Drug-Drug Interaction Study to Evaluate the Effects of Ecopipam on the Pharmacokinetics of Multiple Substrates for Drug Metabolism and Transport

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

Detailed Description
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Following a Screening period, eligible subjects will be enrolled sequentially to one of three cohorts to receive a single dose of probe substrate(s), followed by repeated titrated doses of ecopipam twice daily (BID) (with subjects in Cohort 3 also receiving a single dose of ecopipam and probe substrates on Day 4 prior to titration). After steady-state ecopipam dosing is reached, ecopipam will be co-administered with a single dose of probe substrate(s) (with continuation of ecopipam BID (every 12 h) dosing during the blood sampling period for the respective probe substrates), followed by an ecopipam tapering period and clinic discharge assessments.

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

Conditions
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Drug Interaction

Intervention / Treatment
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* Drug: Ecopipam
* Combination Product: Cohort 1 Probe Substrate Cocktail
* Drug: Cohort 2 Probe Substrate
* Combination Product: Cohort 3 Probe Substrate Cocktail


Participation Criteria
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Eligibility Criteria
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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 Subjects must be healthy, as determined by the Investigator, based on medical history, physical examination, ECG, and standard panel of blood and laboratory tests at Screening. 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
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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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 Substrate 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<br>* ecopipam HCl  2mg/kg/day<br>Combination Product: Cohort 1 Probe Substrate 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 Substrate given on 2 separate days: - bupropion: 100mg oral tablet | Drug: Ecopipam<br>* ecopipam HCl  2mg/kg/day<br>Drug: Cohort 2 Probe Substrate<br>* bupropion<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 Substrate 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<br>* ecopipam HCl  2mg/kg/day<br>Combination Product: Cohort 3 Probe Substrate Cocktail<br>* dabigatran, pitavastatin, rosuvastatin, atorvastatin, midazolam<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax of IV midazolam (and its 1'-hydroxymidazolam metabolite) in the presence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| Cmax of IV midazolam (and its 1'-hydroxymidazolam metabolite) in the absence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| Cmax of oral midazolam (and its 1'-hydroxymidazolam metabolite) in the presence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| Cmax oral midazolam (and its 1'-hydroxymidazolam metabolite) in the absence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| Cmax of dabigatran in the presence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| Cmax of dabigatran in the absence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| Cmax of pitavastatin (and its pitavastatin lactone metabolite) in the presence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| Cmax of pitavastatin (and its pitavastatin lactone metabolite) in the absence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| Cmax of rosuvastatin in the presence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| Cmax of rosuvastatin in the absence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| Cmax of atorvastatin (and its 4'-hydroxy atorvastatin metabolite) in the presence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| Cmax of atorvastatin (and its 4'-hydroxy atorvastatin metabolite) in the absence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| AUCinf of IV midazolam (and its 1'-hydroxymidazolam metabolite) in the presence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| AUCinf of IV midazolam (and its 1'-hydroxymidazolam metabolite) in the absence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| AUCinf of oral midazolam (and its 1'-hydroxymidazolam metabolite) in the presence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| AUCinf of oral midazolam (and its 1'-hydroxymidazolam metabolite) in the absence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| AUCinf of dabigatran in the presence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| AUCinf of dabigatran in the absence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| AUCinf of pitavastatin (and its pitavastatin lactone metabolite) in the presence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| AUCinf of pitavastatin (and its pitavastatin lactone metabolite) in the absence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| AUCinf of rosuvastatin in the presence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| AUCinf of rosuvastatin in the absence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| AUCinf of atorvastatin (and its 4'-hydroxy atorvastatin metabolite) in the presence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| AUCinf of atorvastatin (and its 4'-hydroxy atorvastatin metabolite) in the absence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| AUClast of IV midazolam (and its 1'-hydroxymidazolam metabolite) in the presence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| AUClast of IV midazolam (and its 1'-hydroxymidazolam metabolite) in the absence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| AUClast of oral midazolam (and its 1'-hydroxymidazolam metabolite) in the presence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| AUClast of oral midazolam (and its 1'-hydroxymidazolam metabolite) in the absence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| AUClast of dabigatran in the presence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| AUClast of dabigatran in the