18F-Dihydroxyphenylalanine (DOPA) Positron Emission Tomography (PET) Study to Explore Dopamine Synthesis Capacity in the Whole Striatum After 2 Weeks of Treatment With Ralmitaront or Placebo in Participants With Schizophrenia

NCT06880328 | Completed Phase 1 FDA Drug

• 1 other identifier: BP39833
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 4

Brief Summary

This study is an exploratory proof of mechanism (POM) study using PET/functional magnetic resonance imaging (fMRI) in a 2-period, 2-sequence, crossover design. The aim of the study is to confirm the potential of Ralmitaront to decrease dopamine synthesis capacity (DSC) - as measured by levels of F-DOPA - in the striatum of participants with schizophrenia.

Conditions

Schizophrenia

Outcome Measures

Primary Outcomes (1)

• Influx Rate Constant (Ki) Value of [18F]-DOPA in the Whole Striatum, as Measured Using [18F]-DOPA PET Imaging

  Baseline, and on Days 13-14 and Days 34-35

Secondary Outcomes (12)

• Bilateral Ventral Striatum Eigenvariates From the T-Contrast of Rewarded vs. Non-reward Expectation During the Monetary Incentive Delay (MID) Task, as Assessed Using fMRI

  Baseline, and on Days 13-14 and Days 34-35

• Percentage of High Effort Choices Under Deterministic Reward Condition for High Reward in the Effort-Choice Benefit Task

  Baseline, and on Days 13-14 and Days 34-35

• Mean Cerebral Blood Flow (CBF) in Different Brain Regions, as Measured by fMRI

  Baseline, and on Days 13-14 and Days 34-35

• Bilateral Eigenvariate From Dorsolateral Prefrontal Regions Defined Based on the 2-back >0-back Contrast in the N-back Working Memory Task, as Assessed Using fMRI

  Baseline, and on Days 13-14 and Days 34-35

• Incidence and Severity of Adverse Events (AEs)

  From first dose until 14 days after the last dose of study treatment (up to 49 days)

Study Arms (2)

Sequence 1: Ralmitaront then Placebo

EXPERIMENTAL

Participants were given a daily dose of Ralmitaront during the treatment period of 14 days, followed by a 7 day washout period, and then a daily dose for 14 days with the placebo.

Drug: Ralmitaront; Other: Radiolabeled PET tracer [18F]-DOPA; Drug: Placebo

Sequence 2: Placebo then Ralmitaront

EXPERIMENTAL

Participants were given a daily dose of the placebo during the 14 day period, followed by a 7 day washout, and then a daily dose of Ralmitaront for 14 days.

Drug: Ralmitaront; Other: Radiolabeled PET tracer [18F]-DOPA; Drug: Placebo

Interventions

Ralmitaront DRUG

Participants were given a once 150 mg daily dose of Ralmitaront orally during the 14 day treatment period.

Also known as: RO6889450

Sequence 1: Ralmitaront then Placebo; Sequence 2: Placebo then Ralmitaront

Radiolabeled PET tracer [18F]-DOPA OTHER

\[18 F\]-DOPA solution for injection is manufactured by the PET imaging centers according to specifications established for the tracer at the site. The injection will happen prior to the scan being done and will last for approximately 30 seconds.

Sequence 1: Ralmitaront then Placebo; Sequence 2: Placebo then Ralmitaront

Placebo DRUG

Participants were given a daily dose of the placebo during the 14 day treatment period.

Sequence 1: Ralmitaront then Placebo; Sequence 2: Placebo then Ralmitaront

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Male patients with non-acute schizophrenia defined by DSM-5 diagnosis of schizophrenia as established by the mini-international neuropsychiatric interview (MINI)
• Medically stable over 1 month and psychiatrically stable for at least 3 months prior to the screening visit
• Patients with evidence of clear treatment response to antipsychotics as documented by chart information or reported by the patient or an informant considered reliable by the Investigator
• Outpatient with no hospitalization for worsening of schizophrenia within 3 months prior to screening (hospitalization for social management within this time was acceptable)
• At least one positive and negative syndrome scale (PANSS) positive subscale item from P1 (delusion), P3 (hallucination), P5 (grandiosity), or P6 (suspiciousness/persecution) of mild or greater severity (score .3), but below 7 (extreme severity)
• Body mass index (BMI) between 18 and 35 kg/m2 inclusive

You may not qualify if:

• Diagnosis for bipolar disorder, schizoaffective disorder or major depressive disorder based on DSM-5
• A prior or current general medical condition that might be impairing central nervous system (CNS) functioning (e.g., head trauma with persistent clinically significant neurological or cognitive sequelae, dementia, seizure disorder, stroke, neurodegenerative, inflammatory, infectious, neoplastic, toxic, metabolic or endocrine disorders)
• Average triplicate QTcF interval greater than 450 msec or other clinically significant abnormality on screening electrocardiogram (ECG) as assessed by the Investigator or deputy based on centralized reading
• Clinically significant abnormalities in laboratory safety test results (including hepatic and renal panels, complete blood count, chemistry panel and urinalysis)
• Positive result at screening for hepatitis B (HBV), hepatitis C (HCV, untreated), or human immunodeficiency virus (HIV)-1 and HIV-2. HCV patients who had been successfully treated and who tested negative for HCV ribonucleic acid (RNA), could be considered eligible for entry into the study
• Patient at current significant risk of suicide or harming him or others according to the Investigator's judgment
• Patients with a history of violent/suicidal/homicidal behavior or history of suicidal/homicidal command hallucinations in the past 10 years
• Patients who have had 3 or more exacerbations associated with violent/suicidal/homicidal behavior or suicidal/homicidal command hallucinations (regardless of time)
• History of electroconvulsive treatment (ECT)
• Patients treated with long-acting injectable antipsychotic drugs or cariprazine
• Patients with known history of treatment resistance or having received clozapine within 3 months of screening
• Treatment with prohibited medication taken within 4 weeks (or within 5 times the elimination half-life of the medication) before the first study drug administration (whichever is longer). This included medications with known effects on cerebral blood flow.
• Use of grapefruit, Seville orange or star fruit containing products within 1 week before the first study drug administration
• Receipt of an investigational drug within 90 days or 5 times the half-life of the investigational drug, whatever was longer, prior to baseline visit
• Current active liver or biliary disease (with the exception of Gilbert's syndrome or asymptomatic gallstones or otherwise stable chronic liver disease per Investigator assessment)

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (4)

Parexel California Clinical Trials Medical Group

Glendale, California, 91206, United States

Location

Collaborative Neuroscience Network Inc.

Torrance, California, 90502, United States

Location

CBH Health

Gaithersburg, Maryland, 20877, United States

Location

St Louis Clinical Trials

St Louis, Missouri, 63141, United States

Location

MeSH Terms

Conditions

Schizophrenia

Interventions

fluorodopa F 18

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 11, 2025
• First Posted: March 17, 2025
• Study Start: November 7, 2018
• Primary Completion: September 4, 2019
• Study Completion: September 4, 2019
• Last Updated: March 17, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)