Binding of Foliglurax to Regions in the Brain in Healthy Participants and in Patients With Parkinson's Disease (PD)

Interventional, Open-label, Positron Emission Tomography (PET) Study With [11C]-PXT012253 Investigating the Brain mGlu4 Receptor Occupancy, Safety, Tolerability and Pharmacokinetics of Foliglurax in Healthy Subjects and Patients With Parkinson's Disease

A study to learn how foliglurax binds in regions of the brain

Study Overview

• Status: Terminated
• Conditions: Healthy; Parkinson Disease
• Intervention / Treatment: Drug: foliglurax; Drug: foliglurax

Detailed Description

To study binding of foliglurax to mGlu4 receptors in human brain, up to 9 healthy subjects (Part A) and up to 8 patients with Parkinson's disease (Part B) will be injected with a liquid dose of a radiolabelled tracer that allows measurement of foliglurax binding in the brain to determine to which degree foliglurax binds to regions of the brain.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 1

Contacts and Locations

Study Locations

• Sweden
  • Stockholm, Sweden
    • Karolinska Institutet

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Part A:

• Healthy subjects
• The subject has a normal structural MRI (sMRI) scan performed in the screening period, as judged by the investigator.
• The subject is, in the opinion of the investigator, generally healthy based on the assessment of medical history, physical examination, vital signs, body weight, ECG, and the results of the haematology, clinical chemistry, urinalysis, serology, and other laboratory tests.
• The subject can tolerate confined spaces for prolonged periods of time.
• The subject is suitable for radial and/or brachial artery blood sampling and cannulation.

Part B:

• Patients with Parkinson's disease
• The subject has a normal sMRI scan performed in the screening period, as judged by the investigator.
• The patient is, in the opinion of the investigator, fit for enrolment in the study based on the assessment of medical history, physical examination, vital signs, body weight, ECG, and the results of the haematology, clinical chemistry, urinalysis, serology, and other laboratory tests.
• The patient has been diagnosed with idiopathic Parkinson's disease for ≥3 years, with a current disease severity of 2 to 4 on the modified Hoehn and Yahr scale in the OFF state.
• The patient has dyskinesia that is not too severe to cause discomfort for the patient during PET imaging and predictable OFF time
• In addition to the above criteria, the patient must, in the opinion of the investigator, also be suitable for the study and the included PET imaging sessions.
• The patient has been receiving a stable regimen of levodopa-containing therapy (total levodopa dose ≤1600 mg per day) (≥3 doses per day of standard levodopa or ≥3 doses per day of carbidopa and levodopa, sustained-release tablets or extended-release capsules of carbidopa and levodopa or benserazide and levodopa), and be on a stable regimen of permitted anti-Parkinsonian drugs (peripheral decarboxylase inhibitors, dopamine agonists [except apomorphine], monoamine oxidase type B [MAO-B] inhibitors [except safinamide], or catechol-O-methyl transferase [COMT] inhibitors) for ≥4 weeks prior to foliglurax dosing
• The patient can tolerate confined spaces for prolonged periods of time
• The patient is suitable for radial and/or brachial artery blood sampling and cannulation

Exclusion Criteria:

• The subject has any concurrent disorder that may affect the particular target or absorption, distribution, or elimination of the IMP

Other inclusion and exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Healthy subjects	Drug: foliglurax; Capsules of 20/80 mg foliglurax, orally. Single doses of 20-240 mg; Drug: foliglurax; Capsules of 20/80 mg foliglurax, orally. Single doses of 20-160 mg
Experimental: PD patients	Drug: foliglurax; Capsules of 20/80 mg foliglurax, orally. Single doses of 20-240 mg; Drug: foliglurax; Capsules of 20/80 mg foliglurax, orally. Single doses of 20-160 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Receptor Occupancy (RO) on the metabotropic glutamate receptor 4 (mGlu4)	in Healthy Participants and in Patients With Parkinson's Disease	From Day 1 up to Day 3
C(PET) foliglurax	mean plasma concentration of foliglurax during PET measurement in Healthy Participants and in Patients With Parkinson's Disease	From Day 1 up to Day 3

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC(0-24) foliglurax	Area under the plasma concentration curve from zero to 24 hours	From Day 1 up to Day 3
Cmax foliglurax	Maximum observed plasma concentration of foliglurax	From Day 1 up to Day 3
Tmax foliglurax	Corresponding time (tmax) in plasma	From Day 1 up to Day 3

Collaborators and Investigators

• Sponsor: H. Lundbeck A/S

Study record dates

Study Major Dates

• Study Start (Actual): November 12, 2019
• Primary Completion (Actual): March 3, 2020
• Study Completion (Actual): March 10, 2020

Study Registration Dates

• First Submitted: November 12, 2019
• First Submitted That Met QC Criteria: November 21, 2019
• First Posted (Actual): November 22, 2019

Study Record Updates

• Last Update Posted (Actual): December 9, 2020
• Last Update Submitted That Met QC Criteria: December 8, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease
• Other Study ID Numbers: 18124A

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No