PMID- 17473917
OWN - NLM
STAT- MEDLINE
DCOM- 20071203
LR  - 20220410
IS  - 0031-6970 (Print)
IS  - 0031-6970 (Linking)
VI  - 63
IP  - 7
DP  - 2007 Jul
TI  - Safety, pharmacokinetics and pharmacodynamics of atacicept in healthy volunteers.
PG  - 647-56
AB  - OBJECTIVE: Atacicept, a recombinant fusion protein, blocks the activity of BLyS 
      (a B-lymphocyte stimulator) and APRIL (a proliferation-inducing ligand) and may 
      be a potential treatment for B-cell-mediated diseases. This study assesses the 
      safety, pharmacokinetics (PK) and pharmacodynamics (PD) of atacicept. METHODS: In 
      this Phase I study, healthy male volunteers received a single subcutaneous dose 
      of atacicept (2.1, 70, 210 or 630 mg) or placebo and were monitored over 7 weeks 
      for injection-site pain, local tolerability, vital signs, echocardiography, 
      haematology, coagulation, blood chemistry, serum virology, urinalysis and PK/PD 
      markers [lymphocyte cell counts, BLyS-atacicept complex, immunoglobulin G (IgG), 
      IgM]. RESULTS: Atacicept was well tolerated at all doses (n = 23). There were no 
      clinically significant changes in vital signs or laboratory parameters during the 
      study. Treatment-emergent adverse events (AEs) were mainly mild or moderate in 
      severity, and all were transient, resolving without any clinical sequelae. There 
      was no evidence of any relationship between atacicept dose and the incidence of 
      AEs. Local tolerability was good. Serum atacicept peaked 16 h after dosing, and 
      the area under the concentration-time curve increased in an approximately 
      dose-related manner. The 70-, 210- and 630-mg doses of atacicept demonstrated a 
      dose-dependent biological effect on IgM levels, which was apparent up to 210 days 
      post-dose. There were no treatment-related effects on IgG levels or lymphocyte 
      subpopulations. CONCLUSIONS: These results showed that single subcutaneous doses 
      of atacicept were well tolerated in healthy volunteers, demonstrated non-linear 
      PK and were biologically active, according to IgM levels.
FAU - Munafo, Alain
AU  - Munafo A
AD  - Merck Serono S.A., 9 Chemin des Mines, Geneva 1202, Switzerland. 
      alain.munafo@merckserono.net
FAU - Priestley, Anthony
AU  - Priestley A
FAU - Nestorov, Ivan
AU  - Nestorov I
FAU - Visich, Jennifer
AU  - Visich J
FAU - Rogge, Mark
AU  - Rogge M
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070501
PL  - Germany
TA  - Eur J Clin Pharmacol
JT  - European journal of clinical pharmacology
JID - 1256165
RN  - 0 (B-Cell Activating Factor)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (TNFSF13 protein, human)
RN  - 0 (Tumor Necrosis Factor Ligand Superfamily Member 13)
RN  - K3D9A0ICQ3 (TACI receptor-IgG Fc fragment fusion protein)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Area Under Curve
MH  - B-Cell Activating Factor/*antagonists & inhibitors
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Humans
MH  - Injections, Subcutaneous
MH  - Male
MH  - Middle Aged
MH  - Recombinant Fusion Proteins/administration & dosage/*adverse 
      effects/*pharmacokinetics
MH  - Tumor Necrosis Factor Ligand Superfamily Member 13/*antagonists & inhibitors
EDAT- 2007/05/03 09:00
MHDA- 2007/12/06 09:00
CRDT- 2007/05/03 09:00
PHST- 2007/01/23 00:00 [received]
PHST- 2007/04/02 00:00 [accepted]
PHST- 2007/05/03 09:00 [pubmed]
PHST- 2007/12/06 09:00 [medline]
PHST- 2007/05/03 09:00 [entrez]
AID - 10.1007/s00228-007-0311-7 [doi]
PST - ppublish
SO  - Eur J Clin Pharmacol. 2007 Jul;63(7):647-56. doi: 10.1007/s00228-007-0311-7. Epub 
      2007 May 1.