Effect of Lu AF35700 in Patients With Treatment-resistant Schizophrenia (DayBreak)

October 30, 2019 updated by: H. Lundbeck A/S

Interventional, Randomised, Double-blind, Active-controlled, Fixed-dose Study of Lu AF35700 in Patients With Treatment-resistant Schizophrenia

To evaluate the efficacy of 10 and 20 mg/day of Lu AF35700 on schizophrenia symptoms in patients with treatment-resistant schizophrenia (TRS)

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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Patients who did not fulfil the randomization criteria for the DBT Period, were withdrawn from the study after the PC period.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

Study Type

Interventional

Enrollment (Actual)

1098

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Bulgaria
      • Burgas, Bulgaria
        • BG1030
      • Kazanlak, Bulgaria
        • BG1028
      • Lovech, Bulgaria
        • BG1003
      • Pazardzhik, Bulgaria
        • BG1032
      • Plovdiv, Bulgaria
        • BG1008
      • Sofia, Bulgaria
        • BG1024
      • Sofia, Bulgaria
        • BG1026
      • Tserova Koria, Bulgaria
        • BG1022
      • Varna, Bulgaria
        • BG1033
      • Varna, Bulgaria
        • BG1034
      • Veliko Tŭrnovo, Bulgaria
        • BG1029
      • Vratsa, Bulgaria
        • BG1027
  • Canada
      • Chatham, Canada
        • CA1017
      • Kingston, Canada
        • CA1034
      • Montréal, Canada
        • CA1003
      • Montréal, Canada
        • CA1033
      • Penticton, Canada
        • CA1029
      • Québec, Canada
        • CA1039
  • Czechia
      • Brno, Czechia
        • CZ1023
      • Brno, Czechia
        • CZ1032
      • Hostivice, Czechia
        • CZ1037
      • Lnare, Czechia
        • CZ1013
      • Praha, Czechia
        • CZ1038
  • Estonia
      • Pärnu, Estonia
        • EE1016
      • Tallinn, Estonia
        • EE1007
      • Viljandi, Estonia
        • EE1017
  • Finland
      • Espoo, Finland
        • FI1032
      • Kuopio, Finland
        • FI1030
      • Turku, Finland
        • FI1027
  • Mexico
      • Durango, Mexico
        • MX1024
      • Guadalajara, Mexico
        • MX1011
      • Guadalajara, Mexico
        • MX1022
      • Guadalajara, Mexico
        • MX1021
      • Mexico, Mexico
        • MX1020
      • Monterrey, Mexico
        • MX1005
      • Monterrey, Mexico
        • MX1007
      • Monterrey, Mexico
        • MX1015
      • Monterrey, Mexico
        • MX1016
      • San Luis Potosi, Mexico
        • MX1018
  • Poland
      • Bełchatów, Poland
        • PL1025
      • Bialystok, Poland
        • PL1043
      • Gorlice, Poland
        • PL1026
      • Lodz, Poland
        • PL1060
      • Lublin, Poland
        • PL1027
      • Pruszcz Gdanski, Poland
        • PL1058
      • Pruszkow, Poland
        • PL1061
      • Torun, Poland
        • PL1059
      • Wroclaw, Poland
        • PL1051
  • Romania
      • Bucuresti, Romania
        • RO1024
      • Câmpulung, Romania
        • RO1022
      • Sibiu, Romania
        • RO1025
      • Târgu-Mureş, Romania
        • RO1004
  • Russian Federation
      • Arkhangelsk, Russian Federation
        • RU1009
      • Moscow, Russian Federation
        • RU1006
      • Moscow, Russian Federation
        • RU1051
      • Moscow, Russian Federation
        • RU1055
      • Saint Petersburg, Russian Federation
        • RU1023
      • Saint Petersburg, Russian Federation
        • RU1028
      • Saint Petersburg, Russian Federation
        • RU1030
      • Saint Petersburg, Russian Federation
        • RU1031
      • Saint Petersburg, Russian Federation
        • RU1052
      • Saint Petersburg, Russian Federation
        • RU1053
      • Saint Petersburg, Russian Federation
        • RU1056
      • St. Petersburg, Russian Federation
        • RU1049
      • Yaroslavl, Russian Federation
        • RU1050
    • Gatchinckiy District
      • Nikol'skoye, Gatchinckiy District, Russian Federation
        • RU1021
  • Serbia
      • Belgrade, Serbia
        • RS1008
      • Belgrade, Serbia
        • RS1010
      • Belgrade, Serbia
        • RS1012
      • Kragujevac, Serbia
        • RS1011
      • Kragujevac, Serbia
        • RS1016
      • Kragujevac, Serbia
        • RS1017
      • Nis, Serbia
        • RS1003
      • Novi Knezevac, Serbia
        • RS1009
  • Slovakia
      • Bratislava, Slovakia
        • SK1014
      • Bratislava, Slovakia
        • SK1024
      • Roznava, Slovakia
        • SK1015
      • Svidnik, Slovakia
        • SK1025
