Drug-Drug Interaction Study to Evaluate the Effects of Ecopipam on the Pharmacokinetics of Multiple Substrates

Study Overview
=================
Brief Summary
-----------------
This is a single center, open-label, fixed sequence Phase 1, drug-drug interaction (DDI) study in healthy subjects.

Detailed Description
-----------------
Following a screening period of up to 28 days, subjects will be admitted to the clinical research unit into one of three cohorts. On the morning of Day 1, subjects in cohorts 1, 2, and 3 will receive fasted doses of probe substrate(s) per assigned cohort. On Day 5, Cohort 2 only will receive a second fasted dose of probe substrates. Subjects in cohorts 1, 2, and 3 will receive the final fasted dose of probe substrate(s) on Day 13. Fasted ecopipam administration will begin on Day 5 and will continue through Day 17 at  2mg/kg for all cohorts. Ecopipam doses will be tapered starting on Day 18 by 25 mg/day increments until subjects are off drug, with final discharge occurring 24 hours after the ecopipam HCl dose has been reduced to 25 mg (Day 21, 23, or 25).

Official Title
-----------------
A Phase 1, Open-Label, Fixed Sequence Drug-Drug Interaction Study to Evaluate the Effects of Repeat Doses of Ecopipam on the Pharmacokinetics of Multiple Substrates for Drug Metabolism and Transport in Healthy Subjects

Conditions
-----------------
Drug-Interactions

Intervention / Treatment
-----------------
* Drug: ecopipam HCl  2mg/kg/day
* Combination Product: Cohort 1 Probe Cocktail
* Combination Product: Cohort 2 Probe Cocktail
* Combination Product: Cohort 3 Probe Cocktail


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male subjects or female subjects of non-childbearing potential ≥18 and <55 years of age at the time of consent BMI >18.5 and <30 kg/m2 and a weight of ≥50 kg for males or ≥45 kg for females Sexually active males must use a double barrier method of contraception during the study and for at least 90 days after the last dose of study drug Male subjects must be willing not to donate sperm until 90 days following the last study drug administration Exclusion Criteria: Personal or family History of significant medical illness Clinically significant abnormalities on screening tests/exams History of or significant risk of committing suicide Donation of plasma within 7 days prior to dosing Donation or significant loss of blood within 30 days prior to the first dosing Major surgery within 3 months or minor surgery within 1 month prior to admission Use of prohibited prescription, over-the-counter medications or natural health products Alcohol-based products 24 hours prior to admission Female subjects who are currently pregnant or lactating Positive pregnancy test Use of tobacco or nicotine products within 3 months prior to Screening Significant alcohol consumption History of drug abuse within the previous 2 years, or a positive drug screen History of allergy to study medications Undergoing abrupt discontinuation of alcohol or sedatives Not suitable for study in the opinion of the Principal Investigator

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Cohort 1<br>ecopipam HCl oral tablets of 12.5, 50, 75, and 100 mg daily for up to 20 days Cohort 1 Probe Cocktail given on 2 separate days: midazolam: 1 µg infused IV caffeine: 200 mg oral tablet omeprazole: two 20 mg oral tablets dextromethorphan: 1.6mL (containing  10 mg) oral solution | Drug: ecopipam HCl  2mg/kg/day<br>* oral tablet<br>Combination Product: Cohort 1 Probe Cocktail<br>* dextromethorphan, caffeine, omeprazole, and midazolam<br>|
| Other: Cohort 2<br>ecopipam HCl oral tablets of 12.5, 50, 75, and 100 mg daily for up to 20 days Cohort 2 Probe Cocktail given on 3 separate days: midazolam: 10 µg/mL given as 1mL oral solution. dabigatran: 375 µg/mL and pitavastatin: 10 µg/mL given as 1mL oral solution rosuvastatin: 25 µg/mL and atorvastatin: 50 µg/mL given as 2mL oral solution | Drug: ecopipam HCl  2mg/kg/day<br>* oral tablet<br>Combination Product: Cohort 2 Probe Cocktail<br>* dabigatran, pitavastatin, rosuvastatin, atorvastatin, midazolam<br>|
| Other: Cohort 3<br>ecopipam HCl oral tablets of 12.5, 50, 75, and 100 mg daily for up to 20 days Cohort 3 Probe Cocktail given on 2 separate days: - bupropion: 100mg oral tablet | Drug: ecopipam HCl  2mg/kg/day<br>* oral tablet<br>Combination Product: Cohort 3 Probe Cocktail<br>* bupropion<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax of dextromethorphan (and its dextrorphan metabolite) in the presence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 18 | 
| Cmax of dextromethorphan (and its dextrorphan metabolite) in the absence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 18 | 
| Cmax of IV midazolam (and its 1'-hydroxymidazolam metabolite) in the presence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 18 | 
| Cmax of IV midazolam (and its 1'-hydroxymidazolam metabolite) in the absence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 18 | 
| Cmax of oral midazolam (and its 1'-hydroxymidazolam metabolite) in the presence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 18 | 
| Cmax oral midazolam (and its 1'-hydroxymidazolam metabolite) in the absence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 18 | 
| Cmax of dabigatran in the presence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 18 | 
