Duchenne and Becker Muscular Dystrophy, Polycytemia Vera
Conditions
Brief summary
The study will evaluate the effect of a therapeutic dose and a supratherapeutic dose of ITF2357 on the QT/QTc interval.
Interventions
DRUGITF2357 10 mg/mL
Dose: 100 mg (administered as 10 mL); Dosage form: suspension; Route of administration: oral
DRUGPlacebo
Dose: 20 mL; Dosage form: suspension; Route of administration: oral
Dose: 400 mg; Dosage form: tablet; Route of administration: oral
Sponsors
Italfarmaco
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
ITF2357 (therapeutic dose and supratherapeutic dose, and placebo) will be administered in a double-blinded fashion whereas no blinding will be needed with treatment moxifloxacin.
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
1. 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. 2. 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. 3. 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). 4. 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; 5. 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. 6. 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. 7. Male participants must be willing not to donate sperm until 90 days following the last study drug administration. 8. Female participants must be willing not to donate ovules until 90 days following the last study drug administration. 9. Participant's written informed consent obtained prior to any study-related procedure. 10. Willingness and capability to comply with the requirements of the study and ability to understand the study procedures and the risks involved. 11. Willing to take out dentures and mouth piercings for study procedures.
Exclusion criteria
1. 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. 2. 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. 3. 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Placebo-corrected Change From Baseline in Fridericia's Corrected QT Interval (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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in PR Interval | At 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 12, 24, and 36 hours post-dose | 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. |
| Change From Baseline in QRS Interval | At 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 12, 24, and 36 hours post-dose | 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. |
| Change From Baseline in Heart Rate (HR) Interval | At 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 12, 24, and 36 hours post-dose | 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. |
| Placebo-corrected Change From Baseline in PR Interval | At 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 12, 24, and 36 hours post-dose | 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. |
| Placebo-corrected Change From Baseline in QRS Interval | At 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 12, 24, and 36 hours post-dose | 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. |
| Placebo-corrected Change From Baseline in HR Interval | At 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 12, 24, and 36 hours post-dose | Placebo-corrected change from baseline in HR, (ΔΔHR) was calculated based on model-predicted effect. |
| Number of Participants With Changes in Categorical Outliers for QTcF, PR, and QRS Intervals in the ECG and HR | Baseline, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 12, 24, and 36 hours post-dose | 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. |
| Number of Participants With Treatment-Emergent Changes of T-Wave Morphology and U Wave Presence | Up to 44 days | 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. |
| Plasma Pharmacokinetic (PK): Area Under the Concentration-Time Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of ITF2357 and Its Metabolites | 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 | 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. |
| Plasma PK: Area Under the Concentration-Time Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of Moxifloxacin | 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 | 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). |
| Plasma PK: Area Under the Concentration-Time Curve From Time Zero to 12 Hours (AUC0-12) of ITF2357 and Its Metabolites | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, and 12 hours post-dose | 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. |
| Plasma PK: Area Under the Concentration-Time Curve From Time Zero to 12 Hours (AUC0-12) of Moxifloxacin | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8 and 12 hours post-dose | AUC0-12 was calculated using the trapezoidal method for Moxifloxacin. |
| Plasma PK: Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of ITF2357 and Its Metabolites | 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 | 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. |
| Plasma PK: Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of Moxifloxacin | 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 | AUC0-inf was calculated as AUC0-t + Clast/Kel, where Clast is the last measurable concentration for Moxifloxacin. |
| Plasma PK: Percentage of Residual Area for ITF2357 and Its Metabolites | 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 | Residual area was calculated as 100\*(1- AUC0-t / AUC0-inf) for ITF2357 and Metabolites: ITF2374, ITF2375, ITF2440, ITF2563, and ITF2955 glucuronide. |
| Plasma PK: Percentage of Residual Area for Moxifloxacin | 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 | Residual area was calculated as 100\*(1- AUC0-t / AUC0-inf) for moxifloxacin. |
| Plasma PK: Maximum Observed Plasma Concentration (Cmax) of ITF2357 and Its Metabolites | 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 | Cmax was calculated for ITF2357 and Metabolites: ITF2374, ITF2375, ITF2440, ITF2563, and ITF2955 glucuronide. Cmax was taken directly from the observed concentration-time curve. |
| Plasma PK: Maximum Observed Plasma Concentration (Cmax) of Moxifloxacin | 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 | Cmax was calculated for moxifloxacin. Cmax was taken directly from the observed concentration-time curve. |
| Plasma PK: Time of Observed Cmax (Tmax) of ITF2357 and Its Metabolites | 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 | 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. |
| Change From Baseline in QTcF Interval | At 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 12, 24, and 36 hours post-dose | 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). |
| Plasma PK: Elimination Rate Constant (Kel) of ITF2357 and Its Metabolites | 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 | 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. |
| Plasma PK: Elimination Rate Constant (Kel) of Moxifloxacin | 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 | 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 Moxifloxacin. |
| Plasma PK: Elimination Half-life (T½ el) of ITF2357 and Its Metabolites | 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 | T½ el was calculated as ln(2)/kel for ITF2357 and Metabolites : ITF2374, ITF2375, ITF2440, ITF2563, ITF2955 glucuronide, and Moxifloxacin. |
| Plasma PK: Elimination Half-life (T½ el) of Moxifloxacin | 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 | T½ el was calculated as ln(2)/kel for moxifloxacin. |
| Plasma PK: Apparent Total Body Clearance (CL/F) of ITF2357 and Its Metabolites | 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 | CL/F was calculated as Dose/AUC0-inf for ITF2357 and Metabolites: ITF2374, ITF2375, ITF2440, ITF2563, and ITF2955 glucuronide. |
| Plasma PK: Apparent Total Body Clearance (CL/F) of Moxifloxacin | 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 | CL/F was calculated as Dose/AUC0-inf for moxifloxacin. |
| Plasma PK: Apparent Volume of Distribution (Vd/F) of ITF2357 and Its Metabolites | 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 | Vd/F was calculated as Dose/Kel x AUC0-inf for ITF2357 and Metabolites: ITF2374, ITF2375, ITF2440, ITF2563, and ITF2955 glucuronide. |
| Plasma PK: Apparent Volume of Distribution (Vd/F) of Moxifloxacin | 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 | Vd/F was calculated as Dose/Kel x AUC0-inf for moxifloxacin. |
| Urine PK: Cumulative Urinary Excretion From Time Zero to Time t (Ae0-t) for ITF2357 and Its Metabolites | Pre-dose (within 2 hours before dosing), 0-8 hours, 8-24 hours, 24-48 hours, and 48-72 hours post-dose | 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. |
| Urine PK: Maximum Rate of Urinary Excretion (Rmax) for ITF2357 and Its Metabolites | Pre-dose (within 2 hours before dosing), 0-8 hours, 8-24 hours, 24-48 hours, and 48-72 hours post-dose | 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. |
| Urine PK: Time of Rmax (TRmax) for ITF2357 and Its Metabolites | Pre-dose (within 2 hours before dosing), 0-8 hours, 8-24 hours, 24-48 hours, and 48-72 hours post-dose | TRmax was calculated as the midpoint of the collection interval during which Rmax occurred for ITF2357 and Metabolites: ITF2374, ITF2375, ITF2440, ITF2563, ITF2955 glucuronide. |
| Urine PK: Renal Clearance (Clr) for ITF2357 and Its Metabolites | Pre-dose (within 2 hours before dosing), 0-8 hours, 8-24 hours, 24-48 hours, and 48-72 hours post-dose | Clr was calculated as Ae0-t / AUC0-t (plasma) for ITF2357 and Metabolites: ITF2374, ITF2375, ITF2440, ITF2563, ITF2955 glucuronide. |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs | Baseline up to 44 days | 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. |
| Number of Treatment-Related TEAEs | Baseline up to 44 days | 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. |
| Number of TEAEs Based on Severity | Baseline up to 44 days | 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. |
| Number of Participants With Clinically Significant Changes in Vital Signs | Baseline up to 44 days | 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. |
| Number of Participants With Clinically Significant Changes in Clinical Laboratory Parameters | Baseline up to 44 days | 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. |
| Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Findings | Baseline up to 44 days | 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. |
| Plasma PK: Time of Observed Cmax (Tmax) of Moxifloxacin | 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 | Tmax was calculated for Moxifloxacin. The time to reach the maximum observed plasma concentration obtained directly from plasma concentration time curve. |
Countries
Canada
Participant flow
Recruitment details
The study was conducted at a single center in Canada. A total of 34 healthy non-smoker were screened in the study, of which 31 participants were enrolled and received the study treatment. Screen failures were mainly due to not meeting inclusion criteria.
Pre-assignment details
Participants were administered the following treatments: Treatment T (Therapeutic dose of ITF2357 100 mg), Treatment ST (Supratherapeutic dose of ITF2357 300 mg), Treatment P (Placebo), and Treatment M (Moxifloxacin) in 4-periods and 12-sequences in this study.
Participants by arm
| Arm | Count |
|---|---|
| All Participants All participants received a single dose of placebo matched to ITL2357 and moxifloxacin hydrochloride 400 mg tablets under fasted conditions, followed by a single dose of ITF2357 100 and 300 mg oral suspensions in respective 12 fixed sequences (TSTPM, STMTP, PTMST, MPSTT, STPTM, PMSTT, TSTMP, MTPST, PTSTM, TMPST, STPMT, MSTTP) in Periods 1, 2, 3 and 4. Each period was separated by a washout period of 7 days. | 31 |
| Total | 31 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Continuous | 40.6 years STANDARD_DEVIATION 10.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 10 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 21 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 27 Participants |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 29 | 0 / 31 | 0 / 31 | 0 / 31 |
| other Total, other adverse events | 5 / 29 | 15 / 31 | 6 / 31 | 4 / 31 |
| serious Total, serious adverse events | 0 / 29 | 0 / 31 | 0 / 31 | 0 / 31 |
Outcome results
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.
Time frame: At 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 12, 24, and 36 hours post-dose
Population: 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.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Therapeutic Dose: ITF2357 100 mg | Placebo-corrected Change From Baseline in Fridericia's Corrected QT Interval (QTcF) | 3 hours Post-dose | 2.3 Milliseconds (msec) | Standard Error 1.06 |
| Therapeutic Dose: ITF2357 100 mg | Placebo-corrected Change From Baseline in Fridericia's Corrected QT Interval (QTcF) | 1.5 hours Post-dose | 1.0 Milliseconds (msec) | Standard Error 0.99 |
| Therapeutic Dose: ITF2357 100 mg | Placebo-corrected Change From Baseline in Fridericia's Corrected QT Interval (QTcF) | 7 hours Post-dose | 3.0 Milliseconds (msec) | Standard Error 1.76 |
| Therapeutic Dose: ITF2357 100 mg | Placebo-corrected Change From Baseline in Fridericia's Corrected QT Interval (QTcF) | 3.5 hours Post-dose | 2.8 Milliseconds (msec) | Standard Error 1.14 |
| Therapeutic Dose: ITF2357 100 mg | Placebo-corrected Change From Baseline in Fridericia's Corrected QT Interval (QTcF) | 1 hours post-dose | 0.3 Milliseconds (msec) | Standard Error 1.01 |
| Therapeutic Dose: ITF2357 100 mg | Placebo-corrected Change From Baseline in Fridericia's Corrected QT Interval (QTcF) | 6 hours Post-dose | 3.8 Milliseconds (msec) | Standard Error 1.82 |
| Therapeutic Dose: ITF2357 100 mg | Placebo-corrected Change From Baseline in Fridericia's Corrected QT Interval (QTcF) | 4 hours Post-dose | 4.0 Milliseconds (msec) | Standard Error 1.13 |
| Therapeutic Dose: ITF2357 100 mg | Placebo-corrected Change From Baseline in Fridericia's Corrected QT Interval (QTcF) | 24 hours Post-dose | 2.3 Milliseconds (msec) | Standard Error 1.62 |
| Therapeutic Dose: ITF2357 100 mg | Placebo-corrected Change From Baseline in Fridericia's Corrected QT Interval (QTcF) | 5 hours Post-dose | 5.5 Milliseconds (msec) | Standard Error 2.11 |
| Therapeutic Dose: ITF2357 100 mg | Placebo-corrected Change From Baseline in Fridericia's Corrected QT Interval (QTcF) | 2 hours Post-dose | 2.1 Milliseconds (msec) | Standard Error 1 |
| Therapeutic Dose: ITF2357 100 mg | Placebo-corrected Change From Baseline in Fridericia's Corrected QT Interval (QTcF) | 0.5 hours post-dose | 1.0 Milliseconds (msec) | Standard Error 1.06 |
| Therapeutic Dose: ITF2357 100 mg | Placebo-corrected Change From Baseline in Fridericia's Corrected QT Interval (QTcF) | 12 hours Post-dose | 2.5 Milliseconds (msec) | Standard Error 1.85 |
| Therapeutic Dose: ITF2357 100 mg | Placebo-corrected Change From Baseline in Fridericia's Corrected QT Interval (QTcF) | 2.5 hours Post-dose | 3.6 Milliseconds (msec) | Standard Error 1.17 |
| Therapeutic Dose: ITF2357 100 mg | Placebo-corrected Change From Baseline in Fridericia's Corrected QT Interval (QTcF) | 36 hours Post-dose | -0.9 Milliseconds (msec) | Standard Error 1.86 |
| Therapeutic Dose: ITF2357 100 mg | Placebo-corrected Change From Baseline in Fridericia's Corrected QT Interval (QTcF) | 8 hours Post-dose | 3.5 Milliseconds (msec) | Standard Error 1.57 |
| Supratherapeutic Dose: ITF2357 300 mg | Placebo-corrected Change From Baseline in Fridericia's Corrected QT Interval (QTcF) | 8 hours Post-dose | 11.5 Milliseconds (msec) | Standard Error 1.54 |
| Supratherapeutic Dose: ITF2357 300 mg | Placebo-corrected Change From Baseline in Fridericia's Corrected QT Interval (QTcF) | 0.5 hours post-dose | 0.5 Milliseconds (msec) | Standard Error 1.04 |
| Supratherapeutic Dose: ITF2357 300 mg | Placebo-corrected Change From Baseline in Fridericia's Corrected QT Interval (QTcF) | 1 hours post-dose | 0.8 Milliseconds (msec) | Standard Error 0.99 |
| Supratherapeutic Dose: ITF2357 300 mg | Placebo-corrected Change From Baseline in Fridericia's Corrected QT Interval (QTcF) | 1.5 hours Post-dose | 2.7 Milliseconds (msec) | Standard Error 0.97 |
| Supratherapeutic Dose: ITF2357 300 mg | Placebo-corrected Change From Baseline in Fridericia's Corrected QT Interval (QTcF) | 2 hours Post-dose | 4.3 Milliseconds (msec) | Standard Error 0.98 |
| Supratherapeutic Dose: ITF2357 300 mg | Placebo-corrected Change From Baseline in Fridericia's Corrected QT Interval (QTcF) | 2.5 hours Post-dose | 6.1 Milliseconds (msec) | Standard Error 1.15 |
| Supratherapeutic Dose: ITF2357 300 mg | Placebo-corrected Change From Baseline in Fridericia's Corrected QT Interval (QTcF) | 3 hours Post-dose | 6.6 Milliseconds (msec) | Standard Error 1.04 |
| Supratherapeutic Dose: ITF2357 300 mg | Placebo-corrected Change From Baseline in Fridericia's Corrected QT Interval (QTcF) | 3.5 hours Post-dose | 9.1 Milliseconds (msec) | Standard Error 1.12 |
| Supratherapeutic Dose: ITF2357 300 mg | Placebo-corrected Change From Baseline in Fridericia's Corrected QT Interval (QTcF) | 4 hours Post-dose | 10.4 Milliseconds (msec) | Standard Error 1.11 |
| Supratherapeutic Dose: ITF2357 300 mg | Placebo-corrected Change From Baseline in Fridericia's Corrected QT Interval (QTcF) | 5 hours Post-dose | 13.6 Milliseconds (msec) | Standard Error 2.08 |
| Supratherapeutic Dose: ITF2357 300 mg | Placebo-corrected Change From Baseline in Fridericia's Corrected QT Interval (QTcF) | 6 hours Post-dose | 11.4 Milliseconds (msec) | Standard Error 1.79 |
| Supratherapeutic Dose: ITF2357 300 mg | Placebo-corrected Change From Baseline in Fridericia's Corrected QT Interval (QTcF) | 7 hours Post-dose | 9.2 Milliseconds (msec) | Standard Error 1.73 |
| Supratherapeutic Dose: ITF2357 300 mg | Placebo-corrected Change From Baseline in Fridericia's Corrected QT Interval (QTcF) | 12 hours Post-dose | 10.2 Milliseconds (msec) | Standard Error 1.82 |
| Supratherapeutic Dose: ITF2357 300 mg | Placebo-corrected Change From Baseline in Fridericia's Corrected QT Interval (QTcF) | 24 hours Post-dose | 11.0 Milliseconds (msec) | Standard Error 1.59 |
| Supratherapeutic Dose: ITF2357 300 mg | Placebo-corrected Change From Baseline in Fridericia's Corrected QT Interval (QTcF) | 36 hours Post-dose | 1.5 Milliseconds (msec) | Standard Error 1.83 |
| Moxifloxacin | Placebo-corrected Change From Baseline in Fridericia's Corrected QT Interval (QTcF) | 3 hours Post-dose | 14.0 Milliseconds (msec) | Standard Error 1.05 |
| Moxifloxacin | Placebo-corrected Change From Baseline in Fridericia's Corrected QT Interval (QTcF) | 1 hours post-dose | 13.1 Milliseconds (msec) | Standard Error 1 |
| Moxifloxacin | Placebo-corrected Change From Baseline in Fridericia's Corrected QT Interval (QTcF) | 7 hours Post-dose | 9.6 Milliseconds (msec) | Standard Error 1.74 |
| Moxifloxacin | Placebo-corrected Change From Baseline in Fridericia's Corrected QT Interval (QTcF) | 2.5 hours Post-dose | 14.8 Milliseconds (msec) | Standard Error 1.16 |
| Moxifloxacin | Placebo-corrected Change From Baseline in Fridericia's Corrected QT Interval (QTcF) | 8 hours Post-dose | 11.3 Milliseconds (msec) | Standard Error 1.55 |
| Moxifloxacin | Placebo-corrected Change From Baseline in Fridericia's Corrected QT Interval (QTcF) | 2 hours Post-dose | 14.0 Milliseconds (msec) | Standard Error 0.99 |
| Moxifloxacin | Placebo-corrected Change From Baseline in Fridericia's Corrected QT Interval (QTcF) | 0.5 hours post-dose | 10.2 Milliseconds (msec) | Standard Error 1.05 |
| Moxifloxacin | Placebo-corrected Change From Baseline in Fridericia's Corrected QT Interval (QTcF) | 12 hours Post-dose | 7.9 Milliseconds (msec) | Standard Error 1.83 |
| Moxifloxacin | Placebo-corrected Change From Baseline in Fridericia's Corrected QT Interval (QTcF) | 1.5 hours Post-dose | 12.3 Milliseconds (msec) | Standard Error 0.98 |
| Moxifloxacin | Placebo-corrected Change From Baseline in Fridericia's Corrected QT Interval (QTcF) | 4 hours Post-dose | 11.9 Milliseconds (msec) | Standard Error 1.12 |
| Moxifloxacin | Placebo-corrected Change From Baseline in Fridericia's Corrected QT Interval (QTcF) | 36 hours Post-dose | 1.8 Milliseconds (msec) | Standard Error 1.84 |
| Moxifloxacin | Placebo-corrected Change From Baseline in Fridericia's Corrected QT Interval (QTcF) | 5 hours Post-dose | 12.1 Milliseconds (msec) | Standard Error 2.09 |
| Moxifloxacin | Placebo-corrected Change From Baseline in Fridericia's Corrected QT Interval (QTcF) | 3.5 hours Post-dose | 12.8 Milliseconds (msec) | Standard Error 1.13 |
| Moxifloxacin | Placebo-corrected Change From Baseline in Fridericia's Corrected QT Interval (QTcF) | 24 hours Post-dose | 5.6 Milliseconds (msec) | Standard Error 1.61 |
| Moxifloxacin | Placebo-corrected Change From Baseline in Fridericia's Corrected QT Interval (QTcF) | 6 hours Post-dose | 9.7 Milliseconds (msec) | Standard Error 1.81 |
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.