absence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| AUClast of pitavastatin (and its pitavastatin lactone metabolite) in the presence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| AUClast of pitavastatin (and its pitavastatin lactone metabolite) in the absence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| AUClast of rosuvastatin in the presence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| AUClast of rosuvastatin in the absence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| AUClast of atorvastatin (and its 4'-hydroxy atorvastatin metabolite) in the presence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| AUClast of atorvastatin (and its 4'-hydroxy atorvastatin metabolite) in the absence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| AUC0-24 of oral midazolam (and its 1'-hydroxymidazolam metabolite) in the presence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| AUC0-24 of oral midazolam (and its 1'-hydroxymidazolam metabolite) in the absence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| AUC0-24 of dabigatran in the presence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| AUC0-24 of dabigatran in the absence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| AUC0-24 of pitavastatin (and its pitavastatin lactone metabolite) in the presence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| AUC0-24 of pitavastatin (and its pitavastatin lactone metabolite) in the absence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| AUC0-24 of rosuvastatin in the presence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| AUC0-24 of rosuvastatin in the absence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| AUC0-24 of atorvastatin (and its 4'-hydroxy atorvastatin metabolite) in the presence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| AUC0-24 of atorvastatin (and its 4'-hydroxy atorvastatin metabolite) in the absence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax of bupropion (and its 4-hydroxybupropion metabolite) in the presence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| Cmax of bupropion (and its 4-hydroxybupropion metabolite) in the absence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| Cmax omeprazole (and its 5'-hydroxy omeprazole metabolite) in the presence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| Cmax omeprazole (and its 5'-hydroxy omeprazole metabolite) in the absence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| AUCinf of bupropion (and its 4-hydroxybupropion metabolite) in the presence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| AUCinf of bupropion (and its 4-hydroxybupropion metabolite) in the absence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| AUCinf of omeprazole (and its 5'-hydroxy omeprazole metabolite) in the presence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| AUCinf of omeprazole (and its 5'-hydroxy omeprazole metabolite) in the absence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| AUClast of bupropion (and its 4-hydroxybupropion metabolite) in the presence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| AUClast of bupropion (and its 4-hydroxybupropion metabolite) in the absence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| AUClast of omeprazole (and its 5'-hydroxy omeprazole metabolite) in the presence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| AUClast of omeprazole (and its 5'-hydroxy omeprazole metabolite) in the absence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| CL/F for dextromethorphan in the presence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| CL/F for dextromethorphan in the absence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| CL for IV midazolam in the presence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| CL for IV midazolam in the absence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| CL/F for oral midazolam in the presence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| CL/F for oral midazolam in the absence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| CL/F for dabigatran in the presence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| CL/F for dabigatran in the absence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| CL/F for pitavastatin in the presence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| CL/F for pitavastatin in the absence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| CL/F for rosuvastatin in the presence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| CL/F for rosuvastatin in the absence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| CL/F for atorvastatin in the presence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| CL/F for atorvastatin in the absence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| CL/F for bupropion in the presence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| CL/F for bupropion in the absence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| CL/F for caffeine in the presence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| CL/F for caffeine in the absence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| CL/F for omeprazole in the presence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| CL/F for omeprazole in the absence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| V/F for dextromethorphan in the presence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| V/F for dextromethorphan in the absence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| V for IV midazolam in the presence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| V for IV midazolam in the absence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| V/F for oral midazolam in the presence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| V/F for oral midazolam in the absence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| V/F for dabigatran in the presence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| V/F for dabigatran in the absence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| V/F for pitavastatin in the presence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| V/F