Clinical trial NCT03162874: Study to Evaluate the Efficacy, Safety and Tolerability of PXT002331 (Foliglurax) in Reducing Motor Complications of Levodopa Therapy in Parkinson Disease's Patients
Official title: A Multi-centre, Double-blind, Randomised, Placebo-controlled, Parallel-arm Phase IIa Trial to Evaluate the Efficacy, Safety and Tolerability of 28-Day Oral Treatment With PXT002331 (Foliglurax) in Reducing Motor Complications of Levodopa Therapy in Subjects With Parkinson's Disease Experiencing End-of-dose Wearing Off and Levodopa-Induced Dyskinesia (AMBLED)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Parkinson Disease
Keywords: Levodopa-Induced Dyskinesia (LID)
Wearing-off
Foliglurax
Parkinson's Disease
mGluR4 PAM
Lead sponsor: Prexton Therapeutics
Sponsor class: INDUSTRY
First posted: 2017-05-22
Enrollment: 157
Sex: ALL
Minimum age (years): 35
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This will be a double-blind, randomised, placebo-controlled parallel-arm phase II proof of concept in subjects with PD treated with a stable dose of levodopa who are experiencing both end-of-dose wearing off and Levodopa-Induced Dyskinesia (LID)


Eligibility criteria: Inclusion Criteria:

* Males or females diagnosed after the age of 30 years with idiopathic PD for at least 3 years
* Disease severity of 2 to 4 on the modified Hoehn and Yahr scale when in the OFF state
* Been treated with a stable regimen of levodopa-containing therapy
* Subjects who are on a long-acting formulation of levodopa-containing therapy, including Apodespan PR (or equivalent), must be on a stable dose for at least 6 weeks prior to the first screening visit
* Experienced motor fluctuations with wearing off over a period of at least 3 months prior to randomisation
* Experienced LID over a period of at least 3 months prior to randomisation
* Female subjects will be women of non-childbearing potential
* Subjects must pass a Hauser diary concordance test
* Subjects are able, with or without the help of a caregiver, to understand the purpose and risks of the study and provide signed and dated informed consent and authorisation to use confidential health information in accordance with national and local subject privacy regulations

Exclusion Criteria:

* Subjects with atypical, secondary or drug-induced Parkinsonism
* Subjects with a Mini-Mental State Examination (MMSE) score \<25
* Any known contraindication to the use of levodopa, including a history of malignant melanoma or a history of narrow-angle glaucoma.
* Subjects who have had a clinically significant illness within 4 weeks of first dose, as determined by the Investigator.
* Any advanced, severe or unstable disease (other than PD) that may interfere with the primary and secondary study outcome evaluations
* Subjects who have undergone prior neurosurgical operation for PD or transcranial magnetic stimulation.
* Subjects who are participating in another clinical study (eg, attending follow-up visits) or who have participated in a clinical study involving administration of an investigational drug (new chemical entity) in the past 3 months prior to the baseline visit.
* Female subjects of childbearing potential
* Subjects who are pregnant (as determined by positive serum pregnancy test at screening and/or baseline), breastfeeding or lactating.
* Subjects who, in the opinion of the Investigator, should not participate in this study.

Primary outcomes:
measure: Change from baseline to end of Treatment Period in the daily awake OFF time based on subject Hauser diary entries
timeFrame: 28 days
Secondary outcomes:
Other outcomes:
Locations:
city: Innsbruck
country: Austria
facility: Universitätsklinik für Innere Medizin VI Innsbruck, Neurologisches Studienzentrum
city: Amiens
country: France
facility: Centre Hospitalier Universitaire d'Amiens
city: Bayonne
country: France
facility: Centre Hospitalier de la Côte Basque
city: Bobigny
country: France
facility: Hôpital Avicenne APHP
city: Bron
country: France
facility: Hôpital Pierre Wertheimer
city: Clermont-Ferrand
country: France
facility: CHU Gabriel-Montpied
city: Grenoble
country: France
facility: CHU Grenoble - Pôle Psychiatrie et Neurologie
city: Lille
country: France
facility: CHRU - Hôpital Roger Salengro
city: Nice
country: France
facility: CHU de Nice - Hôpital Pasteur
city: Paris
country: France
facility: Hopital Pitie-Salpetriere
city: Poitiers
country: France
facility: CHU de Poitiers
city: Rouen
country: France
facility: Hôpital Universitaire
city: Saint-Herblain
country: France
facility: CHU de Nantes - Hôpital Nord Laennec
city: Strasbourg
country: France
facility: Hôpitaux Universitaires de Strasbourg - Hôpital de Hautepierre
city: Toulouse
country: France
facility: Centre Hospitalier Universitaire de Toulouse - Hôpital Purpan
city: Bad Homburg
country: Germany
facility: Practice for Neurology, Psychiatry & Psychotherapy Dr. med. I. Schoell & colleagues
city: Berlin
country: Germany
facility: St. Joseph-Krankenhaus Berlin-Weissensee
city: Erlangen
country: Germany
facility: University Hospital Erlangen - Abteilung fur Molekulare Neurologie
city: Gera
country: Germany
facility: Neurological Praxis
city: Jena
country: Germany
facility: Am Klinikum 1 Jena
city: Kassel
country: Germany
facility: Paracelsus-Elena-Klinik Kassel
city: Mühldorf
country: Germany
facility: MVZ Kliniken Mühldorf a. Inn
city: Arcugnano
country: Italy
facility: Villa Margherita
city: Chieti
country: Italy
facility: Fondazione Universita G. D'Annunzio Centro Studi sull'invecchiamento Centro di Ricerca Clinica
city: Fisciano
country: Italy
facility: Universita degli Studi di Salerno
city: Messina
country: Italy
facility: IRCCS Centro Neurolesi Bonino Pulejo
city: Milano
country: Italy
facility: Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta
city: Pisa
country: Italy
facility: Azienda Ospedaliero Universitaria Pisana - Stabilimento Ospedaliero di Santa Chiara
city: Roma
country: Italy
facility: Policlinico Tor Vergata
city: Roma
country: Italy
facility: IRCCS San Raffaele Pisana
city: Roma
country: Italy
facility: Università degli Studi di Roma "La Sapienza"
city: Rozzano
country: Italy
facility: Humanitas Research Hospital
city: Venezia
country: Italy
facility: IRCCS Fondazione Ospedale San Camillo (SC)
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital Clínic de Barcelona
city: Elche
country: Spain
facility: Hospital General Universitario de Elche
city: Sant Cugat del Vallès
country: Spain
facility: Hospital Universitari General de Catalunya
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocío
city: Valencia
country: Spain
facility: Hospital Universitari i Politècnic La Fe
city: Bury
country: United Kingdom
facility: Fairfield General Hospital
city: London
country: United Kingdom
facility: Imperial College Healthcare NHS Trust - Charing Cross Hospital
city: Newcastle upon Tyne
country: United Kingdom
facility: Clinical Ageing Research Unit, Campus for Ageing and Vitality
city: North Shields
country: United Kingdom
facility: North Tyneside General Hospital
city: Plymouth
country: United Kingdom
facility: Plymouth Hospitals NHS Trust - Derriford Hospital
Study officials:
References: