Evaluation of Whether Deferiprone Affects QT Interval in Healthy Subjects

NCT ID: NCT01860703

Last Updated: 2014-11-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-11-30
• Study Completion Date: 2013-07-31

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.

Detailed Description

Post-marketing study to evaluate the effect of deferiprone and deferiprone 3-O-glucuronide on QTc prolongation in healthy volunteers after administration of a single therapeutic (33 mg/kg) and supratherapeutic (50 mg/kg) oral dose of deferiprone and moxifloxacin (Avelox®).

Conditions

Prolonged QTc Interval

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Arm A - Maximum Therapeutic Dose

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

Group Type: EXPERIMENTAL

Deferiprone

Intervention Type: DRUG

Ferriprox 500 mg tablets

Treatment Arm B - Supratherapeutic Dose

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

Group Type: EXPERIMENTAL

Deferiprone

Intervention Type: DRUG

Ferriprox 500 mg tablets

Arm C - Placebo Control

Single dose of matching deferiprone and moxifloxacin placebo tablets.

Group Type: EXPERIMENTAL

deferiprone matching placebo tablets

Intervention Type: DRUG

deferiprone matching placebo tablets

placebo

Intervention Type: DRUG

moxifloxacin-matching placebo

Arm D - Positive Control

Single dose of one 400 mg moxifloxacin tablet.

Group Type: EXPERIMENTAL

moxifloxacin

Intervention Type: DRUG

Active control

Interventions

Deferiprone

Ferriprox 500 mg tablets

Intervention Type: DRUG

deferiprone matching placebo tablets

deferiprone matching placebo tablets

Intervention Type: DRUG

moxifloxacin

Active control

Intervention Type: DRUG

placebo

moxifloxacin-matching placebo

Intervention Type: DRUG

Other Intervention Names

Ferriprox; L1; Placebo; Avelox

Eligibility Criteria

Inclusion Criteria

1. Healthy adult males or females, 18 - 45 years of age (inclusive).

2. Body weight ≥ 50 kg.

3. Body mass index (BMI) ≥ 19 and ≤ 32 kg/m2.

4. Medically healthy with clinically insignificant screening results (e.g., laboratory profiles, medical history, vital signs, physical examination).

5. Absolute neutrophil count (ANC) of >1.5x109/L.

6. 12-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:

1. Normal sinus rhythm (heart rate between 45 and 100 bpm);

2. QTcF interval ≤ 450 msec;

3. QRS interval ≤ 110 msec; and

4. PR interval ≤ 220 msec.

7. Subject must be capable of providing written informed consent, and must voluntarily consent to participate in the study.

Exclusion Criteria

1. History or presence of significant respiratory, cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic,neurologic, or psychiatric disease.

2. 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.).

3. Presence of liver impairment: aspartate aminotransferase (AST), alanine aminotransferase (ALT) above the normal reference range.

4. Presence of significant kidney impairment: serum creatinine higher than the normal reference range.

5. Allergy to band aids, adhesive dressing or medical tape.

6. Clinically significant history or presence of ECG abnormalities such as second- or third-degree atrioventricular block; evidence, or family history, of prolonged QT syndrome.

7. 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.

8. History or presence of hypersensitivity or idiosyncratic reaction to deferiprone, moxifloxacin, iron chelators, or quinolone antibiotics.

9. History or presence of:

• agranulocytosis;
• asthma;
• chronic bronchitis;
• diabetes;
• migraine;
• hypertension;
• hypotension;
• hypokalemia;
• seizures or epilepsy;
• anaemia.

10. History or presence of alcoholism or drug abuse within the past 2 years.

11. Used tobacco/nicotine-containing product for at least 3 months prior to the first dose of study.

12. Used Depo-Provera® or levonorgestrel implant within 90 days prior to the first dose and throughout the study.

13. Participation in another clinical trial within 28 days prior to the first dose of the study.

14. Had a clinically significant illness during the 4 weeks prior to check-in on Day -1 of Period 1.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

ApoPharma

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Fernando Tricta, MD

Role: STUDY_CHAIR

ApoPharma

Caroline Fradette, PhD

Role: STUDY_DIRECTOR

ApoPharma

Locations

Celerion

Tempe, Arizona, United States

Countries

United States

Other Identifiers

LA37-1111

Identifier Type: -

Identifier Source: org_study_id