SchizophreniaPhase 1NCT06880328
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
A Phase 1 study testing Ralmitaront and Radiolabeled PET tracer [18F]-DOPA in people with Schizophrenia, run by Hoffmann-La Roche at 4 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 50 years, men only
- Conditions the study is for
- Schizophrenia
- What is being tested?
- Ralmitaront and Radiolabeled PET tracer [18F]-DOPA
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 35 participants
- Where
- 4 sitesUnited States
- Study dates
- 7 Nov 2018to 4 Sep 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- Men only
- No healthy volunteers
- Adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 22Show fewer
- 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)
- Moderate-to-severe substance use disorder within 6 months of screening (excluding caffeine) as defined by DSM-5
- Heavy smokers as defined by a high dependence score in the Fagerstrom Tolerance Scale (score ≥ 6)
- Positive urine drug screen for amphetamines, methamphetamines, opiates, buprenorphine, methadone, cannabinoids, cocaine and barbiturates after informed consent and prior to randomization
- Any sensorial impairment such as deafness and reduced visual acuity, which could not be corrected in the MRI scanner
- Clinically significant abnormal findings on the baseline MRI images such as stroke, infarction, space-occupying lesion such as tumor, structural abnormalities, or vascular pathology
- Known exposure to radiation in the last year that would mean the total exposure to radiation with participation in the study was likely to exceed 30 mSv
- Donation of blood over 400 mL within 3 months prior to screening
Trial locations and contacts
4 sites in 1 country.
United States4 sites
CBH Health
Gaithersburg, Maryland, 20877
Parexel California Clinical Trials Medical Group
Glendale, California, 91206
St Louis Clinical Trials
St Louis, Missouri, 63141
Collaborative Neuroscience Network Inc.
Torrance, California, 90502
About this study
Official title: 18F-Dihydroxyphenylalanine (DOPA) Positron Emission Tomography (PET), Randomized, Double-blind, Crossover Study to Explore Dopamine Synthesis Capacity in the Whole Striatum After 2 Weeks of Treatment With 150mg of RO6889450 or Placebo in Patients With Schizophrenia
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
- Being tested
- Ralmitaront, Radiolabeled PET tracer [18F]-DOPA, Placebo
- Medical subject headings
- Schizophrenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RalmitarontDrug
Also called RO6889450
Participants were given a once 150 mg daily dose of Ralmitaront orally during the 14 day treatment period.
Radiolabeled PET tracer [18F]-DOPAOther
[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.
PlaceboDrug
Participants were given a daily dose of the placebo during the 14 day treatment period.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Ralmitaront; Other: Radiolabeled PET tracer [18F]-DOPA; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Influx Rate Constant (Ki) Value of [18F]-DOPA in the Whole Striatum, as Measured Using [18F]-DOPA PET Imaging
Measured: 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
Measured: 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
Measured: Baseline, and on Days 13-14 and Days 34-35
Mean Cerebral Blood Flow (CBF) in Different Brain Regions, as Measured by fMRI
Measured: 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
Measured: Baseline, and on Days 13-14 and Days 34-35
Incidence and Severity of Adverse Events (AEs)
Measured: From first dose until 14 days after the last dose of study treatment (up to 49 days)
Incidence of Treatment Discontinuations Due to AEs
Measured: From first dose until 14 days after the last dose of study treatment (up to 49 days)
Incidence of Vitals Sign Abnormalities (Resting and Orthostatic)
Measured: From first dose until 14 days after the last dose of study treatment (up to 49 days)
Change From Baseline in ECG Intervals: PQ (PR), QRS, QT, RR and QTcF
Measured: Baseline, Days 13-14, 21, 34-35, and during the follow-up visit (14-18 days after last dose)
Incidence of Laboratory Abnormalities, Based on Hematology, Clinical Chemistry, and Urinalysis Test Results
Measured: From first dose until 14 days after the last dose of study treatment (up to 49 days)
Concentration of Ralmitaront and Ralmitaront-derived Metabolite(s) Per Time-point
Measured: Days 2, 7, 13-14, 23, 28, 34-35, and during the follow up visit (14-18 days after last dose)
Area Under the Curve (AUCss) of Ralmitaront and Ralmitaront-derived Metabolite(s)
Measured: Days 2, 7, 13-14, 23, 28, 34-35, and during the follow up visit (14-18 days after last dose)
Cmax of Ralmitaront and Ralmitaront-derived Metabolite(s)
Measured: Days 2, 7, 13-14, 23, 28, 34-35, and during the follow up visit (14-18 days after last dose)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Mar 2025
- Study start7 Nov 2018
- Primary completion4 Sep 2019
- Study completion4 Sep 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SchizophreniaStudies of the same condition, open and under way.
- More trials run by Hoffmann-La RocheThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 35 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06880328
- Sponsor's protocol ID
- BP39833
- Status last verified
- Mar 2025
- First submitted
- 11 Mar 2025
- Last updated
- 17 Mar 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 18F-Dihydroxyphenylalanine (DOPA) Positron Emission Tomography (PET), Randomized, Double-blind, Crossover Study to Explore Dopamine Synthesis Capacity in the Whole Striatum After 2 Weeks of Treatment With 150mg of RO6889450 or Placebo in Patients With Schizophrenia
- ClinicalTrials.gov ID
- NCT06880328
- Acronym / sponsor ID
- BP39833
- Conditions
- Schizophrenia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 35 participants (actual)
- Lead sponsor
- Hoffmann-La RocheIndustry (pharma, biotech, devices)
- Study start
- 7 Nov 2018 (actual)
- Primary completion
- 4 Sep 2019 (actual)
- Study completion
- 4 Sep 2019 (actual)
- First posted
- 17 Mar 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sequence 1: Ralmitaront then Placebo | Experimental | Drug: Ralmitaront, Other: Radiolabeled PET tracer [18F]-DOPA, Drug: PlaceboParticipants 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. |
| Sequence 2: Placebo then Ralmitaront | Experimental | Drug: Ralmitaront, Other: Radiolabeled PET tracer [18F]-DOPA, Drug: PlaceboParticipants 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. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- 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)
Key exclusion criteria (22 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RalmitarontAlso: RO6889450Participants were given a once 150 mg daily dose of Ralmitaront orally during the 14 day treatment period. | Drug | Sequence 1: Ralmitaront then Placebo, Sequence 2: Placebo then Ralmitaront |
| Radiolabeled PET tracer [18F]-DOPA[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. | Other | Sequence 1: Ralmitaront then Placebo, Sequence 2: Placebo then Ralmitaront |
| PlaceboParticipants were given a daily dose of the placebo during the 14 day treatment period. | Drug | Sequence 1: Ralmitaront then Placebo, Sequence 2: Placebo then Ralmitaront |
Primary outcome
Influx Rate Constant (Ki) Value of [18F]-DOPA in the Whole Striatum, as Measured Using [18F]-DOPA PET Imaging
Time frame: Baseline, and on Days 13-14 and Days 34-35
12 secondary outcomes
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
Time frame: 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
Time frame: Baseline, and on Days 13-14 and Days 34-35
Mean Cerebral Blood Flow (CBF) in Different Brain Regions, as Measured by fMRI
Time frame: 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
Time frame: Baseline, and on Days 13-14 and Days 34-35
Incidence and Severity of Adverse Events (AEs)
Time frame: From first dose until 14 days after the last dose of study treatment (up to 49 days)
Incidence of Treatment Discontinuations Due to AEs
Time frame: From first dose until 14 days after the last dose of study treatment (up to 49 days)
Incidence of Vitals Sign Abnormalities (Resting and Orthostatic)
Time frame: From first dose until 14 days after the last dose of study treatment (up to 49 days)
Change From Baseline in ECG Intervals: PQ (PR), QRS, QT, RR and QTcF
Time frame: Baseline, Days 13-14, 21, 34-35, and during the follow-up visit (14-18 days after last dose)
Incidence of Laboratory Abnormalities, Based on Hematology, Clinical Chemistry, and Urinalysis Test Results
Time frame: From first dose until 14 days after the last dose of study treatment (up to 49 days)
Concentration of Ralmitaront and Ralmitaront-derived Metabolite(s) Per Time-point
Time frame: Days 2, 7, 13-14, 23, 28, 34-35, and during the follow up visit (14-18 days after last dose)
Area Under the Curve (AUCss) of Ralmitaront and Ralmitaront-derived Metabolite(s)
Time frame: Days 2, 7, 13-14, 23, 28, 34-35, and during the follow up visit (14-18 days after last dose)
Cmax of Ralmitaront and Ralmitaront-derived Metabolite(s)
Time frame: Days 2, 7, 13-14, 23, 28, 34-35, and during the follow up visit (14-18 days after last dose)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Mar 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Trials study director
Hoffmann-La Roche
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Ralmitaront and Radiolabeled PET tracer [18F]-DOPA in people with Schizophrenia, run by Hoffmann-La Roche at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Influx Rate Constant (Ki) Value of [18F]-DOPA in the Whole Striatum, as Measured Using [18F]-DOPA PET Imaging (time frame: Baseline, and on Days 13-14 and Days 34-35). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Mar 2025.