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The purpose of this study is to evaluate the effect of a continuous intravenous infusion of unfractionated heparin on the multiple-dose pharmacodynamics of palifermin in healthy adult subjects.
The planned study is designed to characterize the impact of heparin on the biologic activity of palifermin and assess the impact of the combination of palifermin and heparin on tolerability. Approximately forty-three (43) eligible healthy adult men and oophorectomized or postmenopausal women between 18-45 years of age will be assigned to one of three treatment groups where treatment group A will receive a daily dose of palifermin 40 µg/kg for three consecutive days as intravenous (IV) bolus injections and continuous heparin IV infusion, treatment B will receive a daily dose of palifermin 40 µg/kg for three consecutive days as IV bolus injections and treatment C will be a control group without any treatment administered. The subjects will be randomized in a 20:15:8 ratio (Treatment A:B:C).
The study consists of a up to 21-days screening period, a 5-days treatment period and a up to 45-days follow-up period.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Palifermin 40 µg/kg and heparin IV infusion | Experimental | Treatment A: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections and continuous heparin IV infusion |
|
| Palifermin 40 µg/kg | Experimental | Treatment B: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections |
|
| Control group without any treatment | No Intervention | Treatment C: control group without any treatment administered. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Palifermin | Drug | 40 µg/kg IV bolus injections for three consecutive days |
|
| Measure | Description | Time Frame |
|---|---|---|
| Ratio to Baseline of Epithelial Cell Proliferation as Assessed by Ki67 Staining of Buccal Mucosal Tissue. | 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. | Day 4 |
| Incidence of Grade 2 or Higher Specific Skin-related Adverse Events. | 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) | Day 45 |
| Ratio to Baseline of Amylase | Ratio to baseline amylase at Day 5 was calculated as Day 5 amylase divided by baseline amylase. | Day 5 |
| Ratio to Baseline of Lipase. | Ratio to baseline lipase at Day 5 was calculated as Day 5 lipase divided by baseline lipase. | Day 5 |
| Ratio to Baseline of Protein/Creatinine | 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. | Day 4 |
| Measure | Description | Time Frame |
|---|---|---|
| Palifermin Pharmacokinetic (PK) Parameters: Clearance (CL) | 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Maarten de Chateau, MD PhD | Swedish Orphan Biovitrum | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| New Orleans Center for Clinical Research (NOCCR) | Knoxville | Tennessee | 37920 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25880826 | Derived | Yang BB, Gillespie B, Smith B, Smith W, Lissmats A, Rudebeck M, Kullenberg T, Olsson B. Pharmacokinetic and pharmacodynamic interactions between palifermin and heparin. J Clin Pharmacol. 2015 Oct;55(10):1109-18. doi: 10.1002/jcph.516. Epub 2015 May 28. |
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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.
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.
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| ID | Title | Description |
|---|---|---|
| FG000 | Palifermin - Heparin | Treatment A: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections and continuous heparin IV infusion |
| FG001 | Palifermin Alone | Treatment B: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections |
| FG002 | Untreated Control | Treatment C: control group without any treatment administered |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Palifermin - Heparin | Treatment A: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections and continuous heparin IV infusion |
| BG001 | Palifermin Alone | Treatment B: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Ratio to Baseline of Epithelial Cell Proliferation as Assessed by Ki67 Staining of Buccal Mucosal Tissue. | 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. | 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. | Posted | Geometric Mean | 90% Confidence Interval | ratio | Day 4 |
|
From signing of informed consent to subject´s end of study.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Palifermin - Heparin | Treatment A: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections and continuous heparin IV infusion |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Alanine aminotransferase increased | Investigations | MedDRA 13.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Program Director | Swedish Orphan Biovitrum | +46 8 697 20 00 | clinical@sobi.com |
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| ID | Term |
|---|---|
| D013280 | Stomatitis |
| ID | Term |
|---|---|
| D009059 | Mouth Diseases |
| D009057 | Stomatognathic Diseases |
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| ID | Term |
|---|---|
| D051523 | Fibroblast Growth Factor 7 |
| D006493 | Heparin |
| ID | Term |
|---|---|
| D005346 | Fibroblast Growth Factors |
| D036341 | Intercellular Signaling Peptides and Proteins |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
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| Heparin | Drug | Heparin continuous IV infusion |
|
| Day 1 |
| Palifermin PK Parameters: CL | 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. | Day 3 |
| Palifermin PK Parameters: Area Under the Serum Curve (AUC) (0-24) | 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. | Day 1 |
| Palifermin PK Parameters: AUC (0-24) | 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. | Day 3 |
| Palifermin PK Parameters: Estimated Concentration at Time 0 (C0) | 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. | Day 1 |
| Palifermin PK Parameters: C0 | 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. | Day 3 |
| Palifermin PK Parameters: Apparent Volume of Distribution at Steady State (Vss) | 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. | Day 1 |
| Palifermin PK Parameters: Vss | 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. | Day 3 |
| Subject Incidence of Treatment-emergent Adverse Event | 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). | Day 45 |
| Subject Incidence of Proteinuria | 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. | Day 4 |
| Ratio to Baseline of Protein/Creatinine | 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. | Day 1 |
| Ratio to Baseline of Protein/Creatinine | 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. | Day 2 |
| Ratio to Baseline of Protein/Creatinine | 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. | Day 3 |
| Ratio to Baseline of Albumin/Creatinine | 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. | Day 1 |
| Ratio to Baseline of Albumin/Creatinine | 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. | Day 2 |
| Ratio to Baseline of Albumin/Creatinine | 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. | Day 3 |
| Ratio to Baseline of Albumin/Creatinine | 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. | Day 4 |
| BG002 | Untreated Control | Treatment C: control group without any treatment administered |
| BG003 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Body Mass Index | Mean | Standard Deviation | kg/m2 |
|
| OG001 | Palifermin Alone | Treatment B: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections |
|
|
|
| Primary | Incidence of Grade 2 or Higher Specific Skin-related Adverse Events. | 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) | 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. | Posted | Number | proportion of participants | Day 45 |
|
|
|
| Primary | Ratio to Baseline of Amylase | Ratio to baseline amylase at Day 5 was calculated as Day 5 amylase divided by baseline amylase. | 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. | Posted | Geometric Mean | 95% Confidence Interval | ratio | Day 5 |
|
|
|
|
| Primary | Ratio to Baseline of Lipase. | Ratio to baseline lipase at Day 5 was calculated as Day 5 lipase divided by baseline lipase. | 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. | Posted | Geometric Mean | 95% Confidence Interval | ratio | Day 5 |
|
|
|
|
| Primary | Ratio to Baseline of Protein/Creatinine | 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. | 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. | Posted | Geometric Mean | 95% Confidence Interval | ratio | Day 4 |
|
|
|
|
| Secondary | Palifermin Pharmacokinetic (PK) Parameters: Clearance (CL) | 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. | 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 | Posted | Geometric Mean | Geometric Coefficient of Variation | (mL/hr/kg) | Day 1 |
|
|
|
|
| Secondary | Palifermin PK Parameters: CL | 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. | 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 | Posted | Geometric Mean | Geometric Coefficient of Variation | (mL/hr/kg) | Day 3 |
|
|
|
|
| Secondary | Palifermin PK Parameters: Area Under the Serum Curve (AUC) (0-24) | 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. | 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 | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*hr/mL | Day 1 |
|
|
|
|
| Secondary | Palifermin PK Parameters: AUC (0-24) | 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. | 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 | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*hr/mL | Day 3 |
|
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|
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| Secondary | Palifermin PK Parameters: Estimated Concentration at Time 0 (C0) | 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. | 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 | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Day 1 |
|
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| Secondary | Palifermin PK Parameters: C0 | 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. | 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 | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Day 3 |
|
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| Secondary | Palifermin PK Parameters: Apparent Volume of Distribution at Steady State (Vss) | 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. | 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 | Posted | Geometric Mean | Geometric Coefficient of Variation | mL/kg | Day 1 |
|
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|
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| Secondary | Palifermin PK Parameters: Vss | 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. | 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 | Posted | Geometric Mean | Geometric Coefficient of Variation | mL/Kg | Day 3 |
|
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| Secondary | Subject Incidence of Treatment-emergent Adverse Event | 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). | 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) | Posted | Number | participants | Day 45 |
|
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| Secondary | Subject Incidence of Proteinuria | 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. | 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. | Posted | Number | participants | Day 4 |
|
|
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| Secondary | Ratio to Baseline of Protein/Creatinine | 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. | 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. | Posted | Mean | Standard Deviation | ratio | Day 1 |
|
|
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| Secondary | Ratio to Baseline of Protein/Creatinine | 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. | 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. | Posted | Mean | Standard Deviation | ratio | Day 2 |
|
|
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| Secondary | Ratio to Baseline of Protein/Creatinine | 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. | 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. | Posted | Mean | Standard Deviation | ratio | Day 3 |
|
|
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| Secondary | Ratio to Baseline of Albumin/Creatinine | 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. | 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. | Posted | Mean | Standard Deviation | ratio | Day 1 |
|
|
|
| Secondary | Ratio to Baseline of Albumin/Creatinine | 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. | 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. | Posted | Mean | Standard Deviation | ratio | Day 2 |
|
|
|
| Secondary | Ratio to Baseline of Albumin/Creatinine | 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. | 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. | Posted | Mean | Standard Deviation | ratio | Day 3 |
|
|
|
| Secondary | Ratio to Baseline of Albumin/Creatinine | 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. | 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. | Posted | Mean | Standard Deviation | ratio | Day 4 |
|
|
|
| 0 |
| 20 |
| 9 |
| 20 |
| EG001 | Palifermin Alone | Treatment B: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections | 0 | 16 | 9 | 16 |
| EG002 | Untreated Control | Treatment C: control group without any treatment administered | 0 | 8 | 3 | 8 |
| Aspartate aminotransferase increased | Investigations | MedDRA 13.0 | Systematic Assessment |
|
| Procedural pain | Injury, poisoning and procedural complications | MedDRA 13.0 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 13.0 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
|
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA 13.0 | Systematic Assessment |
|
| Injection site rash | General disorders | MedDRA 13.0 | Systematic Assessment |
|
| Hypoaesthesia oral | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
|
| Dysgeusia | Nervous system disorders | MedDRA 13.0 | Systematic Assessment |
|
| Poor venous access | Vascular disorders | MedDRA 13.0 | Systematic Assessment |
|
| Vessel puncture site haematoma | General disorders | MedDRA 13.0 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
|
| Paraesthesia oral | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
|
| Feeling hot | General disorders | MedDRA 13.0 | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 13.0 | Systematic Assessment |
|
| Vision blurred | Eye disorders | MedDRA 13.0 | Systematic Assessment |
|
| Blister | Skin and subcutaneous tissue disorders | MedDRA 13.0 | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 13.0 | Systematic Assessment |
|
| Urine odour abnormal | Renal and urinary disorders | MedDRA 13.0 | Systematic Assessment |
|
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.
| D011506 | Proteins |
| D001685 | Biological Factors |
| D006025 | Glycosaminoglycans |
| D011134 | Polysaccharides |
| D002241 | Carbohydrates |