Clinical trial NCT04902105: Drug-Drug Interaction Study to Evaluate the Effect of Inhibition of UGTs on the PK of Ecopipam and Its Active Metabolite
Official title: 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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Drug Interaction
Lead sponsor: Emalex Biosciences Inc.
Sponsor class: INDUSTRY
Collaborators: name: Syneos Health
name: Nuventra, Inc.
First posted: 2021-05-26
Enrollment: 38
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, 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.

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
* 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

Primary outcomes:
measure: Cmax of ecopipam in the presence of mefenamic acid
timeFrame: Up to Day 16
measure: Cmax of ecopipam in the absence of mefenamic acid
timeFrame: Up to Day 16
measure: Cmax of ecopipam in the presence of divalproex sodium ER
timeFrame: Up to Day 16
measure: Cmax of ecopipam in the absence of divalproex sodium ER
timeFrame: Up to Day 16
measure: AUCinf of ecopipam in the presence of mefenamic acid
timeFrame: Up to Day 16
measure: AUCinf of ecopipam in the absence of mefenamic acid
timeFrame: Up to Day 16
measure: AUCinf of ecopipam in the presence of divalproex sodium ER
timeFrame: Up to Day 16
measure: AUCinf of ecopipam in the absence of divalproex sodium ER
timeFrame: Up to Day 16
measure: AUC0-143 of ecopipam in the presence of mefenamic acid
timeFrame: Up to Day 16
measure: AUC0-143 of ecopipam in the absence of mefenamic acid
timeFrame: Up to Day 16
measure: AUC0-143 of ecopipam in the presence of divalproex sodium ER
timeFrame: Up to Day 16
measure: AUC0-143 of ecopipam in the absence of divalproex sodium ER
timeFrame: Up to Day 16
Secondary outcomes:
measure: Cmax of EBS-101-40853
timeFrame: Up to Day 16
measure: AUCinf of EBS-101-40853
timeFrame: Up to Day 16
measure: AUC0-143 of EBS-101-40853
timeFrame: Up to Day 16
measure: Cmax of mefenamic acid
timeFrame: Up to Day 16
measure: Tmax of mefenamic acid
timeFrame: Up to Day 16
measure: AUCtau of mefenamic acid
timeFrame: Up to Day 16
measure: t½ of mefenamic acid
timeFrame: Up to Day 16
measure: Cmax of VPA
timeFrame: Up to Day 16
measure: Tmax of VPA
timeFrame: Up to Day 16
measure: AUCtau of VPA
timeFrame: Up to Day 16
measure: Safety and tolerability as demonstrated by MOAA/S
timeFrame: Up to Day 17
measure: Safety and tolerability as demonstrated by C-SSRS
timeFrame: Up to Day 17
measure: Safety and tolerability as demonstrated by concomitant medications
timeFrame: Up to Day 42
measure: AEs with relatedness associated with mefenamic acid
timeFrame: Up to Day 42
measure: AEs with relatedness associated with divalproex sodium ER
timeFrame: Up to Day 42
measure: AEs with relatedness associated with ecopipam
timeFrame: Up to Day 42
measure: Absolute values of white blood cell (WBC) count (K/Ul)
timeFrame: Up to Day 17
measure: Absolute values of neutrophils, lymphocytes, monocytes, eosinophils, and basophils (10E3/uL)
timeFrame: Up to Day 17
measure: Absolute values of platelets (K/uL)
timeFrame: Up to Day 17
measure: Absolute values of hematocrit (%)
timeFrame: Up to Day 17
measure: Absolute values of hemoglobin (g/dL)
timeFrame: Up to Day 17
measure: Absolute values of Red blood cell (RBC) count (M/uL)
timeFrame: Up to Day 17
measure: Absolute values of blood sodium, magnesium, urea, phosphorus, potassium, and chloride (mg/dL)
timeFrame: Up to Day 17
measure: Absolute values of creatinine, calcium, glucose, and direct and total bilirubin (mg/dL)
timeFrame: Up to Day 17
measure: Absolute values of albumin and total protein (g/dL)
timeFrame: Up to Day 17
measure: Absolute values of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), and creatinine phosphokinase (CPK)
