Study With Lu AF11167 for the Treatment of Negative Symptoms in Patients With Schizophrenia

Schizophrenia Clinical Trial

Official title:

Interventional, Randomized, Double-blind, Parallel-group, Placebo-controlled, Fixed-flexible-dose Study of Lu AF11167 for the Treatment of Persistent Prominent Negative Symptoms in Patients With Schizophrenia

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03793712
• Other study ID #: 17972A
• Status: Terminated
• Phase: Phase 2
• Start date: December 27, 2018
• Est. completion date: September 3, 2020

Study information

• Verified date: September 2020
• Source: H. Lundbeck A/S
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A study to evaluate the efficacy of 2 fixed-flexible doses of Lu AF11167 on negative symptoms in patients with schizophrenia

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 168
• Est. completion date: September 3, 2020
• Est. primary completion date: August 20, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria

• The patient has schizophrenia, diagnosed according to DSM-5® as confirmed by the Mini-International Neuropsychiatric Interview for Schizophrenia and Psychotic Disorders Studies (MINI-Schz).

• The patient has been known to the site or investigator and treated by the site or investigator for at least the last 6 months prior to Screening Visit 1.

• The patient has suffered from persistent prominent negative symptoms for the last 6 months prior to the Screening Visit 1, in the opinion of the investigator and recorded in medical records.

• The patient has been treated for schizophrenia with stable doses of an oral antipsychotic within the approved dose range and without any dose increase during the last 6 months prior to Screening Visit 1 (dose reductions are acceptable). Combination therapy of two antipsychotics is only allowed with the written approval of the Medical Monitor in cases where the second antipsychotic is a low-potency first generation antipsychotic drug (e.g., chlorpromazine, promazine or chlorprothixene at low doses) or quetiapine at a dose of =150 mg, given in the evening for sleep problems and where both can be discontinued during the washout phase without endangering the patient's safety. Both antipsychotics will be withdrawn during the washout phase and need to be discontinued before Screening Visit 2. Combination therapy of more than 2 antipsychotic medications is not allowed during the previous 6 months prior to Screening Visit 1.

• The patient has had no psychiatric admissions/hospitalization due to a clinical deterioration during the last 6 months prior to Screening Visit 1, this excludes ambulatory visits to ask for advice from the psychiatry team.Patients hospitalized during the last 6 months for social reasons only or patients who are currently hospitalized for social reasons can be included with the Medical Monitor's approval.

• The patient is in a clinically stable phase of schizophrenia and has not more than moderate severity on relevant positive symptoms, that is a score of =4 (moderate) out of score of 7 on each of the following PANSS items: Delusions (P1), Hallucinatory behaviour (P3), Suspiciousness / persecution (P6), Uncooperativeness (G8), Unusual thought content (G9) at Screening Visit 1, Washout Visit(s), Screening Visit 2, and Baseline Visit and a score =5 on Conceptual disorganization (P2).

• The patient currently has no clinically significant acute extrapyramidal side effects (acute EPS) or tardive dyskinesia (TD) based upon the protocol-specified clinical examination.

• The patient has prominent negative symptoms as demonstrated by a PANSS Marder Negative Symptom Factor Score (NSFS) =20 at Screening Visit 1, Washout Visit(s) and Screening Visit 2. NSFS is the sum of scores of the following PANSS items: Blunted affect (N1), Emotional withdrawal (N2), Poor rapport (N3), Passive/apathetic social withdrawal (N4), Lack of spontaneity & flow of conversation (N6), Motor retardation (G7) and Active social avoidance (G16).

• The patient has a Clinical Global Impression-Schizophrenia Severity of Illness (CGI-SCH-S) overall severity score =4 at Screening Visit 1.

• The patient does not currently have a diagnosis of Major Depressive Disorder or have depressive symptoms rated with a total score =5 on the Calgary Depression Scale for Schizophrenia (CDSS).

• The patient has no history of violent behaviour for the last 12 months prior to Screening Visit 1.

• The patient has a caregiver or an identified responsible person (for example, partner, family member, social worker, case worker, or nurse) considered reliable by the investigator in providing support to the patient to ensure compliance with study treatment, outpatient visits, and protocol procedures.

Exclusion criteria

• The patient has had an acute exacerbation requiring hospitalization within the last 6 months prior to Screening Visit 1.

• The patient has had an acute exacerbation requiring change in antipsychotic medication (with reference to drug or dose) within the last 6 months prior to Screening Visit 1.

• The patient has a current diagnosis or a history of substance use disorder according to DSM-5® criteria within 6 months prior to Screening Visit 1 with the exception of tobacco, or mild cannabis or mild alcohol use disorder (occasional - but not weekly recreational cannabis use is acceptable). Patients with a positive drug screen test for opiates, methadone, cocaine, amphetamines [including ecstasy], barbiturates, verified by repeated testing, are excluded from the study.

• The patient is at significant risk of harming himself/herself or others in the investigator's opinion.

• The patient has tested positive for hepatitis A virus antibody (anti-HAV IgM), hepatitis B surface antigen (HBsAg), or hepatitis C virus antibody (anti-HCV). If the anti-HCV test result is positive, but acute/chronic infection is excluded with a negative HCV RNA test patient can be included in the study.

• The patient has tested positive for human immunodeficiency virus (HIV).

• The patient has a present condition that might compromise liver function (for example, alcohol abuse, hepatitis, hepatic insufficiency, cholestasis, haemachromatosis, deficit in alpha 1 antitrypsine, Wilson's Disease, autoimmune diseases, cirrhosis).

• The patient has any other disorder for which the treatment takes priority over treatment of schizophrenia or is likely to interfere with the study treatment or impair treatment compliance.

Other in- and exclusion criteria may apply.

Related Conditions & MeSH terms

• Schizophrenia

Intervention

Drug:
• Lu AF11167 (1-2 mg/day)
Fixed-flexible oral dose, tablets. Once daily. 12 weeks.
• Lu AF11167 (3-4 mg/day)
Fixed-flexible oral dose, tablets. Once daily. 12 weeks.
• Placebo
Placebo oral dose, tablets. Once daily. 12 weeks.

Locations

Country	Name	City	State
Bulgaria	Mental Health Center Prof. Dr. Ivan Temkov EOOD (BG0001)	Bourgas
Bulgaria	MHAT Dr. Hristo Stambolski (BG0007)	Kazanlak
Bulgaria	State Psychiatric Hospital Lovech (BG0012)	Lovech
Bulgaria	First Department for men with acute mental diseases-NPH Sv. Ivan Rilski (BG0010)	Novi Iskar
Bulgaria	UMHAT Dr.Georgi Stranski EAD (BG0006)	Pleven
Bulgaria	Dr.Svetlozar Georgiev MD, Office of Office of Ambulatory for Group Practice for Specialized Psychiartic Help ¿ PHILIPOPOLIS OOD (BG0014)	Plovdiv
Bulgaria	State Psychiatric Hospital - Sevlievo (BG009)	Sevlievo
Bulgaria	Medical Center INTERMEDICA (BG0003)	Sofia
Bulgaria	DCC Mladost-M (BG0004)	Varna
Bulgaria	DCC Mladost-M Varna OOD (BG0005)	Varna
Bulgaria	Med Centre Medical plus (BG008)	Varna
Bulgaria	Center for Mental Health Veliko Tarnovo (BG0013)	Veliko Tarnovo
Bulgaria	Mental Health Center-Vratsa EOOD (BG0002)	Vratsa
Czechia	Dr.Jan Holan MD, Office of (CZ0003)	Brno
Czechia	Meditrine s.r.o. - Psychiatricka Ambulance, Lecebne Centrum (CZ0005)	Havírov
Czechia	Clinline services s.r.o. (CZ0006)	Hostivice
Czechia	Neuropsychiatrie HK, s.r.o. (CZ0004)	Hradec Králové
Czechia	A-Shine s.r.o. (CZ0001)	Plzen
Czechia	Institute of Neuropsychiatric Care (INEP) (CZ0007)	Praha 8
Estonia	Marienthali Kliinik (EE0001)	Tallinn
Estonia	OU Jaanson & Laane (EE0002)	Tartu
Germany	Medical Pratice For Neurology/Psychiatry (DE0003)	Berlin
Germany	Office of Dr.Kirsten Hahn (DE0002)	Berlin
Germany	Zentralinstitut fur Seelische Gesundheit (ZI)-Leitung Abteilung Molekulares Neuroimaging (DE0004)	Mannheim
Germany	Dr. Frank Kuehn MD, Office Of (DE001)	Oranienburg
Germany	Klinikum der Eberhard-Karls-Universitaet Tuebingen (DE0007)	Tuebingen
Hungary	Nyiro Gyula Hospital - OPAI (HU0006)	Budapest
Hungary	Semmelweis Egyetem-Neurologiai Klinika (HU0005)	Budapest
Hungary	Bugat Pal Hospital (HU0008)	Gyöngyös
Hungary	Dr Mathe es Tarsa Bt (HU0001)	Kalocsa
Hungary	Somogy Megyei Kaposi Mor Oktato Korhaz (HU0003)	Kaposvár
Hungary	Szabolcs-Szatmar-Bereg megyei Korhazak es Egyetemi Oktatokorhaz, Josa Andras Oktatokorhaz, Pszichiatriai es Pszichoterapias Osztaly (HU0002)	Nyíregyháza
Hungary	Javorszky Odon Hospital (HU0004)	Vác
Latvia	Daugavpils Psychoneurological Hospital (LV0005)	Daugavpils
Latvia	Hospital Gintermuiza (LV0001)	Jelgava
Latvia	Jsc Piejuras Slimnica Psychiatry Clinic (LV0003)	Liepaja
Latvia	Riga Centre Of Psychiatry And Addiction Disorders (LV0002)	Riga
Latvia	Sigulda Hospital Outpatient Clinic (LV0006)	Sigulda
Poland	Gabinet Lekarski Psychiatryczny Ireneusz Kaczorowski (PL0012)	Belchatów
Poland	Wlokiennicza Med Specjalistyczna Praktyka Lekarska dr n. med. Tomasz Markowski (PL0005)	Bialystok
Poland	Med-Ars (Pl0010)	Bydgoszcz
Poland	Centrum Zdrowia Psychicznego Biomed - Jan Latala (PL0006)	Kielce
Poland	Przychodnia Syntonia Izabela Chojnowska-Cwiakala (PL0011)	Kielce
Poland	Syntonia Sp. z o.o. (PL0002)	Pruszcz Gdanski
Ukraine	Si Inpn Namsu (Ua0003)	Kharkiv
Ukraine	Si Inpn Namsu (Ua0008)	Kharkiv
Ukraine	Kherson Regional Psychiatric Hospital (UA0009)	Kherson
Ukraine	Kiev Regional Specialized Psycho-Narcological Medical Care (UA0005)	Kiev
Ukraine	Communal Institution Kirovograd Regional Psychiatric Hospital. Donetsk National Medical University, Chair of psychiatry, psychotherapy, narcology and medical psychology (UA0004)	Kropyvnytskyi
Ukraine	Railway Clinical Hospital #1, Ukr Research Institute, Social And Forensic Psychatriy And Drug Abuse (UA0007)	Kyiv
Ukraine	Odessa Regional Medical Centre of Mental Health (UA0006)	Odessa
Ukraine	Ukrainian Medical Stomatological Academy, Chair Of Psychiatry, Narcology And Medical Psychology Based On O.F. Maltsev Poltava Regional Clinical Psychiatric Hospital (UA0001)	Poltava
Ukraine	Vinnitsa National Medical University (UA0002)	Vinnitsa

