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

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

Detailed Description
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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.

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

Conditions
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Iron Overload Due to Repeated Red Blood Cell Transfusions

Intervention / Treatment
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* Drug: Deferiprone DR tablets 1000 mg (Low dosage)
* Drug: Deferiprone DR tablets 1000 mg (High dosage)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female aged ≥ 18 years. Diagnosis of thalassemia syndrome, sickle cell disease, or other disorder requiring a regular regimen of red blood cell transfusions. On a stable regimen (≥3 months) of Ferriprox tablets for the treatment of systemic iron overload. Absolute neutrophil count ≥1.5 x 10^9/L at screening. A record of at least 12 measured alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. Exclusion Criteria: 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. ALT and/or AST value > 5 times the upper limit of normal (ULN) at screening Active case of hepatitis B or C at screening.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low dosage<br>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)<br>* Deferiprone DR tablets 1000 mg<br>|
| Experimental: High dosage<br>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)<br>* Deferiprone DR tablets 1000 mg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Day 28 | 
| 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. | Day 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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iron overload, chelation, deferiprone, Ferriprox