Drug-Drug Interaction Study to Evaluate the Effect of Inhibition of UGTs on the PK of Ecopipam and Its Active Metabolite
Study Details
Study Description
Brief Summary
This is a single center, open-label, fixed sequence, drug-drug interaction (DDI) study in healthy subjects.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
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 Design
Arms and Interventions
| 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
|
Outcome Measures
Primary Outcome Measures
- Cmax of ecopipam in the presence of mefenamic acid [Up to Day 16]
Up to 35 blood samples will be collected at the indicated time points for pharmacokinetic analysis
- Cmax of ecopipam in the absence of mefenamic acid [Up to Day 16]
Up to 35 blood samples will be collected at the indicated time points for pharmacokinetic analysis
- Cmax of ecopipam in the presence of divalproex sodium ER [Up to Day 16]
Up to 35 blood samples will be collected at the indicated time points for pharmacokinetic analysis
- Cmax of ecopipam in the absence of divalproex sodium ER [Up to Day 16]
Up to 35 blood samples will be collected at the indicated time points for pharmacokinetic analysis
- AUCinf of ecopipam in the presence of mefenamic acid [Up to Day 16]
Up to 35 blood samples will be collected at the indicated time points for pharmacokinetic analysis
- AUCinf of ecopipam in the absence of mefenamic acid [Up to Day 16]
Up to 35 blood samples will be collected at the indicated time points for pharmacokinetic analysis
- AUCinf of ecopipam in the presence of divalproex sodium ER [Up to Day 16]
Up to 35 blood samples will be collected at the indicated time points for pharmacokinetic analysis
- AUCinf of ecopipam in the absence of divalproex sodium ER [Up to Day 16]
Up to 35 blood samples will be collected at the indicated time points for pharmacokinetic analysis
- AUC0-143 of ecopipam in the presence of mefenamic acid [Up to Day 16]
Up to 35 blood samples will be collected at the indicated time points for pharmacokinetic analysis
- AUC0-143 of ecopipam in the absence of mefenamic acid [Up to Day 16]
Up to 35 blood samples will be collected at the indicated time points for pharmacokinetic analysis
- AUC0-143 of ecopipam in the presence of divalproex sodium ER [Up to Day 16]
Up to 35 blood samples will be collected at the indicated time points for pharmacokinetic analysis
- AUC0-143 of ecopipam in the absence of divalproex sodium ER [Up to Day 16]
Up to 35 blood samples will be collected at the indicated time points for pharmacokinetic analysis
Secondary Outcome Measures
- Cmax of EBS-101-40853 [Up to Day 16]
Up to 35 blood samples will be collected at the indicated time points for pharmacokinetic analysis
- AUCinf of EBS-101-40853 [Up to Day 16]
Up to 35 blood samples will be collected at the indicated time points for pharmacokinetic analysis
- AUC0-143 of EBS-101-40853 [Up to Day 16]
Up to 35 blood samples will be collected at the indicated time points for pharmacokinetic analysis
- Cmax of mefenamic acid [Up to Day 16]
Up to 15 blood samples will be collected at the indicated time points for pharmacokinetic analysis
- Tmax of mefenamic acid [Up to Day 16]
Up to 15 blood samples will be collected at the indicated time points for pharmacokinetic analysis
- AUCtau of mefenamic acid [Up to Day 16]
Up to 15 blood samples will be collected at the indicated time points for pharmacokinetic analysis
- t½ of mefenamic acid [Up to Day 16]
Up to 15 blood samples will be collected at the indicated time points for pharmacokinetic analysis
- Cmax of VPA [Up to Day 16]
Up to 19 blood samples will be collected at the indicated time points for pharmacokinetic analysis
- Tmax of VPA [Up to Day 16]
Up to 19 blood samples will be collected at the indicated time points for pharmacokinetic analysis
- AUCtau of VPA [Up to Day 16]
Up to 19 blood samples will be collected at the indicated time points for pharmacokinetic analysis
- Safety and tolerability as demonstrated by MOAA/S [Up to Day 17]
Safety and tolerability measures will be recorded at the indicated timepoints.
