PMID- 24242902
OWN - NLM
STAT- MEDLINE
DCOM- 20141112
LR  - 20211021
IS  - 1573-0646 (Electronic)
IS  - 0167-6997 (Print)
IS  - 0167-6997 (Linking)
VI  - 32
IP  - 2
DP  - 2014 Apr
TI  - Safety, tolerability, and pharmacokinetics of the novel alphav-integrin antibody EMD 
      525797 (DI17E6) in healthy subjects after ascending single intravenous doses.
PG  - 347-54
LID - 10.1007/s10637-013-0038-5 [doi]
AB  - PURPOSE: We evaluated the safety, tolerability, and pharmacokinetics (PK) of EMD 
      525797 (DI17E6), a humanized monoclonal antibody targeting alphav-integrins, in 
      healthy subjects. METHODS: In this first-in-human, double-blind, 
      placebo-controlled, randomized Phase 1 study, healthy male volunteers were 
      consecutively assigned to 6 ascending single-dose cohorts of 35, 100, 250, 500, 
      1000, or 1500 mg. Per dose cohort, EMD 525797 or placebo was administered over 1 
      h as an intravenous 250-mL infusion to 6 and 3 volunteers, respectively. 
      Escalation to the next dose level was based on evaluation of safety, 
      tolerability, and PK data. RESULTS: Fifty-five subjects (aged 18-45 years) were 
      randomized. Twenty-seven of 37 (73 %) subjects receiving EMD 525797 reported a 
      total of 61 adverse events (AEs), including 38 events (in 17 subjects) considered 
      by the investigator to be treatment related. A total of 35 AEs were reported by 
      14 of 18 (78 %) placebo-treated subjects. The most commonly occurring AEs were 
      gastrointestinal disorders, abnormal laboratory values, and increased or 
      decreased biochemistry and/or hematology values, as well as headaches, which 
      occurred at a slightly higher frequency in the EMD 525797 group compared with 
      placebo. There were no serious AEs or deaths. EMD 525797 PK appeared to be dose 
      dependent, especially at lower doses. CONCLUSION: Ascending single doses of EMD 
      525797 were shown to be safe and well tolerated. No safety concerns were 
      identified. This study supports the ongoing investigation of EMD 525797.
FAU - Uhl, Wolfgang
AU  - Uhl W
AD  - Merck KGaA, CPPK (Clinical Pharmacology & Pharmacokinetics), Frankfurter Str. 
      250, 64293, Darmstadt, Germany, Wolfgang.Uhl@merckgroup.com.
FAU - Zuhlsdorf, Michael
AU  - Zuhlsdorf M
FAU - Koernicke, Thomas
AU  - Koernicke T
FAU - Forssmann, Ulf
AU  - Forssmann U
FAU - Kovar, Andreas
AU  - Kovar A
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20131119
PL  - United States
TA  - Invest New Drugs
JT  - Investigational new drugs
JID - 8309330
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Integrin alphaV)
RN  - 724QD330RD (Abituzumab)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Antibodies, Monoclonal, Humanized/*administration & dosage/adverse 
      effects/pharmacokinetics
MH  - Antineoplastic Agents/*administration & dosage/adverse effects/pharmacokinetics
MH  - Double-Blind Method
MH  - Healthy Volunteers
MH  - Humans
MH  - Infusions, Intravenous
MH  - Integrin alphaV/*immunology
MH  - Male
MH  - Middle Aged
MH  - Young Adult
PMC - PMC3945639
EDAT- 2013/11/19 06:00
MHDA- 2014/11/13 06:00
PMCR- 2013/11/19
CRDT- 2013/11/19 06:00
PHST- 2013/09/12 00:00 [received]
PHST- 2013/10/07 00:00 [accepted]
PHST- 2013/11/19 06:00 [entrez]
PHST- 2013/11/19 06:00 [pubmed]
PHST- 2014/11/13 06:00 [medline]
PHST- 2013/11/19 00:00 [pmc-release]
AID - 38 [pii]
AID - 10.1007/s10637-013-0038-5 [doi]
PST - ppublish
SO  - Invest New Drugs. 2014 Apr;32(2):347-54. doi: 10.1007/s10637-013-0038-5. Epub 
      2013 Nov 19.