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

Phase 1

Completed

• Conditions: Sickle Cell Disease
• Interventions: Drug: single 1500 mg dose of Ferriprox

• Registration Number: NCT01835496
• Lead Sponsor: ApoPharma

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.

Study Timeline

• Status Verified: 2013-04
• Study First Submitted: 2013-04-11
• Study First Submitted QC: 2013-04-16
• Study First Posted: 2013-04-19
• Study Start: 2013-05
• Primary Completion: 2014-04
• Study Completion: 2014-04
• Results First Submitted: 2015-06-26
• Results First Submitted QC: 2015-07-22
• Last Update Submitted: 2015-07-22
• Results First Posted: 2015-07-24
• Last Update Posted: 2015-07-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 8

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Ferriprox	single 1500 mg dose of Ferriprox	single 1500 mg dose of Ferriprox

Primary Outcome Measures

Name	Time	Method
AUC0-∞ for Serum Deferiprone and Deferiprone 3-O-glucuronide	10-hour interval	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.
T1/2 for Serum Deferiprone and Deferiprone 3-O-glucuronide	10-hour interval	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.
Cmax for Serum Deferiprone and Deferiprone 3-O-glucuronide	10-hour interval	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.
Tmax for Deferiprone and Deferiprone 3-O-glucuronide	10-hour interval	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).

Secondary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (1)

CHUM-Hôpital Notre-Dame; 🇨🇦 Montreal, Quebec, Canada