Open Label, Adaptive, Parallel Group PET Study Using RO7017773 And [11C] RO15-4513
Study Details
Study Description
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.
Condition or Disease | Intervention/Treatment | Phase |
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Phase 1 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: RO7017773 The first two participants of the first cohort are anticipated to receive a single dose of RO7017773 orally. The doses to be tested in the subsequent cohorts of participants will be determined by review of PET scan, PK, and safety results from the previous dose level. |
Drug: RO7017773
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.
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Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- Number of Participants With Adverse Events (AEs) [From treatment initiation until 14 days after the last dose of study treatment.]
Eligibility Criteria
Criteria
Inclusion Criteria:
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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.
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Males and women of non-childbearing potential (WONCBP)
Exclusion Criteria:
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History of convulsions (other than benign febrile convulsions of childhood) including epilepsy, or personal history of significant cerebral trauma or CNS infections
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Clinically significant abnormal finding from the MRI performed after the initial screening examination
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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
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Abnormal pulse rate, resting pulse rate greater than 100 or less than 40 bpm
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History or presence of clinically significant ECG abnormalities before study drug administration or cardiovascular disease
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Show evidence of human immunodeficiency virus (HIV) infection and/or positive human HIV antibodies
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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
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Hammersmith Medicines Research; Central Middlesex Hospital | London | United Kingdom | NW10 7EW |
Sponsors and Collaborators
- Hoffmann-La Roche
Investigators
None specified.Study Documents (Full-Text)
More Information
Publications
None provided.- BP40257
Study Results
Participant Flow
Recruitment Details | Healthy subjects between the ages of 23 and 55 years (inclusive) were enrolled at one site in the United Kingdom. |
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Pre-assignment Detail |
Arm/Group Title | RO7017773 - 15mg | RO7017773 - 30mg | RO7017773 - 75mg | RO7017773 - 375mg |
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Arm/Group Description | 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. | 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. | 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. | 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. |
Period Title: Overall Study | ||||
STARTED | 2 | 1 | 2 | 1 |
COMPLETED | 2 | 1 | 2 | 1 |
NOT COMPLETED | 0 | 0 | 0 | 0 |
Baseline Characteristics
Arm/Group Title | RO7017773 - 15mg | RO7017773 - 30mg | RO7017773 - 75mg | RO7017773 - 375mg | Total |
---|---|---|---|---|---|
Arm/Group Description | 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. | 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. | 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. | 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. | Total of all reporting groups |
Overall Participants | 2 | 1 | 2 | 1 | 6 |
Age (years) [Mean (Standard Deviation) ] | |||||
Sex: Female, Male (Count of Participants) | |||||
Female |
0
0%
|
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Male |
0
0%
|
||||
Ethnicity (NIH/OMB) (Count of Participants) | |||||
Hispanic or Latino |
0
0%
|
||||
Not Hispanic or Latino |
0
0%
|
||||
Unknown or Not Reported |
0
0%
|
||||
Race (NIH/OMB) (Count of Participants) | |||||
American Indian or Alaska Native |
0
0%
|
||||
Asian |
0
0%
|
||||
Native Hawaiian or Other Pacific Islander |
0
0%
|
||||
Black or African American |
0
0%
|
||||
White |
0
0%
|
||||
More than one race |
0
0%
|
||||
Unknown or Not Reported |
0
0%
|
Outcome Measures
Title | Percentage of Brain Alpha5-Containing GABA-A Receptors Occupied by RO7017773 |
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Description | |
Time Frame | Baseline up to 48 hours (hrs) |
Outcome Measure Data
Analysis Population Description |
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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. |
Arm/Group Title | RO7017773 - 15mg | RO7017773 - 30mg | RO7017773 - 75mg | RO7017773 - 375mg |
---|---|---|---|---|
Arm/Group Description | 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. | 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. | 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. | 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. |
Measure Participants | 0 | 0 | 0 | 0 |
Title | Plasma Concentrations of RO7017773 |
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Description | |
Time Frame | Baseline up to 48 hrs |
Outcome Measure Data
Analysis Population Description |
---|
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. |
Arm/Group Title | RO7017773 - 15mg | RO7017773 - 30mg | RO7017773 - 75mg | RO7017773 - 375mg |
---|---|---|---|---|
Arm/Group Description | 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. | 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. | 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. | 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. |
Measure Participants | 0 | 0 | 0 | 0 |
Title | Number of Participants With Adverse Events (AEs) |
---|---|
Description | |
Time Frame | From treatment initiation until 14 days after the last dose of study treatment. |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | RO7017773 - 15mg | RO7017773 - 30mg | RO7017773 - 75mg | RO7017773 - 375mg |
---|---|---|---|---|
Arm/Group Description | 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. | 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. | 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. | 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. |
Measure Participants | 2 | 1 | 2 | 1 |
Number [Participants] |
2
100%
|
0
0%
|
1
50%
|
1
100%
|
Adverse Events
Time Frame | From treatment initiation until 14 days after the last dose of study treatment. | |||||||
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Adverse Event Reporting Description | All participants randomized to study treatment and who received at least one dose of the study treatment, whether prematurely withdrawn from the study or not, were included in the safety analysis. | |||||||
Arm/Group Title | RO7017773 - 15mg | RO7017773 - 30mg | RO7017773 - 75mg | RO7017773 - 375mg | ||||
Arm/Group Description | 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. | 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. | 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. | 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. | ||||
All Cause Mortality |
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RO7017773 - 15mg | RO7017773 - 30mg | RO7017773 - 75mg | RO7017773 - 375mg | |||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/2 (0%) | 0/1 (0%) | 0/2 (0%) | 0/1 (0%) | ||||
Serious Adverse Events |
||||||||
RO7017773 - 15mg | RO7017773 - 30mg | RO7017773 - 75mg | RO7017773 - 375mg | |||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/2 (0%) | 0/1 (0%) | 0/2 (0%) | 0/1 (0%) | ||||
Other (Not Including Serious) Adverse Events |
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RO7017773 - 15mg | RO7017773 - 30mg | RO7017773 - 75mg | RO7017773 - 375mg | |||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 2/2 (100%) | 0/1 (0%) | 1/2 (50%) | 1/1 (100%) | ||||
Gastrointestinal disorders | ||||||||
Nausea | 0/2 (0%) | 0/1 (0%) | 0/2 (0%) | 0/1 (0%) | ||||
General disorders | ||||||||
Catheter site pain | 2/2 (100%) | 0/1 (0%) | 0/2 (0%) | 0/1 (0%) | ||||
Catheter site paraesthesia | 1/2 (50%) | 0/1 (0%) | 0/2 (0%) | 0/1 (0%) | ||||
Catheter site bruise | 0/2 (0%) | 0/1 (0%) | 0/2 (0%) | 1/1 (100%) | ||||
Musculoskeletal and connective tissue disorders | ||||||||
Back pain | 0/2 (0%) | 0/1 (0%) | 1/2 (50%) | 0/1 (0%) | ||||
Nervous system disorders | ||||||||
Muscle contractions involuntary | 0/2 (0%) | 0/1 (0%) | 0/2 (0%) | 1/1 (100%) | ||||
Somnolence | 0/2 (0%) | 0/1 (0%) | 0/2 (0%) | 1/1 (100%) |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Results Point of Contact
Name/Title | Medical Communications |
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Organization | Hoffmann-La Roche |
Phone | 800-821-8590 |
genentech@druginfo.com |
- BP40257