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Trial record 98 of 990 for:    Heparin sodium

Study to Characterize the Effect of Heparin on Palifermin Activity

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01163097
Recruitment Status : Completed
First Posted : July 15, 2010
Results First Posted : August 23, 2012
Last Update Posted : November 6, 2014
Sponsor:
Information provided by (Responsible Party):
Swedish Orphan Biovitrum

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Oral Mucositis
Interventions Drug: Palifermin
Drug: Heparin
Enrollment 44
Recruitment Details 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.
Pre-assignment Details 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.
Arm/Group Title Palifermin - Heparin Palifermin Alone Untreated Control
Hide Arm/Group Description Treatment A: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections and continuous heparin IV infusion Treatment B: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections Treatment C: control group without any treatment administered
Period Title: Overall Study
Started 20 [1] 16 8
Completed 14 16 8
Not Completed 6 0 0
[1]
15 subjects were successfully titrated and entered the palifermin treatment
Arm/Group Title Palifermin - Heparin Palifermin Alone Untreated Control Total
Hide Arm/Group Description Treatment A: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections and continuous heparin IV infusion Treatment B: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections Treatment C: control group without any treatment administered Total of all reporting groups
Overall Number of Baseline Participants 15 16 8 39
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15 participants 16 participants 8 participants 39 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
15
 100.0%
16
 100.0%
8
 100.0%
39
 100.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 15 participants 16 participants 8 participants 39 participants
25.9  (5.29) 32.9  (7.82) 22.8  (3.62) 28.1  (7)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15 participants 16 participants 8 participants 39 participants
Female
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Male
15
 100.0%
16
 100.0%
8
 100.0%
39
 100.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15 participants 16 participants 8 participants 39 participants
Hispanic or Latino
1
   6.7%
0
   0.0%
0
   0.0%
1
   2.6%
Not Hispanic or Latino
14
  93.3%
16
 100.0%
8
 100.0%
38
  97.4%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15 participants 16 participants 8 participants 39 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
3
  20.0%
2
  12.5%
1
  12.5%
6
  15.4%
White
12
  80.0%
14
  87.5%
7
  87.5%
33
  84.6%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 15 participants 16 participants 8 participants 39 participants
15 16 8 39
Body Mass Index  
Mean (Standard Deviation)
Unit of measure:  Kg/m2
Number Analyzed 15 participants 16 participants 8 participants 39 participants
24.95  (2.144) 26.08  (2.111) 25.98  (3.185) 25.62  (2.5)
1.Primary Outcome
Title Ratio to Baseline of Epithelial Cell Proliferation as Assessed by Ki67 Staining of Buccal Mucosal Tissue.
Hide Description 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.
Time Frame Day 4
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Palifermin - Heparin Palifermin Alone
Hide Arm/Group Description:
Treatment A: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections and continuous heparin IV infusion
Treatment B: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections
Overall Number of Participants Analyzed 14 16
Geometric Mean (90% Confidence Interval)
Unit of Measure: ratio
0.267
(0.173 to 0.361)
0.414
(0.326 to 0.502)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Palifermin - Heparin, Palifermin Alone
Comments H0: mean ratio<0.7 or mean ratio>1.43; H1: 0.7< mean ratio <1.43 Sample size calculation assumed change in Ki67 expression following palifermin administration would not be affected by co-administration of heparin. With n=26 (13 + 13), an approx. 80% probability that the 90% CI of the ratio of geometric means of Ki67 for palifermin when co-administered with heparin compared to palifermin alone would fall in the interval (0.7, 1.43). This assumed a Coefficient of Variation (CV) for Ki67 of 31%.
Type of Statistical Test Non-Inferiority or Equivalence
Comments The equivalence of the treatments was assessed using the 90% confidence interval (CI) of the geometric mean ratio for Ki67. The lower bound of the CI needed to be greater than 0.70 and the upper bound needed to be below 1.43 for the treatments to be considered equivalent.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA was used to estimate the treatment effect and the Schuirmann's two one-sided test was used to test for statistical equivalence.
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 0.863
Confidence Interval (2-Sided) 90%
0.759 to 0.982
Estimation Comments [Not Specified]
2.Primary Outcome
Title Incidence of Grade 2 or Higher Specific Skin-related Adverse Events.
Hide Description

