Transition Therapeutics (NASDAQ:TTHI; TSX:TTH) has reported positive results from two Phase 1 clinical studies of its neuropsychiatric drug candidate ELND005.
The studies were an absorption metabolism excretion (AME) study and a renal clearance study. They are specialized clinical pharmacology trials that are required by the FDA for the approval of most drugs in development.
The AME study enrolled eight subjects and the renal clearance study enrolled 42 subjects. In both studies, ELND005 showed good safety and tolerability.
The key result of the AME study was that ELND005 showed good oral bioavailability as there was nearly 100% absorption. ELND005 showed no evidence of hepatic or intermediary metabolism and the study demonstrated that the main excretion route of ELND005 is via the kidney.
AME properties of good oral bioavailability, low protein binding, and lack of CYP metabolism are usually associated with consistent plasma levels and with a reduced risk of drug-drug interactions.
The AME profile of ELND005 is well suited for an Alzheimer’s disease (AD) patient population that is commonly administered multiple concomitant medications, many of which are metabolized by the liver.
The renal clearance study evaluated the pharmacokinetic profile of ELND005 in subjects with various degrees of renal impairment. In the study, ELND005 showed minimal protein binding in plasma regardless of renal function. Across the five study arms, subjects with worse renal function had increased plasma drug exposure, compared with those with normal renal function.
The study provided important guidance for the minimum creatinine clearance needed to allow patient participation in studies with a fixed dose regimen of ELND005. This minimum creatinine clearance is consistent with the threshold used as exclusion criterion in the ongoing Harmony study of ELND005 in agitation and aggression of AD.
“The informative results from these studies together with the thorough QT study results reported last November, showing no QTc prolongation, are supportive of the suitability of ELND005 in the elderly AD population,” chairman and CEO, Dr. Tony Cruz, said in a statement.
The studies are part of a comprehensive package of data being complied by subsidiary, Transition Therapeutics Ireland, to advance ELND005 toward regulatory approval, he added.