- Safety and tolerability as demonstrated by C-SSRS [Up to Day 17]
Safety and tolerability measures will be recorded at the indicated timepoints.
- Safety and tolerability as demonstrated by concomitant medications [Up to Day 42]
Safety and tolerability measures will be recorded at the indicated timepoints.
- AEs with relatedness associated with mefenamic acid [Up to Day 42]
Subjects will be continually monitored for adverse events
- AEs with relatedness associated with divalproex sodium ER [Up to Day 42]
Subjects will be continually monitored for adverse events
- AEs with relatedness associated with ecopipam [Up to Day 42]
Subjects will be continually monitored for adverse events
- Absolute values of white blood cell (WBC) count (K/Ul) [Up to Day 17]
Blood samples will be collected for the assessment of hematology parameters.
- Absolute values of neutrophils, lymphocytes, monocytes, eosinophils, and basophils (10E3/uL) [Up to Day 17]
Blood samples will be collected for the assessment of hematology parameters.
- Absolute values of platelets (K/uL) [Up to Day 17]
Blood samples will be collected for the assessment of hematology parameters.
- Absolute values of hematocrit (%) [Up to Day 17]
Blood samples will be collected for the assessment of hematology parameters.
- Absolute values of hemoglobin (g/dL) [Up to Day 17]
Blood samples will be collected for the assessment of hematology parameters.
- Absolute values of Red blood cell (RBC) count (M/uL) [Up to Day 17]
Blood samples will be collected for the assessment of hematology parameters.
- Absolute values of blood sodium, magnesium, urea, phosphorus, potassium, and chloride (mg/dL) [Up to Day 17]
Blood samples will be collected for the assessment of clinical chemistry parameters.
- Absolute values of creatinine, calcium, glucose, and direct and total bilirubin (mg/dL) [Up to Day 17]
Blood samples will be collected for the assessment of clinical chemistry parameters.
- Absolute values of albumin and total protein (g/dL) [Up to Day 17]
Blood samples will be collected for the assessment of clinical chemistry parameters.
- Absolute values of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), and creatinine phosphokinase (CPK) [Up to Day 17]
Blood samples will be collected for the assessment of clinical chemistry parameters.
- Absolute values of urine specific gravity [Up to Day 17]
Urine samples will be collected for the assessment of urine parameters.
- Absolute values of urine pH [Up to Day 17]
Urine samples will be collected for the assessment of urine parameters.
- Absolute values of urine glucose [Up to Day 17]
Urine samples will be collected for the assessment of urine parameters.
- Absolute values of urine protein [Up to Day 17]
Urine samples will be collected for the assessment of urine parameters.
- Absolute values of urine blood [Up to Day 17]
Urine samples will be collected for the assessment of urine parameters.
- Absolute values of urine ketones [Up to Day 17]
Urine samples will be collected for the assessment of urine parameters.
- Absolute values of urine bilirubin, urobilinogen, and nitrite [Up to Day 17]
Urine samples will be collected for the assessment of urine parameters.
- Absolute values of urine leukocytes by dipstick [Up to Day 17]
Urine samples will be collected for the assessment of urine parameters.
- Change from Day -1 to Day of Discharge in white blood cell (WBC) count (K/Ul) [Up to Day 17]
Blood samples will be collected for the assessment of hematology parameters.
- Change from Day -1 to Day of Discharge in neutrophils, lymphocytes, monocytes, eosinophils, and basophils (10E3/uL) [Up to Day 17]
Blood samples will be collected for the assessment of hematology parameters.
- Change from Day -1 to Day of Discharge in platelets (K/uL) [Up to Day 17]
Blood samples will be collected for the assessment of hematology parameters.
- Change from Day -1 to Day of Discharge in hematocrit (%) [Up to Day 17]
Blood samples will be collected for the assessment of hematology parameters.
- Change from Day -1 to Day of Discharge in hemoglobin (g/dL) [Up to Day 17]
Blood samples will be collected for the assessment of hematology parameters.
- Change from Day -1 to Day of Discharge in Red blood cell (RBC) count (M/uL) [Up to Day 17]
Blood samples will be collected for the assessment of hematology parameters.
- Change from Day -1 to Day of Discharge in blood sodium, magnesium, urea, phosphorus, potassium, and chloride (mg/dL) [Up to Day 17]
Blood samples will be collected for the assessment of clinical chemistry parameters.
- Change from Day -1 to Day of Discharge in creatinine, calcium, glucose, and direct and total bilirubin (mg/dL) [Up to Day 17]
Blood samples will be collected for the assessment of clinical chemistry parameters.
- Change from Day -1 to Day of Discharge in albumin and total protein (g/dL) [Up to Day 17]
Blood samples will be collected for the assessment of clinical chemistry parameters.
- 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) [Up to Day 17]
Blood samples will be collected for the assessment of clinical chemistry parameters.
- Change from Day -1 to Day of Discharge in urine specific gravity [Up to Day 17]
Urine samples will be collected for the assessment of urine parameters.
- Change from Day -1 to Day of Discharge in urine pH [Up to Day 17]
Urine samples will be collected for the assessment of urine parameters.
- Change from Day -1 to Day of Discharge in urine glucose [Up to Day 17]
Urine samples will be collected for the assessment of urine parameters.
- Change from Day -1 to Day of Discharge in urine protein [Up to Day 17]
Urine samples will be collected for the assessment of urine parameters.
- Change from Day -1 to Day of Discharge in urine blood [Up to Day 17]
Urine samples will be collected for the assessment of urine parameters.
- Change from Day -1 to Day of Discharge in urine ketones [Up to Day 17]
Urine samples will be collected for the assessment of urine parameters.
- Change from Day -1 to Day of Discharge in urine bilirubin, urobilinogen, and nitrite (Milligrams per deciliter) [Up to Day 17]
Urine samples will be collected for the assessment of urine parameters.
- Change from Day -1 to Day of Discharge in urine leukocytes by dipstick [Up to Day 17]
Urine samples will be collected for the assessment of urine parameters.
- Change from Day 6 to Day of Discharge in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) (U/L) [Up to Day 17]
Blood samples will be collected for the assessment of clinical chemistry parameters.
- Absolute values of electrocardiogram (ECG) parameters: PR, QRS, QT, and QT interval corrected for heart rate using Fridericia's formula (QTcF) (Milliseconds) [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.
- Change from pre-dose for the respective day in ECG parameters: PR, QRS, QT, and QTcF (Milliseconds) [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.
- Absolute values of oral temperature (degrees Celsius) [Up to Day 17]
Temperature will be assessed as part of vital signs.
- Change from pre-dose for the respective day in oral temperature (degrees Celsius) [Up to Day 17]
Temperature will be assessed as part of vital signs.
- Absolute values of heart rate (beats/minute) [Up to Day 17]
Heart rate will be assessed as part of vital signs.
- Change from pre-dose for the respective day in heart rate (beats/minute) [Up to Day 17]
Heart rate will be assessed as part of vital signs.
- Absolute values of respiratory rate (breaths/minute) [Up to Day 17]
Respiratory rate will be assessed as part of vital signs.
- Change from pre-dose for the respective day in respiratory rate (breaths/minute) [Up to Day 17]
Respiratory rate will be assessed as part of vital signs.
- Absolute values of systolic blood pressure (SBP) and diastolic blood pressure (DBP) (mmHG) [Up to Day 17]
Blood pressure will be assessed as part of vital signs.
- Change from pre-dose for the respective day in SBP and DBP (mmHG) [Up to Day 17]
Blood pressure will be assessed as part of vital signs.
Eligibility Criteria
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
-
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Syneos Health Clinical Research Services, LLC. | Miami | Florida | United States | 33136 |
Sponsors and Collaborators
- Emalex Biosciences Inc.
- Syneos Health
- Nuventra
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- EBS-101-HV-102