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CompletedNCT03802916TWICEUpdated Jul 16, 2021Results posted

Safety and Acceptability of Deferiprone Delayed Release Tablets in Patients With Systemic Iron Overload

A Phase 2 interventional study of Deferiprone DR tablets 1000 mg (Low dosage) and Deferiprone DR tablets 1000 mg (High dosage) in Iron Overload Due to Repeated Red Blood Cell Transfusions, sponsored by ApoPharma. Completed at 5 sites in 4 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2021-07-16.

Sponsored by ApoPharma · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
30
Allocation
Non-randomized
Ages
18 Years and older
Sex
All
01

Study summary

Safety, tolerability, and acceptability of twice-daily dosing with deferiprone delayed-release (DR) tablets in patients with systemic iron overload.

Read the detailed description

This study is looking at the safety, tolerability, and acceptability of twice-daily dosing with deferiprone delayed-release (DR) tablets in patients with systemic iron overload who are currently taking deferiprone immediate-release tablets (Ferriprox) three times a day. Ferriprox doses range from 75 milligrams per kilogram of body weight (mg/kg) per day to 100 mg/kg per day. Half the patients in the study will be on a dosage that is closer to the low end of the range, and half will be on a dosage that is closer to the high end. Both groups will be switched for one month to deferiprone DR tablets at approximately the same total daily dosage that they have been taking for Ferriprox.

02

Conditions studied

  • Iron Overload Due to Repeated Red Blood Cell Transfusions

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Keywords

  • iron overload
  • chelation
  • deferiprone
  • Ferriprox
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  1. Male or female aged ≥ 18 years.
  2. Diagnosis of thalassemia syndrome, sickle cell disease, or other disorder requiring a regular regimen of red blood cell transfusions.
  3. On a stable regimen (≥3 months) of Ferriprox tablets for the treatment of systemic iron overload.
  4. Absolute neutrophil count ≥1.5 x 10\^9/L at screening.
  5. A record of at least 12 measured alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels.

Exclusion criteria

Exclusion Criteria:

  1. Receipt of any iron chelator other than Ferriprox (i.e., combination therapy) in the last 3 months, or planning to receive it at any time during the period of the study.
  2. ALT and/or AST value > 5 times the upper limit of normal (ULN) at screening
  3. Active case of hepatitis B or C at screening.
04

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
30 participants (actual)

Study arms

  • Experimental
    Low dosage

    Patients in this group will receive a total daily dosage of deferiprone DR tablets that is closer to 75 mg/kg/day. The total dosage will be divided into two equal parts, taken about 12 hours apart.

    Drug: Deferiprone DR tablets 1000 mg (Low dosage)

  • Experimental
    High dosage

    Patients in this group will receive a total daily dosage of deferiprone DR tablets that is closer to 100 mg/kg/day. The total dosage will be divided into two equal parts, taken about 12 hours apart.

    Drug: Deferiprone DR tablets 1000 mg (High dosage)

Interventions

  • DrugDeferiprone DR tablets 1000 mg (Low dosage)

    Deferiprone DR tablets 1000 mg

  • DrugDeferiprone DR tablets 1000 mg (High dosage)

    Deferiprone DR tablets 1000 mg

05

What researchers measure

Primary outcomes

  1. The Percentage of Patients in Each Treatment Group Who Experience Post-dose Increases in Liver Enzyme Levels That Are Considered a Safety Concern.

    Levels of the liver enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST) will be assessed throughout the study to determine if any patients have post-dose increases that are considered to be a safety concern. The criteria for being considered a safety concern are meeting one of the following: * For a patient whose level was within the normal range at baseline, the criterion is reaching a value of 5 times the upper limit of normal (ULN) * For a patient whose level was above the ULN at baseline, the criterion is reaching either 5 times the baseline value or 10 x ULN

    Time frame: Day 28

Secondary outcomes

  1. The Percentage of Patients in Each Treatment Group Who Report Post-dose Occurrences of Gastrointestinal (GI) Distress.

    Patients will be asked to report any events of GI distress during the study, such as nausea, vomiting, diarrhea, abdominal pain, and dyspepsia.

    Time frame: Day 28

  2. The Percentage of Patients in Each Group Who Indicate That They Prefer the Deferiprone DR Formulation Over the Immediate-release Formulation.

    At the end of the study, patients will complete a questionnaire to indicate which formulation they prefer.

    Time frame: Day 28

06

Results

Posted Jun 18, 2021

Participant flow

Participant flow — Overall Study
MilestoneLow DosageHigh Dosage
Started1515
Completed1513
Not completed02
Withdrew: Adverse event01
Withdrew: Withdrawal by subject01

Outcome measures

PrimaryThe Percentage of Patients in Each Treatment Group Who Experience Post-dose Increases in Liver Enzyme Levels That Are Considered a Safety Concern.

Levels of the liver enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST) will be assessed throughout the study to determine if any patients have post-dose increases that are considered to be a safety concern. The criteria for being considered a safety concern are meeting one of the following: * For a patient whose level was within the normal range at baseline, the criterion is reaching a value of 5 times the upper limit of normal (ULN) * For a patient whose level was above the ULN at baseline, the criterion is reaching either 5 times the baseline value or 10 x ULN

Time frame:
Day 28
Reported as:
Count of participants · Participants
The Percentage of Patients in Each Treatment Group Who Experience Post-dose Increases in Liver Enzyme Levels That Are Considered a Safety Concern.
ParticipantsLow DosageHigh Dosage
Patients with elevated ALT of clinical concern00
Patients with elevated AST of clinical concern00
SecondaryThe Percentage of Patients in Each Treatment Group Who Report Post-dose Occurrences of Gastrointestinal (GI) Distress.

Patients will be asked to report any events of GI distress during the study, such as nausea, vomiting, diarrhea, abdominal pain, and dyspepsia.

Time frame:
Day 28
Reported as:
Count of participants · Participants
The Percentage of Patients in Each Treatment Group Who Report Post-dose Occurrences of Gastrointestinal (GI) Distress.
ParticipantsLow DosageHigh Dosage
The Percentage of Patients in Each Treatment Group Who Report Post-dose Occurrences of Gastrointestinal (GI) Distress.33
SecondaryThe Percentage of Patients in Each Group Who Indicate That They Prefer the Deferiprone DR Formulation Over the Immediate-release Formulation.

At the end of the study, patients will complete a questionnaire to indicate which formulation they prefer.

Time frame:
Day 28
Reported as:
Count of participants · Participants
The Percentage of Patients in Each Group Who Indicate That They Prefer the Deferiprone DR Formulation Over the Immediate-release Formulation.
ParticipantsLow DosageHigh Dosage
The Percentage of Patients in Each Group Who Indicate That They Prefer the Deferiprone DR Formulation Over the Immediate-release Formulation.1313
Statistical analysis
  • Low Dosage · One-sample proportion test · p = 0.0074 (A p-value was calculated for the one-sample proportion test.)
  • High Dosage · One-sample proportion test · p = 0.0002 (A p-value was calculated for the one-sample proportion test.)

Adverse events

Collected over Baseline to Day 28. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Low Dosage0/15 (0%)0/15 (0%)10/15 (66.7%)
High Dosage0/14 (0%)0/14 (0%)9/14 (64.3%)
Most frequent other events
Showing 10 of 26
Most frequent other events
EventLow DosageHigh Dosage
DiarrhoeaGastrointestinal disorders0/153/14
HeadacheNervous system disorders3/153/14
ArthralgiaMusculoskeletal and connective tissue disorders3/151/14
BlepharitisEye disorders0/152/14
Joint injuryInjury, poisoning and procedural complications2/150/14
Ear painEar and labyrinth disorders1/151/14
PyrexiaGeneral disorders1/151/14
ConjunctivitisInfections and infestations0/151/14
PharyngitisInfections and infestations0/151/14
Alanine aminotransferase increasedInvestigations0/151/14

Baseline characteristics

One patient in the high-dosage group withdrew before receiving any study product

Age, Continuous
Age, Continuous(years)Low DosageHigh DosageTotal
Mean41.9 ± 9.940.4 ± 6.841.1 ± 8.4
Sex: Female, Male
Sex: Female, Male(Participants)Low DosageHigh DosageTotal
Female6713
Male9716
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Low DosageHigh DosageTotal
Hispanic or Latino011
Not Hispanic or Latino151328
Unknown or Not Reported000
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Low DosageHigh DosageTotal
American Indian or Alaska Native000
Asian202
Native Hawaiian or Other Pacific Islander000
Black or African American000
White131326
More than one race000
Unknown or Not Reported011
Region of Enrollment
Region of Enrollment(participants)Low DosageHigh DosageTotal
Greece358
Canada303
United States123
Italy8716
Level of liver enzymes at baseline for low-dosage group
Level of liver enzymes at baseline for low-dosage group(units per liter)Low DosageHigh DosageTotal
Baseline ALT29.60 ± 19.88—29.60 ± 19.88
Baseline AST27.53 ± 10.00—27.53 ± 10.00
Level of liver enzymes at baseline for high-dosage group
Level of liver enzymes at baseline for high-dosage group(units per liter)Low DosageHigh DosageTotal
Baseline ALT—38.29 ± 22.4338.29 ± 22.43
Baseline AST—28.50 ± 11.3928.50 ± 11.39
07

Study locations

5 sites
  • Ann & Robert H. Lurie Children's Hospital of Chicago
    Chicago, Illinois 60611, United States
  • New York Presbyterian Hospital/Weill Cornell Medical Center
    New York, New York 10065, United States
  • St.Paul's Hospital
    Vancouver, British Columbia V6Z 1Y6, Canada
  • National and Kapodistrian University of Athens, Aghia Sophia Children's Hospital
    Goudí, Athens 11527, Greece
  • San Luigi Gonzaga University Hospital Reparto Microcitemie-Pediatria
    Orbassano (TO), Regione Gonzole 10043, Italy
08

References and documents

Study documents

  • Protocol and statistical analysis plan · Oct 10, 2018

Documents are hosted by the registry — open the source record to download them.

09

Registry details

Key details

Study ID
NCT03802916
Lead sponsor
ApoPharma
Responsible party
Sponsor
First posted
Jan 14, 2019
Start date
Mar 6, 2019
Primary completion
Dec 4, 2019
Completion
Dec 19, 2019
Results posted
Jun 18, 2021
Last update
Jul 16, 2021

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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