Thorough QT/QTc Study to Evaluate the Effects of Ecopipam (EBS-101) on Cardiac Repolarization

Study Overview
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Brief Summary
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THOROUGH QT/QTc STUDY TO EVALUATE THE EFFECTS OF ECOPIPAM (EBS-101) ON CARDIAC REPOLARIZATION

Detailed Description
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This is a single-center, randomized, partially double-blind (open-label moxifloxacin), placebo- and positive-controlled, 4-way crossover study in healthy subjects. Following a 28 day screening period, eligible subjects will enter the clinical research unit (CRU) on Day -1. A total of 32 subjects will be randomized in a 1:1:1:1 ratio to 1 of 4 treatment sequences (8 subjects per treatment sequence). Subjects will receive the assigned study drug as a single oral dose in the morning on Day 1 of each treatment period (Day 1 [Period 1], Day 8 [Period 2], Day 15 [Period 3], and Day 22 [Period 4]) after an overnight fast. Subjects will have serially matched blood samples (for determination of plasma concentrations) and 12-lead ECGs collected at predose and up to 48 hours after each dose for C QTc analysis. Subjects will be discharged from the CRU 96 hours after the last dose of the study drug (Day 26). A follow-up telephone call will occur 5 ±2 days after discharge (Day 31 ±2).

Official Title
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A Randomized, Double-Blind, Placebo- and Positive Controlled, Crossover, Thorough QT/QTc Study to Evaluate the Effects of a Therapeutic and Supratherapeutic Dose of Ecopipam (EBS-101) on Cardiac Repolarization in Healthy Subjects

Conditions
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QT/QTc

Intervention / Treatment
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* Drug: Ecopipam Hydrochloride
* Drug: Moxifloxacin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female of nonchildbearing potential 18 to 55 years of age BMI of 18 to 30 kg/m2, and weight of at least 50 kg for males and 45 kg for females. Subject considered by the investigator to be in good general health as determined by medical history, clinical laboratory test results, vital sign measurements, 12-lead ECG results, and PE findings. Male subjects with female partners of childbearing potential must agree to use a double-barrier method of contraception during the study and agree to continue the use of male contraception for at least 90 days after the last dose of study drug. Male subjects must be willing to refrain from donating sperm during study participation and for 90 days after the last dose of study drug. The subject is able to provide written informed consent and agrees to comply with all protocol requirements. Exclusion Criteria: Female subjects of childbearing potential or who are currently pregnant or lactating Subjects with a history of significant medical illness Clinically significant abnormalities on screening tests/exams History of or serious risk of committing suicide Donation of plasma within 7 days prior to dosing Donation of significant loss of blood within 30 days prior to dosing Major surgery within 3 months or minor surgery within 1 month prior to CRU admission Use of prohibited prescription, over-the-counter medications or natural health products Alcohol-based products within 24 hours prior to check-in on Day -1 Vaccinations within 72 hours prior to check-in on Day -1 Subjects with a history of any clinically significant ECG or vital sign abnormalities or presence of any clinically significant ECG or vital sign abnormalities or changes at screening or on Day -1 Positive test result for drugs of abuse, alcohol, or cotinine Use of nicotine or nicotine-containing products within 90 days before the first dose of study drug. Subjects with a history of excessive alcohol intake or abuse or drug addiction within the last year Subjects with a history of allergy, allergic skin rash, asthma, or an intolerance, sensitivity, or photosensitivity to moxifloxacin or ecopipam Subjects who have participated in a clinical research study involving the administration of an investigational or marketed drug or device within 30 days prior to the first dose or administration of a biological product in the context of a clinical research study within 90 days prior to the first dose Subjects with prior exposure to ecopipam Any subject who, in the opinion of the investigator, is not a suitable candidate for the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 200 mg ecopipam HCL<br>Single 200 mg dose of ecopipam HCL given as 2 x 100 mg ecopipam HCL oral tablets and 4 placebo oral tablets | Drug: Ecopipam Hydrochloride<br>* oral tablets<br>Drug: Placebo<br>* oral tablet<br>|
| Experimental: 600 mg ecopipam HCL<br>Single 600 mg dose of ecopipam HCL given as 6 x 100 mg ecopipam HCL oral tablets | Drug: Ecopipam Hydrochloride<br>* oral tablets<br>|
| Active Comparator: 400 mg moxifloxacin<br>Single 400 mg dose of moxifloxacin given as 1 x 400 mg oral tablet | Drug: Moxifloxacin<br>* oral tablet<br>|
| Placebo Comparator: Placebo<br>Single oral dose of 6 x placebo tablets | Drug: Placebo<br>* oral tablet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate ecopipam's effect on the QTc interval after administration of therapeutic and supratherapeutic doses, compared to placebo as a negative control using C-QTc analysis. | ECGs and PK samples will be collected for up to 96 hours after each dose | Up to Day 25 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the effect of ecopipam at a therapeutic dose on heart rate | ECGs will be collected for up to 48 hours after each dose | Up to Day 25 | 
| Evaluate the effect of ecopipam at a therapeutic dose on PR interval | ECGs will be collected for up to 48 hours after each dose | Up to Day 25 | 
| Evaluate the effect of ecopipam at a therapeutic dose on QRS interval | ECGs will be collected for up to 48 hours after each dose | Up to Day 25 | 
| Evaluate the effect of ecopipam at a therapeutic dose on T-wave morphology | ECGs will be collected for up to 48 hours after each dose | Up to Day 25 | 
| Evaluate the effect of ecopipam at a therapeutic dose on U wave presence | ECGs will be collected for up to 48 hours after each dose | Up to Day 25 | 
| Evaluate the effect of ecopipam at supratherapeutic dose on heart rate | ECGs will be collected for up to 48 hours after each dose | Up to Day 25 | 
| Evaluate the effect of ecopipam at supratherapeutic dose on PR interval | ECGs will be collected for up to 48 hours after each dose | Up to Day 25 | 
| Evaluate the effect of ecopipam at supratherapeutic dose on QRS interval | ECGs will be collected for up to 48 hours after each dose | Up to Day 25 | 
| Evaluate the effect of ecopipam at supratherapeutic dose on T-wave morphology | ECGs will be collected for up to 48 hours after each dose | Up to Day 25 | 
| Evaluate the effect of ecopipam at supratherapeutic dose on U wave presence | ECGs will be collected for up to 48 hours after each dose | Up to Day 25 | 
| Evaluate the ECG assay sensitivity to detect a change in the QT interval corrected for heart rate using Fridericia's formula (QTcF interval) using 400 mg moxifloxacin as the positive control | ECGs will be collected for up to 48 hours after each dose | Up to Day 25 | 
| Evaluate the effects of ecopipam on the emergence of arrhythmias | ECGs will be collected for up to 48 hours after each dose | Up to Day 25 | 
| Describe the incidence of treatment-emergent adverse events after a single therapeutic dose of ecopipam | AEs will be collected throughout the duration of the study | Up to Day 33 | 
| Describe the incidence of treatment-emergent adverse events after a single supratherapeutic dose of ecopipam | AEs will be collected throughout the duration of the study | Up to Day 33 | 
| Describe the incidence of treatment-emergent adverse events after a single dose of moxifloxacin 400 mg | AEs will be collected throughout the duration of the study | Up to Day 33 | 
| Describe the Cmax of ecopipam after single therapeutic dose of ecopipam | 17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis | Up to Day 33 | 
| Describe the Tmax of ecopipam after single therapeutic dose of ecopipam | 17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis | Up to Day 33 | 
| Describe the AUClast of ecopipam after single therapeutic dose of ecopipam | 17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis | Up to Day 33 | 
| Describe the AUCinf of ecopipam after single therapeutic dose of ecopipam | 17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis | Up to Day 33 | 
| Describe the AUCext of ecopipam after single therapeutic dose of ecopipam | 17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis | Up to Day 33 | 
| Describe the λz of ecopipam after single therapeutic dose of ecopipam | 17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis | Up to Day 33 | 
| Describe the t1/2 of ecopipam after single therapeutic dose of ecopipam | 17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis | Up to Day 33 | 