timeFrame: Up to Day 17
measure: Absolute values of urine specific gravity
timeFrame: Up to Day 17
measure: Absolute values of urine pH
timeFrame: Up to Day 17
measure: Absolute values of urine glucose
timeFrame: Up to Day 17
measure: Absolute values of urine protein
timeFrame: Up to Day 17
measure: Absolute values of urine blood
timeFrame: Up to Day 17
measure: Absolute values of urine ketones
timeFrame: Up to Day 17
measure: Absolute values of urine bilirubin, urobilinogen, and nitrite
timeFrame: Up to Day 17
measure: Absolute values of urine leukocytes by dipstick
timeFrame: Up to Day 17
measure: Change from Day -1 to Day of Discharge in white blood cell (WBC) count (K/Ul)
timeFrame: Up to Day 17
measure: Change from Day -1 to Day of Discharge in neutrophils, lymphocytes, monocytes, eosinophils, and basophils (10E3/uL)
timeFrame: Up to Day 17
measure: Change from Day -1 to Day of Discharge in platelets (K/uL)
timeFrame: Up to Day 17
measure: Change from Day -1 to Day of Discharge in hematocrit (%)
timeFrame: Up to Day 17
measure: Change from Day -1 to Day of Discharge in hemoglobin (g/dL)
timeFrame: Up to Day 17
measure: Change from Day -1 to Day of Discharge in Red blood cell (RBC) count (M/uL)
timeFrame: Up to Day 17
measure: Change from Day -1 to Day of Discharge in blood sodium, magnesium, urea, phosphorus, potassium, and chloride (mg/dL)
timeFrame: Up to Day 17
measure: Change from Day -1 to Day of Discharge in creatinine, calcium, glucose, and direct and total bilirubin (mg/dL)
timeFrame: Up to Day 17
measure: Change from Day -1 to Day of Discharge in albumin and total protein (g/dL)
timeFrame: Up to Day 17
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 17
measure: Change from Day -1 to Day of Discharge in urine specific gravity
timeFrame: Up to Day 17
measure: Change from Day -1 to Day of Discharge in urine pH
timeFrame: Up to Day 17
measure: Change from Day -1 to Day of Discharge in urine glucose
timeFrame: Up to Day 17
measure: Change from Day -1 to Day of Discharge in urine protein
timeFrame: Up to Day 17
measure: Change from Day -1 to Day of Discharge in urine blood
timeFrame: Up to Day 17
measure: Change from Day -1 to Day of Discharge in urine ketones
timeFrame: Up to Day 17
measure: Change from Day -1 to Day of Discharge in urine bilirubin, urobilinogen, and nitrite (Milligrams per deciliter)
timeFrame: Up to Day 17
measure: Change from Day -1 to Day of Discharge in urine leukocytes by dipstick
timeFrame: Up to Day 17
measure: Change from Day 6 to Day of Discharge in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) (U/L)
timeFrame: Up to Day 17
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 10
measure: Change from pre-dose for the respective day in ECG parameters: PR, QRS, QT, and QTcF (Milliseconds)
timeFrame: Up to Day 10
measure: Absolute values of oral temperature (degrees Celsius)
timeFrame: Up to Day 17
measure: Change from pre-dose for the respective day in oral temperature (degrees Celsius)
timeFrame: Up to Day 17
measure: Absolute values of heart rate (beats/minute)
timeFrame: Up to Day 17
measure: Change from pre-dose for the respective day in heart rate (beats/minute)
timeFrame: Up to Day 17
measure: Absolute values of respiratory rate (breaths/minute)
timeFrame: Up to Day 17
measure: Change from pre-dose for the respective day in respiratory rate (breaths/minute)
timeFrame: Up to Day 17
measure: Absolute values of systolic blood pressure (SBP) and diastolic blood pressure (DBP) (mmHG)
timeFrame: Up to Day 17
measure: Change from pre-dose for the respective day in SBP and DBP (mmHG)
timeFrame: Up to Day 17
Other outcomes:
Locations:
city: Miami
country: United States
facility: Syneos Health Clinical Research Services, LLC.
state: Florida
Study officials:
References: