Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
The purpose of this study is to determine whether Iloperidone is effective in the prevention of relapse in patients with schizophrenia
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Iloperidone | Experimental | After meeting all entry criteria, completing a 1-week open-label iloperidone titation period (up to 12 mg/day), followed by a 14-24 week open-label iloperidone flexible dose-stabilization period (up to 24 mg/day), approximately 260 patients will be randomized to one of two arms in a 1:1 ratio of iloperidone (flexible dosing 8-24 mg/day) to placebo. Post-randomization double-blind study medication will be administered orally twice daily for up to 26 weeks to evaluate relapse prevention. Subsequently, during the extension period, after a 1-week mock double-blind titration, open-label iloperidone (8-24 mg/day) is administered for up to 51 weeks to evaluate long-term safety. |
|
| Placebo | Placebo Comparator | Post-randomization matching placebo is administered orally bid during the double-blind period. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Iloperidone | Drug | Over-encapsulated iloperidone tablets were administered orally using a bid schedule; the strengths used include 1, 2, 4, 6, 8, 10, and 12 mg. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Time to Relapse or Impending Relapse | Relapse or impending relapse was defined as any of the following: hospitalization due to worsening of schizophrenia; increase (worsening) of the PANSS total score of greater than or equal to 30% from randomization, PANSS total score confirmed at a second visit conducted within 1-7 days; clinically significant emergent or worsening suicidal, homicidal, or aggressive behavior; a CGI-Improvement (CGI-I) score of 6 (much worse) or 7 (very much worse) after randomization; a dose increase in study medication or a need for additional open-label antipsychotic treatment. | Up to 26 weeks post-randomization |
| Measure | Description | Time Frame |
|---|---|---|
| PANSS Total Score, Change From Baseline to Last Visit | The 30-item Positive and Negative Syndrome Scale (PANSS) was developed to assess the severity of symptoms of schizophrenia. The PANSS items are divided into positive, negative, and general psychopathology factors. All items were rated on a scale of 1 (absent) to 7 (extremely severe). The PANSS total score (or rating) is the sum of all 30 PANSS items taken together (the sum of its 3 subscales), with a maximum score of 210. Change from baseline is calculated as post value minus baseline value. A negative change indicates improvement. |
Not provided
Inclusion Criteria:
Exclusion Criteria:-
Other protocol-defined inclusion/exclusion criteria may apply
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Vanda Investigative Site | Anaheim | California | 92604 | United States | ||
| Vanda Investigative Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 27379654 | Result | Weiden PJ, Manning R, Wolfgang CD, Ryan JM, Mancione L, Han G, Ahmed S, Mayo MG. A Randomized Trial of Iloperidone for Prevention of Relapse in Schizophrenia: The REPRIEVE Study. CNS Drugs. 2016 Aug;30(8):735-47. doi: 10.1007/s40263-016-0345-4. |
Not provided
Not provided
A total of 635 patients were enrolled and received iloperidone in the Cross-Titration Phase and entered Stabilization Phase. A total of 303 were randomized and received either iloperidone (n=153) or placebo (n=150) in the Double-Blind Relapse Prevention Phase.
