Date: 2017-09-20
Type of
information: Initiation of the trial
phase: 1b
Announcement: initiation of the trial
Company: Poxel (France)
Product: PXL770
Action
mechanism:
- AMPK activator. PXL770 is a first-in-class direct adenosine monophosphate-activated protein kinase (AMPK) activator, a key enzyme in energy metabolism acting as an energy sensor regulating glucose and lipid levels. Based on this central role, targeting AMPK offers the opportunity to pursue a wide range of indications to treat chronic metabolic diseases, including diseases that affect the liver, such as NASH, as well as type 2 diabetes and diabetes-related complications, such as diabetic nephropathy.
Disease: type 2 diabetes
Therapeutic
area: Metabolic diseases
Country:
Trial
details:
Latest
news:
- • On September 20, 2017, Poxel announced that it has initiated a phase 1b multiple ascending dose trial for PXL770 and subjects have been dosed. The trial will include up to 76 subjects and evaluate the safety, tolerability and pharmacokinetics of PXL770 in at least four dose groups. Completion of the trial is anticipated in early 2018.
- In the PXL770 Phase 1a study, safety, tolerability and pharmacokinetics of six single ascending oral doses of PXL770 were assessed in 64 healthy male subjects. The results demonstrated that PXL770 exhibited a favorable safety and tolerability profile with no serious adverse events reported nor safety signals. Pharmacokinetic assessment showed that PXL770 plasma exposure (Cmax and AUC) increased in a dose dependent manner following oral administration with moderate inter-individual variability.
- • On September 12, 2016, Poxel presented its results for the first half of 2016 ended June 30, 2016, and provided a corporate update. The company announced that it will present new PXL770 data at the upcoming 2016 EASD meeting. These data show effect on de novo lipid synthesis and on weight and fat mass loss in an animal model of diabetes and obesity. Poxel announced in June 2016 that results from the first part of the study indicate that PXL770 exhibits a favorable safety and tolerability profile with no serious adverse events reported or safety signal.
During the Phase 1 study, Poxel observed a different metabolic pattern in humans compared to animals that were treated with PXL770. Therefore, based on regulatory guidelines, Poxel will need to further evaluate the profile of the metabolites, which may be pharmacologically active, prior to the start of the second part of the Phase 1 study. As a result of this additional preclinical work, the second part of the Phase 1b study will be delayed until 2017.
- • On June 20, 2016, Poxel announced positive results from the single ascending dose stage, which is the first stage of the ongoing PXL770 Phase 1 clinical trial. In the first part of the study, safety, tolerability and pharmacokinetics of six single ascending oral doses of PXL770 were assessed in 64 healthy male subjects. Overall, the results indicate that PXL770 exhibits a favorable safety and tolerability profile with no serious adverse events reported nor safety signals. Pharmacokinetic assessment showed that PXL770 plasma exposure (Cmax and AUC) increased in a dose dependent manner following oral administration with moderate inter-individual variability. The second part of the trial is on track and will assess safety, tolerability, pharmacokinetics and target engagement of multiple ascending doses. Poxel presented the first preclinical data on PXL770 at the World Congress on Insulin Resistance, Diabetes and Cardiovascular Diseases in Los Angeles last November, demonstrating that PXL770 significantly improves glucose tolerance, lipid profile as well as liver weight in a type 2 diabetes mouse model. Together, the results highlight the potential of PXL770 as a novel oral agent for the treatment of type 2 diabetic patients with added benefits on lipid abnormalities.
Is
general: Yes
