Clinical trial NCT01989455: A Blinded, Placebo-Controlled Study of the Safety and Pharmacokinetics of Single Doses of Intravenous Deferiprone in Healthy Volunteers
Official title: A Single Center, Phase I, Double-blind, Placebo-controlled Evaluation of the Safety, Tolerability, and Pharmacokinetics of Single Ascending Doses of Deferiprone Administered by Intravenous Infusion to Healthy Male and Female Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: Healthy
Deferiprone
DFP
L1
Lead sponsor: ApoPharma
Sponsor class: INDUSTRY
First posted: 2013-11-21
Enrollment: 64
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL

Brief summary: Single center, randomized, double-blind, placebo-controlled, adaptive sequential ascending-dose study for the evaluation of the safety, tolerability, and pharmacokinetics of single doses of deferiprone administered by intravenous infusion to healthy males and females. A bioavailability comparison will be included.


Eligibility criteria: Main Inclusion Criteria:

1. Healthy adult males or females, at least 18 years old but not older than 50 years.
2. Body weight at least 60kg.
3. Body Mass Index (BMI) ≥ 18.50 and ≤ 30.00 kg/m2
4. Medically healthy with clinically insignificant screening results (e.g., laboratory profiles, medical history, ECG, vital signs, physical examination.
5. Non or ex-smoker (someone who has completely stopped smoking 6 months before study start)
6. For females, negative result on a serum pregnancy test.

Main Exclusion Criteria:

1. Absolute neutrophil count (ANC) \<1.5x10\^9/L.
2. History or presence of hypersensitivity to deferiprone or any related products.
3. History or presence of gastrointestinal, liver or kidney disease, or any other conditions known to interfere with the absorption, distribution, metabolism or excretion of drugs.
4. Presence of significant cardiovascular, pulmonary, hematologic, neurologic, psychiatric, endocrine, immunologic or dermatologic disease.
5. Any history of tuberculosis (TB) or prophylaxis for TB.
6. Suicidal tendency, history of seizures, head trauma with coma or craniotomy/trepanation, state of confusion or relevant psychiatric disease.
7. Inadequate venous access in either arm.
8. Presence of out-of-range cardiac interval or clinically significant ECG abnormalities (PR \<110 msec or \> 220 msec, QRS \<60 msec or \>119 msec, QTcB \> 450 msec for males and \>460 msec for females).
9. Use of acetaminophen, acetylsalicylic acid (ASA), or non-steroidal anti-inflammatory drugs (NSAIDs) in the previous 7 days before study start.
10. Use of any enzyme-modifying drugs, including strong inhibitors of P450 (CYP) enzymes such as cimetidine, fluoxetine, quinidine, erythromycin, ciprofloxacin, fluconazole, ketoconazole, diltiazem, and HIV antivirals OR strong inducers of CYP enzymes such as: barbiturates, carbamazepine, glucocorticoids, phenytoin, rifampin, and St. John's wart within 28 days prior to study start.
11. Maintenance therapy with any drug, or significant history of drug dependency or alcohol abuse.
12. Had a clinically significant illness during the 28 days prior to study start.
13. Receipt of an investigational product in another clinical trial within 28 days prior prior to study start.
14. Enrolment in a previous cohort of this study.

Primary outcomes:
measure: Maximum Measured Serum Concentration (Cmax) for Serum Deferiprone and Deferiprone 3-O-glucuronide
timeFrame: 14-hour interval
measure: Time to Maximum Observed Serum Concentration (Tmax) for Serum Deferiprone and Deferiprone 3-O-glucuronide
timeFrame: 14-hour interval
measure: Area Under the Curve From Zero to Infinity (AUC0-∞) for Serum Deferiprone and Deferiprone 3-O-glucuronide
timeFrame: 14-hour interval
measure: The Terminal Elimination Half-life (T1/2el) for Serum Deferiprone and Deferiprone 3-O-glucuronide
timeFrame: 14-hour interval
measure: Safety and Tolerability of Single Ascending Doses of Deferiprone When Administered by Intravenous Infusion in Healthy Volunteers.
timeFrame: From start of intravenous dosing until Day 5 post-dose for all subjects; and from time of oral dose until 24 hours post-dose for subjects who additionally received oral deferiprone
Secondary outcomes:
measure: Comparison of Cmax for Serum Deferiprone and Deferiprone 3-O-glucuronide Between Deferiprone for Infusion and Oral Deferiprone
timeFrame: 14-hour interval
measure: Absolute Bioavailability of Deferiprone
timeFrame: 14-hour interval
measure: Safety and Tolerability of a Single 1000 mg Oral Dose of Deferiprone
timeFrame: From dosing until 24 hours post-dose
Other outcomes:
Locations:
city: Mont-Royal
country: Canada
facility: Algorithme Pharma Inc.
state: Quebec
Study officials:
affiliation: ApoPharma Inc.
name: Fernando Tricta, MD
role: STUDY_CHAIR
References: