PMID- 29531784
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220317
IS  - 2056-5933 (Print)
IS  - 2056-5933 (Electronic)
IS  - 2056-5933 (Linking)
VI  - 4
IP  - 1
DP  - 2018
TI  - Pharmacodynamic and pharmacokinetic effects and safety of verinurad in 
      combination with allopurinol in adults with gout: a phase IIa, open-label study.
PG  - e000584
LID - 10.1136/rmdopen-2017-000584 [doi]
LID - e000584
AB  - OBJECTIVES: Verinurad (RDEA3170) is a high affinity, selective uric acid 
      transporter (URAT1) inhibitor indevelopment for treating gout and asymptomatic 
      hyperuricaemia. This phase IIa study evaluated the pharmacodynamics, 
      pharmacokinetics and safety of verinurad combined with allopurinol versus 
      allopurinol alone in adults with gout. METHODS: Forty-one subjects were 
      randomised into two cohorts of verinurad (2.5-20 mg) plus allopurinol (300 mg 
      once daily) versus allopurinol 300 mg once daily, 600 mg once daily or 300 mg 
      twice daily alone. Each treatment period was 7 days. Serial plasma/serum and 
      urine samples were assayed for verinurad, allopurinol, oxypurinol and uric acid. 
      RESULTS: Serum pharmacodynamic data pooled across cohorts demonstrated maximum 
      per cent decreases in serum urate (sUA) from baseline (E(max)) at 7-12 hours 
      after verinurad plus allopurinol treatment. Combination treatment decreased sUA 
      in dose-dependent manner: least-squares means E(max) was 47%, 59%, 60%, 67%, 68% 
      and 74% for verinurad doses 2.5, 5, 7.5, 10, 15 and 20 mg plus allopurinol 300 mg 
      once daily, versus 40%, 54% and 54% for allopurinol 300 mg once daily, 600 mg 
      once daily and 300 mg twice daily. Verinurad had no effect on allopurinol plasma 
      pharmacokinetics, but decreased oxypurinol C(max) by 19.0%-32.4% and area under 
      the plasma concentration-time curve from time zero to the last measurable time 
      point by 20.8%-39.2%. Verinurad plus allopurinol was well tolerated with no 
      serious adverse events (AEs), AE-related withdrawals or renal-related events. 
      Laboratory values showed no clinically meaningful changes. CONCLUSION: Verinurad 
      coadministered with allopurinol produced dose-dependent decreases in sUA. All 
      dose combinations of verinurad and allopurinol were generally well tolerated. 
      These data support continued investigation of oral verinurad in patients with 
      gout. TRIAL REGISTRATION NUMBER: NCT02498652.
FAU - Fleischmann, Roy
AU  - Fleischmann R
AD  - Metroplex Clinical Research Center, University of Texas, SW Medical Center, 
      Dallas, Texas, USA.
FAU - Winkle, Peter
AU  - Winkle P
AD  - Anaheim Clinical Trials, Anaheim, California, USA.
FAU - Miner, Jeffrey N
AU  - Miner JN
AD  - Ardea Biosciences, San Diego, California, USA.
FAU - Yan, Xiaohong
AU  - Yan X
AD  - Ardea Biosciences, San Diego, California, USA.
FAU - Hicks, Liz
AU  - Hicks L
AD  - Ardea Biosciences, San Diego, California, USA.
FAU - Valdez, Shakti
AU  - Valdez S
AD  - Ardea Biosciences, San Diego, California, USA.
FAU - Hall, Jesse
AU  - Hall J
AD  - Ardea Biosciences, San Diego, California, USA.
FAU - Liu, Sha
AU  - Liu S
AD  - Metroplex Clinical Research Center, University of Texas, SW Medical Center, 
      Dallas, Texas, USA.
AD  - Anaheim Clinical Trials, Anaheim, California, USA.
AD  - Ardea Biosciences, San Diego, California, USA.
AD  - AstraZeneca LP, Gaithersburg, Maryland, USA.
AD  - QPS MRA (Miami Clinical Research), Miami, Florida, USA.
FAU - Shen, Zancong
AU  - Shen Z
AD  - Ardea Biosciences, San Diego, California, USA.
FAU - Gillen, Michael
AU  - Gillen M
AD  - AstraZeneca LP, Gaithersburg, Maryland, USA.
FAU - Hernandez-Illas, Martha
AU  - Hernandez-Illas M
AD  - QPS MRA (Miami Clinical Research), Miami, Florida, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT02498652
PT  - Journal Article
DEP - 20180208
PL  - England
TA  - RMD Open
JT  - RMD open
JID - 101662038
PMC - PMC5845419
OTO - NOTNLM
OT  - gout
OT  - pharmacokinetics
OT  - treatment
COIS- Competing interests: RF received a clinical study grant from Ardea Biosciences. 
      PW is a full-time employee of Anaheim Clinical Trials. JNM, XY, LH, SV, JH, SL 
      and ZS are/were full-time employees of Ardea Biosciences, a member of the 
      AstraZeneca Group. MG is a full-time employee of AstraZeneca. MHI reports no 
      conflict of interest.
EDAT- 2018/03/14 06:00
MHDA- 2018/03/14 06:01
PMCR- 2018/02/08
CRDT- 2018/03/14 06:00
PHST- 2017/09/21 00:00 [received]
PHST- 2017/12/22 00:00 [revised]
PHST- 2017/12/29 00:00 [accepted]
PHST- 2018/03/14 06:00 [entrez]
PHST- 2018/03/14 06:00 [pubmed]
PHST- 2018/03/14 06:01 [medline]
PHST- 2018/02/08 00:00 [pmc-release]
AID - rmdopen-2017-000584 [pii]
AID - 10.1136/rmdopen-2017-000584 [doi]
PST - epublish
SO  - RMD Open. 2018 Feb 8;4(1):e000584. doi: 10.1136/rmdopen-2017-000584. eCollection 
      2018.