Back to resultsA 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
Primary Purpose
Health Volunteers, Huntington Disease
Status
Completed
Phase
Phase 1
Locations
Germany
Study Type
Interventional
Intervention
pridopidine (90 mg)
Sponsored by
About this trial
This is an interventional other trial for Health Volunteers, Huntington Disease
Eligibility Criteria
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
Sites / Locations
- Teva Investigational Site 32648
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
pridopidine
Arm Description
Pridopidine (TV-7820) capsules
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
Maximum Plasma Concentration of Pridopidine
Maximum plasma concentration of pridopidine based on noncompartmental analysis
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03019289
Brief Title
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
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
November 2021
Overall Recruitment Status
Completed
Study Start Date
April 19, 2017 (Actual)
Primary Completion Date
February 9, 2018 (Actual)
Study Completion Date
February 9, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Prilenia
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Health Volunteers, Huntington Disease
7. Study Design
Primary Purpose
Other
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
23 (Actual)
8. Arms, Groups, and Interventions
Arm Title
pridopidine
Arm Type
Experimental
Arm Description
Pridopidine (TV-7820) capsules
Intervention Type
Drug
Intervention Name(s)
pridopidine (90 mg)
Intervention Description
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.
Primary Outcome Measure Information:
Title
Sigma-1 Receptor Occupancy
Description
Receptor occupancy of pridopidine to Sigma-1 receptors (S1R) in the brain was assessed from Positron Emission Tomography (PET) imaging with (S)-(-)-[18F]fluspidine
Time Frame
2 hours after oral administration of pridopidine
Secondary Outcome Measure Information:
Title
Maximum Plasma Concentration of Pridopidine
Description
Maximum plasma concentration of pridopidine based on noncompartmental analysis
Time Frame
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.
Title
Time to Reach Maximum (Peak) Concentration (Tmax)
Description
Multiple PK samples over 24 hours will be calculated for pridopidine and its metabolite TV-45065 in plasma using non-compartmental methods, when possible.
Time Frame
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 Pre-specified Outcome Measures:
Title
Dopamine-2 Receptor Occupancy
Description
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
Time Frame
2 h after pridopidine dosing
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
25 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Teva Medical Expert, MD
Organizational Affiliation
Teva Pharmaceuticals USA
Official's Role
Study Director
Facility Information:
Facility Name
Teva Investigational Site 32648
City
Leipzig
ZIP/Postal Code
04103
Country
Germany
12. IPD Sharing Statement
Citations:
PubMed Identifier
32995944
Citation
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.
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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
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