Placebo-Corrected Effects of Therapeutic Dose (100 mg) and Supratherapeutic Dose (300 mg) of ITF2357 (Givinostat) and Moxifloxacin on QT/QTC Interval

NCT04821063 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: ITF/2357/542020-003105-63
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief Summary

The study will evaluate the effect of a therapeutic dose and a supratherapeutic dose of ITF2357 on the QT/QTc interval.

Conditions

Duchenne and Becker Muscular Dystrophy; Polycytemia Vera

Outcome Measures

Primary Outcomes (1)

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

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

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

Secondary Outcomes (39)

• 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

• 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

• 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

• 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

• 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

Study Arms (4)

Therapeutic dose: ITF2357 100 mg

EXPERIMENTAL

Participants will receive a single dose of ITF2357 100 mg administered as 10 milliliters (mL) of ITF2357 10 milligrams per milliliter (mg/mL) oral suspension and 20 mL of placebo matched to ITF2357 oral suspension under fasting conditions on Day 1 of respective period as per the assigned treatment sequence.

Drug: ITF2357 10 mg/mL; Drug: Placebo

Supratherapeutic dose: ITF2357 300 mg

EXPERIMENTAL

Participants will receive a single dose of ITF2357 300 mg administered as 30 mL of ITF2357 10 mg/mL oral suspension under fasting conditions on Day 1 of respective period as per the assigned treatment sequence.

Drug: ITF2357 10 mg/mL

Placebo

PLACEBO COMPARATOR

Participants will receive a single dose of placebo matched to ITF2357 administered as 30 mL oral suspension under fasting conditions on Day 1 of respective period as per the assigned treatment sequence.

Drug: Placebo

Moxifloxacin

ACTIVE COMPARATOR

Participants will receive a single dose of moxifloxacin 400 mg tablet under fasting conditions on Day 1 of respective period as per the assigned treatment sequence.

Drug: Moxifloxacin Hydrochloride

Interventions

ITF2357 10 mg/mL DRUG

Dose: 100 mg (administered as 10 mL); Dosage form: suspension; Route of administration: oral

Also known as: Givinostat

Therapeutic dose: ITF2357 100 mg

Placebo DRUG

Dose: 20 mL; Dosage form: suspension; Route of administration: oral

Therapeutic dose: ITF2357 100 mg

Moxifloxacin Hydrochloride DRUG

Dose: 400 mg; Dosage form: tablet; Route of administration: oral

Moxifloxacin

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male or female, non-smoker (no use of tobacco or nicotine products within 3 months prior to screening), greater than or equal to (\>=) 18 and less than or equal to (\<=) 55 years of age, with body mass index (BMI) greater than (\>) 18.5 and less than (\<) 30.0 kilograms per meter square (kg/m\^2) and body weight \>=55 kilograms (kg) and \<=100 kg for females and body weight \>=60 kg and \<=100 kg for males.
• Healthy as defined by:
• The absence of clinically significant history of neurological, endocrinal, cardiovascular, pulmonary, hematological, immunologic, psychiatric, gastrointestinal, renal, hepatic, and metabolic disease.
• Non-childbearing potential female defined as:
• 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
• Surgically sterile female (hysterectomy or tubal ligation at least 6 months prior to drug administration).
• Females of childbearing potential who are sexually active with a male partner must be willing to use one of the following acceptable contraceptive methods throughout the study and for at least 90 days after the last study drug administration:
• 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;
• Simultaneous use of diaphragm or cervical cap with intravaginally applied spermicide and male condom for the male partner, started at least 21 days prior to study drug administration;
• Male participants who are not vasectomized for at least 6 months, and who are sexually active with a female partner of childbearing potential (childbearing potential females are defined as women that are neither post-menopausal nor surgically sterile) must be willing to use one of the following acceptable contraceptive methods from the first study drug administration until at least 90 days after the last study drug administration:
• 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;
• Simultaneous use of a male condom and, for the female partner, a diaphragm or cervical cap with intravaginally applied spermicide.
• Male participants (including men who have had a vasectomy) with a pregnant partner must agree to use a condom from the first study drug administration until at least 90 days after the last study drug administration.
• Male participants must be willing not to donate sperm until 90 days following the last study drug administration.
• Female participants must be willing not to donate ovules until 90 days following the last study drug administration.

You may not qualify if:

• Any clinically significant abnormality at physical examination, clinically significant abnormal laboratory test results or positive test for human immunodeficiency virus (HIV), hepatitis B, or hepatitis C found during medical screening.
• Clinically significant vital sign abnormalities (systolic blood pressure lower than 90 or over 140 millimeter of mercury \[mmHg\], diastolic blood pressure lower than 60 or over 90 mmHg, or heart rate less than 40 or over 100 beats per minute \[bpm\]) at screening. For eligibility purposes, not the mean value, but the two single measurements will be considered.
• Participants with history of sustained and non-sustained cardiac arrhythmias (ECG demonstrated), participants with a family history of sudden cardiac death and participants with a history of additional risk factors for TdP, heart failure, hypokalemia, LQTS).
• Any of the following abnormal laboratory test values at screening or at baseline (Day -1) of Period 1:
• Platelet count \<125\*10\^9 per liter (/L)
• Absolute neutrophil count \<1.2\*10\^9/L
• Participants who have cardiovascular condition such as, but not limited to unstable ischemic heart disease, New York Heart Association (NYHA) Class III/IV left ventricular failure, acute ischemic heart disease in the last year prior to study screening, which may impact the safety of the participant or the evaluation of the result of the study according to the Investigator's judgment; cardiovascular conditions should be discarded based on the results obtained on the ECG, medical examination and routine lab test.
• Positive urine drug screen, alcohol breath test or urine cotinine test at screening or at baseline (Day -1).
• History of anaphylaxis reaction or clinically significant drug hypersensitivity reaction (e.g., angioedema, Stevens-Johnson syndrome, Acute Generalized Exanthematous Pustulosis, Drug-induced hypersensitivity syndrome, Drug-induced neutropenia).
• History of allergic reactions to ITF2357, histone deacetylases (HDAC) inhibitors, or other related drugs, moxifloxacin, other quinolones, or to any excipient in the formulation.
• Positive pregnancy test at screening or at baseline (Day -1).
• Participants with a sorbitol intolerance or sorbitol malabsorption or have fructose intolerance.
• Current or recent (within 3 months of study drug administration) clinically significant gastrointestinal disease that can interfere with drug absorption.
• Gastrointestinal surgery that interferes with physiological absorption and motility (i.e., gastric bypass, duodenectomy) or gastric bands.
• History of significant alcohol abuse within 1 year prior to screening or regular use of alcohol within 6 months prior to the screening visit (more than 14 units of alcohol per week \[1 unit = 150 milliliter \[mL\] of wine, 360 mL of beer, or 45 mL of 40 percent \[%\] alcohol\]).

Sponsors & Collaborators

• Italfarmaco: lead

Study Sites (1)

Québec

Québec, G1P 0A2, Canada

Location

MeSH Terms

Conditions

Muscular Dystrophy, Duchenne

Interventions

givinostat hydrochloride; givinostat; Moxifloxacin

Condition Hierarchy (Ancestors)

Muscular Dystrophies; Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Maurizio Caserini, MD
• Organization: Italfarmaco SpA

m.caserini@italfarmacogroup.com

+39 02 6443 2575

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 26, 2021
• First Posted: March 29, 2021
• Study Start: April 13, 2021
• Primary Completion: June 18, 2021
• Study Completion: June 18, 2021
• Last Updated: January 11, 2024
• Results First Posted: January 11, 2024

Record last verified: 2023-04

Locations

CA (1)