PMID- 19049340
OWN - NLM
STAT- MEDLINE
DCOM- 20090716
LR  - 20151119
IS  - 1523-4681 (Electronic)
IS  - 0884-0431 (Linking)
VI  - 24
IP  - 4
DP  - 2009 Apr
TI  - Single-dose, randomized, double-blind, placebo-controlled study of ACE-011 
      (ActRIIA-IgG1) in postmenopausal women.
PG  - 744-52
LID - 10.1359/jbmr.081208 [doi]
AB  - The effects of ACE-011 on safety, pharmacokinetics, and bone biomarkers were 
      evaluated in healthy, postmenopausal women. Our data indicate that ACE-011 
      results in a sustained increase in biomarkers of bone formation and reduction in 
      markers of bone resorption. The activin type IIA receptor (ActRIIA) is the 
      high-affinity receptor for activin. ACE-011 is a dimeric fusion protein 
      consisting of the extracellular domain of the human ActRIIA linked to the Fc 
      portion of human IgG1. ACE-011 binds to activin, preventing activin from binding 
      endogenous receptors. A randomized, double-blind, placebo-controlled study was 
      conducted to evaluate the safety and tolerability of ACE-011. Forty-eight 
      healthy, postmenopausal women were randomized to receive either a single dose of 
      ACE-011 or placebo and were followed for 4 mo. Dose levels ranged from 0.01 to 
      3.0 mg/kg intravenously and from 0.03 to 0.1 mg/kg subcutaneously. Safety and 
      pharmacokinetic (PK) analyses and the biological activity of ACE-011, as assessed 
      by markers of bone turnover, and follicle stimulating hormone (FSH) levels were 
      measured. No serious adverse events (AEs) were reported. AEs were generally mild 
      and transient. The PK of ACE-011 was linear over the dose range studied, with a 
      mean half-life of 24-32 days. The absorption after subcutaneous dosing was 
      essentially complete. ACE-011 caused a rapid and sustained dose-dependent 
      increase in serum levels of bone-specific alkaline phosphatase (BSALP) and a 
      dose-dependent decrease in C-terminal type 1 collagen telopeptide (CTX) and 
      TRACP-5b levels. There was also a dose-dependent decrease in serum FSH levels 
      consistent with inhibition of activin. ACE-011 is a novel agent with biological 
      evidence of both an increase in bone formation and a decrease in bone resorption. 
      ACE-011 may be an effective therapy in a variety of diseases involving bone loss.
FAU - Ruckle, Jon
AU  - Ruckle J
AD  - Covance Clinical Research, Honolulu, Hawaii, USA.
FAU - Jacobs, Mark
AU  - Jacobs M
FAU - Kramer, William
AU  - Kramer W
FAU - Pearsall, Amelia E
AU  - Pearsall AE
FAU - Kumar, Ravindra
AU  - Kumar R
FAU - Underwood, Kathryn W
AU  - Underwood KW
FAU - Seehra, Jasbir
AU  - Seehra J
FAU - Yang, Yijun
AU  - Yang Y
FAU - Condon, Carolyn H
AU  - Condon CH
FAU - Sherman, Matthew L
AU  - Sherman ML
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Bone Miner Res
JT  - Journal of bone and mineral research : the official journal of the American 
      Society for Bone and Mineral Research
JID - 8610640
RN  - 0 (ACE-011)
RN  - 0 (Biomarkers)
RN  - 0 (Placebos)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 9002-68-0 (Follicle Stimulating Hormone)
SB  - IM
MH  - Aged
MH  - Biomarkers/metabolism
MH  - Bone Resorption/metabolism
MH  - Demography
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Female
MH  - Follicle Stimulating Hormone/blood
MH  - Humans
MH  - Injections, Intravenous
MH  - Injections, Subcutaneous
MH  - Middle Aged
MH  - Osteogenesis/drug effects
MH  - Placebos
MH  - Postmenopause/blood/*drug effects
MH  - Recombinant Fusion Proteins/*administration & dosage/adverse 
      effects/pharmacokinetics/*pharmacology
EDAT- 2008/12/04 09:00
MHDA- 2009/07/17 09:00
CRDT- 2008/12/04 09:00
PHST- 2008/12/04 09:00 [pubmed]
PHST- 2009/07/17 09:00 [medline]
PHST- 2008/12/04 09:00 [entrez]
AID - 10.1359/jbmr.081208 [doi]
PST - ppublish
SO  - J Bone Miner Res. 2009 Apr;24(4):744-52. doi: 10.1359/jbmr.081208.