Evaluation of Whether Deferiprone Affects QT Interval in Healthy Subjects
Condition: Prolonged QTc Interval
Intervention: Deferiprone; deferiprone matching placebo tablets; moxifloxacin; placebo
Intervention description: Ferriprox 500 mg tablets; deferiprone matching placebo tablets; Active control; moxifloxacin-matching placebo
Intervention MeSH terms: Moxifloxacin; Deferiprone
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 50.0
Sex: All
Minimum age: 18 Years
Maximum age: 45 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Ferriprox®; LI; DFP; Deferiprone; Healthy Volunteers

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.
    

Eligibility criteria:

        Main 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.

          8. Willing to answer inclusion and exclusion criteria questionnaire at check-in.

        Main 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.