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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02717195
Recruitment Status : Completed
First Posted : March 23, 2016
Results First Posted : November 25, 2019
Last Update Posted : November 25, 2019
Sponsor:
Information provided by (Responsible Party):
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)

Condition or disease Intervention/treatment Phase
Schizophrenia Drug: Risperidone Drug: Olanzapine Drug: Lu AF35700 Phase 3

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Patients who did not fulfil the randomization criteria for the DBT Period, were withdrawn from the study after the PC period.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

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1098 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Interventional, Randomised, Double-blind, Active-controlled, Fixed-dose Study of Lu AF35700 in Patients With Treatment-resistant Schizophrenia
Study Start Date : April 2016
Actual Primary Completion Date : August 30, 2018
Actual Study Completion Date : October 8, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Schizophrenia

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

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
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




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.


  4. 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.

  5. 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.

  6. 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.

  7. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02717195


Locations
Show Show 147 study locations
Sponsors and Collaborators
H. Lundbeck A/S
Investigators
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Study Director: Email contact via H. Lundbeck A/S LundbeckClinicalTrials@Lundbeck.com
  Study Documents (Full-Text)

Documents provided by H. Lundbeck A/S:
Study Protocol  [PDF] June 27, 2017
Statistical Analysis Plan  [PDF] October 18, 2018

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Responsible Party: H. Lundbeck A/S
ClinicalTrials.gov Identifier: NCT02717195    
Other Study ID Numbers: 16159A
2014-003569-12 ( EudraCT Number )
First Posted: March 23, 2016    Key Record Dates
Results First Posted: November 25, 2019
Last Update Posted: November 25, 2019
Last Verified: October 2019
Additional relevant MeSH terms:
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Schizophrenia
Schizophrenia Spectrum and Other Psychotic Disorders
Mental Disorders
Olanzapine
Risperidone
Serotonin Antagonists
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Dopamine Antagonists
Dopamine Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Gastrointestinal Agents
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators