This study seeks to understand if the medication pramipexole improves social connectedness and functioning in adults (ages 18-50) who experience anxiety or depression. The study plans to enroll 108 participants total across two sites (University of California San Diego and New York State Psychiatric Institute). Pramipexole will be given in a 6-week randomized, double-blind, placebo-controlled trial. Social reward processing will be assessed using measures of brain function (fMRI), behavior, and self-report at baseline and week 6. Knowledge gained from this study will help determine the therapeutic potential of targeting the dopamine system to remediate social disconnection as an anxiety and depression intervention.

Start Date13 May 2024

Sponsor / Collaborator

University of California San Diego

[+2]

CTR20232945 / CompletedNot Applicable

盐酸普拉克索片在中国健康受试者中单中心、随机、开放、单次给药、两制剂、两周期交叉人体生物等效性试验

[Translation] A single-center, randomized, open-label, single-dose, two-formulation, two-period crossover bioequivalence study of pramipexole hydrochloride tablets in healthy Chinese subjects

主要研究目的：以植恩生物技术股份有限公司生产的盐酸普拉克索片（规格：0.25mg）为受试制剂（T），按有关生物等效性试验的规定，以持证商为Boehringer Ingelheim International GmbH的盐酸普拉克索片（规格：0.25mg，商品名：森福罗®）为参比制剂（R）进行生物等效性试验。次要研究目的：观察受试制剂和参比制剂盐酸普拉克索片在健康受试者中的安全性。

[Translation]

The main purpose of the study was to use pramipexole hydrochloride tablets (specification: 0.25 mg) produced by Zhien Biotechnology Co., Ltd. as the test preparation (T), and pramipexole hydrochloride tablets (specification: 0.25 mg, trade name: Senforo®) produced by Boehringer Ingelheim International GmbH as the reference preparation (R) for bioequivalence testing according to the relevant provisions of bioequivalence testing. Secondary purpose of the study was to observe the safety of the test preparation and the reference preparation pramipexole hydrochloride tablets in healthy subjects.

Start Date19 Oct 2023

Sponsor / Collaborator

Chongqing Zhi'en Pharmaceutical Co., Ltd.

CTR20231566 / CompletedNot Applicable

盐酸普拉克索缓释片在中国健康受试者中单中心、随机、开放、单次给药、两制剂、两周期交叉人体生物等效性试验

[Translation] A single-center, randomized, open-label, single-dose, two-formulation, two-period crossover bioequivalence study of pramipexole hydrochloride extended-release tablets in healthy Chinese subjects

主要研究目的：以植恩生物技术股份有限公司生产的盐酸普拉克索缓释片（0.375mg）为受试制剂（T），按有关生物等效性试验的规定，以 Boehringer Ingelheim Pharma GmbH & Co.KG 生产的盐酸普拉克索缓释片（0.375mg）为参比制剂（R）进行生物等效性试验。次要研究目的：观察受试制剂和参比制剂盐酸普拉克索缓释片在健康受试者中的安全性。

[Translation]

Main research purpose: The pramipexole hydrochloride extended-release tablets (0.375 mg) produced by Zhien Biotechnology Co., Ltd. were used as the test preparation (T), and according to the relevant provisions of the bioequivalence test, the pramipexole hydrochloride extended-release tablets (0.375 mg) produced by Boehringer Ingelheim Pharma GmbH & Co.KG were used as the reference preparation (R) for bioequivalence test. Secondary research purpose: Observe the safety of the test preparation and the reference preparation pramipexole hydrochloride extended-release tablets in healthy subjects.

Start Date25 May 2023

Sponsor / Collaborator

Chongqing Zhi'en Pharmaceutical Co., Ltd.

100 Clinical Results associated with Pramipexole Dihydrochloride

100 Translational Medicine associated with Pramipexole Dihydrochloride

100 Patents (Medical) associated with Pramipexole Dihydrochloride

1,433

Literatures (Medical) associated with Pramipexole Dihydrochloride

01 Dec 2024·Molecular biology reports

Oxidative stress in Alzheimer’s disease: current knowledge of signaling pathways and therapeutics

Review

Author: Sharma, Prajjwal ; Singh, Sunil K ; Dhapola, Rishika ; HariKrishnaReddy, Dibbanti ; Beura, Samir K

