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

Sickle Cell Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01835496
• Other study ID #: LA41-0412
• Status: Completed
• Phase: Phase 1
• First received: April 11, 2013
• Last updated: July 22, 2015
• Start date: May 2013
• Est. completion date: April 2014

Study information

• Verified date: April 2013
• Source: ApoPharma
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 8
• Est. completion date: April 2014
• Est. primary completion date: April 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 45 Years

Eligibility

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

Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• Sickle Cell Disease

Intervention

Drug:
• single 1500 mg dose of Ferriprox
A single dose of 1500mg of Ferriprox (three 500mg tablets) administered under fasting conditions

Locations

Country	Name	City	State
Canada	CHUM-Hôpital Notre-Dame	Montreal	Quebec

Sponsors (1)

Lead Sponsor	Collaborator
ApoPharma

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	No
Primary	AUC0-8 for Serum Deferiprone and Deferiprone 3-O-glucuronide	AUC0-8 (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	No
Primary	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	No
Secondary	Frequency of Adverse Events		From Day 1 (Dosing) to Day 7 plus/minus 3 days (Follow-up)	Yes
Secondary	Frequency of Serious Adverse Events		From Day 1 (Dosing) to Day 30 post-dose	Yes