Safety, Tolerability, and Pharmacokinetics of APN1125 in Subjects With Schizophrenia

• Status: Suspended
• Trial end date: 2016-12-01
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study in patients with schizophrenia is to evaluate the safety, tolerability, and pharmacokinetics of 3 doses (low, mid, high) of APN1125 compared with placebo when administered as repeated daily oral doses.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: CoMentis
• Collaborator: Alpharmagen, Inc.

Criteria

Inclusion Criteria:

• Males and females of any race

• 18 to 45 years of age, inclusive

• Diagnosed with schizophrenia, as defined in Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), in a non-acute (e.g., chronic) phase and clinically stable for at least 12 weeks before screening

• Currently on a stable second-generation anti-psychotic regimen (stable dose and medication for 12 weeks)

• Subjects (male and female) of childbearing potential must use two effective methods of contraception starting from the time of providing informed consent throughout the duration of the study and for 3 months after discharge

• Women of childbearing potential must have a negative pregnancy test at screening and at admission

Exclusion Criteria:

• Clinically significant abnormal serum electrolytes (sodium, potassium, calcium, and magnesium) after repeat testing

• Insulin-dependent diabetes or insufficiently controlled diabetes mellitus in the judgment of the Investigator

• Renal insufficiency with serum creatinine >1.6 mg/dL Malignant tumor within the 5 years before Screening with the exception of treated squamous and basal cell carcinoma, cervical carcinoma in situ, or brachytherapy for localized prostate cancer

• Female subjects who are pregnant, breastfeeding, or planning to become pregnant during the study

• Unstable medical condition that is clinically significant in the judgment of the Investigator

• Body mass index (BMI) >38 kg/m^2 at Screening ALT or AST >1.5 times the upper limit of normal

• Positive serology for hepatitis B surface antigen, hepatitis C antibody, or human immunodeficiency virus (HIV) 1 and/or 2 antibodies

• Untreated clinically significant hypo- or hyperthyroidism; treated hypo- or hyperthyroidism should be stable for at least 8 weeks prior to Screening

• History of myocardial infarction or unstable angina within 6 months before Screening

• Cardiovascular disease history including symptomatic hypotension (supine systolic blood pressure [SBP] <90 mmHg or supine diastolic blood pressure [DBP] <60 mmHg), symptomatic orthostatic hypotension (orthostatic change in SBP >20 mmHg or DBP >15 mmHg), or hypertension (supine SBP >160 mmHg or supine DBP >95 mmHg ) or significant cardiac arrhythmia (in the judgment of the Investigator)

• Clinically significant abnormality on Screening or Baseline electrocardiogram (ECG), including but not necessarily limited to a confirmed QTcF (QT interval corrected for heart rate using Fridericia's formula) interval value >450 msec for males or >470 msec for females

• Current treatment with more than 2 atypical antipsychotics Psychiatric hospitalization due to breakthrough psychotic symptoms or acute exacerbations within 3 months before Day -1. Subjects with a recent "social" hospitalization may be screened after consultation with the Medical Monitor.

• Subjects with other DSM-5 disorders are ineligible if the comorbid condition is clinically unstable or has been the primary focus of treatment within 3 months prior to Screening

• Subjects meeting DSM-5 criteria for moderate to severe alcohol or substance use disorder (other than nicotine- or caffeine-related disorders) within 6 months prior to Screening

• Urine drug screen (UDS) positive for drugs of abuse (excluding prescribed benzodiazepines) or positive alcohol breath test at Screening and/or Baseline (may be repeated once if, in the judgment of the Investigator, the subject does not meet DSM-5 criteria for moderate to severe substance abuse disorder)

• Significant suicide risk as defined by 1) suicidal ideations as endorsed on items 4 or 5 on the Columbia-Suicide Severity Rating Scale (C-SSRS) within the year prior to Screening or Baseline, 2) suicidal behaviors within the 2 years prior to Screening, or 3) Investigator assessment

• History of stroke, brain tumor, subdural hematoma, Parkinson's Disease, dementia or other clinically significant neurological condition

• Head trauma with loss of consciousness within 12 months prior to Screening

• Active acute or chronic CNS infection

• History of a seizure disorder

• Immunosuppressants, including systemic corticosteroids (administered at an immunosuppressant dose in the judgment of the Investigator) (Note: Inhaled, nasal, or topical steroid use for allergy or other inflammation is permitted)

• Any drugs with CNS activity (Note: Occasional (as needed) use of a sedative-hypnotic (e.g., benzodiazepine or nonbenzodiazepine [e.g., zolpidem, zaleplon, zopiclone, and eszopiclone]) as a sleep aid and stable second generation psychotics are permitted)

• Prohibited antipsychotic medications (e.g., clozapine or typical, first-generation antipsychotics)

• Excessive alcohol consumption (regular alcohol intake 14 units per week or more) or has a history of alcohol use disorder. Use of alcohol up to 48 hours before admission to the EPCU is not allowed.

• Failure or inability to perform Screening or Baseline assessments

• Exposure to an experimental drug or experimental medical device within 2 months before Screening, or an experimental biologic within 3 months before Screening