Valbenazine for Schizophrenia
Recruiting in Palo Alto (17 mi)
+77 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Waitlist Available
Sponsor: Neurocrine Biosciences
Stay on Your Current Meds
Pivotal Trial (Near Approval)
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?
The primary objective for this study is to evaluate the effect of adjunctive valbenazine versus placebo on symptoms of schizophrenia in participants who have inadequate response to antipsychotic treatment.
Do I have to stop taking my current medications for this trial?
The trial does not specify that you need to stop taking your current medications. In fact, you must be on a stable regimen of antipsychotic medication to participate.
What data supports the idea that Valbenazine for Schizophrenia is an effective drug?
The available research does not provide specific data supporting the effectiveness of Valbenazine for treating schizophrenia. The studies mentioned focus on other drugs or placebo effects in schizophrenia treatment, but do not include Valbenazine. Therefore, there is no direct evidence from the provided information to support Valbenazine's effectiveness for schizophrenia.12345
What safety data exists for Valbenazine in treating schizophrenia?
The provided research does not contain specific safety data for Valbenazine or its other names (Ingrezza, Ingrezza Sprinkle, DYSVAL, MT 5199, NBI-98854, REMLEAS, Valbenazine-tosylate) in the treatment of schizophrenia. The studies focus on other antipsychotic drugs and their safety profiles, but Valbenazine is not mentioned. Further research specifically targeting Valbenazine would be needed to answer this question.678910
Eligibility Criteria
This trial is for individuals aged 13 or older with a medically confirmed diagnosis of schizophrenia for at least one year. They must be on stable antipsychotic medication and not responding adequately to treatment. Participants need an adult informant and agree to use contraception. Excluded are those pregnant, breastfeeding, resistant to treatments, recently suicidal, or with severe substance disorders.Inclusion Criteria
The participant must have an adult informant (for example, a family member, relative, partner, social worker, caseworker, residential facility staff, or nurse).
My antipsychotic medication dose has not changed recently.
My symptoms are stable and I am not hospitalized.
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Exclusion Criteria
You have been diagnosed with schizophrenia that does not respond well to treatment.
Pregnant or breastfeeding or plans to become pregnant during the study. This criterion must be reconfirmed prior to the first dose of study treatment on Day 1.
You have had thoughts of hurting yourself or have attempted suicide in the past 6 months.
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Treatment Details
Interventions
- Placebo (Other)
- Valbenazine (Vesicular Monoamine Transporter 2 (VMAT2) Inhibitor)
Trial OverviewThe Journey Study tests Valbenazine as an additional treatment against a placebo in people with schizophrenia who aren't fully helped by their current antipsychotics. The goal is to see if Valbenazine can better alleviate symptoms when used alongside standard medications.
Participant Groups
2Treatment groups
Experimental Treatment
Placebo Group
Group I: Vesicular monoamine transporter 2 (VMAT2) inhibitorExperimental Treatment1 Intervention
Valbenazine once daily
Group II: PlaceboPlacebo Group1 Intervention
Placebo once daily.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Neurocrine Clinical SiteStanford, CA
Neurocrine Clinical SiteCoral Gables, FL
Neurocrine Clinical SiteLincoln, NE
Neurocrine Clinical SiteSaint Louis, MO
More Trial Locations
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Who Is Running the Clinical Trial?
Neurocrine BiosciencesLead Sponsor
References
Early onset of antipsychotic action in schizophrenia: evaluating the possibility of shorter acute efficacy trials. [2021]Extended placebo-controlled clinical trials in schizophrenia research pose an ethical challenge. This study examines factors that have implications for the design and duration of placebo-controlled acute efficacy trials: Does early response discriminate active drug (AD) from placebo, and are the early differences sustained over time? A post hoc pooled analysis of 2 randomized 6-week double-blind clinical trials was performed comparing patients with schizophrenia treated with placebo or low-dose olanzapine (1 mg/d; placebo/low dose [PBO] group, n = 170) to patients treated with a 10- to 20-mg/d dose of haloperidol or medium- to high-dose olanzapine (7.5 to 17.5 mg/d; AD group, n = 252). Mixed-model repeated-measure analysis tested for group differences. Power analysis was undertaken to compare study designs with shorter durations. At 2 weeks, the mean reduction in the Brief Psychiatric Rating Scale total score was significantly greater for the AD group (-10.1) compared with the PBO group (-4.1; P
Placebo effects in adult and adolescent patients with schizophrenia: combined analysis of nine RCTs. [2020]To examine characteristics of placebo responders and seek optimal criteria of early improvement with placebo for predicting subsequent placebo response in patients with schizophrenia.
