Clinical trial NCT04764851: Drug-Drug Interaction Study to Evaluate the Effects of Ecopipam on the Pharmacokinetics of Multiple Substrates
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Drug-Interactions
Lead sponsor: Emalex Biosciences Inc.
Sponsor class: INDUSTRY
Collaborators: name: Syneos Health
name: Nuventra, Inc.
First posted: 2021-02-21
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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).

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

Primary outcomes:
measure: Cmax of dextromethorphan (and its dextrorphan metabolite) in the presence of ecopipam
timeFrame: Up to Day 18
measure: Cmax of dextromethorphan (and its dextrorphan metabolite) in the absence of ecopipam
timeFrame: Up to Day 18
measure: Cmax of IV midazolam (and its 1'-hydroxymidazolam metabolite) in the presence of ecopipam
timeFrame: Up to Day 18
measure: Cmax of IV midazolam (and its 1'-hydroxymidazolam metabolite) in the absence of ecopipam
timeFrame: Up to Day 18
measure: Cmax of oral midazolam (and its 1'-hydroxymidazolam metabolite) in the presence of ecopipam
timeFrame: Up to Day 18
measure: Cmax oral midazolam (and its 1'-hydroxymidazolam metabolite) in the absence of ecopipam
timeFrame: Up to Day 18
measure: Cmax of dabigatran in the presence of ecopipam
timeFrame: Up to Day 18
measure: Cmax of dabigatran in the absence of ecopipam
timeFrame: Up to Day 18
measure: Cmax of pitavastatin (and its pitavastatin lactone metabolite) in the presence of ecopipam
timeFrame: Up to Day 18
measure: Cmax of pitavastatin (and its pitavastatin lactone metabolite) in the absence of ecopipam
timeFrame: Up to Day 18
measure: Cmax of rosuvastatin in the presence of ecopipam
timeFrame: Up to Day 18
measure: Cmax of rosuvastatin in the absence of ecopipam
timeFrame: Up to Day 18
measure: Cmax of atorvastatin (and its 4'-hydroxy atorvastatin metabolite) in the presence of ecopipam
timeFrame: Up to Day 18
measure: Cmax of atorvastatin (and its 4'-hydroxy atorvastatin metabolite) in the absence of ecopipam
timeFrame: Up to Day 18
measure: AUCinf of dextromethorphan (and its dextrorphan metabolite) in the presence of ecopipam
timeFrame: Up to Day 18
measure: AUCinf of dextromethorphan (and its dextrorphan metabolite) in the absence of ecopipam
timeFrame: Up to Day 18
measure: AUCinf of IV midazolam (and its 1'-hydroxymidazolam metabolite) in the presence of ecopipam
timeFrame: Up to Day 18
measure: AUCinf of IV midazolam (and its 1'-hydroxymidazolam metabolite) in the absence of ecopipam
timeFrame: Up to Day 18
measure: AUCinf of oral midazolam (and its 1'-hydroxymidazolam metabolite) in the presence of ecopipam
timeFrame: Up to Day 18
measure: AUCinf of oral midazolam (and its 1'-hydroxymidazolam metabolite) in the absence of ecopipam
timeFrame: Up to Day 18
measure: AUCinf of dabigatran in the presence of ecopipam
timeFrame: Up to Day 18
measure: AUCinf of dabigatran in the absence of ecopipam
timeFrame: Up to Day 18
measure: AUCinf of pitavastatin (and its pitavastatin lactone metabolite) in the presence of ecopipam
timeFrame: Up to Day 18
measure: AUCinf of pitavastatin (and its pitavastatin lactone metabolite) in the absence of ecopipam
timeFrame: Up to Day 18
measure: AUCinf of rosuvastatin in the presence of ecopipam
timeFrame: Up to Day 18
measure: AUCinf of rosuvastatin in the absence of ecopipam
timeFrame: Up to Day 18
measure: AUCinf of atorvastatin (and its 4'-hydroxy atorvastatin metabolite) in the presence of ecopipam
timeFrame: Up to Day 18
measure: AUCinf of atorvastatin (and its 4'-hydroxy atorvastatin metabolite) in the absence of ecopipam
timeFrame: Up to Day 18
measure: AUClast of dextromethorphan (and its dextrorphan metabolite) in the presence of ecopipam
timeFrame: Up to Day 18
measure: AUClast of dextromethorphan (and its dextrorphan metabolite) in the absence of ecopipam
timeFrame: Up to Day 18
measure: AUClast of IV midazolam (and its 1'-hydroxymidazolam metabolite) in the presence of ecopipam
timeFrame: Up to Day 18
measure: AUClast of IV midazolam (and its 1'-hydroxymidazolam metabolite) in the absence of ecopipam
timeFrame: Up to Day 18
measure: AUClast of oral midazolam (and its 1'-hydroxymidazolam metabolite) in the presence of ecopipam
timeFrame: Up to Day 18
measure: AUClast of oral midazolam (and its 1'-hydroxymidazolam metabolite) in the absence of ecopipam
timeFrame: Up to Day 18
measure: AUClast of dabigatran in the presence of ecopipam
timeFrame: Up to Day 18
measure: AUClast of dabigatran in the absence of ecopipam
timeFrame: Up to Day 18
measure: AUClast of pitavastatin (and its pitavastatin lactone metabolite) in the presence of ecopipam
timeFrame: Up to Day 18
measure: AUClast of pitavastatin (and its pitavastatin lactone metabolite) in the absence of ecopipam
timeFrame: Up to Day 18
measure: AUClast of rosuvastatin in the presence of ecopipam
timeFrame: Up to Day 18
measure: AUClast of rosuvastatin in the absence of ecopipam
timeFrame: Up to Day 18
measure: AUClast of atorvastatin (and its 4'-hydroxy atorvastatin metabolite) in the presence of ecopipam
timeFrame: Up to Day 18
measure: AUClast of atorvastatin (and its 4'-hydroxy atorvastatin metabolite) in the absence of ecopipam
timeFrame: Up to Day 18
Secondary outcomes:
measure: Cmax of bupropion (and its 4-hydroxybupropion metabolite) in the presence of ecopipam
timeFrame: Up to Day 18
measure: Cmax of bupropion (and its 4-hydroxybupropion metabolite) in the absence of ecopipam
timeFrame: Up to Day 18
measure: Cmax of caffeine (and its metabolite paraxanthine) in the presence of ecopipam
timeFrame: Up to Day 18
measure: Cmax of caffeine (and its metabolite paraxanthine) in the absence of ecopipam
timeFrame: Up to Day 18
measure: Cmax omeprazole (and its 5'-hydroxy omeprazole metabolite) in the presence of ecopipam
timeFrame: Up to Day 18
measure: Cmax omeprazole (and its 5'-hydroxy omeprazole metabolite) in the absence of ecopipam
timeFrame: Up to Day 18
measure: AUCinf of bupropion (and its 4-hydroxybupropion metabolite) in the presence of ecopipam
timeFrame: Up to Day 18
measure: AUCinf of bupropion (and its 4-hydroxybupropion metabolite) in the absence of ecopipam
timeFrame: Up to Day 18
measure: AUCinf of caffeine (and its metabolite paraxanthine) in the presence of ecopipam
timeFrame: Up to Day 18
measure: AUCinf of caffeine (and its metabolite paraxanthine) in the absence of ecopipam
timeFrame: Up to Day 18
measure: AUCinf of omeprazole (and its 5'-hydroxy omeprazole metabolite) in the presence of ecopipam
timeFrame: Up to Day 18
measure: AUCinf of omeprazole (and its 5'-hydroxy omeprazole metabolite) in the absence of ecopipam
timeFrame: Up to Day 18
measure: AUClast of bupropion (and its 4-hydroxybupropion metabolite) in the presence of ecopipam
timeFrame: Up to Day 18
measure: AUClast of bupropion (and its 4-hydroxybupropion metabolite) in the absence of ecopipam
timeFrame: Up to Day 18
measure: AUClast of caffeine (and its metabolite paraxanthine) in the presence of ecopipam
timeFrame: Up to Day 18
measure: AUClast of caffeine (and its metabolite paraxanthine) in the absence of ecopipam
timeFrame: Up to Day 18
measure: AUClast of omeprazole (and its 5'-hydroxy omeprazole metabolite) in the presence of ecopipam
timeFrame: Up to Day 18
measure: AUClast of omeprazole (and its 5'-hydroxy omeprazole metabolite) in the absence of ecopipam
timeFrame: Up to Day 18
measure: CL/F for dextromethorphan in the presence of ecopipam
timeFrame: Up to Day 18
measure: CL/F for dextromethorphan in the absence of ecopipam
timeFrame: Up to Day 18
measure: CL/F for IV midazolam in the presence of ecopipam
timeFrame: Up to Day 18
measure: CL/F for IV midazolam in the absence of ecopipam
timeFrame: Up to Day 18
measure: CL/F for oral midazolam in the presence of ecopipam
timeFrame: Up to Day 18
measure: CL/F for oral midazolam in the absence of ecopipam
timeFrame: Up to Day 18
measure: CL/F for dabigatran in the presence of ecopipam
timeFrame: Up to Day 18
measure: CL/F for dabigatran in the absence of ecopipam
timeFrame: Up to Day 18
measure: CL/F for pitavastatin in the presence of ecopipam
timeFrame: Up to Day 18
measure: CL/F for pitavastatin in the absence of ecopipam
timeFrame: Up to Day 18
measure: CL/F for rosuvastatin in the presence of ecopipam
timeFrame: Up to Day 18
measure: CL/F for rosuvastatin in the absence of ecopipam
timeFrame: Up to Day 18
measure: CL/F for atorvastatin in the presence of ecopipam
timeFrame: Up to Day 18
measure: CL/F for atorvastatin in the absence of ecopipam
timeFrame: Up to Day 18
measure: CL/F for bupropion in the presence of ecopipam
timeFrame: Up to Day 18
measure: CL/F for bupropion in the absence of ecopipam
timeFrame: Up to Day 18
measure: CL/F for caffeine in the presence of ecopipam
timeFrame: Up to Day 18
measure: CL/F for caffeine in the absence of ecopipam
timeFrame: Up to Day 18
measure: CL/F for omeprazole in the presence of ecopipam
timeFrame: Up to Day 18
measure: CL/F for omeprazole in the absence of ecopipam
timeFrame: Up to Day 18
measure: V/F for dextromethorphan in the presence of ecopipam
timeFrame: Up to Day 18
measure: V/F for dextromethorphan in the absence of ecopipam
timeFrame: Up to Day 18
measure: V/F for IV midazolam in the presence of ecopipam
timeFrame: Up to Day 18
measure: V/F for IV midazolam in the absence of ecopipam
timeFrame: Up to Day 18
measure: V/F for oral midazolam in the presence of ecopipam
timeFrame: Up to Day 18
measure: V/F for oral midazolam in the absence of ecopipam
timeFrame: Up to Day 18
measure: V/F for dabigatran in the presence of ecopipam
timeFrame: Up to Day 18
measure: V/F for dabigatran in the absence of ecopipam
timeFrame: Up to Day 18
measure: V/F for pitavastatin in the presence of ecopipam
timeFrame: Up to Day 18
measure: V/F for pitavastatin in the absence of ecopipam
timeFrame: Up to Day 18
measure: V/F for rosuvastatin in the presence of ecopipam
timeFrame: Up to Day 18
measure: V/F for rosuvastatin in the absence of ecopipam
timeFrame: Up to Day 18
measure: V/F for atorvastatin in the presence of ecopipam
timeFrame: Up to Day 18
measure: V/F for atorvastatin in the absence of ecopipam
timeFrame: Up to Day 18
measure: V/F for bupropion in the presence of ecopipam
