A Study to Determine the Maximum Tolerated Dose of an Investigational Drug in Subjects With Schizophrenia
Condition: Schizophrenia
MeSH terms: Schizophrenia
Intervention: DSP-1349M; placebo
Intervention description: DSP-1349M injectable; placebo injection
Intervention MeSH terms: Lurasidone Hydrochloride
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 40.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Schizophrenia

Summary:

      A study to determine the maximum tolerated dose of an investigational drug in subjects with
      schizophrenia
    

Eligibility criteria:

        Inclusion Criteria:

          -  1. Subject has capacity; is willing and able to provide written consent for use and
             disclosure of protected health information per requirements of 45CFR164.508 (Health
             Insurance Portability and Accountability Act; HIPAA) prior to initiating any study
             procedure after being informed of the nature of the study, in the opinion of the study
             staff and PI.

             2. Subject is male or female 18 to 65 years of age, inclusive. 3. Subject has a
             diagnosis of schizophrenia as per DSM-IV-TR criteria, which in the opinion of the
             Investigator has been clinically stable for the past 6 months.

             4. Subject has a Body Mass Index (BMI) greater than or equal to 19.5 and less than or
             equal to 38 kg/m2.

             5. Subject does not have clinically relevant abnormal laboratory values per
             Investigator discretion.

             6. Subject does not have clinically relevant findings from vital signs measurements
             per Investigator discretion.

             7. Female subject is eligible to enter and participate in the study if she is of:

             a. Non-childbearing potential (ie, physiologically incapable of becoming pregnant,
             including any female who is pre-menarchal or post-menopausal);

          -  Postmenopausal females defined as being amenorrheic for greater than 2 years (or
             confirmed by FSH level) with an appropriate clinical profile.

          -  Women who have not been confirmed as postmenopausal should be advised to use
             contraception as outlined below.

          -  Women who have had a hysterectomy, bilateral oophorectomy or bilateral salpingectomy
             (as determined by subject's medical history).

             b. Child-bearing potential (all females ≤ 65 years of age), has a negative pregnancy
             test at screening and agrees to satisfy one of the following requirements:

          -  Complete abstinence from intercourse (as part of an abstinent lifestyle) a minimum of
             2 months prior to administration of the first dose of study drug, throughout the
             Treatment Period, and for a minimum of 3 months after completion or premature
             discontinuation from the study drug; or,

          -  Established use of highly effective methods of contraception from 1 month prior to
             administration of the first dose of study drug, during the Treatment Period, and 60
             days after completion or premature discontinuation from the study drug.

               -  Because of the unacceptable failure rate of barrier (chemical and/or physical)
                  methods, the barrier method of contraception must only be used in combination
                  with a highly effective method. Post-coital methods of contraception are not
                  permitted.

                  8. Male subjects with partners of child bearing potential must be practicing
                  abstinence, part of an abstinent life style or using protocol-specified methods
                  of birth control throughout the study and for 30 days after completion or
                  premature discontinuation from the study drug.

                  9. Subject is able and willing to remain off of prior antipsychotic medication
                  until the protocol-specified restabilization period.

                  10. Subject has a stable living arrangement for at least 3 months prior to Day
                  -12 and agrees to return to a similar living arrangement after discharge. Such
                  subjects remain eligible to participate in this protocol with approval from the
                  PI. Chronically homeless subjects should not be enrolled. The Medical Monitor
                  should be consulted for individual cases as

        Exclusion Criteria:

          1. Subject had an acute exacerbation of psychiatric symptoms requiring change in
             antipsychotic medication (with reference to drug or dose) within 3 months (90 days)
             before screening.

          2. Subject has known or suspected carcinoma.

          3. Subject has known presence or history of renal or hepatic insufficiency.

          4. Subject has significant disease(s) or clinically significant finding(s) on physical
             examination determined by the Investigator to pose a health concern to the subject
             while on study.

          5. Subject has a history or presence of clinically significant abnormal ECG (based on ECG
             central overread report) that may jeopardize the subject's safety to participate in
             this study, or a screening 12-lead ECG demonstrating any one of the following: heart
             rate (HR) > 100 bpm, QRS > 120 msec, QTcF > 450 msec, or PR > 220 msec.

