A Study to Evaluate Sigma-1 and Dopamine-2 Receptor Occupancy by Pridopidine in the Human Brain of Healthy Volunteers and in Patients With Huntington's Disease

A Phase I, Open-Label, Single-Dose, Adaptive (S)-(-)-[18F]Fluspidine and [18F]Fallypride Positron Emission Tomography Study to Evaluate Sigma-1 and Dopamine-2 Receptor Occupancy by Pridopidine in the Human Brain of Healthy Volunteers and in Patients With Huntington's Disease

The purpose of this study is to demonstrate engagement of pridopidine with S1R and D2R (optional) in the living human brain. No formal statistical analysis will be conducted

Study Overview

• Status: Completed
• Conditions: Health Volunteers, Huntington Disease
• Intervention / Treatment: Drug: pridopidine (90 mg)

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Leipzig, Germany, 04103
    • Teva Investigational Site 32648

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• In general, good physical health as determined by medical history and psychiatric history, suicidality assessment & physical examination
• Men who are potentially fertile (not surgically [eg, vasectomy] or congenitally sterile

• Patients with Huntington's disease (HD): diagnosis of HD and with an onset of HD after 18 years of age

  • Additional criteria apply, please contact the investigator for more information

Exclusion Criteria:

• The subject has been previously exposed to ionizing radiation or radioactive substances as a result of clinical research or medical treatment in the past 10 years.
• The subject has a counterindication to having an MRI
• History of alcohol, narcotic, or any other substance dependence in the past 2 years
• Additional Exclusion criteria to patients with Huntington's disease:
• The patient has a severe motor impairment that might cause artifacts.
• Patients with a known history of Long QT Syndrome or a first degree relative with this condition.

• Treatment with any investigational product within 6 weeks of screening or patients planning to participate in another clinical study assessing any investigational product during the study.

  • Additional criteria apply, please contact the investigator for more information

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: pridopidine; Pridopidine (TV-7820) capsules	Drug: pridopidine (90 mg); single dose will be administered in Cohort 1. Other optional cohorts 2 and 3 may include single dose 0.5 mg, 1 mg, 2.5 mg, 5 mg, 10 mg, 22.5 mg, 45 mg, or 90 mg. The dose will be selected based on the results obtained from Cohorts 1 and 2.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sigma-1 Receptor Occupancy	Receptor occupancy of pridopidine to Sigma-1 receptors (S1R) in the brain was assessed from Positron Emission Tomography (PET) imaging with (S)-(-)-[18F]fluspidine	2 hours after oral administration of pridopidine

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Plasma Concentration of Pridopidine	Maximum plasma concentration of pridopidine based on noncompartmental analysis	PK sampling 1 h before pridopidine dosing, and 5, 15, 30, 45, 60 min, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, and 24 h after dosing.
Time to Reach Maximum (Peak) Concentration (Tmax)	Multiple PK samples over 24 hours will be calculated for pridopidine and its metabolite TV-45065 in plasma using non-compartmental methods, when possible.	PK sampling 1 h before pridopidine dosing, and 5, 15, 30, 45, 60 min, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, and 24 h after dosing.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dopamine-2 Receptor Occupancy	RO of D2 (Dopamine-2) at 2 hours after oral administration of pridopidine (90 mg dose level) was investigated in 4 healthy volunteers using [18F]fallypride	2 h after pridopidine dosing

Collaborators and Investigators

• Sponsor: Prilenia

Publications and helpful links

General Publications

• Grachev ID, Meyer PM, Becker GA, Bronzel M, Marsteller D, Pastino G, Voges O, Rabinovich L, Knebel H, Zientek F, Rullmann M, Sattler B, Patt M, Gerhards T, Strauss M, Kluge A, Brust P, Savola JM, Gordon MF, Geva M, Hesse S, Barthel H, Hayden MR, Sabri O. Sigma-1 and dopamine D2/D3 receptor occupancy of pridopidine in healthy volunteers and patients with Huntington disease: a [18F] fluspidine and [18F] fallypride PET study. Eur J Nucl Med Mol Imaging. 2021 Apr;48(4):1103-1115. doi: 10.1007/s00259-020-05030-3. Epub 2020 Sep 29.

Study record dates

Study Major Dates

• Study Start (Actual): April 19, 2017
• Primary Completion (Actual): February 9, 2018
• Study Completion (Actual): February 9, 2018

Study Registration Dates

• First Submitted: January 3, 2017
• First Submitted That Met QC Criteria: January 11, 2017
• First Posted (Estimate): January 12, 2017

Study Record Updates

• Last Update Posted (Actual): November 19, 2021
• Last Update Submitted That Met QC Criteria: November 18, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Genetic Diseases, Inborn; Basal Ganglia Diseases; Movement Disorders; Neurodegenerative Diseases; Dyskinesias; Heredodegenerative Disorders, Nervous System; Dementia; Cognition Disorders; Chorea; Huntington Disease
• Other Study ID Numbers: TV7820-IMG-10082; 2016-001757-41 (EudraCT Number)

Drug and device information, study documents

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