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Completed

NCT Number: NCT01989455

A Blinded, Placebo-Controlled Study of the Safety and Pharmacokinetics of Single Doses of Intravenous Deferiprone in Healthy Volunteers

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.

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Key information

Conditions

Healthy Volunteers

Age range

18 year–50 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Algorithme Pharma Inc.

Mount Royal, Quebec, H3P3P1, Canada

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Main Inclusion Criteria:

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

Main Exclusion Criteria:

  • Absolute neutrophil count (ANC) <1.5x10^9/L.
  • History or presence of hypersensitivity to deferiprone or any related products.
  • 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.
  • Presence of significant cardiovascular, pulmonary, hematologic, neurologic, psychiatric, endocrine, immunologic or dermatologic disease.
  • Any history of tuberculosis (TB) or prophylaxis for TB.
  • Suicidal tendency, history of seizures, head trauma with coma or craniotomy/trepanation, state of confusion or relevant psychiatric disease.
  • Inadequate venous access in either arm.
  • 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).
  • Use of acetaminophen, acetylsalicylic acid (ASA), or non-steroidal anti-inflammatory drugs (NSAIDs) in the previous 7 days before study start.
  • 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.
  • Maintenance therapy with any drug, or significant history of drug dependency or alcohol abuse.
  • Had a clinically significant illness during the 28 days prior to study start.
  • Receipt of an investigational product in another clinical trial within 28 days prior prior to study start.
  • Enrolment in a previous cohort of this study.

Treatment and study plan

Deferiprone

Drug

Deferiprone for infusion, 10mg/mL for intravenous infusion.

Oral dose of deferiprone: 80mg/mL oral solution. (Cohort 2)

Other names: Ferriprox, DFP, L1

Placebo

Drug

Placebo: normal saline solution.

Other names: Saline solution.

Primary outcomes

  1. Maximum Measured Serum Concentration (Cmax) for Serum Deferiprone and Deferiprone 3-O-glucuronide

    Time frame: 14-hour interval

    Cmax was assessed over a 14-hour interval for analyses of deferiprone and its 3-O-glucuronide metabolite in healthy volunteers who received single intravenous doses of 500 mg, 1000 mg, 1500 mg, and 2000 mg of intravenous deferiprone. Blood samples were obtained pre-dose and at 0.17, 0.33, 0.50, 0.75, 1, 1.33, 1.67, 2, 2.5, 3, 4, 6, 9, 12, and 14 hours post-dose.

  2. Time to Maximum Observed Serum Concentration (Tmax) for Serum Deferiprone and Deferiprone 3-O-glucuronide

    Time frame: 14-hour interval

    Tmax was assessed over a 14-hour interval for analyses of deferiprone and its 3-O-glucuronide metabolite in healthy volunteers who received single intravenous doses of 500 mg, 1000 mg, 1500 mg, and 2000 mg of intravenous deferiprone. Blood samples were obtained pre-dose and at 0.17, 0.33, 0.50, 0.75, 1, 1.33, 1.67, 2, 2.5, 3, 4, 6, 9, 12, and 14 hours post-dose.

    The results of the Tmax parameter are reported as the median and range (other parameters are reported as mean and standard deviation).

  3. Area Under the Curve From Zero to Infinity (AUC0-∞) for Serum Deferiprone and Deferiprone 3-O-glucuronide

    Time frame: 14-hour interval

    AUC0-∞ was assessed over a 14-hour interval for analyses of deferiprone and its 3-O-glucuronide metabolite in healthy volunteers who received single intravenous doses of 500 mg, 1000 mg, 1500 mg, and 2000 mg of intravenous deferiprone. Blood samples were obtained pre-dose and at 0.17, 0.33, 0.50, 0.75, 1, 1.33, 1.67, 2, 2.5, 3, 4, 6, 9, 12, and 14 hours post-dose.

  4. The Terminal Elimination Half-life (T1/2el) for Serum Deferiprone and Deferiprone 3-O-glucuronide

    Time frame: 14-hour interval

    T1/2el was assessed over a 14-hour interval for analyses of deferiprone and its 3-O-glucuronide metabolite in healthy volunteers who received single intravenous doses of 500 mg, 1000 mg, 1500 mg, and 2000 mg of intravenous deferiprone. Blood samples were obtained pre-dose and at 0.17, 0.33, 0.50, 0.75, 1, 1.33, 1.67, 2, 2.5, 3, 4, 6, 9, 12, and 14 hours post-dose.

  5. Safety and Tolerability of Single Ascending Doses of Deferiprone When Administered by Intravenous Infusion in Healthy Volunteers.

    Time frame: 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

    The number of participants who experienced adverse events (including any changes of clinical significance in physical examinations, vital signs, 12-lead ECG, and clinical laboratory tests) following a single dose of intravenous deferiprone.

Secondary outcomes

  1. Comparison of Cmax for Serum Deferiprone and Deferiprone 3-O-glucuronide Between Deferiprone for Infusion and Oral Deferiprone

    Time frame: 14-hour interval

    Cmax was assessed over a 14-hour interval for deferiprone in healthy volunteers who received a single intravenous dose of 1000 mg and then one week later received a single oral dose of 1000 mg deferiprone oral solution. In both cases, blood samples were obtained pre-dose and at 0.17, 0.33, 0.50, 0.75, 1, 1.33, 1.67, 2, 2.5, 3, 4, 6, 9, 12, and 14 hours post-dose.

  2. Absolute Bioavailability of Deferiprone

    Time frame: 14-hour interval

    The pharmacokinetic profile was assessed over a 14-hour interval for deferiprone in healthy volunteers who received a single intravenous dose of 1000 mg and then one week later received a single oral dose of 1000 mg deferiprone oral solution. In both cases, blood samples were obtained pre-dose and at 0.17, 0.33, 0.50, 0.75, 1, 1.33, 1.67, 2, 2.5, 3, 4, 6, 9, 12, and 14 hours post-dose.

  3. Safety and Tolerability of a Single 1000 mg Oral Dose of Deferiprone

    Time frame: From dosing until 24 hours post-dose

    The number of participants who experienced adverse events (including any changes of clinical significance in physical examinations, vital signs, 12-lead ECG, and clinical laboratory tests) following a single dose of oral deferiprone. Note: All subjects in the 1000 mg cohort received active product, including the 2 who had received placebo for the intravenous infusion.

Sponsors and collaborators

Lead sponsor

ApoPharma

Industry

Registry information

Official study 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

Important dates

Study start
2013
Primary completion
2014
Study completion
2014
First posted
Nov 21, 2013
Registry last updated
Dec 23, 2014

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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