Safety and tolerability of the antimicrobial peptide human lactoferrin 1-11 (hLF1-11).
BACKGROUND
The treatment of patients with haematological malignancies by means of haematopoietic stem cell transplantation (HSCT) is often accompanied by life threatening infections. With emerging antimicrobial resistance there is an increased need for new agents, with a beneficial safety profile. Therefore we evaluated the safety of the promising new antimicrobial peptide human lactoferrrin 1-11 (hLF1-11) in healthy volunteers and patients.


METHODS
We undertook a sequential, randomised, double-blind, placebo-controlled study using ascending single (0.005, 0.05, 0.5, 5 mg) and multiple intravenous doses (0.5, 5 mg) in healthy volunteers, and open-label, single intravenous 5 mg doses in autologous HSCT recipients.


RESULTS
Single and multiple doses of hLF1-11 were tolerable up to 5 mg intravenously in healthy volunteers, while 5 mg single dose was tolerable in patients. Elevations in transaminases possibly related to treatment were reversible and not serious.


CONCLUSIONS
The new antimicrobial hLF1-11 is well tolerated in healthy volunteers with repeated daily doses up to 5 mg. The side-effect profile is very favourable for an antimicrobial, the only undesirable effect being a possible elevation of transaminases, which may be related to hLF1-11 although the current data do not allow conclusive interpretation of treatment relationship. A lower dose is recommended for the forthcoming multiple dosing studies in HSCT patients.


BACKGROUND
ClinicalTrials.gov: nct00509938.
Velden
Walter J F M van der
WJ
Department of Haematology, Radboud University Nijmegen Medical Centre, The Netherlands. w.vandervelden@hemat.umcn.nl
van Iersel
Thijs M P
TM
Blijlevens
Nicole M A
NM
Donnelly
J Peter
JP
D000293:Adolescent; D000328:Adult; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D007781:Lactoferrin; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D010919:Placebos / Q000008:administration & dosage; D000637:Transaminases / Q000097:blood; D055815:Young Adult
D000890:Anti-Infective Agents; D010446:Peptide Fragments; D010919:Placebos; C466658:lactoferrin (1-11), human; D000637:Transaminases; D007781:Lactoferrin