| Describe the Cmax of ecopipam after single supratherapeutic dose of ecopipam | 17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis | Up to Day 33 | 
| Describe the Tmax of ecopipam after single supratherapeutic dose of ecopipam | 17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis | Up to Day 33 | 
| Describe the AUClast of ecopipam after single supratherapeutic dose of ecopipam | 17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis | Up to Day 33 | 
| Describe the AUCinf of ecopipam after single supratherapeutic dose of ecopipam | 17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis | Up to Day 33 | 
| Describe the AUCext of ecopipam after single supratherapeutic dose of ecopipam | 17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis | Up to Day 33 | 
| Describe the λz of ecopipam after single supratherapeutic dose of ecopipam | 17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis | Up to Day 33 | 
| Describe the t1/2 of ecopipam after single supratherapeutic dose of ecopipam | 17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis | Up to Day 33 | 
| Describe the Cmax of EBS-101-40853 after single therapeutic dose of ecopipam | 17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis | Up to Day 33 | 
| Describe the Tmax of EBS-101-40853 after single therapeutic dose of ecopipam | 17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis | Up to Day 33 | 
| Describe the AUClast of EBS-101-40853 after single therapeutic dose of ecopipam | 17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis | Up to Day 33 | 
| Describe the AUCinf of EBS-101-40853 after single therapeutic dose of ecopipam | 17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis | Up to Day 33 | 
| Describe the AUCext of EBS-101-40853 after single therapeutic dose of ecopipam | 17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis | Up to Day 33 | 
| Describe the λz of EBS-101-40853 after single therapeutic dose of ecopipam | 17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis | Up to Day 33 | 
| Describe the t1/2 of EBS-101-40853 after single therapeutic dose of ecopipam | 17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis | Up to Day 33 | 
| Describe the Cmax of EBS-101-40853 after single supratherapeutic dose of ecopipam | 17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis | Up to Day 33 | 
| Describe the Tmax of EBS-101-40853 after single supratherapeutic dose of ecopipam | 17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis | Up to Day 33 | 
| Describe the AUClast of EBS-101-40853 after single supratherapeutic dose of ecopipam | 17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis | Up to Day 33 | 
| Describe the AUCinf of EBS-101-40853 after single supratherapeutic dose of ecopipam | 17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis | Up to Day 33 | 
| Describe the AUCext of EBS-101-40853 after single supratherapeutic dose of ecopipam | 17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis | Up to Day 33 | 
| Describe the λz of EBS-101-40853 after single supratherapeutic dose of ecopipam | 17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis | Up to Day 33 | 
| Describe the t1/2 of EBS-101-40853 after single supratherapeutic dose of ecopipam | 17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis | Up to Day 33 | 
| Describe the Cmax of ecopipam glucuronide after single therapeutic dose of ecopipam | 17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis | Up to Day 33 | 
| Describe the Tmax of ecopipam glucuronide after single therapeutic dose of ecopipam | 17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis | Up to Day 33 | 
| Describe the AUClast of ecopipam glucuronide after single therapeutic dose of ecopipam | 17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis | Up to Day 33 | 
| Describe the AUCinf of ecopipam glucuronide after single therapeutic dose of ecopipam | 17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis | Up to Day 33 | 
| Describe the AUCext of ecopipam glucuronide after single therapeutic dose of ecopipam | 17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis | Up to Day 33 | 
| Describe the λz of ecopipam glucuronide after single therapeutic dose of ecopipam | 17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis | Up to Day 33 | 
| Describe the t1/2 of ecopipam glucuronide after single therapeutic dose of ecopipam | 17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis | Up to Day 33 | 
| Describe the Cmax of ecopipam glucuronide after single supratherapeutic dose of ecopipam | 17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis | Up to Day 33 | 
| Describe the Tmax of ecopipam glucuronide after single supratherapeutic dose of ecopipam | 17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis | Up to Day 33 | 
| Describe the AUClast of ecopipam glucuronide after single supratherapeutic dose of ecopipam | 17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis | Up to Day 33 | 
| Describe the AUCinf of ecopipam glucuronide after single supratherapeutic dose of ecopipam | 17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis | Up to Day 33 | 
| Describe the AUCext of ecopipam glucuronide after single supratherapeutic dose of ecopipam | 17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis | Up to Day 33 | 
| Describe the λz of ecopipam glucuronide after single supratherapeutic dose of ecopipam | 17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis | Up to Day 33 | 
| Describe the t1/2 of ecopipam glucuronide after single supratherapeutic dose of ecopipam | 17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis | Up to Day 33 | 
| Describe the Cmax of EBS-101-40853 glucuronide after single therapeutic dose of ecopipam | 17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis | Up to Day 33 | 
| Describe the Tmax of EBS-101-40853 glucuronide after single therapeutic dose of ecopipam | 17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis | Up to Day 33 | 
| Describe the AUClast of EBS-101-40853 glucuronide after single therapeutic dose of ecopipam | 17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis | Up to Day 33 | 
| Describe the AUCinf of EBS-101-40853 glucuronide after single therapeutic dose of ecopipam | 17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis | Up to Day 33 | 
| Describe the AUCext of EBS-101-40853 glucuronide after single therapeutic dose of ecopipam | 17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis | Up to Day 33 | 
| Describe the λz of EBS-101-40853 glucuronide after single therapeutic dose of ecopipam | 17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis | Up to Day 33 | 
| Describe the t1/2 of EBS-101-40853 glucuronide after single therapeutic dose of ecopipam | 17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis | Up to Day 33 | 
| Describe the Cmax of EBS-101-40853 glucuronide after single supratherapeutic dose of ecopipam | 17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis | Up to Day 33 | 
| Describe the Tmax of EBS-101-40853 glucuronide after single supratherapeutic dose of ecopipam | 17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis | Up to Day 33 | 
| Describe the AUClast of EBS-101-40853 glucuronide after single supratherapeutic dose of ecopipam | 17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis | Up to Day 33 | 
| Describe the AUCinf of EBS-101-40853 glucuronide after single supratherapeutic dose of ecopipam | 17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis | Up to Day 33 | 
| Describe the AUCext of EBS-101-40853 glucuronide after single supratherapeutic dose of ecopipam | 17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis | Up to Day 33 | 
| Describe the λz of EBS-101-40853 glucuronide after single supratherapeutic dose of ecopipam | 17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis | Up to Day 33 | 
| Describe the t1/2 of EBS-101-40853 glucuronide after single supratherapeutic dose of ecopipam | 17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis | Up to Day 33 | 
| Describe the Cmax of moxifloxacin after a single dose of moxifloxacin 400 mg | 17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis | Up to Day 33 | 
| Describe the Tmax of moxifloxacin after a single dose of moxifloxacin 400 mg | 17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis | Up to Day 33 | 
| Describe the AUClast of moxifloxacin after a single dose of moxifloxacin 400 mg | 17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis | Up to Day 33 | 
| Describe the AUCinf of moxifloxacin after a single dose of moxifloxacin 400 mg | 17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis | Up to Day 33 | 
| Describe the AUCext of moxifloxacin after a single dose of moxifloxacin 400 mg | 17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis | Up to Day 33 | 
| Describe the λz of moxifloxacin after a single dose of moxifloxacin 400 mg | 17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis | Up to Day 33 | 
| Describe the t1/2 of moxifloxacin after a single dose of moxifloxacin 400 mg | 17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis | Up to Day 33 |