Neoplasm
Conditions
Brief summary
The primary objective of this trial is: Part A \- To determine the Maximum tolerated dose (MTD) and/or the recommended dose (RD) of BI 891065 monotherapy for further development in Asian patients with advanced solid tumours Part B \- To determine the MTD and/or the RD of BI 891065 in combination with a fixed dose of BI 754091 at 240 mg for further development in Asian patients with advanced solid tumours The secondary objectives are: Part A \- To document the safety and tolerability, and characterise pharmacokinetics (PK) of BI 891065 as monotherapy in Asian patients with advanced solid tumours Part B \- To document the safety and tolerability, and characterise PK of the combination therapy of BI 891065 and BI 754091 in Asian patients with advanced solid tumours
Interventions
DRUGBI 891065
film-coated tablets
Sponsors
Boehringer Ingelheim
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Of legal age (according to local legislation) at screening. No upper limit. * Signed and dated written informed consent in accordance with International Council on Harmonisation (ICH) Good Clinical Practice (GCP) and local legislation prior to admission to the trial. * Male or female patients. Women of childbearing potential (WOCBP) and men able to father a child must be ready and able to use highly effective methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly, starting with the screening visit and through 6 months after the last dose of study treatment. A list of contraception methods meeting these criteria is provided in the patient information. The requirement of contraception does not apply to women of no childbearing potential and men not able to father a child, but they must have an evidence of such at screening. * Eastern Cooperative Oncology Group (ECOG) performance status: 0 to 1 * Patients with a confirmed diagnosis of advanced, unresectable and/or metastatic solid tumours, who have failed standard treatment, or for whom no therapy of proven efficacy exists, or who are not amenable to standard therapies. * Presence of at least one measureable lesion according to Response Evaluation Criteria In Solid Tumours (RECIST) 1.1. * Life expectancy of at least 12 weeks after the start of the treatment according to the Investigator's judgement * For Part B: Patients must have at least 1 tumour lesion amenable to biopsy, and must be willing to undergo a biopsy prior to first treatment and after 3 weeks while on therapy. * For Part B: Patients with following cancer types: bladder, colon, breast, NSCLC, ovarian, pancreatic, renal, esophagogastric, sarcoma, prostate, and melanoma
Exclusion criteria
* Major surgeries (major according to the Investigator's assessment) performed within 12 weeks prior to the first administration or planned within 12 months after screening (e.g., hip replacement), or moderate surgeries (moderate according to the Investigator's assessment) performed within 4 weeks prior to the first administration. * Presence of active invasive cancers other than the one treated in this trial within 5 years prior to screening, except for appropriately treated basal cell carcinoma of the skin, or in situ carcinoma of uterine cervix, or other local tumours considered cured by local treatment * Patients who must or wish to continue the intake of restricted medications or any drug considered likely to interfere with the safe conduct of the trial * Previous administration of BI 891065 or other Second Mitochondrial Activator of Caspases (SMAC) mimetic/IAP inhibitor * Patients who have been treated with any other anticancer drug or investigational drug, within 4 weeks or within 5 half-life periods (whichever is shorter) prior to first administration of BI 891065 * Persistent toxicity from previous treatments that has not resolved to ≤ Grade 1 (except for alopecia and Grade 2 neuropathy due to previous treatments) * Active, known or suspected autoimmune disease except vitiligo or resolved asthma/atopy * (Part B only) Patients removed from previous anti-Programmed-cell-death-protein-1 (PD-1) or anti-Programmed-cell-death ligand-1 (PD-L1) therapy because of a severe immune-related adverse event (irAE) * History (including current) of interstitial lung disease or pneumonitis within 5 years * Any of the following cardiac criteria: * Mean resting corrected QT interval (QTcF) \>480 msec * Any clinically important abnormalities (as assessed by the investigator) in rhythm, conduction, or morphology of resting Electrocardiograms (ECGs), e.g., complete left bundle branch block, third degree heart block * Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalaemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years-of-age, or any concomitant medication with known or possible risk of QT interval prolongation * Patients with an ejection fraction (EF) of either \<50% or less than the lower limit of normal of the institutional standard will be excluded, whichever is lower. Only in cases where the Investigator (or the treating physician or both) suspects cardiac disease with negative effect on the EF, will the EF be measured during screening using an appropriate method according to local standards to confirm eligibility (e.g., echocardiogram \[ECHO\], multi-gated acquisition scan \[MUGA\]). A historic measurement of EF no older than 6 months prior to first administration of study drug can be accepted provided that there is clinical evidence that the EF value has not worsened since this measurement in the opinion of the Investigator or of the treating physician or both * Inadequate organ function or bone marrow reserve as demonstrated by the following laboratory values: * Absolute neutrophil count (ANC) \<1.5 x 109/L (\<1500/mm\^3) * Platelet count \<100 x 10\^9/L (\<100,000/mm\^3) * Haemoglobin \<9.0 g/dL * Alanine transaminase (ALT) \>3 times the upper limit of normal (ULN) if no demonstrable liver lesion(s) (primary or metastases) or \>5 times ULN in the presence of liver lesion(s) * Aspartate aminotransferase (AST) \>3 times the ULN if no demonstrable liver lesion(s) or \>5 times ULN in the presence of liver lesion(s) * Total bilirubin \>1.5 times ULN, except for patients with Gilbert's syndrome who are excluded if total bilirubin \>3.0 times ULN or direct bilirubin \>1.5 times ULN * Serum creatinine \> 1.5 x ULN (measured by enzymatic assay, Isotope dilution mass spectroscopy \[IDMS\] standardised Jaffe assay, or non-IDMS Jaffe assay). If serum creatinine is \> 1.5 x ULN, patient is eligible if concurrent estimated glomerular filtration rate (eGFR) is ≥ 30 mL/min/1.73m\^3 (measured or calculated by Chronic Kidney Disease Epidemiology \[CKD-EPI\] formula) * Human immunodeficiency virus (HIV) infection. Test results obtained in routine diagnostics are acceptable if done within 6 months before the informed consent date. * Any of the following laboratory evidence of hepatitis virus infection. * Positive results of hepatitis B surface (HBs) antigen * Presence of hepatitis B core (HBc) antibody together with hepatitis virus B (HBV) Deoxyribonucleic acid (DNA) * Presence of hepatitis virus C (HCV) antibody together with HCV Ribonucleic acid (RNA) In Part A, test results obtained in routine clinical practice are acceptable if done within 6 months before the informed consent date. * Known relevant hypersensitivity to the trial drugs or their excipients based on the investigator's assessment * Serious concomitant disease or medical condition affecting compliance with trial requirements or which are considered relevant for the evaluation of the efficacy or safety of the trial drug, such as cardiac, neurologic, psychiatric, infectious disease or active ulcers (gastro-intestinal tract, skin) or laboratory abnormality that may increase the risk associated with trial participation or trial drug administration, and in the judgment of the Investigator would make the patient inappropriate for entry into the trial. * Chronic alcohol or drug abuse or any condition that, in the Investigator's opinion, makes them an unreliable trial patients, unlikely to complete the trial, or unable to comply with the protocol procedures * Women who are pregnant, nursing, or who plan to become pregnant during the trial. Women who are nursing can be enrolled if they stop nursing. In this case, the patient cannot resume nursing even after discontinuation of study treatment. * Untreated brain metastasis(es) that may be considered active. Patients with previously treated brain metastases may participate provided they are stable (i.e., without evidence of Progressive disease (PD) by imaging for at least 4 weeks prior to the first dose of trial treatment, and any neurologic symptoms have returned to baseline), and there is no evidence of new or enlarging brain metastases * Patients with known leptomeningeal disease * Patients receiving systemic treatment with any immunosuppressive medication within 1 week prior to treatment start (steroids of max. 10 mg/day prednisolone equivalent per day are allowed, topical and inhaled steroids are not considered as immunosuppressive).