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Open Dose Escalating Trial to Determine the Maximum Tolerated Dose in Paediatric Patients With Advanced Cancers for Whom no Therapy is Known

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ClinicalTrials.gov Identifier: NCT01971476
Recruitment Status : Completed
First Posted : October 29, 2013
Results First Posted : July 30, 2018
Last Update Posted : July 30, 2018
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Leukemia
Neoplasms
Intervention Drug: volasertib
Enrollment 22
Recruitment Details In the age group 2 to <12 years, 12 patients were entered and treated. In the age group 12 to <18 years, 10 patients were entered and treated.
Pre-assignment Details In the age group 2 to <12 years, 15 patients were screened, with 3 screen failures. In the age group 12 to <18 years, 14 patients were screened, with 4 screen failures.
Arm/Group Title Volasertib 200 mg/m2 Volasertib 250 mg/m2 Volasertib 300 mg/m2
Hide Arm/Group Description The patients were administered Volasertib 200 mg/m2 (solution for infusion) by intravenous infusion over approximately 1 hour (h) on Day 1 of 14-day cycle. The patients were administered Volasertib 250 mg/m2 (solution for infusion) by intravenous infusion over approximately 1 hour on Day 1 of 14-day cycle. The patients were administered Volasertib 300 mg/m2 (solution for infusion) by intravenous infusion over approximately 1 hour on Day 1 of 14-day cycle.
Period Title: Cohort 1: 2 to <12 Years
Started 3 3 6
Completed 0 0 0
Not Completed 3 3 6
Reason Not Completed
Other not defined             3             3             6
Period Title: Cohort 2: 12 to <18 Years
Started 6 4 0
Completed 0 0 0
Not Completed 6 4 0
Reason Not Completed
Other not defined             6             3             0
Adverse Event             0             1             0
Arm/Group Title Volasertib 200 mg/m2 Volasertib 250 mg/m2 Volasertib 300 mg/m2 Total
Hide Arm/Group Description The patients were administered Volasertib 200 mg/m2 (solution for infusion) by intravenous infusion over approximately 1 hour on Day 1 of 14-day cycle. The patients were administered Volasertib 250 mg/m2 (solution for infusion) by intravenous infusion over approximately 1 hour on Day 1 of 14-day cycle. The patients were administered Volasertib 300 mg/m2 (solution for infusion) by intravenous infusion over approximately 1 hour on Day 1 of 14-day cycle. Total of all reporting groups
Overall Number of Baseline Participants 9 7 6 22
Hide Baseline Analysis Population Description
Treated Set: The treated set consisted of all patients who have received at least 1 dose of trial medication at the time of clinical cut-off. 2 to <12 years (N=3, 3, 6). 12 to < 18 years (N=6, 4, 0).
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 9 participants 7 participants 6 participants 22 participants
2 to <12 years 7.0  (3.6) 6.3  (3.1) 7.0  (3.3) 6.8  (3.0)
12 to <18 years 14.3  (2.3) 15.8  (1.5) NA [1]   (NA) 14.9  (2.1)
[1]
No patients entered.
Sex/Gender, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 9 participants 7 participants 6 participants 22 participants
Female (2 to <12 years) 1 2 3 6
Male (2 to <12 years) 2 1 3 6
Female (12 to <18 years) 2 0 0 2
Male (12 to <18 years) 4 4 0 8
1.Primary Outcome
Title Number of Participants With Dose Limiting Toxicities (DLTs) in the First Cycle for the Determination of the Maximum Tolerated Dose (MTD)
Hide Description This outcome measure presents number of participants with DLTs in the first cycle for the determination of MTD. DLTs were defined as drug related Common Terminology Criteria for Adverse Events (CTCAE) ≥Grade 3 (haematological and nonhaematological) Adverse Events (AEs) with the exception of a) Reduced blood cell count (any grade) without associated clinical complications qualifying for DLT. b) Febrile neutropenia Grade 3. c) Infection Grade 3 with neutrophil count <1000/mm3. d) Uric acid Grade ≥3. e) Nausea, vomiting and/or diarrhoea managed by adequate therapy (i.e. recovery to CTCAE Grade ≤2).
Time Frame Up to 14 days.
Hide Outcome Measure Data
Hide Analysis Population Description
Treated Set: The treated set consisted of all patients who have received at least 1 dose of trial medication at the time of clinical cut-off.
Arm/Group Title 2 to <12 Years: Volasertib 200 mg/m2 2 to <12 Years: Volasertib 250 mg/m2 2 to <12 Years: Volasertib 300 mg/m2 12 to <18 Years: Volasertib 200 mg/m2 12 to <18 Years: Volasertib 250 mg/m2 12 to <18 Years: Volasertib 300 mg/m2
Hide Arm/Group Description:
The patients were administered Volasertib 200 mg/m2 (solution for infusion) by intravenous infusion over approximately 1 hour on Day 1 of 14-day cycle.
The patients were administered Volasertib 250 mg/m2 (solution for infusion) by intravenous infusion over approximately 1 hour on Day 1 of 14-day cycle.
The patients were administered Volasertib 300 mg/m2 (solution for infusion) by intravenous infusion over approximately 1 hour on Day 1 of 14-day cycle.
The patients were administered Volasertib 200 mg/m2 (solution for infusion) by intravenous infusion over approximately 1 hour on Day 1 of 14-day cycle.
The patients were administered Volasertib 250 mg/m2 (solution for infusion) by intravenous infusion over approximately 1 hour on Day 1 of 14-day cycle.
The patients were administered Volasertib 300 mg/m2 (solution for infusion) by intravenous infusion over approximately 1 hour on Day 1 of 14-day cycle.
Overall Number of Participants Analyzed 3 3 6 6 4 0
Measure Type: Number
Unit of Measure: Participants
0 0 0 0 2
2.Primary Outcome
Title Maximum Tolerated Dose of Volasertib
Hide Description This outcome measure presents MTD of Volasertib. The MTD was defined as the highest dose level at which DLTs were reported in not more than 1 in 6 evaluable patients during Cycle 1.
Time Frame Up to 14 days.
Hide Outcome Measure Data
Hide Analysis Population Description
Treated Set: The treated set consisted of all patients who have received at least 1 dose of trial medication at the time of clinical cut-off.
Arm/Group Title 12 to <18 Years: Volasertib 300 mg/m2 12 to <18 Years: Volasertib 200 mg/m2
Hide Arm/Group Description:
The patients were administered Volasertib 300 mg/m2 (solution for infusion) by intravenous infusion over approximately 1 hour on Day 1 of 14-day cycle.
The patients were administered Volasertib 200 mg/m2 (solution for infusion) by intravenous infusion over approximately 1 hour on Day 1 of 14-day cycle.
Overall Number of Participants Analyzed 12 10
Measure Type: Number
Unit of Measure: mg
300 200
3.Secondary Outcome
Title Number of Patients With Hepatic Injury Defined as Adverse Events of Special Interest (AESI)
Hide Description This outcome measure presents number of patients with hepatic injury defined as AESI. Hepatic injury was defined by the following alterations of liver parameters: an elevation of Aspartate Transaminase (AST) and/or Alanine Transaminase (ALT) >3x Upper Limit of Normal (ULN) combined with an elevation of total bilirubin >2x ULN measured in the same blood sample.
Time Frame Up to 879 days.
Hide Outcome Measure Data
Hide Analysis Population Description
Treated Set: The treated set consisted of all patients who have received at least 1 dose of trial medication at the time of clinical cut-off.
Arm/Group Title 2 to <12 Years: Volasertib 200 mg/m2 2 to <12 Years: Volasertib 250 mg/m2 2 to <12 Years: Volasertib 300 mg/m2 12 to <18 Years: Volasertib 200 mg/m2 12 to <18 Years: Volasertib 250 mg/m2 12 to <18 Years: Volasertib 300 mg/m2
Hide Arm/Group Description:
The patients were administered Volasertib 200 mg/m2 (solution for infusion) by intravenous infusion over approximately 1 hour on Day 1 of 14-day cycle.
The patients were administered Volasertib 250 mg/m2 (solution for infusion) by intravenous infusion over approximately 1 hour on Day 1 of 14-day cycle.
The patients were administered Volasertib 300 mg/m2 (solution for infusion) by intravenous infusion over approximately 1 hour on Day 1 of 14-day cycle.
The patients were administered Volasertib 200 mg/m2 (solution for infusion) by intravenous infusion over approximately 1 hour on Day 1 of 14-day cycle.
The patients were administered Volasertib 250 mg/m2 (solution for infusion) by intravenous infusion over approximately 1 hour on Day 1 of 14-day cycle.
The patients were administered Volasertib 300 mg/m2 (solution for infusion) by intravenous infusion over approximately 1 hour on Day 1 of 14-day cycle.
Overall Number of Participants Analyzed 3 3 6 6 4 0
Measure Type: Number
Unit of Measure: Participants
Total AEs in grouped category hepatic impairment 0 1 1 3 1
Alanine aminotransferase increased 0 1 0 2 0
Aspartate aminotransferase increased 0 1 0 0 0
Blood alkaline phosphatase increased 0 0 1 0 0
Metabolism and nutrition disorders 0 0 0 0 1
Hypoalbuminaemia 0 0 0 0 1
Hepatobiliary disorders 0 0 0 1 0
Hyperbilirubinaemia 0 0 0 1 0
Blood bilirubin increased 0 0 0 1 0
Gamma-glutamyltransferase increased 0 0 0 1 0
4.Secondary Outcome
Title Number of Patients With Clinically Relevant Laboratory Value Changes of Calcium (Hyper- and/or Hypocalcaemia) as Judged by the Investigator and Reported as AEs, CTCAE Grade ≥3
Hide Description This outcome measure presents number of patients with clinically relevant laboratory value changes of calcium (hyper- and/or hypocalcaemia) as judged by the investigator and reported as AEs, CTCAE Grade ≥3. CTCAE Grade 3 (severe AE), 4 (life-threatening or disabling AE), 5 (death related to AE).
Time Frame Up to 879 days.
Hide Outcome Measure Data
Hide Analysis Population Description
Treated Set: The treated set consisted of all patients who have received at least 1 dose of trial medication at the time of clinical cut-off.
Arm/Group Title 2 to <12 Years: Volasertib 200 mg/m2 2 to <12 Years: Volasertib 250 mg/m2 2 to <12 Years: Volasertib 300 mg/m2 12 to <18 Years: Volasertib 200 mg/m2 12 to <18 Years: Volasertib 250 mg/m2 12 to <18 Years: Volasertib 300 mg/m2
Hide Arm/Group Description:
The patients were administered Volasertib 200 mg/m2 (solution for infusion) by intravenous infusion over approximately 1 hour on Day 1 of 14-day cycle.
The patients were administered Volasertib 250 mg/m2 (solution for infusion) by intravenous infusion over approximately 1 hour on Day 1 of 14-day cycle.
The patients were administered Volasertib 300 mg/m2 (solution for infusion) by intravenous infusion over approximately 1 hour on Day 1 of 14-day cycle.
The patients were administered Volasertib 200 mg/m2 (solution for infusion) by intravenous infusion over approximately 1 hour on Day 1 of 14-day cycle.
The patients were administered Volasertib 250 mg/m2 (solution for infusion) by intravenous infusion over approximately 1 hour on Day 1 of 14-day cycle.
The patients were administered Volasertib 300 mg/m2 (solution for infusion) by intravenous infusion over approximately 1 hour on Day 1 of 14-day cycle.
Overall Number of Participants Analyzed 3 3 6 6 4 0
Measure Type: Number
Unit of Measure: Participants
Total AEs clinically relevant changes of calcium 0 0 0 0 0
Metabolism and nutrition disorders 0 0 0 0 0
Hypocalcaemia 0 0 0 0 0
Hypercalcaemia 0 0 0 0 0
5.Secondary Outcome
Title The Number of Patients With Changes in Cardiac Activity (Prolonged QTc Interval) Reported as Clinically Relevant Observations
Hide Description

This outcome measure presents the number of patients with changes in cardiac activity (prolonged QTc interval) reported as clinically relevant observations to assess cardiac activity based on Electrocardiogram (ECG) recordings (digital, triplicate) before and at the end of each Volasertib administration and at least at 2 more time points within the first 24 hours after end of the first Volasertib administration. Two methods of heart rate correction of the QT interval were used: the fixed corrections Fridericia's correction (QTcF) and Bazett's correction (QTcB).

SMQ: Standardised Medical Dictionary for Regulatory Activities (MedDRA) query.

Time Frame Up to 879 days.
Hide Outcome Measure Data
Hide Analysis Population Description
Treated Set: The treated set consisted of all patients who have received at least 1 dose of trial medication at the time of clinical cut-off.
Arm/Group Title 2 to <12 Years: Volasertib 200 mg/m2 2 to <12 Years: Volasertib 250 mg/m2 2 to <12 Years: Volasertib 300 mg/m2 12 to <18 Years: Volasertib 200 mg/m2 12 to <18 Years: Volasertib 250 mg/m2 12 to <18 Years: Volasertib 300 mg/m2
Hide Arm/Group Description:
The patients were administered Volasertib 200 mg/m2 (solution for infusion) by intravenous infusion over approximately 1 hour on Day 1 of 14-day cycle.
The patients were administered Volasertib 250 mg/m2 (solution for infusion) by intravenous infusion over approximately 1 hour on Day 1 of 14-day cycle.
The patients were administered Volasertib 300 mg/m2 (solution for infusion) by intravenous infusion over approximately 1 hour on Day 1 of 14-day cycle.
The patients were administered Volasertib 200 mg/m2 (solution for infusion) by intravenous infusion over approximately 1 hour on Day 1 of 14-day cycle.
The patients were administered Volasertib 250 mg/m2 (solution for infusion) by intravenous infusion over approximately 1 hour on Day 1 of 14-day cycle.
The patients were administered Volasertib 300 mg/m2 (solution for infusion) by intravenous infusion over approximately 1 hour on Day 1 of 14-day cycle.
Overall Number of Participants Analyzed 3 3 6 6 4 0
Measure Type: Number
Unit of Measure: Participants
Total AEs in the MedDRA SMQ of QT prolongation 0 0 1 2 1
Electrocardiogram QT prolonged 0 0 1 1 1
Cardiac disorders 0 0 0 1 0
Conduction disorder 0 0 0 1 0
6.Secondary Outcome
Title Best Overall Response [in Leukaemia Patients]: (Complete Remission (CR)), CR With Incomplete Neutrophil or Platelet Recovery (CRi), Partial Remission (PR), Stable Disease (SD), Progressive Disease (PD) and Death in Aplasia
Hide Description This outcome measure includes, CR: Bone marrow blasts <5%; absence of blasts with Auer rods; absence of extramedullary (EM) disease; absolute neutrophil count ≥ 1.0 x 109/L (1000/μL); platelet count ≥80 x 109/L (80000/μL); independence of red blood cells transfusions. CRi: All CR criteria except for residual neutropenia (<1.0 x 109/L [1000/μL]) or thrombocytopenia (<800 x 109/L [80000/μL]), independence of red blood cell transfusions not required. PR: Decrease of bone marrow blast percentage to 5%-25%; decrease of pretreatment bone marrow (baseline) blast percentage by at least 50%; absence of EM disease. SD: Neither qualifies for CR, CRi, PR or PD. PD: At least one of the criteria a) 50% increase in bone marrow blast count over baseline b) 50% increase in peripheral blast count over baseline - evidence of new EM disease - clinically PD based on the judgment of the investigator. Death in aplasia: Deaths occurring ≥7 days after last administration of the trial drug while cytopenic.
Time Frame Up to 849 days.
Hide Outcome Measure Data
Hide Analysis Population Description

Treated Set: The treated set consisted of all patients who have received at least 1 dose of trial medication at the time of clinical cut-off.

The number of participants analysed displays the number of participants with available data at the timepoint of interest.

Arm/Group Title 2 to <12 Years: Volasertib 200 mg/m2 2 to <12 Years: Volasertib 250 mg/m2 2 to <12 Years: Volasertib 300 mg/m2 12 to <18 Years: Volasertib 200 mg/m2 12 to <18 Years: Volasertib 250 mg/m2 12 to <18 Years: Volasertib 300 mg/m2
Hide Arm/Group Description:
The patients were administered Volasertib 200 mg/m2 (solution for infusion) by intravenous infusion over approximately 1 hour on Day 1 of 14-day cycle.
The patients were administered Volasertib 250 mg/m2 (solution for infusion) by intravenous infusion over approximately 1 hour on Day 1 of 14-day cycle.
The patients were administered Volasertib 300 mg/m2 (solution for infusion) by intravenous infusion over approximately 1 hour on Day 1 of 14-day cycle.
The patients were administered Volasertib 200 mg/m2 (solution for infusion) by intravenous infusion over approximately 1 hour on Day 1 of 14-day cycle.
The patients were administered Volasertib 250 mg/m2 (solution for infusion) by intravenous infusion over approximately 1 hour on Day 1 of 14-day cycle.
The patients were administered Volasertib 300 mg/m2 (solution for infusion) by intravenous infusion over approximately 1 hour on Day 1 of 14-day cycle.
Overall Number of Participants Analyzed 2 2 0 2 1 0
Measure Type: Number
Unit of Measure: Participants
Complete remission 0 0 0 0
CRi* 0 0 0 0
Partial remission 0 0 0 0
Stable disease 2 2 1 0
Progressive disease 0 0 1 1
Death in aplasia 0 0 0 0
Not evaluable 0 0 0 0
Missing 0 0 0 0
7.Secondary Outcome
Title Event-Free Survival (EFS) [in Leukaemia Patients]
Hide Description EFS was defined as the time from the first infusion of Volasertib to the date of PD or relapse, occurrence of secondary malignancy, or death from any cause, whichever occurred first. EFS was censored at the date of last disease assessment for patients who were not reported with PD, relapse, occurrence of secondary malignancy or death.
Time Frame Up to 849 days.
Hide Outcome Measure Data
Hide Analysis Population Description

Treated Set: The treated set consisted of all patients who have received at least 1 dose of trial medication at the time of clinical cut-off.

The number of participants analysed displays the number of participants with available data at the timepoint of interest.

Arm/Group Title 2 to <12 Years: Volasertib 200 mg/m2 2 to <12 Years: Volasertib 250 mg/m2 2 to <12 Years: Volasertib 300 mg/m2 12 to <18 Years: Volasertib 200 mg/m2 12 to <18 Years: Volasertib 250 mg/m2 12 to <18 Years: Volasertib 300 mg/m2
Hide Arm/Group Description:
The patients were administered Volasertib 200 mg/m2 (solution for infusion) by intravenous infusion over approximately 1 hour on Day 1 of 14-day cycle.
The patients were administered Volasertib 250 mg/m2 (solution for infusion) by intravenous infusion over approximately 1 hour on Day 1 of 14-day cycle.
The patients were administered Volasertib 300 mg/m2 (solution for infusion) by intravenous infusion over approximately 1 hour on Day 1 of 14-day cycle.
The patients were administered Volasertib 200 mg/m2 (solution for infusion) by intravenous infusion over approximately 1 hour on Day 1 of 14-day cycle.
The patients were administered Volasertib 250 mg/m2 (solution for infusion) by intravenous infusion over approximately 1 hour on Day 1 of 14-day cycle.
The patients were administered Volasertib 300 mg/m2 (solution for infusion) by intravenous infusion over approximately 1 hour on Day 1 of 14-day cycle.
Overall Number of Participants Analyzed 2 2 0 2 1 0
Median (95% Confidence Interval)
Unit of Measure: Months
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
Median EFS not estimated due to small number of patients per treatment arm.
8.Secondary Outcome
Title Overall Survival (OS) [in Leukaemia Patients]
Hide Description Overall survival was defined as time from first infusion of Volasertib to death from any cause. For patients who were lost to follow-up, OS were censored on the last date the patients were known to be alive.
Time Frame Up to 849 days.
Hide Outcome Measure Data
Hide Analysis Population Description

Treated Set: The treated set consisted of all patients who have received at least 1 dose of trial medication at the time of clinical cut-off.

The number of participants analysed displays the number of participants with available data at the timepoint of interest.

Arm/Group Title 2 to <12 Years: Volasertib 200 mg/m2 2 to <12 Years: Volasertib 250 mg/m2 2 to <12 Years: Volasertib 300 mg/m2 12 to <18 Years: Volasertib 200 mg/m2 12 to <18 Years: Volasertib 250 mg/m2 12 to <18 Years: Volasertib 300 mg/m2
Hide Arm/Group Description:
The patients were administered Volasertib 200 mg/m2 (solution for infusion) by intravenous infusion over approximately 1 hour on Day 1 of 14-day cycle.
The patients were administered Volasertib 250 mg/m2 (solution for infusion) by intravenous infusion over approximately 1 hour on Day 1 of 14-day cycle.
The patients were administered Volasertib 300 mg/m2 (solution for infusion) by intravenous infusion over approximately 1 hour on Day 1 of 14-day cycle.
The patients were administered Volasertib 200 mg/m2 (solution for infusion) by intravenous infusion over approximately 1 hour on Day 1 of 14-day cycle.
The patients were administered Volasertib 250 mg/m2 (solution for infusion) by intravenous infusion over approximately 1 hour on Day 1 of 14-day cycle.
The patients were administered Volasertib 300 mg/m2 (solution for infusion) by intravenous infusion over approximately 1 hour on Day 1 of 14-day cycle.
Overall Number of Participants Analyzed 2 2 0 2 1 0
Median (95% Confidence Interval)
Unit of Measure: Months
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
Median OS not estimated due to small number of patients per treatment arm.
9.Secondary Outcome
Title Maximum Measured Concentration (Cmax, Norm) of Volasertib
Hide Description This outcome measure presents dose normalized maximum measured concentration of Volasertib in plasma (Cmax, norm).
Time Frame Cycle 1: -0:05 (hour/s: minute/s) before drug administration and 1:00, 1:30, 3:00, 24:00, 96:00, 216:00 after drug administration. Cycle >=2: -0:05 (hour/s: minute/s) before drug administration and 1:00 after drug administration.
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic Set (PKS): All evaluable patients were included in the PK analysis. A patient was considered to be not evaluable, if the patient had an important protocol violation relevant to the evaluation of PK or had insufficient data.
Arm/Group Title 2 to <12 Years: Volasertib 200 mg/m2 2 to <12 Years: Volasertib 250 mg/m2 2 to <12 Years: Volasertib 300 mg/m2 12 to <18 Years: Volasertib 200 mg/m2 12 to <18 Years: Volasertib 250 mg/m2 12 to <18 Years: Volasertib 300 mg/m2
Hide Arm/Group Description:
The patients were administered Volasertib 200 mg/m2 (solution for infusion) by intravenous infusion over approximately 1 hour on Day 1 of 14-day cycle.
The patients were administered Volasertib 250 mg/m2 (solution for infusion) by intravenous infusion over approximately 1 hour on Day 1 of 14-day cycle.
The patients were administered Volasertib 300 mg/m2 (solution for infusion) by intravenous infusion over approximately 1 hour on Day 1 of 14-day cycle.
The patients were administered Volasertib 200 mg/m2 (solution for infusion) by intravenous infusion over approximately 1 hour on Day 1 of 14-day cycle.
The patients were administered Volasertib 250 mg/m2 (solution for infusion) by intravenous infusion over approximately 1 hour on Day 1 of 14-day cycle.
The patients were administered Volasertib 300 mg/m2 (solution for infusion) by intravenous infusion over approximately 1 hour on Day 1 of 14-day cycle.
Overall Number of Participants Analyzed 3 3 6 6 4 0
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL/mg
5.34
(22.0%)
9.71
(128%)
3.60
(35.1%)
2.46
(54.9%)
2.50
(94.6%)
10.Secondary Outcome
Title Trough Concentration (Cpre, 2) of Volasertib
Hide Description

This outcome measure presents pre-dose concentration of Volasertib in plasma immediately before administration of the second dose (Cpre,2).

