A Phase 1b/2a, Double-blind, Placebo-controlled, Multiple Ascending Dose Study to Evaluate the Safety, Tolerability and Pharmacokinetics of APN1125 in Subjects With Schizophrenia
Overview
- Phase
- Phase 1
- Intervention
- APN1125
- Conditions
- Schizophrenia
- Sponsor
- CoMentis
- Enrollment
- 30
- Locations
- 1
- Primary Endpoint
- Assessment of safety and tolerability of APN1125 in subjects with schizophrenia via adverse events
- Status
- Suspended
- Last Updated
- 9 years ago
Overview
Brief 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.
Detailed Description
The purpose of this study is to evaluate the safety profile, tolerability and pharmacokinetics (PK) of APN1125 following 14 days of once-daily oral dosing in subjects with schizophrenia on stable second-generation antipsychotic therapy. This is a randomized, double-blind, 2-week, multiple ascending dose study of APN1125. This study will enroll up to three sequential cohorts of subjects diagnosed with schizophrenia, each randomly assigned to receive one of three doses (low, medium, or high) of APN1125 or matching placebo. Following admission to an Early Phase Clinical Unit (EPCU), APN1125 will be administered once daily for 2 weeks. All subjects will remain confined to the EPCU for a total of 20 days, consisting of admission, dosing and observation periods.
Investigators
Eligibility 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)
Arms & Interventions
APN1125, Low Dose
APN1125, Low Dose
Intervention: APN1125
APN1125, Mid Dose
APN1125, Mid Dose
Intervention: APN1125
APN1125, High Dose
APN1125, High Dose
Intervention: APN1125
Placebo
Placebo to match
Intervention: Placebo
Outcomes
Primary Outcomes
Assessment of safety and tolerability of APN1125 in subjects with schizophrenia via adverse events
Time Frame: 25 days
Assessment of safety and tolerability of APN1125 in subjects with schizophrenia via clinical laboratory tests (chemistry, hematology, coagulation and urinalysis)
Time Frame: 25 days
Assessment of safety and tolerability of APN1125 in subjects with schizophrenia via vital signs (e.g., blood pressure, pulse rate, respiratory rate, oral temperature)
Time Frame: 25 days
Assessment of safety and tolerability of APN1125 in subjects with schizophrenia via ECGs
Time Frame: 25 days
Assessment of safety and tolerability of APN1125 in subjects with schizophrenia via physical exams
Time Frame: 25 days
Secondary Outcomes
- Maximum observed plasma APN1125 concentration (Cmax)(Days 1 and 14)
- Time corresponding to occurrence of Cmax (Tmax)(Days 1 and 14)
- Area under the Curve from time zero to the last quantifiable plasma APN1125 concentration (AUClast)(Days 1 and 14)
- Area under the Curve from time zero extrapolated to plasma APN1125 concentration at infinity (AUCinf)(Days 1 and 14)
- Terminal plasma APN1125 rate constant (lambda z)(Days 1 and 14)
- Apparent plasma APN1125 terminal half-life (t1/2)(Days 1 and 14)
- Apparent APN1125 plasma clearance (CL/F)(Days 1 and 14)
- Amount of unmetabolized APN1125 excreted in urine (Ae)(Days 1 and 14)
- Fraction of unmetabolized APN1125 dose excreted in urine (Fe)(Days 1 and 14)