Drug Interaction
Conditions
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.
Interventions
DRUGItraconazole
itraconazole 200 mg QD Days 6 to 16
DRUGrifampicin
rifampicin 600 mg QD Days 6 to 20
DRUGEcopipam
89.6 mg on Days 1 and 9 for Part 1 or 179.2 mg on Days 1 and 13 for Part 2
Sponsors
Syneos Health
Cambridge Cognition Ltd
Emalex Biosciences Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
Countries
Canada
Outcome results
None listed