Pharmacokinetics of BF2.649 in Renal Impairment

Pharmacokinetics of 20 mg BF2.649 in Single Dose, in Subjects With Normal Renal Function Compared to Subject With Impaired Renal Function

This is an open, parallel group study in subjects with normal renal function compared to those with renal dysfunction.

Study Overview

• Status: Completed
• Conditions: Renal Impairment
• Intervention / Treatment: Drug: BF2.649

Detailed Description

The pharmacokinetic of BF2.649 (pitolisant) is already well established from several studies in healthy human, and a recent pharmacokinetic study gave data on 12 young healthy volunteers compared to 12 elderly subject receiving 20mg/day during 14 days.

The aim of this study is to investigate effect of renal impairment on the pharmacokinetics of BF2.649 administrated on a single oral dose of 20 mg.

The once daily dose of 20 mg BF2.649 (pitolisant) chosen for this study corresponds to the usual therapeutic dose.

Twenty four subjects will be stratified according to renal function by using assessment of glomerular filtration rate (GFR) as defined by MDRD formula as follows:

• 4 subjects from 18 to 75 years of age with mild impaired renal function defined by GFR between 60 and 89 ml/min (STAGE 2 according to the international classification of chronic kidney disease)
• 4 subjects from 18 to 75 years of age with moderate impaired renal function defined by GFR between 30 and 59 ml/min (STAGE 3 according to the international classification of chronic kidney disease)
• 4 subjects from 18 to 75 years of age with severe impaired renal function defined by GFR between 15 and 29 ml/min (STAGE 4 according to the international classification of chronic kidney disease)
• 12 healthy subjects with normal renal function defined by GFR>90 ml/min with no proteinuria (<0.15g/L determined by urinalysis) matched with impaired renal function subjects on ethnic group, sex, age (+/- 5 years), and BMI (+/- 20%)

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 1

Contacts and Locations

Study Locations

• France
  • Lyon, France
    • EUROFINS OPTIMED Lyon

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

For subjects with impaired renal function:

• Subjects 18 to 75 years old with impaired renal function (MDRD formula between 15 and 89mL/min) medically stable since 3 months
• With body mass index (weight/height2) in the range 18 to 32 kg/m2 (inclusive)

For healthy subjects:

• Healthy subjects 18 to 75 years old with normal renal function (MDRD > 90 mL/min) and no proteinuria (<0.15g/L determined by urinalysis) matched with impaired renal function subjects on ethnic group, sex, age (+/- 5 years), and BMI (+/- 20%)

Exclusion Criteria:

For impaired renal function subjects:

• History of hepatic, cardiovascular (including conduction disturbance) or psychiatric disorder or any other condition which, in the opinion of the investigator, would jeopardize the safety of the subject or impact the validity of study results.
• Evidence of liver disease
• Presence of concomitant pathology requiring intake of any drugs or substances known to be inhibitors or inductors of CYP enzymes
• Presence of metabolic or ionic disorders not controlled by adapted treatment
• Presence of significant anemia,nephrotic syndrome
• Renal transplantation

For healthy subjects:

• history of renal, cardiovascular, gastrointestinal, hepatic, neurological, endocrine or psychiatric disorders or any surgery which puts them at risk in the opinion of the investigator.
• Any treatment within 14 days before inclusion, or within 5 times the elimination half-life of that drug, whichever the longest, including treatment which could lead to inhibition or induction of CYP enzymes - mainly CYP3A4 and CYP2D6 and with the exception of hormonal contraception and menopausal hormone replacement therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: impaired renal function subjects	Drug: BF2.649; single dose 20 mg; Other Names: Pitolisant
Other: Healthy volunteers; matched with impaired renal function subjects on ethnic group, sex, age (+/- 5 years), and BMI (+/- 20%)	Drug: BF2.649; single dose 20 mg; Other Names: Pitolisant

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mesure of classic pharmacokinetic parameters determined on BF2.649 serum and urine concentration	Cmax, Tmax, AUClast, AUC∞, λz, t½term, CL/F, Vz/F	between H0(0hr - Pre-dose) and H96 (96hr) after single oral dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Adverse Events as a Measure of Safety and Tolerability	clinical safety of BF2.649.	during the 4 days following the drug administration
change in lab tests (biological and clinical safety)		during 4 days after drug administration

Collaborators and Investigators

• Sponsor: Bioprojet
• Investigators: Principal Investigator: Claire POUTEIL-NOBLE, MD, Nephrologie, Centre Hospitalier Lyon Sud

Study record dates

Study Major Dates

• Study Start: July 1, 2011
• Primary Completion (Actual): November 1, 2012
• Study Completion (Actual): November 1, 2012

Study Registration Dates

• First Submitted: July 20, 2011
• First Submitted That Met QC Criteria: June 12, 2012
• First Posted (Estimate): June 14, 2012

Study Record Updates

• Last Update Posted (Estimate): April 12, 2013
• Last Update Submitted That Met QC Criteria: April 11, 2013
• Last Verified: April 1, 2013

More Information

Terms related to this study

• Keywords: Renal impairment
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency
• Other Study ID Numbers: P09-13 / BF2.649; 2011-001430-42 (EudraCT Number)