PMID- 24327173
OWN - NLM
STAT- MEDLINE
DCOM- 20150610
LR  - 20211021
IS  - 1179-190X (Electronic)
IS  - 1173-8804 (Print)
IS  - 1173-8804 (Linking)
VI  - 28
IP  - 3
DP  - 2014 Jun
TI  - Safety and pharmacokinetics of escalating doses of human recombinant nerve growth 
      factor eye drops in a double-masked, randomized clinical trial.
PG  - 275-83
LID - 10.1007/s40259-013-0079-5 [doi]
AB  - BACKGROUND AND OBJECTIVES: Nerve growth factor (NGF) is a neurotrophin with 
      therapeutic possibilities that extend from the nervous system to the eye. We 
      tested the safety, maximal tolerated dose, pharmacokinetics, and antigenicity of 
      a novel human recombinant NGF (rhNGF) eye-drop formulation in a phase I study. 
      METHODS: This prospective, randomized, double-masked, vehicle-controlled trial, 
      sponsored by Dompe SpA (registered as NCT01744704 at ClinicalTrials.gov), 
      enrolled 74 healthy volunteers (24 females, 50 males, age 40.2 +/- 11.8 years). 
      Subjects were randomized in three cohorts to receive (1) a single eye-drop 
      containing 0.0175, 0.175, or 0.7 mug rhNGF; (2) a single ascending dose of rhNGF 
      eye drops three times a day for 1 day (total daily dose 2.1, 6.3, or 18.9 mug), or 
      vehicle; or (3) a multiple ascending dose of rhNGF eye drops three times a day 
      for 5 days (total dose 10.5, 31.5, or 94.5 mug), or vehicle. Outcome measures 
      included blood chemistry, urinalyses, vital signs, electrocardiograms (ECGs), 
      serum NGF antibodies, ocular and systemic adverse events (AEs), visual acuity, 
      tear function, intraocular pressure, fundus oculi, and ocular symptoms. RESULTS: 
      Administration of rhNGF eye drops did not result in a significant increase of 
      circulating NGF levels and no antidrug antibodies were detected in serum. No 
      serious AEs were recorded, and a few mild, transient ocular AEs related to rhNGF 
      administration were reported only at the highest concentration. CONCLUSIONS: 
      rhNGF eye drops were well tolerated, with no detectable clinical evidence of 
      systemic AEs. These results pave the way for the development of clinical trials 
      on rhNGF in ophthalmology.
FAU - Ferrari, Mauro P
AU  - Ferrari MP
AD  - Clinical Development, Dompe s.p.a., Milan, Italy.
FAU - Mantelli, Flavio
AU  - Mantelli F
FAU - Sacchetti, Marta
AU  - Sacchetti M
FAU - Antonangeli, Maria Irene
AU  - Antonangeli MI
FAU - Cattani, Franca
AU  - Cattani F
FAU - D'Anniballe, Gaetano
AU  - D'Anniballe G
FAU - Sinigaglia, Francesco
AU  - Sinigaglia F
FAU - Ruffini, Pier Adelchi
AU  - Ruffini PA
FAU - Lambiase, Alessandro
AU  - Lambiase A
LA  - eng
SI  - ClinicalTrials.gov/NCT01744704
PT  - Clinical Trial
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - New Zealand
TA  - BioDrugs
JT  - BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy
JID - 9705305
RN  - 0 (Nerve Growth Factors)
RN  - 0 (Ophthalmic Solutions)
RN  - 0 (Recombinant Proteins)
SB  - IM
MH  - Adult
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Drug Administration Schedule
MH  - Eye Diseases/drug therapy
MH  - Female
MH  - Humans
MH  - Male
MH  - Nerve Growth Factors/administration & dosage/*adverse effects/*pharmacokinetics
MH  - Ophthalmic Solutions/administration & dosage/*adverse effects/*pharmacokinetics
MH  - Prospective Studies
MH  - Recombinant Proteins/administration & dosage/*adverse effects/*pharmacokinetics
PMC - PMC4030100
EDAT- 2013/12/12 06:00
MHDA- 2015/06/11 06:00
PMCR- 2013/12/11
CRDT- 2013/12/12 06:00
PHST- 2013/12/12 06:00 [entrez]
PHST- 2013/12/12 06:00 [pubmed]
PHST- 2015/06/11 06:00 [medline]
PHST- 2013/12/11 00:00 [pmc-release]
AID - 79 [pii]
AID - 10.1007/s40259-013-0079-5 [doi]
PST - ppublish
SO  - BioDrugs. 2014 Jun;28(3):275-83. doi: 10.1007/s40259-013-0079-5.