PMID- 28573777
OWN - NLM
STAT- MEDLINE
DCOM- 20180720
LR  - 20180803
IS  - 1463-1326 (Electronic)
IS  - 1462-8902 (Linking)
VI  - 19
IP  - 12
DP  - 2017 Dec
TI  - Once-weekly administration of a long-acting fibroblast growth factor 21 analogue 
      modulates lipids, bone turnover markers, blood pressure and body weight 
      differently in obese people with hypertriglyceridaemia and in non-human primates.
PG  - 1762-1772
LID - 10.1111/dom.13023 [doi]
AB  - AIMS: To assess the safety, tolerability, pharmacokinetics and pharmacodynamics 
      of PF-05231023, a long-acting fibroblast growth factor 21 (FGF21) analogue, in 
      obese people with hypertriglyceridaemia on atorvastatin, with or without type 2 
      diabetes. METHODS: Participants received PF-05231023 or placebo intravenously 
      once weekly for 4 weeks. Safety (12-lead ECGs, vital signs, adverse events [AEs], 
      laboratory tests) and longitudinal weight assessments were performed. Blood 
      samples were collected for pharmacokinetic and pharmacodynamic analyses. 
      Cardiovascular safety studies were also conducted in telemetered rats and 
      monkeys. Blood pressure (BP; mean, systolic and diastolic) and ECGs were 
      monitored. RESULTS: A total of 107 people were randomized. PF-05231023 
      significantly decreased mean placebo-adjusted fasting triglycerides (day 25, 
      33%-43%) and increased HDL cholesterol (day 25, 15.7%-28.6%) and adiponectin (day 
      25, 1574 to 3272 ng/mL) across all doses, without significant changes in body 
      weight (day 25, -0.45% to -1.21%). Modest decreases from baseline were observed 
      for N-terminal propeptides of type 1 collagen (P1NP) on day 25, although 
      C-telopeptide cross-linking of type 1 collagen (CTX-1) increased minimally. 
      Systolic, diastolic BP, and pulse rate increased in a dose- and time-related 
      manner. There were 5 serious AEs (one treatment-related) and no deaths. Three 
      participants discontinued because of AEs. The majority of AEs were 
      gastrointestinal. PF-05231023 increased BP and heart rate in rats, but not in 
      monkeys. CONCLUSIONS: Once-weekly PF-05231023 lowered triglycerides markedly in 
      the absence of weight loss, with modest changes in markers of bone homeostasis. 
      This is the first report showing increases in BP and pulse rate in humans and 
      rats after pharmacological administration of a long-acting FGF21 molecule.
CI  - (c) 2017 John Wiley & Sons Ltd.
FAU - Kim, Albert M
AU  - Kim AM
AD  - Pfizer Inc., Cambridge, Massachusetts, USA.
FAU - Somayaji, Veena R
AU  - Somayaji VR
AD  - Pfizer Inc., Cambridge, Massachusetts, USA.
FAU - Dong, Jennifer Q
AU  - Dong JQ
AD  - Pfizer Inc., Cambridge, Massachusetts, USA.
FAU - Rolph, Timothy P
AU  - Rolph TP
AD  - Pfizer Inc., Cambridge, Massachusetts, USA.
FAU - Weng, Yan
AU  - Weng Y
AD  - Pfizer Inc., Cambridge, Massachusetts, USA.
FAU - Chabot, Jeffrey R
AU  - Chabot JR
AD  - Pfizer Inc., Cambridge, Massachusetts, USA.
FAU - Gropp, Kathryn E
AU  - Gropp KE
AD  - Pfizer Inc., Groton, Connecticut, USA.
FAU - Talukdar, Saswata
AU  - Talukdar S
AD  - Pfizer Inc., Cambridge, Massachusetts, USA.
FAU - Calle, Roberto A
AU  - Calle RA
AD  - Pfizer Inc., Cambridge, Massachusetts, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT01673178
PT  - Comparative Study
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20170721
PL  - England
TA  - Diabetes Obes Metab
JT  - Diabetes, obesity & metabolism
JID - 100883645
RN  - 0 (Anti-Obesity Agents)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Biomarkers)
RN  - 0 (Delayed-Action Preparations)
RN  - 0 (Hypolipidemic Agents)
RN  - 0 (PF-05231023)
RN  - 62031-54-3 (Fibroblast Growth Factors)
SB  - IM
MH  - Animals
MH  - Anti-Obesity Agents/administration & dosage/adverse 
      effects/pharmacokinetics/*therapeutic use
MH  - Antibodies, Monoclonal, Humanized/administration & dosage/adverse 
      effects/pharmacokinetics/*therapeutic use
MH  - Biomarkers/blood
MH  - Body Mass Index
MH  - Bone Remodeling/*drug effects
MH  - Delayed-Action Preparations/administration & dosage/adverse 
      effects/pharmacokinetics/therapeutic use
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Drug Administration Schedule
MH  - Drug Resistance
MH  - Female
MH  - Fibroblast Growth Factors/administration & dosage/adverse 
      effects/pharmacokinetics/*therapeutic use
MH  - Follow-Up Studies
MH  - Half-Life
MH  - Humans
MH  - Hypertension/chemically induced/physiopathology
MH  - Hypertriglyceridemia/blood/complications/*drug therapy
MH  - Hypolipidemic Agents/administration & dosage/adverse 
      effects/pharmacokinetics/*therapeutic use
MH  - Infusions, Intravenous
MH  - Male
MH  - Middle Aged
MH  - Obesity/blood/complications/*drug therapy
MH  - Severity of Illness Index
MH  - Species Specificity
OTO - NOTNLM
OT  - IGF-1
OT  - blood pressure
OT  - bone biomarkers
OT  - fibroblast growth factor 21
OT  - heart rate
OT  - type 2 diabetes
EDAT- 2017/06/03 06:00
MHDA- 2018/07/22 06:00
CRDT- 2017/06/03 06:00
PHST- 2016/10/31 00:00 [received]
PHST- 2017/05/24 00:00 [revised]
PHST- 2017/05/25 00:00 [accepted]
PHST- 2017/06/03 06:00 [pubmed]
PHST- 2018/07/22 06:00 [medline]
PHST- 2017/06/03 06:00 [entrez]
AID - 10.1111/dom.13023 [doi]
PST - ppublish
SO  - Diabetes Obes Metab. 2017 Dec;19(12):1762-1772. doi: 10.1111/dom.13023. Epub 2017 
      Jul 21.