Time frame: At 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 12, 24, and 36 hours post-dose
Population: 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.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Therapeutic Dose: ITF2357 100 mg | Change From Baseline in Heart Rate (HR) Interval | 24 hours Post-dose | 0.6 beats per minute (bpm) | Standard Error 0.8 |
| Therapeutic Dose: ITF2357 100 mg | Change From Baseline in Heart Rate (HR) Interval | 4 hours Post-dose | 4.3 beats per minute (bpm) | Standard Error 0.94 |
| Therapeutic Dose: ITF2357 100 mg | Change From Baseline in Heart Rate (HR) Interval | 3.5 hours Post-dose | 4.0 beats per minute (bpm) | Standard Error 0.89 |
| Therapeutic Dose: ITF2357 100 mg | Change From Baseline in Heart Rate (HR) Interval | 2.5 hours Post-dose | 3.8 beats per minute (bpm) | Standard Error 0.99 |
| Therapeutic Dose: ITF2357 100 mg | Change From Baseline in Heart Rate (HR) Interval | 12 hours Post-dose | 9.5 beats per minute (bpm) | Standard Error 1.14 |
| Therapeutic Dose: ITF2357 100 mg | Change From Baseline in Heart Rate (HR) Interval | 3 hours Post-dose | 4.3 beats per minute (bpm) | Standard Error 0.86 |
| Therapeutic Dose: ITF2357 100 mg | Change From Baseline in Heart Rate (HR) Interval | 1 hours Post-dose | 1.2 beats per minute (bpm) | Standard Error 0.85 |
| Therapeutic Dose: ITF2357 100 mg | Change From Baseline in Heart Rate (HR) Interval | 0.5 hours Post-dose | 0.6 beats per minute (bpm) | Standard Error 0.76 |
| Therapeutic Dose: ITF2357 100 mg | Change From Baseline in Heart Rate (HR) Interval | 8 hours Post-dose | 7.4 beats per minute (bpm) | Standard Error 0.88 |
| Therapeutic Dose: ITF2357 100 mg | Change From Baseline in Heart Rate (HR) Interval | 7 hours Post-dose | 8.2 beats per minute (bpm) | Standard Error 1.04 |
| Therapeutic Dose: ITF2357 100 mg | Change From Baseline in Heart Rate (HR) Interval | 1.5 hours Post-dose | 3.3 beats per minute (bpm) | Standard Error 0.85 |
| Therapeutic Dose: ITF2357 100 mg | Change From Baseline in Heart Rate (HR) Interval | 36 hours Post-dose | 9.1 beats per minute (bpm) | Standard Error 1.18 |
| Therapeutic Dose: ITF2357 100 mg | Change From Baseline in Heart Rate (HR) Interval | 6 hours Post-dose | 12.4 beats per minute (bpm) | Standard Error 1.1 |
| Therapeutic Dose: ITF2357 100 mg | Change From Baseline in Heart Rate (HR) Interval | 5 hours Post-dose | 15.0 beats per minute (bpm) | Standard Error 1 |
| Therapeutic Dose: ITF2357 100 mg | Change From Baseline in Heart Rate (HR) Interval | 2 hours Post-dose | 3.7 beats per minute (bpm) | Standard Error 0.86 |
| Supratherapeutic Dose: ITF2357 300 mg | Change From Baseline in Heart Rate (HR) Interval | 8 hours Post-dose | 14.0 beats per minute (bpm) | Standard Error 0.86 |
| Supratherapeutic Dose: ITF2357 300 mg | Change From Baseline in Heart Rate (HR) Interval | 0.5 hours Post-dose | 1.1 beats per minute (bpm) | Standard Error 0.75 |
| Supratherapeutic Dose: ITF2357 300 mg | Change From Baseline in Heart Rate (HR) Interval | 1 hours Post-dose | 2.8 beats per minute (bpm) | Standard Error 0.83 |
| Supratherapeutic Dose: ITF2357 300 mg | Change From Baseline in Heart Rate (HR) Interval | 1.5 hours Post-dose | 5.1 beats per minute (bpm) | Standard Error 0.83 |
| Supratherapeutic Dose: ITF2357 300 mg | Change From Baseline in Heart Rate (HR) Interval | 2 hours Post-dose | 7.8 beats per minute (bpm) | Standard Error 0.84 |
| Supratherapeutic Dose: ITF2357 300 mg | Change From Baseline in Heart Rate (HR) Interval | 2.5 hours Post-dose | 9.9 beats per minute (bpm) | Standard Error 0.97 |
| Supratherapeutic Dose: ITF2357 300 mg | Change From Baseline in Heart Rate (HR) Interval | 3 hours Post-dose | 10.5 beats per minute (bpm) | Standard Error 0.84 |
| Supratherapeutic Dose: ITF2357 300 mg | Change From Baseline in Heart Rate (HR) Interval | 3.5 hours Post-dose | 9.9 beats per minute (bpm) | Standard Error 0.87 |
| Supratherapeutic Dose: ITF2357 300 mg | Change From Baseline in Heart Rate (HR) Interval | 4 hours Post-dose | 11.0 beats per minute (bpm) | Standard Error 0.92 |
| Supratherapeutic Dose: ITF2357 300 mg | Change From Baseline in Heart Rate (HR) Interval | 5 hours Post-dose | 22.1 beats per minute (bpm) | Standard Error 0.98 |
| Supratherapeutic Dose: ITF2357 300 mg | Change From Baseline in Heart Rate (HR) Interval | 7 hours Post-dose | 17.0 beats per minute (bpm) | Standard Error 1.02 |
| Supratherapeutic Dose: ITF2357 300 mg | Change From Baseline in Heart Rate (HR) Interval | 6 hours Post-dose | 21.7 beats per minute (bpm) | Standard Error 1.07 |
| Supratherapeutic Dose: ITF2357 300 mg | Change From Baseline in Heart Rate (HR) Interval | 12 hours Post-dose | 12.7 beats per minute (bpm) | Standard Error 1.11 |
| Supratherapeutic Dose: ITF2357 300 mg | Change From Baseline in Heart Rate (HR) Interval | 24 hours Post-dose | 2.1 beats per minute (bpm) | Standard Error 0.79 |
| Supratherapeutic Dose: ITF2357 300 mg | Change From Baseline in Heart Rate (HR) Interval | 36 hours Post-dose | 8.1 beats per minute (bpm) | Standard Error 1.15 |
| Moxifloxacin | Change From Baseline in Heart Rate (HR) Interval | 2 hours Post-dose | 1.4 beats per minute (bpm) | Standard Error 0.85 |
| Moxifloxacin | Change From Baseline in Heart Rate (HR) Interval | 36 hours Post-dose | 10.2 beats per minute (bpm) | Standard Error 1.16 |
| Moxifloxacin | Change From Baseline in Heart Rate (HR) Interval | 4 hours Post-dose | 2.3 beats per minute (bpm) | Standard Error 0.93 |
| Moxifloxacin | Change From Baseline in Heart Rate (HR) Interval | 24 hours Post-dose | 1.6 beats per minute (bpm) | Standard Error 0.8 |
| Moxifloxacin | Change From Baseline in Heart Rate (HR) Interval | 5 hours Post-dose | 10.6 beats per minute (bpm) | Standard Error 0.99 |
| Moxifloxacin | Change From Baseline in Heart Rate (HR) Interval | 1.5 hours Post-dose | 1.9 beats per minute (bpm) | Standard Error 0.84 |
| Moxifloxacin | Change From Baseline in Heart Rate (HR) Interval | 7 hours Post-dose | 7.5 beats per minute (bpm) | Standard Error 1.03 |
| Moxifloxacin | Change From Baseline in Heart Rate (HR) Interval | 1 hours Post-dose | 2.3 beats per minute (bpm) | Standard Error 0.84 |
| Moxifloxacin | Change From Baseline in Heart Rate (HR) Interval | 6 hours Post-dose | 10.2 beats per minute (bpm) | Standard Error 1.08 |
| Moxifloxacin | Change From Baseline in Heart Rate (HR) Interval | 8 hours Post-dose | 6.2 beats per minute (bpm) | Standard Error 0.87 |
| Moxifloxacin | Change From Baseline in Heart Rate (HR) Interval | 12 hours Post-dose | 10.6 beats per minute (bpm) | Standard Error 1.13 |
| Moxifloxacin | Change From Baseline in Heart Rate (HR) Interval | 2.5 hours Post-dose | 0.9 beats per minute (bpm) | Standard Error 0.98 |
| Moxifloxacin | Change From Baseline in Heart Rate (HR) Interval | 3 hours Post-dose | 1.4 beats per minute (bpm) | Standard Error 0.85 |
| Moxifloxacin | Change From Baseline in Heart Rate (HR) Interval | 0.5 hours Post-dose | 1.3 beats per minute (bpm) | Standard Error 0.75 |
| Moxifloxacin | Change From Baseline in Heart Rate (HR) Interval | 3.5 hours Post-dose | 2.2 beats per minute (bpm) | Standard Error 0.88 |
| Placebo | Change From Baseline in Heart Rate (HR) Interval | 12 hours Post-dose | 10.6 beats per minute (bpm) | Standard Error 1.11 |
| Placebo | Change From Baseline in Heart Rate (HR) Interval | 3.5 hours Post-dose | 0.1 beats per minute (bpm) | Standard Error 0.87 |
| Placebo | Change From Baseline in Heart Rate (HR) Interval | 8 hours Post-dose | 5.6 beats per minute (bpm) | Standard Error 0.86 |
| Placebo | Change From Baseline in Heart Rate (HR) Interval | 4 hours Post-dose | 1.3 beats per minute (bpm) | Standard Error 0.92 |
| Placebo | Change From Baseline in Heart Rate (HR) Interval | 1.5 hours Post-dose | 1.1 beats per minute (bpm) | Standard Error 0.84 |
| Placebo | Change From Baseline in Heart Rate (HR) Interval | 0.5 hours Post-dose | 0.5 beats per minute (bpm) | Standard Error 0.75 |
| Placebo | Change From Baseline in Heart Rate (HR) Interval | 36 hours Post-dose | 9.9 beats per minute (bpm) | Standard Error 1.15 |
| Placebo | Change From Baseline in Heart Rate (HR) Interval | 5 hours Post-dose | 10.5 beats per minute (bpm) | Standard Error 0.98 |
| Placebo | Change From Baseline in Heart Rate (HR) Interval | 3 hours Post-dose | 0.7 beats per minute (bpm) | Standard Error 0.84 |
| Placebo | Change From Baseline in Heart Rate (HR) Interval | 6 hours Post-dose | 10.4 beats per minute (bpm) | Standard Error 1.07 |
| Placebo | Change From Baseline in Heart Rate (HR) Interval | 1 hours Post-dose | 1.1 beats per minute (bpm) | Standard Error 0.83 |
| Placebo | Change From Baseline in Heart Rate (HR) Interval | 24 hours Post-dose | 2.2 beats per minute (bpm) | Standard Error 0.79 |
| Placebo | Change From Baseline in Heart Rate (HR) Interval | 2.5 hours Post-dose | 0.5 beats per minute (bpm) | Standard Error 0.97 |
| Placebo | Change From Baseline in Heart Rate (HR) Interval | 7 hours Post-dose | 6.7 beats per minute (bpm) | Standard Error 1.02 |
| Placebo | Change From Baseline in Heart Rate (HR) Interval | 2 hours Post-dose | 1.1 beats per minute (bpm) | Standard Error 0.84 |
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.
Time frame: At 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 12, 24, and 36 hours post-dose
Population: 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.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Therapeutic Dose: ITF2357 100 mg | Change From Baseline in PR Interval | 1.5 hours Post-dose | -1.4 msec | Standard Error 1.03 |
| Therapeutic Dose: ITF2357 100 mg | Change From Baseline in PR Interval | 0.5 hours Post-dose | 0.0 msec | Standard Error 0.83 |
| Therapeutic Dose: ITF2357 100 mg | Change From Baseline in PR Interval | 5 hours Post-dose | -5.3 msec | Standard Error 1.2 |
| Therapeutic Dose: ITF2357 100 mg | Change From Baseline in PR Interval | 6 hours Post-dose | -7.4 msec | Standard Error 1.3 |
| Therapeutic Dose: ITF2357 100 mg | Change From Baseline in PR Interval | 7 hours Post-dose | -7.2 msec | Standard Error 1.3 |
| Therapeutic Dose: ITF2357 100 mg | Change From Baseline in PR Interval | 2 hours Post-dose | 0.4 msec | Standard Error 1.04 |
| Therapeutic Dose: ITF2357 100 mg | Change From Baseline in PR Interval | 1 hours Post-dose | 0.4 msec | Standard Error 1.04 |
| Therapeutic Dose: ITF2357 100 mg | Change From Baseline in PR Interval | 24 hours Post-dose | -3.7 msec | Standard Error 1.32 |
| Therapeutic Dose: ITF2357 100 mg | Change From Baseline in PR Interval | 2.5 hours Post-dose | -2.4 msec | Standard Error 1.03 |
| Therapeutic Dose: ITF2357 100 mg | Change From Baseline in PR Interval | 8 hours Post-dose | -7.4 msec | Standard Error 1.16 |
| Therapeutic Dose: ITF2357 100 mg | Change From Baseline in PR Interval | 3 hours Post-dose | -1.3 msec | Standard Error 1.03 |
| Therapeutic Dose: ITF2357 100 mg | Change From Baseline in PR Interval | 3.5 hours Post-dose | -2.6 msec | Standard Error 0.97 |
| Therapeutic Dose: ITF2357 100 mg | Change From Baseline in PR Interval | 36 hours Post-dose | -7.8 msec | Standard Error 1.39 |
| Therapeutic Dose: ITF2357 100 mg | Change From Baseline in PR Interval | 12 hours Post-dose | -5.8 msec | Standard Error 1.39 |
| Therapeutic Dose: ITF2357 100 mg | Change From Baseline in PR Interval | 4 hours Post-dose | -2.2 msec | Standard Error 1.04 |
| Supratherapeutic Dose: ITF2357 300 mg | Change From Baseline in PR Interval | 0.5 hours Post-dose | -0.7 msec | Standard Error 0.81 |
| Supratherapeutic Dose: ITF2357 300 mg | Change From Baseline in PR Interval | 12 hours Post-dose | -7.9 msec | Standard Error 1.35 |
| Supratherapeutic Dose: ITF2357 300 mg | Change From Baseline in PR Interval | 2.5 hours Post-dose | -2.3 msec | Standard Error 1 |
| Supratherapeutic Dose: ITF2357 300 mg | Change From Baseline in PR Interval | 5 hours Post-dose | -7.3 msec | Standard Error 1.16 |
| Supratherapeutic Dose: ITF2357 300 mg | Change From Baseline in PR Interval | 1.5 hours Post-dose | -0.3 msec | Standard Error 1 |
| Supratherapeutic Dose: ITF2357 300 mg | Change From Baseline in PR Interval | 8 hours Post-dose | -9.0 msec | Standard Error 1.13 |
| Supratherapeutic Dose: ITF2357 300 mg | Change From Baseline in PR Interval | 1 hours Post-dose | 0.7 msec | Standard Error 1.01 |
| Supratherapeutic Dose: ITF2357 300 mg | Change From Baseline in PR Interval | 6 hours Post-dose | -9.3 msec | Standard Error 1.26 |
| Supratherapeutic Dose: ITF2357 300 mg | Change From Baseline in PR Interval | 36 hours Post-dose | -9.3 msec | Standard Error 1.34 |
| Supratherapeutic Dose: ITF2357 300 mg | Change From Baseline in PR Interval | 7 hours Post-dose | -9.8 msec | Standard Error 1.26 |
| Supratherapeutic Dose: ITF2357 300 mg | Change From Baseline in PR Interval | 4 hours Post-dose | -3.4 msec | Standard Error 1.01 |
| Supratherapeutic Dose: ITF2357 300 mg | Change From Baseline in PR Interval | 24 hours Post-dose | -3.8 msec | Standard Error 1.28 |
| Supratherapeutic Dose: ITF2357 300 mg | Change From Baseline in PR Interval | 3.5 hours Post-dose | -2.8 msec | Standard Error 0.94 |
| Supratherapeutic Dose: ITF2357 300 mg | Change From Baseline in PR Interval | 2 hours Post-dose | -1.3 msec | Standard Error 1.01 |
| Supratherapeutic Dose: ITF2357 300 mg | Change From Baseline in PR Interval | 3 hours Post-dose | -1.6 msec | Standard Error 1 |
| Moxifloxacin | Change From Baseline in PR Interval | 8 hours Post-dose | -7.5 msec | Standard Error 1.15 |
| Moxifloxacin | Change From Baseline in PR Interval | 0.5 hours Post-dose | 0.1 msec | Standard Error 0.82 |
| Moxifloxacin | Change From Baseline in PR Interval | 1 hours Post-dose | -0.3 msec | Standard Error 1.02 |
| Moxifloxacin | Change From Baseline in PR Interval | 1.5 hours Post-dose | -0.4 msec | Standard Error 1.01 |
| Moxifloxacin | Change From Baseline in PR Interval | 2 hours Post-dose | -0.1 msec | Standard Error 1.02 |
| Moxifloxacin | Change From Baseline in PR Interval | 2.5 hours Post-dose | 0.8 msec | Standard Error 1 |
| Moxifloxacin | Change From Baseline in PR Interval | 3 hours Post-dose | -1.3 msec | Standard Error 1.01 |
| Moxifloxacin | Change From Baseline in PR Interval | 3.5 hours Post-dose | -2.0 msec | Standard Error 0.95 |
| Moxifloxacin | Change From Baseline in PR Interval | 4 hours Post-dose | -2.6 msec | Standard Error 1.03 |
| Moxifloxacin | Change From Baseline in PR Interval | 5 hours Post-dose | -6.0 msec | Standard Error 1.18 |
| Moxifloxacin | Change From Baseline in PR Interval | 6 hours Post-dose | -8.2 msec | Standard Error 1.28 |
| Moxifloxacin | Change From Baseline in PR Interval | 7 hours Post-dose | -8.0 msec | Standard Error 1.28 |
| Moxifloxacin | Change From Baseline in PR Interval | 12 hours Post-dose | -6.7 msec | Standard Error 1.37 |
| Moxifloxacin | Change From Baseline in PR Interval | 24 hours Post-dose | 2.1 msec | Standard Error 1.3 |
| Moxifloxacin | Change From Baseline in PR Interval | 36 hours Post-dose | -3.3 msec | Standard Error 1.36 |
| Placebo | Change From Baseline in PR Interval | 4 hours Post-dose | 0.1 msec | Standard Error 1.01 |
| Placebo | Change From Baseline in PR Interval | 8 hours Post-dose | -5.2 msec | Standard Error 1.13 |
| Placebo | Change From Baseline in PR Interval | 3.5 hours Post-dose | 0.1 msec | Standard Error 0.94 |
| Placebo | Change From Baseline in PR Interval | 3 hours Post-dose | 0.2 msec | Standard Error 1 |
| Placebo | Change From Baseline in PR Interval | 2.5 hours Post-dose | -1.9 msec | Standard Error 1.01 |
| Placebo | Change From Baseline in PR Interval | 0.5 hours Post-dose | 0.2 msec | Standard Error 0.81 |
| Placebo | Change From Baseline in PR Interval | 12 hours Post-dose | -3.1 msec | Standard Error 1.35 |
| Placebo | Change From Baseline in PR Interval | 2 hours Post-dose | 1.6 msec | Standard Error 1.01 |
| Placebo | Change From Baseline in PR Interval | 1.5 hours Post-dose | 1.1 msec | Standard Error 1 |
| Placebo | Change From Baseline in PR Interval | 36 hours Post-dose | -2.6 msec | Standard Error 1.34 |
| Placebo | Change From Baseline in PR Interval | 24 hours Post-dose | -0.9 msec | Standard Error 1.28 |
| Placebo | Change From Baseline in PR Interval | 6 hours Post-dose | -5.5 msec | Standard Error 1.26 |
| Placebo | Change From Baseline in PR Interval | 1 hours Post-dose | 2.3 msec | Standard Error 1.01 |
| Placebo | Change From Baseline in PR Interval | 7 hours Post-dose | -5.5 msec | Standard Error 1.26 |
| Placebo | Change From Baseline in PR Interval | 5 hours Post-dose | -3.2 msec | Standard Error 1.16 |
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.
Time frame: At 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 12, 24, and 36 hours post-dose
Population: 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.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Therapeutic Dose: ITF2357 100 mg | Change From Baseline in QRS Interval | 5 hours Post-dose | 0.1 msec | Standard Error 0.27 |
| Therapeutic Dose: ITF2357 100 mg | Change From Baseline in QRS Interval | 4 hours Post-dose | 0.1 msec | Standard Error 0.2 |
| Therapeutic Dose: ITF2357 100 mg | Change From Baseline in QRS Interval | 2.5 hours Post-dose | -0.1 msec | Standard Error 0.17 |
| Therapeutic Dose: ITF2357 100 mg | Change From Baseline in QRS Interval | 1 hours Post-dose | 0.2 msec | Standard Error 0.16 |
| Therapeutic Dose: ITF2357 100 mg | Change From Baseline in QRS Interval | 3.5 hours Post-dose | 0.1 msec | Standard Error 0.18 |
| Therapeutic Dose: ITF2357 100 mg | Change From Baseline in QRS Interval | 3 hours Post-dose | 0.1 msec | Standard Error 0.17 |
| Therapeutic Dose: ITF2357 100 mg | Change From Baseline in QRS Interval | 0.5 hours Post-dose | -0.1 msec | Standard Error 0.14 |
| Therapeutic Dose: ITF2357 100 mg | Change From Baseline in QRS Interval | 12 hours Post-dose | 0.2 msec | Standard Error 0.3 |
| Therapeutic Dose: ITF2357 100 mg | Change From Baseline in QRS Interval | 8 hours Post-dose | -0.5 msec | Standard Error 0.22 |
| Therapeutic Dose: ITF2357 100 mg | Change From Baseline in QRS Interval | 1.5 hours Post-dose | 0.0 msec | Standard Error 0.16 |
| Therapeutic Dose: ITF2357 100 mg | Change From Baseline in QRS Interval | 36 hours Post-dose | -0.4 msec | Standard Error 0.27 |
| Therapeutic Dose: ITF2357 100 mg | Change From Baseline in QRS Interval | 7 hours Post-dose | -0.7 msec | Standard Error 0.24 |
| Therapeutic Dose: ITF2357 100 mg | Change From Baseline in QRS Interval | 6 hours Post-dose | -0.4 msec | Standard Error 0.24 |
| Therapeutic Dose: ITF2357 100 mg | Change From Baseline in QRS Interval | 2 hours Post-dose | -0.1 msec | Standard Error 0.15 |
| Therapeutic Dose: ITF2357 100 mg | Change From Baseline in QRS Interval | 24 hours Post-dose | -0.3 msec | Standard Error 0.39 |
| Supratherapeutic Dose: ITF2357 300 mg | Change From Baseline in QRS Interval | 8 hours Post-dose | 0.1 msec | Standard Error 0.21 |
| Supratherapeutic Dose: ITF2357 300 mg | Change From Baseline in QRS Interval | 0.5 hours Post-dose | 0.1 msec | Standard Error 0.13 |
| Supratherapeutic Dose: ITF2357 300 mg | Change From Baseline in QRS Interval | 1 hours Post-dose | 0.1 msec | Standard Error 0.16 |
| Supratherapeutic Dose: ITF2357 300 mg | Change From Baseline in QRS Interval | 1.5 hours Post-dose | 0.0 msec | Standard Error 0.16 |
| Supratherapeutic Dose: ITF2357 300 mg | Change From Baseline in QRS Interval | 2 hours Post-dose | 0.2 msec | Standard Error 0.15 |
| Supratherapeutic Dose: ITF2357 300 mg | Change From Baseline in QRS Interval | 2.5 hours Post-dose | 0.2 msec | Standard Error 0.16 |
| Supratherapeutic Dose: ITF2357 300 mg | Change From Baseline in QRS Interval | 3 hours Post-dose | 0.4 msec | Standard Error 0.17 |
| Supratherapeutic Dose: ITF2357 300 mg | Change From Baseline in QRS Interval | 3.5 hours Post-dose | 0.5 msec | Standard Error 0.17 |
| Supratherapeutic Dose: ITF2357 300 mg | Change From Baseline in QRS Interval | 4 hours Post-dose | 0.4 msec | Standard Error 0.19 |
| Supratherapeutic Dose: ITF2357 300 mg | Change From Baseline in QRS Interval | 5 hours Post-dose | 0.5 msec | Standard Error 0.26 |
| Supratherapeutic Dose: ITF2357 300 mg | Change From Baseline in QRS Interval | 6 hours Post-dose | -0.3 msec | Standard Error 0.24 |
| Supratherapeutic Dose: ITF2357 300 mg | Change From Baseline in QRS Interval | 7 hours Post-dose | -0.6 msec | Standard Error 0.23 |
| Supratherapeutic Dose: ITF2357 300 mg | Change From Baseline in QRS Interval | 12 hours Post-dose | -0.2 msec | Standard Error 0.29 |
| Supratherapeutic Dose: ITF2357 300 mg | Change From Baseline in QRS Interval | 24 hours Post-dose | 0.1 msec | Standard Error 0.38 |
| Supratherapeutic Dose: ITF2357 300 mg | Change From Baseline in QRS Interval | 36 hours Post-dose | -0.4 msec | Standard Error 0.26 |
| Moxifloxacin | Change From Baseline in QRS Interval | 36 hours Post-dose | -0.5 msec | Standard Error 0.26 |
| Moxifloxacin | Change From Baseline in QRS Interval | 4 hours Post-dose | 0.3 msec | Standard Error 0.2 |
| Moxifloxacin | Change From Baseline in QRS Interval | 2 hours Post-dose | 0.2 msec | Standard Error 0.15 |
| Moxifloxacin | Change From Baseline in QRS Interval | 24 hours Post-dose | -0.5 msec | Standard Error 0.39 |
| Moxifloxacin | Change From Baseline in QRS Interval | 5 hours Post-dose | 0.3 msec | Standard Error 0.27 |
| Moxifloxacin | Change From Baseline in QRS Interval | 6 hours Post-dose | -0.4 msec | Standard Error 0.24 |
| Moxifloxacin | Change From Baseline in QRS Interval | 1.5 hours Post-dose | -0.1 msec | Standard Error 0.16 |
| Moxifloxacin | Change From Baseline in QRS Interval | 7 hours Post-dose | -0.5 msec | Standard Error 0.23 |
| Moxifloxacin | Change From Baseline in QRS Interval | 0.5 hours Post-dose | 0.2 msec | Standard Error 0.14 |
| Moxifloxacin | Change From Baseline in QRS Interval | 8 hours Post-dose | -0.2 msec | Standard Error 0.21 |
| Moxifloxacin | Change From Baseline in QRS Interval | 1 hours Post-dose | 0.4 msec | Standard Error 0.16 |
| Moxifloxacin | Change From Baseline in QRS Interval | 12 hours Post-dose | 0.1 msec | Standard Error 0.29 |
| Moxifloxacin | Change From Baseline in QRS Interval | 3 hours Post-dose | 0.3 msec | Standard Error 0.17 |
| Moxifloxacin | Change From Baseline in QRS Interval | 2.5 hours Post-dose | 0.3 msec | Standard Error 0.16 |
| Moxifloxacin | Change From Baseline in QRS Interval | 3.5 hours Post-dose | 0.1 msec | Standard Error 0.18 |
| Placebo | Change From Baseline in QRS Interval | 2 hours Post-dose | 0.0 msec | Standard Error 0.15 |
| Placebo | Change From Baseline in QRS Interval | 3 hours Post-dose | 0.3 msec | Standard Error 0.17 |
| Placebo | Change From Baseline in QRS Interval | 4 hours Post-dose | 0.2 msec | Standard Error 0.19 |
| Placebo | Change From Baseline in QRS Interval | 8 hours Post-dose | -0.2 msec | Standard Error 0.21 |
| Placebo | Change From Baseline in QRS Interval | 3.5 hours Post-dose | 0.3 msec | Standard Error 0.17 |
| Placebo | Change From Baseline in QRS Interval | 36 hours Post-dose | -0.3 msec | Standard Error 0.26 |
| Placebo | Change From Baseline in QRS Interval | 5 hours Post-dose | 0.5 msec | Standard Error 0.26 |
| Placebo | Change From Baseline in QRS Interval | 1.5 hours Post-dose | -0.1 msec | Standard Error 0.16 |
| Placebo | Change From Baseline in QRS Interval | 24 hours Post-dose | -0.3 msec | Standard Error 0.38 |
| Placebo | Change From Baseline in QRS Interval | 0.5 hours Post-dose | 0.2 msec | Standard Error 0.13 |
| Placebo | Change From Baseline in QRS Interval | 6 hours Post-dose | -0.2 msec | Standard Error 0.24 |
| Placebo | Change From Baseline in QRS Interval | 2.5 hours Post-dose | 0.1 msec | Standard Error 0.16 |
| Placebo | Change From Baseline in QRS Interval | 12 hours Post-dose | 0.3 msec | Standard Error 0.29 |
| Placebo | Change From Baseline in QRS Interval | 7 hours Post-dose | -0.2 msec | Standard Error 0.23 |
| Placebo | Change From Baseline in QRS Interval | 1 hours Post-dose | 0.0 msec | Standard Error 0.16 |
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).
