The main objective of this trial is to assess single dose drug exposure of several newly developed formulation prototypes of Nintedanib compared to Ofev® following oral administration.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
21
Ofev®
Nintedanib formulation 1: Monolithic Nintedanib Modified Release Tablet (MR1) as two Prototypes (MR1-1 and MR1-2).
Nintedanib formulation 2: Polyox Nintedanib Modified Release Tablet (MR2) as two Prototypes (MR2-1 and MR2-2).
Quotient Sciences
Nottingham, United Kingdom
Area Under the Concentration-time Curve of 3 Different Formulations of Nintedanib (MR1, MR2 and Ofev®) in Plasma Over the Time Interval From 0 Extrapolated to Infinity Which Includes Also the Second Nintedanib (Ofev®) Dose of the Day (AUC₀-∞)
The area under the concentration-time curve over the time interval from 0 \[first dose\] extrapolated to infinity (AUC₀-∞) was analyzed in 3 different formulations of Nintedanib (MR1, MR2 and Ofev®) and in two cohorts: * Cohort 1: Nintedanib formulation 1: Monolithic Nintedanib Modified Release Tablet (MR1) as two Prototypes (MR1-1 and MR1-2), * Cohort 2: Nintedanib formulation 2: Polyox Nintedanib Modified Release Tablet (MR2) as two Prototypes (MR2-1 and MR2-2), and each compared to the reference (R) treatment: Nintedanib formulation 3: Ofev® capsules. The adjusted geometric least squares mean and adjusted geometric standard error were calculated by an analysis of variance (ANOVA) model on the logarithmic scale.
Time frame: Within 3 hours (h) prior and 1, 2, 3, 4, 6, 8, 10, 12, 13 (except MR1, MR2), 14, 15, 16, 17 (except R), 18, 20, 22, 24, 34, 48, 58, and 72 h after administration.
Area Under the Concentration-time Curve of 3 Different Formulations of Nintedanib (MR1, MR2 and Ofev®) in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC₀-tz)
The area under the concentration-time curve over the time interval from 0 to the last quantifiable data point (AUC₀-tz) was analyzed in 3 different formulations of Nintedanib (MR1, MR2 and Ofev®) and in two cohorts: * Cohort 1: Nintedanib formulation 1: Monolithic Nintedanib Modified Release Tablet (MR1) as two Prototypes (MR1-1 and MR1-2), * Cohort 2: Nintedanib formulation 2: Polyox Nintedanib Modified Release Tablet (MR2) as two Prototypes (MR2-1 and MR2-2), and each compared to the reference (R) treatment: Nintedanib formulation 3: Ofev® capsules. The adjusted geometric least squares mean and adjusted geometric standard error were calculated by an analysis of variance (ANOVA) model on the logarithmic scale.
Time frame: Within 3 hours (h) prior and 1, 2, 3, 4, 6, 8, 10, 12, 13 (except MR1, MR2), 14, 15, 16, 17 (except R), 18, 20, 22, 24, 34, 48, 58, and 72 h after administration.
Maximum Measured Concentration of 3 Different Formulations of Nintedanib (MR1, MR2 and Ofev®) in Plasma Within the 24h Dosing Interval (Cmax)
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The maximum measured concentration in plasma was analyzed in 3 different formulations of Nintedanib (MR1, MR2 and Ofev®) and in two cohorts: * Cohort 1: Nintedanib formulation 1: Monolithic Nintedanib Modified Release Tablet (MR1) as two Prototypes (MR1-1 and MR1-2), * Cohort 2: Nintedanib formulation 2: Polyox Nintedanib Modified Release Tablet (MR2) as two Prototypes (MR2-1 and MR2-2), and each compared to the reference (R) treatment: Nintedanib formulation 3: Ofev® capsules. The adjusted geometric least squares mean and adjusted geometric standard error were calculated by an analysis of variance (ANOVA) model on the logarithmic scale.
Time frame: Within 3 hours (h) prior and 1.0, 2.0, 3.0, 4.0, 6.0, 8.0, 10.0, 12.0, 13.0 (except MR1, MR2), 14.0, 15.0, 16.0, 17.0 (except R), 18.0, 20.0, 22.0, 24.0, 34.0, 48.0, 58.0, and 72 h after administration
Concentration of 3 Different Formulations of Nintedanib (MR1, MR2 and Ofev®) in Plasma 24 Hours After the First Dose (C₂₄)
The measured concentration in plasma 24 hours after first administration was analyzed in 3 different formulations of Nintedanib (MR1, MR2 and Ofev®) and in two cohorts: * Cohort 1: Nintedanib formulation 1: Monolithic Nintedanib Modified Release Tablet (MR1) as two Prototypes (MR1-1 and MR1-2), * Cohort 2: Nintedanib formulation 2: Polyox Nintedanib Modified Release Tablet (MR2) as two Prototypes (MR2-1 and MR2-2), and each compared to the reference (R) treatment: Nintedanib formulation 3: Ofev® capsules. The adjusted geometric least squares mean and adjusted geometric standard error were calculated by an analysis of variance (ANOVA) model on the logarithmic scale.
Time frame: Within 3 hours (h) prior and 1, 2, 3, 4, 6, 8, 10, 12, 13 (except MR1, MR2), 14, 15, 16, 17 (except R), 18, 20, 22, 24, 34, 48, 58, and 72 h after administration.