Trial Outcomes & Findings for Study to Characterize the Effect of Heparin on Palifermin Activity (NCT NCT01163097)

Results Overview

Ratio to baseline lipase at Day 5 was calculated as Day 5 lipase divided by baseline lipase.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

44 participants

Primary outcome timeframe

Day 5

Results posted on

2014-11-06

Participant Flow

This open-label, randomized, parallel-design, Phase I study in healthy adult subjects was performed in 1 center (New Orleans Center for Clinical Research, Knoxville, TN, USA) between July and December 2010.

Subjects randomized to receive palifermin in combination with heparin did first enter a titration period where they received titrated heparin doses to achieve an aPTT of 1.5 to 2.0 × baseline. Subjects who could not be successfully titrated within the heparin titration period were discontinued, and did not enter the palifermin treatment period.

Participant milestones

Participant milestones
Measure	Palifermin - Heparin Treatment A: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections and continuous heparin IV infusion	Palifermin Alone Treatment B: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections	Untreated Control Treatment C: control group without any treatment administered
Overall Study STARTED	20	16	8
Overall Study COMPLETED	14	16	8
Overall Study NOT COMPLETED	6	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Study to Characterize the Effect of Heparin on Palifermin Activity

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Palifermin - Heparin n=15 Participants Treatment A: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections and continuous heparin IV infusion	Palifermin Alone n=16 Participants Treatment B: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections	Untreated Control n=8 Participants Treatment C: control group without any treatment administered	Total n=39 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	15 Participants n=5 Participants	16 Participants n=7 Participants	8 Participants n=5 Participants	39 Participants n=4 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Continuous	25.9 years STANDARD_DEVIATION 5.29 • n=5 Participants	32.9 years STANDARD_DEVIATION 7.82 • n=7 Participants	22.8 years STANDARD_DEVIATION 3.62 • n=5 Participants	28.1 years STANDARD_DEVIATION 7 • n=4 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Sex: Female, Male Male	15 Participants n=5 Participants	16 Participants n=7 Participants	8 Participants n=5 Participants	39 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	14 Participants n=5 Participants	16 Participants n=7 Participants	8 Participants n=5 Participants	38 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	6 Participants n=4 Participants
Race (NIH/OMB) White	12 Participants n=5 Participants	14 Participants n=7 Participants	7 Participants n=5 Participants	33 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Region of Enrollment United States	15 participants n=5 Participants	16 participants n=7 Participants	8 participants n=5 Participants	39 participants n=4 Participants
Body Mass Index	24.95 kg/m2 STANDARD_DEVIATION 2.144 • n=5 Participants	26.08 kg/m2 STANDARD_DEVIATION 2.111 • n=7 Participants	25.98 kg/m2 STANDARD_DEVIATION 3.185 • n=5 Participants	25.62 kg/m2 STANDARD_DEVIATION 2.5 • n=4 Participants

PRIMARY outcome

Timeframe: Day 4

Population: The pharmacodynamic population consist of all randomized subjects who received at least one dose of palifermin (Treatment A or B), or who had a set zero point (Treatment C) and had both baseline and Day 4 buccal biopsy samples collected. This analysis was only performed for Treatment A relative to Treatment B as per study plan.

This outcome is a measure of the palifermin effect on the buccal mucosal cells. Ki67 is a measure of proliferation of cells in the buccal mucosa. This measure assess the number of cells per millimeter (mm) before and after palifermin treatment.

Outcome measures

Outcome measures
Measure	Palifermin - Heparin n=14 Participants Treatment A: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections and continuous heparin IV infusion	Palifermin Alone n=16 Participants Treatment B: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections	Untreated Control Treatment C: control group without any treatment administered
Ratio to Baseline of Epithelial Cell Proliferation as Assessed by Ki67 Staining of Buccal Mucosal Tissue.	0.267 ratio Interval 0.173 to 0.361	0.414 ratio Interval 0.326 to 0.502	—

PRIMARY outcome

Timeframe: Day 45

Population: The safety population consist of all randomized subjects who received at least one dose of palifermin (Treatment A or B), or who had a set zero point (Treatment C). This outcome was assessed for Treatment A and B only as per study plan.

Incidence of grade 2 or higher specific skin-related treatment emergent adverse events following palifermin administration was calculated for subjects in treatment groups A and B. Incidence was calculated by treatment as number of subjects with grade 2 or higher specific skin-related AEs divided by the total number of subjects. The Common Terminology Criteria for Adverse Events (CTCAE v3.0) for Dermatology/Skin was used to determine the toxicity grade for a skin-related adverse event. (http://ctep.cancer.gov/protocolDevelopment/electronic\_applications/docs/ctcaev3.pdf)

Outcome measures

Outcome measures
Measure	Palifermin - Heparin n=15 Participants Treatment A: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections and continuous heparin IV infusion	Palifermin Alone n=16 Participants Treatment B: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections	Untreated Control Treatment C: control group without any treatment administered
Incidence of Grade 2 or Higher Specific Skin-related Adverse Events.	0 proportion of participants	0.0625 proportion of participants	—

PRIMARY outcome

Timeframe: Day 5

Population: The safety population consist of all randomized subjects who received at least one dose of palifermin (Treatment A or B) or who had a set zero point (Treatment C). This outcome was assessed for Treatment A and B only as per study plan.

Ratio to baseline amylase at Day 5 was calculated as Day 5 amylase divided by baseline amylase.

Outcome measures

Outcome measures
Measure	Palifermin - Heparin n=15 Participants Treatment A: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections and continuous heparin IV infusion	Palifermin Alone n=16 Participants Treatment B: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections	Untreated Control Treatment C: control group without any treatment administered
Ratio to Baseline of Amylase	0.242 ratio Interval 0.111 to 0.372	0.547 ratio Interval 0.42 to 0.673	—

PRIMARY outcome

Timeframe: Day 5

Population: The safety population consist of all randomized subjects who received at least one dose of palifermin (Treatment A or B) or who had a set zero point (Treatment C). This outcome was assessed for Treatment A and B only as per study plan.

Ratio to baseline lipase at Day 5 was calculated as Day 5 lipase divided by baseline lipase.

Outcome measures

Outcome measures
Measure	Palifermin - Heparin n=15 Participants Treatment A: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections and continuous heparin IV infusion	Palifermin Alone n=16 Participants Treatment B: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections	Untreated Control Treatment C: control group without any treatment administered
Ratio to Baseline of Lipase.	-0.487 ratio Interval -0.873 to -0.1	0.499 ratio Interval 0.125 to 0.873	—

PRIMARY outcome

Timeframe: Day 4

Population: The safety population consist of all randomized subjects who received at least one dose of palifermin (Treatment A or B) or who had a set zero point (Treatment C). This outcome was assessed for Treatment B and C only as per study plan.

Protein/creatinine ratio is the urinary protein (mg) divided by the urinary creatinine (g) result. Ratio to baseline protein/creatinine ratio was calculated as protein/creatinine ratio at specified day divided by baseline protein/creatinine ratio.

Outcome measures

Outcome measures
Measure	Palifermin - Heparin n=16 Participants Treatment A: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections and continuous heparin IV infusion	Palifermin Alone n=8 Participants Treatment B: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections	Untreated Control Treatment C: control group without any treatment administered
Ratio to Baseline of Protein/Creatinine	0.076 ratio Interval -0.058 to 0.211	0.104 ratio Interval -0.087 to 0.296	—

SECONDARY outcome

Timeframe: Day 1

Population: The pharmacokinetics (PK) population consist of all randomized subjects who received at least one dose of palifermin (Treatment A or B) and at least one post dose PK serum sample

Blood samples for palifermin PK was collected pre-dose on Days 1 and 3 of the treatment period; 2, 5, 15 and 30 minutes; and 1, 2, 4, 6, 12, 18 and 24 hours after the Day 1 and Day 3 dose of palifermin. Descriptive PK parameters for palifermin CL for subjects assigned to Treatment A and Treatment B was determined by linear/log trapezoidal method. Parameters was calculated from individual subject serum concentration-time data using actual subject blood collection times. Serum concentrations reported below the lower limit of quantification (LLOQ) was treated as zero.