Time frame: At 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 12, 24, and 36 hours post-dose
Population: 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.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Therapeutic Dose: ITF2357 100 mg | Change From Baseline in QTcF Interval | 6 hours Post-dose | 0.4 msec | Standard Error 1.38 |
| Therapeutic Dose: ITF2357 100 mg | Change From Baseline in QTcF Interval | 2.5 hours Post-dose | 3.1 msec | Standard Error 0.95 |
| Therapeutic Dose: ITF2357 100 mg | Change From Baseline in QTcF Interval | 8 hours Post-dose | -2.8 msec | Standard Error 1.21 |
| Therapeutic Dose: ITF2357 100 mg | Change From Baseline in QTcF Interval | 1.5 hours Post-dose | 0.8 msec | Standard Error 0.84 |
| Therapeutic Dose: ITF2357 100 mg | Change From Baseline in QTcF Interval | 24 hours Post-dose | -1.5 msec | Standard Error 1.25 |
| Therapeutic Dose: ITF2357 100 mg | Change From Baseline in QTcF Interval | 3 hours Post-dose | 2.9 msec | Standard Error 0.88 |
| Therapeutic Dose: ITF2357 100 mg | Change From Baseline in QTcF Interval | 7 hours Post-dose | -2.3 msec | Standard Error 1.34 |
| Therapeutic Dose: ITF2357 100 mg | Change From Baseline in QTcF Interval | 0.5 hours Post-dose | -0.7 msec | Standard Error 0.88 |
| Therapeutic Dose: ITF2357 100 mg | Change From Baseline in QTcF Interval | 36 hours Post-dose | -2.1 msec | Standard Error 1.41 |
| Therapeutic Dose: ITF2357 100 mg | Change From Baseline in QTcF Interval | 3.5 hours Post-dose | 4.5 msec | Standard Error 0.93 |
| Therapeutic Dose: ITF2357 100 mg | Change From Baseline in QTcF Interval | 2 hours Post-dose | 1.3 msec | Standard Error 0.85 |
| Therapeutic Dose: ITF2357 100 mg | Change From Baseline in QTcF Interval | 5 hours Post-dose | 4.0 msec | Standard Error 1.58 |
| Therapeutic Dose: ITF2357 100 mg | Change From Baseline in QTcF Interval | 12 hours Post-dose | 3.5 msec | Standard Error 1.4 |
| Therapeutic Dose: ITF2357 100 mg | Change From Baseline in QTcF Interval | 4 hours Post-dose | 6.0 msec | Standard Error 0.93 |
| Therapeutic Dose: ITF2357 100 mg | Change From Baseline in QTcF Interval | 1 hours Post-dose | -0.3 msec | Standard Error 0.85 |
| Supratherapeutic Dose: ITF2357 300 mg | Change From Baseline in QTcF Interval | 4 hours Post-dose | 12.4 msec | Standard Error 0.9 |
| Supratherapeutic Dose: ITF2357 300 mg | Change From Baseline in QTcF Interval | 5 hours Post-dose | 12.1 msec | Standard Error 1.53 |
| Supratherapeutic Dose: ITF2357 300 mg | Change From Baseline in QTcF Interval | 7 hours Post-dose | 3.8 msec | Standard Error 1.3 |
| Supratherapeutic Dose: ITF2357 300 mg | Change From Baseline in QTcF Interval | 6 hours Post-dose | 8.1 msec | Standard Error 1.34 |
| Supratherapeutic Dose: ITF2357 300 mg | Change From Baseline in QTcF Interval | 1.5 hours Post-dose | 2.5 msec | Standard Error 0.81 |
| Supratherapeutic Dose: ITF2357 300 mg | Change From Baseline in QTcF Interval | 2 hours Post-dose | 3.6 msec | Standard Error 0.82 |
| Supratherapeutic Dose: ITF2357 300 mg | Change From Baseline in QTcF Interval | 24 hours Post-dose | 7.1 msec | Standard Error 1.21 |
| Supratherapeutic Dose: ITF2357 300 mg | Change From Baseline in QTcF Interval | 2.5 hours Post-dose | 5.5 msec | Standard Error 0.93 |
| Supratherapeutic Dose: ITF2357 300 mg | Change From Baseline in QTcF Interval | 1 hours Post-dose | 0.2 msec | Standard Error 0.83 |
| Supratherapeutic Dose: ITF2357 300 mg | Change From Baseline in QTcF Interval | 3 hours Post-dose | 7.1 msec | Standard Error 0.86 |
| Supratherapeutic Dose: ITF2357 300 mg | Change From Baseline in QTcF Interval | 0.5 hours Post-dose | -1.3 msec | Standard Error 0.86 |
| Supratherapeutic Dose: ITF2357 300 mg | Change From Baseline in QTcF Interval | 12 hours Post-dose | 11.2 msec | Standard Error 1.36 |
| Supratherapeutic Dose: ITF2357 300 mg | Change From Baseline in QTcF Interval | 3.5 hours Post-dose | 10.7 msec | Standard Error 0.91 |
| Supratherapeutic Dose: ITF2357 300 mg | Change From Baseline in QTcF Interval | 36 hours Post-dose | 0.2 msec | Standard Error 1.36 |
| Supratherapeutic Dose: ITF2357 300 mg | Change From Baseline in QTcF Interval | 8 hours Post-dose | 5.2 msec | Standard Error 1.18 |
| Moxifloxacin | Change From Baseline in QTcF Interval | 4 hours Post-dose | 13.9 msec | Standard Error 0.91 |
| Moxifloxacin | Change From Baseline in QTcF Interval | 0.5 hours Post-dose | 8.5 msec | Standard Error 0.87 |
| Moxifloxacin | Change From Baseline in QTcF Interval | 1 hours Post-dose | 12.5 msec | Standard Error 0.84 |
| Moxifloxacin | Change From Baseline in QTcF Interval | 1.5 hours Post-dose | 12.1 msec | Standard Error 0.82 |
| Moxifloxacin | Change From Baseline in QTcF Interval | 2 hours Post-dose | 13.2 msec | Standard Error 0.83 |
| Moxifloxacin | Change From Baseline in QTcF Interval | 2.5 hours Post-dose | 14.2 msec | Standard Error 0.94 |
| Moxifloxacin | Change From Baseline in QTcF Interval | 3 hours Post-dose | 14.5 msec | Standard Error 0.87 |
| Moxifloxacin | Change From Baseline in QTcF Interval | 3.5 hours Post-dose | 14.4 msec | Standard Error 0.92 |
| Moxifloxacin | Change From Baseline in QTcF Interval | 5 hours Post-dose | 10.6 msec | Standard Error 1.56 |
| Moxifloxacin | Change From Baseline in QTcF Interval | 6 hours Post-dose | 6.3 msec | Standard Error 1.36 |
| Moxifloxacin | Change From Baseline in QTcF Interval | 7 hours Post-dose | 4.3 msec | Standard Error 1.32 |
| Moxifloxacin | Change From Baseline in QTcF Interval | 8 hours Post-dose | 5.0 msec | Standard Error 1.19 |
| Moxifloxacin | Change From Baseline in QTcF Interval | 12 hours Post-dose | 8.8 msec | Standard Error 1.38 |
| Moxifloxacin | Change From Baseline in QTcF Interval | 24 hours Post-dose | 1.7 msec | Standard Error 1.23 |
| Moxifloxacin | Change From Baseline in QTcF Interval | 36 hours Post-dose | 0.5 msec | Standard Error 1.38 |
| Placebo | Change From Baseline in QTcF Interval | 0.5 hours Post-dose | -1.8 msec | Standard Error 0.86 |
| Placebo | Change From Baseline in QTcF Interval | 1.5 hours Post-dose | -0.2 msec | Standard Error 0.81 |
| Placebo | Change From Baseline in QTcF Interval | 8 hours Post-dose | -6.3 msec | Standard Error 1.18 |
| Placebo | Change From Baseline in QTcF Interval | 3.5 hours Post-dose | 1.6 msec | Standard Error 0.91 |
| Placebo | Change From Baseline in QTcF Interval | 3 hours Post-dose | 0.5 msec | Standard Error 0.86 |
| Placebo | Change From Baseline in QTcF Interval | 1 hours Post-dose | -0.6 msec | Standard Error 0.83 |
| Placebo | Change From Baseline in QTcF Interval | 12 hours Post-dose | 1.0 msec | Standard Error 1.36 |
| Placebo | Change From Baseline in QTcF Interval | 2.5 hours Post-dose | -0.5 msec | Standard Error 0.93 |
| Placebo | Change From Baseline in QTcF Interval | 2 hours Post-dose | -0.8 msec | Standard Error 0.82 |
| Placebo | Change From Baseline in QTcF Interval | 36 hours Post-dose | -1.3 msec | Standard Error 1.36 |
| Placebo | Change From Baseline in QTcF Interval | 6 hours Post-dose | -3.3 msec | Standard Error 1.34 |
| Placebo | Change From Baseline in QTcF Interval | 5 hours Post-dose | -1.5 msec | Standard Error 1.53 |
| Placebo | Change From Baseline in QTcF Interval | 24 hours Post-dose | -3.9 msec | Standard Error 1.21 |
| Placebo | Change From Baseline in QTcF Interval | 7 hours Post-dose | -5.3 msec | Standard Error 1.3 |
| Placebo | Change From Baseline in QTcF Interval | 4 hours Post-dose | 2.0 msec | Standard Error 0.9 |
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.
Time frame: Baseline, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 12, 24, and 36 hours post-dose
Population: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Therapeutic Dose: ITF2357 100 mg | Number of Participants With Changes in Categorical Outliers for QTcF, PR, and QRS Intervals in the ECG and HR | QTcF > 480 and <= 500 ms | 0 Participants |
| Therapeutic Dose: ITF2357 100 mg | Number of Participants With Changes in Categorical Outliers for QTcF, PR, and QRS Intervals in the ECG and HR | HR > 100 (bpm) with an increase in ΔHR > 25% | 0 Participants |
| Therapeutic Dose: ITF2357 100 mg | Number of Participants With Changes in Categorical Outliers for QTcF, PR, and QRS Intervals in the ECG and HR | HR < 50 (bpm) with a decrease in ΔHR > 25% | 0 Participants |
| Therapeutic Dose: ITF2357 100 mg | Number of Participants With Changes in Categorical Outliers for QTcF, PR, and QRS Intervals in the ECG and HR | ΔQTcF > 30 and <= 60 ms | 0 Participants |
| Therapeutic Dose: ITF2357 100 mg | Number of Participants With Changes in Categorical Outliers for QTcF, PR, and QRS Intervals in the ECG and HR | QRS > 120 (ms) with an increase in ΔQRS > 25% | 0 Participants |
| Therapeutic Dose: ITF2357 100 mg | Number of Participants With Changes in Categorical Outliers for QTcF, PR, and QRS Intervals in the ECG and HR | QTcF > 500 ms | 0 Participants |
| Therapeutic Dose: ITF2357 100 mg | Number of Participants With Changes in Categorical Outliers for QTcF, PR, and QRS Intervals in the ECG and HR | PR > 210 (ms) with an increase in ΔPR > 25% | 0 Participants |
| Therapeutic Dose: ITF2357 100 mg | Number of Participants With Changes in Categorical Outliers for QTcF, PR, and QRS Intervals in the ECG and HR | ΔQTcF > 60 ms | 0 Participants |
| Therapeutic Dose: ITF2357 100 mg | Number of Participants With Changes in Categorical Outliers for QTcF, PR, and QRS Intervals in the ECG and HR | QTcF > 450 and <= 480 ms | 0 Participants |
| Supratherapeutic Dose: ITF2357 300 mg | Number of Participants With Changes in Categorical Outliers for QTcF, PR, and QRS Intervals in the ECG and HR | ΔQTcF > 60 ms | 0 Participants |
| Supratherapeutic Dose: ITF2357 300 mg | Number of Participants With Changes in Categorical Outliers for QTcF, PR, and QRS Intervals in the ECG and HR | HR > 100 (bpm) with an increase in ΔHR > 25% | 0 Participants |
| Supratherapeutic Dose: ITF2357 300 mg | Number of Participants With Changes in Categorical Outliers for QTcF, PR, and QRS Intervals in the ECG and HR | HR < 50 (bpm) with a decrease in ΔHR > 25% | 0 Participants |
| Supratherapeutic Dose: ITF2357 300 mg | Number of Participants With Changes in Categorical Outliers for QTcF, PR, and QRS Intervals in the ECG and HR | QTcF > 480 and <= 500 ms | 0 Participants |
| Supratherapeutic Dose: ITF2357 300 mg | Number of Participants With Changes in Categorical Outliers for QTcF, PR, and QRS Intervals in the ECG and HR | QTcF > 500 ms | 0 Participants |
| Supratherapeutic Dose: ITF2357 300 mg | Number of Participants With Changes in Categorical Outliers for QTcF, PR, and QRS Intervals in the ECG and HR | QRS > 120 (ms) with an increase in ΔQRS > 25% | 0 Participants |
| Supratherapeutic Dose: ITF2357 300 mg | Number of Participants With Changes in Categorical Outliers for QTcF, PR, and QRS Intervals in the ECG and HR | PR > 210 (ms) with an increase in ΔPR > 25% | 0 Participants |
| Supratherapeutic Dose: ITF2357 300 mg | Number of Participants With Changes in Categorical Outliers for QTcF, PR, and QRS Intervals in the ECG and HR | ΔQTcF > 30 and <= 60 ms | 2 Participants |
| Supratherapeutic Dose: ITF2357 300 mg | Number of Participants With Changes in Categorical Outliers for QTcF, PR, and QRS Intervals in the ECG and HR | QTcF > 450 and <= 480 ms | 1 Participants |
| Moxifloxacin | Number of Participants With Changes in Categorical Outliers for QTcF, PR, and QRS Intervals in the ECG and HR | ΔQTcF > 60 ms | 0 Participants |
| Moxifloxacin | Number of Participants With Changes in Categorical Outliers for QTcF, PR, and QRS Intervals in the ECG and HR | QTcF > 450 and <= 480 ms | 2 Participants |
| Moxifloxacin | Number of Participants With Changes in Categorical Outliers for QTcF, PR, and QRS Intervals in the ECG and HR | QTcF > 480 and <= 500 ms | 0 Participants |
| Moxifloxacin | Number of Participants With Changes in Categorical Outliers for QTcF, PR, and QRS Intervals in the ECG and HR | QTcF > 500 ms | 0 Participants |
| Moxifloxacin | Number of Participants With Changes in Categorical Outliers for QTcF, PR, and QRS Intervals in the ECG and HR | ΔQTcF > 30 and <= 60 ms | 2 Participants |
| Moxifloxacin | Number of Participants With Changes in Categorical Outliers for QTcF, PR, and QRS Intervals in the ECG and HR | HR < 50 (bpm) with a decrease in ΔHR > 25% | 0 Participants |
| Moxifloxacin | Number of Participants With Changes in Categorical Outliers for QTcF, PR, and QRS Intervals in the ECG and HR | HR > 100 (bpm) with an increase in ΔHR > 25% | 0 Participants |
| Moxifloxacin | Number of Participants With Changes in Categorical Outliers for QTcF, PR, and QRS Intervals in the ECG and HR | PR > 210 (ms) with an increase in ΔPR > 25% | 0 Participants |
| Moxifloxacin | Number of Participants With Changes in Categorical Outliers for QTcF, PR, and QRS Intervals in the ECG and HR | QRS > 120 (ms) with an increase in ΔQRS > 25% | 0 Participants |
| Placebo | Number of Participants With Changes in Categorical Outliers for QTcF, PR, and QRS Intervals in the ECG and HR | HR > 100 (bpm) with an increase in ΔHR > 25% | 0 Participants |
| Placebo | Number of Participants With Changes in Categorical Outliers for QTcF, PR, and QRS Intervals in the ECG and HR | ΔQTcF > 30 and <= 60 ms | 0 Participants |
| Placebo | Number of Participants With Changes in Categorical Outliers for QTcF, PR, and QRS Intervals in the ECG and HR | QTcF > 500 ms | 0 Participants |
| Placebo | Number of Participants With Changes in Categorical Outliers for QTcF, PR, and QRS Intervals in the ECG and HR | QRS > 120 (ms) with an increase in ΔQRS > 25% | 0 Participants |
| Placebo | Number of Participants With Changes in Categorical Outliers for QTcF, PR, and QRS Intervals in the ECG and HR | PR > 210 (ms) with an increase in ΔPR > 25% | 0 Participants |
| Placebo | Number of Participants With Changes in Categorical Outliers for QTcF, PR, and QRS Intervals in the ECG and HR | QTcF > 480 and <= 500 ms | 0 Participants |
| Placebo | Number of Participants With Changes in Categorical Outliers for QTcF, PR, and QRS Intervals in the ECG and HR | HR < 50 (bpm) with a decrease in ΔHR > 25% | 0 Participants |
| Placebo | Number of Participants With Changes in Categorical Outliers for QTcF, PR, and QRS Intervals in the ECG and HR | ΔQTcF > 60 ms | 0 Participants |
| Placebo | Number of Participants With Changes in Categorical Outliers for QTcF, PR, and QRS Intervals in the ECG and HR | QTcF > 450 and <= 480 ms | 0 Participants |
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.
Time frame: Baseline up to 44 days
Population: 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).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Therapeutic Dose: ITF2357 100 mg | Number of Participants With Clinically Significant Changes in Clinical Laboratory Parameters | 0 Participants |
| Supratherapeutic Dose: ITF2357 300 mg | Number of Participants With Clinically Significant Changes in Clinical Laboratory Parameters | 2 Participants |
| Moxifloxacin | Number of Participants With Clinically Significant Changes in Clinical Laboratory Parameters | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Changes in Clinical Laboratory Parameters | 0 Participants |
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.
Time frame: Baseline up to 44 days
Population: 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).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Therapeutic Dose: ITF2357 100 mg | Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Findings | 0 Participants |
| Supratherapeutic Dose: ITF2357 300 mg | Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Findings | 0 Participants |
| Moxifloxacin | Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Findings | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Findings | 0 Participants |
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.
Time frame: Baseline up to 44 days
Population: 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).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Therapeutic Dose: ITF2357 100 mg | Number of Participants With Clinically Significant Changes in Vital Signs | 0 Participants |
| Supratherapeutic Dose: ITF2357 300 mg | Number of Participants With Clinically Significant Changes in Vital Signs | 0 Participants |
| Moxifloxacin | Number of Participants With Clinically Significant Changes in Vital Signs | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Changes in Vital Signs | 0 Participants |
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.
Time frame: Baseline up to 44 days
Population: 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).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Therapeutic Dose: ITF2357 100 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with TEAEs | 5 Participants |
| Therapeutic Dose: ITF2357 100 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with Serious TEAEs | 0 Participants |
| Supratherapeutic Dose: ITF2357 300 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with Serious TEAEs | 0 Participants |
| Supratherapeutic Dose: ITF2357 300 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with TEAEs | 15 Participants |
| Moxifloxacin | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with TEAEs | 4 Participants |
| Moxifloxacin | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with Serious TEAEs | 0 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with TEAEs | 6 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs | Participants with Serious TEAEs | 0 Participants |
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.
Time frame: Up to 44 days
Population: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Therapeutic Dose: ITF2357 100 mg | Number of Participants With Treatment-Emergent Changes of T-Wave Morphology and U Wave Presence | U-Wave presence | 0 Participants |
| Therapeutic Dose: ITF2357 100 mg | Number of Participants With Treatment-Emergent Changes of T-Wave Morphology and U Wave Presence | Notched (-) | 0 Participants |
| Therapeutic Dose: ITF2357 100 mg | Number of Participants With Treatment-Emergent Changes of T-Wave Morphology and U Wave Presence | Notched (+) | 0 Participants |
| Therapeutic Dose: ITF2357 100 mg | Number of Participants With Treatment-Emergent Changes of T-Wave Morphology and U Wave Presence | Normal (-) | 0 Participants |
| Therapeutic Dose: ITF2357 100 mg | Number of Participants With Treatment-Emergent Changes of T-Wave Morphology and U Wave Presence | Biphasic | 0 Participants |
| Therapeutic Dose: ITF2357 100 mg | Number of Participants With Treatment-Emergent Changes of T-Wave Morphology and U Wave Presence | Flat | 0 Participants |
| Supratherapeutic Dose: ITF2357 300 mg | Number of Participants With Treatment-Emergent Changes of T-Wave Morphology and U Wave Presence | U-Wave presence | 0 Participants |
| Supratherapeutic Dose: ITF2357 300 mg | Number of Participants With Treatment-Emergent Changes of T-Wave Morphology and U Wave Presence | Normal (-) | 0 Participants |
| Supratherapeutic Dose: ITF2357 300 mg | Number of Participants With Treatment-Emergent Changes of T-Wave Morphology and U Wave Presence | Notched (-) | 0 Participants |
| Supratherapeutic Dose: ITF2357 300 mg | Number of Participants With Treatment-Emergent Changes of T-Wave Morphology and U Wave Presence | Biphasic | 0 Participants |
| Supratherapeutic Dose: ITF2357 300 mg | Number of Participants With Treatment-Emergent Changes of T-Wave Morphology and U Wave Presence | Flat | 0 Participants |
| Supratherapeutic Dose: ITF2357 300 mg | Number of Participants With Treatment-Emergent Changes of T-Wave Morphology and U Wave Presence | Notched (+) | 0 Participants |
| Moxifloxacin | Number of Participants With Treatment-Emergent Changes of T-Wave Morphology and U Wave Presence | Normal (-) | 0 Participants |
| Moxifloxacin | Number of Participants With Treatment-Emergent Changes of T-Wave Morphology and U Wave Presence | U-Wave presence | 0 Participants |
| Moxifloxacin | Number of Participants With Treatment-Emergent Changes of T-Wave Morphology and U Wave Presence | Biphasic | 0 Participants |
| Moxifloxacin | Number of Participants With Treatment-Emergent Changes of T-Wave Morphology and U Wave Presence | Notched (-) | 0 Participants |
| Moxifloxacin | Number of Participants With Treatment-Emergent Changes of T-Wave Morphology and U Wave Presence | Flat | 0 Participants |
| Moxifloxacin | Number of Participants With Treatment-Emergent Changes of T-Wave Morphology and U Wave Presence | Notched (+) | 0 Participants |
| Placebo | Number of Participants With Treatment-Emergent Changes of T-Wave Morphology and U Wave Presence | Normal (-) | 0 Participants |
| Placebo | Number of Participants With Treatment-Emergent Changes of T-Wave Morphology and U Wave Presence | U-Wave presence | 0 Participants |
| Placebo | Number of Participants With Treatment-Emergent Changes of T-Wave Morphology and U Wave Presence | Notched (+) | 0 Participants |
| Placebo | Number of Participants With Treatment-Emergent Changes of T-Wave Morphology and U Wave Presence | Flat | 0 Participants |
| Placebo | Number of Participants With Treatment-Emergent Changes of T-Wave Morphology and U Wave Presence | Biphasic | 0 Participants |
| Placebo | Number of Participants With Treatment-Emergent Changes of T-Wave Morphology and U Wave Presence | Notched (-) | 0 Participants |
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.