for pitavastatin in the absence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| V/F for rosuvastatin in the presence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| V/F for rosuvastatin in the absence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| V/F for bupropion in the presence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| V/F for bupropion in the absence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| V/F for atorvastatin in the presence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| V/F for atorvastatin in the absence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| V/F for caffeine in the presence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| V/F for caffeine in the absence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| V/F for omeprazole in the presence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| V/F for omeprazole in the absence of ecopipam | Up to 46 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 22 | 
| Total concentration of bilirubin in the presence of ecopipam | Bilirubin sampling will occur on Day 1 and Day 18 | Up to Day 18 | 
| Total concentration of bilirubin in the absence of ecopipam | Bilirubin sampling will occur on Day 1 and Day 18 | Up to Day 18 | 
| Unconjugated concentration of bilirubin in the presence of ecopipam | Bilirubin sampling will occur on Day 1 and Day 18 | Up to Day 18 | 
| Unconjugated concentration of bilirubin in the absence of ecopipam | Bilirubin sampling will occur on Day 1 and Day 18 | Up to Day 18 | 
| Conjugated concentration of bilirubin in the presence of ecopipam | Bilirubin sampling will occur on Day 1 and Day 18 | Up to Day 18 | 
| Conjugated concentration of bilirubin in the absence of ecopipam | Bilirubin sampling will occur on Day 1 and Day 18 | Up to Day 18 | 
| Average of the 6-hour plasma dextromethorphan: dextrorphan ratio in the presence of ecopipam | 6 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 14 | 
| Average of the 8-hour plasma dextromethorphan: dextrorphan ratio in the presence of ecopipam | 6 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 14 | 
| Average of the 12-hour plasma dextromethorphan: dextrorphan ratio in the presence of ecopipam | 6 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 14 | 
| Average of the 6-hour plasma dextromethorphan: dextrorphan ratio in the absence of ecopipam | 6 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 14 | 
| Average of the 8-hour plasma dextromethorphan: dextrorphan ratio in the absence of ecopipam | 6 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 14 | 
| Average of the 12-hour plasma dextromethorphan: dextrorphan ratio in the absence of ecopipam | 6 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 14 | 
| Average of the 6-hour plasma caffeine: paraxanthine metabolite ratio in the presence of ecopipam | 6 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 14 | 
| Average of the 8-hour plasma caffeine: paraxanthine metabolite ratio in the presence of ecopipam | 6 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 14 | 
| Average of the 12-hour plasma caffeine: paraxanthine metabolite ratio in the presence of ecopipam | 6 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 14 | 
| Average of the 6-hour plasma caffeine: paraxanthine metabolite ratio in the absence of ecopipam | 6 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 14 | 
| Average of the 8-hour plasma caffeine: paraxanthine metabolite ratio in the absence of ecopipam | 6 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 14 | 
| Average of the 12-hour plasma caffeine: paraxanthine metabolite ratio in the absence of ecopipam | 6 blood samples will be collected at the indicated time points for pharmacokinetic analysis | Up to Day 14 | 
| Safety and tolerability as demonstrated by the Modified Observer's Assessment of Alertness/Sedation (MOAA/S) | Score from 0-5 where 0 is no response and 5 is responds readily. MOAA/S measures will be recorded at the indicated timepoints | Up to Day 63 | 
| Safety and tolerability as demonstrated by the Columbia Suicide Severity Rating Scale (C-SSRS) | Safety and tolerability measures will be recorded at the indicated timepoints | Up to Day 63 | 
| Number of participants requiring concomitant medications | Participants will be continuously monitored for the use of concomitant medications | Up to Day 63 | 
| AEs with relatedness associated with dextromethorphan | Subjects will be continually monitored for adverse events | Up to Day 63 | 
| AEs with relatedness associated with IV midazolam | Subjects will be continually monitored for adverse events | Up to Day 63 | 
| AEs with relatedness associated with oral midazolam | Subjects will be continually monitored for adverse events | Up to Day 63 | 
| AEs with relatedness associated with dabigatran | Subjects will be continually monitored for adverse events | Up to Day 63 | 
| AEs with relatedness associated with pitavastatin | Subjects will be continually monitored for adverse events | Up to Day 63 | 
| AEs with relatedness associated with rosuvastatin | Subjects will be continually monitored for adverse events | Up to Day 63 | 
| AEs with relatedness associated with atorvastatin | Subjects will be continually monitored for adverse events | Up to Day 63 | 
| AEs with relatedness associated with bupropion | Subjects will be continually monitored for adverse events | Up to Day 63 | 
| AEs with relatedness associated with caffeine | Subjects will be continually monitored for adverse events | Up to Day 63 | 
| AEs with relatedness associated with omeprazole | Subjects will be continually monitored for adverse events | Up to Day 63 | 
| AEs with relatedness associated with ecopipam | Subjects will be continually monitored for adverse events | Up to Day 63 | 
| Absolute values of white blood cell (WBC), neutrophils, lymphocytes, monocytes, eosinophils, basophils and platelets (1000/mm3) | Blood samples will be collected for the assessment of hematology parameters | Up to Day 26 | 
| Absolute values of hematocrit (percent) | Blood samples will be collected for the assessment of hematology parameters | Up to Day 26 | 