Early Placebo Improvement Is a Marker for Subsequent Placebo Response in Long-Acting Injectable Antipsychotic Trials for Schizophrenia: Combined Analysis of 4 RCTs. [2019]Placebo effects remain largely unexplored in clinical trials of long-acting injectable (LAI) antipsychotics for schizophrenia. This study aims to characterize patients showing improvements after placebo injections and to search for criteria for the prediction of subsequent response based on the magnitude of score changes after the first week of treatment.
Deprenyl augmentation for treating negative symptoms of schizophrenia: a double-blind, controlled study. [2019]Augmentation of dopaminergic neurotransmission has been suggested as a treatment strategy for negative symptoms of schizophrenia. On the basis of open studies that reported the potential benefit of deprenyl (selegiline) as augmentation to antipsychotic treatment, this double-blind, controlled study was designed to further address this question. Sixteen schizophrenic patients with predominately negative symptoms, manifesting clinical stability on maintenance antipsychotic treatment, were randomly assigned to receive either deprenyl 15 mg/day or placebo in addition to their antipsychotic treatment for 8 weeks. Clinical follow-up and ratings were done during this period and for 8 more weeks after deprenyl discontinuation. Both groups showed a statistically significant but clinically marginal improvement over the 8 weeks of deprenyl or placebo treatment. This improvement was abolished during the postdiscontinuation follow-up period. Deprenyl at a dose of 15 mg/day did not offer therapeutic benefit in our patients. A significant placebo effect was observed, which may be the result of increased patient-doctor contact during the study.
Paliperidone palmitate versus risperidone long-acting injection in markedly-to-severely ill schizophrenia subjects: onset of efficacy with recommended initiation regimens. [2015]To examine onset of efficacy of two long-acting injectable atypical antipsychotics in markedly-to-severely ill schizophrenia subjects.
Adverse effects associated with second-generation antipsychotic long-acting injection treatment: a comprehensive systematic review. [2018]As second-generation antipsychotic long-acting injections (SGA-LAIs) are rapidly replacing depot first-generation antipsychotics as first-line agents in treating schizophrenia spectrum disorders, a systematic assessment of their adverse effects is timely. English-language, peer-reviewed articles reporting original data on the safety and tolerability of SGA-LAIs were identified electronically by searching the MEDLINE, EMBASE, PsycINFO, and DARE databases and the Cochrane Library (January 2001-April 2013). In addition to second-generation (atypical) antipsychotics and long-acting injection (depot) antipsychotics, a separate search was performed for each available drug: aripiprazole LAI, olanzapine pamoate, paliperidone palmitate, and risperidone LAI. Articles were excluded if they were review articles, post hoc analyses, analyses of subsets of patients enrolled in previous trials, single case reports, case series studies, small naturalistic studies (involving less than 50 patients), studies providing no safety data, and studies lasting less than 8 weeks. Of 181 articles identified from the search, 140 were excluded; thus, 41 articles met the inclusion criteria. Predictably, the reviewed information revealed that SGA-LAIs have safety profiles consistent with their oral parent formulations. However, they seem to also show unforeseen and worrisome safety signals. Indeed, the routine use of olanzapine-LAI in clinical practice could be limited not only by the well-known risk of postinjection syndrome, whose clinical management remains a matter of concern, but also by the risk of worsening of psychosis. The reviewed information seems to suggest that worsening of psychotic symptoms and depression could also be associated with both risperidone-LAI and paliperidone palmitate. The leading cause of death among patients enrolled in risperidone-LAI studies was suicide. Given the exponential growth in the clinical use of SGA-LAIs, further studies must be urgently performed in order to confirm or exclude the potential safety signals associated with such drugs.
Safety and efficacy of long-acting injectable risperidone in daily practice: an open-label, noninterventional, prospective study in schizophrenia and related disorders. [2019]This postauthorization safety study evaluated the long-term safety, tolerability, and efficacy of risperidone long-acting injectable (RLAI) in routine clinical practice. In this 6-month, multicenter, European, naturalistic study, patients were included if, during routine clinical practice, long-term antipsychotic therapy with RLAI was deemed necessary by the treating physician. Efficacy measures included Clinical Global Impression-Severity and Global Assessment of Functioning. Safety was evaluated by recording treatment-emergent adverse events (AE). RLAI was initiated in 5134 patients (aged 14-94 years); predominantly male (58.6%) with paranoid schizophrenia (69.8%). RLAI initial doses were 25 mg every 2 weeks (37.0% patients), 37.5 mg (18.0%), and 50 mg (44.4%). Treatment was completed by 4314 patients (84.0%). RLAI was discontinued on account of loss to follow-up (n=346; 6.7%), insufficient response (n=116; 2.3%), and AEs (n=106; 2.1%). Clinical Global Impression-Severity significantly improved from baseline to endpoint (P or = 5% of patients were akathisia, extrapyramidal disorders, depression, psychotic disorder, anxiety, and weight gain. Serious AEs were reported by 384 (8%) patients. This study confirms good safety, tolerability, and efficacy with RLAI in routine clinical practice.
Antipsychotic drugs versus placebo for relapse prevention in schizophrenia: a systematic review and meta-analysis. [2022]Relapse prevention with antipsychotic drugs compared with placebo in patients with schizophrenia has not been sufficiently addressed by previous systematic reviews. We aimed to assess the association between such drugs and various outcomes in patients with schizophrenia to resolve controversial issues.
The risk of death among adult participants in trials of antipsychotic drugs in schizophrenia. [2010]In this paper we investigate mortality in short-term placebo-controlled trials conducted to demonstrate efficacy and safety of atypical antipsychotic drugs for the treatment of schizophrenic patients in the acute phase of illness. Arguments are provided, why short-term placebo-controlled studies are required. This is an integrated analysis of results from randomized placebo-controlled trials conducted pre-licensing for risperidone, olanzapine, quetiapine IR, ziprasidone, risperidone consta, aripiprazole, paliperidone, and quetiapine XR. Information was retrieved from study publications, EPAR, and from the FDA SBA, all in the public domain. 7553 patients were randomized in the remaining 23 short-term acute phase clinical trials. 2/5738 patients died after having been randomized to an active treatment. 5/1815 died in the placebo group. The crude odds-ratio for an increased death risk with placebo treatment is 7.92 (95% confidence interval (1.45 to 40.87), two sided P=0.0134). Death narratives show: (i) both deaths in active treatment groups occurred during randomized treatment period, (ii) two deaths in the placebo group of a trial in the elderly were observed in patients with severe co-morbidities not usually included in a randomized trial, and (iii) two further deaths in the placebo groups occurred 9 and 23 days after the end of the randomized treatment period. Under these circumstances the crude odds-ratio for an increased risk of death for patient with placebo as compared to active treatment is 1.58 (95% confidence interval (0.14-17.45), two sided P=0.71). Confidence intervals are generally wide indicating a still limited knowledge about a potential increase in mortality with placebo treatment. Unless, however, society is willing to take the risk that ineffective drugs are licensed and cause undetected harm thereafter, or is willing to restrict licensing to drugs that are superior to current treatments, short-term placebo-controlled trials in the acute phase of schizophrenia are necessary. Measures are proposed to minimize risks.
Upcoming agents for the treatment of schizophrenia: mechanism of action, efficacy and tolerability. [2018]Since the introduction of a group of atypical antipsychotics in the 1990s, there has been a decline in the rate of new antipsychotics being introduced into clinical practice. However, with increasing safety and efficacy concerns over currently available drugs and a dearth of options available for atypical depot formulations, there is a considerable need for the development of new formulations and agents. This review examines the profile of seven antipsychotic drugs currently in the premarketing stage of development and summarizes their mechanism of action, clinical potential and safety.Asenapine is an antipsychotic with activity for multiple receptors and has potential to improve negative and cognitive symptoms of schizophrenia. Bifeprunox is a partial dopamine D2 and serotonin 5-HT(1A) receptor agonist showing a less than convincing efficacy profile, but which may offer safety advantages over available agents by means of a reduced risk of metabolic complications. Iloperidone is a D2 and 5-HT(2A) receptor antagonist requiring further studies to establish its effectiveness. It has a high affinity for alpha(1)-adrenoceptors, which can lead to associated haemodynamic adverse effects. Nemonapride is essentially a typical antipsychotic drug, similar in structure to sulpiride, which has been available for some time in Japan. It has efficacy against positive symptoms and has shown some antidepressant and anxiolytic properties, although efficacy data for it are somewhat limited. Norclozapine (N-desmethylclozapine) is a major metabolite of clozapine formed by its demethylation. Its partial agonist activity at D2 receptors has raised interest in it as an antipsychotic in its own right. In addition, it appears to have muscarinic agonist activity, which is believed to be responsible for the observed positive effects it has on cognition. It was envisaged to be effective as an adjunct to other agents or at high doses in the treatment of refractory schizophrenia, although a recent randomized, controlled study showed that it was no more effective than placebo in patients with schizophrenia experiencing an acute psychotic episode. Olanzapine pamoate depot injection has shown comparable efficacy to oral olanzapine in several studies. However, it has provoked considerable safety concerns by its association with inadvertent intravascular injection events in numerous patients. This accidental intravascular administration of olanzapine pamoate leads to excessive sedation, confusion, dizziness and altered speech. Post-injection observation periods and postmarketing surveillance are planned following the introduction of the depot. Paliperidone palmitate is the palmitate ester of paliperidone, the major metabolite of risperidone, and is formulated as a long-acting injection for intramuscular use. Its pharmacology is comparable to risperidone, having D2 and 5-HT(2A) receptor antagonist activity. Efficacy studies have shown positive results, and because paliperidone has no antagonistic activity at cholinergic receptors, it has low potential for anticholinergic adverse effects, including cognitive dysfunction. However, with higher doses, the frequency of extrapyramidal side effects and orthostatic hypotension have been shown to be greater than with placebo.
Predictors of Placebo Response in Pharmacological Clinical Trials of Negative Symptoms in Schizophrenia: A Meta-regression Analysis. [2022]We conducted a meta-regression analysis of all double-blind, randomized, placebo-controlled clinical trials (DBRCTs) reporting effects of drug and placebo on negative symptoms in people with stable schizophrenia and predominant or prominent negative symptoms to assess predictors of placebo response in these individuals. We used Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines for systematic reviews and meta-analyses to conduct a systematic literature search to identify DBRCTs assessing treatment efficacy on negative symptoms, as primary outcome, in patients with stable schizophrenia and predominant or prominent negative symptoms. We used Cohen's d, with 95% CIs, as the effect size measure for placebo response, based on negative symptom change scores from baseline to endpoint (range 4 to 24 wk) in the placebo-treated group. We included 18 DBRCTs from 17 publications, assessing the effect of 13 drugs vs placebo on negative symptoms and comprising 998 patients, in the meta-regression analyses. Overall, drugs showed greater efficacy than placebo in reducing negative symptoms, with small effect size (Cohen's d: 0.208, P = .020). Placebo response was significant (P
60 years of placebo-controlled antipsychotic drug trials in acute schizophrenia: Meta-regression of predictors of placebo response. [2019]A recent meta-regression had shown that the degree of placebo response, which has increased over the decades, is the major predictor of drug-placebo differences in antipsychotic drug trials in acutely ill patients with schizophrenia. Drug response, however, had remained stable. In the current meta-regression we explored the factors that are associated with placebo-response.