Clinical trial NCT06194864: Drug Interaction Study
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Drug Interaction
Lead sponsor: Emalex Biosciences Inc.
Sponsor class: INDUSTRY
Collaborators: name: Syneos Health
name: Cambridge Cognition Ltd
First posted: 2024-01-08
Enrollment: 45
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, 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.


Eligibility criteria: 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

Primary outcomes:
measure: AUC0-inf of ecopipam when administered with itraconazole
timeFrame: Up to Day 21
measure: AUC0-inf of ecopipam when administered without itraconazole
timeFrame: Up to Day 21
measure: AUC0-inf of ecopipam when administered with rifampicin
timeFrame: Up to Day 21
measure: AUC0-inf of ecopipam when administered without rifampicin
timeFrame: Up to Day 21
measure: AUC0-t of ecopipam when administered with itraconazole
timeFrame: Up to Day 21
measure: AUC0-t of ecopipam when administered without itraconazole
timeFrame: Up to Day 21
measure: AUC0-t of ecopipam when administered with rifampicin
timeFrame: Up to Day 21
measure: AUC0-t of ecopipam when administered without rifampicin
timeFrame: Up to Day 21
measure: Cmax of ecopipam when administered with itraconazole
timeFrame: Up to Day 21
measure: Cmax of ecopipam when administered without itraconazole
timeFrame: Up to Day 21
measure: Cmax of ecopipam when administered with rifampicin
timeFrame: Up to Day 21
measure: Cmax of ecopipam when administered without rifampicin
timeFrame: Up to Day 21
measure: T½ el of ecopipam when administered with itraconazole
timeFrame: Up to Day 21
measure: T½ el of ecopipam when administered without itraconazole
timeFrame: Up to Day 21
measure: T½ el of ecopipam when administered with rifampicin
timeFrame: Up to Day 21
measure: T½ el of ecopipam when administered without rifampicin
timeFrame: Up to Day 21
Secondary outcomes:
measure: AUC0-inf of EBS-101-40853
timeFrame: Up to Day 21
measure: AUC0-inf of ecopipam glucuronide
timeFrame: Up to Day 21
measure: AUC0-inf of EBS-101-40853 glucuronide
timeFrame: Up to Day 21
measure: AUC0-t of EBS-101-40853
timeFrame: Up to Day 21
measure: AUC0-t of ecopipam glucuronide
timeFrame: Up to Day 21
measure: AUC0-t of EBS-101-40853 glucuronide
timeFrame: Up to Day 21
measure: Cmax of EBS-101-40853
timeFrame: Up to Day 21
measure: Cmax of ecopipam glucuronide
timeFrame: Up to Day 21
measure: Cmax of EBS-101-40853 glucuronide
timeFrame: Up to Day 21
measure: T½ el of EBS-101-40853
timeFrame: Up to Day 21
measure: T½ el of ecopipam glucuronide
timeFrame: Up to Day 21
measure: T½ el of EBS-101-40853 glucuronide
timeFrame: Up to Day 21
measure: AUC0-4 for ecopipam
timeFrame: Up to Day 21
measure: AUC0-4 for EBS-101-40853
timeFrame: Up to Day 21
measure: AUC0-4 for ecopipam glucuronide
timeFrame: Up to Day 21
measure: AUC0-4 for EBS 101-40853 glucuronide
timeFrame: Up to Day 21
measure: Minimum Modified Observer's Assessment of Alertness/Sedation (MOAA/S) score
timeFrame: Up to Day 21
measure: AUEC for Visual Analogue Scale (VAS)
timeFrame: Up to Day 21
measure: Maximum sedation for Visual Analogue Scale (VAS)
timeFrame: Up to Day 21
measure: AUEC for Reaction Time Index (RTI) score
timeFrame: Up to Day 21
measure: Maximum sedation for Reaction Time Index (RTI) score
timeFrame: Up to Day 21
measure: Safety and tolerability as demonstrated by AEs with itraconazole
timeFrame: Up to Day 30
measure: Safety and tolerability as demonstrated by AEs without itraconazole
timeFrame: Up to Day 30
measure: Safety and tolerability as demonstrated by AEs with rifampicin
timeFrame: Up to Day 30
measure: Safety and tolerability as demonstrated by AEs without rifampicin
timeFrame: Up to Day 30
measure: Safety and tolerability as demonstrated by Systolic blood pressure (SBP) and diastolic blood pressure (DBP) with itraconazole (mmHG)
timeFrame: Up to Day 21
measure: Safety and tolerability as demonstrated by Systolic blood pressure (SBP) and diastolic blood pressure (DBP) without itraconazole(mmHG)
timeFrame: Up to Day 21
measure: Safety and tolerability as demonstrated by Systolic blood pressure (SBP) and diastolic blood pressure (DBP) with rifampicin(mmHG)
timeFrame: Up to Day 21
measure: Safety and tolerability as demonstrated by Systolic blood pressure (SBP) and diastolic blood pressure (DBP) without rifampicin(mmHG)
timeFrame: Up to Day 21
measure: Heart rate with itraconazole (beats/minute)
timeFrame: Up to Day 21
measure: Heart rate without itraconazole (beats/minute)
timeFrame: Up to Day 21
measure: Heart rate with rifampicin (beats/minute)
timeFrame: Up to Day 21
measure: Heart rate without rifampicin (beats/minute)
timeFrame: Up to Day 21
measure: Respiratory rate pressure with itraconazole (breaths/minute)
timeFrame: Up to Day 21
measure: Respiratory rate without itraconazole (breaths/minute)
timeFrame: Up to Day 21
measure: Respiratory rate with rifampicin (breaths/minute)
timeFrame: Up to Day 21
measure: Respiratory rate without rifampicin (breaths/minute)
timeFrame: Up to Day 21
measure: Oral temperature with itraconazole (degrees Celsius)
timeFrame: Up to Day 21
measure: Oral temperature without itraconazole (degrees Celsius)
timeFrame: Up to Day 21
measure: Oral temperature with rifampicin (degrees Celsius)
timeFrame: Up to Day 21
measure: Oral temperature without rifampicin (degrees Celsius)
timeFrame: Up to Day 21
measure: Electrocardiogram (ECG) parameters: PR, RR, QRS, QT, and QT interval corrected for heart rate using Fridericia's formula (QTcF) with itraconazole (Milliseconds)
timeFrame: Up to Day 21
measure: Electrocardiogram (ECG) parameters: PR, RR, QRS, QT, and QT interval corrected for heart rate using Fridericia's formula (QTcF) without itraconazole (Milliseconds)
timeFrame: Up to Day 21
measure: Electrocardiogram (ECG) parameters: PR, RR, QRS, QT, and QT interval corrected for heart rate using Fridericia's formula (QTcF) with rifampicin (Milliseconds)
timeFrame: Up to Day 21
measure: Electrocardiogram (ECG) parameters: PR, RR, QRS, QT, and QT interval corrected for heart rate using Fridericia's formula (QTcF) without rifampicin (Milliseconds)
timeFrame: Up to Day 21
measure: Safety and tolerability as demonstrated by the Columbia Suicide Severity Rating Scale (C-SSRS)
timeFrame: Up to Day 21
measure: Values of white blood cell (WBC), neutrophils, lymphocytes, monocytes, eosinophils, basophils and platelets (1000/mm3)
timeFrame: Up to Day 21
measure: Value of hematocrit (percent)
timeFrame: Up to Day 21
measure: Value of hemoglobin (g/dL)
timeFrame: Up to Day 21
measure: Red blood cell (RBC) count (M/mm3)
timeFrame: Up to Day 21
measure: Values of sodium, potassium, chloride (mmol/L)
timeFrame: Up to Day 21
measure: Values of urea, phosphorus, calcium, glucose, and total, direct and indirect bilirubin (mg/dL)
timeFrame: Up to Day 21
measure: Values of albumin and total protein (g/dL)
timeFrame: Up to Day 21
measure: Values of alanine aminotransferase (ALT), aspartate aminotransferase (AST),alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), creatininephosphokinase (CPK), and creatinine (U/L)
timeFrame: Up to Day 21
measure: Values of urine specific gravity
timeFrame: Up to Day 21
measure: Values of urine pH
timeFrame: Up to Day 21
measure: Values of urine glucose
timeFrame: Up to Day 21
measure: Values of urine protein
timeFrame: Up to Day 21
measure: Values of urine blood
timeFrame: Up to Day 21
measure: Values of urine ketones
timeFrame: Up to Day 21
measure: Values of urine bilirubin and nitrite
timeFrame: Up to Day 21
measure: Values of urobilinogen
timeFrame: Up to Day 21
measure: Values of urine leukocyte esterase by dipstick
timeFrame: Up to Day 21
Other outcomes:
Locations:
city: Québec
country: Canada
facility: Syneos Health Clinic Inc.
state: Quebec
Study officials:
affiliation: Emalex Biosciences
name: Rick Munschauer, MSc, MD, FAAN
role: STUDY_DIRECTOR
References: