Evaluation of Whether Deferiprone Affects QT Interval in Healthy Subjects

NCT01860703 | Completed Phase 4 Results

• 1 other identifier: LA37-1111
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

Randomized, single-dose, double-blind, placebo and active controlled, four-period crossover study to evaluate the effect of deferiprone on QTc prolongation after administration of a single therapeutic (33 mg/kg) and supratherapeutic(50 mg/kg) oral doses of deferiprone in healthy volunteers as compared to placebo treatment.

Conditions

Prolonged QTc Interval

Keywords

Ferriprox®; LI; DFP; Deferiprone; Healthy Volunteers

Outcome Measures

Primary Outcomes (4)

• Maximum Difference in Change From Baseline in ddQTcF Following a Single Dose of 33 mg/kg Deferiprone

  Change from baseline in QTcF interval was measured by looking at the post-dose difference in change from baseline in Fridericia's QT corrected heart rate (dQTcF) between treatment and placebo (ddQTcF) at each time interval. ECG recordings were obtained within a 5-minute time window at Hours -0.75, -0.5, and -0.25 (prior to dosing) and Hours 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, and 24 post-dose.

  24-hour interval

• Maximum Difference in Change From Baseline in ddQTcF Following a Single Dose of 50 mg/kg Deferiprone

  Change from baseline in QTcF interval was measured by looking at the post-dose difference in change from baseline in Fridericia's QT corrected heart rate (dQTcF) between treatment and placebo (ddQTcF) at each time interval. ECG recordings were obtained within a 5-minute time window at Hours -0.75, -0.5, and -0.25 (prior to dosing) and Hours 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, and 24 post-dose.

  24-hour interval

• Maximum Postdose QT/QTc Interval

  The maximum post-dose QT/QTc interval for deferiprone and placebo. ECG recordings were obtained within a 5-minute time window at Hours -0.75, -0.5, and -0.25 (prior to dosing) and Hours 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, and 24 post-dose.

  24-hour interval

• Maximum Change From Baseline (dQT/dQTc)

  Maximum Change From Baseline (dQT/dQTc) for deferiprone and placebo. ECG recordings were obtained within a 5-minute time window at Hours -0.75, -0.5, and -0.25 (prior to dosing) and Hours 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 10, and 24 post-dose.

  24-hour interval

Secondary Outcomes (6)

• Number of Participants With Adverse Events

  From administration of the first dose until 7 days +/- 1 day following the final dose

• Cmax of Deferiprone and Deferiprone 3-O Glucuronide

  24-hour interval

• Tmax of Deferiprone and Deferiprone 3-O-glucuronide

  24-hour interval

• AUC0-infinity for Serum Deferiprone and Deferiprone 3-O-glucuronide

  24-hour interval

• T1/2 for Serum Deferiprone and Deferiprone 3-O-glucuronide

  24-hour interval

Study Arms (4)

Arm A - Maximum Therapeutic Dose

EXPERIMENTAL

Single dose of 33 mg/kg rounded to the nearest 250 mg of deferiprone tablets

Drug: Deferiprone

Treatment Arm B - Supratherapeutic Dose

EXPERIMENTAL

Single dose of 50 mg/kg rounded to the nearest 250 mg of deferiprone tablets

Drug: Deferiprone

Arm C - Placebo Control

EXPERIMENTAL

Single dose of matching deferiprone and moxifloxacin placebo tablets.

Drug: deferiprone matching placebo tablets; Drug: placebo

Arm D - Positive Control

EXPERIMENTAL

Single dose of one 400 mg moxifloxacin tablet.

Drug: moxifloxacin

Interventions

Deferiprone DRUG

Ferriprox 500 mg tablets

Also known as: Ferriprox, L1

Arm A - Maximum Therapeutic Dose; Treatment Arm B - Supratherapeutic Dose

deferiprone matching placebo tablets DRUG

deferiprone matching placebo tablets

Also known as: Placebo

Arm C - Placebo Control

moxifloxacin DRUG

Active control

Also known as: Avelox

Arm D - Positive Control

placebo DRUG

moxifloxacin-matching placebo

Arm C - Placebo Control

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy adult males or females, 18 - 45 years of age (inclusive).
• Body weight ≥ 50 kg.
• Body mass index (BMI) ≥ 19 and ≤ 32 kg/m2.
• Medically healthy with clinically insignificant screening results (e.g., laboratory profiles, medical history, vital signs, physical examination).
• Absolute neutrophil count (ANC) of \>1.5x109/L.
• lead ECGs which have no clinically significant findings as judged by the Principal Investigator (PI) or the PI's designee at screening and check-in of each study period,including:
• Normal sinus rhythm (heart rate between 45 and 100 bpm);
• QTcF interval ≤ 450 msec;
• QRS interval ≤ 110 msec; and
• PR interval ≤ 220 msec.
• Subject must be capable of providing written informed consent, and must voluntarily consent to participate in the study.

You may not qualify if:

• History or presence of significant respiratory, cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic,neurologic, or psychiatric disease.
• Disorders or surgery of the gastrointestinal tract which may interfere with drug absorption or may otherwise influence the PK of the investigational medicinal products (e.g. cholecystectomy, resections of the small or large intestine, febrile conditions, chronic diarrhea, chronic vomiting, endocrine disease, severe infections,acute inflammations, etc.).
• Presence of liver impairment: aspartate aminotransferase (AST), alanine aminotransferase (ALT) above the normal reference range.
• Presence of significant kidney impairment: serum creatinine higher than the normal reference range.
• Allergy to band aids, adhesive dressing or medical tape.
• Clinically significant history or presence of ECG abnormalities such as second- or third-degree atrioventricular block; evidence, or family history, of prolonged QT syndrome.
• Sustained sitting systolic blood pressure of \<90 mmHg or \>140 mmHg, or diastolic blood pressure of \>95 mmHg at screening or check-in of Period 1.
• History or presence of hypersensitivity or idiosyncratic reaction to deferiprone, moxifloxacin, iron chelators, or quinolone antibiotics.
• History or presence of:
• agranulocytosis;
• asthma;
• chronic bronchitis;
• diabetes;
• migraine;
• hypertension;

Sponsors & Collaborators

• ApoPharma: lead

Study Sites (1)

Celerion

Tempe, Arizona, 85283, United States

Location

MeSH Terms

Interventions

Deferiprone; Long Interspersed Nucleotide Elements; Moxifloxacin

Intervention Hierarchy (Ancestors)

Pyridones; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Retroelements; Interspersed Repetitive Sequences; Repetitive Sequences, Nucleic Acid; Base Sequence; Molecular Structure; Biochemical Phenomena; Chemical Phenomena; Genetic Structures; Genetic Phenomena; Genome Components; Genome; Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Fernando Tricta, MD
• Organization: ApoPharma Inc.

ftricta@apopharma.com

416-401-7332

Study Officials

• Fernando Tricta, MD

  ApoPharma

  STUDY CHAIR

• Caroline Fradette, PhD

  ApoPharma

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 6, 2013
• First Posted: May 23, 2013
• Study Start: November 1, 2012
• Primary Completion: December 1, 2012
• Study Completion: July 1, 2013
• Last Updated: November 12, 2014
• Results First Posted: November 12, 2014

Record last verified: 2014-11

Locations

US (1)