Treatment-resistant SchizophreniaPhase 3AnewNCT03230864
Efficacy of Lu AF35700 in Patients With Early-in-disease or Late-in-disease Treatment-resistant Schizophrenia
A Phase 3 study testing Lu AF35700, Risperidone and Olanzapine in people with Treatment-resistant Schizophrenia, run by H. Lundbeck A/S at 41 sites in 5 countries.
Trial summary
This study evaluates the efficacy of 10 mg/day Lu AF35700 on symptoms of schizophrenia in patients with early-in-disease (ED) or late-in-disease (LD) treatment-resistant schizophrenia (TRS) Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Treatment-resistant Schizophrenia
- What is being tested?
- Lu AF35700, Risperidone and Olanzapine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 119 participants
- Where
- 41 sitesin 5 countries
- Study dates
- 20 Jul 2017to 5 Feb 2019
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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 (MINI-Schz).
- The patient is receiving treatment with a psychiatrist in either an inpatient or outpatient facility.
- The patient has been treated with adequate dose(s) of antipsychotic drug treatment for at least 2 weeks prior to the Screening Visit.
- The patient has failed to show an adequate response in the level of psychotic symptoms during at least one documented treatment trial with an adequate dose of an antipsychotic drug prescribed for an adequate time (at least lasting for 6 weeks) within 2 years prior to the Screening Visit. The failure to respond to the current antipsychotic drug treatment trial may be considered a retrospective failed treatment, if the patient has been treated for 6 weeks with adequate dose(s) of antipsychotic drug(s).
- The patient has a PANSS total score of ≥80 (on 1-7 scale) and a score of ≥4 (≥ "Moderate" on 1-7 scale) on at least 2 of the following PANSS items at the Screening and at Baseline 1 [Week 0] Visits: P2 - Conceptual disorganization, P3 - Hallucinatory behavior, P6 - Suspiciousness/persecution, G9 - Unusual thought content; AND the patient has a CGI-S score of ≥4 (≥ "Moderately ill") at the Screening and at Baseline 1 (Week 0) Visits.
Who cannot join
- The patient has any current primary psychiatric disorder other than schizophrenia, as assessed using the MINI-Schz.
- The patient suffers from mental retardation, organic mental disorders, or mental disorders due to a general medical condition (DSM-5™ criteria).
- The patient is experiencing an acute exacerbation of his/her psychotic symptoms.
- The patient has been treated with, AND is resistant to, clozapine according to the investigator's judgement.
Trial locations and contacts
41 sites in 5 countries.
41 sites in 5 countries
United States10 sites
Michigan Clinical Research Institute PC
Ann Arbor, Michigan, 48108
Emory University Cognitive Neurology Clinic & ADRC
Atlanta, Georgia, 30329
Northwestern University
Chicago, Illinois, 60611
Corrigan Mental Health Center
Fall River, Massachusetts, 02720
Kalamazoo Community Mental Health and Substance Abuse Services
Kalamazoo, Michigan, 49001
Creighton University
Omaha, Nebraska, 68131
Psychiatric and Behavioral Solutions
Salt Lake City, Utah, 84105
University of California San Diego Health System
San Diego, California, 92103
PsychCare Consultants Research
St Louis, Missouri, 63128
University Of Massachusetts Medical Center
Worcester, Massachusetts, 01605-2610
Japan10 sites
Takeda General Hospital - JP0009
Aizu-Wakamatsu
Takeda General Hospital
Fukushima
Kohnodai Hospital
Ichikawa
Nara Medical University Hospital
Kashihara
Sankeikai Nishigahara Hospital - JP0008
Kita-ku
University of Occupational and Environmental Health Hospital
Kitakyushu
National Center of Neurology and Psychiatry
Kodaira
Satokai Yuge Hospital
Kumamoto
NHO Ryukyu Hospital
Kunigami
Fujita Health University Hospital
Toyoake
Russia9 sites
GUZ Lipetsk Regional psychoneurological Hospital 1
Lipetsk
Lipetsk Regional Psychoneurological Hospital
Lipetsk
City Psychiatric Hospital # 6
