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

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

Study Overview

• Status: Completed
• Conditions: Drug Interaction
• Intervention / Treatment: Drug: ecopipam HCL; Drug: Mefenamic acid; Drug: Divalproex Sodium ER

Detailed Description

Following a 28-day Screening period, eligible subjects will enter the clinical research unit (CRU) and will be enrolled into either Cohort A or B. Subjects in both cohorts will receive a single dose of ecopipam on Day 1. On Day 7, subjects will begin taking a UGT inhibitor according to their assigned cohort. Subjects in Cohort A will receive mefenamic acid 250 mg every 6 hours for 7 days, while subjects in Cohort B will receive divalproex sodium ER 1250 mg once a day for 10 days. A single oral dose of ecopipam will also be administered to Cohort A on Day 7, 1 hour after the first dose of mefenamic acid, and to Cohort B on Day 10, 1 hour after administration of divalproex sodium ER. Subjects in Cohort A will continue taking mefenamic acid through the evening of Day 13 and will remain in the CRU until discharged on Day 14/ET. Subjects in Cohort B will continue taking divalproex sodium ER through Day 16 and will remain in the CRU until discharge on Day 17/ET.

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33136
      • Syneos Health Clinical Research Services, LLC.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Cohort A; Ecopipam HCL - 2 doses of 200mg Mefenamic acid 250mg Q6H for 7 days	Drug: ecopipam HCL; oral tablets; Drug: Mefenamic acid; oral capsules
Other: Cohort B; Ecopipam HCL - 2 doses of 200mg Divalproex acid 1250mg QD for 10 days	Drug: ecopipam HCL; oral tablets; Drug: Divalproex Sodium ER; oral tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax of ecopipam in the presence of mefenamic acid	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	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	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	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	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	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	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	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	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	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	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	Up to 35 blood samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax of EBS-101-40853	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	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	Up to 35 blood samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 16
Cmax of mefenamic acid	Up to 15 blood samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 16
Tmax of mefenamic acid	Up to 15 blood samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 16
AUCtau of mefenamic acid	Up to 15 blood samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 16
t½ of mefenamic acid	Up to 15 blood samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 16
Cmax of VPA	Up to 19 blood samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 16
Tmax of VPA	Up to 19 blood samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 16
AUCtau of VPA	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	Safety and tolerability measures will be recorded at the indicated timepoints.	Up to Day 17
Safety and tolerability as demonstrated by C-SSRS	Safety and tolerability measures will be recorded at the indicated timepoints.	Up to Day 17
Safety and tolerability as demonstrated by concomitant medications	Safety and tolerability measures will be recorded at the indicated timepoints.	Up to Day 42
AEs with relatedness associated with mefenamic acid	Subjects will be continually monitored for adverse events	Up to Day 42
AEs with relatedness associated with divalproex sodium ER	Subjects will be continually monitored for adverse events	Up to Day 42
AEs with relatedness associated with ecopipam	Subjects will be continually monitored for adverse events	Up to Day 42
Absolute values of white blood cell (WBC) count (K/Ul)	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)	Blood samples will be collected for the assessment of hematology parameters.	Up to Day 17
Absolute values of platelets (K/uL)	Blood samples will be collected for the assessment of hematology parameters.	Up to Day 17
Absolute values of hematocrit (%)	Blood samples will be collected for the assessment of hematology parameters.	Up to Day 17
Absolute values of hemoglobin (g/dL)	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)	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)	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)	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)	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)	Blood samples will be collected for the assessment of clinical chemistry parameters.	Up to Day 17
Absolute values of urine specific gravity	Urine samples will be collected for the assessment of urine parameters.	Up to Day 17
Absolute values of urine pH	Urine samples will be collected for the assessment of urine parameters.	Up to Day 17
Absolute values of urine glucose	Urine samples will be collected for the assessment of urine parameters.	Up to Day 17
Absolute values of urine protein	Urine samples will be collected for the assessment of urine parameters.	Up to Day 17
Absolute values of urine blood	Urine samples will be collected for the assessment of urine parameters.	Up to Day 17
Absolute values of urine ketones	Urine samples will be collected for the assessment of urine parameters.	Up to Day 17
Absolute values of urine bilirubin, urobilinogen, and nitrite	Urine samples will be collected for the assessment of urine parameters.	Up to Day 17
Absolute values of urine leukocytes by dipstick	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)	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)	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)	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 (%)	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)	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)	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)	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)	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)	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)	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	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	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	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	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	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	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)	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	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)	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)	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)	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)	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)	Temperature will be assessed as part of vital signs.	Up to Day 17
Absolute values of heart rate (beats/minute)	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)	Heart rate will be assessed as part of vital signs.	Up to Day 17
Absolute values of respiratory rate (breaths/minute)	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)	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)	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)	Blood pressure will be assessed as part of vital signs.	Up to Day 17

Collaborators and Investigators

• Sponsor: Emalex Biosciences Inc.
• Collaborators: Syneos Health; Nuventra

Study record dates

Study Major Dates

• Study Start (Actual): May 13, 2021
• Primary Completion (Actual): July 6, 2021
• Study Completion (Actual): July 6, 2021

Study Registration Dates

• First Submitted: May 20, 2021
• First Submitted That Met QC Criteria: May 20, 2021
• First Posted (Actual): May 26, 2021

Study Record Updates

• Last Update Posted (Actual): July 22, 2021
• Last Update Submitted That Met QC Criteria: July 20, 2021
• Last Verified: July 1, 2021

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: EBS-101-HV-102

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes