ESP Pharma” 10 mg film-coated tablets Montelukast sodium DK/H/17

where the latter employ slightly wider related substances limits. Stability data provided to date support
widening of the sulphoxide and total impurities limits to the extent suggested.
Batch analysis data are provided for three pilot scale batches showing compliance with the release
requirements and confirming consistency of product manufacture.
Stability data are provided for 2 batches of each strength stored in the proposed market packaging. A
shelf-life of 3 years when stored in the original package in order to protect from light and moisture is
accepted.
III. NON-CLINICAL ASPECTS
This product is a generic formulation of Singulair 10 mg film-coated tablets, which is available on the
European market. No new preclinical data have been submitted, and therefore the application has not
undergone preclinical assessment. This is acceptable for this type of application
Environmental risk assessment
The product is intended as a substitute for other identical products on the market. The approval of this
product will not result in an increase in the total quantity of montelukast sodium released into the
environment. It does not contain any component, which results in an additional hazard to the
environment during storage, distribution, use and disposal.
IV. CLINICAL ASPECTS
IV.1 Introduction
Montelukast sodium is a well-known active substance with established efficacy and tolerability.
For this generic application, the MAH has submitted three single dose bioequivalence studies, though
two of these relate to alternative dosage forms and are therefore not directly relevant to the application
and hence will not be reviewed here. The single dose study on the 10 mg film-coated tablets under
fasting conditions compares the pharmacokinetic profile of the test product Montelukast ”ESP
Pharma” 10 mg film-coated tablets with the pharmacokinetic profile of the reference product Singulair
10 mg film-coated tablets, Merck Sharp & Dohme, from the German market.
The study was a single centre, open label, randomised, single dose, two-way crossover study
conducted under fasting conditions with a wash out period of 7 days between administrations. 10 mg
was administered in each period with 240 ml water under yellow monochromatic light, after an
overnight fast of at least 10 hours. Subjects were confined to the clinical research centre from at least
13 hours prior to drug administration until after the 24 hour post-dose blood draw in each period.
Water was permitted ad lib until 1 hour before dosing and again 2 hours after dosing, otherwise ad
libitum. Standardised meals were provided at 4, 8 and 12 hours post dose in each period.
Blood sampling was performed predosing (within 1 hour) and at 0.5, 1.0, 1.333, 1.667, 2.0, 2.25, 2.5,
2.75, 3.0, 3.5, 3.75, 4.0, 5.0, 6.0, 7.0, 8.0, 12.0, 16.0 and 24.0 hours post-dose in each period under
yellow monochromatic light.
36 healthy volunteers were randomised into the study and 33 completed.
Primary pharmacokinetic variables were AUC0-t, AUC0-∞ and Cmax. Secondary parameters were AUC0t/AUC0-∞,
tmax, Kel, and t½. Safety was also analysed.
90% CIs for AUC0-t and Cmax are to be within 80-125% in order to conclude bioequivalence.
4/7