Thorough QT/QTc Study to Evaluate the Effects of Ecopipam (EBS-101) on Cardiac Repolarization
Study Details
Study Description
Brief Summary
THOROUGH QT/QTc STUDY TO EVALUATE THE EFFECTS OF ECOPIPAM (EBS-101) ON CARDIAC REPOLARIZATION
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Detailed Description
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).
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 200 mg ecopipam HCL 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
oral tablets
Drug: Placebo
oral tablet
|
| Experimental: 600 mg ecopipam HCL Single 600 mg dose of ecopipam HCL given as 6 x 100 mg ecopipam HCL oral tablets |
Drug: Ecopipam Hydrochloride
oral tablets
|
| Active Comparator: 400 mg moxifloxacin Single 400 mg dose of moxifloxacin given as 1 x 400 mg oral tablet |
Drug: Moxifloxacin
oral tablet
|
| Placebo Comparator: Placebo Single oral dose of 6 x placebo tablets |
Drug: Placebo
oral tablet
|
Outcome Measures
Primary Outcome Measures
- 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. [Up to Day 25]
ECGs and PK samples will be collected for up to 96 hours after each dose
Secondary Outcome Measures
- Evaluate the effect of ecopipam at a therapeutic dose on heart rate [Up to Day 25]
ECGs will be collected for up to 48 hours after each dose
- Evaluate the effect of ecopipam at a therapeutic dose on PR interval [Up to Day 25]
ECGs will be collected for up to 48 hours after each dose
- Evaluate the effect of ecopipam at a therapeutic dose on QRS interval [Up to Day 25]
ECGs will be collected for up to 48 hours after each dose
- Evaluate the effect of ecopipam at a therapeutic dose on T-wave morphology [Up to Day 25]
ECGs will be collected for up to 48 hours after each dose
- Evaluate the effect of ecopipam at a therapeutic dose on U wave presence [Up to Day 25]
ECGs will be collected for up to 48 hours after each dose
- Evaluate the effect of ecopipam at supratherapeutic dose on heart rate [Up to Day 25]
ECGs will be collected for up to 48 hours after each dose
- Evaluate the effect of ecopipam at supratherapeutic dose on PR interval [Up to Day 25]
ECGs will be collected for up to 48 hours after each dose
- Evaluate the effect of ecopipam at supratherapeutic dose on QRS interval [Up to Day 25]
ECGs will be collected for up to 48 hours after each dose
- Evaluate the effect of ecopipam at supratherapeutic dose on T-wave morphology [Up to Day 25]
ECGs will be collected for up to 48 hours after each dose
- Evaluate the effect of ecopipam at supratherapeutic dose on U wave presence [Up to Day 25]
ECGs will be collected for up to 48 hours after each dose
- 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 [Up to Day 25]
ECGs will be collected for up to 48 hours after each dose
- Evaluate the effects of ecopipam on the emergence of arrhythmias [Up to Day 25]
ECGs will be collected for up to 48 hours after each dose
- Describe the incidence of treatment-emergent adverse events after a single therapeutic dose of ecopipam [Up to Day 33]
AEs will be collected throughout the duration of the study
- Describe the incidence of treatment-emergent adverse events after a single supratherapeutic dose of ecopipam [Up to Day 33]
AEs will be collected throughout the duration of the study
- Describe the incidence of treatment-emergent adverse events after a single dose of moxifloxacin 400 mg [Up to Day 33]
AEs will be collected throughout the duration of the study
- Describe the Cmax of ecopipam after single therapeutic dose of ecopipam [Up to Day 33]
17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis
- Describe the Tmax of ecopipam after single therapeutic dose of ecopipam [Up to Day 33]
17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis
- Describe the AUClast of ecopipam after single therapeutic dose of ecopipam [Up to Day 33]
17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis
- Describe the AUCinf of ecopipam after single therapeutic dose of ecopipam [Up to Day 33]
17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis
- Describe the AUCext of ecopipam after single therapeutic dose of ecopipam [Up to Day 33]
17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis
- Describe the λz of ecopipam after single therapeutic dose of ecopipam [Up to Day 33]
17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis
- Describe the t1/2 of ecopipam after single therapeutic dose of ecopipam [Up to Day 33]
17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis
- Describe the Cmax of ecopipam after single supratherapeutic dose of ecopipam [Up to Day 33]
17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis
- Describe the Tmax of ecopipam after single supratherapeutic dose of ecopipam [Up to Day 33]
17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis
- Describe the AUClast of ecopipam after single supratherapeutic dose of ecopipam [Up to Day 33]
17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis
- Describe the AUCinf of ecopipam after single supratherapeutic dose of ecopipam [Up to Day 33]
17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis
- Describe the AUCext of ecopipam after single supratherapeutic dose of ecopipam [Up to Day 33]
17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis
- Describe the λz of ecopipam after single supratherapeutic dose of ecopipam [Up to Day 33]
17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis
- Describe the t1/2 of ecopipam after single supratherapeutic dose of ecopipam [Up to Day 33]
17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis
- Describe the Cmax of EBS-101-40853 after single therapeutic dose of ecopipam [Up to Day 33]
17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis
- Describe the Tmax of EBS-101-40853 after single therapeutic dose of ecopipam [Up to Day 33]
17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis
- Describe the AUClast of EBS-101-40853 after single therapeutic dose of ecopipam [Up to Day 33]
17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis
- Describe the AUCinf of EBS-101-40853 after single therapeutic dose of ecopipam [Up to Day 33]
17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis
- Describe the AUCext of EBS-101-40853 after single therapeutic dose of ecopipam [Up to Day 33]
17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis
- Describe the λz of EBS-101-40853 after single therapeutic dose of ecopipam [Up to Day 33]
17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis
- Describe the t1/2 of EBS-101-40853 after single therapeutic dose of ecopipam [Up to Day 33]
17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis
- Describe the Cmax of EBS-101-40853 after single supratherapeutic dose of ecopipam [Up to Day 33]
17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis
- Describe the Tmax of EBS-101-40853 after single supratherapeutic dose of ecopipam [Up to Day 33]
17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis
- Describe the AUClast of EBS-101-40853 after single supratherapeutic dose of ecopipam [Up to Day 33]
17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis
- Describe the AUCinf of EBS-101-40853 after single supratherapeutic dose of ecopipam [Up to Day 33]
17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis
- Describe the AUCext of EBS-101-40853 after single supratherapeutic dose of ecopipam [Up to Day 33]
17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis
- Describe the λz of EBS-101-40853 after single supratherapeutic dose of ecopipam [Up to Day 33]
17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis
- Describe the t1/2 of EBS-101-40853 after single supratherapeutic dose of ecopipam [Up to Day 33]
17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis
- Describe the Cmax of ecopipam glucuronide after single therapeutic dose of ecopipam [Up to Day 33]
17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis
- Describe the Tmax of ecopipam glucuronide after single therapeutic dose of ecopipam [Up to Day 33]
17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis
- Describe the AUClast of ecopipam glucuronide after single therapeutic dose of ecopipam [Up to Day 33]
17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis
- Describe the AUCinf of ecopipam glucuronide after single therapeutic dose of ecopipam [Up to Day 33]
17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis
- Describe the AUCext of ecopipam glucuronide after single therapeutic dose of ecopipam [Up to Day 33]
17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis
- Describe the λz of ecopipam glucuronide after single therapeutic dose of ecopipam [Up to Day 33]
17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis
- Describe the t1/2 of ecopipam glucuronide after single therapeutic dose of ecopipam [Up to Day 33]
17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis
- Describe the Cmax of ecopipam glucuronide after single supratherapeutic dose of ecopipam [Up to Day 33]
17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis
- Describe the Tmax of ecopipam glucuronide after single supratherapeutic dose of ecopipam [Up to Day 33]
17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis
- Describe the AUClast of ecopipam glucuronide after single supratherapeutic dose of ecopipam [Up to Day 33]
17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis
- Describe the AUCinf of ecopipam glucuronide after single supratherapeutic dose of ecopipam [Up to Day 33]
17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis
- Describe the AUCext of ecopipam glucuronide after single supratherapeutic dose of ecopipam [Up to Day 33]
17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis
- Describe the λz of ecopipam glucuronide after single supratherapeutic dose of ecopipam [Up to Day 33]
17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis
- Describe the t1/2 of ecopipam glucuronide after single supratherapeutic dose of ecopipam [Up to Day 33]
17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis
- Describe the Cmax of EBS-101-40853 glucuronide after single therapeutic dose of ecopipam [Up to Day 33]
17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis
- Describe the Tmax of EBS-101-40853 glucuronide after single therapeutic dose of ecopipam [Up to Day 33]
17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis
- Describe the AUClast of EBS-101-40853 glucuronide after single therapeutic dose of ecopipam [Up to Day 33]
17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis
- Describe the AUCinf of EBS-101-40853 glucuronide after single therapeutic dose of ecopipam [Up to Day 33]
17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis
- Describe the AUCext of EBS-101-40853 glucuronide after single therapeutic dose of ecopipam [Up to Day 33]
17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis
- Describe the λz of EBS-101-40853 glucuronide after single therapeutic dose of ecopipam [Up to Day 33]
17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis
- Describe the t1/2 of EBS-101-40853 glucuronide after single therapeutic dose of ecopipam [Up to Day 33]
17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis
- Describe the Cmax of EBS-101-40853 glucuronide after single supratherapeutic dose of ecopipam [Up to Day 33]
17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis
- Describe the Tmax of EBS-101-40853 glucuronide after single supratherapeutic dose of ecopipam [Up to Day 33]
17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis
- Describe the AUClast of EBS-101-40853 glucuronide after single supratherapeutic dose of ecopipam [Up to Day 33]
17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis
- Describe the AUCinf of EBS-101-40853 glucuronide after single supratherapeutic dose of ecopipam [Up to Day 33]
17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis
- Describe the AUCext of EBS-101-40853 glucuronide after single supratherapeutic dose of ecopipam [Up to Day 33]
17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis
- Describe the λz of EBS-101-40853 glucuronide after single supratherapeutic dose of ecopipam [Up to Day 33]
17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis
- Describe the t1/2 of EBS-101-40853 glucuronide after single supratherapeutic dose of ecopipam [Up to Day 33]
17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis
- Describe the Cmax of moxifloxacin after a single dose of moxifloxacin 400 mg [Up to Day 33]
17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis
- Describe the Tmax of moxifloxacin after a single dose of moxifloxacin 400 mg [Up to Day 33]
17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis
- Describe the AUClast of moxifloxacin after a single dose of moxifloxacin 400 mg [Up to Day 33]
17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis
- Describe the AUCinf of moxifloxacin after a single dose of moxifloxacin 400 mg [Up to Day 33]
17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis
- Describe the AUCext of moxifloxacin after a single dose of moxifloxacin 400 mg [Up to Day 33]
17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis
- Describe the λz of moxifloxacin after a single dose of moxifloxacin 400 mg [Up to Day 33]
17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis
- Describe the t1/2 of moxifloxacin after a single dose of moxifloxacin 400 mg [Up to Day 33]
17 blood samples will be collected at the indicated timepoints for pharmacokinetic analysis
Eligibility Criteria
Criteria
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | PPD Austin Phase 1 Clinical Research Unit | Austin | Texas | United States | 78744 |
Sponsors and Collaborators
- Emalex Biosciences Inc.
- PPD
- Clario
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- EBS-101-HV-105