An Open-label, Non-randomized, Parallel Group Study in Subjects With Mild, Moderate, Severe, or No Renal Impairment

Renal Impairment Clinical Trial

Official title:

An Open-label Study to Compare the Pharmacokinetic Profiles of a Single Dose of Ferriprox in Subjects With Impaired Renal Function and Healthy Volunteers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01770652
• Other study ID #: LA39-0412
• Status: Completed
• Phase: Phase 4
• First received: January 16, 2013
• Last updated: August 25, 2014
• Start date: January 2013
• Est. completion date: August 2013

Study information

• Verified date: August 2013
• Source: ApoPharma
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationCanada: Health Canada
• Study type: Interventional

Clinical Trial Summary

Multi-center, non-randomized, open-label, single-dose, parallel group study to determine the effect of impaired renal function on the PK of deferiprone and its 3-O-glucuronide metabolite following a single oral dose of 33mg/kg Ferriprox®.

Description:

Post-marketing study to evaluate the effect of impaired renal function on the pharmacokinetics (PK) of deferiprone and its 3-O-glucuronide metabolite and on the safety of Ferriprox® in subjects with mild, moderate and severe renal impairment as compared to healthy volunteers.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: August 2013
• Est. primary completion date: July 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

Main Inclusion Criteria:

All subjects:

1. Adult males or females, 18 - 75 years of age (inclusive);

2. Body weight = 45 kg;

3. Body mass index (BMI) range of approximately 18.5-32 kg/m^2 (inclusive);

4. Absolute neutrophil count (ANC) of >1.5x10^9/L;

Healthy volunteers:

1. Medically healthy with clinically insignificant screening results (e.g., laboratory profiles, medical history, vital signs, physical examination);

2. eGFR = 90 mL/min/1.73m^2;

Renally impaired subjects:

1. Considered clinically stable in the opinion of the Investigator;

2. Subjects with mild renal impairment (eGFR 60-89 mL/min/1.73m^E2) OR moderate renal impairment (eGFR 30-59 mL/min/1.73m^2) OR severe renal impairment (eGFR 15-29 mL/min/1.73m^2).

Main Exclusion Criteria:

1. History of renal transplant;

2. Subjects undergoing any method of dialysis;

3. History or presence of clinically unstable significant respiratory, cardiovascular, pulmonary, hepatic, renal (except for subjects assigned to one of the renally impaired groups), hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, or psychiatric disease;

4. Disorders or surgery of the gastrointestinal tract which may interfere with drug absorption or may otherwise influence the PK of the investigational medicinal product (e.g. cholecystectomy, resections of the small or large intestine, febrile conditions, chronic diarrhea, chronic vomiting, endocrine disease, severe infections, acute inflammations, etc.);

5. Clinically significant abnormalities on 12-lead ECG (e.g., QTcF=430 ms in males or =450 ms in females);

6. Evidence of liver damage: hepatitis B and C; aspartate aminotransferase (AST), alanine aminotransferase (ALT) that is considered clinically significant by the Investigator;

7. Participation in another clinical trial within 28 days prior to the study drug administration;

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Renal Impairment
• Renal Insufficiency

Intervention

Drug:
• Deferiprone
Oral iron chelator

Locations

Country	Name	City	State
Canada	Hôpital Maisonneuve-Rosemont	Montreal	Quebec
Canada	Algorithme Pharma Inc.	Mount-Royal	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 was assessed over a 24-hour interval for analyses of deferiprone and its 3-O-glucuronide metabolite in subjects with normal, mild, moderate and severe renal impairment. Blood samples were obtained prior to dosing and at 0.25, 0.50, 0.75, 1, 1.33, 1.66, 2, 2.5, 3, 4, 6, 9, 12, 16, and 24 hours post-dose.	24-hour interval	No
Primary	Tmax for Serum Deferiprone and Deferiprone 3-O-glucuronide	Tmax was assessed over a 24-hour interval for analyses of deferiprone and its 3-O-glucuronide metabolite. Blood samples were obtained prior to dosing and at 0.25, 0.50, 0.75, 1, 1.33, 1.66, 2, 2.5, 3, 4, 6, 9, 12, 16, and 24 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).	24 hour interval	No
Primary	AUC Zero to Infinity (AUC0-8) for Serum Deferiprone and Deferiprone 3-O-glucuronide	AUC0-8 was assessed over a 24-hour interval for analyses of deferiprone and its 3-O-glucuronide metabolite. Blood samples were obtained prior to dosing and at 0.25, 0.50, 0.75, 1, 1.33, 1.66, 2, 2.5, 3, 4, 6, 9, 12, 16, and 24 hours post-dose.	24 hour interval	No
Primary	T1/2 for Serum Deferiprone and Deferiprone 3-O-glucuronide	T1/2 was assessed over a 24-hour interval for analyses of deferiprone and its 3-O-glucuronide metabolite. Blood samples were obtained prior to dosing and at 0.25, 0.50, 0.75, 1, 1.33, 1.66, 2, 2.5, 3, 4, 6, 9, 12, 16, and 24 hours post-dose.	24 hour interval	No
Primary	Ae24 for Urine Deferiprone and Deferiprone 3-O-glucuronide	Ae24 (the amount excreted in urine from time zero to 24 hours) was assessed over a 24-hour interval for analyses of deferiprone and its 3-O-glucuronide metabolite. Urine samples were collected at the intervals of -2 to 0 hours pre-dose and 0 to 2, 2 to 4, 4 to 8, 8 to 12, and 12 to 24 hours post-dose.	24 hour interval	No
Primary	Fe24 for Serum Deferiprone and Deferiprone 3-O-glucuronide	Fe24 (fraction of dose excreted in urine from time zero to 24 hours) was assessed over a 24-hour interval for analyses of deferiprone and its 3-O-glucuronide metabolite. Urine samples were collected at the intervals of -2 to 0 hours pre-dose and 0 to 2, 2 to 4, 4 to 8, 8 to 12, and 12 to 24 hours post-dose.; Some of the Fe24 values were over 100% which could be explained by variability in urine collection (e.g. incomplete collection of urine into the container) and volume measurement, as well as analytical imprecision.	24-hour interval	No
Secondary	Safety and Tolerability of Ferriprox® in Subjects With Renal Impairment.	The number of participants who experienced adverse events (including any changes of clinical significance in physical examinations, vital signs, 12-lead ECG, and clinical laboratory tests) following a single dose of Ferriprox.	From time of dosing until 72 hours post-dose	Yes