| Cmax of dabigatran in the absence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 18 | 
| Cmax of pitavastatin (and its pitavastatin lactone metabolite) in the presence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 18 | 
| Cmax of pitavastatin (and its pitavastatin lactone metabolite) in the absence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 18 | 
| Cmax of rosuvastatin in the presence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 18 | 
| Cmax of rosuvastatin in the absence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 18 | 
| Cmax of atorvastatin (and its 4'-hydroxy atorvastatin metabolite) in the presence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 18 | 
| Cmax of atorvastatin (and its 4'-hydroxy atorvastatin metabolite) in the absence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 18 | 
| AUCinf of dextromethorphan (and its dextrorphan metabolite) in the presence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 18 | 
| AUCinf of dextromethorphan (and its dextrorphan metabolite) in the absence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 18 | 
| AUCinf of IV midazolam (and its 1'-hydroxymidazolam metabolite) in the presence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 18 | 
| AUCinf of IV midazolam (and its 1'-hydroxymidazolam metabolite) in the absence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 18 | 
| AUCinf of oral midazolam (and its 1'-hydroxymidazolam metabolite) in the presence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 18 | 
| AUCinf of oral midazolam (and its 1'-hydroxymidazolam metabolite) in the absence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 18 | 
| AUCinf of dabigatran in the presence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 18 | 
| AUCinf of dabigatran in the absence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 18 | 
| AUCinf of pitavastatin (and its pitavastatin lactone metabolite) in the presence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 18 | 
| AUCinf of pitavastatin (and its pitavastatin lactone metabolite) in the absence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic | Up to Day 18 | 
| AUCinf of rosuvastatin in the presence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic | Up to Day 18 | 
| AUCinf of rosuvastatin in the absence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic | Up to Day 18 | 
| AUCinf of atorvastatin (and its 4'-hydroxy atorvastatin metabolite) in the presence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic | Up to Day 18 | 
| AUCinf of atorvastatin (and its 4'-hydroxy atorvastatin metabolite) in the absence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic | Up to Day 18 | 
| AUClast of dextromethorphan (and its dextrorphan metabolite) in the presence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic | Up to Day 18 | 
| AUClast of dextromethorphan (and its dextrorphan metabolite) in the absence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic | Up to Day 18 | 
| AUClast of IV midazolam (and its 1'-hydroxymidazolam metabolite) in the presence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic | Up to Day 18 | 
| AUClast of IV midazolam (and its 1'-hydroxymidazolam metabolite) in the absence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic | Up to Day 18 | 
| AUClast of oral midazolam (and its 1'-hydroxymidazolam metabolite) in the presence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic | Up to Day 18 | 
| AUClast of oral midazolam (and its 1'-hydroxymidazolam metabolite) in the absence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic | Up to Day 18 | 
| AUClast of dabigatran in the presence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic | Up to Day 18 | 
| AUClast of dabigatran in the absence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic | Up to Day 18 | 
| AUClast of pitavastatin (and its pitavastatin lactone metabolite) in the presence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic | Up to Day 18 | 
| AUClast of pitavastatin (and its pitavastatin lactone metabolite) in the absence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic | Up to Day 18 | 
| AUClast of rosuvastatin in the presence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic | Up to Day 18 | 
| AUClast of rosuvastatin in the absence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic | Up to Day 18 | 
| AUClast of atorvastatin (and its 4'-hydroxy atorvastatin metabolite) in the presence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic | Up to Day 18 | 
| AUClast of atorvastatin (and its 4'-hydroxy atorvastatin metabolite) in the absence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic | Up to Day 18 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax of bupropion (and its 4-hydroxybupropion metabolite) in the presence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 18 | 
| Cmax of bupropion (and its 4-hydroxybupropion metabolite) in the absence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 18 | 
| Cmax of caffeine (and its metabolite paraxanthine) in the presence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 18 | 
| Cmax of caffeine (and its metabolite paraxanthine) in the absence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 18 | 