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part A: Number of Patients With Dose Limiting Toxicities (DLTs) in the MTD Evaluation Period | First treatment cycle, 21 days from first administration of BI 891065. | Any of the following adverse events (AEs) were classified as DLTs: Haematologic toxicities: * Any Grade 5 toxicity. * Neutropenia ≥ Grade 4 lasting for \>7 days. * Febrile neutropenia of any duration (absolute neutrophil count (ANC) \<1.0 X 10\^9 cells/Liter (L) and fever ≥38.5°Celsius (C)). * Neutropenia ≥ Grade 3 with documented infection. * Grade 4 thrombocytopenia, or Grade 3 thrombocytopenia with bleeding. * Thrombocytopenia of any Grade which requires platelet transfusions. * Grade 4 anaemia unexplained by underlying disease. * Anaemia of any Grade which requires blood transfusions. Non-haematological toxicities: * Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \>3 times upper level of normal (ULN) and concurrent total bilirubin \>2 times ULN without initial findings of cholestasis. * ≥Grade 4 AST or ALT of any duration. * Any ≥Grade 3 non-haematologic toxicity some exceptions as defined in the protocol. |
| Part A: Maximum Tolerated Dose (MTD) of BI 891065 | First treatment cycle, 21 days from first administration of BI 891065. | Maximum tolerated dose (MTD) of BI 891065 in the Part A of the trial is reported. MTD was defined as the highest dose with less than 25% risk of the true DLT rate being equal or above 33% during the MTD evaluation period. |
| Part A: Number of Patients With Dose Limiting Toxicities (DLTs) During the Treatment Period | From first administration of BI 891065 until the last administration + 30 days of residual effect period, up to 1164 days. | Any of the following adverse events (AEs) were classified as DLTs: Haematologic toxicities: * Any Grade 5 toxicity. * Neutropenia ≥ Grade 4 lasting for \>7 days. * Febrile neutropenia of any duration (absolute neutrophil count (ANC) \<1.0 X 10\^9 cells/Liter (L) and fever ≥38.5°Celsius (C)). * Neutropenia ≥ Grade 3 with documented infection. * Grade 4 thrombocytopenia, or Grade 3 thrombocytopenia with bleeding. * Thrombocytopenia of any Grade which requires platelet transfusions. * Grade 4 anaemia unexplained by underlying disease. * Anaemia of any Grade which requires blood transfusions. Non-haematological toxicities: * Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \>3 times upper level of normal (ULN) and concurrent total bilirubin \>2 times ULN without initial findings of cholestasis. * ≥Grade 4 AST or ALT of any duration. * Any ≥Grade 3 non-haematologic toxicity some exceptions as defined in the protocol. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Measured Concentration in Plasma of BI 891065 After Administration of the First Dose (Cmax) | Within 5 minutes before and 0.5 hours (h), 1h, 2h, 3h, 5h, 6h, 7h, 8h, 10h, 24h, 36h and 48h after first BI 891065 administration. | Maximum measured concentration in plasma of BI 891065 after administration of the first dose (Cmax) is reported. |
| Part A: Area Under the Concentration-time Curve of BI 891065 in Plasma Over a Uniform Dosing Interval τ at Steady State (AUCτ,ss) | Within 5 minutes before and 0.5 hours (h), 1h, 2h, 3h, 5h, 6h, 7h, 8h, 10h and 24 h after drug administration of BI 891065 on Day 15 of Cycle 1. | Area under the concentration-time curve of BI 891065 in plasma over a uniform dosing interval τ at steady state (AUCτ,ss) is reported. τ=24 hours (h) for the once daily dosing arms and τ=12 h for the twice daily dosing arm. |
| Part A: Maximum Measured Concentration in Plasma of BI 891065 at Steady State (Cmax,ss) | Within 5 minutes before and 0.5 hours (h), 1h, 2h, 3h, 5h, 6h, 7h, 8h, 10h and 24 h after drug administration of BI 891065 on Day 15 of Cycle 1. | Maximum measured concentration in plasma of BI 891065 at steady state (Cmax,ss) is reported. |
| Part A: Area Under the Concentration-time Curve of BI 891065 in Plasma 24 Hours After Administration of the First Dose (AUC0-24) | Within 5 minutes before and 0.5 hours (h), 1h, 2h, 3h, 5h, 6h, 7h, 8h, 10h and 24h after first administration of BI 891065 on Day 1 of Cycle 1. | Area under the concentration-time curve of BI 891065 in plasma 24 hours after administration of the first dose (AUC0-24) is reported. |
Countries
Japan
Participant flow
Recruitment details
This trial was designed as a Phase I, open-label, non-randomised, uncontrolled, multicentre trial to determine the maximum tolerated dose (MTD) or recommended dose of BI 891065, administered as single agent in Part A and in combination with 240 mg of BI 754091 (ezabenlimab) in Part B. After completion of Part A of the trial, Part B of the trial was cancelled as a whole.
Pre-assignment details
All subjects were screened for eligibility prior to participation in the trial. Subjects attended a specialist site which ensured that they (the subjects) strictly met all inclusion and none of the exclusion criteria. Subjects were not to be allocated to a treatment group if any of the entry criteria were violated.
