Absorption, Metabolism, and Excretion of a Single Dose of Ferriprox® in Patients With Sickle Cell Disease

Study Overview
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Brief Summary
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The objective of this study is to evaluate the pharmacokinetics of deferiprone and its 3-O-glucuronide metabolite following administration of a single 1500 mg dose of Ferriprox in patients with sickle cell disease.

Detailed Description
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This is a single-arm, single-dose study of Ferriprox in patients with sickle cell disease. Patients found to be eligible will visit the clinic the day before receiving the drug, in order to reconfirm eligibility and to undergo baseline assessments, and will receive a single dose of 1500 mg Ferriprox under fasting conditions. Blood and urine samples for pharmacokinetic assessment will be collected over a 10-hour period. Standard safety assessments will be performed throughout the study, and patients will return for a safety follow-up.

Official Title
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The Pharmacokinetic Profile of a Single Dose of Ferriprox® in Patients With Sickle Cell Disease

Conditions
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Sickle Cell Disease

Intervention / Treatment
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* Drug: single 1500 mg dose of Ferriprox


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, 18-45 years of age (inclusive) Diagnosis of sickle cell disease, confirmed by Hb electrophoresis Body weight ≥ 50 kg Body mass index (BMI) ≥ 18 and ≤ 32 kg/m^2 Absolute neutrophil count (ANC) of >1.5 x 10^9/L Women of childbearing potential must agree to either be sexually inactive or use an acceptable method of birth control for 14 days prior to dosing and for 30 days afterwards A fertile heterosexual male must agree that he or his partner will use an effective method of contraception for 14 days prior to dosing and for 30 days afterwards Exclusion Criteria: History or presence of hypersensitivity or idiosyncratic reaction to Ferriprox Use of Ferriprox within the past 3 months History of malignancy Evidence of abnormal liver function (serum Alanine Transaminase (ALT)level > 5 times upper limit of normal or creatinine levels >2 times upper limit of normal) A serious, unstable illness, as judged by the Investigator, within the past 3 months before screening visit including but not limited to hepatic, renal, gastro-enterologic, respiratory, cardiovascular, endocrinologic, neurologic or immunologic disease Hemodialysis during the week prior to dosing or planned for the day of dosing Known difficulty in providing blood samples Disorders or surgery of the gastrointestinal tract that may interfere with drug absorption or may otherwise influence the Pharmacokinetic (PK) results (e.g., resection of the small or large intestine, febrile conditions, chronic diarrhea, chronic vomiting, endocrine disease, severe infections, acute inflammations, etc.) Clinically significant abnormalities on 12-lead ECG (e.g., QT interval corrected using Fridericia's formula (QTcF) ≥ 430 ms in males or ≥ 450 ms in females) Use of tobacco/nicotine-containing products for at least 3 months prior to study drug administration Use of any drugs within the past 14 days that are metabolized by the Uridine diphosphate glucosyltransferase enzyme (UGT1A6) and hence could affect the PK of Ferriprox Treatment with an investigational drug within the past 30 days or 5 half-lives of that drug (whichever is longer) prior to study drug administration Pregnant or nursing female

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 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

Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Ferriprox<br>single 1500 mg dose of Ferriprox | Drug: single 1500 mg dose of Ferriprox<br>* A single dose of 1500mg of Ferriprox (three 500mg tablets) administered under fasting conditions<br>* Other names: deferiprone;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax for Serum Deferiprone and Deferiprone 3-O-glucuronide | Cmax (maximum measured serum concentration) was assessed over a 10-hour interval for deferiprone and its 3-O-glucuronide metabolite. Blood samples were obtained pre-dose and at 0.25, 0.50, 0.75, 1, 1.33, 1.66, 2, 2.5, 3, 4, 6, 8, and 10 hours post-dose. | 10-hour interval | 
| Tmax for Deferiprone and Deferiprone 3-O-glucuronide | Tmax (time to the maximum measured serum concentration) was assessed over a 10-hour interval for deferiprone and its 3-O-glucuronide metabolite. Blood samples were obtained pre-dose and at 0.25, 0.50, 0.75, 1, 1.33, 1.66, 2, 2.5, 3, 4, 6, 8, and 10 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). | 10-hour interval | 
| AUC0-∞ for Serum Deferiprone and Deferiprone 3-O-glucuronide | AUC0-∞ (area under the curve, zero to infinity) was assessed over a 10-hour interval for deferiprone and its 3-O-glucuronide metabolite. Blood samples were obtained pre-dose and at 0.25, 0.50, 0.75, 1, 1.33, 1.66, 2, 2.5, 3, 4, 6, 8, and 10 hours post-dose. | 10-hour interval | 
| T1/2 for Serum Deferiprone and Deferiprone 3-O-glucuronide | T1/2 (apparent terminal elimination half-life) was assessed over a 10-hour interval for deferiprone and its 3-O-glucuronide metabolite. Blood samples were obtained pre-dose and at 0.25, 0.50, 0.75, 1, 1.33, 1.66, 2, 2.5, 3, 4, 6, 8, and 10 hours post-dose. | 10-hour interval | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of Adverse Events |  | From Day 1 (Dosing) to Day 7 plus/minus 3 days (Follow-up) | 
| Frequency of Serious Adverse Events |  | From Day 1 (Dosing) to Day 30 post-dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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sickle cell disease, iron overload, pharmacokinetics, Ferriprox, deferiprone