| Cmax omeprazole (and its 5'-hydroxy omeprazole metabolite) in the presence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 18 | 
| Cmax omeprazole (and its 5'-hydroxy omeprazole metabolite) in the absence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 18 | 
| AUCinf of bupropion (and its 4-hydroxybupropion metabolite) in the presence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 18 | 
| AUCinf of bupropion (and its 4-hydroxybupropion metabolite) in the absence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 18 | 
| AUCinf of caffeine (and its metabolite paraxanthine) in the presence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 18 | 
| AUCinf of caffeine (and its metabolite paraxanthine) in the absence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 18 | 
| AUCinf of omeprazole (and its 5'-hydroxy omeprazole metabolite) in the presence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 18 | 
| AUCinf of omeprazole (and its 5'-hydroxy omeprazole metabolite) in the absence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 18 | 
| AUClast of bupropion (and its 4-hydroxybupropion metabolite) in the presence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 18 | 
| AUClast of bupropion (and its 4-hydroxybupropion metabolite) in the absence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 18 | 
| AUClast of caffeine (and its metabolite paraxanthine) in the presence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 18 | 
| AUClast of caffeine (and its metabolite paraxanthine) in the absence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 18 | 
| AUClast of omeprazole (and its 5'-hydroxy omeprazole metabolite) in the presence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 18 | 
| AUClast of omeprazole (and its 5'-hydroxy omeprazole metabolite) in the absence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 18 | 
| CL/F for dextromethorphan in the presence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 18 | 
| CL/F for dextromethorphan in the absence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 18 | 
| CL/F for IV midazolam in the presence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 18 | 
| CL/F for IV midazolam in the absence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 18 | 
| CL/F for oral midazolam in the presence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 18 | 
| CL/F for oral midazolam in the absence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 18 | 
| CL/F for dabigatran in the presence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 18 | 
| CL/F for dabigatran in the absence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 18 | 
| CL/F for pitavastatin in the presence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 18 | 
| CL/F for pitavastatin in the absence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 18 | 
| CL/F for rosuvastatin in the presence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 18 | 
| CL/F for rosuvastatin in the absence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 18 | 
| CL/F for atorvastatin in the presence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 18 | 
| CL/F for atorvastatin in the absence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 18 | 
| CL/F for bupropion in the presence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 18 | 
| CL/F for bupropion in the absence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 18 | 
| CL/F for caffeine in the presence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 18 | 
| CL/F for caffeine in the absence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 18 | 
| CL/F for omeprazole in the presence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 18 | 
| CL/F for omeprazole in the absence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 18 | 
| V/F for dextromethorphan in the presence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 18 | 
| V/F for dextromethorphan in the absence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 18 | 
| V/F for IV midazolam in the presence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 18 | 
| V/F for IV midazolam in the absence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 18 | 
| V/F for oral midazolam in the presence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 18 | 
| V/F for oral midazolam in the absence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 18 | 
| V/F for dabigatran in the presence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 18 | 
| V/F for dabigatran in the absence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 18 | 
| V/F for pitavastatin in the presence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 18 | 
| V/F for pitavastatin in the absence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 18 | 
| V/F for rosuvastatin in the presence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 18 | 
| V/F for rosuvastatin in the absence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 18 | 
| V/F for atorvastatin in the presence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 18 | 
| V/F for atorvastatin in the absence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 18 | 
| V/F for bupropion in the presence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 18 | 
| V/F for bupropion in the absence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 18 | 
| V/F for caffeine in the presence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 18 | 
| V/F for caffeine in the absence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 18 | 
| V/F for omeprazole in the presence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 18 | 
| V/F for omeprazole in the absence of ecopipam | Up to 38 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 18 | 
| Total concentration of bilirubin in the presence of ecopipam | Bilirubin sampling will occur on Day 1 and Day 13 | Up to Day 13 | 
| Total concentration of bilirubin in the absence of ecopipam | Bilirubin sampling will occur on Day 1 and Day 13 | Up to Day 13 | 
| Unconjugated concentration of bilirubin in the presence of ecopipam | Bilirubin sampling will occur on Day 1 and Day 13 | Up to Day 13 | 
| Unconjugated concentration of bilirubin in the absence of ecopipam | Bilirubin sampling will occur on Day 1 and Day 13 | Up to Day 13 | 
| Safety and tolerability as demonstrated by MOAA/S | Safety and tolerability measures will be recorded at the indicated timepoints. | Up to Day 55 | 
| Safety and tolerability as demonstrated by C-SSRS | Safety and tolerability measures will be recorded at the indicated timepoints. | Up to Day 55 | 
| Safety and tolerability as demonstrated by concomitant medications | Safety and tolerability measures will be recorded at the indicated timepoints. | Up to Day 55 | 
| AEs with relatedness associated with dextromethorphan | Subjects will be continually monitored for adverse events | Up to Day 55 | 
| AEs with relatedness associated with IV midazolam | Subjects will be continually monitored for adverse events | Up to Day 55 | 
| AEs with relatedness associated with oral midazolam | Subjects will be continually monitored for adverse events | Up to Day 55 | 
| AEs with relatedness associated with dabigatran | Subjects will be continually monitored for adverse events | Up to Day 55 | 
| AEs with relatedness associated with pitavastatin | Subjects will be continually monitored for adverse events | Up to Day 55 | 
| AEs with relatedness associated with rosuvastatin | Subjects will be continually monitored for adverse events | Up to Day 55 | 
| AEs with relatedness associated with atorvastatin | Subjects will be continually monitored for adverse events | Up to Day 55 | 
| AEs with relatedness associated with bupropion | Subjects will be continually monitored for adverse events | Up to Day 55 | 
| AEs with relatedness associated with caffeine | Subjects will be continually monitored for adverse events | Up to Day 55 | 
| AEs with relatedness associated with omeprazole | Subjects will be continually monitored for adverse events | Up to Day 55 | 
| AEs with relatedness associated with ecopipam | Subjects will be continually monitored for adverse events | Up to Day 55 | 
| Absolute values of white blood cell (WBC) count (K/Ul) | Blood samples will be collected for the assessment of hematology parameters. | Up to Day 25 | 
| Absolute values of neutrophils, lymphocytes, monocytes, eosinophils, and basophils (10E3/uL) | Up to Day 25 | Blood samples will be collected for the assessment of hematology parameters. | 
| Absolute values of platelets (K/uL) | Blood samples will be collected for the assessment of hematology parameters. | Up to Day 25 | 
| Absolute values of hematocrit (%) | Blood samples will be collected for the assessment of hematology parameters. | Up to Day 25 | 
| Absolute values of hemoglobin (g/dL) | Blood samples will be collected for the assessment of hematology parameters. | Up to Day 25 | 
| Absolute values of Red blood cell (RBC) count (M/uL) | Blood samples will be collected for the assessment of hematology parameters. | Up to Day 25 | 
| Absolute values of blood sodium, magnesium, urea, phosphorus, potassium, and chloride (mg/dL) | Blood samples will be collected for the assessment of clinical chemistry parameters. | Up to Day 25 | 
| Absolute values of creatinine, calcium, glucose, and direct and total bilirubin (mg/dL) | Blood samples will be collected for the assessment of clinical chemistry parameters. | Up to Day 25 | 
| Absolute values of albumin and total protein (g/dL) | Blood samples will be collected for the assessment of clinical chemistry parameters. | Up to Day 25 | 
| Absolute values of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), and creatinine phosphokinase (CPK) (U/L) | Blood samples will be collected for the assessment of clinical chemistry parameters. | Up to Day 25 | 
| Absolute values of urine specific gravity | Urine samples will be collected for the assessment of urine parameters. | Up to Day 25 | 
| Absolute values of urine pH | Urine samples will be collected for the assessment of urine parameters. | Up to Day 25 | 
| Absolute values of urine glucose | Urine samples will be collected for the assessment of urine parameters. | Up to Day 25 | 
| Absolute values of urine protein | Urine samples will be collected for the assessment of urine parameters. | Up to Day 25 | 
| Absolute values of urine blood | Urine samples will be collected for the assessment of urine parameters. | Up to Day 25 | 
| Absolute values of urine ketones | Urine samples will be collected for the assessment of urine parameters. | Up to Day 25 | 
| Absolute values of urine bilirubin, urobilinogen, and nitrite | Urine samples will be collected for the assessment of urine parameters. | Up to Day 25 | 
| Absolute values of urine leukocytes by dipstick | Urine samples will be collected for the assessment of urine parameters. | Up to Day 25 | 
| Change from Day -1 to Day of Discharge in white blood cell (WBC) count (K/Ul) | Blood samples will be collected for the assessment of hematology parameters. | Up to Day 25 | 
| Change from Day -1 to Day of Discharge in neutrophils, lymphocytes, monocytes, eosinophils, and basophils (10E3/uL) | Blood samples will be collected for the assessment of hematology parameters. | Up to Day 25 | 
| Change from Day -1 to Day of Discharge in platelets (K/uL) | Blood samples will be collected for the assessment of hematology parameters. | Up to Day 25 | 
| Change from Day -1 to Day of Discharge in hematocrit (%) | Blood samples will be collected for the assessment of hematology parameters. | Up to Day 25 | 
| Change from Day -1 to Day of Discharge in hemoglobin (g/dL) | Blood samples will be collected for the assessment of hematology parameters. | Up to Day 25 | 
| Change from Day -1 to Day of Discharge in Red blood cell (RBC) count (M/uL) | Blood samples will be collected for the assessment of hematology parameters. | Up to Day 25 | 
| Change from Day -1 to Day of Discharge in blood sodium, magnesium, urea, phosphorus, potassium, and chloride (mg/dL) | Blood samples will be collected for the assessment of clinical chemistry parameters. | Up to Day 25 | 
| Change from Day -1 to Day of Discharge in creatinine, calcium, glucose, and direct and total bilirubin (mg/dL) | Blood samples will be collected for the assessment of clinical chemistry parameters. | Up to Day 25 | 
| Change from Day -1 to Day of Discharge in albumin and total protein (g/dL) | Blood samples will be collected for the assessment of clinical chemistry parameters. | Up to Day 25 | 
| Change from Day -1 to Day of Discharge in alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), and creatinine phosphokinase (CPK) (U/L) | Blood samples will be collected for the assessment of clinical chemistry parameters. | Up to Day 25 | 
| Change from Day -1 to Day of Discharge in urine specific gravity | Urine samples will be collected for the assessment of urine parameters. | Up to Day 25 | 
| Change from Day -1 to Day of Discharge in urine pH | Urine samples will be collected for the assessment of urine parameters. | Up to Day 25 | 
| Change from Day -1 to Day of Discharge in urine glucose | Urine samples will be collected for the assessment of urine parameters. | Up to Day 25 | 
| Change from Day -1 to Day of Discharge in urine protein | Urine samples will be collected for the assessment of urine parameters. | Up to Day 25 | 
| Change from Day -1 to Day of Discharge in urine blood | Urine samples will be collected for the assessment of urine parameters. | Up to Day 25 | 
| Change from Day -1 to Day of Discharge in urine ketones | Urine samples will be collected for the assessment of urine parameters. | Up to Day 25 | 
| Change from Day -1 to Day of Discharge in urine bilirubin, urobilinogen, and nitrite (Milligrams per deciliter) | Urine samples will be collected for the assessment of urine parameters. | Up to Day 25 | 
| Change from Day -1 to Day of Discharge in urine leukocytes by dipstick | Urine samples will be collected for the assessment of urine parameters. | Up to Day 25 | 
| Absolute values of electrocardiogram (ECG) parameters: PR, QRS, QT, and QT interval corrected for heart rate using Fridericia's formula (QTcF) (Milliseconds) | Twelve-lead ECGs will be obtained with the participant in a supine position after a rest of at least 5 minutes using an automated ECG machine. PR, QRS, QT, and QTcF intervals will be measured. | Up to Day 25 | 
| Change from pre-dose for the respective day in ECG parameters: PR, QRS, QT, and QTcF (Milliseconds) | Twelve-lead ECGs will be obtained with the participant in a supine position after a rest of at least 5 minutes using an automated ECG machine. PR, QRS, QT, and QTcF intervals will be measured. | Up to Day 25 | 
| Absolute values of oral temperature (degrees Celsius) | Temperature will be assessed as part of vital signs. | Up to Day 25 | 
| Change from pre-dose for the respective day in oral temperature (degrees Celsius) | Temperature will be assessed as part of vital signs. | Up to Day 25 | 
| Absolute values of heart rate (beats/minute) | Heart rate will be assessed as part of vital signs. | Up to Day 25 | 
| Change from pre-dose for the respective day in heart rate (beats/minute) | Heart rate will be assessed as part of vital signs. | Up to Day 25 | 
| Absolute values of respiratory rate (breaths/minute) | Respiratory rate will be assessed as part of vital signs. | Up to Day 25 | 
| Change from pre-dose for the respective day in respiratory rate (breaths/minute) | Respiratory rate will be assessed as part of vital signs. | Up to Day 25 | 
| Absolute values of systolic blood pressure (SBP) and diastolic blood pressure (DBP) (mmHG) | Blood pressure will be assessed as part of vital signs. | Up to Day 25 | 
| Change from pre-dose for the respective day in SBP and DBP (mmHG) | Blood pressure will be assessed as part of vital signs. | Up to Day 25 |