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

NCT04764851 | Terminated Phase 1 FDA Drug

• 1 other identifier: EBS-101-HV-101
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Drug-Interactions

Outcome Measures

Primary Outcomes (42)

• 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 Outcomes (122)

• Cmax of bupropion (and its 4-hydroxybupropion metabolite) in the presence of ecopipam

  Up to Day 18

• Cmax of bupropion (and its 4-hydroxybupropion metabolite) in the absence of ecopipam

  Up to Day 18

• Cmax of caffeine (and its metabolite paraxanthine) in the presence of ecopipam

  Up to Day 18

• Cmax of caffeine (and its metabolite paraxanthine) in the absence of ecopipam

  Up to Day 18

• Cmax omeprazole (and its 5'-hydroxy omeprazole metabolite) in the presence of ecopipam

  Up to Day 18

Study Arms (3)

Cohort 1

OTHER

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; Combination Product: Cohort 1 Probe Cocktail

Cohort 2

OTHER

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; Combination Product: Cohort 2 Probe Cocktail

Cohort 3

OTHER

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; Combination Product: Cohort 3 Probe Cocktail

Interventions

ecopipam HCl ~2mg/kg/day DRUG

oral tablet

Cohort 1; Cohort 2; Cohort 3

Cohort 1 Probe Cocktail COMBINATION_PRODUCT

dextromethorphan, caffeine, omeprazole, and midazolam

Cohort 1

Cohort 2 Probe Cocktail COMBINATION_PRODUCT

dabigatran, pitavastatin, rosuvastatin, atorvastatin, midazolam

Cohort 2

Cohort 3 Probe Cocktail COMBINATION_PRODUCT

bupropion

Cohort 3

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Emalex Biosciences Inc.: lead
• Syneos Health: collaborator
• Nuventra, Inc.: collaborator

Study Sites (1)

Syneos Health Clinical Research Services, LLC.

Miami, Florida, 33136, United States

Location

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 18, 2021
• First Posted: February 21, 2021
• Study Start: February 18, 2021
• Primary Completion: April 2, 2021
• Study Completion: May 7, 2021
• Last Updated: May 24, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)