Pharmacokinetics of BF2.649 in Renal Impairment
Pharmacokinetics of BF2.649 in Renal Impairment
This is an open, parallel group study in subjects with normal renal function compared to
 those with renal dysfunction.
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%)
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