Not provided
Not provided
Not provided
Not provided
New data; the study was terminated based on new efficacy data from another study
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
This study evaluates the efficacy of 10 mg/day Lu AF35700 on symptoms of schizophrenia in patients with early-in-disease (ED) or late-in-disease (LD) treatment-resistant schizophrenia (TRS)
In the study, patients will receive risperidone (4-6 mg/day), or, if recently failed on risperidone, olanzapine (15-20mg/day). Later during the study, patients will be randomized to either receive Lu AF35700 (10 mg/day), or continue their treatment from the prospective confirmation (PC) period.
The study consists of a Screening Period (up to 3 weeks), a single-blind PC Period (6 weeks), a Double-blind Treatment (DBT) Period (8 weeks), and a Safety Follow-up Period (6 weeks).
Patients who did not fulfil the randomization criteria for the DBT Period, were withdrawn from the study after the PC period.
Patients who fulfilled the randomization criteria for the DBT Period, continued into the DBT period and were randomized into one of the 2 treatmetn arms (1:1) with either Lu AF35700 10 mg or to continue the treatment allocated in the PC period (olanzapine or risperidone) at the dose set at the last visit of the PC period. This means that approximately half of the confirmed treatment-resistant patients were randomised back to the failed treatment in the PC period.
Data was not collected seperately for the DBT olanzapine and DBT risperidone participants, and there was no intent to compare Lu AF35700 to each drug seperately.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Prospective Confirmation (PC) Period | Experimental | Single (patient)-blinded treatment period with risperidone or olanzapine for 6 weeks |
|
| Double-blind treatment (DBT) period, Lu AF35700 10 mg | Experimental | Eligible patients from PC period (based on criteria to which investigator and patient are blinded ), will be randomly assigned (1:1) double-blind treatment in DBT period, 8 weeks |
|
| DBT Period, Continued treatment from PC Period | Experimental | Eligible patients from PC period (based on criteria to which investigator and patient are blinded ), will be randomly assigned (1:1) double-blind treatment in DBT period, 8 weeks. Patients in this arm will continue with the same treatment and dose as at the last visit of the PC Period |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Lu AF35700 | Drug | 10 mg/day, encapsulated tablets, orally |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change From Randomization to Week 8 in Positive and Negative Syndrome Scale (PANSS) Total Score | PANSS total score administered by the investigator. It included a total of 30 items that evaluated the Positive Symptoms subscale, the Negative Symptoms subscale, the General Psychopathology subscale. Each item is rated from 1 (symptom not present) to 7 (symptom extremely severe). PANSS total score was calculated as sum of all the items on the scale and ranged from 30 to 210. A negative score indicates an improvement compared to Randomization. | From Randomization to Week 8 |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Randomization to Week 8 in Global Clinical Impression - Severity of Illness (CGI-S) Score | CGI-S provides the clinician's impression of the patient's current state of mental illness. The clinician uses his or her clinical experience of this patient population to rate the severity of the patient's current mental illness on a 7-point scale ranging from 1 (normal - not at all ill) to 7 (among the most extremely ill patients). Higher scores indicate worsening |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Email contact via H.Lundbeck A/S | LundbeckClinicalTrials@Lundbeck.com | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of California San Diego Health System | San Diego | California | 92103 | United States | ||
| Emory University Cognitive Neurology Clinic & ADRC |
Not provided
Not provided
Not provided
Not provided
Not provided
Patients who did not fulfil the randomization criteria for the DBT period, were withdrawn from the study after the PC period. Patients who fulfilled the randomization crietria for the DBT period, continued into the DBT period. Patients randomized into the DBT period with risperidone or olanzapine were analyzed as one arm.
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Prospective Confirmation (PC) Period, Risperidone | Single (patient)-blinded treatment period with risperidone or olanzapine for 6 weeks Risperidone: 4-6 mg/day, encapsulated tablets, orally |
| FG001 | PC Period, Olanzapine |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Prospective Confirmation (PC) Period |
|
Not provided
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Sep 7, 2018 | Dec 17, 2019 |
Not provided
Not provided
Not provided
Not provided
Not provided
| Risperidone | Drug | 4-6 mg/day, encapsulated tablets, orally |
|
| Olanzapine | Drug | 15-20 mg/day, encapsulated tablets, orally |
|
| From Randomization to Week 8 |
| Change From Randomization to Week 8 in 16-item Negative Symptom Assessment (NSA-16 Total) Score | The NSA-16 is a clinician-rated scale designed to assess the presence, severity, and range of negative symptoms associated with schizophrenia. The NSA-16 consists of 16 items arranged in 5 subdomains: communication dysfunction (items 1 to 4), emotional/affective dysfunction (items 5 to 7), dysfunction in sociality (items 8 to 10), motivational/hedonic dysfunction (items 11 to 14), and reduced psychomotor activity (items 15 and 16), and a Global Negative Symptom Rating. NSA-16 items are rated on a 6-point scale from 1 (behaviour is normal) to 6 (behaviour severely reduced), and a score of 9 if the item is not-rateable. The Global Negative Symptom Rating is rated from 1 (no evidence of symptoms) to 7 (extremely severe symptoms). The 16 items are summed to yield a total score ranging from 16 to 96 and the global rating ranges from 1 to 7. | From Randomization to Week 8 |
| Change From Randomization to Week 8 in PANSS Marder Negative Factor Score | The PANSS Negative Factor score is a subset of the PANSS assessing negative symptoms of schizophrenia. The factor consist of the seven items: blunted affect, emotional withdrawal, poor rapport, passive social withdrawal, lack of spontaneity, motor retardation, and active social avoidance which are each rated on a 7-point scale, from 1=absent to 7=extreme. The PANSS Negative Factor score (7 items) range from 7 to 49 with a higher score indicating greater severity of symptoms. | From Randomization to Week 8 |
| Response | Response is defined as a ≥20% reduction in PANSS total score from Randomization | at Week 8 |
| Atlanta |
| Georgia |
| 30329 |
| United States |
| Northwestern University | Chicago | Illinois | 60611 | United States |
| Corrigan Mental Health Center | Fall River | Massachusetts | 02720 | United States |
| University Of Massachusetts Medical Center | Worcester | Massachusetts | 01605-2610 | United States |
| Michigan Clinical Research Institute PC | Ann Arbor | Michigan | 48108 | United States |
| Kalamazoo Community Mental Health and Substance Abuse Services | Kalamazoo | Michigan | 49001 | United States |
| PsychCare Consultants Research | St Louis | Missouri | 63128 | United States |
| Creighton University | Omaha | Nebraska | 68131 | United States |
| Psychiatric and Behavioral Solutions | Salt Lake City | Utah | 84105 | United States |
| SPH - Kardzhali | Kardzhali | Bulgaria |
| State Psychiatric Hospital | Novi Iskar | Bulgaria |
| UMHAT | Pleven | Bulgaria |
| State Psychiatric Hospital | Radnevo | Bulgaria |
| DCC St. Vrach and St.St. Kuzma and Damian | Sofia | Bulgaria |
| MHC - Sofia | Sofia | Bulgaria |
| MHAT - Targovishte | Targovishte | Bulgaria |
| Takeda General Hospital - JP0009 | Aizu-Wakamatsu | Japan |
| Takeda General Hospital | Fukushima | Japan |
| Kohnodai Hospital | Ichikawa | Japan |
| Nara Medical University Hospital | Kashihara | Japan |
| Sankeikai Nishigahara Hospital - JP0008 | Kita-ku | Japan |
| University of Occupational and Environmental Health Hospital | Kitakyushu | Japan |
| National Center of Neurology and Psychiatry | Kodaira | Japan |
| Satokai Yuge Hospital | Kumamoto | Japan |
| NHO Ryukyu Hospital | Kunigami | Japan |
| Fujita Health University Hospital | Toyoake | Japan |
| GUZ Lipetsk Regional psychoneurological Hospital 1 | Lipetsk | Russia |
| Lipetsk Regional Psychoneurological Hospital | Lipetsk | Russia |
| City Psychiatric Hospital # 6 | Saint Petersburg | Russia |
| Psychoneurological Dispensary #10 | Saint Petersburg | Russia |
| Psychoneurological Dispensary #1 | Saint Petersburg | Russia |
| Samara Psychiatric Hospital | Samara | Russia |
| Tomsk National Research Medical Centre of the Russian Academy of Sciences | Tomsk | Russia |
| Yaroslavl Regional Clinical Psychiatric Hospital | Yaroslavl | Russia |
| Sverdlovsk Regional Clinical Psychiatric Hospital | Yekaterinburg | Russia |
| Royal Edinburgh Hospital | Edinburgh | United Kingdom |
| The Maudsley Hospital - GB0001 | London | United Kingdom |
| The Maudsley Hospital | London | United Kingdom |
| Manchester Mental Health & Social Care NHS Trust - GB0003 | Manchester | United Kingdom |
| Manchester Mental Health & Social Care NHS Trust | Manchester | United Kingdom |
Single (patient)-blinded treatment period with risperidone or olanzapine for 6 weeks
Olanzapine: 15-20 mg/day, encapsulated tablets, orally
| FG002 | Double-blind (DBT), Lu AF35700 10 mg | Lu AF35700: 10 mg/day, encapsulated tablets, orally for 8 weeks |
| FG003 | DBT, Continued Treatment From PC Period | Patients in this arm will continue the treatment allocated in the PC period at the dose set at the last visit of the PC period. The analysis is made independent on which treatment the patient was done (risperidone or olanzapine). 8 weeks treatment. |
| COMPLETED |
|
| NOT COMPLETED |
|
|
| Double Blind Treatment (DBT) Period |
|
|
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Non-randomized Patients | Patients not randomized to double-blind treatment period, i.e. withdrawn from the study during or after the PC period, were analyzed as one arm, independent of treatment |
| BG001 | Double-blind Treatment (DBT) Period, Lu AF35700 10 mg | Lu AF35700: 10 mg/day, encapsulated tablets, orally for 8 weeks |
| BG002 | DBT, Continued Treatment From PC Period | Patients in this arm continued with the same treatment and dose as at the last visit of the PC period. Patients randomized into the DBT period with risperidone or olanzapine were analyzed as one arm independent of treatment. |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| PANSS total score | Positive and Negative Syndrome Scale (PANNS) total score administered by the investigator. It included a total of 30 items that evaluated the Positive Symptoms subscale, the Negative Symptoms subscale, the General Psychopathology subscale. Each item is rated from 1 (symprom not present) to 7 (symptom extremely severe). PANNS total score was calculated as sum of all items on the scale and ranged from 30 to 210. A higher score corresponded to a worse severity of schizophrenia. | Mean | Standard Deviation | units on a scale |
| ||||||||||||||
| CGI-S score | CGI-S provides the clinician's impression of the patient's current state of mental illness. The clinician uses his or her clinical experience of this patient population to rate the severity of the patient's current mental illness on a 7-point scale ranging from 1 (Normal - not at all ill) to 7 (among the most extremely ill patients). | Mean | Standard Deviation | units on a scale |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change From Randomization to Week 8 in Positive and Negative Syndrome Scale (PANSS) Total Score | PANSS total score administered by the investigator. It included a total of 30 items that evaluated the Positive Symptoms subscale, the Negative Symptoms subscale, the General Psychopathology subscale. Each item is rated from 1 (symptom not present) to 7 (symptom extremely severe). PANSS total score was calculated as sum of all the items on the scale and ranged from 30 to 210. A negative score indicates an improvement compared to Randomization. | Only patients randomized to receive double-blind treatment in the DBT period are analyzed. Patients randomized into the DBT period with risperidone or olanzapine were analyzed as one arm. Overall Number of Participants Analysed is number of patients in the full-analysis set (FAS) with a week 8 observation | Posted | Mean | Standard Error | units on a scale | From Randomization to Week 8 |
|
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change From Randomization to Week 8 in Global Clinical Impression - Severity of Illness (CGI-S) Score | CGI-S provides the clinician's impression of the patient's current state of mental illness. The clinician uses his or her clinical experience of this patient population to rate the severity of the patient's current mental illness on a 7-point scale ranging from 1 (normal - not at all ill) to 7 (among the most extremely ill patients). Higher scores indicate worsening | Only patients randomized to receive double-blind treatment in the DBT period are analyzed. Patients randomized into the DBT period with risperidone or olanzapine were analyzed as one arm. Overall Number of Participants Analysed is number of patients in the FAS with a week 8 observation | Posted | Mean | Standard Error | units on a scale | From Randomization to Week 8 |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change From Randomization to Week 8 in 16-item Negative Symptom Assessment (NSA-16 Total) Score | The NSA-16 is a clinician-rated scale designed to assess the presence, severity, and range of negative symptoms associated with schizophrenia. The NSA-16 consists of 16 items arranged in 5 subdomains: communication dysfunction (items 1 to 4), emotional/affective dysfunction (items 5 to 7), dysfunction in sociality (items 8 to 10), motivational/hedonic dysfunction (items 11 to 14), and reduced psychomotor activity (items 15 and 16), and a Global Negative Symptom Rating. NSA-16 items are rated on a 6-point scale from 1 (behaviour is normal) to 6 (behaviour severely reduced), and a score of 9 if the item is not-rateable. The Global Negative Symptom Rating is rated from 1 (no evidence of symptoms) to 7 (extremely severe symptoms). The 16 items are summed to yield a total score ranging from 16 to 96 and the global rating ranges from 1 to 7. | Only patients randomized to receive double-blind treatment in the DBT period are analyzed. Patients randomized into the DBT period with risperidone or olanzapine were analyzed as one arm. Overall Number of Participants Analysed is number of patients in the FAS with a week 8 observation | Posted | Mean | Standard Error | units on a scale | From Randomization to Week 8 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change From Randomization to Week 8 in PANSS Marder Negative Factor Score | The PANSS Negative Factor score is a subset of the PANSS assessing negative symptoms of schizophrenia. The factor consist of the seven items: blunted affect, emotional withdrawal, poor rapport, passive social withdrawal, lack of spontaneity, motor retardation, and active social avoidance which are each rated on a 7-point scale, from 1=absent to 7=extreme. The PANSS Negative Factor score (7 items) range from 7 to 49 with a higher score indicating greater severity of symptoms. | Only patients randomized to receive double-blind treatment in the DBT period are analyzed. Patients randomized into the DBT period with risperidone or olanzapine were analyzed as one arm. Overall Number of Participants Analysed is number of patients in the FAS with a week 8 observation | Posted | Mean | Standard Error | units on a scale | From Randomization to Week 8 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Response | Response is defined as a ≥20% reduction in PANSS total score from Randomization | Only patients randomized to receive double-blind treatment in the DBT period are analyzed. Patients randomized into the DBT period with risperidone or olanzapine were analyzed as one arm. Overall Number of Participants Analysed is number of patients in the FAS with a week 8 observation | Posted | Count of Participants | Participants | at Week 8 |
|
|
20 weeks
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Prospective Confirmation (PC) Period - Risperidone | Patients not randomized to double-blind treatment | 0 | 68 | 1 | 68 | 16 | 68 |
| EG001 | PC Period - Olanzapine | Patients not randomized to double-blind treatment | 0 | 51 | 1 | 51 | 3 | 51 |
| EG002 | Double Blind Treatment (DBT) Period - Lu AF35700 10 mg | Lu AF35700: 10 mg/day, encapsulated tablets, orally for 8 weeks | 0 | 35 | 0 | 35 | 8 | 35 |
| EG003 | DBT Period, Continued Treatment From PC Period | Patients in this arm continued with the same treatment and dose as at the last visit of the PC Period. This arm is analyzed as one single treatment arm independent on which treatment was administered (olanzapine or risperidone for 8 weeks). | 0 | 33 | 0 | 33 | 7 | 33 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Suicidal ideation | Psychiatric disorders | MedDRA - 21.0 | Non-systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA - 21.0 | Non-systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Weight increased | Investigations | MedDRA - 21.0 | Non-systematic Assessment |
| |
| Akathisia | Nervous system disorders | MedDRA - 21.0 | Non-systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA - 21.0 | Non-systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA - 21.0 | Non-systematic Assessment |
| |
| Schizophrenia | Psychiatric disorders | MedDRA - 21.0 | Non-systematic Assessment |
|
The study was terminated early and hence the statistical analysis was conducted on a smaller sample size than originally planned.
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Email contact via | H. Lundbeck A/S | +4536301311 | LundbeckClinicalTrials@Lundbeck.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Mar 13, 2019 | Dec 17, 2019 | SAP_001.pdf |
| ID | Term |
|---|---|
| D000090663 | Schizophrenia, Treatment-Resistant |
| ID | Term |
|---|---|
| D012559 | Schizophrenia |
| D019967 | Schizophrenia Spectrum and Other Psychotic Disorders |
| D001523 | Mental Disorders |
Not provided
Not provided
| ID | Term |
|---|---|
| C000726227 | Lu AF35700 |
| D018967 | Risperidone |
| D000077152 | Olanzapine |
| ID | Term |
|---|---|
| D011744 | Pyrimidinones |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D001569 | Benzodiazepines |
| D001552 | Benzazepines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
Not provided
Not provided
| Withdrawal by Subject |
|
| Sponsor Decision |
|
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| Participants |
|
|
Patients in this arm will continue on the same treatment and dose as at the last visit of the PC period (olanzapine or risperidone)
|
|
| Units | Counts |
|---|
| Participants |
|
|
|