The investigational mix treatment P2B001 resembled Mirapex (pramipexole) at managing signs of Parkinson’s illness in a scientific trial. But clients treated with P2B001 were less most likely to experience drowsiness and less had orthostatic hypotension (an unexpected drop in high blood pressure on standing) as negative effects.
Lawrence Elmer, MD, PhD from the University of Toledo, provided the trial’s findings at the American Academy of Neurology (AAN) yearly conference, held today practically and in Boston, in a talk entitled, “P2B001 (low dose combination of extended-release pramipexole and rasagiline) versus titrated extended-release pramipexole in the management of early Parkinson’s disease: Exploratory findings from a randomized, controlled trial.”
The research study was moneyed by P2B001’s designer Pharma Two B. The business is preparing to request approval of P2B001 in the U.S. this year, based upon the information.
“We believe the data presented at AAN this year continue to support the development of P2B001 as a potential first-line therapy for people with” Parkinson’s, Dan Teleman, president of Pharma Two B, said in a business news release.
Parkinson’s is marked by low levels of the brain signaling particle dopamine. P2B001 includes a fixed-dose mix of 2 medications in prolonged release form — pramipexole, which imitates dopamine activity in the brain, and rasagiline, which increases dopamine levels by obstructing a protein that generally assists recycle it. Extended release suggests the medication is developed so it’s launched gradually.
Both medications are authorized separately to handle Parkinson’s signs. Pramipexole is marketed by Boehringer Ingelheim as Mirapex; Teva offers rasagiline under the trademark name Azilect.
In animal research studies by Pharma Two B, the mix of the 2 medications revealed synergistic results. “The sum of the parts is much greater than the individual component themselves,” Elmer said, keeping in mind P2B001 includes both treatments at dosages lower than what’s utilized in the single-medication treatments.
Testing P2B001 versus different medications, extended release Mirapex
The business ran a Phase 3 medical trial (NCT033295508) that registered more than 500 individuals with just recently identified Parkinson’s who hadn’t yet started treatment. They were divided into 4 groups and dealt with for 12 weeks, about 3 months.
One group received P2B001 and 2 other groups got pramipexole or rasagiline individually at the exact same dose in the mix treatment. The 4th group was treated with the authorized prolonged release formula of Mirapex. In this group, the dose was changed based upon clients’ reaction and tolerability.
Top-line outcomes, reported in late 2021, revealed P2B001 was more reliable than either of its specific parts at managing signs.
At AAN, Elmer provided a contrast in between the 157 individuals treated with P2B001 and the 77 offered Mirapex.
Demographics and medical attributes in both groups were comparable at the research study’s start. The typical age remained in the early 60s, about two-thirds of clients were male, and more than 95% were white. The typical time in between getting identified with Parkinson’s and getting in the trial had to do with half a year.
At the start, the typical overall rating on the Unified Parkinson’s Disease Rating Scale (UPDRS) — an international procedure of sign intensity in Parkinson’s — had to do with 30 points in both groups. After 12 weeks, the typical rating reduced by about 8 points in both groups, showing less extreme signs. While there was some irregularity in reaction to both medications, about three-quarters of the clients in both groups enhanced by more than 4 points on the motor UPDRS rating.
All in all, both P2B001 and Mirapex revealed “comparable efficacy,” Elmer said, including, for clinicians, the take-home message is “if you see a patient newly diagnosed with Parkinson’s disease, this [P2B001] may be an option if indeed it is approved by the FDA.”
Comparing results on drowsiness
Safety information revealed that noticeably less clients on P2B001 than Mirapex had orthostatic hypotension (2.7% vs. 12.2%) or drowsiness (14.7% vs. 31.1%). Over the 12-week research study, dopamine-related negative effects were considerably less typical with P2B001 (44.7% vs. 66.2%), analytical analyses revealed.
At a different poster at AAN, scientists provided in-depth analyses of the impact of P2B001 on drowsiness, a typical negative effects of dopamine agonists like Mirapex in a poster entitled, “P2B001 significantly reduced risk of daytime sleepiness: results from a randomized controlled phase 3 trial with active pramipexole arm in early Parkinson’s disease (PD).”
Daytime drowsiness was examined with a basic test called the Epworth Sleepiness Scale (ESS). At the start of the research study, the typical ESS rating had to do with 5.5 points in both groups. After 12 weeks, the typical rating had to do with the exact same with P2B001, however increased to more than 8 points with Mirapex, showing more drowsiness.
Most clients (more than 85% in both groups) had ESS ratings of 10 or lower at the start of the research study, which normally shows daytime drowsiness that doesn’t trigger substantial day-to-day issues.
Among those beginning with low ratings, ESS ratings increased past 10 in less than one in 10 (8.5%) of the clients offered P2B001 after 12 weeks of treatment. More than one in 3 (35.7%) clients on Mirapex experienced brand-new substantial drowsiness.
“Patients treated with P2B001 developed significantly less new-onset [excessive daytime sleepiness] and fewer sleepiness-related [side effects],” the scientists said.
“The results of this Phase 3 trial represent positive news for newly diagnosed [Parkinson’s] patients, as there has been a clear unmet need for an initial, once-daily treatment that has demonstrable efficacy and safety, requires no titration, and has a lower incidence of excessive daytime sedation compared to” Mirapex, Elmer said.
Note: The Parkinson’s News Today group is offering protection of the American Academy of Neurology (AAN) 2023 Annual Meeting April 22-27. Go here to see the latest stories from the conference.