timeFrame: Up to Day 18
measure: V/F for bupropion in the absence of ecopipam
timeFrame: Up to Day 18
measure: V/F for caffeine in the presence of ecopipam
timeFrame: Up to Day 18
measure: V/F for caffeine in the absence of ecopipam
timeFrame: Up to Day 18
measure: V/F for omeprazole in the presence of ecopipam
timeFrame: Up to Day 18
measure: V/F for omeprazole in the absence of ecopipam
timeFrame: Up to Day 18
measure: Total concentration of bilirubin in the presence of ecopipam
timeFrame: Up to Day 13
measure: Total concentration of bilirubin in the absence of ecopipam
timeFrame: Up to Day 13
measure: Unconjugated concentration of bilirubin in the presence of ecopipam
timeFrame: Up to Day 13
measure: Unconjugated concentration of bilirubin in the absence of ecopipam
timeFrame: Up to Day 13
measure: Safety and tolerability as demonstrated by MOAA/S
timeFrame: Up to Day 55
measure: Safety and tolerability as demonstrated by C-SSRS
timeFrame: Up to Day 55
measure: Safety and tolerability as demonstrated by concomitant medications
timeFrame: Up to Day 55
measure: AEs with relatedness associated with dextromethorphan
timeFrame: Up to Day 55
measure: AEs with relatedness associated with IV midazolam
timeFrame: Up to Day 55
measure: AEs with relatedness associated with oral midazolam
timeFrame: Up to Day 55
measure: AEs with relatedness associated with dabigatran
timeFrame: Up to Day 55
measure: AEs with relatedness associated with pitavastatin
timeFrame: Up to Day 55
measure: AEs with relatedness associated with rosuvastatin
timeFrame: Up to Day 55
measure: AEs with relatedness associated with atorvastatin
timeFrame: Up to Day 55
measure: AEs with relatedness associated with bupropion
timeFrame: Up to Day 55
measure: AEs with relatedness associated with caffeine
timeFrame: Up to Day 55
measure: AEs with relatedness associated with omeprazole
timeFrame: Up to Day 55
measure: AEs with relatedness associated with ecopipam
timeFrame: Up to Day 55
measure: Absolute values of white blood cell (WBC) count (K/Ul)
timeFrame: Up to Day 25
measure: Absolute values of neutrophils, lymphocytes, monocytes, eosinophils, and basophils (10E3/uL)
timeFrame: Blood samples will be collected for the assessment of hematology parameters.
measure: Absolute values of platelets (K/uL)
timeFrame: Up to Day 25
measure: Absolute values of hematocrit (%)
timeFrame: Up to Day 25
measure: Absolute values of hemoglobin (g/dL)
timeFrame: Up to Day 25
measure: Absolute values of Red blood cell (RBC) count (M/uL)
timeFrame: Up to Day 25
measure: Absolute values of blood sodium, magnesium, urea, phosphorus, potassium, and chloride (mg/dL)
timeFrame: Up to Day 25
measure: Absolute values of creatinine, calcium, glucose, and direct and total bilirubin (mg/dL)
timeFrame: Up to Day 25
measure: Absolute values of albumin and total protein (g/dL)
timeFrame: Up to Day 25
measure: Absolute values of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), and creatinine phosphokinase (CPK) (U/L)
timeFrame: Up to Day 25
measure: Absolute values of urine specific gravity
timeFrame: Up to Day 25
measure: Absolute values of urine pH
timeFrame: Up to Day 25
measure: Absolute values of urine glucose
timeFrame: Up to Day 25
measure: Absolute values of urine protein
timeFrame: Up to Day 25
measure: Absolute values of urine blood
timeFrame: Up to Day 25
measure: Absolute values of urine ketones