Alzheimer's disease's pathophysiology is still a conundrum. Growing number of evidences have elucidated the involvement of oxidative stress in the pathology of AD rendering it a major target for therapeutic development. Reactive oxygen species (ROS) generated by altered mitochondrial function, dysregulated electron transport chain and other sources elevate aggregated Aβ and neurofibrillary tangles which further stimulating the production of ROS. Oxidative stress induced damage to lipids, proteins and DNA result in neuronal death which leads to AD. In addition, oxidative stress induces apoptosis that is triggered by the modulation of ERK1/2 and Nrf2 pathway followed by increased GSK-3β expression and decreased PP2A activity. Oxidative stress exaggerates disease condition by interfering with various signaling pathways like RCAN1, CREB/ERK, Nrf2, PP2A, NFκB and PI3K/Akt. Studies have reported the role of TNF-α in oxidative stress stimulation that has been regulated by drugs like etanercept increasing the level of anti-oxidants. Other drugs like pramipexole, memantine, carvedilol, and melatonin have been reported to activate CREB/RCAN1 and Nrf2 pathways. In line with this, epigallocatechin gallate and genistein also target Nrf2 and CREB pathway leading to activation of downstream pathways like ARE and Keap1 which ameliorate oxidative stress condition. Donepezil and resveratrol reduce oxidative stress and activate AMPK pathway along with PP2A activation thus promoting tau dephosphorylation and neuronal survival. This study describes in detail the role of oxidative stress in AD, major signaling pathways involving oxidative stress induced AD and drugs under development targeting these pathways which may aid in therapeutic advances for AD.

01 Feb 2024·Biological psychiatry

Pramipexole Enhances Reward Learning by Preserving Value Estimates

Article

Author: Geddes, John G ; Harmer, Catherine J ; Halahakoon, Don Chamith ; Kaltenboeck, Alexander ; Cowen, Philip ; Browning, Michael ; Martens, Marieke

BACKGROUND:

Dopamine D₂-like agonists show promise as treatments for depression. They are thought to act by enhancing reward learning; however, the mechanisms by which they achieve this are not clear. Reinforcement learning accounts describe 3 distinct candidate mechanisms: increased reward sensitivity, increased inverse decision-temperature, and decreased value decay. As these mechanisms produce equivalent effects on behavior, arbitrating between them requires measurement of how expectations and prediction errors are altered. We characterized the effects of 2 weeks of the D₂-like agonist pramipexole on reward learning and used functional magnetic resonance imaging measures of expectation and prediction error to assess which of these 3 mechanistic processes were responsible for the behavioral effects.

METHODS:

Forty healthy volunteers (50% female) were randomized to 2 weeks of pramipexole (titrated to 1 mg/day) or placebo in a double-blind, between-subject design. Participants completed a probabilistic instrumental learning task before and after the pharmacological intervention, with functional magnetic resonance imaging data collected at the second visit. Asymptotic choice accuracy and a reinforcement learning model were used to assess reward learning.

RESULTS:

Pramipexole increased choice accuracy in the reward condition with no effect on losses. Participants who received pramipexole had increased blood oxygen level-dependent response in the orbital frontal cortex during the expectation of win trials but decreased blood oxygen level-dependent response to reward prediction errors in the ventromedial prefrontal cortex. This pattern of results indicates that pramipexole enhances choice accuracy by reducing the decay of estimated values during reward learning.

CONCLUSIONS:

The D₂-like receptor agonist pramipexole enhances reward learning by preserving learned values. This is a plausible mechanism for pramipexole's antidepressant effect.

01 Feb 2024·Movement disorders : official journal of the Movement Disorder Society

A Randomized Phase 3 Study Comparing P2B001 to its Components (Low‐Dose Extended‐Release Rasagiline and Pramipexole) and to Optimized Doses of Marketed Extended‐Release Pramipexole in Early Parkinson's Disease

Article

Author: Kieburtz, Karl ; Hauser, Robert A ; Kreitzman, David L ; de Marcaida, Joy Antonelle ; Burdick, Daniel J ; McGarry, Andrew ; Gil, Ramon A ; Olanow, C Warren ; Elmer, Lawrence W ; Dhall, Rohit

Abstract:

Background:

There remains uncertainty as to the optimal way to initiate therapy for Parkinson's disease (PD) to maximize benefit and minimize adversity.

Objectives:

The objective was to determine if P2B001 (a fixed, low‐dose, extended‐release [ER] combination of pramipexole 0.6 mg and rasagiline 0.75 mg) is superior to each of its components and compare its safety and efficacy to optimized treatment with marketed doses of pramipexole‐ER.

Methods:

This was a 12‐week, double‐blind study (NCT03329508). Total of 544 untreated patients with PD were randomized (2:2:2:1) to treatment with P2B001, its individual components (pramipexole‐ER 0.6 mg or rasagiline‐ER 0.75 mg), or commercial doses of pramipexole‐ER titrated to optimal dose (1.5–4.5 mg). The primary endpoint was change from baseline to week 12 in Unified Parkinson's Disease Rating Scale (UPDRS) parts II and III. The key secondary endpoint was the change from baseline in the Epworth Sleepiness Scale (ESS) for P2B001 versus the titrated dose of pramipexole‐ER.

Results:

P2B001 provided superior efficacy compared to each of its components; mean (95% CI) treatment differences in UPDRS II + III scores were −2.66 (95% CI, −4.33 to −1.00) versus pramipexole‐ER 0.6 mg (P = 0.0018) and − 3.30 (95% CI, −4.96 to −1.63) versus rasagiline‐ER 0.75 mg (P < 0.0001). P2B001 had comparable efficacy with the titrated dose of pramipexole‐ER (mean, 3.2 mg), but significantly less worsening in daytime‐sleepiness (ESS treatment difference: −2.66 [95% CI, −3.50 to −1.81]; P < 0.0001). P2B001 was well‐tolerated with fewer sleep‐related and dopaminergic adverse events than titrated doses of pramipexole‐ER including somnolence, orthostatic hypotension, and neuropsychiatric side effects.

Conclusions:

P2B001 had superior efficacy to its individual components and was comparable with commercially used doses of pramipexole‐ER with less worsening of sleepiness and fewer dopaminergic adverse events. These findings support considering once‐daily P2B001 as initial therapy for patients with early PD. © 2023 International Parkinson and Movement Disorder Society.

News (Medical) associated with Pramipexole Dihydrochloride

16 May 2024

·www.sciencedaily.com

New gene delivery vehicle shows promise for human brain gene therapy

In an important step toward more effective gene therapies for brain diseases, researchers have engineered a gene-delivery vehicle that uses a human protein to efficiently cross the blood-brain barrier and deliver a disease-relevant gene to the brain in mice expressing the human protein. Because the vehicle binds to a well-studied protein in the blood-brain barrier, the scientists say it has a good chance at working in patients. In an important step toward more effective gene therapies for brain diseases, researchers from the Broad Institute of MIT and Harvard have engineered a gene-delivery vehicle that uses a human protein to efficiently cross the blood-brain barrier and deliver a disease-relevant gene to the brain in mice expressing the human protein. Because the vehicle binds to a well-studied protein in the blood-brain barrier, the scientists say it has a good chance at working in patients. Gene therapy could potentially treat a range of severe genetic brain disorders, which currently have no cures and few treatment options. But FDA-approved forms of the most commonly used vehicle for packaging and delivering these therapies to target cells, adeno-associated viruses (AAVs), aren't able to efficiently cross the blood-brain barrier at high levels and deliver therapeutic cargo. The enormous challenge of getting therapies past this barrier -- a highly selective membrane separating the blood from the brain -- has stymied the development of safer and more effective gene therapies for brain diseases for decades. Now researchers in the lab of Ben Deverman, an institute scientist and senior director of vector engineering at the Broad, have engineered the first published AAV that targets a human protein to reach the brain in humanized mice. The AAV binds to the human transferrin receptor, which is highly expressed in the blood-brain barrier in humans. In a new study published in Science, the team showed that their AAV, when injected into the bloodstream in mice expressing a humanized transferrin receptor, crossed into the brain at much higher levels than the AAV that is used in an FDA-approved gene therapy for the central nervous system, AAV9. It also reached a large fraction of important types of brain cells, including neurons and astrocytes. The researchers then showed that their AAV could deliver copies of the GBA1 gene, which has been linked to Gaucher's disease, Lewy body dementia, and Parkinson's disease, to a large fraction of cells throughout the brain. The scientists add that their new AAV could be a better option for treating neurodevelopmental disorders caused by mutations in a single gene such as Rett syndrome or SHANK3 deficiency; lysosomal storage diseases like GBA1deficiency; and neurodegenerative diseases such as Huntington's disease, prion disease, Friedreich's ataxia, and single-gene forms of ALS and Parkinson's disease. "Since we came to the Broad we've been focused on the mission of enabling gene therapies for the central nervous system," said Deverman, senior author on the study. "If this AAV does what we think it will in humans based on our mouse studies, it will be so much more effective than current options." "These AAVs have the potential to change a lot of patients' lives," said Ken Chan, a co-first author on the paper and group leader from Deverman's group who has been working on solving gene delivery to the central nervous system for nearly a decade. Mechanism first For years, researchers developed AAVs for specific applications by preparing massive AAV libraries and testing them in animals to identify top candidates. But even when this approach succeeds, the candidates often don't work in other species, and the approach doesn't provide information about how the AAVs reach their targets. This can make it difficult to translate a gene therapy using these AAVs from animals to humans. To find a delivery vehicle with a greater chance of reaching the brain in people, Deverman's team switched to a different approach. They used a method they published last year, which involves screening a library of AAVs in a test tube for ones that bind to a specific human protein. Then they test the most promising candidates in cells and mice that have been modified to express the protein. As their target, the researchers chose human transferrin receptor, which has long been the target of antibody-based therapies that aim to reach the brain. Several of these therapies have shown evidence of reaching the brain in humans. The team's screening technique identified an AAV called BI-hTFR1 that binds human transferrin receptor, enters human brain cells, and bypasses a human cell model of the blood-brain barrier. "We've learned a lot from in vivo screens but it has been tough finding AAVs that worked this well across species," added Qin Huang, a co-first author on the study and a senior research scientist in Deverman's lab who helped develop the screening method to find AAVs that bind specific protein targets. "Finding one that works using a human receptor is a big step forward." Beyond the dish To test the AAVs in animals, the researchers used mice in which the mouse gene that encodes the transferrin receptor was replaced with its human equivalent. The team injected the AAVs into the bloodstream of adult mice and found dramatically higher levels of the AAVs in the brain and spinal cord compared to mice without the human transferrin receptor gene, indicating that the receptor was actively ferrying the AAVs across the blood-brain barrier. The AAVs also showed 40-50 times higher accumulation in brain tissue than AAV9, which is part of an FDA-approved therapy for spinal muscular atrophy in infants but is relatively inefficient at delivering cargo to the adult brain. The new AAVs reached up to 71 percent of neurons and 92 percent of astrocytes in different regions of the brain. In work led by research scientist Jason Wu, Deverman's team also used the AAVs to deliver healthy copies of the human GBA1 gene, which is mutated in several neurological conditions. The new AAVs delivered 30 times more copies of the GBA1 gene than AAV9 in mice and were delivered throughout the brain. The team said that the new AAVs are ideal for gene therapy because they target a human protein and have similar production and purification yields as AAV9 using scalable manufacturing methods. A biotech company co-founded by Deverman, Apertura Gene Therapy, is already developing new therapies using the AAVs to target the central nervous system. With more development, the scientists think it's possible to improve the gene-delivery efficiency of their AAVs to the central nervous system, decrease their accumulation in the liver, and avoid inactivation by antibodies in some patients. Sonia Vallabh and Eric Minikel, two researchers at the Broad who are developing treatments for prion disease, are excited by the potential of the AAVs to deliver brain therapies in humans. "When we think about gene therapy for a whole-brain disease like prion disease, you need really systemic delivery and broad biodistribution in order to achieve anything," said Minikel. "Naturally occurring AAVs just aren't going to get you anywhere. This engineered capsid opens up a world of possibilities."

