NCT01889147

Microdose and First-In-Human (FIH) Study of Recombinant Human Placental Alkaline Phosphatase (hRESCAP)

A Single Dose Study to Assess the Peak Plasma Concentration of a Microdose of Recombinant Human Placental Alkaline Phosphatase (hRESCAP, Part 1) Followed by a Single Ascending Dose, FIH Study to Assess Safety and Tolerability of hRESCAP (Part 2).

• Status: Completed
• Phase: EARLY_Phase 1
• Study type: Interventional
• Enrollment: 4 (estimated)
• Sponsor: TNO · Academic / Other
• Sex: Male
• Age: 18 Years – 45 Years
• Healthy volunteers: Accepted

Summary

In the present study human recombinant placental alkaline phosphatase (hRESCAP) will be investigated. Alkaline Phosphatase is naturally present in the body and reported to use lipopolysaccharde (LPS, bacterial endotoxins) and extracellular nucleotides leaking from damaged and ischemic cells as physiological substrates. The LPS-substrate prevalence makes alkaline phosphatase an interesting novel therapeutic agent in the treatment of LPS-mediated diseases. A bovine homologue of this protein (bovine intestinal alkaline phosphatase, BIAP) has previously been investigated for treatment of acute inflammatory responses such as sepsis, and was shown to be safe in humans. hRESCAP, which will be investigated in the current study, is expected to have a longer half-life in humans than the previously investigated BIAP, due to the fact that it is more sialylated. The possibility to increase the t1/2 to days instead of minutes enables treatment of chronic diseases.

Detailed description

In the current study the peak plasma concentration (pharmacokinetics/elimination) of \[14C\]-labelled hRESCAP in healthy volunteers will be investigated at increasing single doses (up to anticipated therapeutic dose), with a microdose (≤30 nmol) as a safe starting dose. * Part 1: To assess the peak plasma concentration of a single microdose (≤30 nmol) of a recombinant human protein (hRESCAP), administered intravenously, as a suitable technique to predict the pharmacokinetics in humans at pharmacologically relevant doses; * Part 2: To determine the safety and tolerability of single dose of hRESCAP up to 5300 µg in healthy male volunteers administered intravenously; * To determine the peak plasma concentration of hRESCAP in healthy male volunteers within a pharmacologically relevant dose-range and compare this with BIAP pharmacokinetics with emphasis on half-life (t1/2).

Conditions

• Healthy

Interventions

Type	Name	Description
BIOLOGICAL	hRESCAP	one acute bolus administration of different dosages of hRESCAP (microdose, part 1; and FIH: low dose, 414 µg; medium dose, 2480 µg; high dose, 5300 µg; part 2)
BIOLOGICAL	Placebo

Timeline

• Start date: 2013-06-01
• Primary completion: 2013-07-01
• Completion: 2013-10-01
• First posted: 2013-06-28
• Last updated: 2013-10-24

Locations

1 site across 1 country: Netherlands