Trial Evaluating OPC-34712 in Subjects With Normal Renal Function and Renally Impaired Subjects
Condition: Schizophrenia; Psychiatric Disorders
MeSH terms: Schizophrenia; Mental Disorders; Problem Behavior
Intervention: OPC-34712
Intervention description: administered orally
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 19.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Schizophrenia; psychiatric disorders; renal failure

Summary:

      This trial is an open-label, multi-center, parallel-arm, single-dose trial in 2 groups: 1
      group of subjects with normal renal function and 1 group of severely renally impaired
      subjects.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or female (non-childbearing potential) subjects ≥ 18 years of age.

          -  Ability to provide written informed consent prior to initiation of any trial-related
             procedures, and ability, in the opinion of the principal investigator, to comply with
             all the requirements of the trial.

          -  Male and female subjects who are surgically sterile; female subjects who have been
             postmenopausal for at least 12 consecutive months (confirmed by follicle stimulating
             hormone sample at Screening); or male subjects who agree to remain abstinent or to
             practice double-barrier forms of birth control and refrain from sperm donation from
             trial Screening through 90 days from the last dose of the investigational medicinal
             product.

          -  Body weight within ± 35% of ideal body weight as defined in the 1983 Metropolitan
             Height and Weight Tables (see Appendix 4, Appendix 5, and Appendix 6). Minimum body
             weight no less than 50 kg.

        Inclusion Criteria for Subjects with Normal Renal Function

          -  Subjects who are in good health as determined by a medical history, physical
             examination, serum chemistry, hematology, urinalysis, hepatitis B and C tests, and
             human immunodeficiency virus (HIV) testing.

          -  Creatinine clearance > 80 mL/min indicating normal renal function.

        Inclusion Criteria for Renally Impaired Subjects

          -  Renally impaired subjects may be taking medications which, in the opinion of the
             clinical investigator and sponsor, are believed to be therapeutic for the subjects
             (but do not affect OPC-34712 absorption, distribution, metabolism, or elimination).
             Inhibitors and inducers of CYP3A4 and inhibitors of CYP2D6 are not allowed.

          -  Creatinine clearance < 30 mL/min indicating severe renal impairment.

          -  Subjects with renal impairment should have relatively stable renal function as
             determined by creatinine clearance and otherwise be in generally good health.

        Exclusion Criteria:

        Clinically significant abnormality in past medical history, or at the screening physical
        examination, that in the investigator's or sponsor's opinion may place the subject at risk
        or interfere with outcome variables including absorption, distribution, metabolism, and
        excretion of drug.

          -  Any surgical or medical condition (active or chronic) that may interfere with drug
             absorption, distribution, metabolism, or excretion, or any other condition that may
             place the subject at risk.

          -  History of drug and/or alcohol abuse within 2 years prior to Screening.

          -  A positive urine alcohol test and/or urine drug screen for substance of abuse at
             Screening or upon check-in to the trial site.

          -  The donation of blood or plasma within 30 days prior to dosing.

          -  Any history of significant bleeding or hemorrhagic tendencies.

          -  History of or current hepatitis or carriers of hepatitis B surface antigen (HBsAg)
             and/or hepatitis C antibodies (anti-HCV).

          -  History of acquired immunodeficiency syndrome or determined human immunodeficiency
             virus (HIV) positive at Screening.

          -  Use of an investigational drug or product, or participation in a drug trial within 30
             days prior to dosing.

          -  Previous exposure to OPC-34712.

          -  History of clinically significant drug allergies or sensitivities.

          -  Subjects who are pregnant or breastfeeding. A negative serum pregnancy test must be
             confirmed prior to administration of trial medication for all female subjects.

          -  Subjects who have a supine pulse rate, after resting for ≥ 3 minutes, outside the
             range of 40 to 90 bpm. The sponsor may allow exceptions if they are not deemed
             clinically significant.

        Exclusion Criteria for Healthy Subjects

          -  Clinically significant abnormal findings in the serum chemistry, hematology, or
             urinalysis results obtained at Screening or Day -1.

          -  Use of prescription, over-the-counter, herbal medication or vitamin supplements within
             14 days prior to dosing and antibiotics within 30 days prior to dosing. The sponsor
             may allow exceptions only if the medication's administration is deemed unlikely to
             impact the pharmacokinetic result. Inhibitors and inducers of CYP3A4 and inhibitors of
             CYP2D6 are not allowed.

          -  Subjects who have supine, sitting, or standing blood pressure, after resting for ≥ 3
             minutes, higher than 130/80 mmHg or lower than 100/50 mmHg. The sponsor may allow
             exceptions if they are not deemed clinically significant.

        Exclusion Criteria for Renally Impaired Subjects

          -  Subjects that have undergone a renal transplant.

          -  Renally impaired subjects may be taking medications which, in the opinion of the
             clinical investigator and sponsor, are believed to be therapeutic for the subjects
             (but do not affect OPC-34712 absorption, distribution, metabolism, or elimination).
             Inhibitors and inducers of CYP3A4 and inhibitors of CYP2D6 are not allowed.

          -  Clinically significant abnormal findings in the serum chemistry, hematology, or
             urinalysis results obtained at Screening or Day -1, other than those associated with
             underlying renal conditions and other stable medical conditions consistent with the
             disease processes.

          -  Subject requiring dialysis or expected to require dialysis within 45 days.

          -  Subjects who have supine, sitting, or standing blood pressure, after resting for ≥ 3
             minutes, higher than 160/95 mmHg or lower than 100/50 mmHg. The sponsor may allow
             exceptions if they are not deemed clinically significant.

          -  Subjects with evidence of delirium.

          -  Clinically relevant changes on electrocardiogram such as any atrioventricular block,
             prolongation of the QRS complex over 120 msec (for both male and female subjects), or
             with a QTcF interval ≥ 450 msec.

          -  Any subject who, in the opinion of the sponsor or the investigator, should not
             participate in the trial.

          -  Consumption of alcohol and/or food and beverages containing methylxanthines,
             grapefruit, grapefruit juice, Seville oranges, or Seville orange juice within 72 hours
             prior to dosing.

          -  Use of any drug known or suspected of inhibiting or stimulating hepatic drug
             metabolism enzymes within 30 days prior to Screening.

          -  Exposure to any substances known to stimulate hepatic microsomal enzymes within 30
             days prior to Screening through the end of the trial (eg, occupational exposure to
             pesticides, organic solvents).

          -  History of serious mental disorders.

          -  Major surgery of the digestive tract (excluding appendectomy).