Article ; Online: Pharmacokinetics, Pharmacodynamics, and Tolerability of Concomitant Administration of Verinurad and Febuxostat in Healthy Male Volunteers.
Clinical pharmacology in drug development
2018 Volume 8, Issue 2, Page(s) 179–187
Abstract: Verinurad (RDEA3170) is a selective uric acid reabsorption inhibitor in development for treatment of gout and asymptomatic hyperuricemia. This phase 1, single-blind, multiple-dose, drug-drug interaction study evaluated the pharmacokinetics (PK), ... ...
| Abstract | Verinurad (RDEA3170) is a selective uric acid reabsorption inhibitor in development for treatment of gout and asymptomatic hyperuricemia. This phase 1, single-blind, multiple-dose, drug-drug interaction study evaluated the pharmacokinetics (PK), pharmacodynamics, and safety/tolerability of verinurad in combination with febuxostat in healthy male volunteers. Twenty-three subjects were randomized and received once-daily doses of verinurad (or placebo) or febuxostat alone (days 1-7 and days 15-21), or verinurad + febuxostat on days 8-14. For combinations, subjects received verinurad 10 mg + febuxostat 40 mg or verinurad 2.5 mg + febuxostat 80 mg. Plasma/serum and urine samples were analyzed for verinurad, febuxostat, and uric acid. Safety was assessed by adverse events and laboratory tests. Febuxostat 40 mg had no effect on plasma exposure of verinurad 10 mg, whereas febuxostat 80 mg increased the maximum observed plasma concentration and the area under the plasma concentration-time curve of verinurad 2.5 mg by 25% and 33%, respectively. Verinurad had no effect on febuxostat PK. Maximal reduction in serum urate was 76% with verinurad 10 mg + febuxostat 40 mg versus verinurad 10 mg (56%) or febuxostat 40 mg (49%) alone and was 67% with verinurad 2.5 mg + febuxostat 80 mg versus verinurad 2.5 mg (38%) or febuxostat 80 mg (57%) alone. Verinurad increased, whereas febuxostat decreased, 24-hour fractional excretion and renal clearance of uric acid. There was no clinically significant drug-drug interaction between verinurad and febuxostat PK. The combination resulted in greater reductions of serum urate than either drug alone and was well tolerated at the studied doses. |
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| MeSH term(s) | Adult ; Area Under Curve ; Drug Administration Schedule ; Drug Interactions ; Drug Therapy, Combination ; Febuxostat/administration & dosage ; Febuxostat/adverse effects ; Febuxostat/pharmacokinetics ; Healthy Volunteers ; Humans ; Male ; Middle Aged ; Naphthalenes/administration & dosage ; Naphthalenes/adverse effects ; Naphthalenes/pharmacokinetics ; Propionates/administration & dosage ; Propionates/adverse effects ; Propionates/pharmacokinetics ; Pyridines/administration & dosage ; Pyridines/adverse effects ; Pyridines/pharmacokinetics ; Renal Elimination ; Single-Blind Method ; Uric Acid/urine ; Young Adult |
| Chemical Substances | Naphthalenes ; Propionates ; Pyridines ; Febuxostat (101V0R1N2E) ; verinurad (12WJ62D047) ; Uric Acid (268B43MJ25) |
| Language | English |
| Publishing date | 2018-04-24 |
| Publishing country | United States |
| Document type | Clinical Trial, Phase I ; Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 2649010-9 |
| ISSN | 2160-7648 ; 2160-763X |
| ISSN (online) | 2160-7648 |
| ISSN | 2160-763X |
| DOI | 10.1002/cpdd.463 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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