Drug-Drug Interaction Study to Evaluate the Effect of Inhibition of UGTs on the PK of Ecopipam and Its Active Metabolite
A Phase 1, Open-Label, Fixed Sequence, Drug-Drug Interaction Study to Evaluate the Effect of Inhibition of Uridine 5'-Diphosphate-glucuronosyltransferases (UGTs) on the Pharmacokinetics of Ecopipam Tablets and Its Active Metabolite (EBS-101-40853) in Healthy Subjects
Study Overview
Status
Status
Conditions
Conditions
Intervention / Treatment
Intervention / Treatment
Detailed Description
Study Type
Study Type
Enrollment (Actual)
Enrollment
Phase
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Florida
-
Miami, Florida, United States, 33136
- Syneos Health Clinical Research Services, LLC.
-
-
Participation Criteria
Eligibility Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
- 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
- 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
- Not suitable for study in the opinion of the Principal Investigator
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Number of Arms
Arms and Interventions
Participant Group / ArmParticipant Group / Arm |
Intervention / TreatmentIntervention / Treatment |
|---|---|
|
Other: Cohort A
Ecopipam HCL - 2 doses of 200mg Mefenamic acid 250mg Q6H for 7 days |
oral tablets
oral capsules
|
|
Other: Cohort B
Ecopipam HCL - 2 doses of 200mg Divalproex acid 1250mg QD for 10 days |
oral tablets
oral tablets
|
What is the study measuring?
Primary Outcome Measures
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Cmax of ecopipam in the presence of mefenamic acid
Time Frame: Up to Day 16
|
Up to 35 blood samples will be collected at the indicated time points for pharmacokinetic analysis
|
Up to Day 16
|
|
Cmax of ecopipam in the absence of mefenamic acid
Time Frame: Up to Day 16
|
Up to 35 blood samples will be collected at the indicated time points for pharmacokinetic analysis
|
Up to Day 16
|
|
Cmax of ecopipam in the presence of divalproex sodium ER
Time Frame: Up to Day 16
|
Up to 35 blood samples will be collected at the indicated time points for pharmacokinetic analysis
|
Up to Day 16
|
|
Cmax of ecopipam in the absence of divalproex sodium ER
Time Frame: Up to Day 16
|
Up to 35 blood samples will be collected at the indicated time points for pharmacokinetic analysis
|
Up to Day 16
|
|
AUCinf of ecopipam in the presence of mefenamic acid
Time Frame: Up to Day 16
|
Up to 35 blood samples will be collected at the indicated time points for pharmacokinetic analysis
|
Up to Day 16
|
|
AUCinf of ecopipam in the absence of mefenamic acid
Time Frame: Up to Day 16
|
Up to 35 blood samples will be collected at the indicated time points for pharmacokinetic analysis
|
Up to Day 16
|
|
AUCinf of ecopipam in the presence of divalproex sodium ER
Time Frame: Up to Day 16
|
Up to 35 blood samples will be collected at the indicated time points for pharmacokinetic analysis
|
Up to Day 16
|
|
AUCinf of ecopipam in the absence of divalproex sodium ER
Time Frame: Up to Day 16
|
Up to 35 blood samples will be collected at the indicated time points for pharmacokinetic analysis
|
Up to Day 16
|
|
AUC0-143 of ecopipam in the presence of mefenamic acid
Time Frame: Up to Day 16
|
Up to 35 blood samples will be collected at the indicated time points for pharmacokinetic analysis
|
Up to Day 16
|
|
AUC0-143 of ecopipam in the absence of mefenamic acid
Time Frame: Up to Day 16
|
Up to 35 blood samples will be collected at the indicated time points for pharmacokinetic analysis
|
Up to Day 16
|
|
AUC0-143 of ecopipam in the presence of divalproex sodium ER
Time Frame: Up to Day 16
|
Up to 35 blood samples will be collected at the indicated time points for pharmacokinetic analysis
|
Up to Day 16
|
|
AUC0-143 of ecopipam in the absence of divalproex sodium ER
Time Frame: Up to Day 16
|
Up to 35 blood samples will be collected at the indicated time points for pharmacokinetic analysis
|
Up to Day 16
|
Secondary Outcome Measures
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Cmax of EBS-101-40853
Time Frame: Up to Day 16
|
Up to 35 blood samples will be collected at the indicated time points for pharmacokinetic analysis
|
Up to Day 16
|
|
AUCinf of EBS-101-40853
Time Frame: Up to Day 16
|
Up to 35 blood samples will be collected at the indicated time points for pharmacokinetic analysis
|
Up to Day 16
|
|
AUC0-143 of EBS-101-40853
Time Frame: Up to Day 16
|
Up to 35 blood samples will be collected at the indicated time points for pharmacokinetic analysis
|
Up to Day 16
|
|
Cmax of mefenamic acid
Time Frame: Up to Day 16
|
Up to 15 blood samples will be collected at the indicated time points for pharmacokinetic analysis
|
Up to Day 16
|
|
Tmax of mefenamic acid
Time Frame: Up to Day 16
|
Up to 15 blood samples will be collected at the indicated time points for pharmacokinetic analysis
|
Up to Day 16
|
|
AUCtau of mefenamic acid
Time Frame: Up to Day 16
|
Up to 15 blood samples will be collected at the indicated time points for pharmacokinetic analysis
|
Up to Day 16
|
|
t½ of mefenamic acid
Time Frame: Up to Day 16
|
Up to 15 blood samples will be collected at the indicated time points for pharmacokinetic analysis
|
Up to Day 16
|
|
Cmax of VPA
Time Frame: Up to Day 16
|
Up to 19 blood samples will be collected at the indicated time points for pharmacokinetic analysis
|
Up to Day 16
|
|
Tmax of VPA
Time Frame: Up to Day 16
|
Up to 19 blood samples will be collected at the indicated time points for pharmacokinetic analysis
|
Up to Day 16
|
|
AUCtau of VPA
Time Frame: Up to Day 16
|
Up to 19 blood samples will be collected at the indicated time points for pharmacokinetic analysis
|
Up to Day 16
|
|
Safety and tolerability as demonstrated by MOAA/S
Time Frame: Up to Day 17
|
Safety and tolerability measures will be recorded at the indicated timepoints.
|
Up to Day 17
|
|
Safety and tolerability as demonstrated by C-SSRS
Time Frame: Up to Day 17
|
Safety and tolerability measures will be recorded at the indicated timepoints.
|
Up to Day 17
|
|
Safety and tolerability as demonstrated by concomitant medications
Time Frame: Up to Day 42
|
Safety and tolerability measures will be recorded at the indicated timepoints.
|
Up to Day 42
|
|
AEs with relatedness associated with mefenamic acid
Time Frame: Up to Day 42
|
Subjects will be continually monitored for adverse events
|
Up to Day 42
|
|
AEs with relatedness associated with divalproex sodium ER
Time Frame: Up to Day 42
|
Subjects will be continually monitored for adverse events
|
Up to Day 42
|
|
AEs with relatedness associated with ecopipam
Time Frame: Up to Day 42
|
Subjects will be continually monitored for adverse events
|
Up to Day 42
|
|
Absolute values of white blood cell (WBC) count (K/Ul)
Time Frame: Up to Day 17
|
Blood samples will be collected for the assessment of hematology parameters.
|
Up to Day 17
|
|
Absolute values of neutrophils, lymphocytes, monocytes, eosinophils, and basophils (10E3/uL)
Time Frame: Up to Day 17
|
Blood samples will be collected for the assessment of hematology parameters.
|
Up to Day 17
|
|
Absolute values of platelets (K/uL)
Time Frame: Up to Day 17
|
Blood samples will be collected for the assessment of hematology parameters.
|
Up to Day 17
|
|
Absolute values of hematocrit (%)
Time Frame: Up to Day 17
|
Blood samples will be collected for the assessment of hematology parameters.
|
Up to Day 17
|
|
Absolute values of hemoglobin (g/dL)
Time Frame: Up to Day 17
|
Blood samples will be collected for the assessment of hematology parameters.
|
Up to Day 17
|
|
Absolute values of Red blood cell (RBC) count (M/uL)
Time Frame: Up to Day 17
|
Blood samples will be collected for the assessment of hematology parameters.
|
Up to Day 17
|
|
Absolute values of blood sodium, magnesium, urea, phosphorus, potassium, and chloride (mg/dL)
Time Frame: Up to Day 17
|
Blood samples will be collected for the assessment of clinical chemistry parameters.
|
Up to Day 17
|
|
Absolute values of creatinine, calcium, glucose, and direct and total bilirubin (mg/dL)
Time Frame: Up to Day 17
|
Blood samples will be collected for the assessment of clinical chemistry parameters.
|
Up to Day 17
|
|
Absolute values of albumin and total protein (g/dL)
Time Frame: Up to Day 17
|
Blood samples will be collected for the assessment of clinical chemistry parameters.
|
Up to Day 17
|
|
Absolute values of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), and creatinine phosphokinase (CPK)
Time Frame: Up to Day 17
|
Blood samples will be collected for the assessment of clinical chemistry parameters.
|
Up to Day 17
|
|
Absolute values of urine specific gravity
Time Frame: Up to Day 17
|
Urine samples will be collected for the assessment of urine parameters.
|
Up to Day 17
|
|
Absolute values of urine pH
Time Frame: Up to Day 17
|
Urine samples will be collected for the assessment of urine parameters.
|
Up to Day 17
|
|
Absolute values of urine glucose
Time Frame: Up to Day 17
|
Urine samples will be collected for the assessment of urine parameters.
|
Up to Day 17
|
|
Absolute values of urine protein
Time Frame: Up to Day 17
|
Urine samples will be collected for the assessment of urine parameters.
|
Up to Day 17
|
|
Absolute values of urine blood
Time Frame: Up to Day 17
|
Urine samples will be collected for the assessment of urine parameters.
|
Up to Day 17
|
|
Absolute values of urine ketones
Time Frame: Up to Day 17
|
Urine samples will be collected for the assessment of urine parameters.
|
Up to Day 17
|
|
Absolute values of urine bilirubin, urobilinogen, and nitrite
Time Frame: Up to Day 17
|
Urine samples will be collected for the assessment of urine parameters.
|
Up to Day 17
|
|
Absolute values of urine leukocytes by dipstick
Time Frame: Up to Day 17
|
Urine samples will be collected for the assessment of urine parameters.
|
Up to Day 17
|
|
Change from Day -1 to Day of Discharge in white blood cell (WBC) count (K/Ul)
Time Frame: Up to Day 17
|
Blood samples will be collected for the assessment of hematology parameters.
|
Up to Day 17
|
|
Change from Day -1 to Day of Discharge in neutrophils, lymphocytes, monocytes, eosinophils, and basophils (10E3/uL)
Time Frame: Up to Day 17
|
Blood samples will be collected for the assessment of hematology parameters.
|
Up to Day 17
|
|
Change from Day -1 to Day of Discharge in platelets (K/uL)
Time Frame: Up to Day 17
|
Blood samples will be collected for the assessment of hematology parameters.
|
Up to Day 17
|
|
Change from Day -1 to Day of Discharge in hematocrit (%)
Time Frame: Up to Day 17
|
Blood samples will be collected for the assessment of hematology parameters.
|
Up to Day 17
|
|
Change from Day -1 to Day of Discharge in hemoglobin (g/dL)
Time Frame: Up to Day 17
|
Blood samples will be collected for the assessment of hematology parameters.
|
Up to Day 17
|
|
Change from Day -1 to Day of Discharge in Red blood cell (RBC) count (M/uL)
Time Frame: Up to Day 17
|
Blood samples will be collected for the assessment of hematology parameters.
|
Up to Day 17
|
|
Change from Day -1 to Day of Discharge in blood sodium, magnesium, urea, phosphorus, potassium, and chloride (mg/dL)
Time Frame: Up to Day 17
|
Blood samples will be collected for the assessment of clinical chemistry parameters.
|
Up to Day 17
|
|
Change from Day -1 to Day of Discharge in creatinine, calcium, glucose, and direct and total bilirubin (mg/dL)
Time Frame: Up to Day 17
|
Blood samples will be collected for the assessment of clinical chemistry parameters.
|
Up to Day 17
|
|
Change from Day -1 to Day of Discharge in albumin and total protein (g/dL)
Time Frame: Up to Day 17
|
Blood samples will be collected for the assessment of clinical chemistry parameters.
|
Up to Day 17
|
|
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)
Time Frame: Up to Day 17
|
Blood samples will be collected for the assessment of clinical chemistry parameters.
|
Up to Day 17
|
|
Change from Day -1 to Day of Discharge in urine specific gravity
Time Frame: Up to Day 17
|
Urine samples will be collected for the assessment of urine parameters.
|
Up to Day 17
|
|
Change from Day -1 to Day of Discharge in urine pH
Time Frame: Up to Day 17
|
Urine samples will be collected for the assessment of urine parameters.
|
Up to Day 17
|
|
Change from Day -1 to Day of Discharge in urine glucose
Time Frame: Up to Day 17
|
Urine samples will be collected for the assessment of urine parameters.
|
Up to Day 17
|
|
Change from Day -1 to Day of Discharge in urine protein
Time Frame: Up to Day 17
|
Urine samples will be collected for the assessment of urine parameters.
|
Up to Day 17
|
|
Change from Day -1 to Day of Discharge in urine blood
Time Frame: Up to Day 17
|
Urine samples will be collected for the assessment of urine parameters.
|
Up to Day 17
|
|
Change from Day -1 to Day of Discharge in urine ketones
Time Frame: Up to Day 17
|
Urine samples will be collected for the assessment of urine parameters.
|
Up to Day 17
|
|
Change from Day -1 to Day of Discharge in urine bilirubin, urobilinogen, and nitrite (Milligrams per deciliter)
Time Frame: Up to Day 17
|
Urine samples will be collected for the assessment of urine parameters.
|
Up to Day 17
|
|
Change from Day -1 to Day of Discharge in urine leukocytes by dipstick
Time Frame: Up to Day 17
|
Urine samples will be collected for the assessment of urine parameters.
|
Up to Day 17
|
|
Change from Day 6 to Day of Discharge in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) (U/L)
Time Frame: Up to Day 17
|
Blood samples will be collected for the assessment of clinical chemistry parameters.
|
Up to Day 17
|
|
Absolute values of electrocardiogram (ECG) parameters: PR, QRS, QT, and QT interval corrected for heart rate using Fridericia's formula (QTcF) (Milliseconds)
Time Frame: Up to Day 10
|
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 10
|
|
Change from pre-dose for the respective day in ECG parameters: PR, QRS, QT, and QTcF (Milliseconds)
Time Frame: Up to Day 10
|
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 10
|
|
Absolute values of oral temperature (degrees Celsius)
Time Frame: Up to Day 17
|
Temperature will be assessed as part of vital signs.
|
Up to Day 17
|
|
Change from pre-dose for the respective day in oral temperature (degrees Celsius)
Time Frame: Up to Day 17
|
Temperature will be assessed as part of vital signs.
|
Up to Day 17
|
|
Absolute values of heart rate (beats/minute)
Time Frame: Up to Day 17
|
Heart rate will be assessed as part of vital signs.
|
Up to Day 17
|
|
Change from pre-dose for the respective day in heart rate (beats/minute)
Time Frame: Up to Day 17
|
Heart rate will be assessed as part of vital signs.
|
Up to Day 17
|
|
Absolute values of respiratory rate (breaths/minute)
Time Frame: Up to Day 17
|
Respiratory rate will be assessed as part of vital signs.
|
Up to Day 17
|
|
Change from pre-dose for the respective day in respiratory rate (breaths/minute)
Time Frame: Up to Day 17
|
Respiratory rate will be assessed as part of vital signs.
|
Up to Day 17
|
|
Absolute values of systolic blood pressure (SBP) and diastolic blood pressure (DBP) (mmHG)
Time Frame: Up to Day 17
|
Blood pressure will be assessed as part of vital signs.
|
Up to Day 17
|
|
Change from pre-dose for the respective day in SBP and DBP (mmHG)
Time Frame: Up to Day 17
|
Blood pressure will be assessed as part of vital signs.
|
Up to Day 17
|
Collaborators and Investigators
Sponsor
Sponsor
Collaborators
Collaborators
Study record dates
Study Major Dates
Study Start (Actual)
Study Start
Primary Completion (Actual)
Primary Completion
Study Completion (Actual)
Study Completion
Study Registration Dates
First Submitted
First Submitted
First Submitted That Met QC Criteria
First Submitted That Met QC Criteria
First Posted (Actual)
First Posted
Study Record Updates
Last Update Posted (Actual)
Last Update Posted
Last Update Submitted That Met QC Criteria
Last Update Submitted That Met QC Criteria
Last Verified
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Central Nervous System Depressants
- Peripheral Nervous System Agents
- Enzyme Inhibitors
- Analgesics
- Sensory System Agents
- Anti-Inflammatory Agents, Non-Steroidal
- Analgesics, Non-Narcotic
- Anti-Inflammatory Agents
- Antirheumatic Agents
- Cyclooxygenase Inhibitors
- Antipsychotic Agents
- Tranquilizing Agents
- Psychotropic Drugs
- Dopamine Agents
- Dopamine Antagonists
- GABA Agents
- Anticonvulsants
- Antimanic Agents
- Valproic Acid
- Mefenamic Acid
- Ecopipam
Other Study ID Numbers
Other Study ID Numbers
- EBS-101-HV-102
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
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