| Absolute values of hemoglobin (g/dL) | Blood samples will be collected for the assessment of hematology parameters | Up to Day 26 | 
| Absolute values of Red blood cell (RBC) count (M/mm3) | Blood samples will be collected for the assessment of hematology parameters | Up to Day 26 | 
| Absolute values of sodium, potassium, chloride (mmol/L) | Blood samples will be collected for the assessment of clinical chemistry parameters | Up to Day 26 | 
| Absolute values of magnesium, urea, phosphorus, calcium, glucose, and total, conjugated and unconjugated bilirubin (mg/dL) | Blood samples will be collected for the assessment of clinical chemistry parameters | Up to Day 26 | 
| Absolute values of albumin and total protein (g/dL) | Blood samples will be collected for the assessment of clinical chemistry parameters | Up to Day 26 | 
| Absolute values of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), creatinine phosphokinase (CPK), and creatinine (U/L) | Blood samples will be collected for the assessment of clinical chemistry parameters | Up to Day 26 | 
| Absolute values of urine specific gravity | Urine samples will be collected for the assessment of urine parameters | Up to Day 26 | 
| Absolute values of urine pH | Urine samples will be collected for the assessment of urine parameters | Up to Day 26 | 
| Absolute values of urine glucose | Urine samples will be collected for the assessment of urine parameters | Up to Day 26 | 
| Absolute values of urine protein | Urine samples will be collected for the assessment of urine parameters | Up to Day 26 | 
| Absolute values of urine blood | Urine samples will be collected for the assessment of urine parameters | Up to Day 26 | 
| Absolute values of urine ketones | Urine samples will be collected for the assessment of urine parameters | Up to Day 26 | 
| Absolute values of urine bilirubin and nitrite | Urine samples will be collected for the assessment of urine parameters | Up to Day 26 | 
| Absolute values of urobilinogen (Eu/dL) | Urine samples will be collected for the assessment of urine parameters | Up to Day 26 | 
| Absolute values of urine leukocytes by dipstick | Urine samples will be collected for the assessment of urine parameters | Up to Day 26 | 
| Change from Day -1 to Day of Discharge white blood cell (WBC), neutrophils, lymphocytes, monocytes, eosinophils, basophils and platelets (1000/mm3) | Blood samples will be collected for the assessment of hematology parameters | Up to Day 26 | 
| Change from Day -1 to Day of Discharge in hematocrit (percent) | Blood samples will be collected for the assessment of hematology parameters | Up to Day 26 | 
| 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 26 | 
| Change from Day -1 to Day of Discharge in Red blood cell (RBC) count (M/mm3) | Blood samples will be collected for the assessment of hematology parameters | Up to Day 26 | 
| Change from Day -1 to Day of Discharge in sodium, potassium, chloride (mmol/L) | Blood samples will be collected for the assessment of clinical chemistry parameters | Up to Day 26 | 
| Change from Day -1 to Day of Discharge in magnesium, urea, phosphorus, calcium, glucose, and total, conjugated and unconjugated bilirubin (mg/dL) | Blood samples will be collected for the assessment of clinical chemistry parameters | Up to Day 26 | 
| 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 26 | 
| 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), and creatinine (U/L) | Blood samples will be collected for the assessment of clinical chemistry parameters | Up to Day 26 | 
| 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 26 | 
| 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 26 | 
| 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 26 | 
| 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 26 | 
| 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 26 | 
| 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 26 | 
| Change from Day -1 to Day of Discharge in urine bilirubin and nitrite | Urine samples will be collected for the assessment of urine parameters | Up to Day 26 | 
| Change from Day -1 to Day of Discharge in urobilinogen (Eu/dL) | Urine samples will be collected for the assessment of urine parameters | Up to Day 26 | 
| 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 26 | 
| 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 26 | 
| 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 26 | 
| Absolute values of oral temperature (degrees Celsius) | Temperature will be assessed as part of vital signs | Up to Day 26 | 
| 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 26 | 
| Absolute values of heart rate (beats/minute) | Heart rate will be assessed as part of vital signs | Up to Day 26 | 
| 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 26 | 
| Absolute values of respiratory rate (breaths/minute) | Respiratory rate will be assessed as part of vital signs | Up to Day 26 | 
| 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 26 | 
| 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 26 | 
| Absolute values of mean corpuscular hemoglobin (MCH) (pg) | Blood samples will be collected for the assessment of hematology parameters | Up to Day 26 | 
| Change from Day 1 to Day of Discharge of mean corpuscular hemoglobin (MCH) (pg) | Blood samples will be collected for the assessment of hematology parameters | Up to Day 26 | 
| Absolute values of mean corpuscular volume (MCV) (fL) | Blood samples will be collected for the assessment of hematology parameters | Up to Day 26 | 
| Change from Day 1 to Day of Discharge of mean corpuscular volume (MCV) (fL) | Blood samples will be collected for the assessment of hematology parameters | Up to Day 26 | 
| Absolute values of mean corpuscular hemoglobin concentration (MCHC) (g/dL) | Blood samples will be collected for the assessment of hematology parameters | Up to Day 26 | 
| Change from Day 1 to Day of Discharge of mean corpuscular hemoglobin concentration (MCHC) (g/dL) | Blood samples will be collected for the assessment of hematology parameters | Up to Day 26 |