Study to Characterize the Effect of Heparin on Palifermin Activity

NCT01163097 | Completed Phase 1 Results

• 1 other identifier: 20070278
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Oral Mucositis

Outcome Measures

Primary Outcomes (5)

• 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

Secondary Outcomes (17)

• Palifermin Pharmacokinetic (PK) Parameters: Clearance (CL)

  Day 1

• Palifermin PK Parameters: CL

  Day 3

• Palifermin PK Parameters: Area Under the Serum Curve (AUC) (0-24)

  Day 1

• Palifermin PK Parameters: AUC (0-24)

  Day 3

• Palifermin PK Parameters: Estimated Concentration at Time 0 (C0)

  Day 1

Study Arms (3)

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

Drug: Palifermin; Drug: Heparin

Palifermin 40 µg/kg

EXPERIMENTAL

Treatment B: palifermin 40 µg/kg/day for three consecutive days as IV bolus injections

Drug: Palifermin

Control group without any treatment

NO INTERVENTION

Treatment C: control group without any treatment administered.

Interventions

Palifermin DRUG

40 µg/kg IV bolus injections for three consecutive days

Palifermin 40 µg/kg; Palifermin 40 µg/kg and heparin IV infusion

Heparin DRUG

Heparin continuous IV infusion

Palifermin 40 µg/kg and heparin IV infusion

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Swedish Orphan Biovitrum: lead

Study Sites (1)

New Orleans Center for Clinical Research (NOCCR)

Knoxville, Tennessee, 37920, United States

Location

Related Publications (1)

• 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.

  PMID: 25880826 DERIVED

MeSH Terms

Conditions

Stomatitis

Interventions

Fibroblast Growth Factor 7; Heparin

Condition Hierarchy (Ancestors)

Mouth Diseases; Stomatognathic Diseases

Intervention Hierarchy (Ancestors)

Fibroblast Growth Factors; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Glycosaminoglycans; Polysaccharides; Carbohydrates

Results Point of Contact

• Title: Medical Program Director
• Organization: Swedish Orphan Biovitrum

clinical@sobi.com

+46 8 697 20 00

Study Officials

• Maarten de Chateau, MD PhD

  Swedish Orphan Biovitrum

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 14, 2010
• First Posted: July 15, 2010
• Study Start: July 1, 2010
• Primary Completion: January 1, 2011
• Study Completion: January 1, 2011
• Last Updated: November 6, 2014
• Results First Posted: August 23, 2012

Record last verified: 2014-10

Locations

US (1)