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- | ADX88178 / National Institute on Drug Abuse, Addex, foliglurax (PXT2331) / Lundbeck
Preclinical, Journal: Metabotropic Glutamate Receptor 4 (mGlu4) Positive Allosteric Modulators Lack Efficacy in Rat and Marmoset Models of L-DOPA-Induced Dyskinesia. (Pubmed Central) - Mar 11, 2024
Given the weak efficacy and side-effect profile of amantadine, alternative strategies to reduce glutamate transmission are being investigated...We hypothesized that two mGlu4 positive allosteric modulators, Lu AF21934 ((1?S,2?R)-N1-(3,4-dichlorophenyl)cyclohexane-1,2-dicarboxamide) and ADX88178 (5-Methyl-N-(4-methylpyrimidin-2-yl)-4-(1H-pyrazol-4-yl)thiazol-2-amine), would provide relief in rat and primate models of L-DOPA-induced dyskinesia...This study found no benefit of mGlu4 positive allosteric modulators in tackling L-DOPA-induced dyskinesia. These findings are concordant with the recent failure of foliglurax in phase II clinical trials supporting the predictive validity of these pre-clinical dyskinesia models, while raising further doubt on the anti-dyskinetic potential of mGlu4 positive allosteric modulators.
- ADX88178 / National Institute on Drug Abuse, Addex
Effect of ADX-88178, a highly-selective mGlu4 PAM, on parkinsonism, dyskinesia and psychosis-like behaviours in the MPTP-lesioned marmoset () - Aug 30, 2023 - Abstract #MDSCongress2023MDS_Congress_1487;
These results provide additional evidence of the anti-parkinsonian effect of ADX-88178 as an adjunct to L-DOPA and also indicate that ADX-88178 may alleviate L-DOPA-induced dyskinesia. However, they also suggest that ADX-88178 may not be suitable for PD patients with psychotic manifestations; whether it is a drug-specific or a class effect warrants further investigation.
- | foliglurax (PXT2331) / Lundbeck
Preclinical, Journal: Foliglurax, a positive allosteric modulator of the metabotrophic glutamate receptor 4, protects dopaminergic neurons in MPTP-lesioned male mice. (Pubmed Central) - May 8, 2023
There was a negative correlation between dopamine content and GFAP levels. Our results show that positive allosteric modulation of mGlu4 receptors with foliglurax provided neuroprotective effects in the MPTP mouse model of PD.
- | foliglurax (PXT2331) / Lundbeck
Preclinical, Journal: A positive allosteric modulator of mGlu4 receptors restores striatal plasticity in an animal model of l-Dopa-induced dyskinesia. (Pubmed Central) - Sep 14, 2022
This study aimed to clarify the effects of foliglurax, a selective mGlu4-PAM, on the loss of bidirectional synaptic plasticity associated with l-DOPA-induced dyskinesia (LID)...Moreover, this co-treatment rescued striatal bidirectional plasticity and attenuated the intensity of l-DOPA-induced dyskinesia. This is the first demonstration in an animal model of PD and dyskinesia that a mGlu4 PAM can restore striatal synaptic plasticity.
- | Journal: Clinical investigations of compounds targeting metabotropic glutamate receptors. (Pubmed Central) - Sep 14, 2022
Antagonists of mGlu2/3Rs (decoglurant and TS-161) have been studied in depression where TS-161 has advanced into a planned Phase 2 study in treatment-resistant depression...The mGlu4R potentiator, foliglurax, did not meet its primary endpoint in patients with Parkinson's disease. Ongoing efforts to develop mGluR-targeted compounds continue to promise these glutamate modulators as medicines for psychiatric and neurological disorders.
- || foliglurax (PXT2331) / Lundbeck
Clinical, P2 data, Journal: A Randomized, Double-Blind, Controlled Phase II Study of Foliglurax in Parkinson's Disease. (Pubmed Central) - May 25, 2022
Ongoing efforts to develop mGluR-targeted compounds continue to promise these glutamate modulators as medicines for psychiatric and neurological disorders. There was no evidence in this study that foliglurax has efficacy in improving levodopa-induced motor complications in PD.
- |||| foliglurax (PXT2331) / Lundbeck
A lot of interest in metabotropic glutamate receptor 4 as a target for Parkinson's. Breaking, "there was no evidence that foliglurax improved levodopa-induced motor complications in PD." Approach not dead; only one study, but disappointing! https://t.co/WUbpjErqWA (Twitter) - Feb 27, 2022
- || foliglurax (PXT2331) / Lundbeck
Clinical, Journal: A case study of foliglurax, the first clinical mGluR4 PAM for symptomatic treatment of Parkinson's disease: Translational gaps or a failing industry innovation model? (Pubmed Central) - Mar 18, 2021
Expert opinion: Failure to meet the primary and secondary endpoints in a Phase 2 study led Lundbeck to discontinue the development of foliglurax. Understanding the evidence supporting compound progression into Phase 2 will enable the proper assessment of the therapeutic potential of mGluR4 PAMs.
- carbidopa/levodopa / Generic mfg., isradipine / Generic mfg., foliglurax (PXT2331) / Lundbeck
[VIRTUAL] Research Outcomes in Parkinson Disease Emerging Therapies: Impact of a Medical Education Program on Neurologists’ Knowledge () - Sep 30, 2020 - Abstract #ANA2020ANA_710;
The results suggested that the CME-certified 30-minute video discussion between physician experts was effective at improving knowledge in PD related emerging therapies. Future educational efforts should continue to address findings from clinical and other research in PD.
- | foliglurax (PXT2331) / Lundbeck
Journal: Improved Synthesis of the Thiophenol Precursor N-(4-Chloro-3-mercaptophenyl)picolinamide for Making the mGluR4 PET Ligand. (Pubmed Central) - Aug 26, 2020
Recently [C]mG4P012 (previously [C]KALB012 and presently named as [C]PXT012253 by Prexton Therapeutics) had been used as a biomarker during the preclinical development of a potential therapeutic drug, PXT0002331 (an mGluR4 PAM), for PD and L-dopa-induced dyskinesia...To support the translational research of [C]mG4P012 and the other potential applications, we have developed a new route for synthesis of the thiophenol precursor and optimized the reaction conditions. The synthesis of N-(4-chloro-3-mercaptophenyl)picolinamide from 1-chloro-4-nitrobenzene has been greatly improved from 8% to 52% total yield with easy handling and in gram scales.
- foliglurax (PXT2331) / Lundbeck
Enrollment change, Trial termination: Study Investigating Effects of Foliglurax in Patients With Parkinson's Disease (PD) and Healthy Subjects (clinicaltrials.gov) - Jul 7, 2020
P1, N=6, Terminated, Sponsor: H. Lundbeck A/S
The synthesis of N-(4-chloro-3-mercaptophenyl)picolinamide from 1-chloro-4-nitrobenzene has been greatly improved from 8% to 52% total yield with easy handling and in gram scales. N=30 --> 6 | Recruiting --> Terminated; Study termination due to efficacy results of another study
- foliglurax (PXT2331) / Lundbeck
Enrollment change, Trial termination: Binding of Foliglurax to Regions in the Brain in Healthy Participants and in Patients With Parkinson's Disease (PD) (clinicaltrials.gov) - Jun 18, 2020
P1, N=6, Terminated, Sponsor: H. Lundbeck A/S
N=30 --> 6 | Recruiting --> Terminated; Study termination due to efficacy results of another study N=17 --> 6 | Recruiting --> Terminated; New efficacy data from another study
- | foliglurax (PXT2331) / Lundbeck
Journal: Characterization of [C]PXT012253 as a PET Radioligand for mGlu Allosteric Modulators in Nonhuman Primates. (Pubmed Central) - May 7, 2020
MA1 would be the choice of quantitative method. Further development of [C]PXT012253 in human subjects is warranted.
- || foliglurax (PXT2331) / Lundbeck
Trial completion: Effects of Repeated Doses of Foliglurax on Drug Metabolizing Enzymes in Healthy Subjects (clinicaltrials.gov) - Apr 23, 2020
P1, N=20, Completed, Sponsor: H. Lundbeck A/S
Further development of [C]PXT012253 in human subjects is warranted. Recruiting --> Completed
- || foliglurax (PXT2331) / Lundbeck
New P1 trial: Study Investigating Effects of Foliglurax in Patients With Parkinson's Disease (PD) and Healthy Subjects (clinicaltrials.gov) - Mar 25, 2020
P1, N=30, Recruiting, Sponsor: H. Lundbeck A/S
- ||| foliglurax (PXT2331) / Lundbeck
Trial completion: AMBLED: Study to Evaluate the Efficacy, Safety and Tolerability of PXT002331 (Foliglurax) in Reducing Motor Complications of Levodopa Therapy in Parkinson Disease's Patients (clinicaltrials.gov) - Mar 17, 2020
P2a, N=157, Completed, Sponsor: Prexton Therapeutics
Recruiting --> Completed Active, not recruiting --> Completed
- || foliglurax (PXT2331) / Lundbeck
New P1 trial: Effects of Repeated Doses of Foliglurax on Drug Metabolizing Enzymes in Healthy Subjects (clinicaltrials.gov) - Feb 19, 2020
P1, N=20, Recruiting, Sponsor: H. Lundbeck A/S
- || foliglurax (PXT2331) / Lundbeck
Enrollment closed, Trial completion date, Trial primary completion date: AMBLED: Study to Evaluate the Efficacy, Safety and Tolerability of PXT002331 (Foliglurax) in Reducing Motor Complications of Levodopa Therapy in Parkinson Disease's Patients (clinicaltrials.gov) - Feb 10, 2020
P2a, N=157, Active, not recruiting, Sponsor: Prexton Therapeutics
Active, not recruiting --> Completed Recruiting --> Active, not recruiting | Trial completion date: Oct 2019 --> Mar 2020 | Trial primary completion date: Sep 2019 --> Feb 2020
- || foliglurax (PXT2331) / Lundbeck
New P1 trial: Binding of Foliglurax to Regions in the Brain in Healthy Participants and in Patients With Parkinson's Disease (PD) (clinicaltrials.gov) - Nov 21, 2019
P1, N=17, Recruiting, Sponsor: H. Lundbeck A/S
- | foliglurax (PXT2331) / Lundbeck
Journal: An mGlu4-Positive Allosteric Modulator Alleviates Parkinsonism in Primates. (Pubmed Central) - Oct 18, 2019
This work provides a demonstration that a positive allosteric modulator of metabotropic glutamate receptor 4 can alleviate the motor symptoms of PD and the motor complications induced by l-dopa in primates. PXT002331 is the first compound of its class to enter phase IIa clinical trials.
- | foliglurax (PXT2331) / Lundbeck
Trial completion: What the Body Does to Foliglurax in Healthy Volunteers (clinicaltrials.gov) - Sep 5, 2019
P1, N=6, Completed, Sponsor: H. Lundbeck A/S
PXT002331 is the first compound of its class to enter phase IIa clinical trials. Not yet recruiting --> Completed
- || foliglurax (PXT2331) / Lundbeck
New P1 trial: What the Body Does to Foliglurax in Healthy Volunteers (clinicaltrials.gov) - Jun 30, 2019
P1, N=6, Not yet recruiting, Sponsor: H. Lundbeck A/S
- || foliglurax (PXT2331) / Lundbeck
Trial completion date, Trial primary completion date: AMBLED: Study to Evaluate the Efficacy, Safety and Tolerability of PXT002331 (Foliglurax) in Reducing Motor Complications of Levodopa Therapy in Parkinson Disease's Patients (clinicaltrials.gov) - Mar 6, 2019
P2a, N=165, Recruiting, Sponsor: Prexton Therapeutics
Not yet recruiting --> Completed Trial completion date: May 2019 --> Oct 2019 | Trial primary completion date: Apr 2019 --> Sep 2019
- || foliglurax (PXT2331) / Lundbeck
Trial completion date, Trial primary completion date: AMBLED: Study to Evaluate the Efficacy, Safety and Tolerability of PXT002331 (Foliglurax) in Reducing Motor Complications of Levodopa Therapy in Parkinson Disease's Patients (clinicaltrials.gov) - Jul 9, 2018
P2a, N=165, Recruiting, Sponsor: Prexton Therapeutics
Trial completion date: May 2019 --> Oct 2019 | Trial primary completion date: Apr 2019 --> Sep 2019 Trial completion date: Dec 2018 --> May 2019 | Trial primary completion date: Dec 2018 --> Apr 2019
- foliglurax (PXT2331) / Lundbeck
Enrollment change, Trial withdrawal: Study to Evaluate the Efficacy, Safety, and Tolerability of PXT002331 (Foliglurax) in Reducing Levodopa-Induced Dyskinesia and Wearing OFF in Subjects With Parkinson's Disease Experiencing Motor Complications of Levodopa Therapy (ATTUNED) (clinicaltrials.gov) - Mar 22, 2018
P2a, N=0, Withdrawn, Sponsor: Prexton Therapeutics
Trial completion date: Dec 2018 --> May 2019 | Trial primary completion date: Dec 2018 --> Apr 2019 N=86 --> 0 | Not yet recruiting --> Withdrawn
- ||||| foliglurax (PXT2331) / Lundbeck
New P2a trial: Study to Evaluate the Efficacy, Safety, and Tolerability of PXT002331 (Foliglurax) in Reducing Levodopa-Induced Dyskinesia and Wearing OFF in Subjects With Parkinson's Disease Experiencing Motor Complications of Levodopa Therapy (ATTUNED) (clinicaltrials.gov) - Nov 6, 2017
P2a, N=86, Not yet recruiting, Sponsor: Prexton Therapeutics
- |||| foliglurax (PXT2331) / Lundbeck
Enrollment open: AMBLED: Study to Evaluate the Efficacy, Safety and Tolerability of PXT002331 (Foliglurax) in Reducing Motor Complications of Levodopa Therapy in Parkinson Disease's Patients (clinicaltrials.gov) - Jul 11, 2017
P2a, N=165, Recruiting, Sponsor: Prexton Therapeutics
N=86 --> 0 | Not yet recruiting --> Withdrawn Not yet recruiting --> Recruiting
- ||||| foliglurax (PXT2331) / Lundbeck
New P2a trial: AMBLED: Study to Evaluate the Efficacy, Safety and Tolerability of PXT002331 (Foliglurax) in Reducing Motor Complications of Levodopa Therapy in Parkinson Disease's Patients (clinicaltrials.gov) - May 21, 2017
P2a, N=165, Not yet recruiting, Sponsor: Prexton Therapeutics
- ||| foliglurax (PXT2331) / Lundbeck
Trial completion: A Phase I, Double Blind, Placebo Controlled, First in Human, Single and Multiple Ascending Oral Dose, Safety, Tolerability and Pharmacokinetic Study in Healthy Male and Female Subjects (clinicaltrials.gov) - Sep 28, 2016
P1, N=64, Completed, Sponsor: Prexton Therapeutics
Not yet recruiting --> Recruiting Recruiting --> Completed
- ||| foliglurax (PXT2331) / Lundbeck
Enrollment open: A Phase I, Double Blind, Placebo Controlled, First in Human, Single and Multiple Ascending Oral Dose, Safety, Tolerability and Pharmacokinetic Study in Healthy Male and Female Subjects (clinicaltrials.gov) - Jan 29, 2016
P1, N=72, Recruiting, Sponsor: Prexton Therapeutics
Recruiting --> Completed Not yet recruiting --> Recruiting
- ||| foliglurax (PXT2331) / Lundbeck
New P1 trial: A Phase I, Double Blind, Placebo Controlled, First in Human, Single and Multiple Ascending Oral Dose, Safety, Tolerability and Pharmacokinetic Study in Healthy Male and Female Subjects (clinicaltrials.gov) - Dec 24, 2015
P1, N=72, Not yet recruiting, Sponsor: Prexton Therapeutics