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Pilot Study of the Pharmacokinetic Profile of Deferiprone Sustained-Release Formulation in Healthy Volunteers

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ClinicalTrials.gov Identifier: NCT02189941
Recruitment Status : Completed
First Posted : July 15, 2014
Results First Posted : May 20, 2016
Last Update Posted : May 20, 2016
Sponsor:
Information provided by (Responsible Party):
ApoPharma

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Healthy
Interventions Drug: Deferiprone sustained-release
Drug: Deferiprone immediate-release
Enrollment 11
Recruitment Details Subjects were dosed at the clinic between May and June of 2014
Pre-assignment Details Subjects were randomized to receive 3 single-dose treatments in different sequences, with a washout of 7 days between doses. Twenty (20) subjects were screened and 12 were randomized. One subject experienced a medical event prior to the first dosing and was excluded from the study, so only 11 subjects received at least 1 dose of study product.
Arm/Group Title DFP-SR Fed, Then DFP-SR Fasting, Then Ferriprox Fasting DFP-SR Fasting, Then Ferriprox Fasting, Then DFP-SR Fed Ferriprox Fasting, Then DFP-SR Fed, Then DFP-SR Fasting
Hide Arm/Group Description

Subjects received 3 treatments in the following order, with a 7-day washout period between treatments:

  1. One dose of deferiprone sustained-release (DFP-SR) tablets under fed conditions
  2. One dose of deferiprone sustained-release tablets under fasting conditions
  3. One dose of Ferriprox immediate-release (IR) tablets under fasting conditions

Subjects received 3 treatments in the following order, with a 7-day washout period between treatments:

  1. One dose of deferiprone sustained-release tablets under fasting conditions
  2. One dose of Ferriprox immediate-release tablets under fasting conditions
  3. One dose of deferiprone sustained-release tablets under fed conditions

Subjects received 3 treatments in the following order, with a 7-day washout period between treatments:

  1. One dose of Ferriprox immediate-release tablets under fasting conditions
  2. One dose of deferiprone sustained-release tablets under fed conditions
  3. One dose of deferiprone sustained-release tablets under fasting conditions
Period Title: Overall Study
Started 4 4 3
Completed 4 4 2
Not Completed 0 0 1
Reason Not Completed
Non-compliance             0             0             1
Arm/Group Title Healthy Volunteers
Hide Arm/Group Description Subjects received one dose of deferiprone sustained-release tablets under fed conditions, one dose of deferiprone sustained-release tablets under fasting conditions, and one dose of deferiprone immediate-release tablets under fasting conditions, 7 days apart
Overall Number of Baseline Participants 11
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 11 participants
<=18 years
0
   0.0%
Between 18 and 65 years
11
 100.0%
>=65 years
0
   0.0%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 11 participants
Female
4
  36.4%
Male
7
  63.6%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 11 participants
Hispanic or Latino
2
  18.2%
Not Hispanic or Latino
9
  81.8%
Unknown or Not Reported
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 11 participants
American Indian or Alaska Native
0
   0.0%
Asian
1
   9.1%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
5
  45.5%
White
3
  27.3%
More than one race
2
  18.2%
Unknown or Not Reported
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Canada Number Analyzed 11 participants
11
1.Primary Outcome
Title AUCt for Serum Deferiprone and Deferiprone 3-O-glucuronide
Hide Description AUCt (Area Under the Curve to the last measured time) was assessed over a 24-hour interval for analyses of deferiprone and its 3-O-glucuronide metabolite. Blood samples were obtained prior to dosing and at 0.25, 0.5, 0.75, 1, 1.3333, 1.6667, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16 and 24 hours post-dose.
Time Frame 24-hour interval
Hide Outcome Measure Data
Hide Analysis Population Description
All subjects who contributed evaluable pharmacokinetics data
Arm/Group Title Deferiprone Sustained-release (Fed) Deferiprone Sustained-release (Fasting) Deferiprone Immediate-release (Fasting)
Hide Arm/Group Description:

A single 2000 mg dose of deferiprone sustained-release following a high fat high calorie breakfast.

