Clinical trial NCT01835496: Absorption, Metabolism, and Excretion of a Single Dose of Ferriprox® in Patients With Sickle Cell Disease
Official title: The Pharmacokinetic Profile of a Single Dose of Ferriprox® in Patients With Sickle Cell Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Sickle Cell Disease
Keywords: sickle cell disease
iron overload
pharmacokinetics
Ferriprox
deferiprone
Lead sponsor: ApoPharma
Sponsor class: INDUSTRY
First posted: 2013-04-19
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

1. Male or female, 18-45 years of age (inclusive)
2. Diagnosis of sickle cell disease, confirmed by Hb electrophoresis
3. Body weight ≥ 50 kg
4. Body mass index (BMI) ≥ 18 and ≤ 32 kg/m\^2
5. Absolute neutrophil count (ANC) of \>1.5 x 10\^9/L
6. 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
7. 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:

1. History or presence of hypersensitivity or idiosyncratic reaction to Ferriprox
2. Use of Ferriprox within the past 3 months
3. History of malignancy
4. 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)
5. 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
6. Hemodialysis during the week prior to dosing or planned for the day of dosing
7. Known difficulty in providing blood samples
8. 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.)
9. 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)
10. Use of tobacco/nicotine-containing products for at least 3 months prior to study drug administration
11. 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
12. 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
13. Pregnant or nursing female

Primary outcomes:
measure: Cmax for Serum Deferiprone and Deferiprone 3-O-glucuronide
timeFrame: 10-hour interval
measure: Tmax for Deferiprone and Deferiprone 3-O-glucuronide
timeFrame: 10-hour interval
measure: AUC0-∞ for Serum Deferiprone and Deferiprone 3-O-glucuronide
timeFrame: 10-hour interval
measure: T1/2 for Serum Deferiprone and Deferiprone 3-O-glucuronide
timeFrame: 10-hour interval
Secondary outcomes:
measure: Frequency of Adverse Events
timeFrame: From Day 1 (Dosing) to Day 7 plus/minus 3 days (Follow-up)
measure: Frequency of Serious Adverse Events
timeFrame: From Day 1 (Dosing) to Day 30 post-dose
Other outcomes:
Locations:
city: Montreal
country: Canada
facility: CHUM-Hôpital Notre-Dame
state: Quebec
Study officials:
affiliation: CHUM - Hôpital Notre-Dame
name: Denis Soulieres, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Soulieres D, Mercier-Ross J, Fradette C, Rozova A, Tsang YC, Tricta F. The pharmacokinetic and safety profile of single-dose deferiprone in subjects with sickle cell disease. Ann Hematol. 2022 Mar;101(3):533-539. doi: 10.1007/s00277-021-04728-0. Epub 2022 Jan 4.