Gene Therapy

09 Nov 2023

·www.biospace.com

Pharma Two B Announces Publication of Positive Phase 3 Study Results of P2B001, an Investigational Treatment for Early Parkinson’s Disease, in Movement Disorders

Demonstrated that P2B001 provides benefits comparable with commercially used doses of marketed pramipexole-ER (PramiER) while minimizing associated daytime sleep–related and dopaminergic side effects associated P2B001 provided superior efficacy on motor symptoms and activities of daily living, compared to each of its individual components The convenient dosing of P2B001, as a no-titration, once-daily single pill, may be a valuable option for patients, neurologists, and particularly non-specialists who are often the only physicians treating PD patients REHOVOT, Israel, Nov. 09, 2023 (GLOBE NEWSWIRE) -- Pharma Two B Ltd., a private, late-stage pharmaceutical company, today announced that data from a Phase 3 study evaluating P2B001, a fixed, low-dose extended-release (ER) combination of pramipexole 0.6 mg and rasagiline 0.75 mg, were published in Movement Disorders. Results from the international, multicenter, randomized, double-blind parallel-group study evaluated the safety and efficacy of P2B001 in patients with early Parkinson’s disease compared to its components and to commercial doses of the dopamine agonist pramipexole (mean 3.2 mg per day). The study included 544 untreated patients with Parkinson’s disease who were randomized (2:2:2:1) to treatment with P2B001, its individual components (pramipexole-ER 0.6 mg or rasagiline-ER 0.75 mg), or marketed PramiER individually titrated to optimal dose (1.5-4.5 mg). “The present study demonstrates that each component contributes to the benefits of P2B001, and that it provides benefits comparable to commercially used doses of Pramipexole ER but with a reduced frequency of sleep-related and dopaminergic adverse events," said C. Warren Olanow, M.D., FRCPC, Chairman Emeritus of the Department of Neurology and Professor Emeritus in the Department of Neuroscience at the Mount Sinai School of Medicine in New York City. Further, he stated that “P2B001 is a once-a-day treatment that requires no titration. As such, if approved, P2B001 represents an important consideration for initiating treatment in patients with early PD.” “P2B001 represents a novel and easy-to-use therapeutic approach, as there has been a clear unmet need for a once-daily treatment that has demonstrable efficacy and safety, requires no titration and has a lower incidence of excessive daytime sleepiness, a commonly reported side effect among people with PD, often caused by dopamine agonist treatment,1-3” said Robert Hauser, M.D., M.B.A., Director, Parkinson’s Disease & Movement Disorders Center, University of South Florida. The primary endpoint was change from baseline to week 12 in Unified Parkinson’s Disease Rating Scale (UPDRS) parts II and III comparing P2B001 to its individual components. The key secondary endpoint was the change from baseline to week 12 in the Epworth Sleepiness Scale (ESS) for P2B001 versus the titrated dose of commercially available PramiER. The change from baseline in total UPDRS (primary endpoint) showed that P2B001 was significantly superior to each of its individual components demonstrating that each contributed to the P2B001 benefit. Least squares mean (LSM) (standard error) treatment difference between P2B001 and pramipexole ER (PPX-ER 0.6 mg) was –2.66 ± 0.85 points (p = 0.0018), and between P2B001 and rasagiline ER (RAS-ER 0.75 mg) was –3.30 + 0.85 points (p = 0.0001). The change from baseline to week 12 in total UPDRS score between P2B001 and PramiER (individually titrated to optimal dose; mean, 3.2 mg/day) was not significantly different (–8.35 ± 0.86 vs. 7.98 ± 0.60; p = 0.7197). Analysis of the key secondary endpoint (change from baseline to week 12 in the ESS score) demonstrated no worsening in the sleepiness scale with P2B001 treatment, whereas optimized doses of PramiER (mean dose, 3.2 mg) caused significant worsening in ESS. LSM difference between groups was –2.66 ± 0.43 (p < 0.0001). P2B001 was generally well tolerated and showed fewer sleep-related and dopaminergic adverse events in comparison to commercially used doses of pramipexole ER. "We are grateful to the patients, families and clinicians who have contributed to this study as we look to deliver a new, convenient treatment option for patients with early Parkinson’s disease,” said Dan Teleman, CEO of Pharma Two B. “We look forward to moving P2B001 forward towards an NDA submission to make this potential treatment option available to patients.” About P2B001 P2B001 is an investigational, novel, fixed-dose, extended-release combination of pramipexole and rasagiline (0.6 mg/0.75 mg), both at low doses that are not commercially available. Marketed pramipexole and rasagiline are currently indicated for the treatment of Parkinson’s disease (as monotherapy and adjunct therapy for early and more advanced patients). P2B001 is being developed for potential use as a first-line therapy for people with Parkinson’s disease. Extended release rasagiline is a new and proprietary formulation of rasagiline developed by Pharma Two B. Pharma Two B owns worldwide-granted patents for both pharmaceutical composition and method of treatment with P2B001, which are expected to remain in effect until January 2033. About Pharma Two B Pharma Two B is a private, late-stage pharmaceutical company established in 2008 in Rehovot, Israel. Our mission is to improve patients’ quality of life by developing innovative, value-added combination drugs for neurological disorders, with a clear unmet need, that are based on previously approved oral drugs and that may offer meaningful clinical benefits, as well as improved safety and enhanced convenience through easier administration. Our company is led by a highly experienced team in Parkinson’s disease, supported by top-tier scientific and clinical key opinion leaders and backed by a dedicated group of investors. For more information, please visit: . Forward-Looking Statements Some of the statements made herein constitute forward-looking statements. These statements relate to future financial and other performance or anticipated plans and are identified by words such as “will,” “expect,” “could,” “if,” “expected,”” “anticipate,”” look forward,” “believe,” “potential,” “propose” and “continue” or negative variants of such terms. These and similar forward-looking statements discuss the company’s future expectations and plans. The company operates in a very competitive and rapidly changing environment. New risks emerge from time to time. Given these risks and uncertainties, the company cautions against placing undue reliance on these forward-looking statements. These statements are only estimates of future performance. Actual performance or events may not meet such expectations or estimates and may, in fact, differ materially. Although the company believes that the expectations reflected in the forward-looking statements made herein are reasonable, the company cannot and does not guarantee future results, levels of activity, performance or achievements. Moreover, the company does not assume any responsibility for the accuracy and completeness of such forward-looking statements in the future. The company does not plan and, subject to applicable law, undertakes no obligation to update any of the forward-looking statements made herein after the date hereof in order to conform such statements to actual results. Amara AW, Chahine LM, Caspell-Garcia C, et al. Longitudinal assessment of excessive daytime sleepiness in early Parkinson’s disease. JNeurol Neurosurg Psychiatry. 2017;88(8):653-662. doi:10.1136/jnnp-2016-31502 Suzuki K. Current update on clinically relevant sleep issues in Parkinson’s disease: a narrative review. J Parkinsons Dis. 2021;11(3):971-992. doi: 10.3233/JPD-202425 Avorn J, Schneeweiss S, Sudarsky LR, et al. Sudden uncontrollable somnolence and medication use in Parkinson disease. Arch Neurol. 2005;62(8):1242-1248. doi: 10.1001/archneur.62.8.1242 CONTACT INFORMATION Dan Teleman CEO Pharma Two B Ltd. Cell + 972-54-550-0804 Email: dan@pharma2b.com U.S. media contact: Cali Mangel Director Cell: 215-694-1577 Email: Cali.Mangel@calciumco.com

Clinical ResultPhase 3

28 Aug 2023

·www.globenewswire.com

Pharma Two B to Present Additional Phase 3 Positive Results of P2B001, a once-daily, fixed-dose combination of low-dose pramipexole and low-dose rasagiline, at 2023 International Congress of Parkinson’s Disease and Movement Disorders®

Sub-group analyses of patients with early Parkinson's disease (PD) at different age groups or baseline disease severities who were treated with P2B001 showed consistently greater symptomatic control versus its components (pramipexole 0.6 mg and rasagiline 0.75 mg) and comparable efficacy to currently marketed, optimally titrated, extended-release pramipexoleData analysis also showed P2B001 to be consistently superior to currently marketed, optimally titrated, extended-release pramipexole on the Epworth Sleepiness Scale (ESS) score, which is especially important for younger people with PD leading active lives and for older people who typically cannot tolerate dopamine agonist side effects such as excessive daytime sleepiness (EDS) REHOVOT, Israel, Aug. 28, 2023 (GLOBE NEWSWIRE) -- Pharma Two B, a private, late-stage pharmaceutical company, today announced that sub-group analysis results from the Phase 3 pivotal clinical trial evaluating P2B001 are being presented at the 2023 The International Parkinson and Movement Disorder Society® annual meeting, August 27-31, in Copenhagen, Denmark. The data are being presented as a poster presentation on Monday, August 28. In all subgroups, the results demonstrate greater symptomatic benefit of P2B001 versus its components, and comparable efficacy with currently marketed, optimally titrated, extended-release pramipexole, yet with reduced EDS. EDS is a commonly reported side effect among people with PD, which often worsens with dopamine agonist therapy1: The efficacy and safety profile of P2B001 was not significantly different in younger versus older patients (<66 vs >66 years), nor when patients were analyzed by baseline severity (≤29 vs >29 Total-Unified Parkinson’s Disease Rating Scale (UPDRS) score).Across all subgroups, P2B001 provided numerically greater symptomatic benefit versus its components, as assessed by Total-UPDRS, and statistically significant greater benefit in Activities of Daily Living (UPDRS Part II) versus components.Across all subgroups, P2B001 provided comparable symptomatic efficacy versus currently marketed, optimally titrated, extended-release pramipexole.P2B001 was consistently superior to extended-release pramipexole across all subgroups on ESS scores. In the full study cohort, there was significantly less daytime sleepiness compared to extended-release pramipexole at 12 weeks (-2.66 points; p≤0.001). “This study's findings, demonstrating greater symptomatic benefits of P2B001 as compared to its individual components in patients of all ages and disease severities, support the potential usage of P2B001 in patients with early PD. Moreover, the data showed comparable efficacy to the established extended release pramipexole regimen titrated to optimal dosage, exemplifying a potential approach to optimizing patient care, while challenging traditional paradigms,” says Drew Falconer, M.D., of the Inova Parkinson’s and Movement Disorders Center, and a trial investigator. Dan Teleman, CEO of Pharma Two B, adds, “We are encouraged by the consistency of the Phase 3 trial's sub-group analyses. They reinforce our commitment to advancing P2B001 and improving the lives of people with Parkinson's disease.” About the Study The international, multicenter, randomized, double-blind, parallel-group study in adult patients (35-80 years old) with early, untreated PD (<3 years from diagnosis) compared once-daily P2B001 with its individual components, as well as to optimally titrated, extended-release pramipexole (mean dose of 3.2 mg). A total of 544 participants were enrolled and randomized into the study. The primary endpoint was change from baseline to Week 12 in Total-UPDRS score (sum of Parts II and III) comparing P2B001 to its individual components. The key (first) secondary endpoint was the change from baseline to Week 12 in the ESS score comparing P2B001 to the optimized dosage of extended-release pramipexole. For the current analyses, subgroups were categorized by age (< median of 66 years vs > median of 66 years) and baseline severity ( median of 29 of Total-UPDRS (Part II+III scores)). The data are consistent with the positive Phase 3 topline efficacy and safety results presented previously, reemphasizing the potential of P2B001, if approved, to offer a new treatment approach for people with early PD, despite their age. About P2B001 P2B001 is an investigational, novel, fixed-dose, extended-release combination of pramipexole and rasagiline (0.6 mg/0.75 mg), both at low doses that are not commercially available. Marketed pramipexole and rasagiline are currently indicated for the treatment of Parkinson’s disease (as monotherapy and adjunct therapy for early and more advanced patients). P2B001 is being developed for potential use as a first-line therapy for people of all ages with PD. Extended-release rasagiline is a new and proprietary formulation of rasagiline developed by Pharma Two B. Pharma Two B owns worldwide-granted patents for P2B001 for both pharmaceutical composition and method of treatment, which are expected to remain in force until January 2033. About Pharma Two BPharma Two B is a private, venture-backed, late-stage pharmaceutical company established in 2008 in Rehovot, Israel. Our mission is to improve patients’ quality of life by developing innovative, value-added combination drugs for neurological disorders with a clear unmet need, that are based on previously approved oral drugs and that offer meaningful clinical benefits, as well as improved safety and enhanced convenience through easier administration. The company is led by a team highly experienced in PD, supported by top-tier scientific and clinical key opinion leaders, and backed by a dedicated group of investors. For more information, please visit: www.pharma2b.com. Forward Looking StatementsSome of the statements made herein constitute forward-looking statements. These statements relate to future financial and other performance or anticipated plans and are identified by words such as “will,” “expect,” “could,” “if,” “expected,” “anticipate,” ”look forward,” “believe,” “potential,” “propose,” and “continue,” or negative variants of such terms. These and similar forward-looking statements discuss the company’s future expectations and plans. The company operates in a very competitive and rapidly changing environment. New risks emerge from time to time. Given these risks and uncertainties, the company cautions against placing undue reliance on these forward-looking statements. These statements are only estimates of future performance. Actual performance or events may not meet such expectations or estimates and may, in fact, differ materially. Although the company believes that the expectations reflected in the forward-looking statements made herein are reasonable, the company cannot and does not guarantee future results, levels of activity, performance, or achievements. Moreover, the company does not assume any responsibility for the accuracy and completeness of such forward-looking statements in the future. The company does not plan and, subject to applicable law, undertakes no obligation to update any of the forward-looking statements made herein after the date hereof in order to conform such statements to actual results. 1 Amara et al, J Neurol Neurosurg Psychiatry, 2017; Suzuki, J Park Dis, 2021; Avorn et al, Arch Neurol, 2005. Contact:Dan TelemanCEOPharma Two B Ltd.Cell. + 972-54-550-0804email: dan@pharma2b.com www.pharma2b.com U.S. media contact:Cali MangelAssociate DirectorCali.Mangel@calciumusa.com 215-694-1577

Clinical ResultPhase 3

100 Deals associated with Pramipexole Dihydrochloride

External Link

KEGG	Wiki	ATC	Drug Bank
D00559	Pramipexole Dihydrochloride	N04BC05	DB00413

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Restless Legs Syndrome	EU	Boehringer Ingelheim International GmbH	13 Oct 1997
Restless Legs Syndrome	IS	Boehringer Ingelheim International GmbH	13 Oct 1997
Restless Legs Syndrome	LI	Boehringer Ingelheim International GmbH	13 Oct 1997
Restless Legs Syndrome	NO	Boehringer Ingelheim International GmbH	13 Oct 1997
Parkinson Disease	US	Boehringer Ingelheim GmbH	01 Jul 1997

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Tourette Syndrome	Phase 3	US	Boehringer Ingelheim GmbH	01 May 2008
Tourette Syndrome	Phase 3	DE	Boehringer Ingelheim GmbH	01 May 2008
Young onset Parkinson disease	Phase 3	US	Boehringer Ingelheim GmbH	01 May 2007
Young onset Parkinson disease	Phase 3	JP	Boehringer Ingelheim GmbH	01 May 2007
Young onset Parkinson disease	Phase 3	AR	Boehringer Ingelheim GmbH	01 May 2007
Young onset Parkinson disease	Phase 3	AT	Boehringer Ingelheim GmbH	01 May 2007
Young onset Parkinson disease	Phase 3	CZ	Boehringer Ingelheim GmbH	01 May 2007
Young onset Parkinson disease	Phase 3	FI	Boehringer Ingelheim GmbH	01 May 2007
Young onset Parkinson disease	Phase 3	DE	Boehringer Ingelheim GmbH	01 May 2007
Young onset Parkinson disease	Phase 3	HU	Boehringer Ingelheim GmbH	01 May 2007

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


Biospace Manual	Phase 3	Parkinson Disease First line	544	P2B001	rnokgymrly(ccwtkjrfpu) = zfchxnnddp qfbllwrjtn (piqqdtytdc, 0.86)	Positive	09 Nov 2023
				pramipexole	-
AAN2023	Phase 3	Parkinson Disease	519	P2B001	pjargdsddi(haqfrcynin) = ukbulajvyu qhjbjbpkao (ecnswqlciq ) View more	Positive	25 Apr 2023
				Pramipexole-ER-0.6mg (PPX)	pjargdsddi(haqfrcynin) = dzmnxcogdy qhjbjbpkao (ecnswqlciq ) View more
S32.010 (AAN2023)	Not Applicable	Parkinson Disease	-	P2B001 (low dose combination of extended-release pramipexole and rasagiline)	iufmjgbuas(onbmmirxqm) = ezsyiigjqz rfitduchlv (lxdqdviiym ) View more	-	25 Apr 2023
				Extended-Release pramipexole (Prami-ER)	iufmjgbuas(onbmmirxqm) = sqznmcgozu rfitduchlv (lxdqdviiym ) View more
NCT03521635 (CTgov)	Phase 4	Parkinson Disease	98	Pramipexole (Pramipexole Sustained Release)	abdpokabij(dlcjrvjxoy) = pjyzlceanx sdumqyavqb (dzuqigbolf, iqugdkjzfp - pjojnaahuu) View more	-	16 Feb 2021
				Pramipexole (Pramipexole Immediate Release)	abdpokabij(dlcjrvjxoy) = xrhaiolpzo sdumqyavqb (dzuqigbolf, mqmsgaqiml - nqyylqpscq) View more
NCT02397837 (PRAM-BD, CTgov)	Phase 4	Behcet Syndrome \| Bipolar Disorder	103	Pramipexole (Pramipexole)	grrrivdymk(jlelkdvjse) = resnnmfgho zmreohffux (vrisdrwdsd, mhonpqpikt - wqszkxudzr) View more	-	28 Feb 2020
				Placebo (Placebo)	grrrivdymk(jlelkdvjse) = ziabfkhpqe zmreohffux (vrisdrwdsd, eezsnfbxcd - bbtrqwdjsu) View more
NCT03765138 (CTgov)	Phase 3	Stress Disorders, Post-Traumatic \| Depressive Disorder, Major \| Depression	1	PE/Pramipexole	ajoqopvdnq(ttdxiufjrt) = rugstegeks vshjcgcufx (dtlktfjonx, yomyapyysc - qcmyndzilu) View more	-	26 Nov 2019
MDS2017	Not Applicable	D3 receptor -	-	PPX	hoemryylmb(fhbyluhqmd) = hcwusskyqa czixytqmpu (zwifecnyub ) View more	-	04 Jun 2017
Pubmed \| J Sleep Res	Not Applicable	Sleep Bruxism	-	Pramipexole	mgabtydulf(zxrgbhvxzd) = uezbotaocz wobyfwfbfh (bdafonzlfb )	-	01 Feb 2017
				pramipexole	mgabtydulf(zxrgbhvxzd) = bnbyzvhydn wobyfwfbfh (bdafonzlfb )
NCT00144300 (Pubmed \| Parkinsons Dis) Manual	Phase 4	Parkinson Disease	246	pramipexole	egflhgnxis(mijfsfvlpj): RR = 1.07 (95% CI, 0.71 - 1.60)	Negative	01 Jan 2016
				ropinirole
NCT01470859 (CTgov)	Not Applicable	Young onset Parkinson disease	30	Sinemet CR (Levodopa)	diicoafguk(chdyvmumqp) = idqgxnqehy qwqlpcpwst (tacywqcmhy, ahhjsatgxu - blvjflmvwb) View more	-	21 Oct 2015
				pramipexole (Pramipexole)	diicoafguk(chdyvmumqp) = rgoowcotjs qwqlpcpwst (tacywqcmhy, qvvhjxveqj - ffzmpppsxm) View more

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