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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04475848
Recruitment Status : Recruiting
First Posted : July 17, 2020
Last Update Posted : November 4, 2020
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Brief Summary:
This study will evaulate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of single- and multiple-ascending doses (SAD and MAD) and food effect (FE) of RO6953958 following oral administration in healthy male participants.

Condition or disease Intervention/treatment Phase
Autistic Disorder Autism Spectrum Disorder Child Development Disorders, Pervasive Mental Disorders Neurodevelopmental Disorders Drug: RO6953958 Drug: Placebo Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Investigator- /Subject-blind, Single- and Multiple-ascending Dose, Placebo-controlled Study to Investigate Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 Following Oral Administration in Healthy Male Participants
Actual Study Start Date : July 15, 2020
Estimated Primary Completion Date : April 16, 2021
Estimated Study Completion Date : April 16, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Part 1: SAD/FE
There will be 7 cohorts in this study. In each cohort, participants will receive a single oral dose of RO6953958 while fasted. Participants in the fed (FE) cohort will return to receive the same single oral dose of RO6953958 repeated in the fed state.
Drug: RO6953958

Part 1: RO6953958 will be administered in an adaptive manner. The starting dose is planned to be 5mg.

Part 2: The starting dose will be established based on the data from Part 1.


Placebo Comparator: Part 1: SAD placebo
There will be 7 cohorts in this study. In each cohort, participants will receive a single oral dose of a placebo while fasted/fed.
Drug: Placebo

Part 1: A placebo will be administered in an adaptive manner. The starting dose is planned to be 5mg.

Part 2: The starting dose will be established based on the data from Part 1.


Experimental: Part 2: MAD
A maximum of 5 dose levels are anticipated. For each dose level, a minimum of 8 and a maximum of 16 participants will receive a multiple oral dose of RO6953958 once daily (QD) for 10 days.
Drug: RO6953958

Part 1: RO6953958 will be administered in an adaptive manner. The starting dose is planned to be 5mg.

Part 2: The starting dose will be established based on the data from Part 1.


Placebo Comparator: Part 2: MAD placebo
A maximum of 5 dose levels are anticipated. For each dose level, a minimum of 8 and a maximum of 16 participants will receive a multiple oral dose of RO6953958 QD for 10 days.
Drug: Placebo

Part 1: A placebo will be administered in an adaptive manner. The starting dose is planned to be 5mg.

Part 2: The starting dose will be established based on the data from Part 1.





Primary Outcome Measures :
  1. Percentage of Participants with Adverse Events in Part 1 [ Time Frame: From randomization up to 7 weeks (or up to 14 weeks if the participant is part of the food effect cohort) ]
  2. Percentage of Participants with Adverse Events in Part 2 [ Time Frame: From randomization up to 8 weeks ]
  3. Part 2: Change in suicide risk assessed using the Columbia Suicide Severity Rating Scale (C-SSRS) [ Time Frame: From randomization up to 8 weeks ]

