Clinical trial NCT03793712 (phase 2, status: terminated)
Conditions: schizophrenia
ICD codes: F20.0, F20.1, F20.2, F20.3, F20.5, F20.89, F20.9
Drugs: lu af11167 (1-2 mg/day), lu af11167 (3-4 mg/day), placebo
SMILES: CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O
Reason stopped: 
    lack of efficacy based on interim analysis
  
Eligibility criteria:

        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 Both antipsychotics will be withdrawn during the washout phase and need to be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.