Clinical trial NCT01972711 (phase 1, status: completed)
Conditions: schizophrenia
ICD codes: F20.0, F20.1, F20.2, F20.3, F20.5, F20.89, F20.9
Drugs: sep-363856, amisulpride, placebo
SMILES: ClC1=CC=CC(N2CCN(CCCCOC3=CC4=C(CCC(=O)N4)C=C3)CC2)=C1Cl, CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O
Eligibility criteria:

        Inclusion Criteria:

          -  Male or female aged 18 to 45 years, inclusive, at Day 1.

          -  Subject must be healthy as determined by the Investigator, based on a medical
             evaluation including medical history, physical examination, laboratory tests and
             cardiac monitoring within four weeks of randomisation. A subject with a clinical
             abnormality or laboratory parameters outside the reference range for the population
             being studied may be included only if the Investigator considers that the finding is
             unlikely to introduce additional risk factors and will not interfere with the study
             procedures.

          -  Subject must be normotensive with sitting (5 minutes) blood pressure between the range
             of 90 to 150 mm Hg systolic, inclusive, and 60 to 90 mm Hg diastolic, inclusive, at
             Screening.

          -  Subject must have sitting (5 minutes) heart rate ≥ 50 beats per minute at Screening.

          -  Subject must agree to use one of the following birth control/contraception methods
             from Screening until 90 days after receiving study drug.

          -  Female subject of child bearing potential (≤ 65 years) should be surgically sterile or
             abstinent or, if sexually active, must use an adequate method of contraception in
             addition to their partner(s) using a barrier method.

          -  Male subject with female partner(s) of childbearing potential must take appropriate
             precautions to avoid fathering a child and use barrier contraception, in addition to
             their female partner(s) using another method.

          -  Male subject must not donate sperm.

          -  Acceptable forms of contraception are as follows:

          -  Barrier methods: condoms, diaphragms, cervical caps; with a spermicide foam, gel,
             film, cream or pessary.

          -  Non-hormone containing intrauterine methods: intrauterine devices or systems.

          -  Other: prescription oral contraceptives, contraceptive injections, contraceptive
             implant, contraceptive vaginal ring, hormonal intrauterine device, double-barrier
             method, contraceptive patch, or male partner sterilisation.

          -  Subject must have normal ECG results, including QTcF < 450msec (for men) or < 470 ms
             (for women) (based on the Fridericia correction where QTcF = QT/RR0.33) at Screening.

          -  Subject must be a completely fluent English speaker who, in the opinion of the
             Investigator, is capable of completing the fMRI and behavioural tasks.

          -  Subject must be right-handed.

          -  Subject must have acceptable weight as defined by BMI (weight [kg]/height [m]²) range
             of 18 to 35 kg/m², inclusive at Screening.

          -  Subject must be a non-smoker or light smoker (≤ 10 cigarettes per day).

          -  Subject must have signed the informed consent form prior to the first study-related
             procedure indicating they understand the purpose of and procedures required for the
             study and are willing to participate in the study.

          -  Subject in the low schizotypy group must have an SPQ score < 10 at Screening.

          -  Subject in the high schizotypy group must have an SPQ score >43 at Screening

        Exclusion Criteria:

          -  Subject with a history of alcohol or substance dependence within the last 12 months
             from Screening.

          -  Subject with a positive urine drug screen at Screening or Day 1. One re-test within 1
             to 3 days is permitted if positive result is believed to be due to licenced
             opiate-based medication or ingestion of poppy seeds. In this event, re-test result
             will be used for assessing entry criterion and must be completed prior to
             randomisation.

          -  Subject with a positive alcohol breath test at Screening or Day 1.

          -  Female subject with a positive pregnancy test at Screening or Day 1.

          -  Female subject currently pregnant or trying to get pregnant or currently breast
             feeding.

          -  Subject who consumes large amounts of caffeinated drinks (more than 8 cups of standard
             caffeinated drinks (tea, instant coffee) or 6 cups of stronger coffee or other drinks
             containing methylxanthines such as coca cola or Red Bull per day).

          -  Subject with a relevant history, or presence upon clinical examination, of cardiac,
             ophthalmologic, pulmonary, endocrine (diabetes), blood disease, gastro-intestinal,
             hepatic or renal disease or other condition which in the opinion of the Investigator
             could interfere with the test procedures.

          -  Subject with a history of cancer, except for basal cell or Stage 1 squamous cell
             carcinoma of the skin which has been in remission for at least 5 years prior to Day 1.

          -  Subject meets the diagnostic criteria for schizophrenia, or any other psychotic
             disorder, as determined by the SCID-I at Screening

          -  Subject with a history of, or presents (in the opinion of the Investigator) with,
             significant neurological or psychiatric conditions (such as stroke, traumatic brain
             injury, depression, seizures, space occupying lesions, multiple sclerosis, Parkinson's
             disease, vascular dementia, transient ischemic attack, schizophrenia, blackouts
             requiring hospitalisation).

          -  Subject with a history of positive HIV test.

          -  Subject with a history of, or current condition of, migraine headaches or has
             undergone operations to the head.

          -  Subject with a significant hearing impairment which, in the opinion of the
             Investigator, may interfere with the performance of the behavioural tasks or fMRI
             tasks.

          -  Subject with a significant visual impairment including colour blindness, or history of
             ocular treatment including corrective laser eye surgery, or ongoing condition, which
             in the opinion of the Investigator may interfere with the performance of the
             behavioural tasks or fMRI tasks.

          -  Subject received prescribed medication within 28 days prior to Day 1 (apart from the
             contraceptive pill). Subjects who have taken prescription medication may still be
             entered into the study, if, in the opinion of the Investigator, the medication
             received will not interfere with the study procedures or compromise safety (see
             Section 10.2, Concomitant Medications).

          -  Subject received non-prescription medication, including supplements such as vitamins
             and herbal supplements within 48 hours prior to Day 1 (apart from paracetamol).
             Subjects who have taken non-prescription medication may still be entered into the
             study, if, in the opinion of the Investigator, the medication received will not
             interfere with the study procedures or compromise safety (see Section 10.2,
             Concomitant Medications).

          -  Subject received an experimental drug and / or used an experimental medical device
             within 30 days of randomisation or within a period less than 5 times the drug's
             half-life, whichever is longer.

          -  Subject with a known hypersensitivity to SEP-363856 or amisulpride or any of their
             excipients.

          -  Subject with a history of severe drug allergy or hypersensitivity.

          -  Subject who is unable or unwilling to comply with study procedures, including study
             prohibitions and restrictions (see Section 10.2, Concomitant Medications and Section
             10.3, Restrictions).

          -  Subject with previous experience with the ETB.

          -  Subject with a diagnosis of dyslexia.

          -  Subject with a history of claustrophobia or inability to tolerate scanner environment.

          -  Subject who fulfills any of the MRI contraindications on the standard site radiography
             screening questionnaire (e.g. history of surgery involving metal implants).

          -  Subject with a clinically relevant structural brain abnormality as determined by prior
             MRI scan.

          -  Subject with planned medical treatment within the study period that might interfere
             with the study procedures.

          -  Subject who is unlikely to comply with the clinical study protocol or is unsuitable
             for any other reason, in the opinion of the Investigator.

          -  Subject is a staff member or the relative of a staff member, or is in a subordinate
             relationship with the Investigator.

          -  Subject answers "yes" to "Suicidal Ideation" Items 4 or 5 on the C-SSRS.