participants with any (major or minor) bleeding events (adjudicated by Central Adjudication Committee) were reported.
Time frame: Month 1 up to Month 6, Month 7 up to Month 12, Month 1 up to Month 12, Month 2 up to Month 6, and Month 2 up to Month 12
Population: Safety population included all participants who received at least 1 treatment with dalteparin sodium.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dalteparin Sodium | Number of Participants With Any Bleeding Event (Major or Minor) Adjudicated by Central Adjudication Committee | Month 2 up to Month 6 | 47 participants |
| Dalteparin Sodium | Number of Participants With Any Bleeding Event (Major or Minor) Adjudicated by Central Adjudication Committee | Month 1 up to Month 6 | 91 participants |
| Dalteparin Sodium | Number of Participants With Any Bleeding Event (Major or Minor) Adjudicated by Central Adjudication Committee | Month 7 up to Month 12 | 21 participants |
| Dalteparin Sodium | Number of Participants With Any Bleeding Event (Major or Minor) Adjudicated by Central Adjudication Committee | Month 1 up to Month 12 | 112 participants |
| Dalteparin Sodium | Number of Participants With Any Bleeding Event (Major or Minor) Adjudicated by Central Adjudication Committee | Month 2 up to Month 12 | 68 participants |
Secondary
Number of Participants With Fatal Bleeding Events
Fatal bleeding events refers to those bleeding events which leads to death of participant. In this outcome measure, number of participants with fatal bleeding events were reported.
Time frame: Month 1 up to Month 6; Month 7 up to Month 12; Month 1 up to Month 12; Month 2 up to Month 6; Month 2 up to Month 12
Population: Safety population included all participants who received at least 1 treatment with dalteparin sodium.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dalteparin Sodium | Number of Participants With Fatal Bleeding Events | Month 7 up to Month 12 | 1 participants |
| Dalteparin Sodium | Number of Participants With Fatal Bleeding Events | Month 1 up to Month 12 | 2 participants |
| Dalteparin Sodium | Number of Participants With Fatal Bleeding Events | Month 1 up to Month 6 | 1 participants |
| Dalteparin Sodium | Number of Participants With Fatal Bleeding Events | Month 2 up to Month 6 | 1 participants |
| Dalteparin Sodium | Number of Participants With Fatal Bleeding Events | Month 2 up to Month 12 | 2 participants |
Secondary
Number of Participants With Investigator Identified Major Bleeding Events
A bleeding event was considered as major if it was clinically overt and satisfies 1 or more of the following criteria: 1) bleeding accompanied by a decrease in hemoglobin of \>=2 g/dL, 2) bleeding occurred at a critical site (intraocular, spinal/epidural, intracranial, retroperitoneal, or pericardial bleeding), 3) bleeding leads to a transfusion of two or more units of packed red blood cells, 4) bleeding leads to death. In this outcome measure, number of participants with major bleeding events (identified by investigator) were reported.
Time frame: Month 1 up to Month 6; Month 7 up to Month 12; Month 1 up to Month 12; Month 2 up to Month 6; Month 2 up to Month 12
Population: Safety population included all participants who received at least 1 treatment with dalteparin sodium.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dalteparin Sodium | Number of Participants With Investigator Identified Major Bleeding Events | Month 7 up to Month 12 | 7 participants |
| Dalteparin Sodium | Number of Participants With Investigator Identified Major Bleeding Events | Month 1 up to Month 6 | 28 participants |
| Dalteparin Sodium | Number of Participants With Investigator Identified Major Bleeding Events | Month 1 up to Month 12 | 35 participants |
| Dalteparin Sodium | Number of Participants With Investigator Identified Major Bleeding Events | Month 2 up to Month 6 | 15 participants |
| Dalteparin Sodium | Number of Participants With Investigator Identified Major Bleeding Events | Month 2 up to Month 12 | 22 participants |
Secondary
Number of Participants With Investigator Identified New or Recurrent Venous Thromboembolism (VTE) or Central Venous Thrombosis (CVT)
VTEs included both DVT and PE. DVT is a blood clot in the deep veins of the leg. If a DVT clot breaks off (embolizes) from a vein wall and flows towards the lungs and blocks some or all of the blood supply, it becomes PE. When a blood clot (thrombus) breaks, loose and travels in the blood, this is called a venous thromboembolism. DVT was diagnosed using either computed tomography scan or contrast venography. PE was diagnosed by either radionuclide ventilation-perfusion studies, contrast CT scan or an angiogram. CVT is blood clot of the venous channels in the brain. CVT was diagnosed by contrast venography or ultrasonography. In this outcome measure, number of participants with new or recurrent VTE or CVT (identified by investigator) were reported.
Time frame: Month 1 up to Month 6; Month 7 up to Month 12; Month 1 up to Month 12; Month 2 up to Month 6; Month 2 up to Month 12
Population: Efficacy analysis population included all participants who received at least 1 study treatment with dalteparin sodium. Here, 'n' signifies those participants who were evaluable at specified time intervals.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dalteparin Sodium | Number of Participants With Investigator Identified New or Recurrent Venous Thromboembolism (VTE) or Central Venous Thrombosis (CVT) | Month 7 up to Month 12 (n=195) | 8 participants |
| Dalteparin Sodium | Number of Participants With Investigator Identified New or Recurrent Venous Thromboembolism (VTE) or Central Venous Thrombosis (CVT) | Month 1 up to Month 6 (n=334) | 29 participants |
| Dalteparin Sodium | Number of Participants With Investigator Identified New or Recurrent Venous Thromboembolism (VTE) or Central Venous Thrombosis (CVT) | Month 1 up to Month 12 (n=334) | 37 participants |
| Dalteparin Sodium | Number of Participants With Investigator Identified New or Recurrent Venous Thromboembolism (VTE) or Central Venous Thrombosis (CVT) | Month 2 up to Month 6 (n=295) | 9 participants |
| Dalteparin Sodium | Number of Participants With Investigator Identified New or Recurrent Venous Thromboembolism (VTE) or Central Venous Thrombosis (CVT) | Month 2 up to Month 12 (n=295) | 17 participants |
Secondary
Number of Participants With Investigator Identified New or Recurrent Venous Thromboembolism (VTEs)
VTEs included both DVT and PE. DVT is a blood clot in the deep veins of the leg. If a DVT clot breaks off (embolizes) from a vein wall and flows towards the lungs and blocks some or all of the blood supply, it becomes PE. When a blood clot (thrombus) breaks, loose and travels in the blood, this is called a venous thromboembolism. DVT was diagnosed using either computed tomography scan or contrast venography. PE was diagnosed by either radionuclide ventilation-perfusion studies, contrast CT scan or an angiogram. In this outcome measure, number of participants with new or recurrent VTE (identified by investigator) were reported.
Time frame: Month 1 up to Month 6; Month 7 up to Month 12; Month 1 up to Month 12; Month 2 up to Month 6; Month 2 up to Month 12
Population: Efficacy analysis population included all participants who received at least 1 study treatment with dalteparin sodium. Here, 'n' signifies those participants who were evaluable at specified time intervals.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dalteparin Sodium | Number of Participants With Investigator Identified New or Recurrent Venous Thromboembolism (VTEs) | Month 1 up to Month 6 (n=334) | 29 participants |
| Dalteparin Sodium | Number of Participants With Investigator Identified New or Recurrent Venous Thromboembolism (VTEs) | Month 2 up to Month 12 (n=295) | 17 participants |
| Dalteparin Sodium | Number of Participants With Investigator Identified New or Recurrent Venous Thromboembolism (VTEs) | Month 7 up to Month 12 (n=195) | 8 participants |
| Dalteparin Sodium | Number of Participants With Investigator Identified New or Recurrent Venous Thromboembolism (VTEs) | Month 1 up to Month 12 (n=334) | 37 participants |
| Dalteparin Sodium | Number of Participants With Investigator Identified New or Recurrent Venous Thromboembolism (VTEs) | Month 2 up to Month 6 (n=295) | 9 participants |
Secondary
Number of Participants With New or Recurrent Venous Thromboembolism (VTE) or Central Venous Thrombosis (CVT) Adjudicated by Central Adjudication Committee
VTEs included both DVT and PE. DVT is a blood clot in the deep veins of the leg. If a DVT clot breaks off (embolizes) from a vein wall and flows towards the lungs and blocks some or all of the blood supply, it becomes PE. When a blood clot (thrombus) breaks, loose and travels in the blood, this is called a venous thromboembolism. DVT was diagnosed using either computed tomography scan or contrast venography. PE was diagnosed by either radionuclide ventilation-perfusion studies, contrast CT scan or an angiogram. CVT is blood clot of the venous channels in the brain. CVT was diagnosed by contrast venography or ultrasonography. In this outcome measure, number of participants with new or recurrent VTE or CVT (adjudicated by Central Adjudication Committee) were reported.
Time frame: Month 1 up to Month 6; Month 7 up to Month 12; Month 1 up to Month 12; Month 2 up to Month 6; Month 2 up to Month 12
Population: Efficacy analysis population included all participants who received at least 1 study treatment with dalteparin sodium. Here, 'n' signifies those participants who were evaluable at specified time intervals.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dalteparin Sodium | Number of Participants With New or Recurrent Venous Thromboembolism (VTE) or Central Venous Thrombosis (CVT) Adjudicated by Central Adjudication Committee | Month 1 up to Month 12 (n=334) | 37 participants |
| Dalteparin Sodium | Number of Participants With New or Recurrent Venous Thromboembolism (VTE) or Central Venous Thrombosis (CVT) Adjudicated by Central Adjudication Committee | Month 2 up to Month 6 (n=296) | 10 participants |
| Dalteparin Sodium | Number of Participants With New or Recurrent Venous Thromboembolism (VTE) or Central Venous Thrombosis (CVT) Adjudicated by Central Adjudication Committee | Month 2 up to Month 12 (n=296) | 18 participants |
| Dalteparin Sodium | Number of Participants With New or Recurrent Venous Thromboembolism (VTE) or Central Venous Thrombosis (CVT) Adjudicated by Central Adjudication Committee | Month 1 up to Month 6 (n=334) | 29 participants |
| Dalteparin Sodium | Number of Participants With New or Recurrent Venous Thromboembolism (VTE) or Central Venous Thrombosis (CVT) Adjudicated by Central Adjudication Committee | Month 7 up to Month 12 (n=194) | 8 participants |
Secondary
Time to First Occurrence of Any Bleeding Event (Major or Minor) Adjudicated by Central Adjudication Committee
Time to first occurrence of any bleeding event was defined as the time interval (in days) between the date of first study treatment and the date of documentation of first bleeding event (major or minor). A bleeding event was considered as major if it was clinically overt and satisfies 1 or more of the following criteria: 1) bleeding accompanied by a decrease in hemoglobin of \>=2 g/dL, 2) bleeding occurred at a critical site (intraocular, spinal/epidural, intracranial, retroperitoneal, or pericardial bleeding), 3) bleeding leads to a transfusion of two or more units of packed red blood cells, 4) bleeding leads to death. A bleeding event was considered as minor if it was clinically overt but not meeting the criteria for major bleeding.
Time frame: Month 1 up to Month 12
Population: Safety population included all participants who received at least 1 treatment with dalteparin sodium.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dalteparin Sodium | Time to First Occurrence of Any Bleeding Event (Major or Minor) Adjudicated by Central Adjudication Committee | 262.5 days | Standard Error 8.52 |
Secondary
Time to First Occurrence of Major Bleeding Event Adjudicated by Central Adjudication Committee
Time to first occurrence of major bleeding event was defined as the time interval (in days) between the date of first study treatment and the date of documentation of first major bleeding event. A bleeding event was considered as major if it was clinically overt and satisfies 1 or more of the following criteria: 1) bleeding accompanied by a decrease in hemoglobin of \>=2 g/dL, 2) bleeding occurred at a critical site (intraocular, spinal/epidural, intracranial, retroperitoneal, or pericardial bleeding), 3) bleeding leads to a transfusion of two or more units of packed red blood cells, 4) bleeding leads to death.
Time frame: Month 1 up to Month 12
Population: Safety population included all participants who received at least 1 treatment with dalteparin sodium.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dalteparin Sodium | Time to First Occurrence of Major Bleeding Event Adjudicated by Central Adjudication Committee | 332.9 days | Standard Error 5.25 |
Secondary
Time to First Occurrence of New or Recurrent Venous Thromboembolism (VTE) Adjudicated by Central Adjudication Committee
Time to first occurrence of new or recurrent VTE was defined as the time interval (in days) between the date of first study treatment and the date of documentation of first VTE. VTEs included both DVT and PE. DVT is a blood clot in the deep veins of the leg. If a DVT clot breaks off (embolizes) from a vein wall and flows towards the lungs and blocks some or all of the blood supply, it becomes PE. When a blood clot (thrombus) breaks, loose and travels in the blood, this is called a venous thromboembolism. DVT was diagnosed using either computed tomography scan or contrast venography. PE was diagnosed by either radionuclide ventilation-perfusion studies, contrast CT scan or an angiogram.
Time frame: Month 1 up to Month 12
Population: Efficacy analysis population included all participants who received at least 1 study treatment with dalteparin sodium.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dalteparin Sodium | Time to First Occurrence of New or Recurrent Venous Thromboembolism (VTE) Adjudicated by Central Adjudication Committee | 294.1 days | Standard Error 4.87 |
Secondary
Time to First Occurrence of New or Recurrent VTE or CVT Adjudicated by Central Adjudication Committee
Time to first occurrence of new or recurrent VTE or CVT was defined as the time interval (in days) between the date of first study treatment and the date of documentation of first VTE or CVT. VTEs included both deep vein thrombosis (DVT) and pulmonary embolism (PE) .DVT is a blood clot in the deep veins of the leg. If a DVT clot that breaks off (embolizes) from a vein wall and flows towards the lungs and blocks some or all of the blood supply, it becomes pulmonary embolism (PE). When a blood clot (thrombus) breaks, loose and travels in the blood, this is called a venous thromboembolism. DVT was diagnosed using either computed tomography scan, contrast venography or contrast venography. PE was diagnosed by either radionuclide ventilation-perfusion studies, contrast CT scan or an angiogram. CVT is blood clot of the venous channels in the brain. CVT was diagnosed by contrast venography or ultrasonography.
Time frame: Month 1 up to Month 12
Population: Efficacy analysis population included all participants who received at least 1 study treatment with dalteparin sodium.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dalteparin Sodium | Time to First Occurrence of New or Recurrent VTE or CVT Adjudicated by Central Adjudication Committee | 294.1 days | Standard Error 4.87 |
Other Pre-specified
Change From Baseline in Creatinine Clearance at Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 in Severely Renal Impaired Participants
Creatinine clearance is an indicator of renal function. Creatinine clearance is the volume of blood plasma that is cleared of creatinine by the kidneys per unit time. Normal values for healthy, young males are in the range of 100-135 milliliters per minute (mL/min) and for females, 90-125 mL/min. Creatinine clearance decreases with age.
Time frame: Baseline, Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52
Population: Severely renal-impaired population included all participants who had at least 1 dose of study drug and had severe renal impairment at the baseline or developed severe renal impairment (CrCl) \< 30 milliliter per minute during the study. Here, n' signifies those participants who were evaluable at specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dalteparin Sodium | Change From Baseline in Creatinine Clearance at Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 in Severely Renal Impaired Participants | Baseline (n=17) | 46.0 mL/min | Standard Deviation 28.66 |
| Dalteparin Sodium | Change From Baseline in Creatinine Clearance at Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 in Severely Renal Impaired Participants | Week 4 (n=15) | -8.6 mL/min | Standard Deviation 25.39 |
| Dalteparin Sodium | Change From Baseline in Creatinine Clearance at Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 in Severely Renal Impaired Participants | Week 16 (n=4) | -9.2 mL/min | Standard Deviation 21.93 |
| Dalteparin Sodium | Change From Baseline in Creatinine Clearance at Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 in Severely Renal Impaired Participants | Week 40 (n=2) | -21.0 mL/min | Standard Deviation 9.9 |
| Dalteparin Sodium | Change From Baseline in Creatinine Clearance at Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 in Severely Renal Impaired Participants | Week 44 (n=2) | -20.0 mL/min | Standard Deviation 4.24 |
| Dalteparin Sodium | Change From Baseline in Creatinine Clearance at Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 in Severely Renal Impaired Participants | Week 48 (n=6) | -26.0 mL/min | Standard Deviation 18.12 |
| Dalteparin Sodium | Change From Baseline in Creatinine Clearance at Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 in Severely Renal Impaired Participants | Week 52 (n=11) | 4.8 mL/min | Standard Deviation 50.19 |
| Dalteparin Sodium | Change From Baseline in Creatinine Clearance at Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 in Severely Renal Impaired Participants | Week 8 (n=13) | 2.5 mL/min | Standard Deviation 47.02 |
| Dalteparin Sodium | Change From Baseline in Creatinine Clearance at Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 in Severely Renal Impaired Participants | Week 12 (n=13) | 2.1 mL/min | Standard Deviation 58.15 |
| Dalteparin Sodium | Change From Baseline in Creatinine Clearance at Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 in Severely Renal Impaired Participants | Week 20 (n=2) | 7.7 mL/min | Standard Deviation 7.9 |
| Dalteparin Sodium | Change From Baseline in Creatinine Clearance at Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 in Severely Renal Impaired Participants | Week 24 (n=12) | 4.5 mL/min | Standard Deviation 49.62 |
| Dalteparin Sodium | Change From Baseline in Creatinine Clearance at Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 in Severely Renal Impaired Participants | Week 28 (n=1) | -44.0 mL/min | — |
| Dalteparin Sodium | Change From Baseline in Creatinine Clearance at Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 in Severely Renal Impaired Participants | Week 32 (n=1) | -14.0 mL/min | — |
| Dalteparin Sodium | Change From Baseline in Creatinine Clearance at Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 in Severely Renal Impaired Participants | Week 36 (n=8) | 5.8 mL/min | Standard Deviation 56.91 |
Other Pre-specified
Number of Participants With Abnormal Physical Examinations Findings
Physical examinations included head, ears, nose, throat (ENT), neck, heart, chest, lungs, abdomen, extremities, neurological systems, skin, general appearance and others (thigh, abdomen unobtrusive scar, breast, cardio-vascular, constitutional, face, genitalia, genitourinary, gastrointestinal, hematologic, left ankle unobtrusive scar, lymph nodes, lymphatic, malaise/fatigue, mouth, musculoskeletal, musculoskeletal, peripherally inserted central catheters line site left arm, psychiatric, skeletal, urinary, weight, activity level, bladder irritation, dyspnea and eastern cooperative oncology group performance status \[used to assess how the disease affects the daily living abilities of the participant. It ranges on the scale from 0-5 (0= normal activity; 1= symptoms but ambulatory; 2= in bed for less than (\<) 50 percent (%) of the time; 3= in bed for greater than (\>) 50% of the time; 4= 100% bedridden; 5= dead\]). Abnormality in physical examinations was based on investigator's discretion.