      • Zlate Moravce, Slovakia
        • SK1026
  • Spain
      • Barcelona, Spain
        • ES1047
      • Madrid, Spain
        • ES1012
      • Malaga, Spain
        • ES1008
      • Oviedo, Spain
        • ES1048
      • Zamora, Spain
        • ES1049
  • Ukraine
      • Dnipropetrovsk, Ukraine
        • UA1019
      • Kharkiv, Ukraine
        • UA1017
      • Kharkiv, Ukraine
        • UA1022
      • Kharkiv, Ukraine
        • UA1031
      • Kharkiv, Ukraine
        • UA1035
      • Kherson, Ukraine
        • UA1028
      • Kherson, Ukraine
        • UA1029
      • Kiev, Ukraine
        • UA1027
      • Kiev, Ukraine
        • UA1030
      • Lviv, Ukraine
        • UA1033
      • Odessa, Ukraine
        • UA1020
      • Odessa, Ukraine
        • UA1032
      • Poltava, Ukraine
        • UA1001
      • Vinnitsa, Ukraine
        • UA1036
  • United States
    • California
      • Bellflower, California, United States, 90706
        • US1018
      • Cerritos, California, United States, 90703
        • US1041
      • Costa Mesa, California, United States, 92626
        • US1062
      • Culver City, California, United States, 90230
        • US1463
      • Garden Grove, California, United States, 92845
        • US1104
      • Glendale, California, United States, 91206
        • US1118
      • National City, California, United States, 91950
        • US1114
      • Oceanside, California, United States, 92056-4509
        • US1452
      • Oceanside, California, United States, 92056-4515
        • US1459
      • Orange, California, United States, 91945
        • US1399
      • Orange, California, United States, 92868
        • US1368
      • San Bernardino, California, United States, 92408-3332
        • US1391
      • Santa Ana, California, United States, 92705-3610
        • US1464
      • Sherman Oaks, California, United States, 91403-1747
        • US1384
      • Torrance, California, United States, 90502-4432
        • US1392
    • District of Columbia
      • Washington, District of Columbia, United States, 20016
        • US1396
    • Florida
      • Bradenton, Florida, United States, 32751
        • US1395
      • Jacksonville, Florida, United States, 32256
        • US1253
      • Miami, Florida, United States, 33122
        • US1130
      • North Miami, Florida, United States, 33161
        • US1318
      • North Miami, Florida, United States, 33162
        • US1129
      • Oakland Park, Florida, United States, 33334-4400
        • US1402
      • Orange City, Florida, United States, 32763
        • US1229
      • Tampa, Florida, United States, 33609-2231
        • US1453
    • Georgia
      • Atlanta, Georgia, United States, 30328
        • US1403
      • Atlanta, Georgia, United States, 30331
        • US1009
      • Decatur, Georgia, United States, 30030
        • US1442
    • Illinois
      • Chicago, Illinois, United States, 60640
        • US1046
      • Hoffman Estates, Illinois, United States, 60169-1067
        • US1423
    • Louisiana
      • Shreveport, Louisiana, United States, 71101-4603
        • US1398
      • Shreveport, Louisiana, United States, 71104-2136
        • US1404
    • Mississippi
      • Flowood, Mississippi, United States, 39232
        • US1086
    • Nevada
      • Las Vegas, Nevada, United States, 89102-1943
        • US1444
    • New Jersey
      • Berlin, New Jersey, United States, 08009
        • US1426
      • Marlton, New Jersey, United States, 08053
        • US1454
    • New York
      • Glen Oaks, New York, United States, 11004
        • US1405
      • Jamaica, New York, United States, 11432
        • US1244
      • New York, New York, United States, 10032
        • US1394
      • New York, New York, United States, 10035-6000
        • US1416
      • Rochester, New York, United States, 14618
        • US1171
      • Staten Island, New York, United States, 10312
        • US1190
    • North Carolina
      • Charlotte, North Carolina, United States, 28204-3110
        • US1390
      • Charlotte, North Carolina, United States, 28211-1064
        • US1401
      • Hickory, North Carolina, United States, 28601-5045
        • US1441
    • Pennsylvania
      • Norristown, Pennsylvania, United States, 19403
        • US1124
    • South Carolina
      • Charleston, South Carolina, United States, 29407
        • US1319
    • Texas
      • Austin, Texas, United States, 78754-5122
        • US1451
      • Dallas, Texas, United States, 75243
        • US1065
      • Fort Worth, Texas, United States, 76104
        • US1443

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: DOUBLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Prospective Confirmation (PC) Period
Single (patient)-blinded treatment period with risperidone or olanzapine for 6 weeks
Drug: Risperidone
4-6 mg/day, encapsulated tablets, orally
Drug: Olanzapine
15-20 mg/day, encapsulated tablets, orally
EXPERIMENTAL: Double-blind Treatment (DBT) Period, Lu AF35700 10 mg
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
Drug: Lu AF35700
10 mg/day, encapsulated tablets, orally
Drug: Lu AF35700
20 mg/day, encapsulated tablets, orally
EXPERIMENTAL: DBT Period, Lu AF35700 20 mg
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
Drug: Lu AF35700
10 mg/day, encapsulated tablets, orally
Drug: Lu AF35700
20 mg/day, encapsulated tablets, orally
EXPERIMENTAL: DBT Period, Continued treatment from PC Period
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
Drug: Risperidone
4-6 mg/day, encapsulated tablets, orally
Drug: Olanzapine
15-20 mg/day, encapsulated tablets, orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Randomization to Week 10 in Positive and Negative Syndrome Scale (PANSS) Total Score
Time Frame: 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.
From Randomization to Week 10

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Randomization to Week 10 in PSP Total Personal and Social Performance (PSP) Total Score
Time Frame: 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.
From Randomization to Week 10
Change From Randomization to Week 10 in Global Clinical Impression - Severity of Illness (CGI-S) Score
Time Frame: 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.
From Randomization to Week 10
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
Time Frame: 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.
From Randomization to Week 10
Response at Week 10, Defined as ≥20% Reduction in Positive and Negative Syndrome Scale (PANSS) Total Score From Randomization
Time Frame: 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.
From Randomization to Week 10
Response at Week 10, Defined as ≥30% Reduction in PANSS Total Score From Randomization
Time Frame: 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.
From Randomization to Week 10
Response at Week 10, Defined as ≥40% Reduction in Positive and Negative Syndrome Scale (PANSS) Total Score From Randomization
Time Frame: 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.
From Randomization to Week 10
Response at Week 10, Defined as ≥50% Reduction in Positive and Negative Syndrome Scale (PANSS) Total Score From Randomization
Time Frame: 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.
From Randomization to Week 10

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

H. Lundbeck A/S

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2016

Primary Completion (ACTUAL)

August 30, 2018

Study Completion (ACTUAL)

October 8, 2018

Study Registration Dates

First Submitted

March 11, 2016

First Submitted That Met QC Criteria

March 17, 2016

First Posted (ESTIMATE)

March 23, 2016

Study Record Updates

Last Update Posted (ACTUAL)

November 25, 2019

Last Update Submitted That Met QC Criteria

October 30, 2019

Last Verified

October 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 16159A
  • 2014-003569-12 (EUDRACT_NUMBER)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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