Clinical trial NCT01163097: Study to Characterize the Effect of Heparin on Palifermin Activity
Official title: An Open-label, Randomized, Parallel-Design Study to Characterize the Effect of Heparin on Palifermin Activity in Healthy Adult Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Oral Mucositis
Lead sponsor: Swedish Orphan Biovitrum
Sponsor class: INDUSTRY
First posted: 2010-07-15
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Ratio to Baseline of Epithelial Cell Proliferation as Assessed by Ki67 Staining of Buccal Mucosal Tissue.
timeFrame: Day 4
measure: Incidence of Grade 2 or Higher Specific Skin-related Adverse Events.
timeFrame: Day 45
measure: Ratio to Baseline of Amylase
timeFrame: Day 5
measure: Ratio to Baseline of Lipase.
timeFrame: Day 5
measure: Ratio to Baseline of Protein/Creatinine
timeFrame: Day 4
Secondary outcomes:
measure: Palifermin Pharmacokinetic (PK) Parameters: Clearance (CL)
timeFrame: Day 1
measure: Palifermin PK Parameters: CL
timeFrame: Day 3
measure: Palifermin PK Parameters: Area Under the Serum Curve (AUC) (0-24)
timeFrame: Day 1
measure: Palifermin PK Parameters: AUC (0-24)
timeFrame: Day 3
measure: Palifermin PK Parameters: Estimated Concentration at Time 0 (C0)
timeFrame: Day 1
measure: Palifermin PK Parameters: C0
timeFrame: Day 3
measure: Palifermin PK Parameters: Apparent Volume of Distribution at Steady State (Vss)
timeFrame: Day 1
measure: Palifermin PK Parameters: Vss
timeFrame: Day 3
measure: Subject Incidence of Treatment-emergent Adverse Event
timeFrame: Day 45
measure: Subject Incidence of Proteinuria
timeFrame: Day 4
measure: Ratio to Baseline of Protein/Creatinine
timeFrame: Day 1
measure: Ratio to Baseline of Protein/Creatinine
timeFrame: Day 2
measure: Ratio to Baseline of Protein/Creatinine
timeFrame: Day 3
measure: Ratio to Baseline of Albumin/Creatinine
timeFrame: Day 1
measure: Ratio to Baseline of Albumin/Creatinine
timeFrame: Day 2
measure: Ratio to Baseline of Albumin/Creatinine
timeFrame: Day 3
measure: Ratio to Baseline of Albumin/Creatinine
timeFrame: Day 4
Other outcomes:
Locations:
city: Knoxville
country: United States
facility: New Orleans Center for Clinical Research (NOCCR)
state: Tennessee
Study officials:
affiliation: Swedish Orphan Biovitrum
name: Maarten de Chateau, MD PhD
role: STUDY_DIRECTOR
References:
citation: 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.