Deferiprone sustained-release: Deferiprone sustained-release tablets

A single 2000 mg dose of deferiprone sustained-release under fasting conditions.

Deferiprone sustained-release: Deferiprone sustained-release tablets

A single 2000 mg dose of Deferiprone immediate-release under fasting conditions.

Deferiprone immediate-release: Deferiprone immediate-release tablets

Overall Number of Participants Analyzed 10 10 11
Mean (Standard Deviation)
Unit of Measure: mcg*h/mL
Deferiprone 63.5  (10.0) 52.3  (14.8) 71.1  (10.9)
Deferiprone 3-O-glucuronide 171.9  (33.4) 147.2  (41.5) 192.7  (32.8)
2.Primary Outcome
Title AUCinf for Serum Deferiprone and Deferiprone 3-O-glucuronide
Hide Description AUCinf (Area Under the Curve to infinity) was assessed over a 24-hour interval for analyses of deferiprone and its 3-O-glucuronide metabolite. Blood samples were obtained prior to dosing and at 0.25, 0.5, 0.75, 1, 1.3333, 1.6667, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16 and 24 hours post-dose.
Time Frame 24-hour interval
Hide Outcome Measure Data
Hide Analysis Population Description
All subjects who contributed evaluable pharmacokinetics data
Arm/Group Title Deferiprone Sustained-release (Fed) Deferiprone Sustained-release (Fasting) Deferiprone Immediate-release (Fasting)
Hide Arm/Group Description:

A single 2000 mg dose of deferiprone sustained-release following a high fat high calorie breakfast.

Deferiprone sustained-release: Deferiprone sustained-release tablets

A single 2000 mg dose of deferiprone sustained-release under fasting conditions.

Deferiprone sustained-release: Deferiprone sustained-release tablets

A single 2000 mg dose of Deferiprone immediate-release under fasting conditions.

Deferiprone immediate-release: Deferiprone immediate-release tablets

Overall Number of Participants Analyzed 10 10 11
Mean (Standard Deviation)
Unit of Measure: mcg*h/mL
Deferiprone 66.2  (11.1) 57.2  (16.1) 71.6  (11.0)
Deferiprone 3-O-glucuronide 181.3  (39.9) 169.2  (62.3) 193.4  (32.5)
3.Primary Outcome
Title Cmax for Serum Deferiprone and Deferiprone 3-O-glucuronide
Hide Description Cmax (maximum concentration in the serum) was assessed over a 24-hour interval for analyses of deferiprone and its 3-O-glucuronide metabolite. Blood samples were obtained prior to dosing and at 0.25, 0.5, 0.75, 1, 1.3333, 1.6667, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16 and 24 hours post-dose.
Time Frame 24-hour interval
Hide Outcome Measure Data
Hide Analysis Population Description
All subjects who contributed evaluable pharmacokinetics data
Arm/Group Title Deferiprone Sustained-release (Fed) Deferiprone Sustained-release (Fasting) Deferiprone Immediate-release (Fasting)
Hide Arm/Group Description:

A single 2000 mg dose of deferiprone sustained-release following a high fat high calorie breakfast.

Deferiprone sustained-release: Deferiprone sustained-release tablets

A single 2000 mg dose of deferiprone sustained-release under fasting conditions.

Deferiprone sustained-release: Deferiprone sustained-release tablets

A single 2000 mg dose of Deferiprone immediate-release under fasting conditions.