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)

Time Frame Day 45
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Palifermin - Heparin Palifermin Alone
Hide Arm/Group Description:
Treatment A: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections and continuous heparin IV infusion
Treatment B: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections
Overall Number of Participants Analyzed 15 16
Measure Type: Number
Unit of Measure: proportion of participants
0 0.0625
3.Primary Outcome
Title Ratio to Baseline of Amylase
Hide Description Ratio to baseline amylase at Day 5 was calculated as Day 5 amylase divided by baseline amylase.
Time Frame Day 5
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Palifermin - Heparin Palifermin Alone
Hide Arm/Group Description:
Treatment A: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections and continuous heparin IV infusion
Treatment B: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections
Overall Number of Participants Analyzed 15 16
Geometric Mean (95% Confidence Interval)
Unit of Measure: ratio
0.242
(0.111 to 0.372)
0.547
(0.420 to 0.673)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Palifermin - Heparin, Palifermin Alone
Comments 80% power achieved for detecting a 20% increase (or 17% reduction) when Treatment A was compared to Treatment B; assuming that the coefficient of variation of amylase would be 14% (as observed in other study)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA (with dependent variable:natural log of the ratio to baseline, independent variable:treatment, covariate:natural log of the baseline value)
Method of Estimation Estimation Parameter Geometric mean
Estimated Value 0.737
Confidence Interval (2-Sided) 95%
0.614 to 0.885
Estimation Comments [Not Specified]
4.Primary Outcome
Title Ratio to Baseline of Lipase.
Hide Description Ratio to baseline lipase at Day 5 was calculated as Day 5 lipase divided by baseline lipase.
Time Frame Day 5
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Palifermin - Heparin Palifermin Alone
Hide Arm/Group Description:
Treatment A: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections and continuous heparin IV infusion
Treatment B: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections
Overall Number of Participants Analyzed 15 16
Geometric Mean (95% Confidence Interval)
Unit of Measure: ratio
-0.487
(-0.873 to -0.100)
0.499
(0.125 to 0.873)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Palifermin - Heparin, Palifermin Alone
Comments 80% power achieved for detecting a 70% increase (or 41% reduction) when Treatment A was compared to Treatment B; assuming that the coefficient of variation of lipase would be 49% (as observed in other study)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA (with dependent variable:natural log of the ratio to baseline, independent variable:treatment, covariate:natural log of the baseline value)
Method of Estimation Estimation Parameter Geometric mean
Estimated Value 0.373
Confidence Interval (2-Sided) 95%
0.216 to 0.645
Estimation Comments [Not Specified]
5.Primary Outcome
Title Ratio to Baseline of Protein/Creatinine
Hide Description

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.

Time Frame Day 4
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Palifermin Alone Untreated Control
Hide Arm/Group Description:
Treatment B: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections
Treatment C: control group without any treatment administered
Overall Number of Participants Analyzed 16 8
Geometric Mean (95% Confidence Interval)
Unit of Measure: ratio
0.076
(-0.058 to 0.211)
0.104
(-0.087 to 0.296)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Palifermin Alone, Untreated Control
Comments 80% power achieved for detecting a 140% increase with 13 and 6 subjects (respectively) when Treatment B was compared to Treatment C; assuming that the coefficient of variation of the protein/creatinine ratio would be 67% (Ginsberg et al 1983)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA (with dependent variable:natural log of the ratio to baseline, independent variable:treatment, covariate:natural log of the baseline value)
Method of Estimation Estimation Parameter Geometric mean
Estimated Value 0.972
Confidence Interval (2-Sided) 95%
0.768 to 1.231
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Palifermin Pharmacokinetic (PK) Parameters: Clearance (CL)
Hide Description

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.

Time Frame Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
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
Arm/Group Title Palifermin - Heparin Palifermin Alone
Hide Arm/Group Description:
Treatment A: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections and continuous heparin IV infusion
Treatment B: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections
Overall Number of Participants Analyzed 15 16
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: (mL/hr/kg)
121.1
(29.1%)
527.8
(33.5%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Palifermin - Heparin, Palifermin Alone
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
7.Secondary Outcome
Title Palifermin PK Parameters: CL
Hide Description

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.

Time Frame Day 3
Hide Outcome Measure Data
Hide Analysis Population Description
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
Arm/Group Title Palifermin - Heparin Palifermin Alone
Hide Arm/Group Description:
Treatment A: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections and continuous heparin IV infusion
Treatment B: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections
Overall Number of Participants Analyzed 15 16
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: (mL/hr/kg)
121.9
(20.4%)
524.3
(59.4%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Palifermin - Heparin, Palifermin Alone
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
8.Secondary Outcome
Title Palifermin PK Parameters: Area Under the Serum Curve (AUC) (0-24)
Hide Description

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.

Time Frame Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
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
Arm/Group Title Palifermin - Heparin Palifermin Alone
Hide Arm/Group Description:
Treatment A: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections and continuous heparin IV infusion
Treatment B: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections
Overall Number of Participants Analyzed 15 16
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*hr/mL
330.1
(26.9%)
75.80
(37.1%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Palifermin - Heparin, Palifermin Alone
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
9.Secondary Outcome
Title Palifermin PK Parameters: AUC (0-24)
Hide Description

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.

Time Frame Day 3
Hide Outcome Measure Data
Hide Analysis Population Description
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
Arm/Group Title Palifermin - Heparin Palifermin Alone
Hide Arm/Group Description:
Treatment A: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections and continuous heparin IV infusion
Treatment B: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections
Overall Number of Participants Analyzed 15 16
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*hr/mL
328.1
(20.4%)
76.26
(36.3%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Palifermin - Heparin, Palifermin Alone
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
10.Secondary Outcome
Title Palifermin PK Parameters: Estimated Concentration at Time 0 (C0)
Hide Description

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.

Time Frame Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
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
Arm/Group Title Palifermin - Heparin Palifermin Alone
Hide Arm/Group Description:
Treatment A: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections and continuous heparin IV infusion
Treatment B: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections
Overall Number of Participants Analyzed 15 16
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
229.1
(116.6%)
584.7
(111.9%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Palifermin - Heparin, Palifermin Alone
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4123
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
11.Secondary Outcome
Title Palifermin PK Parameters: C0
Hide Description

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.

Time Frame Day 3
Hide Outcome Measure Data
Hide Analysis Population Description
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
Arm/Group Title Palifermin - Heparin Palifermin Alone
Hide Arm/Group Description:
Treatment A: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections and continuous heparin IV infusion
Treatment B: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections
Overall Number of Participants Analyzed 15 16
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
361.0
(92.3%)
563.2
(105.7%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Palifermin - Heparin, Palifermin Alone
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9944
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
12.Secondary Outcome
Title Palifermin PK Parameters: Apparent Volume of Distribution at Steady State (Vss)
Hide Description

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.

Time Frame Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
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
Arm/Group Title Palifermin - Heparin Palifermin Alone
Hide Arm/Group Description:
Treatment A: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections and continuous heparin IV infusion
Treatment B: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections
Overall Number of Participants Analyzed 15 16
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: mL/kg
411.5
(42.4%)
1586
(48.1%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Palifermin - Heparin, Palifermin Alone
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
13.Secondary Outcome
Title Palifermin PK Parameters: Vss
Hide Description

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.

Time Frame Day 3
Hide Outcome Measure Data
Hide Analysis Population Description
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
Arm/Group Title Palifermin - Heparin Palifermin Alone
Hide Arm/Group Description:
Treatment A: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections and continuous heparin IV infusion
Treatment B: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections
Overall Number of Participants Analyzed 15 16
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: mL/Kg
361.7
(28.0%)
1318
(64.4%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Palifermin - Heparin, Palifermin Alone
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
14.Secondary Outcome
Title Subject Incidence of Treatment-emergent Adverse Event
Hide Description 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).
Time Frame Day 45
Hide Outcome Measure Data
Hide Analysis Population Description
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)
Arm/Group Title Palifermin - Heparin Palifermin Alone Untreated Control
Hide Arm/Group Description:
Treatment A: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections and continuous heparin IV infusion
Treatment B: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections
Treatment C: control group without any treatment administered
Overall Number of Participants Analyzed 14 16 8
Measure Type: Number
Unit of Measure: participants
9 8 3
15.Secondary Outcome
Title Subject Incidence of Proteinuria
Hide Description

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.

Time Frame Day 4
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Palifermin Alone Untreated Control
Hide Arm/Group Description:
Treatment B: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections
Treatment C: control group without any treatment administered
Overall Number of Participants Analyzed 16 8
Measure Type: Number
Unit of Measure: participants
0 0
16.Secondary Outcome
Title Ratio to Baseline of Protein/Creatinine
Hide Description

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.

Time Frame Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Palifermin Alone Untreated Control
Hide Arm/Group Description:
Treatment B: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections
Treatment C: control group without any treatment administered
Overall Number of Participants Analyzed 16 8
Mean (Standard Deviation)
Unit of Measure: ratio
1.00  (0.00) 1.00  (0.00)
17.Secondary Outcome
Title Ratio to Baseline of Protein/Creatinine
Hide Description

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.

Time Frame Day 2
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Palifermin Alone Untreated Control
Hide Arm/Group Description:
Treatment B: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections
Treatment C: control group without any treatment administered
Overall Number of Participants Analyzed 16 8
Mean (Standard Deviation)
Unit of Measure: ratio
1.0  (0.42) 1.0  (0.13)
18.Secondary Outcome
Title Ratio to Baseline of Protein/Creatinine
Hide Description

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.

Time Frame Day 3
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Palifermin Alone Untreated Control
Hide Arm/Group Description:
Treatment B: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections
Treatment C: control group without any treatment administered
Overall Number of Participants Analyzed 16 8
Mean (Standard Deviation)
Unit of Measure: ratio
1.1  (0.51) 1.1  (0.33)
19.Secondary Outcome
Title Ratio to Baseline of Albumin/Creatinine
Hide Description

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.

Time Frame Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Palifermin Alone Untreated Control
Hide Arm/Group Description:
Treatment B: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections
Treatment C: control group without any treatment administered
Overall Number of Participants Analyzed 16 8
Mean (Standard Deviation)
Unit of Measure: ratio
1.00  (0.000) 1.00  (0.000)
20.Secondary Outcome
Title Ratio to Baseline of Albumin/Creatinine
Hide Description

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.

Time Frame Day 2
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Palifermin Alone Untreated Control
Hide Arm/Group Description:
Treatment B: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections
Treatment C: control group without any treatment administered
Overall Number of Participants Analyzed 16 8
Mean (Standard Deviation)
Unit of Measure: ratio
1.05  (0.373) 0.95  (0.230)
21.Secondary Outcome
Title Ratio to Baseline of Albumin/Creatinine
Hide Description

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.

Time Frame Day 3
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Palifermin Alone Untreated Control
Hide Arm/Group Description:
Treatment B: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections
Treatment C: control group without any treatment administered
Overall Number of Participants Analyzed 16 8
Mean (Standard Deviation)
Unit of Measure: ratio
1.16  (0.391) 0.99  (0.268)
22.Secondary Outcome
Title Ratio to Baseline of Albumin/Creatinine
Hide Description

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.

Time Frame Day 4
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Palifermin Alone Untreated Control
Hide Arm/Group Description:
Treatment B: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections
Treatment C: control group without any treatment administered
Overall Number of Participants Analyzed 16 8
Mean (Standard Deviation)
Unit of Measure: ratio
1.56  (1.610) 1.25  (0.484)
Time Frame From signing of informed consent to subject´s end of study.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Palifermin - Heparin Palifermin Alone Untreated Control
Hide Arm/Group Description Treatment A: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections and continuous heparin IV infusion Treatment B: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections Treatment C: control group without any treatment administered
All-Cause Mortality
Palifermin - Heparin Palifermin Alone Untreated Control
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Palifermin - Heparin Palifermin Alone Untreated Control
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/20 (0.00%)      0/16 (0.00%)      0/8 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Palifermin - Heparin Palifermin Alone Untreated Control
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   9/20 (45.00%)      9/16 (56.25%)      3/8 (37.50%)    
Eye disorders       
Vision blurred  1  1/20 (5.00%)  1 0/16 (0.00%)  0 0/8 (0.00%)  0
Gastrointestinal disorders       
Constipation  1  0/20 (0.00%)  0 1/16 (6.25%)  1 0/8 (0.00%)  0
Hypoaesthesia oral  1  0/20 (0.00%)  0 1/16 (6.25%)  1 0/8 (0.00%)  0
Nausea  1  0/20 (0.00%)  0 1/16 (6.25%)  1 0/8 (0.00%)  0
Paraesthesia oral  1  1/20 (5.00%)  1 0/16 (0.00%)  0 0/8 (0.00%)  0
General disorders       
Injection site rash  1  0/20 (0.00%)  0 3/16 (18.75%)  3 0/8 (0.00%)  0
Vessel puncture site haematoma  1  1/20 (5.00%)  1 0/16 (0.00%)  0 0/8 (0.00%)  0
Feeling hot  1  1/20 (5.00%)  1 0/16 (0.00%)  0 0/8 (0.00%)  0
Injury, poisoning and procedural complications       
Procedural pain  1  3/20 (15.00%)  4 6/16 (37.50%)  8 3/8 (37.50%)  5
Investigations       
Alanine aminotransferase increased  1  2/20 (10.00%)  2 0/16 (0.00%)  0 0/8 (0.00%)  0
Aspartate aminotransferase increased  1  3/20 (15.00%)  3 0/16 (0.00%)  0 0/8 (0.00%)  0
Metabolism and nutrition disorders       
Decreased appetite  1  3/20 (15.00%)  3 0/16 (0.00%)  0 0/8 (0.00%)  0
Musculoskeletal and connective tissue disorders       
Musculoskeletal pain  1  0/20 (0.00%)  0 1/16 (6.25%)  1 0/8 (0.00%)  0
Nervous system disorders       
Headache  1  0/20 (0.00%)  0 3/16 (18.75%)  4 0/8 (0.00%)  0
Dysgeusia  1  1/20 (5.00%)  1 2/16 (12.50%)  2 0/8 (0.00%)  0
Renal and urinary disorders       
Urine odour abnormal  1  0/20 (0.00%)  0 1/16 (6.25%)  1 0/8 (0.00%)  0
Skin and subcutaneous tissue disorders       
Pruritus  1  1/20 (5.00%)  1 0/16 (0.00%)  0 0/8 (0.00%)  0
Blister  1  1/20 (5.00%)  1 0/16 (0.00%)  0 0/8 (0.00%)  0
Vascular disorders       
Poor venous access  1  1/20 (5.00%)  1 0/16 (0.00%)  0 0/8 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 13.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Name/Title: Medical Program Director
Organization: Swedish Orphan Biovitrum
Phone: +46 8 697 20 00
Responsible Party: Swedish Orphan Biovitrum
ClinicalTrials.gov Identifier: NCT01163097     History of Changes
Other Study ID Numbers: 20070278
First Submitted: July 14, 2010
First Posted: July 15, 2010
Results First Submitted: January 17, 2012
Results First Posted: August 23, 2012
Last Update Posted: November 6, 2014