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

December 4, 2014 updated by: ApoPharma

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

64

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Quebec
      • Mont-Royal, Quebec, Canada, H3P3P1
        • Algorithme Pharma Inc.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 50 years (ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Cohort 1

Single dose of 500mg deferiprone or placebo administered via intravenous infusion.

First 2 subjects to enroll: 1 will be randomized to receive deferiprone and the other to receive placebo.

Next 14 subjects enrolled: 13 will be randomized to receive deferiprone and 1 to receive placebo.

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

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

Other Names:
  • Ferriprox
  • L1
  • DFP
Placebo: normal saline solution.
Other Names:
  • Saline solution.
EXPERIMENTAL: Cohort 2

Single dose of 1000mg deferiprone or placebo administered via intravenous infusion and oral solution.

Randomization will be done for all 16 subjects at the same time: 14 will be randomized to receive deferiprone and 2 to receive placebo.

Subjects enrolled to cohort 2 will receive an oral dose of deferiprone.

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

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

Other Names:
  • Ferriprox
  • L1
  • DFP
Placebo: normal saline solution.
Other Names:
  • Saline solution.
EXPERIMENTAL: Cohort 3

Single dose of 1500mg deferiprone or placebo administered via intravenous infusion.

Randomization will be done for all 16 subjects at the same time, 14 will be randomized to receive deferiprone and 2 to receive placebo.

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

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

Other Names:
  • Ferriprox
  • L1
  • DFP
Placebo: normal saline solution.
Other Names:
  • Saline solution.
EXPERIMENTAL: Cohort 4

Single dose of 2000mg deferiprone or placebo administered via intravenous infusion.

First 2 subjects to enroll: 1 will be randomized to receive deferiprone and the other to receive placebo.

Next 14 subjects enrolled: 13 will be randomized to receive deferiprone and 1 to receive placebo.

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

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

Other Names:
  • Ferriprox
  • L1
  • DFP
Placebo: normal saline solution.
Other Names:
  • Saline solution.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
14-hour interval
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).

14-hour interval
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.
14-hour interval
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.
14-hour interval
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.
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
14-hour interval
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.
14-hour interval
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.
From dosing until 24 hours post-dose

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2013

Primary Completion (ACTUAL)

March 1, 2014

Study Completion (ACTUAL)

March 1, 2014

Study Registration Dates

First Submitted

November 15, 2013

First Submitted That Met QC Criteria

November 15, 2013

First Posted (ESTIMATE)

November 21, 2013

Study Record Updates

Last Update Posted (ESTIMATE)

December 23, 2014

Last Update Submitted That Met QC Criteria

December 4, 2014

Last Verified

December 1, 2014

More Information

Terms related to this study

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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