Drug Interaction Study

A Phase 1, Sequential Drug Interaction Study to Evaluate the Effect of CYP3A4 and P-glycoprotein Inhibition by Itraconazole or Induction by Rifampicin on the Pharmacokinetics of Ecopipam and Its Metabolites in Healthy Subjects

This is a single center, 2-Part, Phase 1, open-label, fixed-sequence, drug-drug interaction study designed to compare the PK of ecopipam when administered alone and in combination with itraconazole (Part 1) or rifampicin (Part 2) in healthy subjects.

Study Overview

• Status: Recruiting
• Conditions: Drug Interaction
• Intervention / Treatment: Drug: Itraconazole; Drug: Ecopipam; Drug: rifampicin

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Emalex Biosciences; Phone Number: 312.847.1340; Email: emalex@emalexbiosciences.com

Study Locations

• Canada
  • Quebec
    • Québec, Quebec, Canada, G1P 0A2
      • Recruiting
      • Syneos Health Clinic Inc.
      • Contact: Lidia Facchinelli, MD; Phone Number: 819.266.8033

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Male subjects or femail subjects of non-childbearing potential
• ≥18 and ≤55 years of age
• BMI >18.5 and <30.0 kg/m2 and body weight ≥50.0 kg for males and ≥45.0 kg for females.
• Subjects must be healthy, as determined by the Investigator, based on medical history, physical examination, ECG, vital signs, and standard panel of blood and laboratory tests at Screening.
• 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.
• Willing to take off dentures or mouth piercing at the time of dosing.

Exclusion Criteria:

• 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 8 weeks 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
• Female subjects who are currently pregnant or lactating
• Positive pregnancy test
• Positive urine drug screen, urine cotinine test, or alcohol breath test
• Use of tobacco or nicotine products within 1 month prior to Screening
• Significant alcohol consumption
• History of drug abuse within the previous year, or a positive drug screen
• History of allergy to study medications
• Part 1 only: Presence of orthodontic braces or orthodontic retention wires
• Recent participation in a clinical research study
• 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
Experimental: Part 1; ecopipam 89.6 mg on Days 1 and 9 with repeat doses of itraconazole Days 6-16.	Drug: Itraconazole; itraconazole 200 mg QD Days 6 to 16; Drug: Ecopipam; 89.6 mg on Days 1 and 9 for Part 1 or 179.2 mg on Days 1 and 13 for Part 2
Experimental: Part 2; ecopipam 179.2 mg on Days 1 and 13 with repeat doses of rifampicin days 6-20.	Drug: Ecopipam; 89.6 mg on Days 1 and 9 for Part 1 or 179.2 mg on Days 1 and 13 for Part 2; Drug: rifampicin; rifampicin 600 mg QD Days 6 to 20

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC0-inf of ecopipam when administered with itraconazole	Up to 38 samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 21
AUC0-inf of ecopipam when administered without itraconazole	Up to 38 samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 21
AUC0-inf of ecopipam when administered with rifampicin	Up to 38 samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 21
AUC0-inf of ecopipam when administered without rifampicin	Up to 38 samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 21
AUC0-t of ecopipam when administered with itraconazole	Up to 38 samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 21
AUC0-t of ecopipam when administered without itraconazole	Up to 38 samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 21
AUC0-t of ecopipam when administered with rifampicin	Up to 38 samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 21
AUC0-t of ecopipam when administered without rifampicin	Up to 38 samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 21
Cmax of ecopipam when administered with itraconazole	Up to 38 samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 21
Cmax of ecopipam when administered without itraconazole	Up to 38 samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 21
Cmax of ecopipam when administered with rifampicin	Up to 38 samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 21
Cmax of ecopipam when administered without rifampicin	Up to 38 samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 21
T½ el of ecopipam when administered with itraconazole	Up to 38 samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 21
T½ el of ecopipam when administered without itraconazole	Up to 38 samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 21
T½ el of ecopipam when administered with rifampicin	Up to 38 samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 21
T½ el of ecopipam when administered without rifampicin	Up to 38 samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 21

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC0-inf of EBS-101-40853	Up to 38 samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 21
AUC0-inf of ecopipam glucuronide	Up to 38 samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 21
AUC0-inf of EBS-101-40853 glucuronide	Up to 38 samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 21
AUC0-t of EBS-101-40853	Up to 38 samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 21
AUC0-t of ecopipam glucuronide	Up to 38 samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 21
AUC0-t of EBS-101-40853 glucuronide	Up to 38 samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 21
Cmax of EBS-101-40853	Up to 38 samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 21
Cmax of ecopipam glucuronide	Up to 38 samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 21
Cmax of EBS-101-40853 glucuronide	Up to 38 samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 21
T½ el of EBS-101-40853	Up to 38 samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 21
T½ el of ecopipam glucuronide	Up to 38 samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 21
T½ el of EBS-101-40853 glucuronide	Up to 38 samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 21
AUC0-4 for ecopipam	Up to 38 samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 21
AUC0-4 for EBS-101-40853	Up to 38 samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 21
AUC0-4 for ecopipam glucuronide	Up to 38 samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 21
AUC0-4 for EBS 101-40853 glucuronide	Up to 38 samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 21
Minimum Modified Observer's Assessment of Alertness/Sedation (MOAA/S) score	Score from 0-5 where 0 is no response and 5 is responds readily. MOAA/S measures will be recorded at the indicated timepoints	Up to Day 21
AUEC for Visual Analogue Scale (VAS)	Score from 0 - 100 where 0 is not sedated and 100 is very sedated. VAS measures will be recorded at the indicated timepoints.	Up to Day 21
Maximum sedation for Visual Analogue Scale (VAS)	Score from 0 - 100 where 0 is not sedated and 100 is very sedated. VAS measures will be recorded at the indicated timepoints.	Up to Day 21
AUEC for Reaction Time Index (RTI) score	Reaction time for subject to release the response button after presentation of target stimulus.	Up to Day 21
Maximum sedation for Reaction Time Index (RTI) score	Reaction time for subject to release the response button after presentation of target stimulus.	Up to Day 21
Safety and tolerability as demonstrated by AEs with itraconazole	Subjects will be continually monitored for adverse events	Up to Day 30
Safety and tolerability as demonstrated by AEs without itraconazole	Subjects will be continually monitored for adverse events	Up to Day 30
Safety and tolerability as demonstrated by AEs with rifampicin	Subjects will be continually monitored for adverse events	Up to Day 30
Safety and tolerability as demonstrated by AEs without rifampicin	Subjects will be continually monitored for adverse events	Up to Day 30
Safety and tolerability as demonstrated by Systolic blood pressure (SBP) and diastolic blood pressure (DBP) with itraconazole (mmHG)	Blood pressure will be assessed as part of vital signs	Up to Day 21
Safety and tolerability as demonstrated by Systolic blood pressure (SBP) and diastolic blood pressure (DBP) without itraconazole(mmHG)	Blood pressure will be assessed as part of vital signs	Up to Day 21
Safety and tolerability as demonstrated by Systolic blood pressure (SBP) and diastolic blood pressure (DBP) with rifampicin(mmHG)	Blood pressure will be assessed as part of vital signs	Up to Day 21
Safety and tolerability as demonstrated by Systolic blood pressure (SBP) and diastolic blood pressure (DBP) without rifampicin(mmHG)	Blood pressure will be assessed as part of vital signs	Up to Day 21
Heart rate with itraconazole (beats/minute)	Heart rate will be assessed as part of vital signs	Up to Day 21
Heart rate without itraconazole (beats/minute)	Heart rate will be assessed as part of vital signs	Up to Day 21
Heart rate with rifampicin (beats/minute)	Heart rate will be assessed as part of vital signs	Up to Day 21
Heart rate without rifampicin (beats/minute)	Heart rate will be assessed as part of vital signs	Up to Day 21
Respiratory rate pressure with itraconazole (breaths/minute)	Respiratory rate will be assessed as part of vital signs	Up to Day 21
Respiratory rate without itraconazole (breaths/minute)	Respiratory rate will be assessed as part of vital signs	Up to Day 21
Respiratory rate with rifampicin (breaths/minute)	Respiratory rate will be assessed as part of vital signs	Up to Day 21
Respiratory rate without rifampicin (breaths/minute)	Respiratory rate will be assessed as part of vital signs	Up to Day 21
Oral temperature with itraconazole (degrees Celsius)	Temperature will be assessed as part of vital signs	Up to Day 21
Oral temperature without itraconazole (degrees Celsius)	Temperature will be assessed as part of vital signs	Up to Day 21
Oral temperature with rifampicin (degrees Celsius)	Temperature will be assessed as part of vital signs	Up to Day 21
Oral temperature without rifampicin (degrees Celsius)	Temperature will be assessed as part of vital signs	Up to Day 21
Electrocardiogram (ECG) parameters: PR, RR, QRS, QT, and QT interval corrected for heart rate using Fridericia's formula (QTcF) with itraconazole (Milliseconds)	Twelve-lead ECGs will be obtained at the indicated timepoints	Up to Day 21
Electrocardiogram (ECG) parameters: PR, RR, QRS, QT, and QT interval corrected for heart rate using Fridericia's formula (QTcF) without itraconazole (Milliseconds)	Twelve-lead ECGs will be obtained at the indicated timepoints	Up to Day 21
Electrocardiogram (ECG) parameters: PR, RR, QRS, QT, and QT interval corrected for heart rate using Fridericia's formula (QTcF) with rifampicin (Milliseconds)	Twelve-lead ECGs will be obtained at the indicated timepoints	Up to Day 21
Electrocardiogram (ECG) parameters: PR, RR, QRS, QT, and QT interval corrected for heart rate using Fridericia's formula (QTcF) without rifampicin (Milliseconds)	Twelve-lead ECGs will be obtained at the indicated timepoints	Up to Day 21
Safety and tolerability as demonstrated by the Columbia Suicide Severity Rating Scale (C-SSRS)	C-SSRS to be administered at the indicated timepoints	Up to Day 21
Values of white blood cell (WBC), neutrophils, lymphocytes, monocytes, eosinophils, basophils and platelets (1000/mm3)	Blood samples will be collected for the assessment of hematology parameters	Up to Day 21
Value of hematocrit (percent)	Blood samples will be collected for the assessment of hematology parameters	Up to Day 21
Value of hemoglobin (g/dL)	Blood samples will be collected for the assessment of hematology parameters	Up to Day 21
Red blood cell (RBC) count (M/mm3)	Blood samples will be collected for the assessment of hematology parameters	Up to Day 21
Values of sodium, potassium, chloride (mmol/L)	Blood samples will be collected for the assessment of clinical chemistry parameters	Up to Day 21
Values of urea, phosphorus, calcium, glucose, and total, direct and indirect bilirubin (mg/dL)	Blood samples will be collected for the assessment of clinical chemistry parameters	Up to Day 21
Values of albumin and total protein (g/dL)	Blood samples will be collected for the assessment of clinical chemistry parameters	Up to Day 21
Values of alanine aminotransferase (ALT), aspartate aminotransferase (AST),alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), creatininephosphokinase (CPK), and creatinine (U/L)	Blood samples will be collected for the assessment of clinical chemistry parameters	Up to Day 21
Values of urine specific gravity	Urine samples will be collected for the assessment of urine parameters	Up to Day 21
Values of urine pH	Urine samples will be collected for the assessment of urine parameters	Up to Day 21
Values of urine glucose	Urine samples will be collected for the assessment of urine parameters	Up to Day 21
Values of urine protein	Urine samples will be collected for the assessment of urine parameters	Up to Day 21
Values of urine blood	Urine samples will be collected for the assessment of urine parameters	Up to Day 21
Values of urine ketones	Urine samples will be collected for the assessment of urine parameters	Up to Day 21
Values of urine bilirubin and nitrite	Urine samples will be collected for the assessment of urine parameters	Up to Day 21
Values of urobilinogen	Urine samples will be collected for the assessment of urine parameters	Up to Day 21
Values of urine leukocyte esterase by dipstick	Urine samples will be collected for the assessment of urine parameters	Up to Day 21

Collaborators and Investigators

• Sponsor: Emalex Biosciences Inc.
• Collaborators: Syneos Health; Cambridge Cognition Ltd
• Investigators: Study Director: Rick Munschauer, MSc, MD, FAAN, Emalex Biosciences

Study record dates

Study Major Dates

• Study Start (Actual): January 18, 2024
• Primary Completion (Estimated): May 1, 2024
• Study Completion (Estimated): May 1, 2024

Study Registration Dates

• First Submitted: December 22, 2023
• First Submitted That Met QC Criteria: December 22, 2023
• First Posted (Actual): January 8, 2024

Study Record Updates

• Last Update Posted (Actual): April 19, 2024
• Last Update Submitted That Met QC Criteria: April 18, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Central Nervous System Depressants; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Anti-Bacterial Agents; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Dopamine Agents; Dopamine Antagonists; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Leprostatic Agents; Hormone Antagonists; Cytochrome P-450 Enzyme Inducers; Antifungal Agents; Steroid Synthesis Inhibitors; Cytochrome P-450 CYP3A Inducers; Antitubercular Agents; 14-alpha Demethylase Inhibitors; Antibiotics, Antitubercular; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C8 Inducers; Cytochrome P-450 CYP2C19 Inducers; Cytochrome P-450 CYP2C9 Inducers; Rifampin; Itraconazole; Ecopipam
• Other Study ID Numbers: EBS-101-HV-106

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No