Healthy Volunteers
Conditions
Brief summary
The purpose of this study is to investigate the effect of multiple oral doses of itraconazole on the pharmacokinetics of RO7017773 in healthy volunteers.
Interventions
DRUGRO7017773
Single doses of RO7017773
DRUGItraconazole
Multiple doses of Itraconazole
Sponsors
Hoffmann-La Roche
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 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 chemistry, serology and urinalysis) as judged by the Investigator. * Male 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 central nervous system (CNS) infections (e.g., meningitis) * History of clinically significant hypersensitivity or allergic reactions * Abnormal blood pressure * Abnormal pulse rate * History or presence of clinically significant ECG abnormalities before study drug administration or cardiovascular disease * Current or chronic history of liver disease, or known hepatic or biliary abnormalities * Positive test for drugs of abuse or alcohol * Evidence of human immunodeficiency virus (HIV) infection * Presence of hepatitis B surface antigen (HBsAg) or positive HCV antibody test result at screening or within 3 months prior to starting study treatment * Participants who regularly smoke more than 5 cigarettes daily or the equivalent and are unable or unwilling not to smoke during the in-house period
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Maximum Concentration (Cmax) of RO7017773 in Plasma | Period 1 (RO7017773) and Period 2 (RO7017773 + Itraconazole) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Adverse Events (AEs) | 12 weeks | — |
| Change in Suicide Risk as Assessed Using the Columbia Suicide Severity Rating Scale (C-SSRS) | From screening visit through Period 2 Day 11 | The C-SSRS is an assessment tool to evaluate suicidal ideation and behavior. Categories have binary responses (yes/no) and include: Wish to be Dead; Non-specific Active Suicidal Thoughts; Active Suicidal Ideation with Any Methods (Not Plan) without Intent to Act; Active Suicidal Ideation with Some Intent to Act, without Specific Plan; Active Suicidal Ideation with Specific Plan and Intent, Preparatory Acts and Behavior; Aborted Attempt; Interrupted Attempt; Actual Attempt (non-fatal); Completed Suicide. Suicidal ideation or behavior is indicated by a yes answer to any of the listed categories. A score of 0 is assigned if no suicide risk is present. |
| Cmax of Itraconazole in Plasma | Period 2 | — |
Countries
France
Participant flow
Recruitment details
Healthy male and female participants between 18 and 55 years old. Female participants were women of non-childbearing potential (WONCBP).
Participants by arm
| Arm | Count |
|---|---|
| RO7017773 Alone, Then RO7017773 + Itraconazole In Period 1, participants received a single dose of RO7017773 alone in a fed state. In Period 2, participants received a single dose of RO7017773 after repeated doses of itraconazole in a fed state. | 14 |
| Total | 14 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Period 2 | Adverse Event | 1 |
Baseline characteristics
| Characteristic | RO7017773 Alone, Then RO7017773 + Itraconazole |
|---|---|
| Age, Continuous | 44.1 Years STANDARD_DEVIATION 10.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 14 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 14 | 0 / 14 | 0 / 13 |
| other Total, other adverse events | 8 / 14 | 2 / 14 | 7 / 13 |
| serious Total, serious adverse events | 0 / 14 | 0 / 14 | 0 / 13 |
Outcome results
Primary
Maximum Concentration (Cmax) of RO7017773 in Plasma
Time frame: Period 1 (RO7017773) and Period 2 (RO7017773 + Itraconazole)
Population: The pharmacokinetic set (PKS) included all participants who received at least one dose of study treatment and who had data from at least one post-dose sample. This outcome measure is specific to the reported arms.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| RO7017773 Alone | Maximum Concentration (Cmax) of RO7017773 in Plasma | 458 ng/mL | Geometric Coefficient of Variation 32.1 |
| RO7017773 + Itraconazole | Maximum Concentration (Cmax) of RO7017773 in Plasma | 516 ng/mL | Geometric Coefficient of Variation 22.7 |
Secondary
Change in Suicide Risk as Assessed Using the Columbia Suicide Severity Rating Scale (C-SSRS)
The C-SSRS is an assessment tool to evaluate suicidal ideation and behavior. Categories have binary responses (yes/no) and include: Wish to be Dead; Non-specific Active Suicidal Thoughts; Active Suicidal Ideation with Any Methods (Not Plan) without Intent to Act; Active Suicidal Ideation with Some Intent to Act, without Specific Plan; Active Suicidal Ideation with Specific Plan and Intent, Preparatory Acts and Behavior; Aborted Attempt; Interrupted Attempt; Actual Attempt (non-fatal); Completed Suicide. Suicidal ideation or behavior is indicated by a yes answer to any of the listed categories. A score of 0 is assigned if no suicide risk is present.
Time frame: From screening visit through Period 2 Day 11
Population: The included set (IS) contained all study participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| RO7017773 Alone | Change in Suicide Risk as Assessed Using the Columbia Suicide Severity Rating Scale (C-SSRS) | Screening | 0 Units on a scale | Standard Deviation 0 |
| RO7017773 Alone | Change in Suicide Risk as Assessed Using the Columbia Suicide Severity Rating Scale (C-SSRS) | Period 2 Day 11 | 0 Units on a scale | Standard Deviation 0 |
| RO7017773 + Itraconazole | Change in Suicide Risk as Assessed Using the Columbia Suicide Severity Rating Scale (C-SSRS) | Screening | 0 Units on a scale | Standard Deviation 0 |
| RO7017773 + Itraconazole | Change in Suicide Risk as Assessed Using the Columbia Suicide Severity Rating Scale (C-SSRS) | Period 2 Day 11 | 0 Units on a scale | Standard Deviation 0 |
Secondary
Cmax of Itraconazole in Plasma
Time frame: Period 2
Population: The pharmacokinetic set (PKS) included all participants who received at least one dose of study treatment and who had data from at least one post-dose sample. This outcome measure is specific to the reported arm.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| RO7017773 Alone | Cmax of Itraconazole in Plasma | 724 ng/mL | Geometric Coefficient of Variation 43.2 |
Secondary
Percentage of Participants With Adverse Events (AEs)
Time frame: 12 weeks
Population: The safety set (SS) included all participants who received at least one dose of study treatment and included any participant(s) that were withdrawn from the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| RO7017773 Alone | Percentage of Participants With Adverse Events (AEs) | 57.1 Percentage of Participants |
| RO7017773 + Itraconazole | Percentage of Participants With Adverse Events (AEs) | 14.3 Percentage of Participants |
| RO7017773 + Itraconazole | Percentage of Participants With Adverse Events (AEs) | 53.8 Percentage of Participants |