Saint Petersburg
Psychoneurological Dispensary #10
Saint Petersburg
Psychoneurological Dispensary #1
Saint Petersburg
Samara Psychiatric Hospital
Samara
Tomsk National Research Medical Centre of the Russian Academy of Sciences
Tomsk
Yaroslavl Regional Clinical Psychiatric Hospital
Yaroslavl
Sverdlovsk Regional Clinical Psychiatric Hospital
Yekaterinburg
Bulgaria7 sites
SPH - Kardzhali
Kardzhali
State Psychiatric Hospital
Novi Iskar
UMHAT
Pleven
State Psychiatric Hospital
Radnevo
DCC St. Vrach and St.St. Kuzma and Damian
Sofia
MHC - Sofia
Sofia
MHAT - Targovishte
Targovishte
United Kingdom5 sites
Royal Edinburgh Hospital
Edinburgh
The Maudsley Hospital - GB0001
London
The Maudsley Hospital
London
Manchester Mental Health & Social Care NHS Trust - GB0003
Manchester
Manchester Mental Health & Social Care NHS Trust
Manchester
About this study
Official title: Interventional, Randomized, Double-blind, Active-controlled Study of the Efficacy of Lu AF35700 in Patients With Early-in-disease or Late-in-disease Treatment-resistant Schizophrenia
This study evaluates the efficacy of 10 mg/day Lu AF35700 on symptoms of schizophrenia in patients with early-in-disease (ED) or late-in-disease (LD) treatment-resistant schizophrenia (TRS)
Read the detailed description
In the study, patients will receive risperidone (4-6 mg/day), or, if recently failed on risperidone, olanzapine (15-20mg/day). Later during the study, patients will be randomized to either receive Lu AF35700 (10 mg/day), or continue their treatment from the prospective confirmation (PC) period.
The study consists of a Screening Period (up to 3 weeks), a single-blind PC Period (6 weeks), a Double-blind Treatment (DBT) Period (8 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 the 2 treatmetn arms (1:1) with either Lu AF35700 10 mg or to continue the treatment allocated in the PC period (olanzapine or risperidone) at the dose set at the last visit of the PC period. This means that approximately half of the confirmed treatment-resistant patients were randomised back to the failed treatment in the PC period.
Data was not collected seperately for the DBT olanzapine and DBT risperidone participants, and there was no intent to compare Lu AF35700 to each drug seperately.
- Conditions
- Treatment-resistant Schizophrenia
- Being tested
- Lu AF35700, Risperidone, Olanzapine
- Keywords
- Treatment-resistant schizophrenia, Lu AF35700
- Medical subject headings
- Schizophrenia, Treatment-Resistant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lu AF35700Drug
10 mg/day, encapsulated tablets, orally
RisperidoneDrug
4-6 mg/day, encapsulated tablets, orally
OlanzapineDrug
15-20 mg/day, encapsulated tablets, orally
| Study group | Role | What they receive |
|---|---|---|
| Prospective Confirmation (PC) Period | Experimental | Single (patient)-blinded treatment period with risperidone or olanzapine for 6 weeks Receives: Drug: Risperidone; Drug: Olanzapine |
| Double-blind treatment (DBT) period, Lu AF35700 10 mg | Experimental | Eligible patients from PC period (based on criteria to which investigator and patient are blinded ), will be randomly assigned (1:1) double-blind treatment in DBT period, 8 weeks Receives: Drug: Lu AF35700 |
| DBT Period, Continued treatment from PC Period | Experimental | Eligible patients from PC period (based on criteria to which investigator and patient are blinded ), will be randomly assigned (1:1) double-blind treatment in DBT period, 8 weeks. Patients in this arm will continue with the same treatment and dose as at the last visit of the PC Period Receives: Drug: Risperidone; Drug: Olanzapine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Randomization to Week 8 in Positive and Negative Syndrome Scale (PANSS) Total Score
PANSS total score administered by the investigator. It included 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 negative score indicates an improvement compared to Randomization.
Measured: From Randomization to Week 8
Secondary outcomes (4)
Change From Randomization to Week 8 in Global Clinical Impression - Severity of Illness (CGI-S) Score
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
Measured: From Randomization to Week 8
Change From Randomization to Week 8 in 16-item Negative Symptom Assessment (NSA-16 Total) Score
The NSA-16 is a clinician-rated scale designed to assess the presence, severity, and range of negative symptoms associated with schizophrenia. The NSA-16 consists of 16 items arranged in 5 subdomains: communication dysfunction (items 1 to 4), emotional/affective dysfunction (items 5 to 7), dysfunction in sociality (items 8 to 10), motivational/hedonic dysfunction (items 11 to 14), and reduced psychomotor activity (items 15 and 16), and a Global Negative Symptom Rating. NSA-16 items are rated on a 6-point scale from 1 (behaviour is normal) to 6 (behaviour severely reduced), and a score of 9 if the item is not-rateable. The Global Negative Symptom Rating is rated from 1 (no evidence of symptoms) to 7 (extremely severe symptoms). The 16 items are summed to yield a total score ranging from 16 to 96 and the global rating ranges from 1 to 7.
Measured: From Randomization to Week 8
Change From Randomization to Week 8 in PANSS Marder Negative Factor Score
The PANSS Negative Factor score is a subset of the PANSS assessing negative symptoms of schizophrenia. The factor consist of the seven items: blunted affect, emotional withdrawal, poor rapport, passive social withdrawal, lack of spontaneity, motor retardation, and active social avoidance which are each rated on a 7-point scale, from 1=absent to 7=extreme. The PANSS Negative Factor score (7 items) range from 7 to 49 with a higher score indicating greater severity of symptoms.
Measured: From Randomization to Week 8
Response
Response is defined as a ≥20% reduction in PANSS total score from Randomization
Measured: at Week 8
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jul 2017
- Study start20 Jul 2017
- Primary completion23 Dec 2018
- Study completion5 Feb 2019
Why it stopped: New data; the study was terminated based on new efficacy data from another study
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Treatment-resistant SchizophreniaStudies of the same condition, open and under way.
- More trials run by H. Lundbeck A/SThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 119 participants (actual)
Sponsor and investigators
- Lead sponsor
- H. Lundbeck A/S
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Email contact via H.Lundbeck A/S, Study director, LundbeckClinicalTrials@Lundbeck.com
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03230864
- Sponsor's protocol ID
- 17303A
- Acronym
- Anew
- Status last verified
- Jan 2020
- First submitted
- 24 Jul 2017
- Last updated
- 21 Jan 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Interventional, Randomized, Double-blind, Active-controlled Study of the Efficacy of Lu AF35700 in Patients With Early-in-disease or Late-in-disease Treatment-resistant Schizophrenia
- ClinicalTrials.gov ID
- NCT03230864
- Acronym / sponsor ID
- Anew / 17303A
- Conditions
- Treatment-resistant Schizophrenia
- Keywords
- Treatment-resistant schizophrenia, Lu AF35700
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: New data; the study was terminated based on new efficacy data from another study
- Enrolment
- 119 participants (actual)
- Lead sponsor
- H. Lundbeck A/SIndustry (pharma, biotech, devices)
- Study start
- 20 Jul 2017 (actual)
- Primary completion
- 23 Dec 2018 (actual)
- Study completion
- 5 Feb 2019 (actual)
- First posted
- 27 Jul 2017 (actual)
- Results
- Posted 7 Jan 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study evaluates the efficacy of 10 mg/day Lu AF35700 on symptoms of schizophrenia in patients with early-in-disease (ED) or late-in-disease (LD) treatment-resistant schizophrenia (TRS)
Detailed description
In the study, patients will receive risperidone (4-6 mg/day), or, if recently failed on risperidone, olanzapine (15-20mg/day). Later during the study, patients will be randomized to either receive Lu AF35700 (10 mg/day), or continue their treatment from the prospective confirmation (PC) period.
The study consists of a Screening Period (up to 3 weeks), a single-blind PC Period (6 weeks), a Double-blind Treatment (DBT) Period (8 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 the 2 treatmetn arms (1:1) with either Lu AF35700 10 mg or to continue the treatment allocated in the PC period (olanzapine or risperidone) at the dose set at the last visit of the PC period. This means that approximately half of the confirmed treatment-resistant patients were randomised back to the failed treatment in the PC period.
Data was not collected seperately for the DBT olanzapine and DBT risperidone participants, and there was no intent to compare Lu AF35700 to each drug seperately.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Prospective Confirmation (PC) Period | Experimental | Drug: Risperidone, Drug: OlanzapineSingle (patient)-blinded treatment period with risperidone or olanzapine for 6 weeks |
| Double-blind treatment (DBT) period, Lu AF35700 10 mg | Experimental | Drug: Lu AF35700Eligible patients from PC period (based on criteria to which investigator and patient are blinded ), will be randomly assigned (1:1) double-blind treatment in DBT period, 8 weeks |
| DBT Period, Continued treatment from PC Period | Experimental | Drug: Risperidone, Drug: OlanzapineEligible patients from PC period (based on criteria to which investigator and patient are blinded ), will be randomly assigned (1:1) double-blind treatment in DBT period, 8 weeks. Patients in this arm will continue with the same treatment and dose as at the last visit of the PC Period |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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 (MINI-Schz).
- The patient is receiving treatment with a psychiatrist in either an inpatient or outpatient facility.
- The patient has been treated with adequate dose(s) of antipsychotic drug treatment for at least 2 weeks prior to the Screening Visit.
- The patient has failed to show an adequate response in the level of psychotic symptoms during at least one documented treatment trial with an adequate dose of an antipsychotic drug prescribed for an adequate time (at least lasting for 6 weeks) within 2 years prior to the Screening Visit. The failure to respond to the current antipsychotic drug treatment trial may be considered a retrospective failed treatment, if the patient has been treated for 6 weeks with adequate dose(s) of antipsychotic drug(s).
- The patient has a PANSS total score of ≥80 (on 1-7 scale) and a score of ≥4 (≥ "Moderate" on 1-7 scale) on at least 2 of the following PANSS items at the Screening and at Baseline 1 [Week 0] Visits: P2 - Conceptual disorganization, P3 - Hallucinatory behavior, P6 - Suspiciousness/persecution, G9 - Unusual thought content; AND the patient has a CGI-S score of ≥4 (≥ "Moderately ill") at the Screening and at Baseline 1 (Week 0) Visits.
Key exclusion criteria (4 listed)
- The patient has any current primary psychiatric disorder other than schizophrenia, as assessed using the MINI-Schz.
- The patient suffers from mental retardation, organic mental disorders, or mental disorders due to a general medical condition (DSM-5™ criteria).
- The patient is experiencing an acute exacerbation of his/her psychotic symptoms.
- The patient has been treated with, AND is resistant to, clozapine according to the investigator's judgement.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Lu AF3570010 mg/day, encapsulated tablets, orally | Drug | Double-blind treatment (DBT) period, Lu AF35700 10 mg |
| Risperidone4-6 mg/day, encapsulated tablets, orally | Drug | DBT Period, Continued treatment from PC Period, Prospective Confirmation (PC) Period |
| Olanzapine15-20 mg/day, encapsulated tablets, orally | Drug | DBT Period, Continued treatment from PC Period, Prospective Confirmation (PC) Period |
Primary outcome
Change From Randomization to Week 8 in Positive and Negative Syndrome Scale (PANSS) Total Score
Time frame: From Randomization to Week 8
PANSS total score administered by the investigator. It included 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 negative score indicates an improvement compared to Randomization.
4 secondary outcomes
Change From Randomization to Week 8 in Global Clinical Impression - Severity of Illness (CGI-S) Score
Time frame: From Randomization to Week 8
Change From Randomization to Week 8 in 16-item Negative Symptom Assessment (NSA-16 Total) Score
Time frame: From Randomization to Week 8
Change From Randomization to Week 8 in PANSS Marder Negative Factor Score
Time frame: From Randomization to Week 8
Response
Time frame: at Week 8
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jan 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Email contact via H.Lundbeck A/S study director
LundbeckClinicalTrials@Lundbeck.com
41 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Lu AF35700, Risperidone and Olanzapine in people with Treatment-resistant Schizophrenia, run by H. Lundbeck A/S at 41 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 21 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 41 sites in United States, Japan, Russia, Bulgaria, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 7 Jan 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Randomization to Week 8 in Positive and Negative Syndrome Scale (PANSS) Total Score (time frame: From Randomization to Week 8). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jan 2020.