Fragmin for the Treatment of Acute VTE in Pediatric Cancer Patients

Percentage of Participants With Clinical Response of Progression, Regression, Resolution and No Change in Venous Thromboembolism (VTE)

VTEs included both DVT and PE. DVT is a blood clot in the deep veins of the leg. PE is a blood clot in the lungs. Clinical response of progression was defined as progression of clot burden in terms of severity of occlusion, or involvement of new venous segments at any time after the initial diagnosis. Clinical response of regression: Regressed clot burden utilizing the same imaging modality as the screening visit. Clinical response of resolution: Thrombus resolution of the qualifying event measured by repeat imaging at the end of study (EOS) visit.

Time frame: Baseline up to 28 days after the last dose of study drug (up to Day 132)

Percentage of Participants With Major and Minor Bleeding Event

A bleeding event was considered as major if it was clinically overt and satisfies 1 or more of the following criteria: fatal bleeding, bleeding accompanied by a decrease in hemoglobin of at least 2 grams per deciliter 24 hours, Overt bleeding deemed by the attending physician to necessitate permanent discontinuation of trial medication, Overt bleeding deemed by the attending physician to be unrelated to the participant's underlying condition and accompanied by blood product administration or bleeding occurred at a critical site (intraocular, intracranial, retroperitoneal). A bleeding event was considered as minor if it was clinically overt but not meeting the criteria for major or clinically relevant no major bleeding (bleeding resulting in any medical or surgical interventions but which did not meet the criteria for major bleeding).

Time frame: Baseline up to 28 days after the last dose of study drug (up to Day 132)

Number of Participants With Treatment Emergent Adverse Events (AEs) 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. 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 were events between first dose of study drug and up to 28 days after the last dose of study drug (up to Day 132) that were absent before treatment or that worsened relative to pretreatment state. AEs included both SAEs and non-SAEs.

Time frame: Baseline up to 28 days after the last dose of study drug (up to Day 132)

Number of Participants With Laboratory Abnormalities

Criteria:hematology:hemoglobin, hematocrit, erythrocytes less than(\<)0.8\*lower limit of normal(LLN), platelets \<0.5\*LLN \>1.75\*upper limit of normal (ULN),leukocytes \<0.6\* LLN \>1.5\* ULN, lymphocytes, lymphocytes/Leukocytes, neutrophils, neutrophils/leukocytes \<0.8\* LLN \>1.2\* ULN, basophils, basophils/leukocytes, eosinophils, eosinophils/leukocytes monocytes monocytes/leukocytes \>1.2\*ULN, activated partial thromboplastin time, prothrombin time, prothrombin international normalized ratio \>1.1\* ULN. Clinical chemistry: bilirubin \>1.5\*ULN, aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, alkaline phosphatase \>3.0\*ULN, protein, albumin \<0.8\* LLN \>1.2\* ULN, blood urea nitrogen, creatinine \>1.3\* ULN, sodium \<0.95\*LLN \>1.05\*ULN, potassium, chloride, calcium, magnesium \<0.9\* LLN \>1.1\* ULN, phosphate \<0.8\* LLN \>1.2\* ULN, glucose \<0.6\*LLN \>1.5\*ULN, estimated(est) creatinine clearance, est GFR modified and bedside schwartz, \>1.0\* ULN. Urinalysis: creatinine \>1.0\*ULN.

Time frame: Baseline up to 104 days

Absolute Values of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DSBP) in Participants

Time frame: Baseline, Day 1, Day 2, Day 30, Day 60, Day 90

Absolute Values of Heart Rate (HR) and Pulse Rate (PR) of Participants

Heart rate and pulse rate of participants were measured in terms of beats per minute.

Time frame: Baseline, Day 1, Day 2, Day 30, Day 60, Day 90

Absolute Values of Height of Participants

Time frame: Baseline, Day 1, Day 2, Day 30, Day 60, Day 90

Absolute Values of Weight of Participants

Time frame: Baseline, Day 1, Day 2, Day 30, Day 60, Day 90

Absolute Values of Respiratory Rate of Participants

Respiratory rate was defined as the number of breaths per minute.

Time frame: Baseline, Day 1, Day 2, Day 30, Day 60, Day 90

Absolute Values of Body Temperature of Participants

Time frame: Baseline, Day 1, Day 2, Day 30, Day 60, Day 90

Absolute Values of Body Length of Participants

Time frame: Baseline, Day 1, Day 2, Day 30, Day 60, Day 90

Number of Participants With Physical Examination Abnormalities of Participants

Physical examinations included head, eyes, ears, nose, throat, neck, heart, chest, lungs, abdomen, extremities, skin, neurological status and general appearance. Abnormality in physical examination was based on investigator's discretion. Only those categories in which at least 1 participant had abnormality were reported.

Time frame: Screening, Visit 2 (Baseline), Visit 3 (Day 1), Visit 4 (Day 2), Visit 5 (Day 30), Visit 6 (Day 60), Visit 7 (Day 90)

Time to First Occurrence of Major Bleeding Event

Time to first occurrence of major bleeding event was defined as the time interval (in days) between date of first study treatment and 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: fatal bleeding, bleeding accompanied by a decrease in hemoglobin of at least 2 grams per deciliter, overt bleeding deemed by the attending physician to necessitate permanent discontinuation of trial medication, overt bleeding deemed by the attending physician to be unrelated to the participant's underlying condition and accompanied by blood product administration, bleeding occurred at a critical site (intraocular, intracranial, retroperitoneal or intraspinal).

Time frame: Baseline up to 28 days after the last dose of study drug (up to Day 132)

Percentage of Participants Who Remained Within Prespecified Therapeutic Anti-Factor Xa Levels at Day 30, 60 and 90 in Follow up Phase

Prespecified therapeutic anti-factor Xa level was 0.5-1.0 IU/mL. The percentage of participants who had anti factor-Xa levels within the prespecified therapeutic range at Day 30, 60 and 90 during the follow up phase were reported in this outcome measure.

Time frame: Day 30, Day 60, Day 90 in follow up phase

Percentage of Participants With Anti-Factor Xa Levels Outside the Prespecified Range at Day 30, 60 and 90 in Follow up Phase

Prespecified therapeutic anti-factor Xa range was 0.5-1.0 IU/mL. The percentage of participants who had anti-factor Xa levels outside the prespecified therapeutic range at Day 30, 60 and 90 during the follow up phase were reported in this outcome measure.

Time frame: Day 30, Day 60, Day 90 in follow-up phase

Maintenance Dose of Dalteparin Required to Achieve Prespecified Therapeutic Anti- Factor Xa Levels

Prespecified therapeutic anti-factor Xa level was 0.5-1.0 IU/mL. Cumulative data for day 1 to 7 has been reported.

Time frame: 4 hours post-dose at each Day 1 to 7 in dose adjustment phase

Time to Achieve Prespecified Therapeutic Anti- Factor Xa Levels

Time to achieve the target range (prespecified therapeutic anti- factor Xa levels) was defined as the number of days from the first dose of study drug to the final dose that achieves the target anti-factor Xa level. Prespecified therapeutic anti-factor Xa level was 0.5-1.0 IU/mL. Cumulative data of Day 1 to 7 is reported.

Time frame: Day 1 to 7 in dose adjustment phase

Number of Dose Adjustments Required to Achieve Prespecified Therapeutic Anti-Xa Levels

During dose adjustment phase, doses were adjusted according to prespecified therapeutic anti-Xa levels in order to achieve target prespecified therapeutic anti-factor Xa levels (0.5 to 1.0 IU/mL). Number of dose adjustments which were done within the specified time window of up to 4 hours post dose on all days (1 to 7) to achieve the prespecified therapeutic anti-Xa levels are reported.

Time frame: 4 hours post-dose at each Day 1 to 7 in dose adjustment phase