Concomitant antidementia drug use does not affect pimavanserin safety, PK profile

In patients with neurodegenerative and/or neurovascular disease (NDD) and dementia-related psychosis (DRP), concomitant antidementia medications (cADMs) used alongside the selective serotonin receptor modulating agent pimavanserin did not adversely impact its safety and pharmacokinetic (PK) profile, according to data presented at AAIC 2021.

cADMs such as acetylcholinesterase inhibitors (AChEIs) or memantine are mostly given to patients with DRP. Pimavanserin, which has gained approval for managing delusions and hallucinations associated with Parkinson’s disease psychosis, is under investigation for managing delusions and hallucinations associated with DRP.

Safety

One study looked into the incidence of treatment-emergent adverse events (TEAEs) in patients with NDD and DRP who are taking cADMs. The team used pooled data from studies comparing pimavanserin 34 mg against placebo in patients with NDD (n=580 and 649, respectively) and data from the phase III HARMONY trial evaluating pimavanserin for DRP. HARMONY included a 12-week open-label phase (OL; n=392) followed by a 26-week double-blind (DB) phase wherein participants either continued pimavanserin or switched to placebo (n=105 and 112, respectively). [AAIC 2021, abstract 57661]

Among pimavanserin-treated patients in the pooled NDD cohort, those who took cADMs (50 percent) had lower rates of TEAEs compared with those without history of cADM use (51 percent vs 57 percent).

In HARMONY, patients on pimavanserin with history of cADM use (70 percent and 77 percent in the OL and DB phases, respectively) also had lower rates of AEs vs those without, both in the OL (32 percent vs 45 percent [TEAEs] and 3 percent vs 9 percent [serious TEAEs]), and DB phases (37 percent vs 54 percent and 4 percent vs 8 percent, respectively).

“[Our findings did not show] evidence that concomitant pimavanserin use resulted in a differential TEAE or serious TEAE profile in patients taking antidementia medications,” said the researchers.

Pharmacokinetic profile

Another study evaluated data from 47 percent of HARMONY participants who reported concomitant AChEI use (eg, donepezil, galantamine, rivastigmine). PK samples were gathered at baseline and at weeks 12, 13, 22, and 38 (or end of treatment). [AAIC 2021, abstract 57479]

Apparent clearance (CL/F) and apparent volume of distribution (V/F) did not show any differences between patients who did and did not have history of AChEI use. AChEI use did not generate a statistically significant effect on CL/F or V/F (α=0.05).

Compared with individuals without history of AChEI use, those who took AChEIs had higher maximum drug concentrations (median C_max, 57.9 vs 53.4 ng/mL) and steady‑state area under the plasma concentration-time curve (median AUC, 1,328.9 and 1,216.5 ng x h/mL). “[However, the] differences in exposure measures between arms were negligible as these were below 10 percent,” said the researchers.

“[As such, our findings imply that] concomitant AChEIs had no clinically relevant effect on the PK parameters of pimavanserin,” they said.