Deferiprone immediate-release: Deferiprone immediate-release tablets

Overall Number of Participants Analyzed 10 10 11
Mean (Standard Deviation)
Unit of Measure: mcg/mL
Deferiprone 8.7  (1.8) 5.8  (1.6) 21.9  (6.9)
Deferiprone 3-O-glucuronide 18.5  (4.2) 14.3  (2.9) 33.2  (5.0)
4.Primary Outcome
Title Tmax for Serum Deferiprone and Deferiprone 3-O-glucuronide
Hide Description Tmax (the time to Cmax) was assessed over a 24-hour interval for analyses of deferiprone and its 3-O-glucuronide metabolite. Blood samples were obtained prior to dosing and at 0.25, 0.5, 0.75, 1, 1.3333, 1.6667, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16 and 24 hours post-dose.
Time Frame 24-hour interval
Hide Outcome Measure Data
Hide Analysis Population Description
All subjects who contributed evaluable pharmacokinetics data
Arm/Group Title Deferiprone Sustained-release (Fed) Deferiprone Sustained-release (Fasting) Deferiprone Immediate-release (Fasting)
Hide Arm/Group Description:

A single 2000 mg dose of deferiprone sustained-release following a high fat high calorie breakfast.

Deferiprone sustained-release: Deferiprone sustained-release tablets

A single 2000 mg dose of deferiprone sustained-release under fasting conditions.

Deferiprone sustained-release: Deferiprone sustained-release tablets

A single 2000 mg dose of Deferiprone immediate-release under fasting conditions.

Deferiprone immediate-release: Deferiprone immediate-release tablets

Overall Number of Participants Analyzed 10 10 10
Mean (Standard Deviation)
Unit of Measure: h
Deferiprone 4.4  (0.9) 3.3  (1.4) 1.3  (1.1)
Deferiprone 3-O-glucuronide 6.0  (1.5) 4.5  (1.5) 3.0  (0.9)
5.Primary Outcome
Title Thalf for Serum Deferiprone and Deferiprone 3-O-glucuronide
Hide Description Thalf (the apparent terminal elimination half-life of the drug) was assessed over a 24-hour interval for analyses of deferiprone and its 3-O-glucuronide metabolite. Blood samples were obtained prior to dosing and at 0.25, 0.5, 0.75, 1, 1.3333, 1.6667, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 16 and 24 hours post-dose.
Time Frame 24-hour interval
Hide Outcome Measure Data
Hide Analysis Population Description
All subjects who contributed evaluable pharmacokinetics data
Arm/Group Title Deferiprone Sustained-release (Fed) Deferiprone Sustained-release (Fasting) Deferiprone Immediate-release (Fasting)
Hide Arm/Group Description:

A single 2000 mg dose of deferiprone sustained-release following a high fat high calorie breakfast.

Deferiprone sustained-release: Deferiprone sustained-release tablets

A single 2000 mg dose of deferiprone sustained-release under fasting conditions.

Deferiprone sustained-release: Deferiprone sustained-release tablets

A single 2000 mg dose of Deferiprone immediate-release under fasting conditions.

Deferiprone immediate-release: Deferiprone immediate-release tablets

Overall Number of Participants Analyzed 10 10 11
Mean (Standard Deviation)
Unit of Measure: h
Deferiprone 2.8  (1.4) 5.0  (3.5) 1.9  (0.3)
Deferiprone 3-O-glucuronide 3.7  (3.4) 6.1  (4.9) 2.4  (0.5)
6.Secondary Outcome
Title Safety and Tolerability of Deferiprone Sustained Release Tablets
Hide Description The number of participants who experienced adverse events between the time of dosing up to 24 hours post-dose, including any changes of clinical significance in vital signs, 12-lead ECG, and clinical laboratory tests
Time Frame From time of dose until 24 hours post dose
Hide Outcome Measure Data
Hide Analysis Population Description
All subjects who received at least one dose of study medication and had at least one safety assessment
Arm/Group Title Deferiprone Sustained-release (Fed) Deferiprone Sustained-release (Fasting) Deferiprone Immediate-release (Fasting)
Hide Arm/Group Description:

A single 2000 mg dose of deferiprone sustained-release following a high fat high calorie breakfast.

Deferiprone sustained-release: Deferiprone sustained-release tablets

A single 2000 mg dose of deferiprone sustained-release under fasting conditions.

Deferiprone sustained-release: Deferiprone sustained-release tablets

A single 2000 mg dose of Deferiprone immediate-release under fasting conditions.

Deferiprone immediate-release: Deferiprone immediate-release tablets

Overall Number of Participants Analyzed 10 10 11
Measure Type: Number
Unit of Measure: participants
5 5 6
Time Frame 1 day
Adverse Event Reporting Description Safety data were collected from the time of dosing up to 24 hours post-dose
 
Arm/Group Title Deferiprone Sustained-release (Fed) Deferiprone Sustained-release (Fasting) Deferiprone Immediate-release (Fasting)
Hide Arm/Group Description

A single 2000 mg dose of deferiprone sustained-release following a high fat high calorie breakfast.

Deferiprone sustained-release: Deferiprone sustained-release tablets

A single 2000 mg dose of deferiprone sustained-release under fasting conditions.

Deferiprone sustained-release: Deferiprone sustained-release tablets

A single 2000 mg dose of Deferiprone immediate-release under fasting conditions.

Deferiprone immediate-release: Deferiprone immediate-release tablets

All-Cause Mortality
Deferiprone Sustained-release (Fed) Deferiprone Sustained-release (Fasting) Deferiprone Immediate-release (Fasting)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Hide Serious Adverse Events
Deferiprone Sustained-release (Fed) Deferiprone Sustained-release (Fasting) Deferiprone Immediate-release (Fasting)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/10 (0.00%)      0/10 (0.00%)      0/11 (0.00%)    
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Deferiprone Sustained-release (Fed) Deferiprone Sustained-release (Fasting) Deferiprone Immediate-release (Fasting)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   5/10 (50.00%)      5/10 (50.00%)      6/11 (54.55%)    
Cardiac disorders       
Sinus bradycardia  1  0/10 (0.00%)  0 0/10 (0.00%)  0 1/11 (9.09%)  1
General disorders       
Catheter site bruise  1  1/10 (10.00%)  1 0/10 (0.00%)  0 0/11 (0.00%)  0
Investigations       
Heart rate decreased  1  2/10 (20.00%)  3 2/10 (20.00%)  2 2/11 (18.18%)  3
Blood pressure decreased  1  0/10 (0.00%)  0 0/10 (0.00%)  0 1/11 (9.09%)  1
Blood pressure increased  1  1/10 (10.00%)  1 1/10 (10.00%)  1 1/11 (9.09%)  1
Blood urine present  1  1/10 (10.00%)  1 0/10 (0.00%)  0 1/11 (9.09%)  1
White blood cells urine positive  1  1/10 (10.00%)  2 0/10 (0.00%)  0 0/11 (0.00%)  0
Alanine aminotransferase increased  1  1/10 (10.00%)  1 2/10 (20.00%)  2 0/11 (0.00%)  0
Body temperature increased  1  0/10 (0.00%)  0 1/10 (10.00%)  1 0/11 (0.00%)  0
Amylase increased  1  0/10 (0.00%)  0 1/10 (10.00%)  1 0/11 (0.00%)  0
Serum ferritin decreased  1  1/10 (10.00%)  1 0/10 (0.00%)  0 0/11 (0.00%)  0
Metabolism and nutrition disorders       
C-reactive protein increased  1  1/10 (10.00%)  1 0/10 (0.00%)  0 0/11 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (Unspecified)
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Fernando Tricta, MD
Organization: ApoPharma Inc.
Phone: 416-401-7332
EMail: ftricta@apopharma.com
Layout table for additonal information
Responsible Party: ApoPharma
ClinicalTrials.gov Identifier: NCT02189941    
Other Study ID Numbers: LA43-0114
First Submitted: July 11, 2014
First Posted: July 15, 2014
Results First Submitted: December 23, 2015
Results First Posted: May 20, 2016
Last Update Posted: May 20, 2016