          6. Subject has known history of a severe reaction to a previous antipsychotic (in the
             Investigator's opinion), including up to 80 mg/day of oral lurasidone.

          7. Subject has a history of drug-dependence as per DSM-IV-TR criteria during the six
             month period immediately prior to study entry.

          8. Subject has known or suspected excessive alcohol consumption, (exceeding more than 4
             drinks on any single day or more than 14 drinks per week; 1 drink = 5 ounces of wine
             or 12 ounces of beer or 1.5 ounces of hard liquor) within 6 months of the screening
             visit or a positive urine alcohol test at screening.

          9. Subject answers "yes" to "Suicidal Ideation" Items 4 or 5 on the C-SSRS at screening
             (in the past 1 month [30 days]) or at any point prior to randomization or history of
             suicidal behavior within the last two years.

         10. Subject has significant orthostatic hypotension at screening (ie, a drop in systolic
             blood pressure of 30 mmHg or more and/or drop in diastolic blood pressure of 20 mmHg
             or more on standing).

         11. Subject has presence or history (within the last year) of a medical or surgical
             condition that might interfere with the absorption, metabolism, or excretion of
             administered Lurasidone injectable suspension.

         12. Subject has a history of epilepsy or risk of having seizures.

         13. Subject has a positive urine alcohol at screening or on Day -12.

         14. Subject has positive test results within 28 days prior to the start of the study for:

               1. Human immunodeficiency virus (HIV).

               2. Hepatitis B surface antigen and Hepatitis C antibody.

               3. Urine drug test (marijuana, amphetamines, barbiturates, cocaine, opiates,
                  benzodiazepines, methadone, or other drugs of abuse). However, a positive test
                  for benzodiazepines may not result in exclusion of subjects if the Investigator
                  determines that the use of a prescription benzodiazepine is appropriate.

               4. Serum β-human chorionic gonadotropin (HCG) consistent with pregnancy (females
                  only).

         15. Subject has used of any inhibitor or inducer of CYP3A4 taken within 28 days prior to
             drug administration and until discharge.

         16. Subject has have used of concomitant medications that prolong the QT/QTc interval
             within 28 days prior to Day -12 through follow-up.

         17. Subject has received depot neuroleptics unless the last injection was at least one
             treatment cycle before Day -12.

         18. Subject has poor peripheral venous access or does not tolerate venipuncture that would
             cause difficulty for collecting blood samples.

         19. Subject has experienced significant blood loss (≥ 473 mL) or donated blood within 30
             days prior to screening, or intends to donate plasma or blood or undergo elective
             surgery during study participation or within 30 days after the last study visit.

         20. Subject has a prolactin concentration greater than or equal to 200 ng/mL at screening.

         21. Subject is unwilling to abstain from vigorous exercise from Day -12 until study
             discharge.

         22. Subjects has a significant risk of violent behavior or a significant risk of suicidal
             behavior based on history or in the PI's judgment OR is considered by the Investigator
             to be at imminent risk of suicide or injury to self, others, or property.

         23. Subject has a history of allergic reaction (clinically relevant history of drug
             hypersensitivity) or has a known or suspected sensitivity to any substance that is
             contained in the study drug or to Polysorbate 80, sodium chloride, or sodium
             phosphate.

         24. Subject requires treatment with a drug that consistently prolongs the QTc interval.

         25. Subject is currently participating, or has participated in a study with an
             investigational or marketed compound or device within 30 days prior to signing the
             informed consent, or Protocol D1052024, Version 2.00 Lurasidone Injectable Suspension
             Confidential and Proprietary 36 13 June 2018 has participated in 3 or more studies
             within 18 months prior to signing the informed consent.

         26. Subject is a staff member or the relative of a staff member.

         27. Subject, in the Investigator's opinion, is unsuitable in any other way to participate
             in the study.

         28. Subject is unable or unwilling to comply with study instructions, procedures or
             restrictions.