A Randomized, investigator/subject blind, adaptive, single and multiple ascending dose, placebo-controlled study to investigate safety, tolerability , pharmacokinetics, pharmacodynamics, food effect and taste of RO7017773 following oral administration in healthy participants.

Completed

Conditions: Autism Spectrum Disorder
10010118

Registration Number: NL-OMON46688

Lead Sponsor: F. Hoffmann-La Roche Ltd

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 184

Inclusion Criteria

1. Able and willing to provide written informed consent and to comply with the study protocol according to ICH and local regulations.
2. Participants 18 to 55 years of age inclusive, at the time of signing the informed consent.
3. Healthy, as judged by the Investigator. Healthy status will be defined as the absence of evidence of any active or chronic disease following a detailed medical and surgical history, a complete physical examination, vital signs, 12-lead ECG, hematology, blood chemistry, serology and urinalysis.;4. Body mass index (BMI) within the range 18 to 30 kg/m2 (inclusive).
5. Male and female participants
The contraception and abstinence requirements are intended to prevent exposure of an embryo to the study treatment. The reliability of sexual abstinence for male enrollment eligibility needs to be evaluated in relation to the duration of the clinical study and the preferred and usual lifestyle of the participant. Periodic abstinence and withdrawal are not acceptable methods of contraception.
e) Female Participants
A female participant is eligible to participate if she is not pregnant (see Appendix 5), not
breastfeeding, and the following condition applies:
* Women of non-childbearing potential (WONCBP), as defined in Appendix 5 who:
* Have a negative pregnancy test (blood) within the 21 days prior to the first study
drug administration.
f) Male Participants
During the treatment period and for at least 28 days after the last dose of study drug,
agreement to:
* Remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures such as a condom, with partners who are women of childbearing potential (WOCBP, as defined in Section 1 of Appendix 5), or pregnant female partners, to avoid exposing the embryo.
*Refrain from donating sperm 28 days.

Exclusion Criteria

1. Any condition or disease detected during the medical interview/physical examination that would render the participant unsuitable for the study, place the participant at undue risk or interfere with the ability of the participant to complete the study, as determined by the Investigator.
2. History or evidence of any medical condition potentially altering the absorption, metabolism or elimination of drugs. This includes a surgical history of the gastrointestinal tract affecting gastric motility or altering the gastrointestinal tract.
3. History of any clinically significant gastrointestinal, renal, hepatic, bronchopulmonary, neurological, psychiatric, cardiovascular, endocrinological, hematological or allergic disease, metabolic disorder, hypofertility, cancer or cirrhosis.
4. Use of any psychoactive medication, or medications known to have effects on CNS or blood flow taken within 4 weeks prior to first dosing (or within 5 times the elimination half-life of the medication) prior to first dosing (whichever is longer).
5. History of convulsions (other than benign febrile convulsions of childhood) including epilepsy, or personal history of significant cerebral trauma or CNS infections (e.g., meningitis).
6. History or current significant ophthalmologic or neurologic condition that would adversely affect the eye movement assessments.
7. A history of clinically significant hypersensitivity (e.g., drugs, excipients) or allergic reactions.
8. Any major illness within one month before the screening examination or any febrile illness within one week prior to screening and up to first study drug administration.
9. Abnormal blood pressure, defined as confirmed (based on the average of >/=3 consecutive measurements) 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.
10. Abnormal pulse rate, defined as confirmed (based on the average of >/=3 consecutive measurements) resting pulse rate greater than 100 or less than 40 bpm.
11. History or presence of clinically significant ECG abnormalities before study drug administration (e.g. PQ/PR interval >210 ms, QTcF > 450 ms (>470 ms females) or cardiovascular disease (e.g., cardiac insufficiency, coronary artery disease, cardiomyopathy, congestive heart failure, family history of congenital long QT syndrome, family history of sudden death).
12. Clinically significant abnormalities in laboratory test results (including hepatic and renal panels, complete blood count, chemistry panel and urinalysis). In the case of uncertain or questionable results, tests performed during screening may be repeated before randomization to confirm eligibility.
13.ALT and bilirubin > 1.5 X ULN (isolated bilirubin > 1.5 X ULN is acceptable if bilirubin is fractionated and direct bilirubin < 35%).
14. Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).;15. Participants who, in the Investigator's judgment, pose a suicidal or homicidal risk, or any participant with a history of suicidal or homicidal attempts.
16. Have used or intend to use over-the-counter or prescription medication including herbal medications within 30 days prior to dosing.
17. Participants likely to need concomitant medication during the study period (including for dental conditions).
18. Participation

Study & Design

Study Type: Observational invasive

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Part 1, 2 and 3;<br /><br>Incidence and severity of AEs.<br /><br>Changes in vital signs, physical findings, ECG parameters, and clinical<br /><br>laboratory results during and following RO7017773 administration.<br /><br>Change in suicide risk (using Columbia Suicide Severity Rating Scale).</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>All parts<br /><br><br /><br>PK parameters of RO7017773.<br /><br>Change from baseline in spontaneous brain electrical activity by qEEG<br /><br><br /><br>part 2a<br /><br>PK parameters of RO7017773 in fasted and in fed state. </p><br>