Non-respiratory sleep disturbances in people with neurodevelopmental disorders (NDDs) Nervous System Diseases
Conditions
Interventions
Period 1: Participants will be administered a single oral dose of RO6953958 under fed conditions (30 minutes after starting a standard breakfast). Follow up for 7 days.
Period 2: Participants will be
Sponsors
Roche (Switzerland)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Participants who are healthy as determined by medical evaluation including medical history, surgical history, physical examination, laboratory tests, and cardiac monitoring 2. Body mass index within the range 18 to 32 kg/m² (inclusive).
Exclusion criteria
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; unexplained syncope (within 12 months prior to screening); metabolic disorder; cancer; or cirrhosis. 4. Use of any psychoactive medication, or medications known to have effects on the CNS or blood flow, taken within 30 days prior to the first dosing (or within 5 times the elimination half-life of the medication) prior to the 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 of clinically significant hypersensitivity (e.g., drugs, excipients) or allergic reactions. 7. Any major illness within 1 month before the screening examination or any febrile illness within 1 week prior to screening and up to the first study drug administration. 8. Current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones). 9. Known active infection or any major episode of infection within 4 weeks prior to the start of drug administration. 10. Participants who test positive for SARS-CoV-2 should not be enrolled. 11. Known hypersensitivity to itraconazole or to any of the other excipients, or to any other triazole antifungals. 12. Any other known contraindications to itraconazole as stated in the U.S. Prescribing Information. 13. Have used or intend to use over-the-counter (OTC or prescription medication including herbal medications as described in the list of prohibited medications. 14. Participants likely to need concomitant medication during the study period (including for dental conditions). 15. Positive result on hepatitis B or hepatitis C virus (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. NOTE: Participants with positive hepatitis C antibody test due to prior resolved disease can be enrolled if a confirmatory negative hepatitis C ribonucleic acid test is obtained. 16. A positive pregnancy test (women of childbearing potential only). 17. Positive test for drugs of abuse or alcohol. 18. Show evidence of human immunodeficiency virus (HIV) infection and/or positive test for HIV antibody at screening. 19. Dietary restrictions that would prohibit the consumption of standardized meals. 20. Participants who regularly smoke more than 5 cigarettes daily on average or vape equivalent amounts of nicotine and are unable or unwilling to stop smoking/vaping during the in-house period. 21. Only for the participants who will undergo taste assessment in Period 1: history or evidence of any medical condition that has altered taste sensory perception including age
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Current primary outcome measure as of 23/05/2024: 1. Maximum observed plasma concentration (Cmax) of RO6953958, and its metabolites (M1, and M3) measured using non-compartmental methods 2. Area under the concentration-time curve from time 0 to infinity (AUC0-inf) of RO6953958, and its metabolites (M1, and M3) measured using non-compartmental methods 3. Area under the concentration-time curve up to last measurable concentration (AUClast) of RO6953958, and its metabolites (M1, and M3) measured using non-compartmental methods Cmax, AUC0-inf, and AUClast were assessed based on samples collected at the following timepoints: Period 1: Predose and 0.25, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10 and 12 hours post dose on Day 1, and on Days 2, 3, 4, 5, 6, 7; Period 2: Predose and 0.25, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10 and 12 hours post dose on Day 4, and on Days 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 and 18 ______ Previous primary outcome measure: 1. Plasma concentrations and pharmacokinetic parameters of RO6953958, M1, and M3 measured using blood samples on days 1, 2, 3, 4, 5, 6, 7 of period 1 and days 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 of period 2 and at follow up. The following PK parameters will be calculated if data allows: Maximum concentration (Cmax), area under the concentration-time curve from time 0 to infinity (AUC0-inf), or area under the concentration-time curve up to last measurable concentration (AUClast) if AUCinf can’t be estimated. | — |
Secondary
| Measure | Time frame |
|---|---|
| Current secondary outcome measures as of 23/05/2024: 1. Percentage of participants with adverse events and severity of AEs assessed by the investigator as mild, moderate, or severe from screening up to follow up (approximately 9 weeks) 2. Concentrations of itraconazole and its metabolite hydroxy-itraconazole measured using non-compartmental methods from blood samples collected on days 2, 3, 4, 6, 8, and 10 of period 2. _____ Previous secondary outcome measures: 1. Percentage of participants with adverse events measured by the investigator throughout the study. 2. Concentrations of itraconazole and its metabolite hydroxy-itraconazole measured using blood samples on days 2, 3, 4, 6, 8, and 10 of period 2. | — |
Countries
United States of America
Contacts
Public ContactClinical Trials
Outcome results
None listed