Date: 2012-11-02
Type of information: Presentation of results at a congress
phase: 1
Announcement: presentation of phase 1 data at Kidney Week 2012, the annual meeting of the American Society of Nephrology
Company: Genkyotex (Switzerland)
Product: GKT137831
Action
mechanism: GKT137831 is a first in class inhibitor targeting NOX1 and NOX4 enzymes. NOX enzymes exist in seven isoforms and produce reactive oxygen species (ROS). ROS can cause tissue damage and modify biological pathways that may be important in a number of pathologies, including metabolic, cardiovascular, pulmonary and neurological diseases. In the kidney, NOX4 is the most abundantly expressed NOX enzyme and even further upregulated in diabetic nephropathy. The causal role of NOX enzymes in diabetic complications is well recognised. NOX4 plays a key role in glomerular damage and kidney fibrosis, which lead to albuminuria and end-stage renal disease, respectively. NOX1 is also involved in angiogenesis, atherosclerosis and other diabetic co-morbidities, making the inhibition of both the NOX1 and NOX4 enzymes by GKT137831, an attractive therapeutic option for this hard to treat and growing global disease. This competitive therapeutic profile of GKT137831 has been validated in several animal models of diabetic nephropathy.
Disease: diabetic nephropathy
Therapeutic area: Metabolic diseases - Renal diseases - Kidney diseases
Country:
Trial
details: The Phase I study initially involves the oral administration of single ascending doses of GKT137831 to 36 healthy volunteers. This will be followed by a multiple ascending dose study where GKT137831 will be administered orally for 10 consecutive days.
Latest
news: * On November 2, 2012, Genkyotex, a developer of NOX inhibitors to treat oxygen-radical mediated diseases, has announced that Phase I studies have demonstrated excellent safety and tolerability following single and multiple oral doses of GKT137831, the first in class NOX 1 and 4 inhibitor. In addition, GKT137831 demonstrated a favourable pharmacokinetic profile in these subjects.
These data were presented at Kidney Week 2012, the annual meeting of the American Society of Nephrology. GKT137831 was found to be safe and well tolerated when administered orally to a total of 72 healthy adult males, at single doses of up to1800 mg OD, and at multiple doses of up to 900 mg OD for 10 days. No safety signals were identified, and dose limiting toxicities were not reached. Orally administered GKT137831 is rapidly absorbed and has a broadly dose proportional PK over the 10-900 mg dose range. Multiple dose administration does not modify the PK of GKT137831 and there is no accumulation.
* On June 22, 2012, Genkyotex has announced the successful completion of a Phase Ia study with GKT137831, a first in class inhibitor targeting NOX1 and NOX4 enzymes. The results show that GKT137831 is safe and well tolerated following oral administration of single doses in 36 healthy subjects. Pharmacokinetic analysis demonstrates good dose proportional exposure to GKT137831 and confirms that once or twice a day oral dosing is a suitable regimen for further studies. A multiple dose Phase Ib study is currently underway.
GKT137831 is being evaluated initially for the treatment of diabetic nephropathy. However, preclinical studies conducted in multiple in vivo models suggest it may have application in a broad range of indications, including other fibrotic diseases.
* On October 31, 2011, GenKyoTex has announced that a Phase I study has been initiated with GKT137831, a first in class dual inhibitor of NOX1 and NOX4 enzymes. GKT137831 is being developed for the treatment of diabetic nephropathy. The company has started dosing healthy volunteers. Now Genkyotex aims to start Phase II studies in diabetic nephropathy before the end of 2012.
