AVP-786 for Schizophrenia

No longer recruiting at 121 trial locations

Overseen By Nadine Knowles

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Avanir Pharmaceuticals

Must be taking: Atypical antipsychotics

Must not be taking: Anticholinergics

Disqualifiers: Major depressive disorder, Pseudo-parkinsonism, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 15 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new medication, AVP-786, to evaluate its effectiveness in treating negative symptoms of schizophrenia, such as lack of motivation or social withdrawal. The trial compares the effects of AVP-786 against a placebo (a pill with no active drug) to ensure the medication's safety and effectiveness. Individuals with schizophrenia who have stable positive symptoms but noticeable negative symptoms and are on a steady dose of a second-generation antipsychotic may be suitable candidates. As a Phase 2/3 trial, this study measures the treatment's effectiveness in a larger group and represents the final step before FDA approval, offering participants a chance to contribute to advancing schizophrenia treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must be stable on a second-generation atypical antipsychotic drug to participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that AVP-786 has been tested in other studies for conditions like agitation in Alzheimer's disease. In a study with over 200 patients, AVP-786 was generally well tolerated. Common side effects included falls, urinary tract infections, headaches, and diarrhea. Although some participants experienced these issues, the treatment was deemed safe enough to continue testing. The current trial is in advanced stages, indicating sufficient safety information to include more participants. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for schizophrenia?

Unlike the standard treatments for schizophrenia, which primarily target positive symptoms or aim to stabilize mood, AVP-786 is focused on alleviating negative symptoms, such as lack of motivation or social withdrawal. What makes AVP-786 stand out is its dual mechanism of action: it combines a deuterated form of dextromethorphan with quinidine, potentially enhancing neurotransmitter activity in the brain. Researchers are excited about AVP-786 because it offers a novel approach that could address a significant unmet need in schizophrenia care, offering hope for improved quality of life for patients.

What evidence suggests that AVP-786 might be an effective treatment for negative symptoms of schizophrenia?

This trial will compare AVP-786 with a placebo. Research suggests that AVP-786 might alleviate symptoms in other conditions, such as agitation in dementia. In one study, patients taking AVP-786 showed noticeable improvement in agitation compared to those on a placebo. However, not all studies have demonstrated clear benefits. This treatment combines drugs that may influence brain chemicals related to mood and behavior. Although these findings are promising, further research is needed to confirm AVP-786's effectiveness for the negative symptoms of schizophrenia. ^{1 2 4 6 7}

Are You a Good Fit for This Trial?

Inclusion Criteria

Participants who meet the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-V) diagnostic criteria for schizophrenia confirmed by the Mini International Neuropsychiatric Interview (M.I.N.I) Version 7.0.2

Participants must have well-controlled positive symptoms and prominent negative symptoms as defined by Positive and Negative Syndrome Scale (PANSS) criteria.

Participants currently receiving a second-generation atypical antipsychotic drug (SGA) are eligible if they are stable and adherent to their dosing schedule.

Exclusion Criteria

Participants with pseudo-parkinsonism secondary to their ongoing antipsychotic medication

Participants currently using anticholinergic medications

Participants recently hospitalized as in-patients

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive AVP-786 or placebo capsules administered orally twice a day

15 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• AVP-786
• Placebo

How Is the Trial Designed?

Group I: AVP-786 Experimental Treatment 1 Intervention

AVP-786 capsules will be administered orally twice a day over a 15-week period.

Group II: Placebo Placebo Group 1 Intervention

Placebo capsules will be administered orally twice a day over a 15-week period.

Who Is Running the Clinical Trial?

Avanir Pharmaceuticals

Lead Sponsor

Trials

32

Recruited

12,100+

Otsuka Pharmaceutical Development & Commercialization, Inc.

Lead Sponsor

Trials

271

Recruited

170,000+

John Kraus

Otsuka Pharmaceutical Development & Commercialization, Inc.

Chief Medical Officer since 2023

MD, PhD

Tarek Rabah

Otsuka Pharmaceutical Development & Commercialization, Inc.

Chief Executive Officer since 2022

BS in Biology and BA in Business from the American University of Beirut, MBA from McGill University

Published Research Related to This Trial

In a study involving 100 patients undergoing lumbar spine fusion surgeries, batroxobin and its combination with tranexamic acid significantly reduced both intraoperative and postoperative blood loss compared to a placebo.

The mean intraoperative blood loss was lowest in the batroxobin group (268.32 mL) and the combination group (256.96 mL), indicating their effectiveness, while no significant differences were found in blood transfusion needs or complications like deep vein thrombosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness and Safety of Batroxobin, Tranexamic Acid and a Combination in Reduction of Blood Loss in Lumbar Spinal Fusion Surgery. Nagabhushan, RM., Shetty, AP., Dumpa, SR., et al.[2021]

A new checklist called TIDieR-Placebo has been developed to improve the reporting of placebo or sham interventions in clinical trials, ensuring that researchers clearly describe these components alongside active treatments.

The checklist was created through expert consultation and aims to enhance the transparency of trial results, which is crucial for accurately assessing the benefits and harms of active interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TIDieR-Placebo: A guide and checklist for reporting placebo and sham controls. Howick, J., Webster, RK., Rees, JL., et al.[2020]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02442765

NCT02442765 | Efficacy, Safety and Tolerability of AVP- ... Participants received AVP-786-18 mg orally once daily (QD) in the morning and placebo orally QD in the evening for the first 7 days, followed by AVP-786-18 mg ...

2. otsuka-us.com otsuka-us.com/news/otsuka-announces-phase-3-topline-results-avp-786-treatment-agitation-associated-dementia-due

Otsuka Announces Phase 3 Topline Results of AVP-786 in ... There were 4 deaths reported in the trial; 1 (0.5%) in the AVP-786 low dose group and 3 (1.4%) in the placebo group. Full study results are not ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/27936965/

AVP-786 for the treatment of agitation in dementia ... AVP-923 reduced agitation in AD and was well tolerated in a phase II RCT that included more than 200 patients.

4. neurologylive.com neurologylive.com/view/avp-786-falls-short-phase-3-study-alzheimer-disease-agitation

AVP-786 Falls Short in Phase 3 Study of Alzheimer ... Results demonstrated a significant improvement on the primary end point—change in CMAI—for 1 of the 2 doses being studied. In terms of safety, ...

5. alzres.biomedcentral.com alzres.biomedcentral.com/articles/10.1186/s13195-025-01780-0

Deuteration may reduce the efficacy of dextromethorphan in ... We hypothesize that AVP-786 failed to demonstrate efficacy in treating agitation in AD dementia due to the negative impact of deuteration on dextromethorphan's ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03393520

Study Details | NCT03393520 | Assessment of the Efficacy, ... This study will be conducted to evaluate the efficacy, safety, and tolerability of AVP-786 compared to placebo, for the treatment of agitation in participants ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33615952/

AVP-786 as a promising treatment option for Alzheimer's ... Areas covered: The authors review the pharmacology, mechanism of action, pharmacokinetics, efficacy, safety and tolerability data of AVP-786, ...