A Phase I / II Trial of Nintedanib in Asian Hepatocellular Carcinoma Patients

Progression Free Survival (PFS)

PFS by RECIST 1.0 was defined as the duration from date of randomisation to date of progression or death, whichever occurred earlier, based on central independent review.

Time frame: From randomization until data cut-off (16 July 2014); Up to 171 weeks

Overall Survival

Overall survival was defined as the duration from date of randomisation to the date of death.

Time frame: From randomization until data cut-off (16 July 2014); Up to 171 weeks

AUC0-12,ss,Norm (Area Under the Plasma Concentration-time Curve Between 0 and 12 Hours at Steady State, Normalised Values) of Nintedanib

AUC0-12,ss,norm (area under the plasma concentration-time curve between 0 and 12 hours at steady state, normalised values) of Nintedanib Detailed time points of sampling are: Phase I and selected phase II patients in the Nintedanib arm: Cycle 1, Day 15 to 16: Immediately prior to swallowing the dose of nintedanib (predose) and 1 hour (h), 2 h, 3 h, 4 h, 5 h, 7 h, 10 h, 12 h and 24 h after drug administration on Day 15; Cycle 2, Day 1: Immediately prior to swallowing the dose of nintedanib (predose) and 2 h after drug administration on Day 1; Cycle 2, Day 15: Immediately prior to swallowing the dose of nintedanib (predose) and 2 h after drug administration on Day 15.

Time frame: Day1, Day15 and Day 16

AUC0-12,ss,Norm (Area Under the Plasma Concentration-time Curve Between 0 and 12 Hours at Steady State, Normalised Values) of BIBF 1202 (Metabolite of Nintedanib)

AUC0-12,ss,norm (area under the plasma concentration-time curve between 0 and 12 hours at steady state, normalised values) of BIBF 1202 (metabolite of Nintedanib). Detailed time points of sampling are: Phase I and selected phase II patients in the Nintedanib arm: Cycle 1, Day 15 to 16: Immediately prior to swallowing the dose of nintedanib (predose) and 1 hour (h), 2 h, 3 h, 4 h, 5 h, 7 h, 10 h, 12 h and 24 h after drug administration on Day 15; Cycle 2, Day 1: Immediately prior to swallowing the dose of nintedanib (predose) and 2 h after drug administration on Day 1; Cycle 2, Day 15: Immediately prior to swallowing the dose of nintedanib (predose) and 2 h after drug administration on Day 15.

Time frame: Day1, Day15 and Day 16

AUC0-12,ss,Norm (Area Under the Plasma Concentration-time Curve Between 0 and 12 Hours at Steady State, Normalised Values) of BIBF 1202 Glucuronide (Metabolite of Nintedanib)

AUC0-12,ss,norm of BIBF 1202 glucuronide (Metabolite of Nintedanib): Detailed time points of sampling are: Phase I and selected phase II patients in the Nintedanib arm: Cycle 1, Day 15 to 16: Immediately prior to swallowing the dose of nintedanib (predose) and 1 hour (h), 2 h, 3 h, 4 h, 5 h, 7 h, 10 h, 12 h and 24 h after drug administration on Day 15; Cycle 2, Day 1: Immediately prior to swallowing the dose of nintedanib (predose) and 2 h after drug administration on Day 1; Cycle 2, Day 15: Immediately prior to swallowing the dose of nintedanib (predose) and 2 h after drug administration on Day 15.

Time frame: Day1, Day15 and Day 16

Cmax,ss,Norm (Maximum Concentration of the Nintedanib in Plasma at Steady State, Normalised Values)

Cmax,ss,norm (maximum concentration of the Nintedanib in plasma at steady state, normalised values). Detailed time points of sampling are: Phase I and selected phase II patients in the Nintedanib arm: Cycle 1, Day 15 to 16: Immediately prior to swallowing the dose of nintedanib (predose) and 1 hour (h), 2 h, 3 h, 4 h, 5 h, 7 h, 10 h, 12 h and 24 h after drug administration on Day 15; Cycle 2, Day 1: Immediately prior to swallowing the dose of nintedanib (predose) and 2 h after drug administration on Day 1; Cycle 2, Day 15: Immediately prior to swallowing the dose of nintedanib (predose) and 2 h after drug administration on Day 15.

Time frame: Day1, Day15 and Day 16

Cmax,ss,Norm (Maximum Concentration of the BIBF 1202 in Plasma at Steady State, Normalised Values)

Cmax,ss,norm (maximum concentration of the BIBF 1202 in plasma at steady state, normalised values). Detailed time points of sampling are: Phase I and selected phase II patients in the Nintedanib arm: Cycle 1, Day 15 to 16: Immediately prior to swallowing the dose of nintedanib (predose) and 1 hour (h), 2 h, 3 h, 4 h, 5 h, 7 h, 10 h, 12 h and 24 h after drug administration on Day 15; Cycle 2, Day 1: Immediately prior to swallowing the dose of nintedanib (predose) and 2 h after drug administration on Day 1; Cycle 2, Day 15: Immediately prior to swallowing the dose of nintedanib (predose) and 2 h after drug administration on Day 15.

Time frame: Day1, Day15 and Day 16

Cmax,ss,Norm (Maximum Concentration of the BIBF 1202 Glucuronide in Plasma at Steady State, Normalised Values)

Cmax,ss,norm (maximum concentration of the BIBF 1202 glucuronide in plasma at steady state, normalised values). Detailed time points of sampling are: Phase I and selected phase II patients in the Nintedanib arm: Cycle 1, Day 15 to 16: Immediately prior to swallowing the dose of nintedanib (predose) and 1 hour (h), 2 h, 3 h, 4 h, 5 h, 7 h, 10 h, 12 h and 24 h after drug administration on Day 15; Cycle 2, Day 1: Immediately prior to swallowing the dose of nintedanib (predose) and 2 h after drug administration on Day 1; Cycle 2, Day 15: Immediately prior to swallowing the dose of nintedanib (predose) and 2 h after drug administration on Day 15.

Time frame: Day1, Day15 and Day 16

fe0-12,ss (Fraction Excreted in Urine Between 0 and 12 Hours at Steady State) for Nintedanib

fe0-12,ss (fraction excreted in urine between 0 and 12 hours at steady state) for Nintedanib. The reported value corresponds to the percentage of administered dose.

Time frame: 0 to 4 hours (h), 4 to 12 h, and 12 to 24 h after nintedanib