Palifermin DDI (Drug Drug Interaction)
- Registration Number
- NCT00361348
- Lead Sponsor
- Swedish Orphan Biovitrum
- Brief Summary
The purpose of this study is to determine if Paliferim interacts with Heparin.
- Detailed Description
Heparin has been shown to modulate binding of palifermin to the KGF receptor. Therefore, as part of a post-marketing regulatory commitment with the Food and Drug Administration (FDA), the purpose of this study is to characterize the potential pharmacokinetic and pharmacodynamic drug-drug interaction between a continuous IV infusion of heparin and an IV bolus injection of palifermin. If an interaction is observed during co-administration, it is expected that the outcome would be modulation of clearance of palifermin or a change in heparin activity. Although not commonly conducted, the literature describes heparin drug-drug interaction studies conducted in healthy subjects using both subcutaneous (Grimaudo et al,1988; Kroon et al, 1992) and intravenous (Caplain at al, 1999; Noveck \& Hubbard, 2004; Spowart et al, 1988) formulations. Based on these experiences, it is appropriate to investigate heparin drug-drug interactions in healthy subjects.
In this study, subjects will receive a single 60 mcg/kg dose of palifermin either as monotherapy or in conjunction with a continuous heparin infusion. The 60 mcg/kg dose of palifermin explored in this study is identical to the current recommended daily dosage for patients with hematologic malignancies who were undergoing autologous PBPC transplantation after receiving total body irradiation and high-dose chemotherapy: 3 consecutive days administered in two cycles with a 5-day non-dosing interval.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 45
- Inclusion: Baseline aPTT values for all subjects must be within normal range. In addition, all subjects must also test negative for occult blood in the stool, have no history of bleeding disorders or no use of aspirin or NSAIDs within 14 days of study Day 1.
- Exclusion: The study will also exclude subjects who have any evidence or history of thrombocytopenia, heparin-induced thrombocytopenia or other contraindications to heparin (e.g., recent surgeries).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Palifermin Palifermin A single 60µg/kg IV bolus dose of palifermin on Day 1 of the treatment period Palifermin + Heparin Heparin A single 60µg/kg IV bolus dose of palifermin on Day 1 of the treatment period + unfractionated heparin for a 2 to 3 day heparin titation/maintenance period and continuing through a 3 day treatment period Heparin Heparin unfractionated heparin for a 2 to 3 day heparin titation/maintenance period and continuing through a 3 day treatment period Palifermin + Heparin Palifermin A single 60µg/kg IV bolus dose of palifermin on Day 1 of the treatment period + unfractionated heparin for a 2 to 3 day heparin titation/maintenance period and continuing through a 3 day treatment period
- Primary Outcome Measures
Name Time Method To evaluate the effect of a continuous intravenous (IV) infusion of unfractionated heparin on the single-dose pharmacokinetics (PK) of palifermin in healthy subjects.
- Secondary Outcome Measures
Name Time Method To evaluate the effect (activated partial thromboplastin time, aPTT) of a single dose of palifermin on unfractionated heparin pharmacodynamics [(PD), AUCaPTT, 0-6, AUCaPTT, 0-24]. To evaluate the safety and tolerability of a single 60 µg/kg intravenous dose of palifermin with or without a continuous IV infusion of heparin.