Time frame: Baseline up to 44 days
Population: 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).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Therapeutic Dose: ITF2357 100 mg | Number of TEAEs Based on Severity | Mild | 6 number of events |
| Therapeutic Dose: ITF2357 100 mg | Number of TEAEs Based on Severity | Severe | 0 number of events |
| Therapeutic Dose: ITF2357 100 mg | Number of TEAEs Based on Severity | Moderate | 0 number of events |
| Supratherapeutic Dose: ITF2357 300 mg | Number of TEAEs Based on Severity | Mild | 21 number of events |
| Supratherapeutic Dose: ITF2357 300 mg | Number of TEAEs Based on Severity | Severe | 0 number of events |
| Supratherapeutic Dose: ITF2357 300 mg | Number of TEAEs Based on Severity | Moderate | 4 number of events |
| Moxifloxacin | Number of TEAEs Based on Severity | Moderate | 0 number of events |
| Moxifloxacin | Number of TEAEs Based on Severity | Mild | 8 number of events |
| Moxifloxacin | Number of TEAEs Based on Severity | Severe | 0 number of events |
| Placebo | Number of TEAEs Based on Severity | Mild | 6 number of events |
| Placebo | Number of TEAEs Based on Severity | Severe | 0 number of events |
| Placebo | Number of TEAEs Based on Severity | Moderate | 0 number of events |
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.
Time frame: Baseline up to 44 days
Population: 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).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Therapeutic Dose: ITF2357 100 mg | Number of Treatment-Related TEAEs | 6 number of events |
| Supratherapeutic Dose: ITF2357 300 mg | Number of Treatment-Related TEAEs | 20 number of events |
| Moxifloxacin | Number of Treatment-Related TEAEs | 6 number of events |
| Placebo | Number of Treatment-Related TEAEs | 4 number of events |
Secondary
Placebo-corrected Change From Baseline in HR Interval
Placebo-corrected change from baseline in HR, (ΔΔHR) was calculated based on model-predicted effect.
Time frame: At 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 12, 24, and 36 hours post-dose
Population: 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.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Therapeutic Dose: ITF2357 100 mg | Placebo-corrected Change From Baseline in HR Interval | 7 hours Post-dose | 1.4 bpm | Standard Error 1.23 |
| Therapeutic Dose: ITF2357 100 mg | Placebo-corrected Change From Baseline in HR Interval | 3 hours Post-dose | 3.6 bpm | Standard Error 0.91 |
| Therapeutic Dose: ITF2357 100 mg | Placebo-corrected Change From Baseline in HR Interval | 24 hours Post-dose | -1.6 bpm | Standard Error 0.82 |
| Therapeutic Dose: ITF2357 100 mg | Placebo-corrected Change From Baseline in HR Interval | 6 hours Post-dose | 1.9 bpm | Standard Error 1.32 |
| Therapeutic Dose: ITF2357 100 mg | Placebo-corrected Change From Baseline in HR Interval | 3.5 hours Post-dose | 3.9 bpm | Standard Error 0.96 |
| Therapeutic Dose: ITF2357 100 mg | Placebo-corrected Change From Baseline in HR Interval | 1.5 hours Post-dose | 2.2 bpm | Standard Error 0.9 |
| Therapeutic Dose: ITF2357 100 mg | Placebo-corrected Change From Baseline in HR Interval | 5 hours Post-dose | 4.5 bpm | Standard Error 1.17 |
| Therapeutic Dose: ITF2357 100 mg | Placebo-corrected Change From Baseline in HR Interval | 4 hours Post-dose | 3.0 bpm | Standard Error 1.06 |
| Therapeutic Dose: ITF2357 100 mg | Placebo-corrected Change From Baseline in HR Interval | 36 hours Post-dose | -0.8 bpm | Standard Error 1.45 |
| Therapeutic Dose: ITF2357 100 mg | Placebo-corrected Change From Baseline in HR Interval | 12 hours Post-dose | -1.1 bpm | Standard Error 1.39 |
| Therapeutic Dose: ITF2357 100 mg | Placebo-corrected Change From Baseline in HR Interval | 2 hours Post-dose | 2.6 bpm | Standard Error 0.92 |
| Therapeutic Dose: ITF2357 100 mg | Placebo-corrected Change From Baseline in HR Interval | 1 hours Post-dose | 0.1 bpm | Standard Error 0.89 |
| Therapeutic Dose: ITF2357 100 mg | Placebo-corrected Change From Baseline in HR Interval | 8 hours Post-dose | 1.9 bpm | Standard Error 0.95 |
| Therapeutic Dose: ITF2357 100 mg | Placebo-corrected Change From Baseline in HR Interval | 2.5 hours Post-dose | 3.3 bpm | Standard Error 1.15 |
| Therapeutic Dose: ITF2357 100 mg | Placebo-corrected Change From Baseline in HR Interval | 0.5 hours Post-dose | 0.1 bpm | Standard Error 0.73 |
| Supratherapeutic Dose: ITF2357 300 mg | Placebo-corrected Change From Baseline in HR Interval | 36 hours Post-dose | -1.8 bpm | Standard Error 1.43 |
| Supratherapeutic Dose: ITF2357 300 mg | Placebo-corrected Change From Baseline in HR Interval | 0.5 hours Post-dose | 0.6 bpm | Standard Error 0.71 |
| Supratherapeutic Dose: ITF2357 300 mg | Placebo-corrected Change From Baseline in HR Interval | 1 hours Post-dose | 1.6 bpm | Standard Error 0.88 |
| Supratherapeutic Dose: ITF2357 300 mg | Placebo-corrected Change From Baseline in HR Interval | 1.5 hours Post-dose | 4.0 bpm | Standard Error 0.88 |
| Supratherapeutic Dose: ITF2357 300 mg | Placebo-corrected Change From Baseline in HR Interval | 2 hours Post-dose | 6.7 bpm | Standard Error 0.9 |
| Supratherapeutic Dose: ITF2357 300 mg | Placebo-corrected Change From Baseline in HR Interval | 2.5 hours Post-dose | 9.3 bpm | Standard Error 1.13 |
| Supratherapeutic Dose: ITF2357 300 mg | Placebo-corrected Change From Baseline in HR Interval | 3 hours Post-dose | 9.8 bpm | Standard Error 0.9 |
| Supratherapeutic Dose: ITF2357 300 mg | Placebo-corrected Change From Baseline in HR Interval | 3.5 hours Post-dose | 9.8 bpm | Standard Error 0.95 |
| Supratherapeutic Dose: ITF2357 300 mg | Placebo-corrected Change From Baseline in HR Interval | 4 hours Post-dose | 9.7 bpm | Standard Error 1.04 |
| Supratherapeutic Dose: ITF2357 300 mg | Placebo-corrected Change From Baseline in HR Interval | 5 hours Post-dose | 11.6 bpm | Standard Error 1.15 |
| Supratherapeutic Dose: ITF2357 300 mg | Placebo-corrected Change From Baseline in HR Interval | 6 hours Post-dose | 11.2 bpm | Standard Error 1.29 |
| Supratherapeutic Dose: ITF2357 300 mg | Placebo-corrected Change From Baseline in HR Interval | 7 hours Post-dose | 10.2 bpm | Standard Error 1.21 |
| Supratherapeutic Dose: ITF2357 300 mg | Placebo-corrected Change From Baseline in HR Interval | 8 hours Post-dose | 8.5 bpm | Standard Error 0.93 |
| Supratherapeutic Dose: ITF2357 300 mg | Placebo-corrected Change From Baseline in HR Interval | 12 hours Post-dose | 2.1 bpm | Standard Error 1.37 |
| Supratherapeutic Dose: ITF2357 300 mg | Placebo-corrected Change From Baseline in HR Interval | 24 hours Post-dose | -0.2 bpm | Standard Error 0.8 |
| Moxifloxacin | Placebo-corrected Change From Baseline in HR Interval | 6 hours Post-dose | -0.3 bpm | Standard Error 1.31 |
| Moxifloxacin | Placebo-corrected Change From Baseline in HR Interval | 2.5 hours Post-dose | 0.3 bpm | Standard Error 1.14 |
| Moxifloxacin | Placebo-corrected Change From Baseline in HR Interval | 36 hours Post-dose | 0.3 bpm | Standard Error 1.44 |
| Moxifloxacin | Placebo-corrected Change From Baseline in HR Interval | 7 hours Post-dose | 0.7 bpm | Standard Error 1.22 |
| Moxifloxacin | Placebo-corrected Change From Baseline in HR Interval | 2 hours Post-dose | 0.3 bpm | Standard Error 0.91 |
| Moxifloxacin | Placebo-corrected Change From Baseline in HR Interval | 24 hours Post-dose | -0.7 bpm | Standard Error 0.81 |
| Moxifloxacin | Placebo-corrected Change From Baseline in HR Interval | 8 hours Post-dose | 0.7 bpm | Standard Error 0.94 |
| Moxifloxacin | Placebo-corrected Change From Baseline in HR Interval | 1.5 hours Post-dose | 0.8 bpm | Standard Error 0.89 |
| Moxifloxacin | Placebo-corrected Change From Baseline in HR Interval | 0.5 hours Post-dose | 0.8 bpm | Standard Error 0.72 |
| Moxifloxacin | Placebo-corrected Change From Baseline in HR Interval | 4 hours Post-dose | 1.0 bpm | Standard Error 1.05 |
| Moxifloxacin | Placebo-corrected Change From Baseline in HR Interval | 3.5 hours Post-dose | 2.1 bpm | Standard Error 0.96 |
| Moxifloxacin | Placebo-corrected Change From Baseline in HR Interval | 12 hours Post-dose | -0.1 bpm | Standard Error 1.38 |
| Moxifloxacin | Placebo-corrected Change From Baseline in HR Interval | 5 hours Post-dose | 0.1 bpm | Standard Error 1.16 |
| Moxifloxacin | Placebo-corrected Change From Baseline in HR Interval | 3 hours Post-dose | 0.7 bpm | Standard Error 0.91 |
| Moxifloxacin | Placebo-corrected Change From Baseline in HR Interval | 1 hours Post-dose | 1.2 bpm | Standard Error 0.88 |
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.
Time frame: At 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 12, 24, and 36 hours post-dose
Population: 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.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Therapeutic Dose: ITF2357 100 mg | Placebo-corrected Change From Baseline in PR Interval | 3 hour Post-dose | -1.4 msec | Standard Error 1.32 |
| Therapeutic Dose: ITF2357 100 mg | Placebo-corrected Change From Baseline in PR Interval | 1.5 hours Post-dose | -2.6 msec | Standard Error 1.33 |
| Therapeutic Dose: ITF2357 100 mg | Placebo-corrected Change From Baseline in PR Interval | 7 hours Post-dose | -1.7 msec | Standard Error 1.73 |
| Therapeutic Dose: ITF2357 100 mg | Placebo-corrected Change From Baseline in PR Interval | 3.5 hours Post-dose | -2.7 msec | Standard Error 1.23 |
| Therapeutic Dose: ITF2357 100 mg | Placebo-corrected Change From Baseline in PR Interval | 1 hour Post-dose | -1.9 msec | Standard Error 1.34 |
| Therapeutic Dose: ITF2357 100 mg | Placebo-corrected Change From Baseline in PR Interval | 6 hours Post-dose | -1.9 msec | Standard Error 1.73 |
| Therapeutic Dose: ITF2357 100 mg | Placebo-corrected Change From Baseline in PR Interval | 4 hours Post-dose | -2.3 msec | Standard Error 1.35 |
| Therapeutic Dose: ITF2357 100 mg | Placebo-corrected Change From Baseline in PR Interval | 12 hours Post-dose | -2.7 msec | Standard Error 1.85 |
| Therapeutic Dose: ITF2357 100 mg | Placebo-corrected Change From Baseline in PR Interval | 5 hours Post-dose | -2.1 msec | Standard Error 1.57 |
| Therapeutic Dose: ITF2357 100 mg | Placebo-corrected Change From Baseline in PR Interval | 2 hours Post-dose | -1.2 msec | Standard Error 1.34 |
| Therapeutic Dose: ITF2357 100 mg | Placebo-corrected Change From Baseline in PR Interval | 36 hours Post-dose | -5.2 msec | Standard Error 1.85 |
| Therapeutic Dose: ITF2357 100 mg | Placebo-corrected Change From Baseline in PR Interval | 0.5 hours Post-dose | -0.2 msec | Standard Error 1.02 |
| Therapeutic Dose: ITF2357 100 mg | Placebo-corrected Change From Baseline in PR Interval | 2.5 hours Post-dose | -3.2 msec | Standard Error 1.32 |
| Therapeutic Dose: ITF2357 100 mg | Placebo-corrected Change From Baseline in PR Interval | 24 hours Post-dose | -2.8 msec | Standard Error 1.76 |
| Therapeutic Dose: ITF2357 100 mg | Placebo-corrected Change From Baseline in PR Interval | 8 hours Post-dose | -2.2 msec | Standard Error 1.53 |
| Supratherapeutic Dose: ITF2357 300 mg | Placebo-corrected Change From Baseline in PR Interval | 8 hours Post-dose | -3.8 msec | Standard Error 1.5 |
| Supratherapeutic Dose: ITF2357 300 mg | Placebo-corrected Change From Baseline in PR Interval | 0.5 hours Post-dose | -0.9 msec | Standard Error 1 |
| Supratherapeutic Dose: ITF2357 300 mg | Placebo-corrected Change From Baseline in PR Interval | 1 hour Post-dose | -1.6 msec | Standard Error 1.31 |
| Supratherapeutic Dose: ITF2357 300 mg | Placebo-corrected Change From Baseline in PR Interval | 1.5 hours Post-dose | -1.5 msec | Standard Error 1.3 |
| Supratherapeutic Dose: ITF2357 300 mg | Placebo-corrected Change From Baseline in PR Interval | 2 hours Post-dose | -2.9 msec | Standard Error 1.31 |
| Supratherapeutic Dose: ITF2357 300 mg | Placebo-corrected Change From Baseline in PR Interval | 2.5 hours Post-dose | -3.1 msec | Standard Error 1.3 |
| Supratherapeutic Dose: ITF2357 300 mg | Placebo-corrected Change From Baseline in PR Interval | 3 hour Post-dose | -1.8 msec | Standard Error 1.3 |
| Supratherapeutic Dose: ITF2357 300 mg | Placebo-corrected Change From Baseline in PR Interval | 3.5 hours Post-dose | -2.9 msec | Standard Error 1.21 |
| Supratherapeutic Dose: ITF2357 300 mg | Placebo-corrected Change From Baseline in PR Interval | 4 hours Post-dose | -3.5 msec | Standard Error 1.32 |
| Supratherapeutic Dose: ITF2357 300 mg | Placebo-corrected Change From Baseline in PR Interval | 5 hours Post-dose | -4.1 msec | Standard Error 1.55 |
| Supratherapeutic Dose: ITF2357 300 mg | Placebo-corrected Change From Baseline in PR Interval | 6 hours Post-dose | -3.8 msec | Standard Error 1.7 |
| Supratherapeutic Dose: ITF2357 300 mg | Placebo-corrected Change From Baseline in PR Interval | 7 hours Post-dose | -4.3 msec | Standard Error 1.7 |
| Supratherapeutic Dose: ITF2357 300 mg | Placebo-corrected Change From Baseline in PR Interval | 12 hours Post-dose | -4.7 msec | Standard Error 1.82 |
| Supratherapeutic Dose: ITF2357 300 mg | Placebo-corrected Change From Baseline in PR Interval | 24 hours Post-dose | -2.9 msec | Standard Error 1.73 |
| Supratherapeutic Dose: ITF2357 300 mg | Placebo-corrected Change From Baseline in PR Interval | 36 hours Post-dose | -6.6 msec | Standard Error 1.82 |
| Moxifloxacin | Placebo-corrected Change From Baseline in PR Interval | 3 hour Post-dose | -1.5 msec | Standard Error 1.31 |
| Moxifloxacin | Placebo-corrected Change From Baseline in PR Interval | 24 hours Post-dose | 3.0 msec | Standard Error 1.74 |
| Moxifloxacin | Placebo-corrected Change From Baseline in PR Interval | 7 hours Post-dose | -2.5 msec | Standard Error 1.71 |
| Moxifloxacin | Placebo-corrected Change From Baseline in PR Interval | 2.5 hours Post-dose | -2.6 msec | Standard Error 1.31 |
| Moxifloxacin | Placebo-corrected Change From Baseline in PR Interval | 2 hours Post-dose | -1.7 msec | Standard Error 1.32 |
| Moxifloxacin | Placebo-corrected Change From Baseline in PR Interval | 8 hours Post-dose | -2.3 msec | Standard Error 1.51 |
| Moxifloxacin | Placebo-corrected Change From Baseline in PR Interval | 1.5 hours Post-dose | -1.6 msec | Standard Error 1.31 |
| Moxifloxacin | Placebo-corrected Change From Baseline in PR Interval | 0.5 hours Post-dose | -0.1 msec | Standard Error 1.01 |
| Moxifloxacin | Placebo-corrected Change From Baseline in PR Interval | 12 hours Post-dose | -3.6 msec | Standard Error 1.84 |
| Moxifloxacin | Placebo-corrected Change From Baseline in PR Interval | 4 hours Post-dose | -2.6 msec | Standard Error 1.33 |
| Moxifloxacin | Placebo-corrected Change From Baseline in PR Interval | 1 hour Post-dose | -2.6 msec | Standard Error 1.32 |
| Moxifloxacin | Placebo-corrected Change From Baseline in PR Interval | 5 hours Post-dose | -2.8 msec | Standard Error 1.56 |
| Moxifloxacin | Placebo-corrected Change From Baseline in PR Interval | 3.5 hours Post-dose | -2.1 msec | Standard Error 1.22 |
| Moxifloxacin | Placebo-corrected Change From Baseline in PR Interval | 36 hours Post-dose | -0.7 msec | Standard Error 1.83 |
| Moxifloxacin | Placebo-corrected Change From Baseline in PR Interval | 6 hours Post-dose | -2.7 msec | Standard Error 1.71 |
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.
