Clinical trial NCT01860703: Evaluation of Whether Deferiprone Affects QT Interval in Healthy Subjects
Official title: A Double-Blind, Randomized, Crossover, Thorough QT/QTc Trial to Evaluate the Potential of Deferiprone to Prolong the QT Interval in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Prolonged QTc Interval
Keywords: Ferriprox®
LI
DFP
Deferiprone
Healthy Volunteers
Lead sponsor: ApoPharma
Sponsor class: INDUSTRY
First posted: 2013-05-23
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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®).

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.

Primary outcomes:
measure: Maximum Difference in Change From Baseline in ddQTcF Following a Single Dose of 33 mg/kg Deferiprone
timeFrame: 24-hour interval
measure: Maximum Difference in Change From Baseline in ddQTcF Following a Single Dose of 50 mg/kg Deferiprone
timeFrame: 24-hour interval
measure: Maximum Postdose QT/QTc Interval
timeFrame: 24-hour interval
measure: Maximum Change From Baseline (dQT/dQTc)
timeFrame: 24-hour interval
Secondary outcomes:
measure: Number of Participants With Adverse Events
timeFrame: From administration of the first dose until 7 days +/- 1 day following the final dose
measure: Cmax of Deferiprone and Deferiprone 3-O Glucuronide
timeFrame: 24-hour interval
measure: Tmax of Deferiprone and Deferiprone 3-O-glucuronide
timeFrame: 24-hour interval
measure: AUC0-infinity for Serum Deferiprone and Deferiprone 3-O-glucuronide
timeFrame: 24-hour interval
measure: T1/2 for Serum Deferiprone and Deferiprone 3-O-glucuronide
timeFrame: 24-hour interval
measure: Maximum Difference in Change From Baseline in ddQTcF Following a Single Dose of Moxifloxacin
timeFrame: 24-hour interval
Other outcomes:
Locations:
city: Tempe
country: United States
facility: Celerion
state: Arizona
Study officials:
affiliation: ApoPharma
name: Fernando Tricta, MD
role: STUDY_CHAIR
affiliation: ApoPharma
name: Caroline Fradette, PhD
role: STUDY_DIRECTOR
References: