- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01163097
Study to Characterize the Effect of Heparin on Palifermin Activity
An Open-label, Randomized, Parallel-Design Study to Characterize the Effect of Heparin on Palifermin Activity in Healthy Adult Subjects
Study Overview
Detailed Description
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.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Tennessee
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Knoxville, Tennessee, United States, 37920
- New Orleans Center for Clinical Research (NOCCR)
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Healthy men or postmenopausal or oophorectomized women.
- Subjects should have a Body Mass Index between 19 and 30 inclusive.
- A negative screen for drug abuse, tobacco use and alcohol breath test.
- Subjects should be willing to be resident in the research facility for up to 6 nights and return to the research facility for scheduled study and follow-up procedures.
- Men must agree for the duration of the study to use an appropriate method of birth control
Exclusion Criteria:
- History or evidence of clinically significant disorder, condition or disease that would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion.
- History or evidence of any oral mucosal disease that may affect mucosal keratinocyte proliferation.
- Evidence or history of thrombocytopenia, heparin-induced thrombocytopenia or other contraindications to heparin (e.g. recent surgeries).
- Known hypersensitivity to heparin or topical or injectable local anesthetic.
- Known allergies to Escherichia coli-derived products or allergies to palifermin or its excipients.
- Use of medications (except vitamins, hormonal replacement therapy and topical medications) within 10 days of admission to research facility.
- Blood donation within 8 weeks prior to dosing of investigational drug.
- History of hypertension, clinically significant bleeding, gastrointestinal ulcers, arteriovenous malformation (AVM), aneurysm, or other vascular malformation.
- History of coagulopathy, bleeding disorders or abnormal platelet counts.
- History of malignancy of any type, other than surgically excised non-melanoma skin cancers or in situ cervical cancer.
- For males, past history of epididymitis.
- Known alcohol abuse or use of illicit drugs within 12 months prior to admission to the research facility.
- History of smoking or using smokeless tobacco within the past year before admission to the research facility.
- Any other condition that might reduce the chance of obtaining data (eg, known poor compliance) required by the protocol or that might compromise the ability to give informed consent.
- Previous participation in a palifermin study.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Palifermin 40 µg/kg and heparin IV infusion
Treatment A: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections and continuous heparin IV infusion
|
40 µg/kg IV bolus injections for three consecutive days
Heparin continuous IV infusion
|
EXPERIMENTAL: Palifermin 40 µg/kg
Treatment B: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections
|
40 µg/kg IV bolus injections for three consecutive days
|
NO_INTERVENTION: Control group without any treatment
Treatment C: control group without any treatment administered.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Ratio to Baseline of Epithelial Cell Proliferation as Assessed by Ki67 Staining of Buccal Mucosal Tissue.
Time Frame: Day 4
|
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.
Time Frame: Day 45
|
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
Time Frame: Day 5
|
Ratio to baseline amylase at Day 5 was calculated as Day 5 amylase divided by baseline amylase.
|
Day 5
|
Ratio to Baseline of Lipase.
Time Frame: Day 5
|
Ratio to baseline lipase at Day 5 was calculated as Day 5 lipase divided by baseline lipase.
|
Day 5
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Ratio to Baseline of Protein/Creatinine
Time Frame: Day 4
|
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
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Palifermin Pharmacokinetic (PK) Parameters: Clearance (CL)
Time Frame: Day 1
|
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 1
|
Palifermin PK Parameters: CL
Time Frame: Day 3
|
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)
Time Frame: Day 1
|
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)
Time Frame: Day 3
|
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)
Time Frame: Day 1
|
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
Time Frame: Day 3
|
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)
Time Frame: Day 1
|
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
Time Frame: Day 3
|
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
Time Frame: Day 45
|
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
Time Frame: Day 4
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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
Time Frame: Day 1
|
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
Time Frame: Day 2
|
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
Time Frame: Day 3
|
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
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Ratio to Baseline of Albumin/Creatinine
Time Frame: Day 1
|
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
Time Frame: Day 2
|
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
Time Frame: Day 3
|
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
Time Frame: Day 4
|
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
|
Collaborators and Investigators
Sponsor
Investigators
- Study Director: Maarten de Chateau, MD PhD, Swedish Orphan Biovitrum
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ESTIMATE)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 20070278
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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