timeFrame: Up to Day 25
measure: Absolute values of urine bilirubin, urobilinogen, and nitrite
timeFrame: Up to Day 25
measure: Absolute values of urine leukocytes by dipstick
timeFrame: Up to Day 25
measure: Change from Day -1 to Day of Discharge in white blood cell (WBC) count (K/Ul)
timeFrame: Up to Day 25
measure: Change from Day -1 to Day of Discharge in neutrophils, lymphocytes, monocytes, eosinophils, and basophils (10E3/uL)
timeFrame: Up to Day 25
measure: Change from Day -1 to Day of Discharge in platelets (K/uL)
timeFrame: Up to Day 25
measure: Change from Day -1 to Day of Discharge in hematocrit (%)
timeFrame: Up to Day 25
measure: Change from Day -1 to Day of Discharge in hemoglobin (g/dL)
timeFrame: Up to Day 25
measure: Change from Day -1 to Day of Discharge in Red blood cell (RBC) count (M/uL)
timeFrame: Up to Day 25
measure: Change from Day -1 to Day of Discharge in blood sodium, magnesium, urea, phosphorus, potassium, and chloride (mg/dL)
timeFrame: Up to Day 25
measure: Change from Day -1 to Day of Discharge in creatinine, calcium, glucose, and direct and total bilirubin (mg/dL)
timeFrame: Up to Day 25
measure: Change from Day -1 to Day of Discharge in albumin and total protein (g/dL)
timeFrame: Up to Day 25
measure: 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)
timeFrame: Up to Day 25
measure: Change from Day -1 to Day of Discharge in urine specific gravity
timeFrame: Up to Day 25
measure: Change from Day -1 to Day of Discharge in urine pH
timeFrame: Up to Day 25
measure: Change from Day -1 to Day of Discharge in urine glucose
timeFrame: Up to Day 25
measure: Change from Day -1 to Day of Discharge in urine protein
timeFrame: Up to Day 25
measure: Change from Day -1 to Day of Discharge in urine blood
timeFrame: Up to Day 25
measure: Change from Day -1 to Day of Discharge in urine ketones
timeFrame: Up to Day 25
measure: Change from Day -1 to Day of Discharge in urine bilirubin, urobilinogen, and nitrite (Milligrams per deciliter)
timeFrame: Up to Day 25
measure: Change from Day -1 to Day of Discharge in urine leukocytes by dipstick
timeFrame: Up to Day 25
measure: Absolute values of electrocardiogram (ECG) parameters: PR, QRS, QT, and QT interval corrected for heart rate using Fridericia's formula (QTcF) (Milliseconds)
timeFrame: Up to Day 25
measure: Change from pre-dose for the respective day in ECG parameters: PR, QRS, QT, and QTcF (Milliseconds)
timeFrame: Up to Day 25
measure: Absolute values of oral temperature (degrees Celsius)
timeFrame: Up to Day 25
measure: Change from pre-dose for the respective day in oral temperature (degrees Celsius)
timeFrame: Up to Day 25
measure: Absolute values of heart rate (beats/minute)
timeFrame: Up to Day 25
measure: Change from pre-dose for the respective day in heart rate (beats/minute)
timeFrame: Up to Day 25
measure: Absolute values of respiratory rate (breaths/minute)
timeFrame: Up to Day 25
measure: Change from pre-dose for the respective day in respiratory rate (breaths/minute)
timeFrame: Up to Day 25
measure: Absolute values of systolic blood pressure (SBP) and diastolic blood pressure (DBP) (mmHG)
timeFrame: Up to Day 25
measure: Change from pre-dose for the respective day in SBP and DBP (mmHG)
timeFrame: Up to Day 25
Other outcomes:
Locations:
city: Miami
country: United States
facility: Syneos Health Clinical Research Services, LLC.
state: Florida
Study officials:
References: