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

NCT01835496 | Completed Phase 1 Results

• 1 other identifier: LA41-0412
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

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.

Conditions

Sickle Cell Disease

Keywords

sickle cell disease; iron overload; pharmacokinetics; Ferriprox; deferiprone

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (2)

• 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

Study Arms (1)

Ferriprox

NO INTERVENTION

single 1500 mg dose of Ferriprox

Drug: single 1500 mg dose of Ferriprox

Interventions

single 1500 mg dose of Ferriprox DRUG

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

Also known as: deferiprone

Ferriprox

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• ApoPharma: lead

Study Sites (1)

CHUM-Hôpital Notre-Dame

Montreal, Quebec, H2L 4M1, Canada

Location

Related Publications (1)

• 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.

  PMID: 34981144 DERIVED

MeSH Terms

Conditions

Anemia, Sickle Cell; Iron Overload

Interventions

Single Person; Deferiprone

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Iron Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Marital Status; Family Characteristics; Demography; Population Characteristics; Socioeconomic Factors; Pyridones; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Caroline Fradette, PhD
• Organization: ApoPharma Inc.

cfradett@apopharma.com

416-401-7543

Study Officials

• Denis Soulieres, MD

  CHUM - Hôpital Notre-Dame

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 11, 2013
• First Posted: April 19, 2013
• Study Start: May 1, 2013
• Primary Completion: April 1, 2014
• Study Completion: April 1, 2014
• Last Updated: July 24, 2015
• Results First Posted: July 24, 2015

Record last verified: 2013-04

Locations

CA (1)