Time frame: Baseline (Day 1), Week 1, 4, 8, 12, 24, 36, 48, 52
Population: Safety population included all participants who received at least 1 treatment with dalteparin sodium. Here 'n' signifies those participants who were evaluable at specified categories.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Baseline : Extremities (n=328) | 203 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Baseline : Neurological systems (n=327) | 18 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 1 : Neck (n=214) | 7 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 1 :Abdomen (n=214) | 62 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 8 : Extremities (n=186) | 80 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 8 : Neurological systems (n=185) | 13 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 24 : Head (n=166) | 2 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 24 : Neck (n=166) | 4 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 24 : Neurological systems (n=166) | 14 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 24 : Skin (n=166) | 35 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 24 : General appearance (n=166) | 9 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 36 : Head (n=127) | 6 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 36 : ENT (n=127) | 9 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 36 : Neurological systems (n=127) | 9 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 48 : Neck (n=103) | 3 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 48 : Neurological systems (n=103) | 8 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 52 : Head (n=193) | 7 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 52 : ENT (n=193) | 13 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Baseline : Head (n=327) | 14 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Baseline : Ears, nose, throat (ENT)(n=327) | 20 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Baseline : Neck (n=327) | 10 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Baseline : Heart (n=327) | 26 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Baseline : Chest (n=326) | 40 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Baseline : Lungs (n=327) | 65 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Baseline : Abdomen (n=327) | 73 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Baseline : Skin (n=327) | 51 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Baseline : General appearance (n=327) | 47 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Baseline : Others (n=47) | 25 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 1 : Head (n=213) | 16 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 1 : ENT (n=214) | 20 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 1 : Heart (n=214) | 10 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 1 : Chest (n=213) | 22 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 1 : Lungs (n=214) | 28 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 1 : Extremities (n=213) | 103 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 1 : Neurological systems (n=213) | 16 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 48 : Heart (n=103) | 7 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 1 : Skin (n=213) | 52 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 1 : General appearance (n=212) | 25 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 1:Others (n=41) | 23 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 4 : Head (n=211) | 12 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 4 : ENT (n=211) | 16 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 4 : Neck (n=211) | 6 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 24 : ENT (n=166) | 12 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 4 : Heart (n=210) | 8 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 4 : Chest (n=211) | 23 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 4 : Lungs (n=211) | 24 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 4 : Abdomen (n=210) | 59 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 4 : Extremities (n=211) | 83 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 4 : Neurological systems (n=211) | 9 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 4 : Skin (n=210) | 49 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 4 : General appearance (n=208) | 25 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 4 : Others (n=23) | 20 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 8 : Head (n=186) | 11 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 8 : ENT (n=186) | 16 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 8 : Neck (n=185) | 4 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 12 : Head (n=183) | 10 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 8 : Heart (n=186) | 8 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 8 : Chest (n=186) | 21 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 8 : Lungs (n=186) | 31 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 8 : Abdomen (n=186) | 49 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 24 : Heart (n=166) | 9 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 8 : Skin (n=186) | 38 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 8 : General appearance (n=186) | 16 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 8 : Others (n=16) | 12 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 12 : ENT (n=183) | 12 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 12 : Neck (n=183) | 1 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 12 : Heart (n=183) | 9 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 24 : Chest (n=166) | 17 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 24 : Lungs (n=166) | 14 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 24 : Abdomen (n=166) | 37 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 24 : Extremities (n=166) | 47 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 24 : Others (n=17) | 11 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 36 : Neck (n=127) | 4 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 36 : Heart (n=127) | 7 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 36 : Chest (n=127) | 18 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 36 : Lungs (n=127) | 12 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 36 : Abdomen (n=126) | 35 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 36 : Extremities (n=127) | 37 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 36 : Skin (n=127) | 32 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 36 : General appearance (n=126) | 11 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 36 : Others (n=14) | 9 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 48 : Head (n=103) | 2 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 48 : ENT (n=103) | 6 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 48 : Chest (n=103) | 11 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 48 : Lungs (n=102) | 14 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 48 : Abdomen (n=103) | 27 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 48 : Extremities (n=103) | 29 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 48 : Skin (n=103) | 29 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 48 : General appearance (n=103) | 9 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 48 : Others (n=7) | 3 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 52 : Neck (n=193) | 5 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 52 : Heart (n=193) | 12 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 52 : Chest (n=193) | 23 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 52 : Lungs (n=191) | 23 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 52 : General appearance (n=193) | 27 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 52 : Abdomen (n=193) | 60 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 52 : Extremities (n=193) | 68 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 52 : Neurological systems (n=193) | 24 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 52 : Skin (n=193) | 38 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 52 : Others (n=25) | 15 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 12 : Chest (n=183) | 22 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 12 : Lungs (n=183) | 15 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 12 : Abdomen (n=183) | 47 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 12 : Extremities (n=183) | 57 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 12 : Neurological systems (n=183) | 19 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 12 : Skin (n=183) | 39 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 12 : General appearance (n=182) | 18 participants |
| Dalteparin Sodium | Number of Participants With Abnormal Physical Examinations Findings | Week 12 : Other (n=27) | 16 participants |
Other Pre-specified
Number of Participants With Clinically Significant Laboratory Abnormalities
Criteria for abnormality: Hemoglobin greater than or equal to(\>=)130\*lower limit of normal(LLN); less than or equal to(\<=)170\*upper limit of normal(ULN), hematocrit \>=0.39\*LLN;\<=0.51\*ULN, red blood cell \>=4.5\*LLN;\<=5.9\*ULN, platelet\>=150\*LLN;\<= 450\*ULN, white blood cells \>=4\*LLN;\<=11\*ULN; lymphocytes\>=0.09;\<=0.44, neutrophils=\>0.16\*LLN;\<=0.7\*ULN, eosinophils\<=0.04\*ULN, basophils\<=0.02\*ULN, monocytes\>0.08\*ULN; bilirubin \>=5.1\*LLN;\<=22.2\*ULN, aspartate aminotransferase \>=13\*LLN;\<=36\*ULN, alanine aminotransferase\>=11\*LLN;\<=54\*ULN, alkaline phosphatase\>=31\*LLN ;\<=104 \*ULN, total protein\>=60\*LLN; \<=76\*ULN, albumin=\>35\*LLN;\<=50\*ULN, glucose\>=3.77 ;\<=6.05;blood urea nitrogen\>=1.785\*LLN;\<=7.5\*ULN, creatinine\>=70.7\*LLN;\<=114.9\*ULN, creatinine kinase\>=30\*LLN ;\<=280\*ULN, lactate dehydrogenase\>=85\*LLN;\<=180\*ULN, sodium\>=137\*LLN ;\<=144\*ULN, potassium \>=3.5\*LLN;\<=5\*ULN, chloride\>=102\*LLN;\<=111\*ULN, calcium\>=2.22\*LLN ;\<=2.57\*ULN, phosphorus=\>0.81 ;\<=1.45); nitrogen cholesterol\>=1.78\*LLN ;\<=7.49\*ULN.
Time frame: Baseline (Day 1) up to Week 52
Population: Safety population included all participants who received at least 1 treatment with dalteparin sodium.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dalteparin Sodium | Number of Participants With Clinically Significant Laboratory Abnormalities | 0 participants |
Other Pre-specified
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to Week 52 that were absent before treatment or that worsened relative to pretreatment state. AEs included both SAEs and non-SAEs.
Time frame: Baseline (Day 1) up to Week 52
Population: Safety population included all participants who received at least 1 treatment with dalteparin sodium.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dalteparin Sodium | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAE | 213 participants |
| Dalteparin Sodium | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | AE | 328 participants |
Other Pre-specified
Other Pre-specified: Number of Participants With Clinically Significant Electrocardiogram Findings
Clinically significant ECG findings included: corrected QT (QTc) \> 450 ms, QTc \>500 ms, change in QTc between 30 and 60 ms, change in QTc greater than or equal to 60 ms.
Time frame: Baseline up to Week 52
Population: Safety population included all participants who received at least 1 treatment with dalteparin sodium.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dalteparin Sodium | Other Pre-specified: Number of Participants With Clinically Significant Electrocardiogram Findings | 8 participants |