Health Volunteers, Huntington Disease
Conditions
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
Interventions
DRUGpridopidine (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.
Sponsors
Prilenia
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
25 Years to No maximum
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Sigma-1 Receptor Occupancy | 2 hours after oral administration of pridopidine | 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
| Measure | Time frame | Description |
|---|---|---|
| Maximum Plasma Concentration of Pridopidine | 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. | Maximum plasma concentration of pridopidine based on noncompartmental analysis |
| Time to Reach Maximum (Peak) Concentration (Tmax) | 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. | Multiple PK samples over 24 hours will be calculated for pridopidine and its metabolite TV-45065 in plasma using non-compartmental methods, when possible. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Dopamine-2 Receptor Occupancy | 2 h after pridopidine dosing | 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 |
Countries
Germany
Participant flow
Recruitment details
Healthy volunteers (HV) and patients with Huntington Disease (HD) were enrolled. The first participant was enrolled on 22 March 2017; the last subject completed the study on 09 February 2018.
Pre-assignment details
The screening period had a duration of up to 8 weeks. A total of 49 healthy subjects and 3 HD patients were screened; of these, 20 healthy subjects and 3 HD patients met the eligibility criteria and were enrolled in the study.
Participants by arm
| Arm | Count |
|---|---|
| A: Cohort 1: P90 + (S)-(-)-FPD; HV Healthy volunteers (HV) receiving a single dose of 90 mg pridopidine (P90) and radiolabeled PET tracer (S)-(-)-\[18F\]fluspidine ((S)-(-)-FPD) for neuroimaging in Part A of the study | 5 |
| A: Cohort 2: P45 + (S)-(-)-FPD; HV Healthy volunteers (HV) receiving a single dose of 45 mg pridopidine (P45) and radiolabeled PET tracer (S)-(-)-\[18F\]fluspidine ((S)-(-)-FPD) for neuroimaging in Part A of the study | 1 |
| A: Cohort 2: P22.5 + (S)-(-)-FPD; HV Healthy volunteers (HV) receiving a single dose of 22.5 mg pridopidine (P22.5) and radiolabeled PET tracer (S)-(-)-\[18F\]fluspidine ((S)-(-)-FPD) for neuroimaging in Part A of the study | 3 |
| A: Cohort 3: P5 + (S)-(-)-FPD; HV Healthy volunteers (HV) receiving a single dose of 5 mg pridopidine (P5) and radiolabeled PET tracer (S)-(-)-\[18F\]fluspidine ((S)-(-)-FPD) for neuroimaging in Part A of the study | 2 |
| A: Cohort 7: P1 + (S)-(-)-FPD; HV Healthy volunteers (HV) receiving a single dose of 1 mg pridopidine (P1) and radiolabeled PET tracer (S)-(-)-\[18F\]fluspidine ((S)-(-)-FPD) for neuroimaging in Part A of the study | 1 |
| A: Cohort 7: P0.5 + (S)-(-)-FPD; HV Healthy volunteers (HV) receiving a single dose of 0.5 mg pridopidine (P0.5) and radiolabeled PET tracer (S)-(-)-\[18F\]fluspidine ((S)-(-)-FPD) for neuroimaging in Part A of the study | 1 |
| A: Cohort 6; P90 + (S)-(-)-FPD; HD Patients with Huntington's Disease (HD) receiving a single dose of 90 mg pridopidine (P90) and radiolabeled PET tracer (S)-(-)-\[18F\]fluspidine ((S)-(-)-FPD) for neuroimaging in Part A of the study | 3 |
| B: Cohort 4: P90 + Fallypride; HV Healthy volunteers (HV) receiving a single dose of 90 mg pridopidine (P90) and radiolabeled PET tracer \[18F\]fallypride for neuroimaging in Part B of the study | 4 |
| Cohort 0: (S)-(-)-FPD, HV Healthy volunteers (HV) receiving a single dose of radiolabeled PET tracer (S)-(-)-\[18F\]fluspidine ((S)-(-)-FPD) for neuroimaging | 3 |
| Total | 23 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 |
|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Other | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | A: Cohort 3: P5 + (S)-(-)-FPD; HV | A: Cohort 1: P90 + (S)-(-)-FPD; HV | A: Cohort 2: P45 + (S)-(-)-FPD; HV | A: Cohort 2: P22.5 + (S)-(-)-FPD; HV | A: Cohort 7: P1 + (S)-(-)-FPD; HV | A: Cohort 7: P0.5 + (S)-(-)-FPD; HV | A: Cohort 6; P90 + (S)-(-)-FPD; HD | B: Cohort 4: P90 + Fallypride; HV | Cohort 0: (S)-(-)-FPD, HV | Total |
|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 27.5 years | 28.0 years | 26.0 years | 25.0 years | 30 years | 25.0 years | 40.0 years | 28.0 years | 29.0 years | 28 years |
| Race/Ethnicity, Customized Black/African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 2 Participants | 5 Participants | 1 Participants | 3 Participants | 1 Participants | 1 Participants | 3 Participants | 4 Participants | 2 Participants | 22 Participants |
| Region of Enrollment Germany | 2 participants | 5 participants | 1 participants | 3 participants | 1 participants | 1 participants | 3 participants | 4 participants | 3 participants | 23 participants |
| Sex: Female, Male Female | 2 Participants | 5 Participants | 1 Participants | 3 Participants | 1 Participants | 1 Participants | 3 Participants | 4 Participants | 3 Participants | 23 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 0 / 1 | 0 / 3 | 0 / 2 | 0 / 1 | 0 / 1 | 0 / 3 | 0 / 4 | 0 / 3 |
| other Total, other adverse events | 2 / 5 | 1 / 1 | 1 / 3 | 0 / 2 | 0 / 1 | 0 / 1 | 1 / 3 | 1 / 4 | 3 / 3 |
| serious Total, serious adverse events | 0 / 5 | 0 / 1 | 0 / 3 | 0 / 2 | 0 / 1 | 0 / 1 | 0 / 3 | 0 / 4 | 0 / 3 |
Outcome results
Primary
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
Time frame: 2 hours after oral administration of pridopidine
Population: Patients enrolled and receiving pridopidine. Patients from Cohort B (receiving fallypride only) and Cohort 0 (no pridopidine treatment) were not included in the analysis
| Arm | Measure | Value (MEAN) |
|---|---|---|
| A: Cohort 1: P90 + (S)-(-)-FPD; HV | Sigma-1 Receptor Occupancy | 91.21 percentage of receptor occupancy |
| A: Cohort 2: P45 + (S)-(-)-FPD; HV | Sigma-1 Receptor Occupancy | 87.19 percentage of receptor occupancy |
| A: Cohort 2: P22.5 + (S)-(-)-FPD; HV | Sigma-1 Receptor Occupancy | 86.67 percentage of receptor occupancy |
| A: Cohort 3: P5 + (S)-(-)-FPD; HV | Sigma-1 Receptor Occupancy | 77.96 percentage of receptor occupancy |
| A: Cohort 7: P1 + (S)-(-)-FPD; HV | Sigma-1 Receptor Occupancy | 41.77 percentage of receptor occupancy |
| A: Cohort 7: P0.5 + (S)-(-)-FPD; HV | Sigma-1 Receptor Occupancy | 17.55 percentage of receptor occupancy |
| A: Cohort 6; P90 + (S)-(-)-FPD; HD | Sigma-1 Receptor Occupancy | 87.37 percentage of receptor occupancy |
Secondary
Maximum Plasma Concentration of Pridopidine
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.
Population: Patients enrolled who received pridopidine and had sufficient data to calculate at least 1 evaluable pharmacokinetic parameter for pridopidine.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| A: Cohort 1: P90 + (S)-(-)-FPD; HV | Maximum Plasma Concentration of Pridopidine | 552 ng/mL |
| A: Cohort 2: P45 + (S)-(-)-FPD; HV | Maximum Plasma Concentration of Pridopidine | 307 ng/mL |
| A: Cohort 2: P22.5 + (S)-(-)-FPD; HV | Maximum Plasma Concentration of Pridopidine | 147 ng/mL |
| A: Cohort 3: P5 + (S)-(-)-FPD; HV | Maximum Plasma Concentration of Pridopidine | 25.9 ng/mL |
| A: Cohort 7: P1 + (S)-(-)-FPD; HV | Maximum Plasma Concentration of Pridopidine | 2.90 ng/mL |
| A: Cohort 7: P0.5 + (S)-(-)-FPD; HV | Maximum Plasma Concentration of Pridopidine | 1.33 ng/mL |
| A: Cohort 6; P90 + (S)-(-)-FPD; HD | Maximum Plasma Concentration of Pridopidine | 764 ng/mL |
| B: Cohort 4: P90 + FPD; HV | Maximum Plasma Concentration of Pridopidine | 452 ng/mL |
Secondary
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.
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.
Population: Patients enrolled who received pridopidine and had sufficient data to calculate at least 1 evaluable pharmacokinetic parameter for pridopidine
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| A: Cohort 1: P90 + (S)-(-)-FPD; HV | Time to Reach Maximum (Peak) Concentration (Tmax) | 1.97 hours |
| A: Cohort 2: P45 + (S)-(-)-FPD; HV | Time to Reach Maximum (Peak) Concentration (Tmax) | 1.98 hours |
| A: Cohort 2: P22.5 + (S)-(-)-FPD; HV | Time to Reach Maximum (Peak) Concentration (Tmax) | 1.00 hours |
| A: Cohort 3: P5 + (S)-(-)-FPD; HV | Time to Reach Maximum (Peak) Concentration (Tmax) | 1.00 hours |
| A: Cohort 7: P1 + (S)-(-)-FPD; HV | Time to Reach Maximum (Peak) Concentration (Tmax) | 1.98 hours |
| A: Cohort 7: P0.5 + (S)-(-)-FPD; HV | Time to Reach Maximum (Peak) Concentration (Tmax) | 1.97 hours |
| A: Cohort 6; P90 + (S)-(-)-FPD; HD | Time to Reach Maximum (Peak) Concentration (Tmax) | 1.00 hours |
| B: Cohort 4: P90 + FPD; HV | Time to Reach Maximum (Peak) Concentration (Tmax) | 2.26 hours |
Other Pre-specified
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
Time frame: 2 h after pridopidine dosing
Population: Patients enrolled and treated
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| A: Cohort 1: P90 + (S)-(-)-FPD; HV | Dopamine-2 Receptor Occupancy | 3.34 percent volume/volume | Standard Deviation 2.05 |