Secondary Outcome Measures :
  1. Part 1: Maximum Observed Plasma Concentration (Cmax) of RO6953958 and its Metabolites RO7021594 and RO7045755 in Fasted and Fed state [ Time Frame: Day 1 ]
  2. Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of RO6953958 and its Metabolites RO7021594 and RO7045755 in Fasted and Fed state [ Time Frame: Day 1 ]
  3. Part 1: Last Quantifiable Concentration (Clast) of RO6953958 and its Metabolites RO7021594 and RO7045755 in Fasted and Fed state [ Time Frame: Day 1 to Day 5 ]
  4. Part 1: Time To the Last Quantifiable Concentration (Tlast) of RO6953958 and its Metabolites RO7021594 and RO7045755 in Fasted and Fed state [ Time Frame: Day 1 to Day 5 ]
  5. Part 1: Terminal Elimination Phase Half-Life (T1/2) of RO6953958 and its Metabolites RO7021594 and RO7045755 in Fasted and Fed state [ Time Frame: Day 1 to Day 5 ]
  6. Part 1: Area Under the Concentration-Time Curve from Time 0 to 12 hours (AUC(0-12h)) of RO6953958 and its Metabolites RO7021594 and RO7045755 in Fasted and Fed state [ Time Frame: Day 1 to Day 5 ]
  7. Part 1: Area Under the Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of RO6953958 and its Metabolites RO7021594 and RO7045755 in Fasted and Fed state [ Time Frame: Day 1 to Day 5 ]
  8. Part 1: Area Under the Concentration-Time Curve from Time Extrapolated to Infinity (AUC (0-inf)) of RO6953958 and its Metabolites RO7021594 and RO7045755 in Fasted and Fed state [ Time Frame: Day 1 to Day 5 ]
  9. Part 1: Apparent Clearance (CL/F) of RO6953958 in Fasted and Fed state [ Time Frame: Day 1 to Day 5 ]
  10. Part 1: Apparent Volume of Distribution (V/F) of RO6953958 in Fasted and Fed state [ Time Frame: Day 1 to Day 5 ]
  11. Part 1: Cumulative Amount of Unchanged Drug Excreted into the Urine (Ae) of RO6953958 and its Metabolites RO7021594 and RO7045755 in Fasted and Fed state [ Time Frame: Day 1 to Day 5 ]
  12. Part 1: Fraction of the Administered Drug Excreted into the Urine (Fe) of RO6953958 in Fasted and Fed state [ Time Frame: Day 1 to Day 5 ]
  13. Part 1: Renal Clearance of the Drug from Urine (CLR) of RO6953958 in Fasted and Fed state [ Time Frame: Day 1 to Day 5 ]
  14. Parts 2: Cmax of RO6953958 and its Metabolites RO7021594 and RO7045755 [ Time Frame: Day 1 and Day 10 ]
  15. Parts 2: Molecular Weight Adjusted Metabolite-to-Parent Ratio for Cmax of RO6953958 and its Metabolites RO7021594 and RO7045755 [ Time Frame: Day 1 and Day 10 ]
  16. Parts 2: Average Plasma Concentration (Cavg) of RO6953958 and its Metabolites RO7021594 and RO7045755 [ Time Frame: Day 1 to Day 14 ]
  17. Part 2: Tmax of RO6953958 and its Metabolites RO7021594 and RO7045755 [ Time Frame: Day 1 and Day 10 ]
  18. Part 2: Area Under the Concentration-Time Curve (AUC(0-t)) of RO6953958 and its Metabolites RO7021594 and RO7045755 [ Time Frame: Day 1 to Day 14 ]
  19. Part 2: Molecular Weight Adjusted Metabolite-to-Parent Ratio for Area Under the Concentration-Time Curve (AUC(0-t)) of RO6953958 and its Metabolites RO7021594 and RO7045755 [ Time Frame: Day 1 to Day 14 ]
  20. Part 2: T1/2 of RO6953958 and its Metabolites RO7021594 and RO7045755 [ Time Frame: Day 1 to Day 14 ]
  21. Part 2: CL/F of RO6953958 [ Time Frame: Day 1 to Day 14 ]
  22. Part 2: V/F of RO6953958 [ Time Frame: Day 1 to Day 14 ]
  23. Part 2: Ae of RO6953958 [ Time Frame: Day 1 to Day 14 ]
  24. Part 2: Fe of RO6953958 [ Time Frame: Day 1 to Day 14 ]
  25. Part 2: CLR of RO6953958 [ Time Frame: Day 1 to Day 14 ]
  26. Part 2: Trough Plasma Concentration (Ctrough) of RO6953958 and its Metabolites RO7021594 and RO7045755 [ Time Frame: Day 1 to Day 14 ]
  27. Part 2: Accumulation Ratio based on AUC (Rauc) of RO6953958 and its Metabolites RO7021594 and RO7045755 [ Time Frame: Day 1 to Day 14 ]
  28. Part 2: Accumulation Ratio Based on Cmax (RCmax) of RO6953958 and its Metabolites RO7021594 and RO7045755 [ Time Frame: Day 1 to Day 14 ]
  29. Part 2: Accumulation Ratio based on Ctrough (RCtrough) of RO6953958 and its Metabolites RO7021594 and RO7045755 [ Time Frame: Day 1 to Day 14 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   Male
Gender Based Eligibility:   Yes
Accepts Healthy Volunteers:   Yes
Criteria

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 should have a habitual bedtime and a consistent sleep pattern.

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), unexplained syncope (within 12 months prior to screening), metabolic disorder, cancer, or cirrhosis
  • Use of any psychoactive medication, or medications known to have effects on central nervous system (CNS), or blood flow
  • History of convulsions
  • History of clinically significant hypersensitivity (e.g., drugs, excipients) or allergic reactions
  • Abnormal blood pressure (BP) and pulse rate
  • Presence of orthostatic hypotension
  • History or presence of clinically significant ECG abnormalities or cardiovascular disease
  • Current or chronic history of liver disease or known hepatic or biliary abnormalities
  • Known active or any major episode of infection within 4 weeks prior to the start of drug 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 medication including 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 who do not have a habitual bedtime
  • Part 2 (MAD) only - Participants who cannot produce sufficient saliva for study assessments
  • Participants who have donated more than 500 mL of blood or blood products or had significant blood loss within 3 months prior to screening

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04475848


Contacts
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Contact: Reference Study ID Number: BP41695 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. and Canada) global-roche-genentech-trials@gene.com

Locations
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United Kingdom
Hammersmith Medicines Research; Central Middlesex Hospital Recruiting
London, United Kingdom, NW10 7EW
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
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Study Director: Clinical Trials Hoffmann-La Roche
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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT04475848    
Other Study ID Numbers: BP41695
2019-004486-41 ( EudraCT Number )
First Posted: July 17, 2020    Key Record Dates
Last Update Posted: November 4, 2020
Last Verified: November 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/members/ourmembers/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Hoffmann-La Roche:
Autism Spectrum Disorder
Additional relevant MeSH terms:
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Disease
Autism Spectrum Disorder
Child Development Disorders, Pervasive
Mental Disorders
Autistic Disorder
Neurodevelopmental Disorders
Developmental Disabilities
Pathologic Processes