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

NCT01770652 | Completed Phase 4 Results

• 1 other identifier: LA39-0412
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 2

Brief 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®.

Conditions

Renal Impairment

Keywords

Renal Impairment; Kidney Impairment; Kidney Disease; Ferriprox; Deferiprone; DFP (deferiprone); L1

Outcome Measures

Primary Outcomes (6)

• 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

• 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

• AUC Zero to Infinity (AUC0-∞) for Serum Deferiprone and Deferiprone 3-O-glucuronide

  AUC0-∞ 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

• 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

• 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

• 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

Secondary Outcomes (1)

• Safety and Tolerability of Ferriprox® in Subjects With Renal Impairment.

  From time of dosing until 72 hours post-dose

Study Arms (4)

Normal renal function

EXPERIMENTAL

Healthy volunteers, defined as having an estimated glomerular filtration rate (eGFR) ≥90 mL/min/1.73m\^2. All subjects received a single 33 mg/kg oral dose of deferiprone.

Drug: Deferiprone

Mild Renal Impairment

EXPERIMENTAL

Mild impairment, defined as having an eGFR 60-89 mL/min/1.73m\^2. All subjects received a single 33 mg/kg oral dose of deferiprone.

Drug: Deferiprone

Moderate Renal Impairment

EXPERIMENTAL

Mild impairment, defined as having an eGFR 30-59 mL/min/1.73m\^2. All subjects received a single 33 mg/kg oral dose of deferiprone.

Drug: Deferiprone

Severe Renal Impairment

EXPERIMENTAL

Severe impairment, defined as having an eGFR 15-19 mL/min/1.73m\^2. All subjects received a single 33 mg/kg oral dose of deferiprone.

Drug: Deferiprone

Interventions

Deferiprone DRUG

Oral iron chelator

Also known as: Ferriprox, L1, DFP

Mild Renal Impairment; Moderate Renal Impairment; Normal renal function; Severe Renal Impairment

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All subjects:
• Adult males or females, 18 - 75 years of age (inclusive);
• Body weight ≥ 45 kg;
• Body mass index (BMI) range of approximately 18.5-32 kg/m\^2 (inclusive);
• Absolute neutrophil count (ANC) of \>1.5x10\^9/L;
• Healthy volunteers:
• Medically healthy with clinically insignificant screening results (e.g., laboratory profiles, medical history, vital signs, physical examination);
• eGFR ≥ 90 mL/min/1.73m\^2;
• Renally impaired subjects:
• Considered clinically stable in the opinion of the Investigator;
• 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).

You may not qualify if:

• History of renal transplant;
• Subjects undergoing any method of dialysis;
• 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;
• 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.);
• Clinically significant abnormalities on 12-lead ECG (e.g., QTcF≥430 ms in males or ≥450 ms in females);
• Evidence of liver damage: hepatitis B and C; aspartate aminotransferase (AST), alanine aminotransferase (ALT) that is considered clinically significant by the Investigator;
• Participation in another clinical trial within 28 days prior to the study drug administration;

Sponsors & Collaborators

• ApoPharma: lead

Study Sites (2)

Hôpital Maisonneuve-Rosemont

Montreal, Quebec, H1T2M4, Canada

Location

Algorithme Pharma Inc.

Mount Royal, Quebec, H3P3P1, Canada

Location

MeSH Terms

Conditions

Renal Insufficiency; Kidney Diseases

Interventions

Deferiprone; Long Interspersed Nucleotide Elements; Isoflurophate

Condition Hierarchy (Ancestors)

Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Pyridones; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Retroelements; Interspersed Repetitive Sequences; Repetitive Sequences, Nucleic Acid; Base Sequence; Molecular Structure; Biochemical Phenomena; Chemical Phenomena; Genetic Structures; Genetic Phenomena; Genome Components; Genome; Organofluorophosphonates; Organophosphonates; Organophosphorus Compounds; Organic Chemicals

Results Point of Contact

• Title: Fernando Tricta, MD
• Organization: ApoPharma Inc.

ftricta@apopharma.com

Phone: 416-401-7332

Study Officials

• Fernando Tricta, MD

  ApoPharma

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 16, 2013
• First Posted: January 18, 2013
• Study Start: January 1, 2013
• Primary Completion: July 1, 2013
• Study Completion: August 1, 2013
• Last Updated: August 26, 2014
• Results First Posted: August 26, 2014

Record last verified: 2013-08

Locations

CA (2)