ICSR 2015

COLORADO SPRINGS – What kinds of early social interventions and cognitive remediation work to improve outcomes in schizophrenia? What’s the importance of stable medication regimens and psychoeducation for family members? Learn the answers to these questions and more in this discussion between Dr. S. Charles Schulz, head of the department of psychiatry at the University of Minnesota, Minneapolis, and his colleague Michael F. Green, Ph.D., who is head of the Green Lab at the University of California, Los Angeles, which was recorded at the International Congress on Schizophrenia Research.

[email protected]

On Twitter @whitneymcknight

COLORADO SPRINGS – What kinds of early social interventions and cognitive remediation work to improve outcomes in schizophrenia? What’s the importance of stable medication regimens and psychoeducation for family members? Learn the answers to these questions and more in this discussion between Dr. S. Charles Schulz, head of the department of psychiatry at the University of Minnesota, Minneapolis, and his colleague Michael F. Green, Ph.D., who is head of the Green Lab at the University of California, Los Angeles, which was recorded at the International Congress on Schizophrenia Research.

[email protected]

On Twitter @whitneymcknight

COLORADO SPRINGS – What kinds of early social interventions and cognitive remediation work to improve outcomes in schizophrenia? What’s the importance of stable medication regimens and psychoeducation for family members? Learn the answers to these questions and more in this discussion between Dr. S. Charles Schulz, head of the department of psychiatry at the University of Minnesota, Minneapolis, and his colleague Michael F. Green, Ph.D., who is head of the Green Lab at the University of California, Los Angeles, which was recorded at the International Congress on Schizophrenia Research.

[email protected]

On Twitter @whitneymcknight

COLORADO SPRINGS– Many clinicians are unaware that nonpharmacologic interventions can lead to positive results for patients with schizophrenia, according to Dr. Sophia Vinogradov and Dr. Joshua Woolley, psychiatrists from the University of California, San Francisco.

“The one message we have is that there is hope,” Dr. Woolley says in this interview, which was recorded at the biennial meeting of the 15th International Congress on Schizophrenia Research. Patients with schizophrenia can still “live a fulfilling life and have a significant recovery.”

Dr. Vinogradov and Dr. Woolley discuss how clinicians can use cognitive training techniques, cognitive-behavioral therapy, social media, and mobile technology to help ensure positive outcomes where patients see their disease not as a reason to withdraw from society but as an opportunity to engage with others who share similar struggles.

 [email protected]

On Twitter @whitneymcknight

COLORADO SPRINGS– Many clinicians are unaware that nonpharmacologic interventions can lead to positive results for patients with schizophrenia, according to Dr. Sophia Vinogradov and Dr. Joshua Woolley, psychiatrists from the University of California, San Francisco.

“The one message we have is that there is hope,” Dr. Woolley says in this interview, which was recorded at the biennial meeting of the 15th International Congress on Schizophrenia Research. Patients with schizophrenia can still “live a fulfilling life and have a significant recovery.”

Dr. Vinogradov and Dr. Woolley discuss how clinicians can use cognitive training techniques, cognitive-behavioral therapy, social media, and mobile technology to help ensure positive outcomes where patients see their disease not as a reason to withdraw from society but as an opportunity to engage with others who share similar struggles.

 [email protected]

On Twitter @whitneymcknight

COLORADO SPRINGS– Many clinicians are unaware that nonpharmacologic interventions can lead to positive results for patients with schizophrenia, according to Dr. Sophia Vinogradov and Dr. Joshua Woolley, psychiatrists from the University of California, San Francisco.

“The one message we have is that there is hope,” Dr. Woolley says in this interview, which was recorded at the biennial meeting of the 15th International Congress on Schizophrenia Research. Patients with schizophrenia can still “live a fulfilling life and have a significant recovery.”

Dr. Vinogradov and Dr. Woolley discuss how clinicians can use cognitive training techniques, cognitive-behavioral therapy, social media, and mobile technology to help ensure positive outcomes where patients see their disease not as a reason to withdraw from society but as an opportunity to engage with others who share similar struggles.

 [email protected]

On Twitter @whitneymcknight

COLORADO SPRINGS – The once monthly long-acting injectable formulation of the atypical antipsychotic aripiprazole was superior to a similar formulation of paliperidone palmitate in health-related quality-of-life scale total scores in people with schizophrenia, new data show.

The primary results in the head-to-head trial were supported by a significant decrease in Clinical Global Impression Scale (CGI-S) scores, better tolerability, and less treatment-related adverse events.

“The field has longed for such trials that fairly compare available treatments. Both treatments were effective, but aripiprazole once monthly was more effective across almost all measures,” Dr. Steven G. Potkin, the Robert R. Sprague Chair in Brain Imaging and a professor of psychiatry at the University of California, Irvine, and a lead author on the study, said in an interview.

Data from the QUALIFY study were presented at the biennial meeting of the 15th International Congress on Schizophrenia Research.

According to Dr. Potkin, the study is the first to use the quality of life scale to compare the effects of two, once-monthly, long-acting injectables (LAIs) with different modes of action in schizophrenia to determine treatment effects on patients’ overall social experience, work capacity, sense of purpose, curiosity, empathy, motivation, and level of presence in the community.

“The study has meaningful clinical impact, as it addresses some of the more important concerns that individuals with schizophrenia face such as ability to socialize and interact with others,” Dr. Potkin said.

In this phase IIIb, multicenter, international 28-week, randomized, open-label, rater-blinded, parallel group study, Dr. Potkin and his colleagues randomly assigned 295 adults with schizophrenia who were switching form an oral antipsychotic to an injectable one, to receive either the partial dopamine D2 agonist aripiprazole once monthly 400 mg or the dopamine D2 antagonist paliperidone palmitate at equivalent flexible dosing equivalent of 50 mg to 150 mg per month in the European Union and Canada, or 78 mg to 234 mg per month in the United States.

Patients were stable at baseline. Nearly 60% were male, and 44% were obese. Mean age was 42 years. Baseline quality of life scale (QLS) scores for the 148 individuals in the aripiprazole arm were 66.1 (standard deviation, 21.4) and 62.5 (SD, 21.3) for the 147 persons in the paliperidone palmitate arm. The baseline CGI-S scores for both groups was 4.0. Patients were assessed every 4th week.

By week 28, 100 in the aripiprazole arm completed treatment, and 83 completed treatment in the paliperidone palmitate arm.

The mean doses at week 24 were 387.0 +/– standard equivalent 3.4 mg for aripiprazole and 110.3 +/– 3.6 mg for paliperidone palmitate for the E.U. and Canada. The U.S. equivalent was 172 mg.

The primary endpoint of QLS scores at week 28 demonstrated the noninferiority and superiority of once-monthly aripiprazole over paliperidone palmitate. The aripiprazole arm improved QLS scores by 7.47 (SD, 1.53) compared with 2.80 (SD, 1.62) in the other group. The least square mean difference between treatments was 4.67 (95% confidence interval, [0.32; 9.02]; P = .036).

“The study was designed as a noninferiority trial, that is, to determine if aripiprazole 400 mg once monthly was as good as paliperidone palmitate,” Dr. Potkin said. “Not only was the aripiprazole as good as paliperidone palmitate, but indeed it was superior in the important health-related quality of life measures.”

Aripiprazole also significantly bested paliperidone palmitate in the secondary endpoint of improvements in the CGI-S score: –0.75 (SD, 0.07), compared with –0.46 (SD, 0.07). The least square mean difference between treatment was –0.28 (95% CI [–0.48; –0.09]; P = .004).

Adverse events assessed during the oral conversion, LAI-initiation, and LAI-continuation phases were more common in the paliperidone palmitate group during all phases but the initiation phase (51 reported events vs. 55 in the aripiprazole group). Significant adverse events were more common in the paliperidone palmitate group during the continuation phase (8 events vs. 6), and treatment-related adverse events leading to discontinuation of therapy during the continuation phase occurred in 13 of the paliperidone palmitate group vs. 6 in the aripiprazole group.

Insomnia was reported in both groups across all phases, as was weight gain, which was more common in the paliperidone palmitate group during the continuation phase (17 vs. 12).

“The study design represents the choice that clinicians face when deciding which atypical long-acting formulation to recommend to which patient,” Dr. Potkin said. “What I think is clinically relevant is that the primary outcome measure was the patient’s quality of life that includes the patient’s negative symptoms such as lack of empathy, motivation, curiosity, and socialization, and the consequence of these symptoms on everyday functioning. These symptoms are the most important to patients and their loved ones once the initial acute symptom episode has been stabilized.”

This trial was underwritten by Otsuka, makers of Abilify Maintena, and by H. Lundbeck A/S. Dr. Potkin is on the speakers bureau for Otsuka, Forest, and Sunovion, and serves on advisory boards of Alkermes, Forest, Genetech, Lundbeck, Otsuka, Roche, Sunovion, and Takeda.

[email protected]

On Twitter @whitneymcknight

COLORADO SPRINGS – The once monthly long-acting injectable formulation of the atypical antipsychotic aripiprazole was superior to a similar formulation of paliperidone palmitate in health-related quality-of-life scale total scores in people with schizophrenia, new data show.

The primary results in the head-to-head trial were supported by a significant decrease in Clinical Global Impression Scale (CGI-S) scores, better tolerability, and less treatment-related adverse events.

“The field has longed for such trials that fairly compare available treatments. Both treatments were effective, but aripiprazole once monthly was more effective across almost all measures,” Dr. Steven G. Potkin, the Robert R. Sprague Chair in Brain Imaging and a professor of psychiatry at the University of California, Irvine, and a lead author on the study, said in an interview.

Data from the QUALIFY study were presented at the biennial meeting of the 15th International Congress on Schizophrenia Research.

According to Dr. Potkin, the study is the first to use the quality of life scale to compare the effects of two, once-monthly, long-acting injectables (LAIs) with different modes of action in schizophrenia to determine treatment effects on patients’ overall social experience, work capacity, sense of purpose, curiosity, empathy, motivation, and level of presence in the community.

“The study has meaningful clinical impact, as it addresses some of the more important concerns that individuals with schizophrenia face such as ability to socialize and interact with others,” Dr. Potkin said.

In this phase IIIb, multicenter, international 28-week, randomized, open-label, rater-blinded, parallel group study, Dr. Potkin and his colleagues randomly assigned 295 adults with schizophrenia who were switching form an oral antipsychotic to an injectable one, to receive either the partial dopamine D2 agonist aripiprazole once monthly 400 mg or the dopamine D2 antagonist paliperidone palmitate at equivalent flexible dosing equivalent of 50 mg to 150 mg per month in the European Union and Canada, or 78 mg to 234 mg per month in the United States.

Patients were stable at baseline. Nearly 60% were male, and 44% were obese. Mean age was 42 years. Baseline quality of life scale (QLS) scores for the 148 individuals in the aripiprazole arm were 66.1 (standard deviation, 21.4) and 62.5 (SD, 21.3) for the 147 persons in the paliperidone palmitate arm. The baseline CGI-S scores for both groups was 4.0. Patients were assessed every 4th week.

By week 28, 100 in the aripiprazole arm completed treatment, and 83 completed treatment in the paliperidone palmitate arm.

The mean doses at week 24 were 387.0 +/– standard equivalent 3.4 mg for aripiprazole and 110.3 +/– 3.6 mg for paliperidone palmitate for the E.U. and Canada. The U.S. equivalent was 172 mg.

The primary endpoint of QLS scores at week 28 demonstrated the noninferiority and superiority of once-monthly aripiprazole over paliperidone palmitate. The aripiprazole arm improved QLS scores by 7.47 (SD, 1.53) compared with 2.80 (SD, 1.62) in the other group. The least square mean difference between treatments was 4.67 (95% confidence interval, [0.32; 9.02]; P = .036).

“The study was designed as a noninferiority trial, that is, to determine if aripiprazole 400 mg once monthly was as good as paliperidone palmitate,” Dr. Potkin said. “Not only was the aripiprazole as good as paliperidone palmitate, but indeed it was superior in the important health-related quality of life measures.”

Aripiprazole also significantly bested paliperidone palmitate in the secondary endpoint of improvements in the CGI-S score: –0.75 (SD, 0.07), compared with –0.46 (SD, 0.07). The least square mean difference between treatment was –0.28 (95% CI [–0.48; –0.09]; P = .004).

Adverse events assessed during the oral conversion, LAI-initiation, and LAI-continuation phases were more common in the paliperidone palmitate group during all phases but the initiation phase (51 reported events vs. 55 in the aripiprazole group). Significant adverse events were more common in the paliperidone palmitate group during the continuation phase (8 events vs. 6), and treatment-related adverse events leading to discontinuation of therapy during the continuation phase occurred in 13 of the paliperidone palmitate group vs. 6 in the aripiprazole group.

Insomnia was reported in both groups across all phases, as was weight gain, which was more common in the paliperidone palmitate group during the continuation phase (17 vs. 12).

“The study design represents the choice that clinicians face when deciding which atypical long-acting formulation to recommend to which patient,” Dr. Potkin said. “What I think is clinically relevant is that the primary outcome measure was the patient’s quality of life that includes the patient’s negative symptoms such as lack of empathy, motivation, curiosity, and socialization, and the consequence of these symptoms on everyday functioning. These symptoms are the most important to patients and their loved ones once the initial acute symptom episode has been stabilized.”

This trial was underwritten by Otsuka, makers of Abilify Maintena, and by H. Lundbeck A/S. Dr. Potkin is on the speakers bureau for Otsuka, Forest, and Sunovion, and serves on advisory boards of Alkermes, Forest, Genetech, Lundbeck, Otsuka, Roche, Sunovion, and Takeda.

[email protected]

On Twitter @whitneymcknight

COLORADO SPRINGS – The once monthly long-acting injectable formulation of the atypical antipsychotic aripiprazole was superior to a similar formulation of paliperidone palmitate in health-related quality-of-life scale total scores in people with schizophrenia, new data show.

The primary results in the head-to-head trial were supported by a significant decrease in Clinical Global Impression Scale (CGI-S) scores, better tolerability, and less treatment-related adverse events.

“The field has longed for such trials that fairly compare available treatments. Both treatments were effective, but aripiprazole once monthly was more effective across almost all measures,” Dr. Steven G. Potkin, the Robert R. Sprague Chair in Brain Imaging and a professor of psychiatry at the University of California, Irvine, and a lead author on the study, said in an interview.

Data from the QUALIFY study were presented at the biennial meeting of the 15th International Congress on Schizophrenia Research.

According to Dr. Potkin, the study is the first to use the quality of life scale to compare the effects of two, once-monthly, long-acting injectables (LAIs) with different modes of action in schizophrenia to determine treatment effects on patients’ overall social experience, work capacity, sense of purpose, curiosity, empathy, motivation, and level of presence in the community.

“The study has meaningful clinical impact, as it addresses some of the more important concerns that individuals with schizophrenia face such as ability to socialize and interact with others,” Dr. Potkin said.

In this phase IIIb, multicenter, international 28-week, randomized, open-label, rater-blinded, parallel group study, Dr. Potkin and his colleagues randomly assigned 295 adults with schizophrenia who were switching form an oral antipsychotic to an injectable one, to receive either the partial dopamine D2 agonist aripiprazole once monthly 400 mg or the dopamine D2 antagonist paliperidone palmitate at equivalent flexible dosing equivalent of 50 mg to 150 mg per month in the European Union and Canada, or 78 mg to 234 mg per month in the United States.

Patients were stable at baseline. Nearly 60% were male, and 44% were obese. Mean age was 42 years. Baseline quality of life scale (QLS) scores for the 148 individuals in the aripiprazole arm were 66.1 (standard deviation, 21.4) and 62.5 (SD, 21.3) for the 147 persons in the paliperidone palmitate arm. The baseline CGI-S scores for both groups was 4.0. Patients were assessed every 4th week.

By week 28, 100 in the aripiprazole arm completed treatment, and 83 completed treatment in the paliperidone palmitate arm.

The mean doses at week 24 were 387.0 +/– standard equivalent 3.4 mg for aripiprazole and 110.3 +/– 3.6 mg for paliperidone palmitate for the E.U. and Canada. The U.S. equivalent was 172 mg.

The primary endpoint of QLS scores at week 28 demonstrated the noninferiority and superiority of once-monthly aripiprazole over paliperidone palmitate. The aripiprazole arm improved QLS scores by 7.47 (SD, 1.53) compared with 2.80 (SD, 1.62) in the other group. The least square mean difference between treatments was 4.67 (95% confidence interval, [0.32; 9.02]; P = .036).

“The study was designed as a noninferiority trial, that is, to determine if aripiprazole 400 mg once monthly was as good as paliperidone palmitate,” Dr. Potkin said. “Not only was the aripiprazole as good as paliperidone palmitate, but indeed it was superior in the important health-related quality of life measures.”

Aripiprazole also significantly bested paliperidone palmitate in the secondary endpoint of improvements in the CGI-S score: –0.75 (SD, 0.07), compared with –0.46 (SD, 0.07). The least square mean difference between treatment was –0.28 (95% CI [–0.48; –0.09]; P = .004).

Adverse events assessed during the oral conversion, LAI-initiation, and LAI-continuation phases were more common in the paliperidone palmitate group during all phases but the initiation phase (51 reported events vs. 55 in the aripiprazole group). Significant adverse events were more common in the paliperidone palmitate group during the continuation phase (8 events vs. 6), and treatment-related adverse events leading to discontinuation of therapy during the continuation phase occurred in 13 of the paliperidone palmitate group vs. 6 in the aripiprazole group.

Insomnia was reported in both groups across all phases, as was weight gain, which was more common in the paliperidone palmitate group during the continuation phase (17 vs. 12).

“The study design represents the choice that clinicians face when deciding which atypical long-acting formulation to recommend to which patient,” Dr. Potkin said. “What I think is clinically relevant is that the primary outcome measure was the patient’s quality of life that includes the patient’s negative symptoms such as lack of empathy, motivation, curiosity, and socialization, and the consequence of these symptoms on everyday functioning. These symptoms are the most important to patients and their loved ones once the initial acute symptom episode has been stabilized.”

This trial was underwritten by Otsuka, makers of Abilify Maintena, and by H. Lundbeck A/S. Dr. Potkin is on the speakers bureau for Otsuka, Forest, and Sunovion, and serves on advisory boards of Alkermes, Forest, Genetech, Lundbeck, Otsuka, Roche, Sunovion, and Takeda.

[email protected]

On Twitter @whitneymcknight

COLORADO SPRINGS– Three-month injectable paliperidone palmitate significantly delayed time to relapse compared to placebo in patients with schizophrenia, according to phase III clinical study data being presented at the biennial meeting of the 15th International Congress on Schizophrenia Research.

The study also was published in JAMA Psychiatry.

If approved, patients would be dosed with only four injections of the atypical antipsychotic per year rather than once per month, which is the current dosing for the injectable formulation. Oral atypical antipsychotics are administered daily.

Whitney McKnight/Frontline Medical News

“It would be nice if there were more use, in general, of the long-acting injectables, and we hope these data will encourage that because it would increase [compliance],” Dr. Adam Savitz, a researcher on the study, said in an interview. “If it gets approved, it’s something clinicians should consider their patients could benefit from.”

Janssen, maker of the drug, has filed a New Drug Application with the Food and Drug Administration for the 3-month paliperidone palmitate injection to treat schizophrenia in adults. According to a statement from the company, a regulatory action is expected on May 18, 2015, after which time Janssen plans to file for markets outside the United States.

The multicenter, international trial conducted from April 26, 2012, through April 9, 2014, included 506 adults randomized to either the study drug or to placebo. Conducted in four phases, the study began with a 3-week screening phase, followed by a flexible-dose 17-week open-label transition phase in which patients received once-monthly doses of the 1-month formulation of paliperidone palmitate (50, 75, 100, or 150 mg). During the 12-week open-label maintenance phase, patients received a single dose of the 3-month formulation at 3.5 times the stabilized dose of their once-monthly formulation dose (JAMA Psychiatry 2015; March 29 [doi.10.1001/jamapsychiatry.2015.024]).

During the final, double-blind phase, 160 stabilized patients were randomized to 3-month paliperidone palmitate (175, 263, 350, or 525 mg), once every 3 months, and 145 stabilized patients similarly received placebo.

In an interim analysis, the time from randomization to relapse significantly favored paliperidone palmitate vs. placebo (hazard ratio, 3.45; 95% confidence interval, 1.73-6.88; P < .001). The median time before relapse was 274 days for placebo but, according to Dr. Savitz, was not estimable for the study arm.

“The interim analysis more was than 270 days after randomization, so if you think about it, that’s a very long time, because even those who were switched to placebo continued to have protection from relapse after having one dose. In the final analysis, it was actually a year-long protection, after people stopped getting the medication,” Dr. Savitz said in the interview.

This primary analysis of the data, also presented this week at the 23rd annual European Congress of Psychiatry in Vienna, is based on the interim results of time to first relapse, which were strong enough to have provoked an early termination for the study.

Treatment-emergent adverse events recorded during the double blind phase occurred in 62% of the 3-month paliperidone palmitate group and in 58% of the placebo group. Headache and weight gain were the most common (9% vs. 4% and 9% vs. 3%), respectively, followed by nasopharyngitis (6% vs. 1%), and akathisia (4% vs. 1%).

Dr. Savitz recommended that if the drug is approved, “It’s important to remember that the person has to be stabilized first using the 1-month dose,” and that it not be used in people who are allergic to risperidone or who have other allergies.

Dr. Savitz is the director of clinical research, neuroscience, and psychiatry at Janssen Pharmaceuticals.

[email protected]

On Twitter @whitneymcknight

COLORADO SPRINGS– Three-month injectable paliperidone palmitate significantly delayed time to relapse compared to placebo in patients with schizophrenia, according to phase III clinical study data being presented at the biennial meeting of the 15th International Congress on Schizophrenia Research.

The study also was published in JAMA Psychiatry.

If approved, patients would be dosed with only four injections of the atypical antipsychotic per year rather than once per month, which is the current dosing for the injectable formulation. Oral atypical antipsychotics are administered daily.

Whitney McKnight/Frontline Medical News

“It would be nice if there were more use, in general, of the long-acting injectables, and we hope these data will encourage that because it would increase [compliance],” Dr. Adam Savitz, a researcher on the study, said in an interview. “If it gets approved, it’s something clinicians should consider their patients could benefit from.”

Janssen, maker of the drug, has filed a New Drug Application with the Food and Drug Administration for the 3-month paliperidone palmitate injection to treat schizophrenia in adults. According to a statement from the company, a regulatory action is expected on May 18, 2015, after which time Janssen plans to file for markets outside the United States.

The multicenter, international trial conducted from April 26, 2012, through April 9, 2014, included 506 adults randomized to either the study drug or to placebo. Conducted in four phases, the study began with a 3-week screening phase, followed by a flexible-dose 17-week open-label transition phase in which patients received once-monthly doses of the 1-month formulation of paliperidone palmitate (50, 75, 100, or 150 mg). During the 12-week open-label maintenance phase, patients received a single dose of the 3-month formulation at 3.5 times the stabilized dose of their once-monthly formulation dose (JAMA Psychiatry 2015; March 29 [doi.10.1001/jamapsychiatry.2015.024]).

During the final, double-blind phase, 160 stabilized patients were randomized to 3-month paliperidone palmitate (175, 263, 350, or 525 mg), once every 3 months, and 145 stabilized patients similarly received placebo.

In an interim analysis, the time from randomization to relapse significantly favored paliperidone palmitate vs. placebo (hazard ratio, 3.45; 95% confidence interval, 1.73-6.88; P < .001). The median time before relapse was 274 days for placebo but, according to Dr. Savitz, was not estimable for the study arm.

“The interim analysis more was than 270 days after randomization, so if you think about it, that’s a very long time, because even those who were switched to placebo continued to have protection from relapse after having one dose. In the final analysis, it was actually a year-long protection, after people stopped getting the medication,” Dr. Savitz said in the interview.

This primary analysis of the data, also presented this week at the 23rd annual European Congress of Psychiatry in Vienna, is based on the interim results of time to first relapse, which were strong enough to have provoked an early termination for the study.

Treatment-emergent adverse events recorded during the double blind phase occurred in 62% of the 3-month paliperidone palmitate group and in 58% of the placebo group. Headache and weight gain were the most common (9% vs. 4% and 9% vs. 3%), respectively, followed by nasopharyngitis (6% vs. 1%), and akathisia (4% vs. 1%).

Dr. Savitz recommended that if the drug is approved, “It’s important to remember that the person has to be stabilized first using the 1-month dose,” and that it not be used in people who are allergic to risperidone or who have other allergies.

Dr. Savitz is the director of clinical research, neuroscience, and psychiatry at Janssen Pharmaceuticals.

[email protected]

On Twitter @whitneymcknight

COLORADO SPRINGS– Three-month injectable paliperidone palmitate significantly delayed time to relapse compared to placebo in patients with schizophrenia, according to phase III clinical study data being presented at the biennial meeting of the 15th International Congress on Schizophrenia Research.

The study also was published in JAMA Psychiatry.

If approved, patients would be dosed with only four injections of the atypical antipsychotic per year rather than once per month, which is the current dosing for the injectable formulation. Oral atypical antipsychotics are administered daily.

Whitney McKnight/Frontline Medical News

“It would be nice if there were more use, in general, of the long-acting injectables, and we hope these data will encourage that because it would increase [compliance],” Dr. Adam Savitz, a researcher on the study, said in an interview. “If it gets approved, it’s something clinicians should consider their patients could benefit from.”

Janssen, maker of the drug, has filed a New Drug Application with the Food and Drug Administration for the 3-month paliperidone palmitate injection to treat schizophrenia in adults. According to a statement from the company, a regulatory action is expected on May 18, 2015, after which time Janssen plans to file for markets outside the United States.

The multicenter, international trial conducted from April 26, 2012, through April 9, 2014, included 506 adults randomized to either the study drug or to placebo. Conducted in four phases, the study began with a 3-week screening phase, followed by a flexible-dose 17-week open-label transition phase in which patients received once-monthly doses of the 1-month formulation of paliperidone palmitate (50, 75, 100, or 150 mg). During the 12-week open-label maintenance phase, patients received a single dose of the 3-month formulation at 3.5 times the stabilized dose of their once-monthly formulation dose (JAMA Psychiatry 2015; March 29 [doi.10.1001/jamapsychiatry.2015.024]).

During the final, double-blind phase, 160 stabilized patients were randomized to 3-month paliperidone palmitate (175, 263, 350, or 525 mg), once every 3 months, and 145 stabilized patients similarly received placebo.

In an interim analysis, the time from randomization to relapse significantly favored paliperidone palmitate vs. placebo (hazard ratio, 3.45; 95% confidence interval, 1.73-6.88; P < .001). The median time before relapse was 274 days for placebo but, according to Dr. Savitz, was not estimable for the study arm.

“The interim analysis more was than 270 days after randomization, so if you think about it, that’s a very long time, because even those who were switched to placebo continued to have protection from relapse after having one dose. In the final analysis, it was actually a year-long protection, after people stopped getting the medication,” Dr. Savitz said in the interview.

This primary analysis of the data, also presented this week at the 23rd annual European Congress of Psychiatry in Vienna, is based on the interim results of time to first relapse, which were strong enough to have provoked an early termination for the study.

Treatment-emergent adverse events recorded during the double blind phase occurred in 62% of the 3-month paliperidone palmitate group and in 58% of the placebo group. Headache and weight gain were the most common (9% vs. 4% and 9% vs. 3%), respectively, followed by nasopharyngitis (6% vs. 1%), and akathisia (4% vs. 1%).

Dr. Savitz recommended that if the drug is approved, “It’s important to remember that the person has to be stabilized first using the 1-month dose,” and that it not be used in people who are allergic to risperidone or who have other allergies.

Dr. Savitz is the director of clinical research, neuroscience, and psychiatry at Janssen Pharmaceuticals.

[email protected]

On Twitter @whitneymcknight