Clinical trial NCT05841160: Thorough QT/QTc Study to Evaluate the Effects of Ecopipam (EBS-101) on Cardiac Repolarization
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: QT/QTc
Lead sponsor: Emalex Biosciences Inc.
Sponsor class: INDUSTRY
Collaborators: name: PPD Development, LP
name: Clario
First posted: 2023-05-03
Enrollment: 29
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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

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).

Eligibility 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.

Primary outcomes:
measure: 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.
timeFrame: Up to Day 25
Secondary outcomes:
measure: Evaluate the effect of ecopipam at a therapeutic dose on heart rate
timeFrame: Up to Day 25
measure: Evaluate the effect of ecopipam at a therapeutic dose on PR interval
timeFrame: Up to Day 25
measure: Evaluate the effect of ecopipam at a therapeutic dose on QRS interval
timeFrame: Up to Day 25
measure: Evaluate the effect of ecopipam at a therapeutic dose on T-wave morphology
timeFrame: Up to Day 25
measure: Evaluate the effect of ecopipam at a therapeutic dose on U wave presence
timeFrame: Up to Day 25
measure: Evaluate the effect of ecopipam at supratherapeutic dose on heart rate
timeFrame: Up to Day 25
measure: Evaluate the effect of ecopipam at supratherapeutic dose on PR interval
timeFrame: Up to Day 25
measure: Evaluate the effect of ecopipam at supratherapeutic dose on QRS interval
timeFrame: Up to Day 25
measure: Evaluate the effect of ecopipam at supratherapeutic dose on T-wave morphology
timeFrame: Up to Day 25
measure: Evaluate the effect of ecopipam at supratherapeutic dose on U wave presence
timeFrame: Up to Day 25
measure: 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
timeFrame: Up to Day 25
measure: Evaluate the effects of ecopipam on the emergence of arrhythmias
timeFrame: Up to Day 25
measure: Describe the incidence of treatment-emergent adverse events after a single therapeutic dose of ecopipam
timeFrame: Up to Day 33
measure: Describe the incidence of treatment-emergent adverse events after a single supratherapeutic dose of ecopipam
timeFrame: Up to Day 33
measure: Describe the incidence of treatment-emergent adverse events after a single dose of moxifloxacin 400 mg
timeFrame: Up to Day 33
measure: Describe the Cmax of ecopipam after single therapeutic dose of ecopipam
timeFrame: Up to Day 33
measure: Describe the Tmax of ecopipam after single therapeutic dose of ecopipam
timeFrame: Up to Day 33
measure: Describe the AUClast of ecopipam after single therapeutic dose of ecopipam
timeFrame: Up to Day 33
measure: Describe the AUCinf of ecopipam after single therapeutic dose of ecopipam
timeFrame: Up to Day 33
measure: Describe the AUCext of ecopipam after single therapeutic dose of ecopipam
timeFrame: Up to Day 33
measure: Describe the λz of ecopipam after single therapeutic dose of ecopipam
timeFrame: Up to Day 33
measure: Describe the t1/2 of ecopipam after single therapeutic dose of ecopipam
timeFrame: Up to Day 33
measure: Describe the Cmax of ecopipam after single supratherapeutic dose of ecopipam
timeFrame: Up to Day 33
measure: Describe the Tmax of ecopipam after single supratherapeutic dose of ecopipam
timeFrame: Up to Day 33
measure: Describe the AUClast of ecopipam after single supratherapeutic dose of ecopipam
timeFrame: Up to Day 33
measure: Describe the AUCinf of ecopipam after single supratherapeutic dose of ecopipam
timeFrame: Up to Day 33
measure: Describe the AUCext of ecopipam after single supratherapeutic dose of ecopipam
timeFrame: Up to Day 33
measure: Describe the λz of ecopipam after single supratherapeutic dose of ecopipam
timeFrame: Up to Day 33
measure: Describe the t1/2 of ecopipam after single supratherapeutic dose of ecopipam
timeFrame: Up to Day 33
measure: Describe the Cmax of EBS-101-40853 after single therapeutic dose of ecopipam
timeFrame: Up to Day 33
measure: Describe the Tmax of EBS-101-40853 after single therapeutic dose of ecopipam
timeFrame: Up to Day 33
measure: Describe the AUClast of EBS-101-40853 after single therapeutic dose of ecopipam
timeFrame: Up to Day 33
measure: Describe the AUCinf of EBS-101-40853 after single therapeutic dose of ecopipam
timeFrame: Up to Day 33
measure: Describe the AUCext of EBS-101-40853 after single therapeutic dose of ecopipam
timeFrame: Up to Day 33
measure: Describe the λz of EBS-101-40853 after single therapeutic dose of ecopipam
timeFrame: Up to Day 33
measure: Describe the t1/2 of EBS-101-40853 after single therapeutic dose of ecopipam
timeFrame: Up to Day 33
measure: Describe the Cmax of EBS-101-40853 after single supratherapeutic dose of ecopipam
timeFrame: Up to Day 33
measure: Describe the Tmax of EBS-101-40853 after single supratherapeutic dose of ecopipam
timeFrame: Up to Day 33
measure: Describe the AUClast of EBS-101-40853 after single supratherapeutic dose of ecopipam
timeFrame: Up to Day 33
measure: Describe the AUCinf of EBS-101-40853 after single supratherapeutic dose of ecopipam
timeFrame: Up to Day 33
measure: Describe the AUCext of EBS-101-40853 after single supratherapeutic dose of ecopipam
timeFrame: Up to Day 33
measure: Describe the λz of EBS-101-40853 after single supratherapeutic dose of ecopipam
timeFrame: Up to Day 33
measure: Describe the t1/2 of EBS-101-40853 after single supratherapeutic dose of ecopipam
timeFrame: Up to Day 33
measure: Describe the Cmax of ecopipam glucuronide after single therapeutic dose of ecopipam
timeFrame: Up to Day 33
measure: Describe the Tmax of ecopipam glucuronide after single therapeutic dose of ecopipam
timeFrame: Up to Day 33
measure: Describe the AUClast of ecopipam glucuronide after single therapeutic dose of ecopipam
timeFrame: Up to Day 33
measure: Describe the AUCinf of ecopipam glucuronide after single therapeutic dose of ecopipam
timeFrame: Up to Day 33
measure: Describe the AUCext of ecopipam glucuronide after single therapeutic dose of ecopipam
timeFrame: Up to Day 33
measure: Describe the λz of ecopipam glucuronide after single therapeutic dose of ecopipam
timeFrame: Up to Day 33
measure: Describe the t1/2 of ecopipam glucuronide after single therapeutic dose of ecopipam
timeFrame: Up to Day 33
measure: Describe the Cmax of ecopipam glucuronide after single supratherapeutic dose of ecopipam
timeFrame: Up to Day 33
measure: Describe the Tmax of ecopipam glucuronide after single supratherapeutic dose of ecopipam
timeFrame: Up to Day 33
measure: Describe the AUClast of ecopipam glucuronide after single supratherapeutic dose of ecopipam
timeFrame: Up to Day 33
measure: Describe the AUCinf of ecopipam glucuronide after single supratherapeutic dose of ecopipam
timeFrame: Up to Day 33
measure: Describe the AUCext of ecopipam glucuronide after single supratherapeutic dose of ecopipam
timeFrame: Up to Day 33
measure: Describe the λz of ecopipam glucuronide after single supratherapeutic dose of ecopipam
timeFrame: Up to Day 33
measure: Describe the t1/2 of ecopipam glucuronide after single supratherapeutic dose of ecopipam
timeFrame: Up to Day 33
measure: Describe the Cmax of EBS-101-40853 glucuronide after single therapeutic dose of ecopipam
timeFrame: Up to Day 33
measure: Describe the Tmax of EBS-101-40853 glucuronide after single therapeutic dose of ecopipam
timeFrame: Up to Day 33
measure: Describe the AUClast of EBS-101-40853 glucuronide after single therapeutic dose of ecopipam
timeFrame: Up to Day 33
measure: Describe the AUCinf of EBS-101-40853 glucuronide after single therapeutic dose of ecopipam
timeFrame: Up to Day 33
measure: Describe the AUCext of EBS-101-40853 glucuronide after single therapeutic dose of ecopipam
timeFrame: Up to Day 33
measure: Describe the λz of EBS-101-40853 glucuronide after single therapeutic dose of ecopipam
timeFrame: Up to Day 33
measure: Describe the t1/2 of EBS-101-40853 glucuronide after single therapeutic dose of ecopipam
timeFrame: Up to Day 33
measure: Describe the Cmax of EBS-101-40853 glucuronide after single supratherapeutic dose of ecopipam
timeFrame: Up to Day 33
measure: Describe the Tmax of EBS-101-40853 glucuronide after single supratherapeutic dose of ecopipam
timeFrame: Up to Day 33
measure: Describe the AUClast of EBS-101-40853 glucuronide after single supratherapeutic dose of ecopipam
timeFrame: Up to Day 33
measure: Describe the AUCinf of EBS-101-40853 glucuronide after single supratherapeutic dose of ecopipam
timeFrame: Up to Day 33
measure: Describe the AUCext of EBS-101-40853 glucuronide after single supratherapeutic dose of ecopipam
timeFrame: Up to Day 33
measure: Describe the λz of EBS-101-40853 glucuronide after single supratherapeutic dose of ecopipam
timeFrame: Up to Day 33
measure: Describe the t1/2 of EBS-101-40853 glucuronide after single supratherapeutic dose of ecopipam
timeFrame: Up to Day 33
measure: Describe the Cmax of moxifloxacin after a single dose of moxifloxacin 400 mg
timeFrame: Up to Day 33
measure: Describe the Tmax of moxifloxacin after a single dose of moxifloxacin 400 mg
timeFrame: Up to Day 33
measure: Describe the AUClast of moxifloxacin after a single dose of moxifloxacin 400 mg
timeFrame: Up to Day 33
measure: Describe the AUCinf of moxifloxacin after a single dose of moxifloxacin 400 mg
timeFrame: Up to Day 33
measure: Describe the AUCext of moxifloxacin after a single dose of moxifloxacin 400 mg
timeFrame: Up to Day 33
measure: Describe the λz of moxifloxacin after a single dose of moxifloxacin 400 mg
timeFrame: Up to Day 33
measure: Describe the t1/2 of moxifloxacin after a single dose of moxifloxacin 400 mg
timeFrame: Up to Day 33
Other outcomes:
Locations:
city: Austin
country: United States
facility: PPD Austin Phase 1 Clinical Research Unit
state: Texas
Study officials:
References: