Pharmacokinetics refers to how a medication is absorbed, distributed, metabolized, and eliminated from the body.
VI-0106 is a soft gel formulation of tacrolimus, an immunosuppressant under development by Vivus for the treatment of PAH.
Originally approved by the U.S. Food and Drug Administration in 1994 to lower the risk of rejection during kidney transplants, tacrolimus is now used in other organ transplant settings and for dermatitis (skin inflammation).
Unlike currently available treatments for PAH, VI-0106 aims to address the underlying cause of the disease. The drug works as an immunosuppressant by increasing the signaling of the BMPR2 pathway, which is dysfunctional in PAH patients and associated with disease worsening.
The U.K.-based Phase 1 study evaluated the effectiveness of VI-0106 in healthy volunteers. In the first part of the trial, 16 participants were given single doses of three different VI-0106 prototypes with at least a 10-day gap between each administration.
Following the last dose, an interim analysis was conducted to identify the prototype formulation with the best pharmacokinetic profile. The effects of eating and fasting conditions was also examined for the selected prototype.
In the second part of the study, 12 healthy volunteers received a single daily dose of the selected prototype formulation. Researchers studied the participant’s pharmacokinetic steady-state parameters; pharmacokinetic steady-state is reached when the amount of drug administered is the same as the amount eliminated by the body.
“The positive Phase 1 data from this study of VI-0106 in healthy volunteers support continued evaluation of this investigational candidate in PAH patients,” John Amos, CEO of Vivus, said in a press release.
“Data from this study demonstrate that once-daily dosing of VI-0106 may facilitate maintenance of the low tacrolimus concentrations required for the treatment of PAH with minimal monitoring of drug levels,” added Santosh T. Varghese, MD, chief medical officer of Vivus.
A previous Phase 2a study (NCT01647945) using a different formulation of tacrolimus demonstrated the safety and effectiveness of the medication in PAH patients. Also, compassionate use of an approved formulation of VI-0106 in three PAH patients resulted in fewer hospitalizations and improvements in disease status.
Based on these results, the company believes that VI-0106 has the potential to become an important new PAH therapy.
Vivus plans to seek FDA fast track and breakthrough therapy status for VI-0106 as a PAH treatment. This would allow the company to expedite the drug’s development and review.