Time frame: At 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 12, 24, and 36 hours post-dose
Population: 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.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Therapeutic Dose: ITF2357 100 mg | Placebo-corrected Change From Baseline in QRS Interval | 3 hours Post-dose | -0.2 msec | Standard Error 0.22 |
| Therapeutic Dose: ITF2357 100 mg | Placebo-corrected Change From Baseline in QRS Interval | 1.5 hours Post-dose | 0.1 msec | Standard Error 0.21 |
| Therapeutic Dose: ITF2357 100 mg | Placebo-corrected Change From Baseline in QRS Interval | 7 hours Post-dose | -0.5 msec | Standard Error 0.32 |
| Therapeutic Dose: ITF2357 100 mg | Placebo-corrected Change From Baseline in QRS Interval | 3.5 hours Post-dose | -0.3 msec | Standard Error 0.23 |
| Therapeutic Dose: ITF2357 100 mg | Placebo-corrected Change From Baseline in QRS Interval | 1 hours Post-dose | 0.1 msec | Standard Error 0.21 |
| Therapeutic Dose: ITF2357 100 mg | Placebo-corrected Change From Baseline in QRS Interval | 6 hours Post-dose | -0.2 msec | Standard Error 0.32 |
| Therapeutic Dose: ITF2357 100 mg | Placebo-corrected Change From Baseline in QRS Interval | 4 hours Post-dose | 0.0 msec | Standard Error 0.26 |
| Therapeutic Dose: ITF2357 100 mg | Placebo-corrected Change From Baseline in QRS Interval | 12 hours Post-dose | 0.0 msec | Standard Error 0.4 |
| Therapeutic Dose: ITF2357 100 mg | Placebo-corrected Change From Baseline in QRS Interval | 5 hours Post-dose | -0.3 msec | Standard Error 0.37 |
| Therapeutic Dose: ITF2357 100 mg | Placebo-corrected Change From Baseline in QRS Interval | 2 hours Post-dose | 0.0 msec | Standard Error 0.19 |
| Therapeutic Dose: ITF2357 100 mg | Placebo-corrected Change From Baseline in QRS Interval | 36 hours Post-dose | -0.1 msec | Standard Error 0.36 |
| Therapeutic Dose: ITF2357 100 mg | Placebo-corrected Change From Baseline in QRS Interval | 0.5 hours Post-dose | -0.2 msec | Standard Error 0.17 |
| Therapeutic Dose: ITF2357 100 mg | Placebo-corrected Change From Baseline in QRS Interval | 2.5 hours Post-dose | -0.2 msec | Standard Error 0.21 |
| Therapeutic Dose: ITF2357 100 mg | Placebo-corrected Change From Baseline in QRS Interval | 24 hours Post-dose | 0.1 msec | Standard Error 0.54 |
| Therapeutic Dose: ITF2357 100 mg | Placebo-corrected Change From Baseline in QRS Interval | 8 hours Post-dose | -0.3 msec | Standard Error 0.28 |
| Supratherapeutic Dose: ITF2357 300 mg | Placebo-corrected Change From Baseline in QRS Interval | 8 hours Post-dose | 0.2 msec | Standard Error 0.28 |
| Supratherapeutic Dose: ITF2357 300 mg | Placebo-corrected Change From Baseline in QRS Interval | 0.5 hours Post-dose | 0.0 msec | Standard Error 0.16 |
| Supratherapeutic Dose: ITF2357 300 mg | Placebo-corrected Change From Baseline in QRS Interval | 1 hours Post-dose | 0.1 msec | Standard Error 0.2 |
| Supratherapeutic Dose: ITF2357 300 mg | Placebo-corrected Change From Baseline in QRS Interval | 1.5 hours Post-dose | 0.1 msec | Standard Error 0.2 |
| Supratherapeutic Dose: ITF2357 300 mg | Placebo-corrected Change From Baseline in QRS Interval | 2 hours Post-dose | 0.2 msec | Standard Error 0.19 |
| Supratherapeutic Dose: ITF2357 300 mg | Placebo-corrected Change From Baseline in QRS Interval | 2.5 hours Post-dose | 0.1 msec | Standard Error 0.2 |
| Supratherapeutic Dose: ITF2357 300 mg | Placebo-corrected Change From Baseline in QRS Interval | 3 hours Post-dose | 0.1 msec | Standard Error 0.22 |
| Supratherapeutic Dose: ITF2357 300 mg | Placebo-corrected Change From Baseline in QRS Interval | 3.5 hours Post-dose | 0.2 msec | Standard Error 0.23 |
| Supratherapeutic Dose: ITF2357 300 mg | Placebo-corrected Change From Baseline in QRS Interval | 4 hours Post-dose | 0.2 msec | Standard Error 0.26 |
| Supratherapeutic Dose: ITF2357 300 mg | Placebo-corrected Change From Baseline in QRS Interval | 5 hours Post-dose | 0.0 msec | Standard Error 0.36 |
| Supratherapeutic Dose: ITF2357 300 mg | Placebo-corrected Change From Baseline in QRS Interval | 6 hours Post-dose | 0.0 msec | Standard Error 0.32 |
| Supratherapeutic Dose: ITF2357 300 mg | Placebo-corrected Change From Baseline in QRS Interval | 7 hours Post-dose | -0.4 msec | Standard Error 0.31 |
| Supratherapeutic Dose: ITF2357 300 mg | Placebo-corrected Change From Baseline in QRS Interval | 12 hours Post-dose | -0.5 msec | Standard Error 0.39 |
| Supratherapeutic Dose: ITF2357 300 mg | Placebo-corrected Change From Baseline in QRS Interval | 24 hours Post-dose | 0.4 msec | Standard Error 0.53 |
| Supratherapeutic Dose: ITF2357 300 mg | Placebo-corrected Change From Baseline in QRS Interval | 36 hours Post-dose | -0.1 msec | Standard Error 0.35 |
| Moxifloxacin | Placebo-corrected Change From Baseline in QRS Interval | 3 hours Post-dose | 0.0 msec | Standard Error 0.22 |
| Moxifloxacin | Placebo-corrected Change From Baseline in QRS Interval | 24 hours Post-dose | -0.1 msec | Standard Error 0.53 |
| Moxifloxacin | Placebo-corrected Change From Baseline in QRS Interval | 7 hours Post-dose | -0.3 msec | Standard Error 0.31 |
| Moxifloxacin | Placebo-corrected Change From Baseline in QRS Interval | 2.5 hours Post-dose | 0.2 msec | Standard Error 0.21 |
| Moxifloxacin | Placebo-corrected Change From Baseline in QRS Interval | 2 hours Post-dose | 0.3 msec | Standard Error 0.19 |
| Moxifloxacin | Placebo-corrected Change From Baseline in QRS Interval | 8 hours Post-dose | 0.0 msec | Standard Error 0.28 |
| Moxifloxacin | Placebo-corrected Change From Baseline in QRS Interval | 1.5 hours Post-dose | 0.0 msec | Standard Error 0.2 |
| Moxifloxacin | Placebo-corrected Change From Baseline in QRS Interval | 0.5 hours Post-dose | 0.1 msec | Standard Error 0.17 |
| Moxifloxacin | Placebo-corrected Change From Baseline in QRS Interval | 12 hours Post-dose | -0.1 msec | Standard Error 0.4 |
| Moxifloxacin | Placebo-corrected Change From Baseline in QRS Interval | 4 hours Post-dose | 0.2 msec | Standard Error 0.26 |
| Moxifloxacin | Placebo-corrected Change From Baseline in QRS Interval | 1 hours Post-dose | 0.4 msec | Standard Error 0.2 |
| Moxifloxacin | Placebo-corrected Change From Baseline in QRS Interval | 5 hours Post-dose | -0.2 msec | Standard Error 0.36 |
| Moxifloxacin | Placebo-corrected Change From Baseline in QRS Interval | 3.5 hours Post-dose | -0.2 msec | Standard Error 0.23 |
| Moxifloxacin | Placebo-corrected Change From Baseline in QRS Interval | 36 hours Post-dose | -0.2 msec | Standard Error 0.36 |
| Moxifloxacin | Placebo-corrected Change From Baseline in QRS Interval | 6 hours Post-dose | -0.1 msec | Standard Error 0.32 |
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.
Time frame: 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
Population: 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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Therapeutic Dose: ITF2357 100 mg | Plasma Pharmacokinetic (PK): Area Under the Concentration-Time Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of ITF2357 and Its Metabolites | ITF2357 | 596.10 hours*nanograms per milliliter (h*ng/mL) | Geometric Coefficient of Variation 22.57 |
| Therapeutic Dose: ITF2357 100 mg | Plasma Pharmacokinetic (PK): Area Under the Concentration-Time Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of ITF2357 and Its Metabolites | ITF2374 | 363.55 hours*nanograms per milliliter (h*ng/mL) | Geometric Coefficient of Variation 63.83 |
| Therapeutic Dose: ITF2357 100 mg | Plasma Pharmacokinetic (PK): Area Under the Concentration-Time Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of ITF2357 and Its Metabolites | ITF2375 | 2672.92 hours*nanograms per milliliter (h*ng/mL) | Geometric Coefficient of Variation 54.88 |
| Therapeutic Dose: ITF2357 100 mg | Plasma Pharmacokinetic (PK): Area Under the Concentration-Time Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of ITF2357 and Its Metabolites | ITF2440 | 5696.28 hours*nanograms per milliliter (h*ng/mL) | Geometric Coefficient of Variation 23.36 |
| Therapeutic Dose: ITF2357 100 mg | Plasma Pharmacokinetic (PK): Area Under the Concentration-Time Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of ITF2357 and Its Metabolites | ITF2563 | 1247.92 hours*nanograms per milliliter (h*ng/mL) | Geometric Coefficient of Variation 23.58 |
| Therapeutic Dose: ITF2357 100 mg | Plasma Pharmacokinetic (PK): Area Under the Concentration-Time Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of ITF2357 and Its Metabolites | ITF2955 glucuronide | 1.53 hours*nanograms per milliliter (h*ng/mL) | Geometric Coefficient of Variation 78 |
| Supratherapeutic Dose: ITF2357 300 mg | Plasma Pharmacokinetic (PK): Area Under the Concentration-Time Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of ITF2357 and Its Metabolites | ITF2563 | 3563.33 hours*nanograms per milliliter (h*ng/mL) | Geometric Coefficient of Variation 20.59 |
| Supratherapeutic Dose: ITF2357 300 mg | Plasma Pharmacokinetic (PK): Area Under the Concentration-Time Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of ITF2357 and Its Metabolites | ITF2357 | 2313.44 hours*nanograms per milliliter (h*ng/mL) | Geometric Coefficient of Variation 20.53 |
| Supratherapeutic Dose: ITF2357 300 mg | Plasma Pharmacokinetic (PK): Area Under the Concentration-Time Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of ITF2357 and Its Metabolites | ITF2440 | 18577.74 hours*nanograms per milliliter (h*ng/mL) | Geometric Coefficient of Variation 21.34 |
| Supratherapeutic Dose: ITF2357 300 mg | Plasma Pharmacokinetic (PK): Area Under the Concentration-Time Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of ITF2357 and Its Metabolites | ITF2374 | 1296.22 hours*nanograms per milliliter (h*ng/mL) | Geometric Coefficient of Variation 59.65 |
| Supratherapeutic Dose: ITF2357 300 mg | Plasma Pharmacokinetic (PK): Area Under the Concentration-Time Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of ITF2357 and Its Metabolites | ITF2955 glucuronide | 15.89 hours*nanograms per milliliter (h*ng/mL) | Geometric Coefficient of Variation 47.69 |
| Supratherapeutic Dose: ITF2357 300 mg | Plasma Pharmacokinetic (PK): Area Under the Concentration-Time Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of ITF2357 and Its Metabolites | ITF2375 | 9599.11 hours*nanograms per milliliter (h*ng/mL) | Geometric Coefficient of Variation 52.7 |
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.
Time frame: 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
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Therapeutic Dose: ITF2357 100 mg | Plasma PK: Apparent Total Body Clearance (CL/F) of ITF2357 and Its Metabolites | ITF2357 | 167.12 liters per hour | Standard Deviation 36.4 |
| Therapeutic Dose: ITF2357 100 mg | Plasma PK: Apparent Total Body Clearance (CL/F) of ITF2357 and Its Metabolites | ITF2374 | 296.86 liters per hour | Standard Deviation 172.71 |
| Therapeutic Dose: ITF2357 100 mg | Plasma PK: Apparent Total Body Clearance (CL/F) of ITF2357 and Its Metabolites | ITF2375 | 43.11 liters per hour | Standard Deviation 27.8 |
| Therapeutic Dose: ITF2357 100 mg | Plasma PK: Apparent Total Body Clearance (CL/F) of ITF2357 and Its Metabolites | ITF2440 | 16.94 liters per hour | Standard Deviation 4.01 |
| Therapeutic Dose: ITF2357 100 mg | Plasma PK: Apparent Total Body Clearance (CL/F) of ITF2357 and Its Metabolites | ITF2563 | 76.77 liters per hour | Standard Deviation 16.33 |
| Therapeutic Dose: ITF2357 100 mg | Plasma PK: Apparent Total Body Clearance (CL/F) of ITF2357 and Its Metabolites | ITF2955 glucuronide | 9808.03 liters per hour | — |
| Supratherapeutic Dose: ITF2357 300 mg | Plasma PK: Apparent Total Body Clearance (CL/F) of ITF2357 and Its Metabolites | ITF2563 | 80.71 liters per hour | Standard Deviation 17.61 |
| Supratherapeutic Dose: ITF2357 300 mg | Plasma PK: Apparent Total Body Clearance (CL/F) of ITF2357 and Its Metabolites | ITF2357 | 131.11 liters per hour | Standard Deviation 27.51 |
| Supratherapeutic Dose: ITF2357 300 mg | Plasma PK: Apparent Total Body Clearance (CL/F) of ITF2357 and Its Metabolites | ITF2440 | 15.73 liters per hour | Standard Deviation 3.6 |
| Supratherapeutic Dose: ITF2357 300 mg | Plasma PK: Apparent Total Body Clearance (CL/F) of ITF2357 and Its Metabolites | ITF2374 | 251.84 liters per hour | Standard Deviation 124.72 |
| Supratherapeutic Dose: ITF2357 300 mg | Plasma PK: Apparent Total Body Clearance (CL/F) of ITF2357 and Its Metabolites | ITF2955 glucuronide | 16631.81 liters per hour | Standard Deviation 5576.18 |
| Supratherapeutic Dose: ITF2357 300 mg | Plasma PK: Apparent Total Body Clearance (CL/F) of ITF2357 and Its Metabolites | ITF2375 | 36.69 liters per hour | Standard Deviation 23.96 |
Secondary
Plasma PK: Apparent Total Body Clearance (CL/F) of Moxifloxacin
CL/F was calculated as Dose/AUC0-inf for moxifloxacin.
Time frame: 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
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Therapeutic Dose: ITF2357 100 mg | Plasma PK: Apparent Total Body Clearance (CL/F) of Moxifloxacin | 14.49 liters per hour | Standard Deviation 2.39 |
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.
