Drug Interaction Study

Drug Interaction Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06194864
• Other study ID #: EBS-101-HV-106
• Status: Recruiting
• Phase: Phase 1
• Start date: January 18, 2024
• Est. completion date: May 2024

Study information

• Verified date: April 2024
• Source: Emalex Biosciences Inc.
• Contact: Emalex Biosciences
• Phone: 312.847.1340
• Email: emalex[@]emalexbiosciences.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: May 2024
• Est. primary completion date: May 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Drug Interaction

Intervention

Drug:
• Itraconazole
itraconazole 200 mg QD Days 6 to 16
• rifampicin
rifampicin 600 mg QD Days 6 to 20
• Ecopipam
89.6 mg on Days 1 and 9 for Part 1 or 179.2 mg on Days 1 and 13 for Part 2

Locations

Country	Name	City	State
Canada	Syneos Health Clinic Inc.	Québec	Quebec

Sponsors (3)

Lead Sponsor	Collaborator
Emalex Biosciences Inc.	Cambridge Cognition Ltd, Syneos Health

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	AUC0-inf of ecopipam glucuronide	Up to 38 samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 21
Secondary	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
Secondary	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
Secondary	AUC0-t of ecopipam glucuronide	Up to 38 samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 21
Secondary	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
Secondary	Cmax of EBS-101-40853	Up to 38 samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 21
Secondary	Cmax of ecopipam glucuronide	Up to 38 samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 21
Secondary	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
Secondary	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
Secondary	T½ el of ecopipam glucuronide	Up to 38 samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 21
Secondary	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
Secondary	AUC0-4 for ecopipam	Up to 38 samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 21
Secondary	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
Secondary	AUC0-4 for ecopipam glucuronide	Up to 38 samples will be collected at the indicated time points for pharmacokinetic analysis	Up to Day 21
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Safety and tolerability as demonstrated by AEs with itraconazole	Subjects will be continually monitored for adverse events	Up to Day 30
Secondary	Safety and tolerability as demonstrated by AEs without itraconazole	Subjects will be continually monitored for adverse events	Up to Day 30
Secondary	Safety and tolerability as demonstrated by AEs with rifampicin	Subjects will be continually monitored for adverse events	Up to Day 30
Secondary	Safety and tolerability as demonstrated by AEs without rifampicin	Subjects will be continually monitored for adverse events	Up to Day 30
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Heart rate with itraconazole (beats/minute)	Heart rate will be assessed as part of vital signs	Up to Day 21
Secondary	Heart rate without itraconazole (beats/minute)	Heart rate will be assessed as part of vital signs	Up to Day 21
Secondary	Heart rate with rifampicin (beats/minute)	Heart rate will be assessed as part of vital signs	Up to Day 21
Secondary	Heart rate without rifampicin (beats/minute)	Heart rate will be assessed as part of vital signs	Up to Day 21
Secondary	Respiratory rate pressure with itraconazole (breaths/minute)	Respiratory rate will be assessed as part of vital signs	Up to Day 21
Secondary	Respiratory rate without itraconazole (breaths/minute)	Respiratory rate will be assessed as part of vital signs	Up to Day 21
Secondary	Respiratory rate with rifampicin (breaths/minute)	Respiratory rate will be assessed as part of vital signs	Up to Day 21
Secondary	Respiratory rate without rifampicin (breaths/minute)	Respiratory rate will be assessed as part of vital signs	Up to Day 21
Secondary	Oral temperature with itraconazole (degrees Celsius)	Temperature will be assessed as part of vital signs	Up to Day 21
Secondary	Oral temperature without itraconazole (degrees Celsius)	Temperature will be assessed as part of vital signs	Up to Day 21
Secondary	Oral temperature with rifampicin (degrees Celsius)	Temperature will be assessed as part of vital signs	Up to Day 21
Secondary	Oral temperature without rifampicin (degrees Celsius)	Temperature will be assessed as part of vital signs	Up to Day 21
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Value of hematocrit (percent)	Blood samples will be collected for the assessment of hematology parameters	Up to Day 21
Secondary	Value of hemoglobin (g/dL)	Blood samples will be collected for the assessment of hematology parameters	Up to Day 21
Secondary	Red blood cell (RBC) count (M/mm3)	Blood samples will be collected for the assessment of hematology parameters	Up to Day 21
Secondary	Values of sodium, potassium, chloride (mmol/L)	Blood samples will be collected for the assessment of clinical chemistry parameters	Up to Day 21
Secondary	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
Secondary	Values of albumin and total protein (g/dL)	Blood samples will be collected for the assessment of clinical chemistry parameters	Up to Day 21
Secondary	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
Secondary	Values of urine specific gravity	Urine samples will be collected for the assessment of urine parameters	Up to Day 21
Secondary	Values of urine pH	Urine samples will be collected for the assessment of urine parameters	Up to Day 21
Secondary	Values of urine glucose	Urine samples will be collected for the assessment of urine parameters	Up to Day 21
Secondary	Values of urine protein	Urine samples will be collected for the assessment of urine parameters	Up to Day 21
Secondary	Values of urine blood	Urine samples will be collected for the assessment of urine parameters	Up to Day 21
Secondary	Values of urine ketones	Urine samples will be collected for the assessment of urine parameters	Up to Day 21
Secondary	Values of urine bilirubin and nitrite	Urine samples will be collected for the assessment of urine parameters	Up to Day 21
Secondary	Values of urobilinogen	Urine samples will be collected for the assessment of urine parameters	Up to Day 21
Secondary	Values of urine leukocyte esterase by dipstick	Urine samples will be collected for the assessment of urine parameters	Up to Day 21