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Iloperidone | After meeting all entry criteria, completing a 1-week open-label iloperidone titration period (up to 12 mg/day), followed by a 14-24 week open-label iloperidone flexible dose-stabilization period (up to 24 mg/day), patients in this arm were randomized to iloperidone (flexible dosing 8-24 mg/day). Post-randomization double-blind study medication was administered orally twice daily for up to 26 weeks to evaluate relapse prevention. Subsequently, during the extension period, after a 1-week mock double-blind titration, open-label iloperidone (8-24 mg/day) was administered for up to 51 weeks to evaluate long-term safety. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Cross-Titration and Stabilization Phase |
|
Not provided
Not provided
Not provided
Not provided
Not provided
|
| Placebo | Drug | Matching placebo capsules were administered orally using a bid schedule during the double-blind period. |
|
| Up to 26 weeks post-randomization |
| CGI-S, Last Visit | The 7-item Clinical Global Impression of Severity (CGI-S) scale was developed to assess the overall, absolute degree of illness at any point in time. A rating of 1 is equivalent to "normal, not at all ill," and a rating of 7 is equivalent to "among the most extremely ill patients." | Up to 26 weeks post-randomization |
| SDS Total Score, Change From Baseline to Last Visit | The Sheehan Disability Scale (SDS) a self-reported measure that was developed to assess functional impairment in 3 inter-related domains (i.e., work/school, social, and family life). It is a 10-point visual analog scale with 0 being not impaired at all and 10 extremely impaired. Change from baseline is calculated as post value minus baseline value. A negative change indicates improvement. | Up to 26 weeks post-randomization |
| Bellflower |
| California |
| 92706 |
| United States |
| Vanda Investigative Site | Costa Mesa | California | 92626 | United States |
| Vanda Investigative Site | Escondido | California | 92025 | United States |
| Vanda Investigative Site | La Habra | California | 90631 | United States |
| Vanda Investigative Site | Oceanside | California | 92056 | United States |
| Vanda Investigative Site | Orange | California | 92868 | United States |
| Vanda Investigative Site | Pico Rivera | California | 90660 | United States |
| Vanda Investigative Site | Riverside | California | 92506 | United States |
| Vanda Investigative Site | San Diego | California | 92102 | United States |
| Vanda Investigative Site | San Diego | California | 92103 | United States |
| Vanda Investigative Site | San Diego | California | 92121 | United States |
| Vanda Investigative Site | Santa Ana | California | 92705 | United States |
| Vanda Investigative Site | Melbourne | Florida | 32901 | United States |
| Vanda Investigative Site | Miami | Florida | 33126 | United States |
| Vanda Investigative Site | Oakland Park | Florida | 33334 | United States |
| Vanda Investigative Site | Atlanta | Georgia | 30308 | United States |
| Vanda Investigative Site | Atlanta | Georgia | 30328 | United States |
| Vanda Investigative Site | St Louis | Missouri | 63109 | United States |
| Vanda Investigative Site | Nashua | New Hampshire | 03060 | United States |
| Vanda Investigative Site | Marlton | New Jersey | 08053 | United States |
| Vanda Investigative Site | Brooklyn | New York | 11235 | United States |
| Vanda Investigative Site | Staten Island | New York | 10312 | United States |
| Vanda Investigative Site | Hickory | North Carolina | 28601 | United States |
| Vanda Investigative Site | Beachwood | Ohio | 44122 | United States |
| Vanda Investigative Site | Philadelphia | Pennsylvania | 19139 | United States |
| Vanda Investigative Site | Irving | Texas | 75062 | United States |
| Vanda Investigative Site | Salt Lake City | Utah | 84106 | United States |
| Vanda Investigative Site | Ahmedabad | Gujarat | 380013 | India |
| Vanda Investigative Site | Madhava Nagar | Karnataka | 576104 | India |
| Vanda Investigative Site | Mangalore | Karnataka | 575001 | India |
| Vanda Investigative Site | Mangalore | Karnataka | 575018 | India |
| Vanda Investigative Site | Mysore | Karnataka | 570004 | India |
| Vanda Investigative Site | Nashik | Maharashtra | 422101 | India |
| Vanda Investigative Site | Pune | Maharashtra | 411030 | India |
| Vanda Investigative Site | Jaipur | Rajasthan | 302021 | India |
| Vanda Investigative Site | Madurai | Tamil Nadu | 625020 | India |
| Vanda Investigative Site | Kanpur | Uttar Pradesh | 208005 | India |
| Vanda Investigative Site | Lucknow | Uttar Pradesh | 226003 | India |
| Vanda Investigative Site | Lucknow | Uttar Pradesh | 226006 | India |
| Vanda Investigative Site | Varanasi | Uttar Pradesh | 221005 | India |
| Vanda Investigative Site | Kerch | AR Crimea | 98310 | Ukraine |
| Vanda Investigative Site | Yevpatoriya | AR Crimea | 97416 | Ukraine |
| Vanda Investigative Site | Chernihiv | 14000 | Ukraine |
| Vanda Investigative Site | Dnipropetrovsk | 49005 | Ukraine |
| Vanda Investigative Site | Dnipropetrovsk | 49115 | Ukraine |
| Vanda Investigative Site | Donetsk | 83008 | Ukraine |
| Vanda Investigative Site | Donetsk | 83037 | Ukraine |
| Vanda Investigative Site | Ivano-Frankivsk | 76014 | Ukraine |
| Vanda Investigative Site | Kharkiv | 61068 | Ukraine |
| Vanda Investigive Site | Kharkiv | 68061 | Ukraine |
| Vanda Investigative Site | Kyiv | 01030 | Ukraine |
| Vanda Investigative Site | Kyiv | 02660 | Ukraine |
| Vanda Investigative Site | Kyiv | 04080 | Ukraine |
| Vanda Investigative Site | Kyiv | 08631 | Ukraine |
| Vanda Investigative Site | Luhansk | 91045 | Ukraine |
| Vanda Investigative Site | Odesa | 65014 | Ukraine |
| Vanda Investigative Site | Poltava | 36006 | Ukraine |
| Vanda Investigative Site | Simferopol | 95006 | Ukraine |
| Vanda Investigative Site | Stepanovka | 73488 | Ukraine |
| Vanda Investigative Site | Ternopil | 46020 | Ukraine |
| Vanda Investigative Site | Uzhhorod | 88000 | Ukraine |
| Vanda Investigative Site | Vinnytsia | 21005 | Ukraine |
| FG001 | Placebo | After meeting all entry criteria, completing a 1-week open-label iloperidone titration period (up to 12 mg/day), followed by a 14-24 week open-label iloperidone flexible dose-stabilization period (up to 24 mg/day), patients in this arm were randomized to matching placebo. Post-randomization double-blind study medication was administered orally twice daily for up to 26 weeks to evaluate relapse prevention. |
| COMPLETED |
|
| NOT COMPLETED |
|
|
| Double-blind Relapse Prevention Phase |
|
|
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Iloperidone | oral, open-label titration up to 12 mg for 1-week followed by open-label flexible dosing (8-24 mg/day), followed by double-blind 8-24 mg/day dosing for 26 weeks |
| BG001 | Placebo | oral, matching placebo administered during double-blind phase for up to 26 weeks |
| BG002 | 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 |
| ||||||||||||||||
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| 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 | Time to Relapse or Impending Relapse | Relapse or impending relapse was defined as any of the following: hospitalization due to worsening of schizophrenia; increase (worsening) of the PANSS total score of greater than or equal to 30% from randomization, PANSS total score confirmed at a second visit conducted within 1-7 days; clinically significant emergent or worsening suicidal, homicidal, or aggressive behavior; a CGI-Improvement (CGI-I) score of 6 (much worse) or 7 (very much worse) after randomization; a dose increase in study medication or a need for additional open-label antipsychotic treatment. | Two subjects lost to follow-up after randomization were excluded from the analysis population. | Posted | Median | 95% Confidence Interval | Days | Up to 26 weeks post-randomization |
|
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | PANSS Total Score, Change From Baseline to Last Visit | The 30-item Positive and Negative Syndrome Scale (PANSS) was developed to assess the severity of symptoms of schizophrenia. The PANSS items are divided into positive, negative, and general psychopathology factors. All items were rated on a scale of 1 (absent) to 7 (extremely severe). The PANSS total score (or rating) is the sum of all 30 PANSS items taken together (the sum of its 3 subscales), with a maximum score of 210. Change from baseline is calculated as post value minus baseline value. A negative change indicates improvement. | Data presented are FAS (Full Analysis set) LOCF (last observation carried forward) Change From DBRP (Double-Blind Relapse Prevention) Baseline to RP Completion. RP Completion visit includes observations from last visit during DBRP period for patients who completed the study or RP Completion visit for patients who discontinued the DBRP phase and not included in previous scheduled visit. | Posted | Mean | Standard Error | units on a scale | Up to 26 weeks post-randomization |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | CGI-S, Last Visit | The 7-item Clinical Global Impression of Severity (CGI-S) scale was developed to assess the overall, absolute degree of illness at any point in time. A rating of 1 is equivalent to "normal, not at all ill," and a rating of 7 is equivalent to "among the most extremely ill patients." | Data presented are FAS (Full Analysis set) OC (observed cases), as this measure does not include a baseline assessment; RP Completion visit includes observations from last visit during DBRP period for patients who completed the study and RP Completion visit that could not be remapped to a previous scheduled visit for patients who discontinued the DBRP phase. | Posted | Mean | Standard Deviation | units on a scale | Up to 26 weeks post-randomization |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | SDS Total Score, Change From Baseline to Last Visit | The Sheehan Disability Scale (SDS) a self-reported measure that was developed to assess functional impairment in 3 inter-related domains (i.e., work/school, social, and family life). It is a 10-point visual analog scale with 0 being not impaired at all and 10 extremely impaired. Change from baseline is calculated as post value minus baseline value. A negative change indicates improvement. | Data presented are FAS (Full Analysis set) LOCF (last observation carried forward) Change From DBRP (Double-Blind Relapse Prevention) Baseline to RP Completion. RP Completion visit includes observations from last visit during DBRP period for patients who completed the study or RP Completion visit for patients who discontinued the DBRP phase and not included in previous scheduled visit. | Posted | Mean | Standard Error | units on a scale | Up to 26 weeks post-randomization |
|
|
Cross-Titration Phase (1 week) and Stabilization Phase (14-24 weeks); Relapse-prevention phase (up to 26 weeks)
For each phase, i.e. Cross-titration/Stabilization Phase and Relapse-prevention Phase, the safety population included all enrolled or randomized patients who received at least 1 dose of study drug during the corresponding phase. For the Relapse-prevention Phase, in case of a treatment error, patients were analyzed according to the treatment received.
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 | Iloperidone (Cross-titration and Stabilization Phase) | During the 1 week Cross-titration phase, patients were titrated up to 12 mg/d open-label iloperidone orally twice a day. The prior antipsychotic was discontinued by day 4. During the 14 to 24 week Stabilization Phase, the dose could be modified within a permitted range of a total daily dose of 8-24 mg/d. | 1 | 629 | 21 | 629 | 244 | 629 |
| EG001 | Iloperidone (Relapse-prevention Phase) | Patients received 8 to 24 mg/d iloperidone orally twice a day for up to 26 weeks. | 1 | 151 | 6 | 151 | 16 | 151 |
| EG002 | Placebo (Relapse-prevention Phase) | Patients received placebo orally twice a day for up to 26 weeks. | 0 | 150 | 4 | 150 | 30 | 150 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Arrhythmia | Cardiac disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Hepatitis acute | Hepatobiliary disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Arthritis viral | Infections and infestations | MedDRA (16.1) | Systematic Assessment |
| |
| Femoral neck fracture | Injury, poisoning and procedural complications | MedDRA (16.1) | Systematic Assessment |
| |
| Alcohol poisoning | Injury, poisoning and procedural complications | MedDRA (16.1) | Systematic Assessment |
| |
| Hypernatraemia | Metabolism and nutrition disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Convulsion | Nervous system disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Ectopic pregnancy | Pregnancy, puerperium and perinatal conditions | MedDRA (16.1) | Systematic Assessment |
| |
| Schizophrenia | Psychiatric disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Acute psychosis | Psychiatric disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Suicidal ideation | Psychiatric disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Agitation | Psychiatric disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Alcoholism | Psychiatric disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Psychotic disorder | Psychiatric disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Suicide attempt | Psychiatric disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Priapism | Reproductive system and breast disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Vaginal haemorrhage | Reproductive system and breast disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Asthma | Respiratory, thoracic and mediastinal disorders | MedDRA (16.1) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Schizophrenia | Psychiatric disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Weight Increased | Investigations | MedDRA (16.1) | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Somnolence | Nervous system disorders | MedDRA (16.1) | Systematic Assessment |
| |
| Dry mouth | Gastrointestinal disorders | MedDRA (16.1) | Systematic Assessment |
|
The primary limitation of the study design is that the length of the placebo-controlled phase of the study lasted for only 6 months. However, ethical considerations around the use of placebo in this patient population necessarily informed the study design. While the flexible-dosing regimen in this study allowed for a more real-world experience, it also prevented the assessment of dose-response.
Pooled site data analysis is restricted to publication by consent of steering committee. PI is restricted from presenting or publishing independently on their own site data until the expiration of eighteen (18) months from the completion of the Clinical Trial or as otherwise noted in the Investigator's clinical trial agreement.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Vanda Pharmaceuticals | Vanda Pharmaceuticals | 202-734-3400 | clinicaltrials@vandapharma.com |
| ID | Term |
|---|---|
| D012559 | Schizophrenia |
| D001523 | Mental Disorders |
| ID | Term |
|---|---|
| D019967 | Schizophrenia Spectrum and Other Psychotic Disorders |
Not provided
Not provided
| ID | Term |
|---|---|
| C081732 | iloperidone |
Not provided
Not provided
Not provided
| Lost to Follow-up |
|
| Adverse Event |
|
| Abnormal Laboratory Value |
|
| Protocol Violation |
|
| Lack of Efficacy |
|
| Abnormal test |
|
| Death |
|
| Male |
|
| Black |
|
| Asian |
|
| Pacific Islander |
|
| Other |
|
| Counts |
|---|
| Participants |
|
|
|
|
|
|
|