Outcome measures

Outcome measures
Measure	Palifermin - Heparin n=15 Participants Treatment A: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections and continuous heparin IV infusion	Palifermin Alone n=16 Participants Treatment B: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections	Untreated Control Treatment C: control group without any treatment administered
Palifermin Pharmacokinetic (PK) Parameters: Clearance (CL)	121.1 (mL/hr/kg) Geometric Coefficient of Variation 29.1	527.8 (mL/hr/kg) Geometric Coefficient of Variation 33.5	—

SECONDARY outcome

Timeframe: Day 3

Population: The pharmacokinetics population consist of all randomized subjects who received at least one dose of palifermin (Treatment A or B) and at least one post dose PK serum sample

Blood samples for palifermin PK was collected pre-dose on Days 1 and 3 of the treatment period; 2, 5, 15 and 30 minutes; and 1, 2, 4, 6, 12, 18 and 24 hours after the Day 1 and Day 3 dose of palifermin. Descriptive PK parameters for palifermin CL for subjects assigned to Treatment A and Treatment B was determined by linear/log trapezoidal method. Parameters was calculated from individual subject serum concentration-time data using actual subject blood collection times. Serum concentrations reported below the lower limit of quantification (LLOQ) was treated as zero.

Outcome measures

Outcome measures
Measure	Palifermin - Heparin n=15 Participants Treatment A: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections and continuous heparin IV infusion	Palifermin Alone n=16 Participants Treatment B: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections	Untreated Control Treatment C: control group without any treatment administered
Palifermin PK Parameters: CL	121.9 (mL/hr/kg) Geometric Coefficient of Variation 20.4	524.3 (mL/hr/kg) Geometric Coefficient of Variation 59.4	—

SECONDARY outcome

Timeframe: Day 1

Population: The pharmacokinetics population consist of all randomized subjects who received at least one dose of palifermin (Treatment A or B) and at least one post dose PK serum sample

Blood samples for palifermin PK was collected pre-dose on Days 1 and 3 of the treatment period; 2, 5, 15 and 30 minutes; and 1, 2, 4, 6, 12, 18 and 24 hours after the Day 1 and Day 3 dose of palifermin. Descriptive pharmacokinetic parameters for palifermin AUC(0-24) was determined by linear/log trapezoidal method. Parameters was calculated from individual subject serum concentration-time data using actual subject blood collection times. Serum concentrations reported below the lower limit of quantification (LLOQ) was deleted from calculation.

Outcome measures

Outcome measures
Measure	Palifermin - Heparin n=15 Participants Treatment A: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections and continuous heparin IV infusion	Palifermin Alone n=16 Participants Treatment B: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections	Untreated Control Treatment C: control group without any treatment administered
Palifermin PK Parameters: Area Under the Serum Curve (AUC) (0-24)	330.1 ng*hr/mL Geometric Coefficient of Variation 26.9	75.80 ng*hr/mL Geometric Coefficient of Variation 37.1	—

SECONDARY outcome

Timeframe: Day 3

Population: The pharmacokinetics population consist of all randomized subjects who received at least one dose of palifermin (Treatment A or B) and at least one post dose PK serum sample

Blood samples for palifermin PK was collected pre-dose on Days 1 and 3 of the treatment period; 2, 5, 15 and 30 minutes; and 1, 2, 4, 6, 12, 18 and 24 hours after the Day 1 and Day 3 dose of palifermin. Descriptive pharmacokinetic parameters for palifermin AUC(0-24) was determined by linear/log trapezoidal method. Parameters was calculated from individual subject serum concentration-time data using actual subject blood collection times. Serum concentrations reported below the lower limit of quantification (LLOQ) was deleted from calculation.

Outcome measures

Outcome measures
Measure	Palifermin - Heparin n=15 Participants Treatment A: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections and continuous heparin IV infusion	Palifermin Alone n=16 Participants Treatment B: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections	Untreated Control Treatment C: control group without any treatment administered
Palifermin PK Parameters: AUC (0-24)	328.1 ng*hr/mL Geometric Coefficient of Variation 20.4	76.26 ng*hr/mL Geometric Coefficient of Variation 36.3	—

SECONDARY outcome

Timeframe: Day 1

Population: The pharmacokinetics population consist of all randomized subjects who received at least one dose of palifermin (Treatment A or B) and at least one post dose PK serum sample

Blood samples for palifermin PK was collected pre-dose on Days 1 and 3 of the treatment period; 2, 5, 15 and 30 minutes; and 1, 2, 4, 6, 12, 18 and 24 hours after the Day 1 and Day 3 dose of palifermin. Descriptive pharmacokinetic parameters for palifermin C0 was determined by linear/log trapezoidal method. Parameters was calculated from individual subject serum concentration-time data using actual subject blood collection times. Serum concentrations reported below the lower limit of quantification (LLOQ) was treated as zero.

Outcome measures

Outcome measures
Measure	Palifermin - Heparin n=15 Participants Treatment A: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections and continuous heparin IV infusion	Palifermin Alone n=16 Participants Treatment B: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections	Untreated Control Treatment C: control group without any treatment administered
Palifermin PK Parameters: Estimated Concentration at Time 0 (C0)	229.1 ng/mL Geometric Coefficient of Variation 116.6	584.7 ng/mL Geometric Coefficient of Variation 111.9	—

SECONDARY outcome

Timeframe: Day 3

Population: The pharmacokinetics population consist of all randomized subjects who received at least one dose of palifermin (Treatment A or B) and at least one post dose PK serum sample

Blood samples for palifermin PK was collected pre-dose on Days 1 and 3 of the treatment period; 2, 5, 15 and 30 minutes; and 1, 2, 4, 6, 12, 18 and 24 hours after the Day 1 and Day 3 dose of palifermin. Descriptive pharmacokinetic parameters for palifermin C0 was determined by linear/log trapezoidal method. Parameters was calculated from individual subject serum concentration-time data using actual subject blood collection times. Serum concentrations reported below the lower limit of quantification (LLOQ) was treated as zero.

Outcome measures

Outcome measures
Measure	Palifermin - Heparin n=15 Participants Treatment A: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections and continuous heparin IV infusion	Palifermin Alone n=16 Participants Treatment B: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections	Untreated Control Treatment C: control group without any treatment administered
Palifermin PK Parameters: C0	361.0 ng/mL Geometric Coefficient of Variation 92.3	563.2 ng/mL Geometric Coefficient of Variation 105.7	—

SECONDARY outcome

Timeframe: Day 1

Population: The pharmacokinetics population consist of all randomized subjects who received at least one dose of palifermin (Treatment A or B) and at least one post dose PK serum sample

Blood samples for palifermin PK was collected pre-dose on Days 1 and 3 of the treatment period; 2, 5, 15 and 30 minutes; and 1, 2, 4, 6, 12, 18 and 24 hours after the Day 1 and Day 3 dose of palifermin (Treatment A and Treatment B only). Descriptive pharmacokinetic parameters for palifermin Vss was determined by linear/log trapezoidal method. Parameters was calculated from individual subject serum concentration-time data using actual subject blood collection times. Serum concentrations reported below the lower limit of quantification (LLOQ) was treated as zero.

Outcome measures

Outcome measures
Measure	Palifermin - Heparin n=15 Participants Treatment A: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections and continuous heparin IV infusion	Palifermin Alone n=16 Participants Treatment B: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections	Untreated Control Treatment C: control group without any treatment administered
Palifermin PK Parameters: Apparent Volume of Distribution at Steady State (Vss)	411.5 mL/kg Geometric Coefficient of Variation 42.4	1586 mL/kg Geometric Coefficient of Variation 48.1	—

SECONDARY outcome

Timeframe: Day 3

Population: The pharmacokinetics population consist of all randomized subjects who received at least one dose of palifermin (Treatment A or B) and at least one post dose PK serum sample

Blood samples for palifermin PK was collected pre-dose on Days 1 and 3 of the treatment period; 2, 5, 15 and 30 minutes; and 1, 2, 4, 6, 12, 18 and 24 hours after the Day 1 and Day 3 dose of palifermin (Treatment A and Treatment B only). Descriptive pharmacokinetic parameters for palifermin Vss was determined by linear/log trapezoidal method. Parameters was calculated from individual subject serum concentration-time data using actual subject blood collection times. Serum concentrations reported below the lower limit of quantification (LLOQ) was treated as zero.

Outcome measures

Outcome measures
Measure	Palifermin - Heparin n=15 Participants Treatment A: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections and continuous heparin IV infusion	Palifermin Alone n=16 Participants Treatment B: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections	Untreated Control Treatment C: control group without any treatment administered
Palifermin PK Parameters: Vss	361.7 mL/Kg Geometric Coefficient of Variation 28.0	1318 mL/Kg Geometric Coefficient of Variation 64.4	—

SECONDARY outcome

Timeframe: Day 45

Population: The safety population consist of all randomized subjects who received at least one dose of palifermin (Treatment A or B) or who had a set zero point (Treatment C)

Adverse events (AE) was considered treatment emergent if the AE started after the time of heparin titration (Treatment A), palifermin dosing on Day 1 (Treatment B), or set zero point (Treatment C).

Outcome measures

Outcome measures
Measure	Palifermin - Heparin n=14 Participants Treatment A: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections and continuous heparin IV infusion	Palifermin Alone n=16 Participants Treatment B: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections	Untreated Control n=8 Participants Treatment C: control group without any treatment administered
Subject Incidence of Treatment-emergent Adverse Event	9 participants	8 participants	3 participants

SECONDARY outcome

Timeframe: Day 4

Population: The safety population consist of all randomized subjects who received at least one dose of palifermin (Treatment A or B) or who had a set zero point (Treatment C). This outcome was assessed for Treatment B and C only as per study plan.

Protein/creatinine ratio is the urinary protein (mg) divided by the urinary creatinine (g) result at the specified time point. Incidence of proteinuria defined as urinary protein/creatinine ratio exceeding 200 mg/g was calculated at Day 4 and overall at any time point. Incidence was calculated by treatment as number of subjects with proteinuria divided by the total number of subjects.

Outcome measures

Outcome measures
Measure	Palifermin - Heparin n=16 Participants Treatment A: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections and continuous heparin IV infusion	Palifermin Alone n=8 Participants Treatment B: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections	Untreated Control Treatment C: control group without any treatment administered
Subject Incidence of Proteinuria	0 participants	0 participants	—

SECONDARY outcome

Timeframe: Day 1

Population: The safety population consist of all randomized subjects who received at least one dose of palifermin (Treatment A or B) or who had a set zero point (Treatment C). This outcome was assessed for Treatment B and C only as per study plan.

Protein/creatinine ratio is the urinary protein (mg) divided by the urinary creatinine (g) result. Ratio to baseline protein/creatinine ratio was calculated as protein/creatinine ratio at specified day divided by baseline protein/creatinine ratio.

Outcome measures

Outcome measures
Measure	Palifermin - Heparin n=16 Participants Treatment A: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections and continuous heparin IV infusion	Palifermin Alone n=8 Participants Treatment B: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections	Untreated Control Treatment C: control group without any treatment administered
Ratio to Baseline of Protein/Creatinine	1.00 ratio Standard Deviation 0.00	1.00 ratio Standard Deviation 0.00	—

SECONDARY outcome

Timeframe: Day 2

Population: The safety population consist of all randomized subjects who received at least one dose of palifermin (Treatment A or B) or who had a set zero point (Treatment C). This outcome was assessed for Treatment B and C only as per study plan.

Protein/creatinine ratio is the urinary protein (mg) divided by the urinary creatinine (g) result. Ratio to baseline protein/creatinine ratio was calculated as protein/creatinine ratio at specified day divided by baseline protein/creatinine ratio.

Outcome measures

Outcome measures
Measure	Palifermin - Heparin n=16 Participants Treatment A: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections and continuous heparin IV infusion	Palifermin Alone n=8 Participants Treatment B: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections	Untreated Control Treatment C: control group without any treatment administered
Ratio to Baseline of Protein/Creatinine	1.0 ratio Standard Deviation 0.42	1.0 ratio Standard Deviation 0.13	—

SECONDARY outcome

Timeframe: Day 3

Population: The safety population consist of all randomized subjects who received at least one dose of palifermin (Treatment A or B) or who had a set zero point (Treatment C). This outcome was assessed for Treatment B and C only as per study plan.

Protein/creatinine ratio is the urinary protein (mg) divided by the urinary creatinine (g) result. Ratio to baseline protein/creatinine ratio was calculated as protein/creatinine ratio at specified day divided by baseline protein/creatinine ratio.

Outcome measures

Outcome measures
Measure	Palifermin - Heparin n=16 Participants Treatment A: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections and continuous heparin IV infusion	Palifermin Alone n=8 Participants Treatment B: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections	Untreated Control Treatment C: control group without any treatment administered
Ratio to Baseline of Protein/Creatinine	1.1 ratio Standard Deviation 0.51	1.1 ratio Standard Deviation 0.33	—

SECONDARY outcome

Timeframe: Day 1

Population: The safety population consist of all randomized subjects who received at least one dose of palifermin (Treatment A or B) or who had a set zero point (Treatment C). This outcome was assessed for Treatment B and C only as per study plan.

The albumin/creatinine ratio is the urinary albumin (mg) divided by the urinary creatinine (g) result at the specified time point. Ratio to baseline was calculated as albumin/creatinine ratio at specified day divided by baseline albumin/creatinine ratio.

Outcome measures

Outcome measures
Measure	Palifermin - Heparin n=16 Participants Treatment A: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections and continuous heparin IV infusion	Palifermin Alone n=8 Participants Treatment B: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections	Untreated Control Treatment C: control group without any treatment administered
Ratio to Baseline of Albumin/Creatinine	1.00 ratio Standard Deviation 0.000	1.00 ratio Standard Deviation 0.000	—

SECONDARY outcome

Timeframe: Day 2

Population: The safety population consist of all randomized subjects who received at least one dose of palifermin (Treatment A or B) or who had a set zero point (Treatment C). This outcome was assessed for Treatment B and C only as per study plan.

The albumin/creatinine ratio is the urinary albumin (mg) divided by the urinary creatinine (g) result at the specified time point. Ratio to baseline was calculated as albumin/creatinine ratio at specified day divided by baseline albumin/creatinine ratio.

Outcome measures

Outcome measures
Measure	Palifermin - Heparin n=16 Participants Treatment A: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections and continuous heparin IV infusion	Palifermin Alone n=8 Participants Treatment B: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections	Untreated Control Treatment C: control group without any treatment administered
Ratio to Baseline of Albumin/Creatinine	1.05 ratio Standard Deviation 0.373	0.95 ratio Standard Deviation 0.230	—

SECONDARY outcome

Timeframe: Day 3

Population: The safety population consist of all randomized subjects who received at least one dose of palifermin (Treatment A or B) or who had a set zero point (Treatment C). This outcome was assessed for Treatment B and C only as per study plan.

The albumin/creatinine ratio is the urinary albumin (mg) divided by the urinary creatinine (g) result at the specified time point. Ratio to baseline was calculated as albumin/creatinine ratio at specified day divided by baseline albumin/creatinine ratio.

Outcome measures

Outcome measures
Measure	Palifermin - Heparin n=16 Participants Treatment A: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections and continuous heparin IV infusion	Palifermin Alone n=8 Participants Treatment B: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections	Untreated Control Treatment C: control group without any treatment administered
Ratio to Baseline of Albumin/Creatinine	1.16 ratio Standard Deviation 0.391	0.99 ratio Standard Deviation 0.268	—

SECONDARY outcome

Timeframe: Day 4

Population: The safety population consist of all randomized subjects who received at least one dose of palifermin (Treatment A or B) or who had a set zero point (Treatment C). This outcome was assessed for Treatment B and C only as per study plan.

The albumin/creatinine ratio is the urinary albumin (mg) divided by the urinary creatinine (g) result at the specified time point. Ratio to baseline was calculated as albumin/creatinine ratio at specified day divided by baseline albumin/creatinine ratio.

Outcome measures

Outcome measures
Measure	Palifermin - Heparin n=16 Participants Treatment A: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections and continuous heparin IV infusion	Palifermin Alone n=8 Participants Treatment B: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections	Untreated Control Treatment C: control group without any treatment administered
Ratio to Baseline of Albumin/Creatinine	1.56 ratio Standard Deviation 1.610	1.25 ratio Standard Deviation 0.484	—

Adverse Events

Palifermin - Heparin

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Palifermin Alone

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Untreated Control

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Medical Program Director

Swedish Orphan Biovitrum

Phone: +46 8 697 20 00

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits sponsor a limited period of time to review material discussing trial results (typically up to 90 days). Sponsor may remove confidential information, but authors have final control and approval of publication content. For multi-center studies, investigator agrees not to publish any results before the first multi-center publication.
Publication restrictions are in place

Restriction type: OTHER

Measure	Palifermin - Heparin n=20 participants at risk Treatment A: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections and continuous heparin IV infusion	Palifermin Alone n=16 participants at risk Treatment B: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections	Untreated Control n=8 participants at risk Treatment C: control group without any treatment administered
Investigations Alanine aminotransferase increased	10.0% 2/20 • Number of events 2 • From signing of informed consent to subject´s end of study.	0.00% 0/16 • From signing of informed consent to subject´s end of study.	0.00% 0/8 • From signing of informed consent to subject´s end of study.
Investigations Aspartate aminotransferase increased	15.0% 3/20 • Number of events 3 • From signing of informed consent to subject´s end of study.	0.00% 0/16 • From signing of informed consent to subject´s end of study.	0.00% 0/8 • From signing of informed consent to subject´s end of study.
Injury, poisoning and procedural complications Procedural pain	15.0% 3/20 • Number of events 4 • From signing of informed consent to subject´s end of study.	37.5% 6/16 • Number of events 8 • From signing of informed consent to subject´s end of study.	37.5% 3/8 • Number of events 5 • From signing of informed consent to subject´s end of study.
Nervous system disorders Headache	0.00% 0/20 • From signing of informed consent to subject´s end of study.	18.8% 3/16 • Number of events 4 • From signing of informed consent to subject´s end of study.	0.00% 0/8 • From signing of informed consent to subject´s end of study.
Gastrointestinal disorders Constipation	0.00% 0/20 • From signing of informed consent to subject´s end of study.	6.2% 1/16 • Number of events 1 • From signing of informed consent to subject´s end of study.	0.00% 0/8 • From signing of informed consent to subject´s end of study.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/20 • From signing of informed consent to subject´s end of study.	6.2% 1/16 • Number of events 1 • From signing of informed consent to subject´s end of study.	0.00% 0/8 • From signing of informed consent to subject´s end of study.
General disorders Injection site rash	0.00% 0/20 • From signing of informed consent to subject´s end of study.	18.8% 3/16 • Number of events 3 • From signing of informed consent to subject´s end of study.	0.00% 0/8 • From signing of informed consent to subject´s end of study.
Gastrointestinal disorders Hypoaesthesia oral	0.00% 0/20 • From signing of informed consent to subject´s end of study.	6.2% 1/16 • Number of events 1 • From signing of informed consent to subject´s end of study.	0.00% 0/8 • From signing of informed consent to subject´s end of study.
Nervous system disorders Dysgeusia	5.0% 1/20 • Number of events 1 • From signing of informed consent to subject´s end of study.	12.5% 2/16 • Number of events 2 • From signing of informed consent to subject´s end of study.	0.00% 0/8 • From signing of informed consent to subject´s end of study.
Vascular disorders Poor venous access	5.0% 1/20 • Number of events 1 • From signing of informed consent to subject´s end of study.	0.00% 0/16 • From signing of informed consent to subject´s end of study.	0.00% 0/8 • From signing of informed consent to subject´s end of study.
General disorders Vessel puncture site haematoma	5.0% 1/20 • Number of events 1 • From signing of informed consent to subject´s end of study.	0.00% 0/16 • From signing of informed consent to subject´s end of study.	0.00% 0/8 • From signing of informed consent to subject´s end of study.
Gastrointestinal disorders Nausea	0.00% 0/20 • From signing of informed consent to subject´s end of study.	6.2% 1/16 • Number of events 1 • From signing of informed consent to subject´s end of study.	0.00% 0/8 • From signing of informed consent to subject´s end of study.
Gastrointestinal disorders Paraesthesia oral	5.0% 1/20 • Number of events 1 • From signing of informed consent to subject´s end of study.	0.00% 0/16 • From signing of informed consent to subject´s end of study.	0.00% 0/8 • From signing of informed consent to subject´s end of study.
General disorders Feeling hot	5.0% 1/20 • Number of events 1 • From signing of informed consent to subject´s end of study.	0.00% 0/16 • From signing of informed consent to subject´s end of study.	0.00% 0/8 • From signing of informed consent to subject´s end of study.
Skin and subcutaneous tissue disorders Pruritus	5.0% 1/20 • Number of events 1 • From signing of informed consent to subject´s end of study.	0.00% 0/16 • From signing of informed consent to subject´s end of study.	0.00% 0/8 • From signing of informed consent to subject´s end of study.
Eye disorders Vision blurred	5.0% 1/20 • Number of events 1 • From signing of informed consent to subject´s end of study.	0.00% 0/16 • From signing of informed consent to subject´s end of study.	0.00% 0/8 • From signing of informed consent to subject´s end of study.
Skin and subcutaneous tissue disorders Blister	5.0% 1/20 • Number of events 1 • From signing of informed consent to subject´s end of study.	0.00% 0/16 • From signing of informed consent to subject´s end of study.	0.00% 0/8 • From signing of informed consent to subject´s end of study.
Metabolism and nutrition disorders Decreased appetite	15.0% 3/20 • Number of events 3 • From signing of informed consent to subject´s end of study.	0.00% 0/16 • From signing of informed consent to subject´s end of study.	0.00% 0/8 • From signing of informed consent to subject´s end of study.
Renal and urinary disorders Urine odour abnormal	0.00% 0/20 • From signing of informed consent to subject´s end of study.	6.2% 1/16 • Number of events 1 • From signing of informed consent to subject´s end of study.	0.00% 0/8 • From signing of informed consent to subject´s end of study.