Effect of Lu AF35700 in Patients With Treatment-resistant Schizophrenia
- Conditions
- Schizophrenia
- Interventions
- Registration Number
- NCT02717195
- Lead Sponsor
- H. Lundbeck A/S
- Brief Summary
To evaluate the efficacy of 10 and 20 mg/day of Lu AF35700 on schizophrenia symptoms in patients with treatment-resistant schizophrenia (TRS)
- Detailed Description
The study consists of a Screening Period (3 weeks), a single-blind Prospective Confirmation (PC) Period (6 weeks), a Double-blind Treatment (DBT) Period (10 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Patients who did not fulfil the randomization criteria for the DBT Period, were withdrawn from the study after the PC period.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 3 treatment arms (1:1:1) with either Lu AF35700 10 mg/day, Lu AF35700 20 mg/day or to continue the treatment allocated in PC Period (olanzapine or risperidone) at the dose set at last visit of PC Period. This mean that approximately one third of the confirmed treatment-resistant patients were randomised back to the failed treatment used in the PC Period.
Data was not collected separately for the DBT Olanzapine and DBT Risperidone participants, and there was no intent to compare Lu AF35700 to each drug separately.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1098
- The patient has schizophrenia, diagnosed according to DSM-5(TM) (Diagnostic and Statistical Manual of Mental Disorders) and confirmed by the Mini International Neuropsychiatric Interview for Schizophrenia and Psychotic Disorders
- The patient is either an inpatient at a psychiatric setting or outpatient consulting a psychiatrist.
- Patients should be treated with adequate dose(s) and agent(s) of antipsychotic treatment for at least 2 weeks prior to Screening
- The patient has failed to show an adequate response in the level of psychotic symptoms despite at least one documented treatment trial with an adequate dose of an antipsychotic agent prescribed for an adequate time (at least lasting for 6 weeks) during 2 years prior to Screening. The failure to respond to the current antipsychotic treatment trial may be considered a retrospective failed treatment, if the patient was treated for 6 weeks with adequate dose(s) and agent(s)
- The patient has a PANSS total score of ≥80 and a score of ≥4 on at least 2 of the following PANSS items (at Screening and at the first visit of Period A)
- The patient has a CGI-S score of ≥4 at Screening and at the first visit of Period A
- The patient has any current primary psychiatric disorder other than schizophrenia as assessed by the Mini International Neuropsychiatric Interview (MINI)
- The patient is experiencing an acute exacerbation of his/her psychotic symptoms
- The patient has not responded to treatment with clozapine
Other protocol defined inclusion and exclusion criteria may apply
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Prospective Confirmation (PC) Period Risperidone Single (patient)-blinded treatment period with risperidone or olanzapine for 6 weeks Prospective Confirmation (PC) Period Olanzapine Single (patient)-blinded treatment period with risperidone or olanzapine for 6 weeks DBT Period, Continued treatment from PC Period Olanzapine Eligible patients from PC Period (based on criteria to which investigator and patient are blinded), will be randomly assigned (1:1:1) double-blind treatment in DBT Period,10 weeks. Patients in this arm will continue with same the treatment and dose as at last visit of PC Period DBT Period, Continued treatment from PC Period Risperidone Eligible patients from PC Period (based on criteria to which investigator and patient are blinded), will be randomly assigned (1:1:1) double-blind treatment in DBT Period,10 weeks. Patients in this arm will continue with same the treatment and dose as at last visit of PC Period Double-blind Treatment (DBT) Period, Lu AF35700 10 mg Lu AF35700 Eligible patients from PC Period (based on criteria to which investigator and patient are blinded), will be randomly assigned (1:1:1) double-blind treatment in DBT Period, 10 weeks DBT Period, Lu AF35700 20 mg Lu AF35700 Eligible patients from PC Period (based on criteria to which investigator and patient are blinded), will be randomly assigned (1:1:1) double-blind treatment in DBT Period, 10 weeks
- Primary Outcome Measures
Name Time Method Change From Randomization to Week 10 in Positive and Negative Syndrome Scale (PANSS) Total Score From Randomization to Week 10 PANSS total score administered by the investigator. It included 3 sub-scales with 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 higher score corresponded to a worse severity of schizophrenia.
- Secondary Outcome Measures
Name Time Method Response at Week 10, Defined as ≥20% Reduction in PANSS Total Score, PANSS (Positive and Negative Syndrome Scale) Total Score ≤70, CGI-S (Clinical Global Impression Scale - Severity of Illness) Score <4 From Randomization to Week 10 PANSS total score administered by the investigator. It included 3 sub-scales with 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 higher score corresponded to a worse severity of schizophrenia. A reduction in score indicates improvement.
The Clinical Global Impression scale - severity of illness (CGI-S) is administered by the investigator. The patient is rated on a 7-point scale ranging from 1 (Normal - not at all ill) to 7 (among the most extremely ill patients). A reduction in scale indicates improvement.Change From Randomization to Week 10 in PSP Total Personal and Social Performance (PSP) Total Score From Randomization to Week 10 PSP is a clinician-rated scale designed and validated to measure a patient's current level of social functioning. It consists of 4 items: socially useful activities, personal and social relationships, self-care, and disturbing and aggressive behaviours. Each items were assessed on a 6-point scale, from 1 (absent) to 6 (very severe). PSP score was calculated as sum of all the items on the scale and ranged from 4 to 100. A higher score represents more severe functional impairment.
Change From Randomization to Week 10 in Global Clinical Impression - Severity of Illness (CGI-S) Score From Randomization to Week 10 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.
Response at Week 10, Defined as ≥20% Reduction in Positive and Negative Syndrome Scale (PANSS) Total Score From Randomization From Randomization to Week 10 PANSS total score administered by the investigator. It included 3 sub-scales with 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 higher score corresponded to a worse severity of schizophrenia. A reduction in score indicates improvement.
Response at Week 10, Defined as ≥30% Reduction in PANSS Total Score From Randomization From Randomization to Week 10 Positive and Negative Syndrome Scale (PANSS) total score administered by the investigator. It included 3 sub-scales with 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 higher score corresponded to a worse severity of schizophrenia. A reduction in score indicates improvement.
Response at Week 10, Defined as ≥50% Reduction in Positive and Negative Syndrome Scale (PANSS) Total Score From Randomization From Randomization to Week 10 PANSS total score administered by the investigator. It included 3 sub-scales with 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 higher score corresponded to a worse severity of schizophrenia. A reduction in score indicates improvement.
Response at Week 10, Defined as ≥40% Reduction in Positive and Negative Syndrome Scale (PANSS) Total Score From Randomization From Randomization to Week 10 PANSS total score administered by the investigator. It included 3 sub-scales with 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 higher score corresponded to a worse severity of schizophrenia. A reduction in score indicates improvement.
Trial Locations
- Locations (147)
BG1029
🇧🇬Veliko Tŭrnovo, Bulgaria
MX1011
🇲🇽Guadalajara, Mexico
MX1022
🇲🇽Guadalajara, Mexico
RU1050
🇷🇺Yaroslavl, Russian Federation
RS1008
🇷🇸Belgrade, Serbia
RS1010
🇷🇸Belgrade, Serbia
RS1011
🇷🇸Kragujevac, Serbia
RS1016
🇷🇸Kragujevac, Serbia
RS1003
🇷🇸Nis, Serbia
RS1009
🇷🇸Novi Knezevac, Serbia
SK1014
🇸🇰Bratislava, Slovakia
SK1024
🇸🇰Bratislava, Slovakia
SK1015
🇸🇰Roznava, Slovakia
SK1025
🇸🇰Svidnik, Slovakia
UA1019
🇺🇦Dnipropetrovsk, Ukraine
UA1017
🇺🇦Kharkiv, Ukraine
UA1022
🇺🇦Kharkiv, Ukraine
UA1031
🇺🇦Kharkiv, Ukraine
UA1035
🇺🇦Kharkiv, Ukraine
UA1028
🇺🇦Kherson, Ukraine
UA1029
🇺🇦Kherson, Ukraine
UA1027
🇺🇦Kiev, Ukraine
UA1033
🇺🇦Lviv, Ukraine
UA1020
🇺🇦Odessa, Ukraine
RO1024
🇷🇴Bucuresti, Romania
MX1005
🇲🇽Monterrey, Mexico
MX1007
🇲🇽Monterrey, Mexico
MX1016
🇲🇽Monterrey, Mexico
PL1026
🇵🇱Gorlice, Poland
PL1027
🇵🇱Lublin, Poland
MX1015
🇲🇽Monterrey, Mexico
MX1018
🇲🇽San Luis Potosi, Mexico
PL1025
🇵🇱Bełchatów, Poland
PL1043
🇵🇱Bialystok, Poland
PL1060
🇵🇱Lodz, Poland
PL1058
🇵🇱Pruszcz Gdanski, Poland
PL1059
🇵🇱Torun, Poland
PL1051
🇵🇱Wroclaw, Poland
RO1022
🇷🇴Câmpulung, Romania
RO1025
🇷🇴Sibiu, Romania
RO1004
🇷🇴Târgu-Mureş, Romania
RU1006
🇷🇺Moscow, Russian Federation
RU1051
🇷🇺Moscow, Russian Federation
RU1023
🇷🇺Saint Petersburg, Russian Federation
RU1028
🇷🇺Saint Petersburg, Russian Federation
RU1030
🇷🇺Saint Petersburg, Russian Federation
RU1056
🇷🇺Saint Petersburg, Russian Federation
MX1024
🇲🇽Durango, Mexico
MX1020
🇲🇽Mexico, Mexico
BG1034
🇧🇬Varna, Bulgaria
PL1061
🇵🇱Pruszkow, Poland
RU1052
🇷🇺Saint Petersburg, Russian Federation
RU1053
🇷🇺Saint Petersburg, Russian Federation
RU1049
🇷🇺St. Petersburg, Russian Federation
RS1012
🇷🇸Belgrade, Serbia
RS1017
🇷🇸Kragujevac, Serbia
UA1030
🇺🇦Kiev, Ukraine
UA1032
🇺🇦Odessa, Ukraine
UA1001
🇺🇦Poltava, Ukraine
UA1036
🇺🇦Vinnitsa, Ukraine
US1398
🇺🇸Shreveport, Louisiana, United States
US1062
🇺🇸Costa Mesa, California, United States
US1464
🇺🇸Santa Ana, California, United States
CZ1038
🇨🇿Praha, Czechia
CA1033
🇨🇦Montréal, Canada
CZ1037
🇨🇿Hostivice, Czechia
BG1028
🇧🇬Kazanlak, Bulgaria
CA1039
🇨🇦Québec, Canada
FI1030
🇫🇮Kuopio, Finland
CZ1023
🇨🇿Brno, Czechia
EE1016
🇪🇪Pärnu, Estonia
FI1027
🇫🇮Turku, Finland
MX1021
🇲🇽Guadalajara, Mexico
CA1029
🇨🇦Penticton, Canada
CZ1032
🇨🇿Brno, Czechia
EE1007
🇪🇪Tallinn, Estonia
FI1032
🇫🇮Espoo, Finland
CZ1013
🇨🇿Lnare, Czechia
CA1003
🇨🇦Montréal, Canada
EE1017
🇪🇪Viljandi, Estonia
ES1048
🇪🇸Oviedo, Spain
ES1012
🇪🇸Madrid, Spain
ES1049
🇪🇸Zamora, Spain
RU1021
🇷🇺Nikol'skoye, Gatchinckiy District, Russian Federation
RU1009
🇷🇺Arkhangelsk, Russian Federation
ES1008
🇪🇸Malaga, Spain
SK1026
🇸🇰Zlate Moravce, Slovakia
ES1047
🇪🇸Barcelona, Spain
US1130
🇺🇸Miami, Florida, United States
US1018
🇺🇸Bellflower, California, United States
US1041
🇺🇸Cerritos, California, United States
US1104
🇺🇸Garden Grove, California, United States
US1459
🇺🇸Oceanside, California, United States
US1368
🇺🇸Orange, California, United States
US1463
🇺🇸Culver City, California, United States
US1118
🇺🇸Glendale, California, United States
US1452
🇺🇸Oceanside, California, United States
US1399
🇺🇸Orange, California, United States
US1114
🇺🇸National City, California, United States
US1384
🇺🇸Sherman Oaks, California, United States
US1392
🇺🇸Torrance, California, United States
US1253
🇺🇸Jacksonville, Florida, United States
US1396
🇺🇸Washington, District of Columbia, United States
US1395
🇺🇸Bradenton, Florida, United States
US1318
🇺🇸North Miami, Florida, United States
US1129
🇺🇸North Miami, Florida, United States
US1402
🇺🇸Oakland Park, Florida, United States
US1229
🇺🇸Orange City, Florida, United States
US1403
🇺🇸Atlanta, Georgia, United States
US1009
🇺🇸Atlanta, Georgia, United States
US1442
🇺🇸Decatur, Georgia, United States
US1423
🇺🇸Hoffman Estates, Illinois, United States
US1046
🇺🇸Chicago, Illinois, United States
US1086
🇺🇸Flowood, Mississippi, United States
US1404
🇺🇸Shreveport, Louisiana, United States
US1426
🇺🇸Berlin, New Jersey, United States
US1444
🇺🇸Las Vegas, Nevada, United States
US1394
🇺🇸New York, New York, United States
US1454
🇺🇸Marlton, New Jersey, United States
US1405
🇺🇸Glen Oaks, New York, United States
US1244
🇺🇸Jamaica, New York, United States
US1171
🇺🇸Rochester, New York, United States
US1190
🇺🇸Staten Island, New York, United States
US1390
🇺🇸Charlotte, North Carolina, United States
US1441
🇺🇸Hickory, North Carolina, United States
US1124
🇺🇸Norristown, Pennsylvania, United States
US1065
🇺🇸Dallas, Texas, United States
US1443
🇺🇸Fort Worth, Texas, United States
BG1030
🇧🇬Burgas, Bulgaria
BG1032
🇧🇬Pazardzhik, Bulgaria
BG1003
🇧🇬Lovech, Bulgaria
BG1008
🇧🇬Plovdiv, Bulgaria
BG1024
🇧🇬Sofia, Bulgaria
BG1026
🇧🇬Sofia, Bulgaria
BG1033
🇧🇬Varna, Bulgaria
BG1022
🇧🇬Tserova Koria, Bulgaria
BG1027
🇧🇬Vratsa, Bulgaria
CA1017
🇨🇦Chatham, Canada
CA1034
🇨🇦Kingston, Canada
RU1031
🇷🇺Saint Petersburg, Russian Federation
US1416
🇺🇸New York, New York, United States
RU1055
🇷🇺Moscow, Russian Federation
US1391
🇺🇸San Bernardino, California, United States
US1401
🇺🇸Charlotte, North Carolina, United States
US1319
🇺🇸Charleston, South Carolina, United States
US1453
🇺🇸Tampa, Florida, United States
US1451
🇺🇸Austin, Texas, United States