Safety, tolerability, pharmacokinetics and pharmacodynamics of ralmitaront and risperidone in healthy participants Not Applicable
Conditions
Interventions
The study duration is up to 8 weeks. This includes a screening period for up to 28 days before the beginning of the study period
an in-house period consisting of two study treatment periods staying at the study center for up to 20 days or 19 nights
and a follow-up visit for 14 days after the last dose of ralmitaront on Day 14. Participants will be asked to come to the study center about three times, if not needed for additional visits. When taki
Sponsors
Roche (Switzerland)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. A body mass index (BMI) between 18–30 kg/m², inclusive, at screening 2. Fluent in English
Exclusion criteria
Exclusion criteria: 1. History of any clinically significant gastrointestinal, renal, hepatic, bronchopulmonary, neurological, psychiatric, cardiovascular, endocrinological, hematological or allergic disease, metabolic disorder, or cancer 2. Disorders of the CNS that are clinically significant as determined by the Investigator, including psychiatric disorders, behavioral disturbances, cerebrovascular events, depression, bipolar disorder, migraine, Parkinson’s, parkinsonism, and seizures 3. Elevated risk of clinically significant suicidal ideation and/or behavior within 2 years prior to screening as determined by the C-SSRS 4. History or evidence of any medical condition potentially altering the absorption, metabolism, or elimination of drugs. Uncomplicated appendectomy and cholecystectomy are acceptable 5. A history of clinically significant hypersensitivity (e.g. drugs, excipients) or allergic reactions 6. Hypersensitivity to risperidone or paliperidone, as stated in the prescribing information for risperidone 7. In the opinion of the Investigator, any major illness within 1 month before the screening examination, or any febrile illness within 1 week prior to screening and up to first study treatment administration 8. Use of prohibited medications (vaccines, over-the-counter [OTC] or prescription medication including herbal medications) taken within 14 days (or 5 times the elimination half-life of the medication, whichever is longer) prior to dosing, with the exception of acetaminophen up to 2 g per day, which is allowed up to 48 hours before dosing, and stable hormonal replacement or contraception therapy; COVID vaccine must be at least 21 days before dosing 9. Use of any drug or herbal inducers of CYP3A, CYP2C19, CYP2D6, or Pgp within 28 days prior to dosing 10. Participants likely to need concomitant medication during the study period (including for dental conditions) 11. Any suspicion or history of alcohol abuse and/or suspicion of regular consumption of drug of abuse in the last 5 years 12. Positive alcohol breath test or urine drug screen at screening or admission to the study site 13. Smokers who regularly smoke more than 5 cigarettes daily or equivalent and are unable or unwilling not to smoke during the confinement in CRU 14. Positive test result for human immunodeficiency virus (HIV) 1 and HIV 2, hepatitis C virus (HCV) antibody, or hepatitis B surface antigen (HBsAg) 15. Dietary restrictions that would prohibit the consumption of standardized meals 16. Participants under judicial supervision, guardianship, or curatorship 17. Women who are lactating 18. History of clinically significant back pain, back pathology, and/or back injury (e.g., degenerative disease, spinal deformity, spinal surgery, lumbar radiculopathy, chronic/recurrent headaches, intracranial tumors, and/or increase intracranial pressure) that may predispose to complications from, or technical difficulty with, a lumbar puncture 19. Criteria that would preclude a lumbar puncture, such as a local infection at the site of the lumbar puncture; clinically significant coagulation parameter abnormalities, thrombocytopenia, or treatment with an anticoagulant or with antiplatelet agents with
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Plasma concentrations and pharmacokinetic parameters of risperidone and 9-OH-risperidone measured using blood samples on days 1, 2, 3, 4, 5 of period 1 and days 14, 15, 16, 17, 18 of period 2 The following PK parameters will be calculated: maximum concentration (Cmax), area under the concentration-time curve from time 0 to infinity (AUC0-inf) and time to reach maximum plasma concentration (tmax) In addition, other parameters may be calculated as outlined below: Risperidone only: Last measurable plasma concentration (Clast), time of Clast (tlast), terminal rate constant (lambda z), t1/2, AUC from time 0 to 24 hours postdose (AUC0-24h), AUC from time 0 to last measurable concentration (AUC0-last), CL/F, and apparent volume of distribution after oral administration (V/F) 9-OH-risperidone only: Clast, tlast, lamda z, t1/2, AUC0-24h, AUC0-last and metabolic ratio of 9-OH-risperidone and risperidone for Cmax and AUC0-inf | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Plasma concentrations and pharmacokinetic parameters of ralmitaront measured using blood samples on days 6-18 of period 2. The following PK parameters will be calculated: Cmax, AUC0-inf and tmax. In addition, other parameters may be calculated as outlined below. Clast, tlast, lamda z, t1/2, AUC0-24h, CL/F*, V/F*, AUC0-last and metabolic ratio of M5 versus ralmitaront for Cmax and AUC0-inf (*not for M5) 2. Percentage of participants with adverse events recorded throughout the study 3. Involuntary movement disorders (Parkinsonism, akathisia, dystonia, and dyskinesia) assessed using the Extrapyramidal Symptom Rating Scale-Abbreviated (ESRS-A) on days -1 and 1 of period 1 and days 13 and 14 of period 2 4. Suicidal thoughts and behaviours assessed using the Columbia-Suicide Severity Rating Scale (C-SSRS) at screening, day -2 of period 1, days 13 and 14 of period 2 and at follow up 5. QTcF (QT corrected for heart rate using the Fridericia’s correction factor) measured from 12-lead ECGs extracted from continuous (Holter) recordings on day 5 of period 1, days 6, 7, 13 and 14 of period 2 6. Heart rate (HR), PR and QRS (QRScomplex) interval measured from 12-lead ECGs extracted from continuous (Holter) recordings on day 5 of period 1, days 6, 7, 13 and 14 of period 2 | — |
Countries
United States of America
Contacts
Public ContactClinical Trials
Outcome results
None listed