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
| Registry | NCT06194864 |
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| Status | Completed |
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| Phase | Phase 1 |
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| Study type | Interventional; non randomized, parallel, masking: none, basic science |
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| Enrollment | 45 (Actual) |
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| Sponsor | Emalex Biosciences Inc. (Industry); collaborators: Syneos Health, Cambridge Cognition Ltd |
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| Conditions | Drug Interaction |
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| Interventions | Itraconazole, rifampicin, Ecopipam (Drug) |
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| Dates | start 2024-01-18, primary completion 2024-05-14, completion 2024-05-22, first posted 2024-01-08, last updated 2024-09-19 |
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| Locations | 1 site in Canada |
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Related Papers Related Patents Related Grants Related Experts
All trials for Drug Interaction All trials of Itraconazole All trials of rifampicin
-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.
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+Arms and interventions
| Arm | Type | Interventions | Description |
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| Part 1 | Experimental | Drug: Itraconazole; Drug: Ecopipam | ecopipam 89.6 mg on Days 1 and 9 with repeat doses of itraconazole Days 6-16. |
| Part 2 | Experimental | Drug: rifampicin; Drug: Ecopipam | ecopipam 179.2 mg on Days 1 and 13 with repeat doses of rifampicin days 6-20. |
- Itraconazole (Drug): itraconazole 200 mg QD Days 6 to 16
- rifampicin (Drug): rifampicin 600 mg QD Days 6 to 20
- Ecopipam (Drug): 89.6 mg on Days 1 and 9 for Part 1 or 179.2 mg on Days 1 and 13 for Part 2
+Outcome measures
Primary outcomes
- AUC0-inf of ecopipam when administered with itraconazole [Up to Day 21]: Up to 38 samples will be collected at the indicated time points for pharmacokinetic analysis
- AUC0-inf of ecopipam when administered without itraconazole [Up to Day 21]: Up to 38 samples will be collected at the indicated time points for pharmacokinetic analysis
- AUC0-inf of ecopipam when administered with rifampicin [Up to Day 21]: Up to 38 samples will be collected at the indicated time points for pharmacokinetic analysis
- AUC0-inf of ecopipam when administered without rifampicin [Up to Day 21]: Up to 38 samples will be collected at the indicated time points for pharmacokinetic analysis
- AUC0-t of ecopipam when administered with itraconazole [Up to Day 21]: Up to 38 samples will be collected at the indicated time points for pharmacokinetic analysis
- AUC0-t of ecopipam when administered without itraconazole [Up to Day 21]: Up to 38 samples will be collected at the indicated time points for pharmacokinetic analysis
- AUC0-t of ecopipam when administered with rifampicin [Up to Day 21]: Up to 38 samples will be collected at the indicated time points for pharmacokinetic analysis
- AUC0-t of ecopipam when administered without rifampicin [Up to Day 21]: Up to 38 samples will be collected at the indicated time points for pharmacokinetic analysis
- Cmax of ecopipam when administered with itraconazole [Up to Day 21]: Up to 38 samples will be collected at the indicated time points for pharmacokinetic analysis
- Cmax of ecopipam when administered without itraconazole [Up to Day 21]: Up to 38 samples will be collected at the indicated time points for pharmacokinetic analysis
- Cmax of ecopipam when administered with rifampicin [Up to Day 21]: Up to 38 samples will be collected at the indicated time points for pharmacokinetic analysis
- Cmax of ecopipam when administered without rifampicin [Up to Day 21]: Up to 38 samples will be collected at the indicated time points for pharmacokinetic analysis
- T½ el of ecopipam when administered with itraconazole [Up to Day 21]: Up to 38 samples will be collected at the indicated time points for pharmacokinetic analysis
- T½ el of ecopipam when administered without itraconazole [Up to Day 21]: Up to 38 samples will be collected at the indicated time points for pharmacokinetic analysis
- T½ el of ecopipam when administered with rifampicin [Up to Day 21]: Up to 38 samples will be collected at the indicated time points for pharmacokinetic analysis
- T½ el of ecopipam when administered without rifampicin [Up to Day 21]: Up to 38 samples will be collected at the indicated time points for pharmacokinetic analysis
Secondary outcomes
- AUC0-inf of EBS-101-40853 [Up to Day 21]: Up to 38 samples will be collected at the indicated time points for pharmacokinetic analysis
- AUC0-inf of ecopipam glucuronide [Up to Day 21]: Up to 38 samples will be collected at the indicated time points for pharmacokinetic analysis
- AUC0-inf of EBS-101-40853 glucuronide [Up to Day 21]: Up to 38 samples will be collected at the indicated time points for pharmacokinetic analysis
- AUC0-t of EBS-101-40853 [Up to Day 21]: Up to 38 samples will be collected at the indicated time points for pharmacokinetic analysis
- AUC0-t of ecopipam glucuronide [Up to Day 21]: Up to 38 samples will be collected at the indicated time points for pharmacokinetic analysis
- AUC0-t of EBS-101-40853 glucuronide [Up to Day 21]: Up to 38 samples will be collected at the indicated time points for pharmacokinetic analysis
- Cmax of EBS-101-40853 [Up to Day 21]: Up to 38 samples will be collected at the indicated time points for pharmacokinetic analysis
- Cmax of ecopipam glucuronide [Up to Day 21]: Up to 38 samples will be collected at the indicated time points for pharmacokinetic analysis
- Cmax of EBS-101-40853 glucuronide [Up to Day 21]: Up to 38 samples will be collected at the indicated time points for pharmacokinetic analysis
- T½ el of EBS-101-40853 [Up to Day 21]: Up to 38 samples will be collected at the indicated time points for pharmacokinetic analysis
- T½ el of ecopipam glucuronide [Up to Day 21]: Up to 38 samples will be collected at the indicated time points for pharmacokinetic analysis
- T½ el of EBS-101-40853 glucuronide [Up to Day 21]: Up to 38 samples will be collected at the indicated time points for pharmacokinetic analysis
- AUC0-4 for ecopipam [Up to Day 21]: Up to 38 samples will be collected at the indicated time points for pharmacokinetic analysis
- AUC0-4 for EBS-101-40853 [Up to Day 21]: Up to 38 samples will be collected at the indicated time points for pharmacokinetic analysis
- AUC0-4 for ecopipam glucuronide [Up to Day 21]: Up to 38 samples will be collected at the indicated time points for pharmacokinetic analysis
- AUC0-4 for EBS 101-40853 glucuronide [Up to Day 21]: Up to 38 samples will be collected at the indicated time points for pharmacokinetic analysis
- Minimum Modified Observer's Assessment of Alertness/Sedation (MOAA/S) score [Up to Day 21]: Score from 0-5 where 0 is no response and 5 is responds readily. MOAA/S measures will be recorded at the indicated timepoints
- AUEC for Visual Analogue Scale (VAS) [Up to Day 21]: Score from 0 - 100 where 0 is not sedated and 100 is very sedated. VAS measures will be recorded at the indicated timepoints.
- Maximum sedation for Visual Analogue Scale (VAS) [Up to Day 21]: Score from 0 - 100 where 0 is not sedated and 100 is very sedated. VAS measures will be recorded at the indicated timepoints.
- AUEC for Reaction Time Index (RTI) score [Up to Day 21]: Reaction time for subject to release the response button after presentation of target stimulus.
- Maximum sedation for Reaction Time Index (RTI) score [Up to Day 21]: Reaction time for subject to release the response button after presentation of target stimulus.
- Safety and tolerability as demonstrated by AEs with itraconazole [Up to Day 30]: Subjects will be continually monitored for adverse events
- Safety and tolerability as demonstrated by AEs without itraconazole [Up to Day 30]: Subjects will be continually monitored for adverse events
- Safety and tolerability as demonstrated by AEs with rifampicin [Up to Day 30]: Subjects will be continually monitored for adverse events
- Safety and tolerability as demonstrated by AEs without rifampicin [Up to Day 30]: Subjects will be continually monitored for adverse events
- Safety and tolerability as demonstrated by Systolic blood pressure (SBP) and diastolic blood pressure (DBP) with itraconazole (mmHG) [Up to Day 21]: Blood pressure will be assessed as part of vital signs
- Safety and tolerability as demonstrated by Systolic blood pressure (SBP) and diastolic blood pressure (DBP) without itraconazole(mmHG) [Up to Day 21]: Blood pressure will be assessed as part of vital signs
- Safety and tolerability as demonstrated by Systolic blood pressure (SBP) and diastolic blood pressure (DBP) with rifampicin(mmHG) [Up to Day 21]: Blood pressure will be assessed as part of vital signs
- Safety and tolerability as demonstrated by Systolic blood pressure (SBP) and diastolic blood pressure (DBP) without rifampicin(mmHG) [Up to Day 21]: Blood pressure will be assessed as part of vital signs
- Heart rate with itraconazole (beats/minute) [Up to Day 21]: Heart rate will be assessed as part of vital signs
- Heart rate without itraconazole (beats/minute) [Up to Day 21]: Heart rate will be assessed as part of vital signs
- Heart rate with rifampicin (beats/minute) [Up to Day 21]: Heart rate will be assessed as part of vital signs
- Heart rate without rifampicin (beats/minute) [Up to Day 21]: Heart rate will be assessed as part of vital signs
- Respiratory rate pressure with itraconazole (breaths/minute) [Up to Day 21]: Respiratory rate will be assessed as part of vital signs
- Respiratory rate without itraconazole (breaths/minute) [Up to Day 21]: Respiratory rate will be assessed as part of vital signs
- Respiratory rate with rifampicin (breaths/minute) [Up to Day 21]: Respiratory rate will be assessed as part of vital signs
- Respiratory rate without rifampicin (breaths/minute) [Up to Day 21]: Respiratory rate will be assessed as part of vital signs
- Oral temperature with itraconazole (degrees Celsius) [Up to Day 21]: Temperature will be assessed as part of vital signs
- Oral temperature without itraconazole (degrees Celsius) [Up to Day 21]: Temperature will be assessed as part of vital signs
- Oral temperature with rifampicin (degrees Celsius) [Up to Day 21]: Temperature will be assessed as part of vital signs
- Oral temperature without rifampicin (degrees Celsius) [Up to Day 21]: Temperature will be assessed as part of vital signs
- Electrocardiogram (ECG) parameters: PR, RR, QRS, QT, and QT interval corrected for heart rate using Fridericia's formula (QTcF) with itraconazole (Milliseconds) [Up to Day 21]: Twelve-lead ECGs will be obtained at the indicated timepoints
- Electrocardiogram (ECG) parameters: PR, RR, QRS, QT, and QT interval corrected for heart rate using Fridericia's formula (QTcF) without itraconazole (Milliseconds) [Up to Day 21]: Twelve-lead ECGs will be obtained at the indicated timepoints
- Electrocardiogram (ECG) parameters: PR, RR, QRS, QT, and QT interval corrected for heart rate using Fridericia's formula (QTcF) with rifampicin (Milliseconds) [Up to Day 21]: Twelve-lead ECGs will be obtained at the indicated timepoints
- Electrocardiogram (ECG) parameters: PR, RR, QRS, QT, and QT interval corrected for heart rate using Fridericia's formula (QTcF) without rifampicin (Milliseconds) [Up to Day 21]: Twelve-lead ECGs will be obtained at the indicated timepoints
- Safety and tolerability as demonstrated by the Columbia Suicide Severity Rating Scale (C-SSRS) [Up to Day 21]: C-SSRS to be administered at the indicated timepoints
- Values of white blood cell (WBC), neutrophils, lymphocytes, monocytes, eosinophils, basophils and platelets (1000/mm3) [Up to Day 21]: Blood samples will be collected for the assessment of hematology parameters
- Value of hematocrit (percent) [Up to Day 21]: Blood samples will be collected for the assessment of hematology parameters
- Value of hemoglobin (g/dL) [Up to Day 21]: Blood samples will be collected for the assessment of hematology parameters
- Red blood cell (RBC) count (M/mm3) [Up to Day 21]: Blood samples will be collected for the assessment of hematology parameters
- Values of sodium, potassium, chloride (mmol/L) [Up to Day 21]: Blood samples will be collected for the assessment of clinical chemistry parameters
- Values of urea, phosphorus, calcium, glucose, and total, direct and indirect bilirubin (mg/dL) [Up to Day 21]: Blood samples will be collected for the assessment of clinical chemistry parameters
- Values of albumin and total protein (g/dL) [Up to Day 21]: Blood samples will be collected for the assessment of clinical chemistry parameters
- Values of alanine aminotransferase (ALT), aspartate aminotransferase (AST),alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), creatininephosphokinase (CPK), and creatinine (U/L) [Up to Day 21]: Blood samples will be collected for the assessment of clinical chemistry parameters
- Values of urine specific gravity [Up to Day 21]: Urine samples will be collected for the assessment of urine parameters
- Values of urine pH [Up to Day 21]: Urine samples will be collected for the assessment of urine parameters
- Values of urine glucose [Up to Day 21]: Urine samples will be collected for the assessment of urine parameters
- Values of urine protein [Up to Day 21]: Urine samples will be collected for the assessment of urine parameters
- Values of urine blood [Up to Day 21]: Urine samples will be collected for the assessment of urine parameters
- Values of urine ketones [Up to Day 21]: Urine samples will be collected for the assessment of urine parameters
- Values of urine bilirubin and nitrite [Up to Day 21]: Urine samples will be collected for the assessment of urine parameters
- Values of urobilinogen [Up to Day 21]: Urine samples will be collected for the assessment of urine parameters
- Values of urine leukocyte esterase by dipstick [Up to Day 21]: Urine samples will be collected for the assessment of urine parameters
+Eligibility
Sex: All, ages: 18 Years to 55 Years, accepts healthy volunteers
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
+Locations (1)
| Facility | City | Country | Status |
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| Syneos Health Clinic Inc. | Québec, Quebec | Canada | |
+Investigators