Placebo-Corrected Effects of Therapeutic Dose (100 mg) an... | NCT04821063

ID	Type	Description	Link
2020-003105-63	EudraCT Number

Label	Type	Description	Intervention Names
Therapeutic dose: ITF2357 100 mg	Experimental	Participants will receive a single dose of ITF2357 100 mg administered as 10 milliliters (mL) of ITF2357 10 milligrams per milliliter (mg/mL) oral suspension and 20 mL of placebo matched to ITF2357 oral suspension under fasting conditions on Day 1 of respective period as per the assigned treatment sequence.	Drug: ITF2357 10 mg/mL Drug: Placebo
Supratherapeutic dose: ITF2357 300 mg	Experimental	Participants will receive a single dose of ITF2357 300 mg administered as 30 mL of ITF2357 10 mg/mL oral suspension under fasting conditions on Day 1 of respective period as per the assigned treatment sequence.	Drug: ITF2357 10 mg/mL
Placebo	Placebo Comparator	Participants will receive a single dose of placebo matched to ITF2357 administered as 30 mL oral suspension under fasting conditions on Day 1 of respective period as per the assigned treatment sequence.	Drug: Placebo
Moxifloxacin	Active Comparator	Participants will receive a single dose of moxifloxacin 400 mg tablet under fasting conditions on Day 1 of respective period as per the assigned treatment sequence.	Drug: Moxifloxacin Hydrochloride

Name	Type	Description	Arm Group Labels	Other Names
ITF2357 10 mg/mL	Drug	Dose: 100 mg (administered as 10 mL); Dosage form: suspension; Route of administration: oral	Therapeutic dose: ITF2357 100 mg

Measure	Description	Time Frame
Placebo-corrected Change From Baseline in Fridericia's Corrected QT Interval (QTcF)	The cardio-dynamic assessment was performed through 12-lead electrocardiogram (ECG) extracted from continuous recordings at pre-specified time points. Participants rested in supine position for at least 10 minutes prior to and 5 minutes after each time point for ECG extractions. The QT interval is the time from electrocardiogram Q wave to the end of the T wave corresponding to electrical systole. QT interval was corrected for heart rate using QTcF. Placebo-corrected change from baseline in QTcF (ΔΔQTcF) was calculated based on model-predicted effect.	At 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 12, 24, and 36 hours post-dose

Measure	Description	Time Frame
Change From Baseline in QTcF Interval	The cardio-dynamic assessment was performed through 12-lead ECGs extracted from continuous recordings at pre-specified time points. Participants rested in supine position for at least 10 minutes prior to and 5 minutes after each time point for ECG extractions. QT interval was corrected for heart rate using Fridericia's correction (QTcF).	At 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 12, 24, and 36 hours post-dose

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Male or female, non-smoker (no use of tobacco or nicotine products within 3 months prior to screening), greater than or equal to (>=) 18 and less than or equal to (<=) 55 years of age, with body mass index (BMI) greater than (>) 18.5 and less than (<) 30.0 kilograms per meter square (kg/m^2) and body weight >=55 kilograms (kg) and <=100 kg for females and body weight >=60 kg and <=100 kg for males.
Healthy as defined by:
1. The absence of clinically significant illness and major surgery within 4 weeks prior to dosing. Participants vomiting within 24 hours pre-dose will be carefully evaluated for upcoming illness/disease. Inclusion pre-dosing of the patient in the study is at the discretion of the Investigator, depending on his/her clinical judgement.
2. The absence of clinically significant history of neurological, endocrinal, cardiovascular, pulmonary, hematological, immunologic, psychiatric, gastrointestinal, renal, hepatic, and metabolic disease.
Non-childbearing potential female defined as:
1. Post-menopausal female (absence of menses for 12 months prior to the first study drug administration, bilateral oophorectomy or hysterectomy with bilateral oophorectomy at least 6 months prior to the first study drug administration); or
2. Surgically sterile female (hysterectomy or tubal ligation at least 6 months prior to drug administration).
Females of childbearing potential who are sexually active with a male partner must be willing to use one of the following acceptable contraceptive methods throughout the study and for at least 90 days after the last study drug administration:
1. Simultaneous use of intra-uterine contraceptive device, without hormone release system placed at least 4 weeks prior to study drug administration, and condom for the male partner;
2. Simultaneous use of diaphragm or cervical cap with intravaginally applied spermicide and male condom for the male partner, started at least 21 days prior to study drug administration;
Male participants who are not vasectomized for at least 6 months, and who are sexually active with a female partner of childbearing potential (childbearing potential females are defined as women that are neither post-menopausal nor surgically sterile) must be willing to use one of the following acceptable contraceptive methods from the first study drug administration until at least 90 days after the last study drug administration:
1. Simultaneous use of a male condom and, for the female partner, hormonal contraceptives used since at least 4 weeks or intra-uterine contraceptive device placed since at least 4 weeks;
2. Simultaneous use of a male condom and, for the female partner, a diaphragm or cervical cap with intravaginally applied spermicide.
Male participants (including men who have had a vasectomy) with a pregnant partner must agree to use a condom from the first study drug administration until at least 90 days after the last study drug administration.
Male participants must be willing not to donate sperm until 90 days following the last study drug administration.
Female participants must be willing not to donate ovules until 90 days following the last study drug administration.
Participant's written informed consent obtained prior to any study-related procedure.
Willingness and capability to comply with the requirements of the study and ability to understand the study procedures and the risks involved.
Willing to take out dentures and mouth piercings for study procedures.

Exclusion Criteria:

Any clinically significant abnormality at physical examination, clinically significant abnormal laboratory test results or positive test for human immunodeficiency virus (HIV), hepatitis B, or hepatitis C found during medical screening.
Clinically significant vital sign abnormalities (systolic blood pressure lower than 90 or over 140 millimeter of mercury [mmHg], diastolic blood pressure lower than 60 or over 90 mmHg, or heart rate less than 40 or over 100 beats per minute [bpm]) at screening. For eligibility purposes, not the mean value, but the two single measurements will be considered.
Any of the following abnormalities on 12-lead ECG at screening. PR (PR interval) >210 millisecond (msec); QRS (QRS complex) >120 msec; QTcF >450 msec; any abnormality of cardiac rhythm other than sinus arrhythmia; abnormality of T-wave morphology that will impair the ability to measure the QT interval reliably. The averaged value of three ECGs 5 minutes apart from each other will be used; evaluations have to be used for the evaluation of the QTc interval requested by this exclusion criteria.
Participants with history of sustained and non-sustained cardiac arrhythmias (ECG demonstrated), participants with a family history of sudden cardiac death and participants with a history of additional risk factors for TdP, heart failure, hypokalemia, LQTS).
Any of the following abnormal laboratory test values at screening or at baseline (Day -1) of Period 1:
1. Platelet count <125*10^9 per liter (/L)
2. Absolute neutrophil count <1.2*10^9/L
Participants who have cardiovascular condition such as, but not limited to unstable ischemic heart disease, New York Heart Association (NYHA) Class III/IV left ventricular failure, acute ischemic heart disease in the last year prior to study screening, which may impact the safety of the participant or the evaluation of the result of the study according to the Investigator's judgment; cardiovascular conditions should be discarded based on the results obtained on the ECG, medical examination and routine lab test.
Positive urine drug screen, alcohol breath test or urine cotinine test at screening or at baseline (Day -1).
History of anaphylaxis reaction or clinically significant drug hypersensitivity reaction (e.g., angioedema, Stevens-Johnson syndrome, Acute Generalized Exanthematous Pustulosis, Drug-induced hypersensitivity syndrome, Drug-induced neutropenia).
History of allergic reactions to ITF2357, histone deacetylases (HDAC) inhibitors, or other related drugs, moxifloxacin, other quinolones, or to any excipient in the formulation.
Positive pregnancy test at screening or at baseline (Day -1).
Participants with a sorbitol intolerance or sorbitol malabsorption or have fructose intolerance.
Current or recent (within 3 months of study drug administration) clinically significant gastrointestinal disease that can interfere with drug absorption.
Gastrointestinal surgery that interferes with physiological absorption and motility (i.e., gastric bypass, duodenectomy) or gastric bands.
History of significant alcohol abuse within 1 year prior to screening or regular use of alcohol within 6 months prior to the screening visit (more than 14 units of alcohol per week [1 unit = 150 milliliter [mL] of wine, 360 mL of beer, or 45 mL of 40 percent [%] alcohol]).
History of significant drug abuse within 1 year prior to screening or use of soft drugs (such as marijuana) within 3 months prior to the screening visit or hard drugs (such as cocaine, phencyclidine [PCP], crack, opioid derivatives including heroin, and amphetamine derivatives) within 1 year prior to screening.
Use of ITF2357 for a medical condition or in the context of another clinical trial within a period of 30 days prior to the first dosing.
Participation in a clinical research study involving the administration of an investigational or marketed drug or device within 30 days prior to the first dosing, administration of a biological product in the context of a clinical research study within 90 days prior to the first dosing, or concomitant participation in an investigational study involving no drug or device administration.
Use of medications for the timeframes specified below, with the exception of medications exempted by the Investigator on a case-by-case basis because they are judged unlikely to affect the pharmacokinetic profile of the study drug or participant safety (e.g., topical drug products without significant systemic absorption):
1. Prescription medications within 14 days prior to the first dosing;
2. OTC products (with the exception of the occasional use of acetaminophen [up to 2 grams [g] daily]) and natural health products (including herbal remedies, homeopathic and traditional medicines, probiotics, food supplements such as vitamins, minerals, amino acids, essential fatty acids, and protein supplements used in sports) within 7 days prior to the first dosing;
3. Depot injection or implant of any drug within 3 months prior to the first dosing;
4. Any drugs known to induce or inhibit hepatic drug metabolism (including St. John's wort) within 30 days prior to the first dosing.
Donation of plasma within 7 days prior to dosing. Donation or loss of blood (excluding volume drawn at screening) of 50 mL to 499 mL of blood within 30 days, or more than 499 mL within 56 days prior to the first dosing.
Breast-feeding participant.
Inability to be venipunctured and/or tolerate catheter venous access;
Inability or difficulty to swallow tablets or suspension.
Any reason which, in the opinion of the Investigator, would prevent the participant from participating in the study.
History or presence of other diseases, metabolic dysfunctions, physical examination findings, or any clinically relevant abnormal laboratory value at screening suggesting an unknown disease and requiring further clinical investigation or which may impact the safety of the participant or the evaluation of the result of the study according to the Investigator's judgment.

Facility	Status	City	State	ZIP	Country	Contacts
Québec		Québec		G1P 0A2	Canada

ID	Title	Description
FG000	Sequence TSTPM	Participants received a single dose of ITF2357 100 mg (Treatment T) oral suspension under fasted condition in Period 1, followed by a single dose of ITF2357 300 mg (as 10 mg/mL, Treatment ST) oral suspension under fasted conditions in Period 2, followed by a single dose of placebo matched to ITL2357 (Treatment P) oral suspension under fasted conditions in Period 3, followed by a single dose of moxifloxacin hydrochloride 400 mg tablets (Treatment M) under fasted conditions in Period 4, on Day 1 in the treatment period. Each period was separated by a washout period of 7 days.

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Sep 29, 2020	Jun 7, 2022

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Placebo-corrected Change From Baseline in Fridericia's Corrected QT Interval (QTcF)

The cardio-dynamic assessment was performed through 12-lead electrocardiogram (ECG) extracted from continuous recordings at pre-specified time points. Participants rested in supine position for at least 10 minutes prior to and 5 minutes after each time point for ECG extractions. The QT interval is the time from electrocardiogram Q wave to the end of the T wave corresponding to electrical systole. QT interval was corrected for heart rate using QTcF. Placebo-corrected change from baseline in QTcF (ΔΔQTcF) was calculated based on model-predicted effect.

The QT/QTc Population was defined as all participants in the safety population with measurements at baseline as well as on-treatment with at least one post-dose time point with a valid ΔQTcF value. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure.

Posted

Least Squares Mean

Standard Error

Milliseconds (msec)

At 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 12, 24, and 36 hours post-dose

ID	Title	Description
OG000	Therapeutic Dose: ITF2357 100 mg	Participants received orally a single dose of ITF2357 100 milligrams (mg; 10 mg per milliliter [mL]) oral suspension and placebo (matched to ITF2357) oral suspension under fasted conditions on Day 1 of Treatment T in each treatment sequence under each assigned period. Each of the 4 periods were separated by a washout of 7 days.
OG001	Supratherapeutic Dose: ITF2357 300 mg	Participants received orally a single dose of ITF2357 300 mg (as 10 mg/mL) oral suspension under fasted conditions on Day 1 of Treatment ST in each treatment sequence under each assigned period. Each of the 4 periods were separated by a washout of 7 days.
OG002	Moxifloxacin	Participants received orally a single dose of moxifloxacin hydrochloride 400 mg tablets under fasted conditions on Day 1 of Treatment M in each treatment sequence under each assigned period. Each of the 4 periods were separated by a washout of 7 days.

Units	Counts
Participants	OG00029 OG00131 OG00230

Title

Denominators

Categories

0.5 hours post-dose

Title	Measurements
	OG0001.0± 1.06 OG0010.5± 1.04 OG00210.2± 1.05

1 hours post-dose

Secondary

Change From Baseline in QTcF Interval

The cardio-dynamic assessment was performed through 12-lead ECGs extracted from continuous recordings at pre-specified time points. Participants rested in supine position for at least 10 minutes prior to and 5 minutes after each time point for ECG extractions. QT interval was corrected for heart rate using Fridericia's correction (QTcF).

Posted

Least Squares Mean

Standard Error

msec

At 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 12, 24, and 36 hours post-dose

ID	Title	Description
OG000	Therapeutic Dose: ITF2357 100 mg	Participants received orally a single dose of ITF2357 100 milligrams (mg; 10 mg per milliliter [mL]) oral suspension and placebo (matched to ITF2357) oral suspension under fasted conditions on Day 1 of Treatment T in each treatment sequence under each assigned period. Each of the 4 periods were separated by a washout of 7 days.
OG001	Supratherapeutic Dose: ITF2357 300 mg	Participants received orally a single dose of ITF2357 300 mg (as 10 mg/mL) oral suspension under fasted conditions on Day 1 of Treatment ST in each treatment sequence under each assigned period. Each of the 4 periods were separated by a washout of 7 days.

Secondary

Change From Baseline in PR Interval

The cardio-dynamic assessment was performed through 12-lead ECGs extracted from continuous recordings at pre-specified time points. Participants rested in supine position for at least 10 minutes prior to and 5 minutes after each time point for ECG extractions. The PR interval is the time from the onset of the P-wave to the start of the next QRS complex, corresponding to the end of atrial depolarization and onset of ventricular depolarization.

Posted

Least Squares Mean

Standard Error

msec

At 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 12, 24, and 36 hours post-dose

ID	Title	Description
OG000	Therapeutic Dose: ITF2357 100 mg	Participants received orally a single dose of ITF2357 100 milligrams (mg; 10 mg per milliliter [mL]) oral suspension and placebo (matched to ITF2357) oral suspension under fasted conditions on Day 1 of Treatment T in each treatment sequence under each assigned period. Each of the 4 periods were separated by a washout of 7 days.
OG001	Supratherapeutic Dose: ITF2357 300 mg	Participants received orally a single dose of ITF2357 300 mg (as 10 mg/mL) oral suspension under fasted conditions on Day 1 of Treatment ST in each treatment sequence under each assigned period. Each of the 4 periods were separated by a washout of 7 days.

Secondary

Change From Baseline in QRS Interval

The cardio-dynamic assessment was performed through 12-lead ECGs extracted from continuous recordings at pre-specified time points. Participants rested in supine position for at least 10 minutes prior to and 5 minutes after each time point for ECG extractions. QRS interval is the time from electrocardiogram Q wave to the end of the S wave, corresponding to ventricle depolarization.

Posted

Least Squares Mean

Standard Error

msec

At 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 12, 24, and 36 hours post-dose

ID	Title	Description
OG000	Therapeutic Dose: ITF2357 100 mg	Participants received orally a single dose of ITF2357 100 milligrams (mg; 10 mg per milliliter [mL]) oral suspension and placebo (matched to ITF2357) oral suspension under fasted conditions on Day 1 of Treatment T in each treatment sequence under each assigned period. Each of the 4 periods were separated by a washout of 7 days.
OG001	Supratherapeutic Dose: ITF2357 300 mg	Participants received orally a single dose of ITF2357 300 mg (as 10 mg/mL) oral suspension under fasted conditions on Day 1 of Treatment ST in each treatment sequence under each assigned period. Each of the 4 periods were separated by a washout of 7 days.

Secondary

Change From Baseline in Heart Rate (HR) Interval

The cardio-dynamic assessment was performed through 12-lead ECGs extracted from continuous recordings at pre-specified time points. Participants rested in supine position for at least 10 minutes prior to and 5 minutes after each time point for ECG extractions. Baseline is defined as the last results (scheduled or unscheduled) obtained prior to drug administration in each period.

Posted

Least Squares Mean

Standard Error

beats per minute (bpm)

At 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 12, 24, and 36 hours post-dose

ID	Title	Description
OG000	Therapeutic Dose: ITF2357 100 mg	Participants received orally a single dose of ITF2357 100 milligrams (mg; 10 mg per milliliter [mL]) oral suspension and placebo (matched to ITF2357) oral suspension under fasted conditions on Day 1 of Treatment T in each treatment sequence under each assigned period. Each of the 4 periods were separated by a washout of 7 days.
OG001	Supratherapeutic Dose: ITF2357 300 mg	Participants received orally a single dose of ITF2357 300 mg (as 10 mg/mL) oral suspension under fasted conditions on Day 1 of Treatment ST in each treatment sequence under each assigned period. Each of the 4 periods were separated by a washout of 7 days.

Secondary

Placebo-corrected Change From Baseline in PR Interval

Placebo-corrected change from Baseline in PR, (ΔΔPR) was calculated based on model-predicted effect. PR interval was the time between the beginning of the P wave and the start of the QRS interval, corresponding to the end of atrial depolarization and onset of ventricular depolarization.

Posted

Least Squares Mean

Standard Error

msec

At 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 12, 24, and 36 hours post-dose

ID	Title	Description
OG000	Therapeutic Dose: ITF2357 100 mg	Participants received orally a single dose of ITF2357 100 milligrams (mg; 10 mg per milliliter [mL]) oral suspension and placebo (matched to ITF2357) oral suspension under fasted conditions on Day 1 of Treatment T in each treatment sequence under each assigned period. Each of the 4 periods were separated by a washout of 7 days.
OG001	Supratherapeutic Dose: ITF2357 300 mg	Participants received orally a single dose of ITF2357 300 mg (as 10 mg/mL) oral suspension under fasted conditions on Day 1 of Treatment ST in each treatment sequence under each assigned period. Each of the 4 periods were separated by a washout of 7 days.

Secondary

Placebo-corrected Change From Baseline in QRS Interval

Placebo-corrected change from baseline for QRS interval, (ΔΔQRS) was calculated based on model-predicted effect. QRS interval is the time from Q wave to the end of the S wave, corresponding to ventricle depolarization.

Posted

Least Squares Mean

Standard Error

msec

At 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 12, 24, and 36 hours post-dose

ID	Title	Description
OG000	Therapeutic Dose: ITF2357 100 mg	Participants received orally a single dose of ITF2357 100 milligrams (mg; 10 mg per milliliter [mL]) oral suspension and placebo (matched to ITF2357) oral suspension under fasted conditions on Day 1 of Treatment T in each treatment sequence under each assigned period. Each of the 4 periods were separated by a washout of 7 days.
OG001	Supratherapeutic Dose: ITF2357 300 mg	Participants received orally a single dose of ITF2357 300 mg (as 10 mg/mL) oral suspension under fasted conditions on Day 1 of Treatment ST in each treatment sequence under each assigned period. Each of the 4 periods were separated by a washout of 7 days.

Secondary

Placebo-corrected Change From Baseline in HR Interval

Placebo-corrected change from baseline in HR, (ΔΔHR) was calculated based on model-predicted effect.

Posted

Least Squares Mean

Standard Error

bpm

At 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 12, 24, and 36 hours post-dose

ID	Title	Description
OG000	Therapeutic Dose: ITF2357 100 mg	Participants received orally a single dose of ITF2357 100 milligrams (mg; 10 mg per milliliter [mL]) oral suspension and placebo (matched to ITF2357) oral suspension under fasted conditions on Day 1 of Treatment T in each treatment sequence under each assigned period. Each of the 4 periods were separated by a washout of 7 days.
OG001	Supratherapeutic Dose: ITF2357 300 mg	Participants received orally a single dose of ITF2357 300 mg (as 10 mg/mL) oral suspension under fasted conditions on Day 1 of Treatment ST in each treatment sequence under each assigned period. Each of the 4 periods were separated by a washout of 7 days.
OG002	Moxifloxacin

Secondary

Number of Participants With Changes in Categorical Outliers for QTcF, PR, and QRS Intervals in the ECG and HR

QTcF:

Treatment-emergent value of greater than (>) 450 and less than or equal to (<=) 480 ms when not present at Baseline (new onset).

Treatment-emergent value of > 480 and <= 500 ms when not present at Baseline (new onset).

Treatment-emergent value of > 500 ms when not present at Baseline (new onset). Increase of QTcF (ΔQTcF) from Baseline of > 30 and <= 60 ms. Increase of QTcF from Baseline > 60 ms

HR:

Decrease of HR from Baseline > 25% resulting in HR less than (<) 50 bpm. Increase of HR from Baseline > 25% resulting in HR > 100 bpm.

PR:

Increase of PR from Baseline > 25% resulting in PR > 210 ms.

QRS:

Increase of QRS from Baseline > 25% resulting in QRS > 120 ms.

Posted

Count of Participants

Participants

Baseline, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 12, 24, and 36 hours post-dose

ID	Title	Description
OG000	Therapeutic Dose: ITF2357 100 mg	Participants received orally a single dose of ITF2357 100 milligrams (mg; 10 mg per milliliter [mL]) oral suspension and placebo (matched to ITF2357) oral suspension under fasted conditions on Day 1 of Treatment T in each treatment sequence under each assigned period. Each of the 4 periods were separated by a washout of 7 days.

Secondary

Number of Participants With Treatment-Emergent Changes of T-Wave Morphology and U Wave Presence

T-wave abnormalities were categorized as follows:

Normal T wave (+): Any positive T wave not meeting any criterion below. Flat T wave: T amplitude < 1 mm (either positive or negative) including flat isoelectric line.

Notched T wave (+): Presence of notch(es) of at least 0.05 mV amplitude on ascending or descending arm of the positive T wave.

Biphasic: T wave that contains a second component with an opposite phase that is at least 0.1 mV deep (both positive/negative and negative/positive and polyphasic T waves included).

Normal T wave (-): T amplitude that is negative, without biphasic T wave or notches.

Notched T wave (-): Presence of notch(es) of at least 0.05 mV amplitude on descending or ascending arm of the negative T wave.

U waves: Presence of abnormal U waves.

The safety population was defined as all participants who received at least 1 dose of study drug (therapeutic and supratherapeutic doses of ITF2357, moxifloxacin, or placebo). Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure.

Posted

Count of Participants

Participants

Up to 44 days

ID	Title	Description
OG000	Therapeutic Dose: ITF2357 100 mg	Participants received orally a single dose of ITF2357 100 milligrams (mg; 10 mg per milliliter [mL]) oral suspension and placebo (matched to ITF2357) oral suspension under fasted conditions on Day 1 of Treatment T in each treatment sequence under each assigned period. Each of the 4 periods were separated by a washout of 7 days.

Secondary

Plasma Pharmacokinetic (PK): Area Under the Concentration-Time Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of ITF2357 and Its Metabolites

The area under the concentration time curve (AUC) from time zero (= dosing time) to the last sampling time (tlast) at which the concentration is at or above the lower limit of quantification. AUC0-t was calculated using the mixed log-linear trapezoidal rule (linear up, log down). AUC0-t of ITF2357 and metabolites: ITF2374, ITF2375, ITF2440, ITF2563, and ITF2955 glucuronide were reported.

The PK population was defined as all participants who completed at least 3 periods, including at least Treatments T, ST, and M for whom the PK profile was adequately characterized. Here, "Number Analyzed" signified participants who were evaluable for this outcome measure at specified category.

Posted

Geometric Mean

Geometric Coefficient of Variation

hours*nanograms per milliliter (h*ng/mL)

Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 12, 24, 36, 48, 60, and 72 hours post-dose

ID	Title	Description
OG000	Therapeutic Dose: ITF2357 100 mg	Participants received orally a single dose of ITF2357 100 milligrams (mg; 10 mg per milliliter [mL]) oral suspension and placebo (matched to ITF2357) oral suspension under fasted conditions on Day 1 of Treatment T in each treatment sequence under each assigned period. Each of the 4 periods were separated by a washout of 7 days.
OG001	Supratherapeutic Dose: ITF2357 300 mg

Secondary

Plasma PK: Area Under the Concentration-Time Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of Moxifloxacin

The PK population was defined as all participants who completed at least 3 periods, including at least Treatments T, ST, and M for whom the PK profile was adequately characterized.

Posted

Geometric Mean

Geometric Coefficient of Variation

h*ng/mL

Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 12, 24, 36, 48, 60, and 72 hours post-dose

ID	Title	Description
OG000	Moxifloxacin	Participants received orally a single dose of moxifloxacin hydrochloride 400 mg tablets under fasted conditions on Day 1 of Treatment M in each treatment sequence under each assigned period. Each of the 4 periods were separated by a washout of 7 days.

Units	Counts
Participants	OG000

Secondary

Plasma PK: Area Under the Concentration-Time Curve From Time Zero to 12 Hours (AUC0-12) of ITF2357 and Its Metabolites

AUC0-12 was calculated using the trapezoidal method for ITF2357 and metabolites: ITF2374, ITF2375, ITF2440, ITF2563, and ITF2955 glucuronide. AUC0-12:: of ITF2357 and its metabolites: ITF2374, ITF2375, ITF2440, ITF2563, and ITF2955 glucuronide were reported.

The PK population was defined as all participants who completed at least 3 periods, including at least Treatments T, ST, and M for whom the PK profile was adequately characterized. Here, "Number Analyzed" signifies participants who were evaluable for this outcome measure at specified category.

Posted

Mean

Standard Deviation

h*ng/mL

Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, and 12 hours post-dose

ID	Title	Description
OG000	Therapeutic Dose: ITF2357 100 mg	Participants received orally a single dose of ITF2357 100 milligrams (mg; 10 mg per milliliter [mL]) oral suspension and placebo (matched to ITF2357) oral suspension under fasted conditions on Day 1 of Treatment T in each treatment sequence under each assigned period. Each of the 4 periods were separated by a washout of 7 days.
OG001	Supratherapeutic Dose: ITF2357 300 mg	Participants received orally a single dose of ITF2357 300 mg (as 10 mg/mL) oral suspension under fasted conditions on Day 1 of Treatment ST in each treatment sequence under each assigned period. Each of the 4 periods were separated by a washout of 7 days.

Secondary

Plasma PK: Area Under the Concentration-Time Curve From Time Zero to 12 Hours (AUC0-12) of Moxifloxacin

AUC0-12 was calculated using the trapezoidal method for Moxifloxacin.

The PK population was defined as all participants who completed at least 3 periods, including at least Treatments T, ST, and M for whom the PK profile was adequately characterized.

Posted

Mean

Standard Deviation

h*ng/mL

Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8 and 12 hours post-dose

ID	Title	Description
OG000	Moxifloxacin	Participants received orally a single dose of moxifloxacin hydrochloride 400 mg tablets under fasted conditions on Day 1 of Treatment M in each treatment sequence under each assigned period. Each of the 4 periods were separated by a washout of 7 days.

Units	Counts
Participants	OG000

Secondary

Plasma PK: Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of ITF2357 and Its Metabolites

AUC0-inf was calculated as AUC0-t + Clast/Kel, where Clast is the last measurable concentration. Elimination rate constant (Kel),was defined as the negative of the estimated slope of the linear regression of the in-transformed concentration versus time profile in the terminal elimination phase. AUC0-inf of ITF2357 and metabolites: ITF2374, ITF2375, ITF2440, ITF2563, and ITF2955 glucuronide were reported.

The PK population was defined as all participants who completed at least 3 periods, including at least Treatments T, ST, and M for whom the PK profile was adequately characterized. Here, "Number Analyzed" signifies participants who were evaluable for this outcome measure at specified category.

Posted

Mean

Standard Deviation

h*ng/mL

Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 12, 24, 36, 48, 60, and 72 hours post-dose

ID	Title	Description
OG000	Therapeutic Dose: ITF2357 100 mg	Participants received orally a single dose of ITF2357 100 milligrams (mg; 10 mg per milliliter [mL]) oral suspension and placebo (matched to ITF2357) oral suspension under fasted conditions on Day 1 of Treatment T in each treatment sequence under each assigned period. Each of the 4 periods were separated by a washout of 7 days.
OG001	Supratherapeutic Dose: ITF2357 300 mg	Participants received orally a single dose of ITF2357 300 mg (as 10 mg/mL) oral suspension under fasted conditions on Day 1 of Treatment ST in each treatment sequence under each assigned period. Each of the 4 periods were separated by a washout of 7 days.

Secondary

Plasma PK: Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of Moxifloxacin

AUC0-inf was calculated as AUC0-t + Clast/Kel, where Clast is the last measurable concentration for Moxifloxacin.

The PK population was defined as all participants who completed at least 3 periods, including at least Treatments T, ST, and M for whom the PK profile was adequately characterized.

Posted

Mean

Standard Deviation

h*ng/mL

Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 12, 24, 36, 48, 60, and 72 hours post-dose

ID	Title	Description
OG000	Moxifloxacin	Participants received orally a single dose of moxifloxacin hydrochloride 400 mg tablets under fasted conditions on Day 1 of Treatment M in each treatment sequence under each assigned period. Each of the 4 periods were separated by a washout of 7 days.

Units	Counts
Participants	OG000

Secondary

Plasma PK: Percentage of Residual Area for ITF2357 and Its Metabolites

Residual area was calculated as 100*(1- AUC0-t / AUC0-inf) for ITF2357 and Metabolites: ITF2374, ITF2375, ITF2440, ITF2563, and ITF2955 glucuronide.

The PK population was defined as all participants who completed at least 3 periods, including at least Treatments T, ST, and M for whom the PK profile was adequately characterized. Here, "Number Analyzed" signifies participants who were evaluable for this outcome measure at specified category.

Posted

Mean

Standard Deviation

Percentage of residual area

Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 12, 24, 36, 48, 60, and 72 hours post-dose

ID	Title	Description
OG000	Therapeutic Dose: ITF2357 100 mg	Participants received orally a single dose of ITF2357 100 milligrams (mg; 10 mg per milliliter [mL]) oral suspension and placebo (matched to ITF2357) oral suspension under fasted conditions on Day 1 of Treatment T in each treatment sequence under each assigned period. Each of the 4 periods were separated by a washout of 7 days.
OG001	Supratherapeutic Dose: ITF2357 300 mg	Participants received orally a single dose of ITF2357 300 mg (as 10 mg/mL) oral suspension under fasted conditions on Day 1 of Treatment ST in each treatment sequence under each assigned period. Each of the 4 periods were separated by a washout of 7 days.

Secondary

Plasma PK: Percentage of Residual Area for Moxifloxacin

Residual area was calculated as 100*(1- AUC0-t / AUC0-inf) for moxifloxacin.

The PK population was defined as all participants who completed at least 3 periods, including at least Treatments T, ST, and M for whom the PK profile was adequately characterized.

Posted

Geometric Mean

Geometric Coefficient of Variation

Percentage of residual area

Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 12, 24, 36, 48, 60, and 72 hours post-dose

ID	Title	Description
OG000	Moxifloxacin	Participants received orally a single dose of moxifloxacin hydrochloride 400 mg tablets under fasted conditions on Day 1 of Treatment M in each treatment sequence under each assigned period. Each of the 4 periods were separated by a washout of 7 days.

Units	Counts
Participants	OG000

Secondary

Plasma PK: Maximum Observed Plasma Concentration (Cmax) of ITF2357 and Its Metabolites

Cmax was calculated for ITF2357 and Metabolites: ITF2374, ITF2375, ITF2440, ITF2563, and ITF2955 glucuronide. Cmax was taken directly from the observed concentration-time curve.

The PK population was defined as all participants who completed at least 3 periods, including at least Treatments T, ST, and M for whom the PK profile was adequately characterized. Here, "Number Analyzed" signifies participants who were evaluable for this outcome measure at specified category.

Posted

Mean

Standard Deviation

ng/mL

Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 12, 24, 36, 48, 60, and 72 hours post-dose

ID	Title	Description
OG000	Therapeutic Dose: ITF2357 100 mg	Participants received orally a single dose of ITF2357 100 milligrams (mg; 10 mg per milliliter [mL]) oral suspension and placebo (matched to ITF2357) oral suspension under fasted conditions on Day 1 of Treatment T in each treatment sequence under each assigned period. Each of the 4 periods were separated by a washout of 7 days.
OG001	Supratherapeutic Dose: ITF2357 300 mg	Participants received orally a single dose of ITF2357 300 mg (as 10 mg/mL) oral suspension under fasted conditions on Day 1 of Treatment ST in each treatment sequence under each assigned period. Each of the 4 periods were separated by a washout of 7 days.

Secondary

Plasma PK: Maximum Observed Plasma Concentration (Cmax) of Moxifloxacin

Cmax was calculated for moxifloxacin. Cmax was taken directly from the observed concentration-time curve.

The PK population was defined as all participants who completed at least 3 periods, including at least Treatments T, ST, and M for whom the PK profile was adequately characterized.

Posted

Mean

Standard Deviation

ng/mL

Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 12, 24, 36, 48, 60, and 72 hours post-dose

ID	Title	Description
OG000	Moxifloxacin	Participants received orally a single dose of moxifloxacin hydrochloride 400 mg tablets under fasted conditions on Day 1 of Treatment M in each treatment sequence under each assigned period. Each of the 4 periods were separated by a washout of 7 days.

Units	Counts
Participants	OG000

Secondary

Plasma PK: Time of Observed Cmax (Tmax) of ITF2357 and Its Metabolites

Tmax was calculated for ITF2357 and Metabolites: ITF2374, ITF2375, ITF2440, ITF2563, and ITF2955 glucuronide. The time to reach the maximum observed plasma concentration obtained directly from plasma concentration time curve.

The PK population was defined as all participants who completed at least 3 periods, including at least Treatments T, ST, and M for whom the PK profile was adequately characterized. Here, "Number Analyzed" signifies participants who were evaluable for this outcome measure at specified category.

Posted

Median

Full Range

hours

Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 12, 24, 36, 48, 60, and 72 hours post-dose

ID	Title	Description
OG000	Therapeutic Dose: ITF2357 100 mg	Participants received orally a single dose of ITF2357 100 milligrams (mg; 10 mg per milliliter [mL]) oral suspension and placebo (matched to ITF2357) oral suspension under fasted conditions on Day 1 of Treatment T in each treatment sequence under each assigned period. Each of the 4 periods were separated by a washout of 7 days.
OG001	Supratherapeutic Dose: ITF2357 300 mg	Participants received orally a single dose of ITF2357 300 mg (as 10 mg/mL) oral suspension under fasted conditions on Day 1 of Treatment ST in each treatment sequence under each assigned period. Each of the 4 periods were separated by a washout of 7 days.

Secondary

Plasma PK: Time of Observed Cmax (Tmax) of Moxifloxacin

Tmax was calculated for Moxifloxacin. The time to reach the maximum observed plasma concentration obtained directly from plasma concentration time curve.

The PK population was defined as all participants who completed at least 3 periods, including at least Treatments T, ST, and M for whom the PK profile was adequately characterized.

Posted

Mean

Full Range

hours

Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 12, 24, 36, 48, 60, and 72 hours post-dose

ID	Title	Description
OG000	Moxifloxacin	Participants received orally a single dose of moxifloxacin hydrochloride 400 mg tablets under fasted conditions on Day 1 of Treatment M in each treatment sequence under each assigned period. Each of the 4 periods were separated by a washout of 7 days.

Units	Counts
Participants	OG000

Secondary

Plasma PK: Elimination Rate Constant (Kel) of ITF2357 and Its Metabolites

Kel was defined as the negative of the estimated slope of the linear regression of the ln-transformed concentration versus time profile in the terminal elimination phase. Kel was calculated for ITF2357 and Metabolites: ITF2374, ITF2375, ITF2440, ITF2563, andITF2955 glucuronide.

The PK population was defined as all participants who completed at least 3 periods, including at least Treatments T, ST, and M for whom the PK profile was adequately characterized. Here, "Number Analyzed" signifies participants who were evaluable for this outcome measure at specified category.

Posted

Mean

Standard Deviation

fraction per hour

Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 12, 24, 36, 48, 60, and 72 hours post-dose

ID	Title	Description
OG000	Therapeutic Dose: ITF2357 100 mg	Participants received orally a single dose of ITF2357 100 milligrams (mg; 10 mg per milliliter [mL]) oral suspension and placebo (matched to ITF2357) oral suspension under fasted conditions on Day 1 of Treatment T in each treatment sequence under each assigned period. Each of the 4 periods were separated by a washout of 7 days.
OG001	Supratherapeutic Dose: ITF2357 300 mg	Participants received orally a single dose of ITF2357 300 mg (as 10 mg/mL) oral suspension under fasted conditions on Day 1 of Treatment ST in each treatment sequence under each assigned period. Each of the 4 periods were separated by a washout of 7 days.

Secondary

Plasma PK: Elimination Rate Constant (Kel) of Moxifloxacin

The PK population was defined as all participants who completed at least 3 periods, including at least Treatments T, ST, and M for whom the PK profile was adequately characterized.

Posted

Mean

Standard Deviation

fraction per hour

Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 12, 24, 36, 48, 60, and 72 hours post-dose

ID	Title	Description
OG000	Moxifloxacin	Participants received orally a single dose of moxifloxacin hydrochloride 400 mg tablets under fasted conditions on Day 1 of Treatment M in each treatment sequence under each assigned period. Each of the 4 periods were separated by a washout of 7 days.

Units	Counts
Participants	OG000

Secondary

Plasma PK: Elimination Half-life (T½ el) of ITF2357 and Its Metabolites

T½ el was calculated as ln(2)/kel for ITF2357 and Metabolites : ITF2374, ITF2375, ITF2440, ITF2563, ITF2955 glucuronide, and Moxifloxacin.

The PK population was defined as all participants who completed at least 3 periods, including at least Treatments T, ST, and M for whom the PK profile was adequately characterized. Here, "Number Analyzed" signifies participants who were evaluable for this outcome measure at specified category.

Posted

Median

Full Range

hours

Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 12, 24, 36, 48, 60, and 72 hours post-dose

ID	Title	Description
OG000	Therapeutic Dose: ITF2357 100 mg	Participants received orally a single dose of ITF2357 100 milligrams (mg; 10 mg per milliliter [mL]) oral suspension and placebo (matched to ITF2357) oral suspension under fasted conditions on Day 1 of Treatment T in each treatment sequence under each assigned period. Each of the 4 periods were separated by a washout of 7 days.
OG001	Supratherapeutic Dose: ITF2357 300 mg	Participants received orally a single dose of ITF2357 300 mg (as 10 mg/mL) oral suspension under fasted conditions on Day 1 of Treatment ST in each treatment sequence under each assigned period. Each of the 4 periods were separated by a washout of 7 days.

Secondary

Plasma PK: Elimination Half-life (T½ el) of Moxifloxacin

T½ el was calculated as ln(2)/kel for moxifloxacin.

The PK population was defined as all participants who completed at least 3 periods, including at least Treatments T, ST, and M for whom the PK profile was adequately characterized.

Posted

Median

Full Range

hours

Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 12, 24, 36, 48, 60, and 72 hours post-dose

ID	Title	Description
OG000	Moxifloxacin	Participants received orally a single dose of moxifloxacin hydrochloride 400 mg tablets under fasted conditions on Day 1 of Treatment M in each treatment sequence under each assigned period. Each of the 4 periods were separated by a washout of 7 days.

Units	Counts
Participants	OG000

Secondary

Plasma PK: Apparent Total Body Clearance (CL/F) of ITF2357 and Its Metabolites

CL/F was calculated as Dose/AUC0-inf for ITF2357 and Metabolites: ITF2374, ITF2375, ITF2440, ITF2563, and ITF2955 glucuronide.

The PK population was defined as all participants who completed at least 3 periods, including at least Treatments T, ST, and M for whom the PK profile was adequately characterized. Here, "Number Analyzed" signifies participants who were evaluable for this outcome measure at specified category.

Posted

Mean

Standard Deviation

liters per hour

Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 12, 24, 36, 48, 60, and 72 hours post-dose

ID	Title	Description
OG000	Therapeutic Dose: ITF2357 100 mg	Participants received orally a single dose of ITF2357 100 milligrams (mg; 10 mg per milliliter [mL]) oral suspension and placebo (matched to ITF2357) oral suspension under fasted conditions on Day 1 of Treatment T in each treatment sequence under each assigned period. Each of the 4 periods were separated by a washout of 7 days.
OG001	Supratherapeutic Dose: ITF2357 300 mg	Participants received orally a single dose of ITF2357 300 mg (as 10 mg/mL) oral suspension under fasted conditions on Day 1 of Treatment ST in each treatment sequence under each assigned period. Each of the 4 periods were separated by a washout of 7 days.

Secondary

Plasma PK: Apparent Total Body Clearance (CL/F) of Moxifloxacin

CL/F was calculated as Dose/AUC0-inf for moxifloxacin.

The PK population was defined as all participants who completed at least 3 periods, including at least Treatments T, ST, and M for whom the PK profile was adequately characterized.

Posted

Mean

Standard Deviation

liters per hour

Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 12, 24, 36, 48, 60, and 72 hours post-dose

ID	Title	Description
OG000	Moxifloxacin	Participants received orally a single dose of moxifloxacin hydrochloride 400 mg tablets under fasted conditions on Day 1 of Treatment M in each treatment sequence under each assigned period. Each of the 4 periods were separated by a washout of 7 days.

Units	Counts
Participants	OG000

Secondary

Plasma PK: Apparent Volume of Distribution (Vd/F) of ITF2357 and Its Metabolites

Vd/F was calculated as Dose/Kel x AUC0-inf for ITF2357 and Metabolites: ITF2374, ITF2375, ITF2440, ITF2563, and ITF2955 glucuronide.

The PK population was defined as all participants who completed at least 3 periods, including at least Treatments T, ST, and M for whom the PK profile was adequately characterized. Here, "Number Analyzed" signifies participants who were evaluable for this outcome measure at specified category.

Posted

Mean

Standard Deviation

liters

Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 12, 24, 36, 48, 60, and 72 hours post-dose

ID	Title	Description
OG000	Therapeutic Dose: ITF2357 100 mg	Participants received orally a single dose of ITF2357 100 milligrams (mg; 10 mg per milliliter [mL]) oral suspension and placebo (matched to ITF2357) oral suspension under fasted conditions on Day 1 of Treatment T in each treatment sequence under each assigned period. Each of the 4 periods were separated by a washout of 7 days.
OG001	Supratherapeutic Dose: ITF2357 300 mg	Participants received orally a single dose of ITF2357 300 mg (as 10 mg/mL) oral suspension under fasted conditions on Day 1 of Treatment ST in each treatment sequence under each assigned period. Each of the 4 periods were separated by a washout of 7 days.

Secondary

Plasma PK: Apparent Volume of Distribution (Vd/F) of Moxifloxacin

Vd/F was calculated as Dose/Kel x AUC0-inf for moxifloxacin.

The PK population was defined as all participants who completed at least 3 periods, including at least Treatments T, ST, and M for whom the PK profile was adequately characterized.

Posted

Mean

Standard Deviation

liters

Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 12, 24, 36, 48, 60, and 72 hours post-dose

ID	Title	Description
OG000	Moxifloxacin	Participants received orally a single dose of moxifloxacin hydrochloride 400 mg tablets under fasted conditions on Day 1 of Treatment M in each treatment sequence under each assigned period. Each of the 4 periods were separated by a washout of 7 days.

Units	Counts
Participants	OG000

Secondary

Urine PK: Cumulative Urinary Excretion From Time Zero to Time t (Ae0-t) for ITF2357 and Its Metabolites

Ae0-t was calculated as the sum of the amounts excreted over each collection interval. The amount excreted in the urine for each time interval is calculated as the urine concentration multiplied by the urine volume for ITF2357 and Metabolites: ITF2374, ITF2375, ITF2440, ITF2563, ITF2955 glucuronide.

The PK population was defined as all participants who completed at least 3 periods, including at least Treatments T, ST, and M for whom the PK profile was adequately characterized. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure.

Posted

Mean

Standard Deviation

Nanograms (ng)

Pre-dose (within 2 hours before dosing), 0-8 hours, 8-24 hours, 24-48 hours, and 48-72 hours post-dose

ID	Title	Description
OG000	Therapeutic Dose: ITF2357 100 mg	Participants received orally a single dose of ITF2357 100 milligrams (mg; 10 mg per milliliter [mL]) oral suspension and placebo (matched to ITF2357) oral suspension under fasted conditions on Day 1 of Treatment T in each treatment sequence under each assigned period. Each of the 4 periods were separated by a washout of 7 days.
OG001	Supratherapeutic Dose: ITF2357 300 mg	Participants received orally a single dose of ITF2357 300 mg (as 10 mg/mL) oral suspension under fasted conditions on Day 1 of Treatment ST in each treatment sequence under each assigned period. Each of the 4 periods were separated by a washout of 7 days.

Secondary

Urine PK: Maximum Rate of Urinary Excretion (Rmax) for ITF2357 and Its Metabolites

Rmax was calculated by dividing the amount of drug excreted in each collection interval by the time over which it was collected for ITF2357 and Metabolites: ITF2374, ITF2375, ITF2440, ITF2563, ITF2955 glucuronide.

The PK population was defined as all participants who completed at least 3 periods, including at least Treatments T, ST, and M for whom the PK profile was adequately characterized. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure.

Posted

Mean

Standard Deviation

Nanogram per hour (ng/h)

Pre-dose (within 2 hours before dosing), 0-8 hours, 8-24 hours, 24-48 hours, and 48-72 hours post-dose

ID	Title	Description
OG000	Therapeutic Dose: ITF2357 100 mg	Participants received orally a single dose of ITF2357 100 milligrams (mg; 10 mg per milliliter [mL]) oral suspension and placebo (matched to ITF2357) oral suspension under fasted conditions on Day 1 of Treatment T in each treatment sequence under each assigned period. Each of the 4 periods were separated by a washout of 7 days.
OG001	Supratherapeutic Dose: ITF2357 300 mg	Participants received orally a single dose of ITF2357 300 mg (as 10 mg/mL) oral suspension under fasted conditions on Day 1 of Treatment ST in each treatment sequence under each assigned period. Each of the 4 periods were separated by a washout of 7 days.

Secondary

Urine PK: Time of Rmax (TRmax) for ITF2357 and Its Metabolites

TRmax was calculated as the midpoint of the collection interval during which Rmax occurred for ITF2357 and Metabolites: ITF2374, ITF2375, ITF2440, ITF2563, ITF2955 glucuronide.

The PK population was defined as all participants who completed at least 3 periods, including at least Treatments T, ST, and M for whom the PK profile was adequately characterized. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure.

Posted

Median

Full Range

hours

Pre-dose (within 2 hours before dosing), 0-8 hours, 8-24 hours, 24-48 hours, and 48-72 hours post-dose

ID	Title	Description
OG000	Therapeutic Dose: ITF2357 100 mg	Participants received orally a single dose of ITF2357 100 milligrams (mg; 10 mg per milliliter [mL]) oral suspension and placebo (matched to ITF2357) oral suspension under fasted conditions on Day 1 of Treatment T in each treatment sequence under each assigned period. Each of the 4 periods were separated by a washout of 7 days.
OG001	Supratherapeutic Dose: ITF2357 300 mg	Participants received orally a single dose of ITF2357 300 mg (as 10 mg/mL) oral suspension under fasted conditions on Day 1 of Treatment ST in each treatment sequence under each assigned period. Each of the 4 periods were separated by a washout of 7 days.

Secondary

Urine PK: Renal Clearance (Clr) for ITF2357 and Its Metabolites

Clr was calculated as Ae0-t / AUC0-t (plasma) for ITF2357 and Metabolites: ITF2374, ITF2375, ITF2440, ITF2563, ITF2955 glucuronide.

The PK population was defined as all participants who completed at least 3 periods, including at least Treatments T, ST, and M for whom the PK profile was adequately characterized. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure and "Number Analyzed" signifies participants evaluable at specific category.

Posted

Mean

Standard Deviation

L/h

Pre-dose (within 2 hours before dosing), 0-8 hours, 8-24 hours, 24-48 hours, and 48-72 hours post-dose

ID	Title	Description
OG000	Therapeutic Dose: ITF2357 100 mg	Participants received orally a single dose of ITF2357 100 milligrams (mg; 10 mg per milliliter [mL]) oral suspension and placebo (matched to ITF2357) oral suspension under fasted conditions on Day 1 of Treatment T in each treatment sequence under each assigned period. Each of the 4 periods were separated by a washout of 7 days.
OG001	Supratherapeutic Dose: ITF2357 300 mg	Participants received orally a single dose of ITF2357 300 mg (as 10 mg/mL) oral suspension under fasted conditions on Day 1 of Treatment ST in each treatment sequence under each assigned period. Each of the 4 periods were separated by a washout of 7 days.

Secondary

Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs

Adverse event (AE) was defined as any untoward medical occurrence in a subject or clinical investigation participant administered a pharmaceutical product and which did not necessarily have a causal relationship with the study drug. Serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; required initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAE were defined as an AEs following the start of treatment or AEs increasing in severity during treatment. TEAEs include both serious and non-serious TEAEs.

The Safety population was defined as all participants who received at least 1 dose of study drug (therapeutic and supratherapeutic doses of ITF2357, moxifloxacin, or placebo).

Posted

Count of Participants

Participants

Baseline up to 44 days

ID	Title	Description
OG000	Therapeutic Dose: ITF2357 100 mg	Participants received orally a single dose of ITF2357 100 milligrams (mg; 10 mg per milliliter [mL]) oral suspension and placebo (matched to ITF2357) oral suspension under fasted conditions on Day 1 of Treatment T in each treatment sequence under each assigned period. Each of the 4 periods were separated by a washout of 7 days.
OG001	Supratherapeutic Dose: ITF2357 300 mg

Secondary

Number of Treatment-Related TEAEs

Adverse event (AE) was defined as any untoward medical occurrence in a subject or clinical investigation participant administered a pharmaceutical product and which did not necessarily have a causal relationship with the study drug. Any AEs which occurred due to study drug treatment are reported as Treatment-related AEs. Number of treatment related TEAEs were reported.

The Safety population was defined as all participants who received at least 1 dose of study drug (therapeutic and supratherapeutic doses of ITF2357, moxifloxacin, or placebo).

Posted

Number

number of events

Baseline up to 44 days

ID	Title	Description
OG000	Therapeutic Dose: ITF2357 100 mg	Participants received orally a single dose of ITF2357 100 milligrams (mg; 10 mg per milliliter [mL]) oral suspension and placebo (matched to ITF2357) oral suspension under fasted conditions on Day 1 of Treatment T in each treatment sequence under each assigned period. Each of the 4 periods were separated by a washout of 7 days.
OG001	Supratherapeutic Dose: ITF2357 300 mg	Participants received orally a single dose of ITF2357 300 mg (as 10 mg/mL) oral suspension under fasted conditions on Day 1 of Treatment ST in each treatment sequence under each assigned period. Each of the 4 periods were separated by a washout of 7 days.
OG002

Secondary

Number of TEAEs Based on Severity

All AEs were analyzed using National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0 and were graded as Grade 1: mild asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated, Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living (ADL), Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL, Grade 4: Life-threatening consequences; urgent intervention indicated, Grade 5: death related AE, where higher grade indicated more severe condition. Number of TEAEs based on severity were reported.

The Safety population was defined as all participants who received at least 1 dose of study drug (therapeutic and supratherapeutic doses of ITF2357, moxifloxacin, or placebo).

Posted

Number

number of events

Baseline up to 44 days

ID	Title	Description
OG000	Therapeutic Dose: ITF2357 100 mg	Participants received orally a single dose of ITF2357 100 milligrams (mg; 10 mg per milliliter [mL]) oral suspension and placebo (matched to ITF2357) oral suspension under fasted conditions on Day 1 of Treatment T in each treatment sequence under each assigned period. Each of the 4 periods were separated by a washout of 7 days.
OG001	Supratherapeutic Dose: ITF2357 300 mg

Secondary

Number of Participants With Clinically Significant Changes in Vital Signs

Vital signs, including semi supine blood pressure, pulse rate, respiratory rate, weight, and oral temperature were assessed. Clinical significance was decided by the investigator. Number of participants with clinically significant change from baseline in vital signs were reported.

The safety population was defined as all participants who received at least 1 dose of study drug (therapeutic and supratherapeutic doses of ITF2357, moxifloxacin, or placebo).

Posted

Count of Participants

Participants

Baseline up to 44 days

ID	Title	Description
OG000	Therapeutic Dose: ITF2357 100 mg	Participants received orally a single dose of ITF2357 100 milligrams (mg; 10 mg per milliliter [mL]) oral suspension and placebo (matched to ITF2357) oral suspension under fasted conditions on Day 1 of Treatment T in each treatment sequence under each assigned period. Each of the 4 periods were separated by a washout of 7 days.
OG001	Supratherapeutic Dose: ITF2357 300 mg	Participants received orally a single dose of ITF2357 300 mg (as 10 mg/mL) oral suspension under fasted conditions on Day 1 of Treatment ST in each treatment sequence under each assigned period. Each of the 4 periods were separated by a washout of 7 days.
OG002

Secondary

Number of Participants With Clinically Significant Changes in Clinical Laboratory Parameters

Clinical laboratory parameters included biochemistry, hematology, and urinalysis. Clinical significance was decided by the investigator. Number of participants with clinically significant change from baseline in clinical laboratory parameters were reported.

The Safety population was defined as all participants who received at least 1 dose of study drug (therapeutic and supratherapeutic doses of ITF2357, moxifloxacin, or placebo).

Posted

Count of Participants

Participants

Baseline up to 44 days

ID	Title	Description
OG000	Therapeutic Dose: ITF2357 100 mg	Participants received orally a single dose of ITF2357 100 milligrams (mg; 10 mg per milliliter [mL]) oral suspension and placebo (matched to ITF2357) oral suspension under fasted conditions on Day 1 of Treatment T in each treatment sequence under each assigned period. Each of the 4 periods were separated by a washout of 7 days.
OG001	Supratherapeutic Dose: ITF2357 300 mg	Participants received orally a single dose of ITF2357 300 mg (as 10 mg/mL) oral suspension under fasted conditions on Day 1 of Treatment ST in each treatment sequence under each assigned period. Each of the 4 periods were separated by a washout of 7 days.
OG002	Placebo

Secondary

Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Findings

ECG parameters included rhythm, ventricular rate, PR interval, QRS duration, and QT interval. Clinical significance was decided by the investigator. Number of participants with clinically significant change from baseline in ECG were reported.

The Safety population was defined as all participants who received at least 1 dose of study drug (therapeutic and supratherapeutic doses of ITF2357, moxifloxacin, or placebo).

Posted

Count of Participants

Participants

Baseline up to 44 days

ID	Title	Description
OG000	Therapeutic Dose: ITF2357 100 mg	Participants received orally a single dose of ITF2357 100 milligrams (mg; 10 mg per milliliter [mL]) oral suspension and placebo (matched to ITF2357) oral suspension under fasted conditions on Day 1 of Treatment T in each treatment sequence under each assigned period. Each of the 4 periods were separated by a washout of 7 days.
OG001	Supratherapeutic Dose: ITF2357 300 mg	Participants received orally a single dose of ITF2357 300 mg (as 10 mg/mL) oral suspension under fasted conditions on Day 1 of Treatment ST in each treatment sequence under each assigned period. Each of the 4 periods were separated by a washout of 7 days.
OG002	Placebo

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Nausea	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG0000 events0 affected29 at risk EG0015 events5 affected31 at risk EG0020 events0 affected31 at risk EG0032 events2 affected31 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG0002 events2 affected29 at risk EG0011 events1 affected31 at risk EG0022 events2 affected31 at risk EG003
Abdominal discomfort	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG0000 events0 affected29 at risk EG0013 events3 affected31 at risk EG0020 events0 affected31 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG0000 events0 affected29 at risk EG0011 events1 affected31 at risk EG0021 events1 affected31 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG0000 events0 affected29 at risk EG0011 events1 affected31 at risk EG0020 events0 affected31 at risk EG003
Abdominal distension	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG0000 events0 affected29 at risk EG0010 events0 affected31 at risk EG0021 events1 affected31 at risk EG003
Eructation	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG0000 events0 affected29 at risk EG0011 events1 affected31 at risk EG0020 events0 affected31 at risk EG003
Faeces soft	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG0000 events0 affected29 at risk EG0011 events1 affected31 at risk EG0020 events0 affected31 at risk EG003
Headache	Nervous system disorders	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected29 at risk EG0014 events4 affected31 at risk EG0021 events1 affected31 at risk EG003
Disturbance in attention	Nervous system disorders	MedDRA 24.0	Systematic Assessment	EG0000 events0 affected29 at risk EG0011 events1 affected31 at risk EG0020 events0 affected31 at risk EG003
Dizziness	Nervous system disorders	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected29 at risk EG0010 events0 affected31 at risk EG0020 events0 affected31 at risk EG003
Dysgeusia	Nervous system disorders	MedDRA 24.0	Systematic Assessment	EG0000 events0 affected29 at risk EG0011 events1 affected31 at risk EG0020 events0 affected31 at risk EG003
White blood cells urine positive	Investigations	MedDRA 24.0	Systematic Assessment	EG0000 events0 affected29 at risk EG0011 events1 affected31 at risk EG0020 events0 affected31 at risk EG003
Blood triglycerides increased	Investigations	MedDRA 24.0	Systematic Assessment	EG0000 events0 affected29 at risk EG0011 events1 affected31 at risk EG0020 events0 affected31 at risk EG003
Heart rate irregular	Investigations	MedDRA 24.0	Systematic Assessment	EG0000 events0 affected29 at risk EG0011 events1 affected31 at risk EG0020 events0 affected31 at risk EG003
Sensation of foreign body	General disorders	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected29 at risk EG0010 events0 affected31 at risk EG0020 events0 affected31 at risk EG003
Vessel puncture site haematoma	General disorders	MedDRA 24.0	Systematic Assessment	EG0000 events0 affected29 at risk EG0010 events0 affected31 at risk EG0021 events1 affected31 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected29 at risk EG0011 events1 affected31 at risk EG0020 events0 affected31 at risk EG003
Pain in jaw	Musculoskeletal and connective tissue disorders	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected29 at risk EG0010 events0 affected31 at risk EG0020 events0 affected31 at risk EG003
Dermatitis contact	Skin and subcutaneous tissue disorders	MedDRA 24.0	Systematic Assessment	EG0000 events0 affected29 at risk EG0011 events1 affected31 at risk EG0021 events1 affected31 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 24.0	Systematic Assessment	EG0000 events0 affected29 at risk EG0010 events0 affected31 at risk EG0020 events0 affected31 at risk EG003
Nasal dryness	Respiratory, thoracic and mediastinal disorders	MedDRA 24.0	Systematic Assessment	EG0000 events0 affected29 at risk EG0010 events0 affected31 at risk EG0020 events0 affected31 at risk EG003
Folliculitis	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0000 events0 affected29 at risk EG0011 events1 affected31 at risk EG0020 events0 affected31 at risk EG003

ID	Term
D009136	Muscular Dystrophies
D020966	Muscular Disorders, Atrophic
D009135	Muscular Diseases
D009140	Musculoskeletal Diseases
D009468	Neuromuscular Diseases
D009422	Nervous System Diseases
D040181	Genetic Diseases, X-Linked
D030342	Genetic Diseases, Inborn
D009358	Congenital, Hereditary, and Neonatal Diseases and Abnormalities

ID	Term
C502418	givinostat hydrochloride
C575255	givinostat
D000077266	Moxifloxacin

ID	Term
D024841	Fluoroquinolones
D042462	4-Quinolones
D015363	Quinolones
D011804	Quinolines
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D006571	Heterocyclic Compounds

ID	Title	Description	Deaths (At Risk)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Therapeutic Dose: ITF2357 100 mg	Participants received orally a single dose of ITF2357 100 milligrams (mg; 10 mg per milliliter [mL]) oral suspension and placebo (matched to ITF2357) oral suspension under fasted conditions on Day 1 of Treatment T in each treatment sequence under each assigned period. Each of the 4 periods were separated by a washout of 7 days.	29	29	5	29
EG001	Supratherapeutic Dose: ITF2357 300 mg	Participants received orally a single dose of ITF2357 300 mg (as 10 mg/mL) oral suspension under fasted conditions on Day 1 of Treatment ST in each treatment sequence under each assigned period. Each of the 4 periods were separated by a washout of 7 days.	31	31	15	31
EG002	Placebo	Participants received orally a single dose of placebo (matched to ITL2357) oral suspension under fasted conditions on Day 1 of Treatment P in each treatment sequence under each assigned period. Each of the 4 periods were separated by a washout of 7 days.	31	31	6	31
EG003	Moxifloxacin	Participants received orally a single dose of moxifloxacin hydrochloride 400 mg tablets under fasted conditions on Day 1 of Treatment M in each treatment sequence under each assigned period. Each of the 4 periods were separated by a washout of 7 days.	31	31	4	31