Time frame: 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
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Therapeutic Dose: ITF2357 100 mg | Plasma PK: Apparent Volume of Distribution (Vd/F) of ITF2357 and Its Metabolites | ITF2357 | 1897.03 liters | Standard Deviation 588.15 |
| Therapeutic Dose: ITF2357 100 mg | Plasma PK: Apparent Volume of Distribution (Vd/F) of ITF2357 and Its Metabolites | ITF2374 | 5094.92 liters | Standard Deviation 2676.37 |
| Therapeutic Dose: ITF2357 100 mg | Plasma PK: Apparent Volume of Distribution (Vd/F) of ITF2357 and Its Metabolites | ITF2375 | 795.34 liters | Standard Deviation 636.25 |
| Therapeutic Dose: ITF2357 100 mg | Plasma PK: Apparent Volume of Distribution (Vd/F) of ITF2357 and Its Metabolites | ITF2440 | 354.01 liters | Standard Deviation 123.39 |
| Therapeutic Dose: ITF2357 100 mg | Plasma PK: Apparent Volume of Distribution (Vd/F) of ITF2357 and Its Metabolites | ITF2563 | 1702.58 liters | Standard Deviation 749.67 |
| Therapeutic Dose: ITF2357 100 mg | Plasma PK: Apparent Volume of Distribution (Vd/F) of ITF2357 and Its Metabolites | ITF2955 glucuronide | 64779.37 liters | — |
| Supratherapeutic Dose: ITF2357 300 mg | Plasma PK: Apparent Volume of Distribution (Vd/F) of ITF2357 and Its Metabolites | ITF2563 | 1757.38 liters | Standard Deviation 556.98 |
| Supratherapeutic Dose: ITF2357 300 mg | Plasma PK: Apparent Volume of Distribution (Vd/F) of ITF2357 and Its Metabolites | ITF2357 | 2125.49 liters | Standard Deviation 764.32 |
| Supratherapeutic Dose: ITF2357 300 mg | Plasma PK: Apparent Volume of Distribution (Vd/F) of ITF2357 and Its Metabolites | ITF2440 | 311.58 liters | Standard Deviation 96.04 |
| Supratherapeutic Dose: ITF2357 300 mg | Plasma PK: Apparent Volume of Distribution (Vd/F) of ITF2357 and Its Metabolites | ITF2374 | 5027.46 liters | Standard Deviation 3106.93 |
| Supratherapeutic Dose: ITF2357 300 mg | Plasma PK: Apparent Volume of Distribution (Vd/F) of ITF2357 and Its Metabolites | ITF2955 glucuronide | 58366.39 liters | Standard Deviation 12977.61 |
| Supratherapeutic Dose: ITF2357 300 mg | Plasma PK: Apparent Volume of Distribution (Vd/F) of ITF2357 and Its Metabolites | ITF2375 | 576.42 liters | Standard Deviation 436.72 |
Secondary
Plasma PK: Apparent Volume of Distribution (Vd/F) of Moxifloxacin
Vd/F was calculated as Dose/Kel x AUC0-inf for moxifloxacin.
Time frame: 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
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Therapeutic Dose: ITF2357 100 mg | Plasma PK: Apparent Volume of Distribution (Vd/F) of Moxifloxacin | 303.02 liters | Standard Deviation 72.21 |
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.
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, and 12 hours post-dose
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Therapeutic Dose: ITF2357 100 mg | Plasma PK: Area Under the Concentration-Time Curve From Time Zero to 12 Hours (AUC0-12) of ITF2357 and Its Metabolites | ITF2357 | 480.70 h*ng/mL | Standard Deviation 114.09 |
| Therapeutic Dose: ITF2357 100 mg | Plasma PK: Area Under the Concentration-Time Curve From Time Zero to 12 Hours (AUC0-12) of ITF2357 and Its Metabolites | ITF2374 | 178.10 h*ng/mL | Standard Deviation 81.57 |
| Therapeutic Dose: ITF2357 100 mg | Plasma PK: Area Under the Concentration-Time Curve From Time Zero to 12 Hours (AUC0-12) of ITF2357 and Its Metabolites | ITF2375 | 1680.76 h*ng/mL | Standard Deviation 725.8 |
| Therapeutic Dose: ITF2357 100 mg | Plasma PK: Area Under the Concentration-Time Curve From Time Zero to 12 Hours (AUC0-12) of ITF2357 and Its Metabolites | ITF2440 | 1448.97 h*ng/mL | Standard Deviation 362.63 |
| Therapeutic Dose: ITF2357 100 mg | Plasma PK: Area Under the Concentration-Time Curve From Time Zero to 12 Hours (AUC0-12) of ITF2357 and Its Metabolites | ITF2563 | 299.77 h*ng/mL | Standard Deviation 85.39 |
| Therapeutic Dose: ITF2357 100 mg | Plasma PK: Area Under the Concentration-Time Curve From Time Zero to 12 Hours (AUC0-12) of ITF2357 and Its Metabolites | ITF2955 glucuronide | 0.88 h*ng/mL | Standard Deviation 1.62 |
| Supratherapeutic Dose: ITF2357 300 mg | Plasma PK: Area Under the Concentration-Time Curve From Time Zero to 12 Hours (AUC0-12) of ITF2357 and Its Metabolites | ITF2563 | 776.22 h*ng/mL | Standard Deviation 259.98 |
| Supratherapeutic Dose: ITF2357 300 mg | Plasma PK: Area Under the Concentration-Time Curve From Time Zero to 12 Hours (AUC0-12) of ITF2357 and Its Metabolites | ITF2357 | 1893.60 h*ng/mL | Standard Deviation 423.33 |
| Supratherapeutic Dose: ITF2357 300 mg | Plasma PK: Area Under the Concentration-Time Curve From Time Zero to 12 Hours (AUC0-12) of ITF2357 and Its Metabolites | ITF2440 | 3924.21 h*ng/mL | Standard Deviation 1130.05 |
| Supratherapeutic Dose: ITF2357 300 mg | Plasma PK: Area Under the Concentration-Time Curve From Time Zero to 12 Hours (AUC0-12) of ITF2357 and Its Metabolites | ITF2374 | 607.16 h*ng/mL | Standard Deviation 258.73 |
| Supratherapeutic Dose: ITF2357 300 mg | Plasma PK: Area Under the Concentration-Time Curve From Time Zero to 12 Hours (AUC0-12) of ITF2357 and Its Metabolites | ITF2955 glucuronide | 18.08 h*ng/mL | Standard Deviation 8.39 |
| Supratherapeutic Dose: ITF2357 300 mg | Plasma PK: Area Under the Concentration-Time Curve From Time Zero to 12 Hours (AUC0-12) of ITF2357 and Its Metabolites | ITF2375 | 6018.02 h*ng/mL | Standard Deviation 2430.06 |
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.
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8 and 12 hours post-dose
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Therapeutic Dose: ITF2357 100 mg | Plasma PK: Area Under the Concentration-Time Curve From Time Zero to 12 Hours (AUC0-12) of Moxifloxacin | 13625.09 h*ng/mL | Standard Deviation 2733.45 |
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.
Time frame: 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
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Therapeutic Dose: ITF2357 100 mg | Plasma PK: Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of ITF2357 and Its Metabolites | ITF2357 | 626.57 h*ng/mL | Standard Deviation 139.54 |
| Therapeutic Dose: ITF2357 100 mg | Plasma PK: Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of ITF2357 and Its Metabolites | ITF2374 | 475.82 h*ng/mL | Standard Deviation 318.25 |
| Therapeutic Dose: ITF2357 100 mg | Plasma PK: Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of ITF2357 and Its Metabolites | ITF2375 | 3246.97 h*ng/mL | Standard Deviation 1806.52 |
| Therapeutic Dose: ITF2357 100 mg | Plasma PK: Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of ITF2357 and Its Metabolites | ITF2440 | 6196.74 h*ng/mL | Standard Deviation 1400.6 |
| Therapeutic Dose: ITF2357 100 mg | Plasma PK: Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of ITF2357 and Its Metabolites | ITF2563 | 1357.46 h*ng/mL | Standard Deviation 290.51 |
| Therapeutic Dose: ITF2357 100 mg | Plasma PK: Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of ITF2357 and Its Metabolites | ITF2955 glucuronide | 10.20 h*ng/mL | — |
| Supratherapeutic Dose: ITF2357 300 mg | Plasma PK: Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of ITF2357 and Its Metabolites | ITF2563 | 3864.88 h*ng/mL | Standard Deviation 757.94 |
| Supratherapeutic Dose: ITF2357 300 mg | Plasma PK: Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of ITF2357 and Its Metabolites | ITF2357 | 2383.27 h*ng/mL | Standard Deviation 484.72 |
| Supratherapeutic Dose: ITF2357 300 mg | Plasma PK: Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of ITF2357 and Its Metabolites | ITF2440 | 19920.16 h*ng/mL | Standard Deviation 4134.67 |
| Supratherapeutic Dose: ITF2357 300 mg | Plasma PK: Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of ITF2357 and Its Metabolites | ITF2374 | 1555.70 h*ng/mL | Standard Deviation 986.4 |
| Supratherapeutic Dose: ITF2357 300 mg | Plasma PK: Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of ITF2357 and Its Metabolites | ITF2955 glucuronide | 20.68 h*ng/mL | Standard Deviation 9.56 |
| Supratherapeutic Dose: ITF2357 300 mg | Plasma PK: Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of ITF2357 and Its Metabolites | ITF2375 | 11373.93 h*ng/mL | Standard Deviation 6045.3 |
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.
Time frame: 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
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Therapeutic Dose: ITF2357 100 mg | Plasma PK: Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of Moxifloxacin | 28327.15 h*ng/mL | Standard Deviation 4616.5 |
Secondary
Plasma PK: Area Under the Concentration-Time Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of Moxifloxacin
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).
Time frame: 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
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Therapeutic Dose: ITF2357 100 mg | Plasma PK: Area Under the Concentration-Time Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of Moxifloxacin | 27077.52 h*ng/mL | Geometric Coefficient of Variation 16.17 |
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.
Time frame: 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
Population: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Therapeutic Dose: ITF2357 100 mg | Plasma PK: Elimination Half-life (T½ el) of ITF2357 and Its Metabolites | ITF2357 | 7.25 hours |
| Therapeutic Dose: ITF2357 100 mg | Plasma PK: Elimination Half-life (T½ el) of ITF2357 and Its Metabolites | ITF2374 | 12.63 hours |
| Therapeutic Dose: ITF2357 100 mg | Plasma PK: Elimination Half-life (T½ el) of ITF2357 and Its Metabolites | ITF2375 | 12.31 hours |
| Therapeutic Dose: ITF2357 100 mg | Plasma PK: Elimination Half-life (T½ el) of ITF2357 and Its Metabolites | ITF2440 | 12.91 hours |
| Therapeutic Dose: ITF2357 100 mg | Plasma PK: Elimination Half-life (T½ el) of ITF2357 and Its Metabolites | ITF2563 | 13.47 hours |
| Therapeutic Dose: ITF2357 100 mg | Plasma PK: Elimination Half-life (T½ el) of ITF2357 and Its Metabolites | ITF2955 glucuronide | 4.58 hours |
| Supratherapeutic Dose: ITF2357 300 mg | Plasma PK: Elimination Half-life (T½ el) of ITF2357 and Its Metabolites | ITF2563 | 13.33 hours |
| Supratherapeutic Dose: ITF2357 300 mg | Plasma PK: Elimination Half-life (T½ el) of ITF2357 and Its Metabolites | ITF2357 | 11.19 hours |
| Supratherapeutic Dose: ITF2357 300 mg | Plasma PK: Elimination Half-life (T½ el) of ITF2357 and Its Metabolites | ITF2440 | 13.07 hours |
| Supratherapeutic Dose: ITF2357 300 mg | Plasma PK: Elimination Half-life (T½ el) of ITF2357 and Its Metabolites | ITF2374 | 12.49 hours |
| Supratherapeutic Dose: ITF2357 300 mg | Plasma PK: Elimination Half-life (T½ el) of ITF2357 and Its Metabolites | ITF2955 glucuronide | 2.27 hours |
| Supratherapeutic Dose: ITF2357 300 mg | Plasma PK: Elimination Half-life (T½ el) of ITF2357 and Its Metabolites | ITF2375 | 10.71 hours |
Secondary
Plasma PK: Elimination Half-life (T½ el) of Moxifloxacin
T½ el was calculated as ln(2)/kel for moxifloxacin.
Time frame: 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
Population: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Therapeutic Dose: ITF2357 100 mg | Plasma PK: Elimination Half-life (T½ el) of Moxifloxacin | 13.97 hours |
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.
Time frame: 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
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Therapeutic Dose: ITF2357 100 mg | Plasma PK: Elimination Rate Constant (Kel) of ITF2357 and Its Metabolites | ITF2357 | 0.0923 fraction per hour | Standard Deviation 0.0198 |
| Therapeutic Dose: ITF2357 100 mg | Plasma PK: Elimination Rate Constant (Kel) of ITF2357 and Its Metabolites | ITF2374 | 0.0570 fraction per hour | Standard Deviation 0.0141 |
| Therapeutic Dose: ITF2357 100 mg | Plasma PK: Elimination Rate Constant (Kel) of ITF2357 and Its Metabolites | ITF2375 | 0.0585 fraction per hour | Standard Deviation 0.0157 |
| Therapeutic Dose: ITF2357 100 mg | Plasma PK: Elimination Rate Constant (Kel) of ITF2357 and Its Metabolites | ITF2440 | 0.0508 fraction per hour | Standard Deviation 0.0126 |
| Therapeutic Dose: ITF2357 100 mg | Plasma PK: Elimination Rate Constant (Kel) of ITF2357 and Its Metabolites | ITF2563 | 0.0499 fraction per hour | Standard Deviation 0.0138 |
| Therapeutic Dose: ITF2357 100 mg | Plasma PK: Elimination Rate Constant (Kel) of ITF2357 and Its Metabolites | ITF2955 glucuronide | 0.1514 fraction per hour | — |
| Supratherapeutic Dose: ITF2357 300 mg | Plasma PK: Elimination Rate Constant (Kel) of ITF2357 and Its Metabolites | ITF2563 | 0.0498 fraction per hour | Standard Deviation 0.0156 |
| Supratherapeutic Dose: ITF2357 300 mg | Plasma PK: Elimination Rate Constant (Kel) of ITF2357 and Its Metabolites | ITF2357 | 0.0652 fraction per hour | Standard Deviation 0.0146 |
| Supratherapeutic Dose: ITF2357 300 mg | Plasma PK: Elimination Rate Constant (Kel) of ITF2357 and Its Metabolites | ITF2440 | 0.0530 fraction per hour | Standard Deviation 0.0124 |
| Supratherapeutic Dose: ITF2357 300 mg | Plasma PK: Elimination Rate Constant (Kel) of ITF2357 and Its Metabolites | ITF2374 | 0.0549 fraction per hour | Standard Deviation 0.0175 |
| Supratherapeutic Dose: ITF2357 300 mg | Plasma PK: Elimination Rate Constant (Kel) of ITF2357 and Its Metabolites | ITF2955 glucuronide | 0.2886 fraction per hour | Standard Deviation 0.0944 |
| Supratherapeutic Dose: ITF2357 300 mg | Plasma PK: Elimination Rate Constant (Kel) of ITF2357 and Its Metabolites | ITF2375 | 0.0667 fraction per hour | Standard Deviation 0.013 |
Secondary
Plasma PK: Elimination Rate Constant (Kel) of Moxifloxacin
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 Moxifloxacin.
Time frame: 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
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Therapeutic Dose: ITF2357 100 mg | Plasma PK: Elimination Rate Constant (Kel) of Moxifloxacin | 0.0493 fraction per hour | Standard Deviation 0.0091 |
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.
Time frame: 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
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Therapeutic Dose: ITF2357 100 mg | Plasma PK: Maximum Observed Plasma Concentration (Cmax) of ITF2357 and Its Metabolites | ITF2357 | 102.84 ng/mL | Standard Deviation 30.55 |
| Therapeutic Dose: ITF2357 100 mg | Plasma PK: Maximum Observed Plasma Concentration (Cmax) of ITF2357 and Its Metabolites | ITF2374 | 24.39 ng/mL | Standard Deviation 11.01 |
| Therapeutic Dose: ITF2357 100 mg | Plasma PK: Maximum Observed Plasma Concentration (Cmax) of ITF2357 and Its Metabolites | ITF2375 | 258.64 ng/mL | Standard Deviation 111.23 |
| Therapeutic Dose: ITF2357 100 mg | Plasma PK: Maximum Observed Plasma Concentration (Cmax) of ITF2357 and Its Metabolites | ITF2440 | 195.23 ng/mL | Standard Deviation 45.41 |
| Therapeutic Dose: ITF2357 100 mg | Plasma PK: Maximum Observed Plasma Concentration (Cmax) of ITF2357 and Its Metabolites | ITF2563 | 43.90 ng/mL | Standard Deviation 13.03 |
| Therapeutic Dose: ITF2357 100 mg | Plasma PK: Maximum Observed Plasma Concentration (Cmax) of ITF2357 and Its Metabolites | ITF2955 glucuronide | 0.42 ng/mL | Standard Deviation 0.62 |
| Supratherapeutic Dose: ITF2357 300 mg | Plasma PK: Maximum Observed Plasma Concentration (Cmax) of ITF2357 and Its Metabolites | ITF2563 | 123.27 ng/mL | Standard Deviation 31.02 |
| Supratherapeutic Dose: ITF2357 300 mg | Plasma PK: Maximum Observed Plasma Concentration (Cmax) of ITF2357 and Its Metabolites | ITF2357 | 409.65 ng/mL | Standard Deviation 133.74 |
| Supratherapeutic Dose: ITF2357 300 mg | Plasma PK: Maximum Observed Plasma Concentration (Cmax) of ITF2357 and Its Metabolites | ITF2440 | 602.02 ng/mL | Standard Deviation 142.15 |
| Supratherapeutic Dose: ITF2357 300 mg | Plasma PK: Maximum Observed Plasma Concentration (Cmax) of ITF2357 and Its Metabolites | ITF2374 | 81.59 ng/mL | Standard Deviation 32.93 |
| Supratherapeutic Dose: ITF2357 300 mg | Plasma PK: Maximum Observed Plasma Concentration (Cmax) of ITF2357 and Its Metabolites | ITF2955 glucuronide | 4.41 ng/mL | Standard Deviation 1.7 |
| Supratherapeutic Dose: ITF2357 300 mg | Plasma PK: Maximum Observed Plasma Concentration (Cmax) of ITF2357 and Its Metabolites | ITF2375 | 820.75 ng/mL | Standard Deviation 273.52 |
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.
Time frame: 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
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Therapeutic Dose: ITF2357 100 mg | Plasma PK: Maximum Observed Plasma Concentration (Cmax) of Moxifloxacin | 1789.49 ng/mL | Standard Deviation 498.08 |
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.
Time frame: 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
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Therapeutic Dose: ITF2357 100 mg | Plasma PK: Percentage of Residual Area for ITF2357 and Its Metabolites | ITF2357 | 2.63 Percentage of residual area | Standard Deviation 0.84 |
| Therapeutic Dose: ITF2357 100 mg | Plasma PK: Percentage of Residual Area for ITF2357 and Its Metabolites | ITF2374 | 8.49 Percentage of residual area | Standard Deviation 4.23 |
| Therapeutic Dose: ITF2357 100 mg | Plasma PK: Percentage of Residual Area for ITF2357 and Its Metabolites | ITF2375 | 3.45 Percentage of residual area | Standard Deviation 2.28 |
| Therapeutic Dose: ITF2357 100 mg | Plasma PK: Percentage of Residual Area for ITF2357 and Its Metabolites | ITF2440 | 5.81 Percentage of residual area | Standard Deviation 3.09 |
| Therapeutic Dose: ITF2357 100 mg | Plasma PK: Percentage of Residual Area for ITF2357 and Its Metabolites | ITF2563 | 6.04 Percentage of residual area | Standard Deviation 4.53 |
| Therapeutic Dose: ITF2357 100 mg | Plasma PK: Percentage of Residual Area for ITF2357 and Its Metabolites | ITF2955 glucuronide | 66.07 Percentage of residual area | — |
| Supratherapeutic Dose: ITF2357 300 mg | Plasma PK: Percentage of Residual Area for ITF2357 and Its Metabolites | ITF2563 | 5.95 Percentage of residual area | Standard Deviation 4.42 |
| Supratherapeutic Dose: ITF2357 300 mg | Plasma PK: Percentage of Residual Area for ITF2357 and Its Metabolites | ITF2357 | 0.95 Percentage of residual area | Standard Deviation 0.36 |
| Supratherapeutic Dose: ITF2357 300 mg | Plasma PK: Percentage of Residual Area for ITF2357 and Its Metabolites | ITF2440 | 4.69 Percentage of residual area | Standard Deviation 3.58 |
| Supratherapeutic Dose: ITF2357 300 mg | Plasma PK: Percentage of Residual Area for ITF2357 and Its Metabolites | ITF2374 | 3.72 Percentage of residual area | Standard Deviation 2.82 |
| Supratherapeutic Dose: ITF2357 300 mg | Plasma PK: Percentage of Residual Area for ITF2357 and Its Metabolites | ITF2955 glucuronide | 24.01 Percentage of residual area | Standard Deviation 6.03 |
| Supratherapeutic Dose: ITF2357 300 mg | Plasma PK: Percentage of Residual Area for ITF2357 and Its Metabolites | ITF2375 | 1.70 Percentage of residual area | Standard Deviation 1.25 |
Secondary
Plasma PK: Percentage of Residual Area for Moxifloxacin
Residual area was calculated as 100\*(1- AUC0-t / AUC0-inf) for moxifloxacin.
Time frame: 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
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Therapeutic Dose: ITF2357 100 mg | Plasma PK: Percentage of Residual Area for Moxifloxacin | 2.81 Percentage of residual area | Geometric Coefficient of Variation 48.66 |
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.
Time frame: 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
Population: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Therapeutic Dose: ITF2357 100 mg | Plasma PK: Time of Observed Cmax (Tmax) of ITF2357 and Its Metabolites | ITF2374 | 5.098 hours |
| Therapeutic Dose: ITF2357 100 mg | Plasma PK: Time of Observed Cmax (Tmax) of ITF2357 and Its Metabolites | ITF2440 | 12.144 hours |
| Therapeutic Dose: ITF2357 100 mg | Plasma PK: Time of Observed Cmax (Tmax) of ITF2357 and Its Metabolites | ITF2357 | 2.139 hours |
| Therapeutic Dose: ITF2357 100 mg | Plasma PK: Time of Observed Cmax (Tmax) of ITF2357 and Its Metabolites | ITF2563 | 12.146 hours |
| Therapeutic Dose: ITF2357 100 mg | Plasma PK: Time of Observed Cmax (Tmax) of ITF2357 and Its Metabolites | ITF2375 | 3.610 hours |
| Therapeutic Dose: ITF2357 100 mg | Plasma PK: Time of Observed Cmax (Tmax) of ITF2357 and Its Metabolites | ITF2955 glucuronide | 0 hours |
| Supratherapeutic Dose: ITF2357 300 mg | Plasma PK: Time of Observed Cmax (Tmax) of ITF2357 and Its Metabolites | ITF2375 | 4.094 hours |
| Supratherapeutic Dose: ITF2357 300 mg | Plasma PK: Time of Observed Cmax (Tmax) of ITF2357 and Its Metabolites | ITF2357 | 2.158 hours |
| Supratherapeutic Dose: ITF2357 300 mg | Plasma PK: Time of Observed Cmax (Tmax) of ITF2357 and Its Metabolites | ITF2374 | 5.634 hours |
| Supratherapeutic Dose: ITF2357 300 mg | Plasma PK: Time of Observed Cmax (Tmax) of ITF2357 and Its Metabolites | ITF2955 glucuronide | 2.606 hours |
| Supratherapeutic Dose: ITF2357 300 mg | Plasma PK: Time of Observed Cmax (Tmax) of ITF2357 and Its Metabolites | ITF2440 | 12.152 hours |
| Supratherapeutic Dose: ITF2357 300 mg | Plasma PK: Time of Observed Cmax (Tmax) of ITF2357 and Its Metabolites | ITF2563 | 12.152 hours |
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.
Time frame: 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
Population: 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.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Therapeutic Dose: ITF2357 100 mg | Plasma PK: Time of Observed Cmax (Tmax) of Moxifloxacin | 2.327 hours |
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.
Time frame: Pre-dose (within 2 hours before dosing), 0-8 hours, 8-24 hours, 24-48 hours, and 48-72 hours post-dose
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Therapeutic Dose: ITF2357 100 mg | Urine PK: Cumulative Urinary Excretion From Time Zero to Time t (Ae0-t) for ITF2357 and Its Metabolites | ITF2357 | 1304747.81 Nanograms (ng) | Standard Deviation 444627.39 |
| Therapeutic Dose: ITF2357 100 mg | Urine PK: Cumulative Urinary Excretion From Time Zero to Time t (Ae0-t) for ITF2357 and Its Metabolites | ITF2374 | 1526630.97 Nanograms (ng) | Standard Deviation 820295.42 |
| Therapeutic Dose: ITF2357 100 mg | Urine PK: Cumulative Urinary Excretion From Time Zero to Time t (Ae0-t) for ITF2357 and Its Metabolites | ITF2375 | 330005.73 Nanograms (ng) | Standard Deviation 244198.09 |
| Therapeutic Dose: ITF2357 100 mg | Urine PK: Cumulative Urinary Excretion From Time Zero to Time t (Ae0-t) for ITF2357 and Its Metabolites | ITF2440 | 20496643.63 Nanograms (ng) | Standard Deviation 3002369.96 |
| Therapeutic Dose: ITF2357 100 mg | Urine PK: Cumulative Urinary Excretion From Time Zero to Time t (Ae0-t) for ITF2357 and Its Metabolites | ITF2563 | 9746260.02 Nanograms (ng) | Standard Deviation 1204246.03 |
| Therapeutic Dose: ITF2357 100 mg | Urine PK: Cumulative Urinary Excretion From Time Zero to Time t (Ae0-t) for ITF2357 and Its Metabolites | ITF2955 glucuronide | 13456.18 Nanograms (ng) | Standard Deviation 3086.53 |
| Supratherapeutic Dose: ITF2357 300 mg | Urine PK: Cumulative Urinary Excretion From Time Zero to Time t (Ae0-t) for ITF2357 and Its Metabolites | ITF2563 | 27259547.79 Nanograms (ng) | Standard Deviation 4213356.29 |
| Supratherapeutic Dose: ITF2357 300 mg | Urine PK: Cumulative Urinary Excretion From Time Zero to Time t (Ae0-t) for ITF2357 and Its Metabolites | ITF2357 | 4284095.88 Nanograms (ng) | Standard Deviation 1031461.74 |
| Supratherapeutic Dose: ITF2357 300 mg | Urine PK: Cumulative Urinary Excretion From Time Zero to Time t (Ae0-t) for ITF2357 and Its Metabolites | ITF2440 | 55319154.12 Nanograms (ng) | Standard Deviation 9058968.83 |
| Supratherapeutic Dose: ITF2357 300 mg | Urine PK: Cumulative Urinary Excretion From Time Zero to Time t (Ae0-t) for ITF2357 and Its Metabolites | ITF2374 | 4634585.90 Nanograms (ng) | Standard Deviation 2469826.92 |
| Supratherapeutic Dose: ITF2357 300 mg | Urine PK: Cumulative Urinary Excretion From Time Zero to Time t (Ae0-t) for ITF2357 and Its Metabolites | ITF2955 glucuronide | 66582.99 Nanograms (ng) | Standard Deviation 18731.8 |
| Supratherapeutic Dose: ITF2357 300 mg | Urine PK: Cumulative Urinary Excretion From Time Zero to Time t (Ae0-t) for ITF2357 and Its Metabolites | ITF2375 | 1051751.97 Nanograms (ng) | Standard Deviation 702770.77 |
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.
Time frame: Pre-dose (within 2 hours before dosing), 0-8 hours, 8-24 hours, 24-48 hours, and 48-72 hours post-dose
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Therapeutic Dose: ITF2357 100 mg | Urine PK: Maximum Rate of Urinary Excretion (Rmax) for ITF2357 and Its Metabolites | ITF2357 | 304920.74 Nanogram per hour (ng/h) | Standard Deviation 327302.13 |
| Therapeutic Dose: ITF2357 100 mg | Urine PK: Maximum Rate of Urinary Excretion (Rmax) for ITF2357 and Its Metabolites | ITF2374 | 155698.10 Nanogram per hour (ng/h) | Standard Deviation 166313.02 |
| Therapeutic Dose: ITF2357 100 mg | Urine PK: Maximum Rate of Urinary Excretion (Rmax) for ITF2357 and Its Metabolites | ITF2375 | 51562.37 Nanogram per hour (ng/h) | Standard Deviation 46045.34 |
| Therapeutic Dose: ITF2357 100 mg | Urine PK: Maximum Rate of Urinary Excretion (Rmax) for ITF2357 and Its Metabolites | ITF2440 | 1323571.78 Nanogram per hour (ng/h) | Standard Deviation 414580.11 |
| Therapeutic Dose: ITF2357 100 mg | Urine PK: Maximum Rate of Urinary Excretion (Rmax) for ITF2357 and Its Metabolites | ITF2563 | 712846.46 Nanogram per hour (ng/h) | Standard Deviation 298304.19 |
| Therapeutic Dose: ITF2357 100 mg | Urine PK: Maximum Rate of Urinary Excretion (Rmax) for ITF2357 and Its Metabolites | ITF2955 glucuronide | 5170.46 Nanogram per hour (ng/h) | Standard Deviation 4743.78 |
| Supratherapeutic Dose: ITF2357 300 mg | Urine PK: Maximum Rate of Urinary Excretion (Rmax) for ITF2357 and Its Metabolites | ITF2563 | 1986177.40 Nanogram per hour (ng/h) | Standard Deviation 904296.76 |
| Supratherapeutic Dose: ITF2357 300 mg | Urine PK: Maximum Rate of Urinary Excretion (Rmax) for ITF2357 and Its Metabolites | ITF2357 | 1224735.12 Nanogram per hour (ng/h) | Standard Deviation 922878.78 |
| Supratherapeutic Dose: ITF2357 300 mg | Urine PK: Maximum Rate of Urinary Excretion (Rmax) for ITF2357 and Its Metabolites | ITF2440 | 3469056.76 Nanogram per hour (ng/h) | Standard Deviation 1554749.72 |
| Supratherapeutic Dose: ITF2357 300 mg | Urine PK: Maximum Rate of Urinary Excretion (Rmax) for ITF2357 and Its Metabolites | ITF2374 | 536094.03 Nanogram per hour (ng/h) | Standard Deviation 361645.28 |
| Supratherapeutic Dose: ITF2357 300 mg | Urine PK: Maximum Rate of Urinary Excretion (Rmax) for ITF2357 and Its Metabolites | ITF2955 glucuronide | 25858.22 Nanogram per hour (ng/h) | Standard Deviation 23838.45 |
| Supratherapeutic Dose: ITF2357 300 mg | Urine PK: Maximum Rate of Urinary Excretion (Rmax) for ITF2357 and Its Metabolites | ITF2375 | 182276.01 Nanogram per hour (ng/h) | Standard Deviation 172602.2 |
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.
Time frame: Pre-dose (within 2 hours before dosing), 0-8 hours, 8-24 hours, 24-48 hours, and 48-72 hours post-dose
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Therapeutic Dose: ITF2357 100 mg | Urine PK: Renal Clearance (Clr) for ITF2357 and Its Metabolites | ITF2955 glucuronide | 16623.97 L/h | Standard Deviation 22459.53 |
| Therapeutic Dose: ITF2357 100 mg | Urine PK: Renal Clearance (Clr) for ITF2357 and Its Metabolites | ITF2374 | 3856.29 L/h | Standard Deviation 979.36 |
| Therapeutic Dose: ITF2357 100 mg | Urine PK: Renal Clearance (Clr) for ITF2357 and Its Metabolites | ITF2375 | 103.35 L/h | Standard Deviation 27.94 |
| Therapeutic Dose: ITF2357 100 mg | Urine PK: Renal Clearance (Clr) for ITF2357 and Its Metabolites | ITF2440 | 3629.92 L/h | Standard Deviation 717.29 |
| Therapeutic Dose: ITF2357 100 mg | Urine PK: Renal Clearance (Clr) for ITF2357 and Its Metabolites | ITF2563 | 7879.16 L/h | Standard Deviation 1464.33 |
| Therapeutic Dose: ITF2357 100 mg | Urine PK: Renal Clearance (Clr) for ITF2357 and Its Metabolites | ITF2357 | 2127.55 L/h | Standard Deviation 402.63 |
| Supratherapeutic Dose: ITF2357 300 mg | Urine PK: Renal Clearance (Clr) for ITF2357 and Its Metabolites | ITF2563 | 7666.41 L/h | Standard Deviation 1279.54 |
| Supratherapeutic Dose: ITF2357 300 mg | Urine PK: Renal Clearance (Clr) for ITF2357 and Its Metabolites | ITF2357 | 1859.30 L/h | Standard Deviation 360.82 |
| Supratherapeutic Dose: ITF2357 300 mg | Urine PK: Renal Clearance (Clr) for ITF2357 and Its Metabolites | ITF2440 | 2994.15 L/h | Standard Deviation 583.57 |
| Supratherapeutic Dose: ITF2357 300 mg | Urine PK: Renal Clearance (Clr) for ITF2357 and Its Metabolites | ITF2374 | 3403.49 L/h | Standard Deviation 1004.83 |
| Supratherapeutic Dose: ITF2357 300 mg | Urine PK: Renal Clearance (Clr) for ITF2357 and Its Metabolites | ITF2955 glucuronide | 4215.01 L/h | Standard Deviation 1176.29 |
| Supratherapeutic Dose: ITF2357 300 mg | Urine PK: Renal Clearance (Clr) for ITF2357 and Its Metabolites | ITF2375 | 96.02 L/h | Standard Deviation 29.26 |
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.
Time frame: Pre-dose (within 2 hours before dosing), 0-8 hours, 8-24 hours, 24-48 hours, and 48-72 hours post-dose
Population: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Therapeutic Dose: ITF2357 100 mg | Urine PK: Time of Rmax (TRmax) for ITF2357 and Its Metabolites | ITF2374 | 4.40 hours |
| Therapeutic Dose: ITF2357 100 mg | Urine PK: Time of Rmax (TRmax) for ITF2357 and Its Metabolites | ITF2440 | 7.24 hours |
| Therapeutic Dose: ITF2357 100 mg | Urine PK: Time of Rmax (TRmax) for ITF2357 and Its Metabolites | ITF2563 | 7.24 hours |
| Therapeutic Dose: ITF2357 100 mg | Urine PK: Time of Rmax (TRmax) for ITF2357 and Its Metabolites | ITF2357 | 1.84 hours |
| Therapeutic Dose: ITF2357 100 mg | Urine PK: Time of Rmax (TRmax) for ITF2357 and Its Metabolites | ITF2955 glucuronide | 1.84 hours |
| Therapeutic Dose: ITF2357 100 mg | Urine PK: Time of Rmax (TRmax) for ITF2357 and Its Metabolites | ITF2375 | 1.84 hours |
| Supratherapeutic Dose: ITF2357 300 mg | Urine PK: Time of Rmax (TRmax) for ITF2357 and Its Metabolites | ITF2955 glucuronide | 1.49 hours |
| Supratherapeutic Dose: ITF2357 300 mg | Urine PK: Time of Rmax (TRmax) for ITF2357 and Its Metabolites | ITF2357 | 1.49 hours |
| Supratherapeutic Dose: ITF2357 300 mg | Urine PK: Time of Rmax (TRmax) for ITF2357 and Its Metabolites | ITF2374 | 1.49 hours |
| Supratherapeutic Dose: ITF2357 300 mg | Urine PK: Time of Rmax (TRmax) for ITF2357 and Its Metabolites | ITF2375 | 1.49 hours |
| Supratherapeutic Dose: ITF2357 300 mg | Urine PK: Time of Rmax (TRmax) for ITF2357 and Its Metabolites | ITF2563 | 6.65 hours |
| Supratherapeutic Dose: ITF2357 300 mg | Urine PK: Time of Rmax (TRmax) for ITF2357 and Its Metabolites | ITF2440 | 6.65 hours |