Sponsors (1)

Lead Sponsor	Collaborator
H. Lundbeck A/S

Countries where clinical trial is conducted

Bulgaria,  Czechia,  Estonia,  Germany,  Hungary,  Latvia,  Poland,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Negative Symptom Scale (BNSS) total score	The BNSS is a brief clinician rating scale, intended to measure negative symptoms. It consists of 13 items organized into 6 subscales: anhedonia, distress, asociality, avolition, blunted affect and alogia. The items score the impairment. Items 1 to 4 are rated from 0 (Normal) to 6 (Extremely severe) and items 5 to 13 are rated from 0 (No impairment) to 6 (Severe deficit). The BNSS total score is calculated by summing the 13 individual items; subscale scores are calculated by summing the individual items within each subscale. Users of the BNSS should have training in psychiatric interview techniques and have clinical experience working with patients with schizophrenia and related psychotic disorders. The BNSS total scores ranges from 0 to 78.	from baseline to Week 12
Secondary	Change in Personal and Social Performance (PSP) score	The PSP is a clinician-rated scale designed and validated to measure a patient's current level of social functioning. The PSP consists of 4 items: socially useful activities (including work and study), personal and social relationships, self-care, and disturbing and aggressive behaviours. The 4 items are assessed on a 6-point scale, from absent to very severe. Based on these assessments and their combination, individual scores are converted into a global score ranging from 1 to 100.	from baseline to Week 12
Secondary	Change in Positive and Negative Syndrome Scale (PANSS) total score	The PANSS is a clinician rated scale designed to measure severity of psychopathology in adult patients with schizophrenia, schizoaffective disorders and other psychotic disorders. It emphasizes positive and negative symptoms. The PANSS includes 3 sub-scales and 30 items	from baseline to Week 12
Secondary	Change in PANSS Marder Negative Symptom Factor score: negative symptoms	The PANSS is a clinician rated scale designed to measure severity of psychopathology in adult patients with schizophrenia, schizoaffective disorders and other psychotic disorders. It emphasizes positive and negative symptoms. The PANSS includes 3 sub-scales and 30 items	from baseline to Week 12
Secondary	Change in PANSS Negative subscale score	The PANSS is a clinician rated scale designed to measure severity of psychopathology in adult patients with schizophrenia, schizoaffective disorders and other psychotic disorders. It emphasizes positive and negative symptoms. The PANSS includes 3 sub-scales and 30 items	from baseline to Week 12
Secondary	Change in Clinical Global Impression - Schizophrenia (CGI-SCH-S) negative symptoms score	The CGI-SCH is a clinician-rated scale to assess global illness severity and degree of change in patients with schizophrenia. For both the global illness severity and degree of change, the CGI-SCH consists of four different groups of symptoms (positive, negative, cognitive and depressive) and the overall severity of the disorder. The CGI-SCH-S severity of illness category symptoms and overall severity are rated on a 7-point scale ranging from 1 (normal - not ill) to 7 (Among the most severely ill). For the first four ratings (positive, negative, depressive, and cognitive symptoms), the assessment should focus on the severity of symptoms only. Additionally, for 'overall severity' rating, both severity of symptoms and interference with functioning should be considered.	from baseline to Week 12
Secondary	Clinical Global Impression - Schizophrenia (CGI-SCH-DC) negative symptoms score	The CGI-SCH is a clinician-rated scale to assess global illness severity and degree of change in patients with schizophrenia. For both the global illness severity and degree of change, the CGI-SCH consists of four different groups of symptoms (positive, negative, cognitive and depressive) and the overall severity of the disorder. In the CGI-SCH-DC degree of change category symptoms and overall severity are rated on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). Each single rating (conditions of severity and degree of improvement) and overall ratings of severity and improvement are scored independently and no total score is derived.	at Week 12
Secondary	CGI-SCH-DC negative symptoms response	The CGI-SCH is a clinician-rated scale to assess global illness severity and degree of change in patients with schizophrenia. For both the global illness severity and degree of change, the CGI-SCH consists of four different groups of symptoms (positive, negative, cognitive and depressive) and the overall severity of the disorder. In the CGI-SCH-DC degree of change category symptoms and overall severity are rated on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). Each single rating (conditions of severity and degree of improvement) and overall ratings of severity and improvement are scored independently and no total score is derived. Response defined as CGI-SCH-DC negative symptoms = 1 or 2	at Week 12
Secondary	BNSS response	The BNSS is a brief clinician rating scale, intended to measure negative symptoms. It consists of 13 items organized into 6 subscales: anhedonia, distress, asociality, avolition, blunted affect and alogia. The items score the impairment. Items 1 to 4 are rated from 0 (Normal) to 6 (Extremely severe) and items 5 to 13 are rated from 0 (No impairment) to 6 (Severe deficit). The BNSS total score is calculated by summing the 13 individual items; subscale scores are calculated by summing the individual items within each subscale. Users of the BNSS should have training in psychiatric interview techniques and have clinical experience working with patients with schizophrenia and related psychotic disorders. The BNSS total scores ranges from 0 to 78. Response criteria defined as 20,30 or 40% decrease in BNSS total score.	at Week 12
Secondary	Change in PANSS -Positive subscale score	The PANSS is a clinician rated scale designed to measure severity of psychopathology in adult patients with schizophrenia, schizoaffective disorders and other psychotic disorders. It emphasizes positive and negative symptoms. The PANSS includes 3 sub-scales and 30 items	from baseline to Week 12
Secondary	Change in Clinical Global Impression - Schizophrenia (CGI-SCH-S) severity of illness overall severity score	The CGI-SCH is a clinician-rated scale to assess global illness severity and degree of change in patients with schizophrenia. For both the global illness severity and degree of change, the CGI-SCH consists of four different groups of symptoms (positive, negative, cognitive and depressive) and the overall severity of the disorder. The CGI-SCH-S severity of illness category symptoms and overall severity are rated on a 7-point scale ranging from 1 (normal - not ill) to 7 (Among the most severely ill). For the first four ratings (positive, negative, depressive, and cognitive symptoms), the assessment should focus on the severity of symptoms only. Additionally, for 'overall severity' rating, both severity of symptoms and interference with functioning should be considered.	from baseline to Week 12
Secondary	Clinical Global Impression - Schizophrenia (CGI-SCH-DC) degree of change in overall severity score	The CGI-SCH is a clinician-rated scale to assess global illness severity and degree of change in patients with schizophrenia. For both the global illness severity and degree of change, the CGI-SCH consists of four different groups of symptoms (positive, negative, cognitive and depressive) and the overall severity of the disorder. In the CGI-SCH-DC degree of change category symptoms and overall severity are rated on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). Each single rating (conditions of severity and degree of improvement) and overall ratings of severity and improvement are scored independently and no total score is derived.	at Week 12
Secondary	Change in Calgary Depression Scale for Schizophrenia (CDSS) total score	The CDSS is a 9-item clinician rated scale specifically developed for the assessment of depression in patients with schizophrenia. The items on the CDSS are all typical depressive symptoms and do not appear to overlap with the negative symptoms of schizophrenia. All items are rated on a 4-point scale from 0 (absent) to 3 (severe)	from baseline to Week 12