Participants by arm
| Arm | Count |
|---|---|
| Part A: 100 mg BI 891065 QD Patients with a confirmed diagnosis of advanced, unresectable, and/or metastatic solid tumours were administered once daily (QD) orally 100 milligrams (mg) of BI 891065, composed of two 50 mg film-coated tablets, with 240 milliliters (mL) of water. | 3 |
| Part A: 200 mg BI 891065 QD Patients with a confirmed diagnosis of advanced, unresectable, and/or metastatic solid tumours were administered once daily (QD) orally 200 mg of BI 891065, composed of four 50 mg film-coated tablets, with 240 mL of water. | 3 |
| Part A: 200 mg BI 891065 BID Patients with a confirmed diagnosis of advanced, unresectable, and/or metastatic solid tumours were administered twice daily (BID) orally 200 mg of BI 891065, composed of four 50 mg film-coated tablets, with 240 mL of water. | 6 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Clinical disease progression | 0 | 0 | 1 |
| Overall Study | Objective disease progression | 3 | 2 | 5 |
Baseline characteristics
| Characteristic | Part A: 100 mg BI 891065 QD | Part A: 200 mg BI 891065 QD | Part A: 200 mg BI 891065 BID | Total |
|---|---|---|---|---|
| Age, Continuous | 53.0 years STANDARD_DEVIATION 12.1 | 45.7 years STANDARD_DEVIATION 7.5 | 54.8 years STANDARD_DEVIATION 10.2 | 52.1 years STANDARD_DEVIATION 10 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 3 Participants | 6 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 3 Participants | 6 Participants | 12 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 2 Participants | 1 Participants | 5 Participants | 8 Participants |
| Sex: Female, Male Male | 1 Participants | 2 Participants | 1 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 3 | 0 / 6 |
| other Total, other adverse events | 3 / 3 | 3 / 3 | 6 / 6 |
| serious Total, serious adverse events | 0 / 3 | 0 / 3 | 2 / 6 |
Outcome results
Primary
Part A: Maximum Tolerated Dose (MTD) of BI 891065
Maximum tolerated dose (MTD) of BI 891065 in the Part A of the trial is reported. MTD was defined as the highest dose with less than 25% risk of the true DLT rate being equal or above 33% during the MTD evaluation period.
Time frame: First treatment cycle, 21 days from first administration of BI 891065.
Population: The MTD evaluation set included all patients who were documented to have received at least one dose of trial medication and were considered evaluable for MTD evaluation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: 100 mg BI 891065 QD | Part A: Maximum Tolerated Dose (MTD) of BI 891065 | NA milligram |
Primary
Part A: Number of Patients With Dose Limiting Toxicities (DLTs) During the Treatment Period
Any of the following adverse events (AEs) were classified as DLTs: Haematologic toxicities: * Any Grade 5 toxicity. * Neutropenia ≥ Grade 4 lasting for \>7 days. * Febrile neutropenia of any duration (absolute neutrophil count (ANC) \<1.0 X 10\^9 cells/Liter (L) and fever ≥38.5°Celsius (C)). * Neutropenia ≥ Grade 3 with documented infection. * Grade 4 thrombocytopenia, or Grade 3 thrombocytopenia with bleeding. * Thrombocytopenia of any Grade which requires platelet transfusions. * Grade 4 anaemia unexplained by underlying disease. * Anaemia of any Grade which requires blood transfusions. Non-haematological toxicities: * Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \>3 times upper level of normal (ULN) and concurrent total bilirubin \>2 times ULN without initial findings of cholestasis. * ≥Grade 4 AST or ALT of any duration. * Any ≥Grade 3 non-haematologic toxicity some exceptions as defined in the protocol.
Time frame: From first administration of BI 891065 until the last administration + 30 days of residual effect period, up to 1164 days.
Population: The treated set (TS) consisted of all patients who received at least one administration of trial medication.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: 100 mg BI 891065 QD | Part A: Number of Patients With Dose Limiting Toxicities (DLTs) During the Treatment Period | 1 Participants |
| Part A: 200 mg BI 891065 QD | Part A: Number of Patients With Dose Limiting Toxicities (DLTs) During the Treatment Period | 0 Participants |
| Part A: 200 mg BI 891065 BID | Part A: Number of Patients With Dose Limiting Toxicities (DLTs) During the Treatment Period | 2 Participants |
Primary
Part A: Number of Patients With Dose Limiting Toxicities (DLTs) in the MTD Evaluation Period
Any of the following adverse events (AEs) were classified as DLTs: Haematologic toxicities: * Any Grade 5 toxicity. * Neutropenia ≥ Grade 4 lasting for \>7 days. * Febrile neutropenia of any duration (absolute neutrophil count (ANC) \<1.0 X 10\^9 cells/Liter (L) and fever ≥38.5°Celsius (C)). * Neutropenia ≥ Grade 3 with documented infection. * Grade 4 thrombocytopenia, or Grade 3 thrombocytopenia with bleeding. * Thrombocytopenia of any Grade which requires platelet transfusions. * Grade 4 anaemia unexplained by underlying disease. * Anaemia of any Grade which requires blood transfusions. Non-haematological toxicities: * Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \>3 times upper level of normal (ULN) and concurrent total bilirubin \>2 times ULN without initial findings of cholestasis. * ≥Grade 4 AST or ALT of any duration. * Any ≥Grade 3 non-haematologic toxicity some exceptions as defined in the protocol.
Time frame: First treatment cycle, 21 days from first administration of BI 891065.
Population: The MTD evaluation set included all patients who were documented to have received at least one dose of trial medication and were considered evaluable for MTD evaluation.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: 100 mg BI 891065 QD | Part A: Number of Patients With Dose Limiting Toxicities (DLTs) in the MTD Evaluation Period | 1 Participants |
| Part A: 200 mg BI 891065 QD | Part A: Number of Patients With Dose Limiting Toxicities (DLTs) in the MTD Evaluation Period | 0 Participants |
| Part A: 200 mg BI 891065 BID | Part A: Number of Patients With Dose Limiting Toxicities (DLTs) in the MTD Evaluation Period | 2 Participants |
Comparison: Probability of DLT rate was determined using a Bayesian 2-parameter logistic regression model with overdose control.Bayesian logistic regression model
Comparison: Probability of DLT rate was determined using a Bayesian 2-parameter logistic regression model with overdose control.
Comparison: Probability of DLT rate was determined using a Bayesian 2-parameter logistic regression model with overdose control.
Comparison: Probability of DLT rate was determined using a Bayesian 2-parameter logistic regression model with overdose control.
Comparison: Probability of DLT rate was determined using a Bayesian 2-parameter logistic regression model with overdose control.~The 200 mg BI 891065 BID dose was modelled as equivalent to a 300 mg QD dose in terms of dose-toxicity relationship.
Comparison: Probability of DLT rate was determined using a Bayesian 2-parameter logistic regression model with overdose control.~The 200 mg BI 891065 BID dose was modelled as equivalent to a 300 mg QD dose in terms of dose-toxicity relationship.
Secondary
Maximum Measured Concentration in Plasma of BI 891065 After Administration of the First Dose (Cmax)
Maximum measured concentration in plasma of BI 891065 after administration of the first dose (Cmax) is reported.
Time frame: Within 5 minutes before and 0.5 hours (h), 1h, 2h, 3h, 5h, 6h, 7h, 8h, 10h, 24h, 36h and 48h after first BI 891065 administration.
Population: The pharmacokinetic parameter set (PKS) consisted of all patients in the TS who had at least one PK endpoint that was not excluded due to a protocol deviation relevant to the evaluation of pharmacokinetic (PK) or due to PK non-evaluability.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: 100 mg BI 891065 QD | Maximum Measured Concentration in Plasma of BI 891065 After Administration of the First Dose (Cmax) | 445 nanomole/Liter | Geometric Coefficient of Variation 8.1 |
| Part A: 200 mg BI 891065 QD | Maximum Measured Concentration in Plasma of BI 891065 After Administration of the First Dose (Cmax) | 761 nanomole/Liter | Geometric Coefficient of Variation 48.3 |
| Part A: 200 mg BI 891065 BID | Maximum Measured Concentration in Plasma of BI 891065 After Administration of the First Dose (Cmax) | 1270 nanomole/Liter | Geometric Coefficient of Variation 45.6 |
Secondary
Part A: Area Under the Concentration-time Curve of BI 891065 in Plasma 24 Hours After Administration of the First Dose (AUC0-24)
Area under the concentration-time curve of BI 891065 in plasma 24 hours after administration of the first dose (AUC0-24) is reported.
Time frame: Within 5 minutes before and 0.5 hours (h), 1h, 2h, 3h, 5h, 6h, 7h, 8h, 10h and 24h after first administration of BI 891065 on Day 1 of Cycle 1.
Population: The pharmacokinetic parameter set (PKS) consisted of all patients in the TS who had at least one PK endpoint that was not excluded due to a protocol deviation relevant to the evaluation of pharmacokinetic (PK) or due to PK non-evaluability.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: 100 mg BI 891065 QD | Part A: Area Under the Concentration-time Curve of BI 891065 in Plasma 24 Hours After Administration of the First Dose (AUC0-24) | 5090 hours*nanmole/Liter (h*nmol/L) | Geometric Coefficient of Variation 1.29 |
| Part A: 200 mg BI 891065 QD | Part A: Area Under the Concentration-time Curve of BI 891065 in Plasma 24 Hours After Administration of the First Dose (AUC0-24) | 9410 hours*nanmole/Liter (h*nmol/L) | Geometric Coefficient of Variation 52.1 |
| Part A: 200 mg BI 891065 BID | Part A: Area Under the Concentration-time Curve of BI 891065 in Plasma 24 Hours After Administration of the First Dose (AUC0-24) | 15500 hours*nanmole/Liter (h*nmol/L) | Geometric Coefficient of Variation 34.6 |
Secondary
Part A: Area Under the Concentration-time Curve of BI 891065 in Plasma Over a Uniform Dosing Interval τ at Steady State (AUCτ,ss)
Area under the concentration-time curve of BI 891065 in plasma over a uniform dosing interval τ at steady state (AUCτ,ss) is reported. τ=24 hours (h) for the once daily dosing arms and τ=12 h for the twice daily dosing arm.
Time frame: Within 5 minutes before and 0.5 hours (h), 1h, 2h, 3h, 5h, 6h, 7h, 8h, 10h and 24 h after drug administration of BI 891065 on Day 15 of Cycle 1.
Population: The pharmacokinetic parameter set (PKS) consisted of all patients in the TS who had at least one PK endpoint that was not excluded due to a protocol deviation relevant to the evaluation of pharmacokinetic (PK) or due to PK non-evaluability.~Only participants with evaluable results for this PK parameter are reported.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: 100 mg BI 891065 QD | Part A: Area Under the Concentration-time Curve of BI 891065 in Plasma Over a Uniform Dosing Interval τ at Steady State (AUCτ,ss) | 11500 hours *nanomole/Liter (h*nmol/L) | Geometric Coefficient of Variation 8.21 |
| Part A: 200 mg BI 891065 QD | Part A: Area Under the Concentration-time Curve of BI 891065 in Plasma Over a Uniform Dosing Interval τ at Steady State (AUCτ,ss) | 20500 hours *nanomole/Liter (h*nmol/L) | Geometric Coefficient of Variation 15.1 |
| Part A: 200 mg BI 891065 BID | Part A: Area Under the Concentration-time Curve of BI 891065 in Plasma Over a Uniform Dosing Interval τ at Steady State (AUCτ,ss) | 47200 hours *nanomole/Liter (h*nmol/L) | Geometric Coefficient of Variation 64.8 |
Secondary
Part A: Maximum Measured Concentration in Plasma of BI 891065 at Steady State (Cmax,ss)
Maximum measured concentration in plasma of BI 891065 at steady state (Cmax,ss) is reported.
Time frame: Within 5 minutes before and 0.5 hours (h), 1h, 2h, 3h, 5h, 6h, 7h, 8h, 10h and 24 h after drug administration of BI 891065 on Day 15 of Cycle 1.
Population: The pharmacokinetic parameter set (PKS) consisted of all patients in the TS who had at least one PK endpoint that was not excluded due to a protocol deviation relevant to the evaluation of pharmacokinetic (PK) or due to PK non-evaluability.~Only participants with evaluable results for this PK parameter are reported.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: 100 mg BI 891065 QD | Part A: Maximum Measured Concentration in Plasma of BI 891065 at Steady State (Cmax,ss) | 996 nanomole/Liter (nmol/L) | Geometric Coefficient of Variation 16.7 |
| Part A: 200 mg BI 891065 QD | Part A: Maximum Measured Concentration in Plasma of BI 891065 at Steady State (Cmax,ss) | 1370 nanomole/Liter (nmol/L) | Geometric Coefficient of Variation 15.8 |
| Part A: 200 mg BI 891065 BID | Part A: Maximum Measured Concentration in Plasma of BI 891065 at Steady State (Cmax,ss) | 4630 nanomole/Liter (nmol/L) | Geometric Coefficient of Variation 65.6 |