Open Label, Adaptive, Parallel Group PET Study Using RO7017773 And [11C] RO15-4513

Sponsor
Hoffmann-La Roche (Industry)
Overall Status
Completed
CT.gov ID
NCT03507569
Collaborator
(none)
6
1
1
1.9
3.1

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
Phase 1

Study Design

Study Type:
Interventional
Actual Enrollment :
6 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Non-Randomized Open Label, Adaptive, Parallel Group, Human Positron Emission Tomography (PET) Study to Assess Occupancy of Brain alpha5-Containing GABAA Receptors of Ro7017773 Using [11C] Ro15-4513 Following Single Oral Doses in Healthy Participants
Actual Study Start Date :
Apr 24, 2018
Actual Primary Completion Date :
Jun 22, 2018
Actual Study Completion Date :
Jun 22, 2018

Arms and Interventions

Arm Intervention/Treatment
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.

Outcome Measures

Primary Outcome Measures

  1. Percentage of Brain Alpha5-Containing GABA-A Receptors Occupied by RO7017773 [Baseline up to 48 hours (hrs)]

  2. Plasma Concentrations of RO7017773 [Baseline up to 48 hrs]

Secondary Outcome Measures

  1. Number of Participants With Adverse Events (AEs) [From treatment initiation until 14 days after the last dose of study treatment.]

Eligibility Criteria

Criteria

Ages Eligible for Study:
23 Years to 55 Years
Sexes Eligible for Study:
All
Accepts 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

Contacts and Locations

Locations

Site City State Country Postal Code
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.
Responsible Party:
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT03507569
Other Study ID Numbers:
  • BP40257
First Posted:
Apr 25, 2018
Last Update Posted:
Sep 30, 2019
Last Verified:
Aug 1, 2019
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:

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.
Pre-assignment Detail
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.
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%
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

1. Primary Outcome
Title Percentage of Brain Alpha5-Containing GABA-A Receptors Occupied by RO7017773
Description
Time Frame Baseline up to 48 hours (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
2. Primary Outcome
Title Plasma Concentrations of RO7017773
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
3. Secondary Outcome
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.
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
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
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

[Not Specified]

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
Organization Hoffmann-La Roche
Phone 800-821-8590
Email genentech@druginfo.com
Responsible Party:
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT03507569
Other Study ID Numbers:
  • BP40257
First Posted:
Apr 25, 2018
Last Update Posted:
Sep 30, 2019
Last Verified:
Aug 1, 2019