A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants

Last updated: July 8, 2024
Sponsor: Hoffmann-La Roche
Overall Status: Completed

Phase

1

Condition

Birth Defects

Tic Disorders

Asperger's Disorder

Treatment

RO6953958

Placebo

Midazolam

Clinical Study ID

NCT04475848
BP41695
2019-004486-41
  • Ages 18-55
  • Male
  • Accepts Healthy Volunteers

Study Summary

This study will evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of single- and multiple-ascending doses (SAD (Part 1) and MAD (Part 2)) and food effect (FE) of RO6953958 following oral administration in healthy male participants. Part 3 (Drug-drug interaction (DDI)) will assess the safety, tolerability, and effect of RO6953958 on the PK of the cytochrome P450 (CYP) 3A substrate midazolam.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • Body mass index (BMI) within 18 to 31 kg/m2

  • During treatment and for at least 14 days after the last dose to remain abstinent

  • Refrain from donating sperm for at least 14 days after last dose

  • Part 2 (MAD) only - Participants must be prepared to collect a sleep log and wear anactigraphy device the week before participation in the study. Participants must alsohave scored 5 or less on the Pittsburgh Sleep Quality Index (PSQI), less than 13 onthe Epworth sleepiness scale (ESS), and not be considered an extreme morning orevening type according to the morningness-eveningness questionnaire (MEQ) atscreening to be eligible.

Exclusion

Exclusion Criteria:

  • History or evidence of any medical condition potentially altering the absorption,metabolism, or elimination of drugs

  • History of any clinically significant gastrointestinal, renal, hepatic,bronchopulmonary, neurological, psychiatric, cardiovascular, endocrinological,hematological, or allergic disease, sleep disorders (Part 2 [MAD] only), unexplainedsyncope (within 12 months prior to screening), metabolic disorder, cancer, orcirrhosis

  • Use of any psychoactive medication, or medications known to have effects on centralnervous system (CNS), or blood flow

  • History of convulsions

  • History of clinically significant hypersensitivity (e.g., drugs, excipients) orallergic reactions

  • Abnormal blood pressure (BP) and pulse rate

  • Presence of orthostatic hypotension

  • History or presence of clinically significant ECG abnormalities or cardiovasculardisease

  • Current or chronic history of liver disease or known hepatic or biliaryabnormalities

  • Known active or any major episode of infection within 4 weeks prior to the start ofdrug administration

  • Participants who test positive for acute respiratory syndrome coronavirus 2 (SARS-CoV-2)

  • Have used or intend to use over-the-counter (OTC) or prescription medicationincluding herbal medications within 30 days prior to dosing

  • Positive test for drugs, abuse of alcohol, human immunodeficiency virus (HIV),hepatitis B or hepatitis C virus (HCV), presence of hepatitis B surface antigen (HBsAg), or positive hepatitis C antibody test

  • Inability or unwillingness to fully consume standardized breakfast at Day 1

  • Part 2 (MAD) only - Participants who have issues sleeping or participants who havetravelled across 2 or more time zones in the past month.

  • Part 2 (MAD) only - Participants who cannot produce sufficient saliva for studyassessments

  • Participants who have donated more than 500 mL of blood or blood products or hadsignificant blood loss within 3 months prior to screening

  • Have a history of clinically significant back pain, back pathology, and/or backinjury that may predispose to complications from, or technical difficulty with,lumbar puncture

  • Complications that would lead to difficulty in obtaining a lumbar puncture

  • Part 3 (DDI) only - History of hypersensitivity to benzodiazepines (includingmidazolam) or its formulation ingredients

Study Design

Total Participants: 88
Treatment Group(s): 3
Primary Treatment: RO6953958
Phase: 1
Study Start date:
July 15, 2020
Estimated Completion Date:
February 06, 2022

Connect with a study center

  • Hammersmith Medicines Research; Central Middlesex Hospital

    London, NW10 7EW
    United Kingdom

    Site Not Available

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