Clinical trial NCT02717195: Effect of Lu AF35700 in Patients With Treatment-resistant Schizophrenia
Official title: Interventional, Randomised, Double-blind, Active-controlled, Fixed-dose Study of Lu AF35700 in Patients With Treatment-resistant Schizophrenia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Schizophrenia
Lead sponsor: H. Lundbeck A/S
Sponsor class: INDUSTRY
First posted: 2016-03-23
Enrollment: 1098
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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Patients who did not fulfil the randomization criteria for the DBT Period, were withdrawn from the study after the PC period.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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Change From Randomization to Week 10 in Positive and Negative Syndrome Scale (PANSS) Total Score
timeFrame: From Randomization to Week 10
Secondary outcomes:
measure: Change From Randomization to Week 10 in PSP Total Personal and Social Performance (PSP) Total Score
timeFrame: From Randomization to Week 10
measure: Change From Randomization to Week 10 in Global Clinical Impression - Severity of Illness (CGI-S) Score
timeFrame: From Randomization to Week 10
measure: 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
timeFrame: From Randomization to Week 10
measure: Response at Week 10, Defined as ≥20% Reduction in Positive and Negative Syndrome Scale (PANSS) Total Score From Randomization
timeFrame: From Randomization to Week 10
measure: Response at Week 10, Defined as ≥30% Reduction in PANSS Total Score From Randomization
timeFrame: From Randomization to Week 10
measure: Response at Week 10, Defined as ≥40% Reduction in Positive and Negative Syndrome Scale (PANSS) Total Score From Randomization
timeFrame: From Randomization to Week 10
measure: Response at Week 10, Defined as ≥50% Reduction in Positive and Negative Syndrome Scale (PANSS) Total Score From Randomization
timeFrame: From Randomization to Week 10
Other outcomes:
Locations:
city: Bellflower
country: United States
facility: US1018
state: California
city: Cerritos
country: United States
facility: US1041
state: California
city: Costa Mesa
country: United States
facility: US1062
state: California
city: Culver City
country: United States
facility: US1463
state: California
city: Garden Grove
country: United States
facility: US1104
state: California
city: Glendale
country: United States
facility: US1118
state: California
city: National City
country: United States
facility: US1114
state: California
city: Oceanside
country: United States
facility: US1452
state: California
city: Oceanside
country: United States
facility: US1459
state: California
city: Orange
country: United States
facility: US1399
state: California
city: Orange
country: United States
facility: US1368
state: California
city: San Bernardino
country: United States
facility: US1391
state: California
city: Santa Ana
country: United States
facility: US1464
state: California
city: Sherman Oaks
country: United States
facility: US1384
state: California
city: Torrance
country: United States
facility: US1392
state: California
city: Washington
country: United States
facility: US1396
state: District of Columbia
city: Bradenton
country: United States
facility: US1395
state: Florida
city: Jacksonville
country: United States
facility: US1253
state: Florida
city: Miami
country: United States
facility: US1130
state: Florida
city: North Miami
country: United States
facility: US1318
state: Florida
city: North Miami
country: United States
facility: US1129
state: Florida
city: Oakland Park
country: United States
facility: US1402
state: Florida
city: Orange City
country: United States
facility: US1229
state: Florida
city: Tampa
country: United States
facility: US1453
state: Florida
city: Atlanta
country: United States
facility: US1403
state: Georgia
city: Atlanta
country: United States
facility: US1009
state: Georgia
city: Decatur
country: United States
facility: US1442
state: Georgia
city: Chicago
country: United States
facility: US1046
state: Illinois
city: Hoffman Estates
country: United States
facility: US1423
state: Illinois
city: Shreveport
country: United States
facility: US1398
state: Louisiana
city: Shreveport
country: United States
facility: US1404
state: Louisiana
city: Flowood
country: United States
facility: US1086
state: Mississippi
city: Las Vegas
country: United States
facility: US1444
state: Nevada
city: Berlin
country: United States
facility: US1426
state: New Jersey
city: Marlton
country: United States
facility: US1454
state: New Jersey
city: Glen Oaks
country: United States
facility: US1405
state: New York
city: Jamaica
country: United States
facility: US1244
state: New York
city: New York
country: United States
facility: US1394
state: New York
city: New York
country: United States
facility: US1416
state: New York
city: Rochester
country: United States
facility: US1171
state: New York
city: Staten Island
country: United States
facility: US1190
state: New York
city: Charlotte
country: United States
facility: US1390
state: North Carolina
city: Charlotte
country: United States
facility: US1401
state: North Carolina
city: Hickory
country: United States
facility: US1441
state: North Carolina
city: Norristown
country: United States
facility: US1124
state: Pennsylvania
city: Charleston
country: United States
facility: US1319
state: South Carolina
city: Austin
country: United States
facility: US1451
state: Texas
city: Dallas
country: United States
facility: US1065
state: Texas
city: Fort Worth
country: United States
facility: US1443
state: Texas
city: Burgas
country: Bulgaria
facility: BG1030
city: Kazanlak
country: Bulgaria
facility: BG1028
city: Lovech
country: Bulgaria
facility: BG1003
city: Pazardzhik
country: Bulgaria
facility: BG1032
city: Plovdiv
country: Bulgaria
facility: BG1008
city: Sofia
country: Bulgaria
facility: BG1024
city: Sofia
country: Bulgaria
facility: BG1026
city: Tserova Koria
country: Bulgaria
facility: BG1022
city: Varna
country: Bulgaria
facility: BG1033
city: Varna
country: Bulgaria
facility: BG1034
city: Veliko Tŭrnovo
country: Bulgaria
facility: BG1029
city: Vratsa
country: Bulgaria
facility: BG1027
city: Chatham
country: Canada
facility: CA1017
city: Kingston
country: Canada
facility: CA1034
city: Montréal
country: Canada
facility: CA1003
city: Montréal
country: Canada
facility: CA1033
city: Penticton
country: Canada
facility: CA1029
city: Québec
country: Canada
facility: CA1039
city: Brno
country: Czechia
facility: CZ1023
city: Brno
country: Czechia
facility: CZ1032
city: Hostivice
country: Czechia
facility: CZ1037
city: Lnare
country: Czechia
facility: CZ1013
city: Praha
country: Czechia
facility: CZ1038
city: Pärnu
country: Estonia
facility: EE1016
city: Tallinn
country: Estonia
facility: EE1007
city: Viljandi
country: Estonia
facility: EE1017
city: Espoo
country: Finland
facility: FI1032
city: Kuopio
country: Finland
facility: FI1030
city: Turku
country: Finland
facility: FI1027
city: Durango
country: Mexico
facility: MX1024
city: Guadalajara
country: Mexico
facility: MX1011
city: Guadalajara
country: Mexico
facility: MX1021
city: Guadalajara
country: Mexico
facility: MX1022
city: Mexico
country: Mexico
facility: MX1020
city: Monterrey
country: Mexico
facility: MX1005
city: Monterrey
country: Mexico
facility: MX1007
city: Monterrey
country: Mexico
facility: MX1015
city: Monterrey
country: Mexico
facility: MX1016
city: San Luis Potosi
country: Mexico
facility: MX1018
city: Bełchatów
country: Poland
facility: PL1025
city: Bialystok
country: Poland
facility: PL1043
city: Gorlice
country: Poland
facility: PL1026
city: Lodz
country: Poland
facility: PL1060
city: Lublin
country: Poland
facility: PL1027
city: Pruszcz Gdanski
country: Poland
facility: PL1058
city: Pruszkow
country: Poland
facility: PL1061
city: Torun
country: Poland
facility: PL1059
city: Wroclaw
country: Poland
facility: PL1051
city: Bucuresti
country: Romania
facility: RO1024
city: Câmpulung
country: Romania
facility: RO1022
city: Sibiu
country: Romania
facility: RO1025
city: Târgu-Mureş
country: Romania
facility: RO1004
city: Nikol'skoye
country: Russian Federation
facility: RU1021
state: Gatchinckiy District
city: Arkhangelsk
country: Russian Federation
facility: RU1009
city: Moscow
country: Russian Federation
facility: RU1006
city: Moscow
country: Russian Federation
facility: RU1051
city: Moscow
country: Russian Federation
facility: RU1055
city: Saint Petersburg
country: Russian Federation
facility: RU1023
city: Saint Petersburg
country: Russian Federation
facility: RU1028
city: Saint Petersburg
country: Russian Federation
facility: RU1030
city: Saint Petersburg
country: Russian Federation
facility: RU1031
city: Saint Petersburg
country: Russian Federation
facility: RU1052
city: Saint Petersburg
country: Russian Federation
facility: RU1053
city: Saint Petersburg
country: Russian Federation
facility: RU1056
city: St. Petersburg
country: Russian Federation
facility: RU1049
city: Yaroslavl
country: Russian Federation
facility: RU1050
city: Belgrade
country: Serbia
facility: RS1008
city: Belgrade
country: Serbia
facility: RS1010
city: Belgrade
country: Serbia
facility: RS1012
city: Kragujevac
country: Serbia
facility: RS1011
city: Kragujevac
country: Serbia
facility: RS1016
city: Kragujevac
country: Serbia
facility: RS1017
city: Nis
country: Serbia
facility: RS1003
city: Novi Knezevac
country: Serbia
facility: RS1009
city: Bratislava
country: Slovakia
facility: SK1014
city: Bratislava
country: Slovakia
facility: SK1024
city: Roznava
country: Slovakia
facility: SK1015
city: Svidnik
country: Slovakia
facility: SK1025
city: Zlate Moravce
country: Slovakia
facility: SK1026
city: Barcelona
country: Spain
facility: ES1047
city: Madrid
country: Spain
facility: ES1012
city: Malaga
country: Spain
facility: ES1008
city: Oviedo
country: Spain
facility: ES1048
city: Zamora
country: Spain
facility: ES1049
city: Dnipropetrovsk
country: Ukraine
facility: UA1019
city: Kharkiv
country: Ukraine
facility: UA1017
city: Kharkiv
country: Ukraine
facility: UA1022
city: Kharkiv
country: Ukraine
facility: UA1031
city: Kharkiv
country: Ukraine
facility: UA1035
city: Kherson
country: Ukraine
facility: UA1028
city: Kherson
country: Ukraine
facility: UA1029
city: Kiev
country: Ukraine
facility: UA1027
city: Kiev
country: Ukraine
facility: UA1030
city: Lviv
country: Ukraine
facility: UA1033
city: Odessa
country: Ukraine
facility: UA1020
city: Odessa
country: Ukraine
facility: UA1032
city: Poltava
country: Ukraine
facility: UA1001
city: Vinnitsa
country: Ukraine
facility: UA1036
Study officials:
affiliation: LundbeckClinicalTrials@Lundbeck.com
name: Email contact via H. Lundbeck A/S
role: STUDY_DIRECTOR
References:
citation: Kane JM, Kinon BJ, Forray C, Such P, Mittoux A, Lemming OM, Hertel P, Howes OD; DayBreak and Debut study investigators. Efficacy and safety of Lu AF35700 in treatment-resistant schizophrenia: A randomized, active-controlled trial with open-label extension. Schizophr Res. 2022 Oct;248:271-278. doi: 10.1016/j.schres.2022.09.012. Epub 2022 Sep 14.