Drug Interaction
Conditions
Brief summary
This is a single center, open-label, fixed sequence, drug-drug interaction (DDI) study in healthy subjects.
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.
Interventions
Sponsors
Syneos Health
Nuventra, Inc.
Emalex Biosciences Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| Absolute values of oral temperature (degrees Celsius) | Up to Day 17 | Temperature will be assessed as part of vital signs. |
| 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. |
| 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. |
| 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. |
| 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. |
Countries
United States
Outcome results
None listed