Autism Spectrum Disorder
Conditions
Brief summary
This is a single dose (SD), non-randomized, open-label, adaptive, parallel group study with the purpose of investigating the occupancy of alpha5-containing GABAA receptors by RO7017773 in healthy participants.
Interventions
DRUGRO7017773
RO7017773 will be administered orally. The doses to be tested will be determined by review of PET scan, PK, and safety results from the previous dose level.
OTHER[11C] Ro15-4513
At the start of each PET scan, participants will receive an intravenous dose of the radiolabeled tracer \[11C\]Ro15-4513.
Sponsors
Hoffmann-La Roche
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
23 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy (absence of evidence of any active or chronic disease following a detailed medical and surgical history, a complete physical examination including vital signs, 12-lead ECG, hematology, blood chemisty, serology, and urinalysis), as judged by the Investigator. * Males and women of non-childbearing potential (WONCBP)
Exclusion criteria
* History of convulsions (other than benign febrile convulsions of childhood) including epilepsy, or personal history of significant cerebral trauma or CNS infections * Clinically significant abnormal finding from the MRI performed after the initial screening examination * Abnormal blood pressure, i.e, systolic blood pressure (SBP) greater than 140 or less than 90 mm Hg, and diastolic blood pressure (DBP) greater than 90 or less than 50 mm Hg * Abnormal pulse rate, resting pulse rate greater than 100 or less than 40 bpm * History or presence of clinically significant ECG abnormalities before study drug administration or cardiovascular disease * Show evidence of human immunodeficiency virus (HIV) infection and/or positive human HIV antibodies * Positive result on hepatitis B (HBV) or hepatitis C (HCV), presence of hepatitis B surface antigen (HBsAg) or positive hepatitis C antibody test result at screening or within 3 months prior to starting study treatment
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage of Brain Alpha5-Containing GABA-A Receptors Occupied by RO7017773 | Baseline up to 48 hours (hrs) |
| Plasma Concentrations of RO7017773 | Baseline up to 48 hrs |
Secondary
| Measure | Time frame |
|---|---|
| Number of Participants With Adverse Events (AEs) | From treatment initiation until 14 days after the last dose of study treatment. |
Countries
United Kingdom
Participant flow
Recruitment details
Healthy subjects between the ages of 23 and 55 years (inclusive) were enrolled at one site in the United Kingdom.
Participants by arm
| Arm | Count |
|---|---|
| RO7017773 - 15mg Healthy participants received a single oral dose of RO7017773, and up to 3 intravenous (IV) doses of the radiolabeled ligand \[11C\]Ro15-4513 administered prior to positron emission tomography/computed tomography (PET/CT) scans over two imaging sessions separated by at least 7 days. | 2 |
| RO7017773 - 30mg Healthy participants received a single oral dose of RO7017773, and up to 3 intravenous (IV) doses of the radiolabeled ligand \[11C\]Ro15-4513 administered prior to positron emission tomography/computed tomography (PET/CT) scans over two imaging sessions separated by at least 7 days. | 1 |
| RO7017773 - 75mg Healthy participants received a single oral dose of RO7017773, and up to 3 intravenous (IV) doses of the radiolabeled ligand \[11C\]Ro15-4513 administered prior to positron emission tomography/computed tomography (PET/CT) scans over two imaging sessions separated by at least 7 days. | 2 |
| RO7017773 - 375mg Healthy participants received a single oral dose of RO7017773, and up to 3 intravenous (IV) doses of the radiolabeled ligand \[11C\]Ro15-4513 administered prior to positron emission tomography/computed tomography (PET/CT) scans over two imaging sessions separated by at least 7 days. | 1 |
| Total | 6 |
Baseline characteristics
| Characteristic | — | Total |
|---|---|---|
| Age, Continuous | — years | — |
| Ethnicity (NIH/OMB) Hispanic or Latino | — | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | — | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | — | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | — | 0 Participants |
| Race (NIH/OMB) Asian | — | 0 Participants |
| Race (NIH/OMB) Black or African American | — | 0 Participants |
| Race (NIH/OMB) More than one race | — | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | — | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | — | 0 Participants |
| Race (NIH/OMB) White | — | 0 Participants |
| Sex: Female, Male Female | — | 0 Participants |
| Sex: Female, Male Male | — | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 2 | 0 / 1 | 0 / 2 | 0 / 1 |
| other Total, other adverse events | 2 / 2 | 0 / 1 | 1 / 2 | 1 / 1 |
| serious Total, serious adverse events | 0 / 2 | 0 / 1 | 0 / 2 | 0 / 1 |
Outcome results
Primary
Percentage of Brain Alpha5-Containing GABA-A Receptors Occupied by RO7017773
Time frame: Baseline up to 48 hours (hrs)
Population: This data/information can potentially be used to re-identify trial participants due to the low sample size, Therefore, this data will not be disclosed in the interest of maintaining participant confidentiality.
Primary
Plasma Concentrations of RO7017773
Time frame: Baseline up to 48 hrs
Population: This data/information can potentially be used to re-identify trial participants due to the low sample size, Therefore, this data will not be disclosed in the interest of maintaining participant confidentiality.
Secondary
Number of Participants With Adverse Events (AEs)
Time frame: From treatment initiation until 14 days after the last dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| RO7017773 - 15mg | Number of Participants With Adverse Events (AEs) | 2 Participants |
| RO7017773 - 30mg | Number of Participants With Adverse Events (AEs) | 0 Participants |
| RO7017773 - 75mg | Number of Participants With Adverse Events (AEs) | 1 Participants |
| RO7017773 - 375mg | Number of Participants With Adverse Events (AEs) | 1 Participants |