The number of participants analysed displays the number of participants with available data at the timepoint of interest.

Time Frame Cycle 1: -0:05 (hour/s: minute/s) before drug administration and 1:00, 1:30, 3:00, 24:00, 96:00, 216:00 after drug administration. Cycle >=2: -0:05 (hour/s: minute/s) before drug administration and 1:00 after drug administration.
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic Set: All evaluable patients were included in the PK analysis. A patient was considered to be not evaluable, if the patient had an important protocol violation relevant to the evaluation of PK or had insufficient data. The number of participants analysed are the number of participants with available data at the timepoint of interest.
Arm/Group Title 2 to <12 Years: Volasertib 200 mg/m2 2 to <12 Years: Volasertib 250 mg/m2 2 to <12 Years: Volasertib 300 mg/m2 12 to <18 Years: Volasertib 200 mg/m2 12 to <18 Years: Volasertib 250 mg/m2 12 to <18 Years: Volasertib 300 mg/m2
Hide Arm/Group Description:
The patients were administered Volasertib 200 mg/m2 (solution for infusion) by intravenous infusion over approximately 1 hour on Day 1 of 14-day cycle.
The patients were administered Volasertib 250 mg/m2 (solution for infusion) by intravenous infusion over approximately 1 hour on Day 1 of 14-day cycle.
The patients were administered Volasertib 300 mg/m2 (solution for infusion) by intravenous infusion over approximately 1 hour on Day 1 of 14-day cycle.
The patients were administered Volasertib 200 mg/m2 (solution for infusion) by intravenous infusion over approximately 1 hour on Day 1 of 14-day cycle.
The patients were administered Volasertib 250 mg/m2 (solution for infusion) by intravenous infusion over approximately 1 hour on Day 1 of 14-day cycle.
The patients were administered Volasertib 300 mg/m2 (solution for infusion) by intravenous infusion over approximately 1 hour on Day 1 of 14-day cycle.
Overall Number of Participants Analyzed 3 2 0 0 0 0
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
1.48
(60.3%)
1.13
(17.6%)
11.Secondary Outcome
Title Area Under the Concentration-Time Curve (AUC0-∞, Norm) of Volasertib in Plasma
Hide Description This outcome measure presents dose normalized area under the concentration-time curve of Volasertib in plasma over the time interval from zero extrapolated to infinity.
Time Frame Cycle 1: -0:05 (hour/s: minute/s) before drug administration and 1:00, 1:30, 3:00, 24:00, 96:00, 216:00 after drug administration. Cycle >=2: -0:05 (hour/s: minute/s) before drug administration and 1:00 after drug administration.
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic Set: All evaluable patients were included in the PK analysis. A patient was considered to be not evaluable, if the patient had an important protocol violation relevant to the evaluation of PK or had insufficient data.
Arm/Group Title 2 to <12 Years: Volasertib 200 mg/m2 2 to <12 Years: Volasertib 250 mg/m2 2 to <12 Years: Volasertib 300 mg/m2 12 to <18 Years: Volasertib 200 mg/m2 12 to <18 Years: Volasertib 250 mg/m2 12 to <18 Years: Volasertib 300 mg/m2
Hide Arm/Group Description:
The patients were administered Volasertib 200 mg/m2 (solution for infusion) by intravenous infusion over approximately 1 hour on Day 1 of 14-day cycle.
The patients were administered Volasertib 250 mg/m2 (solution for infusion) by intravenous infusion over approximately 1 hour on Day 1 of 14-day cycle.
The patients were administered Volasertib 300 mg/m2 (solution for infusion) by intravenous infusion over approximately 1 hour on Day 1 of 14-day cycle.
The patients were administered Volasertib 200 mg/m2 (solution for infusion) by intravenous infusion over approximately 1 hour on Day 1 of 14-day cycle.
The patients were administered Volasertib 250 mg/m2 (solution for infusion) by intravenous infusion over approximately 1 hour on Day 1 of 14-day cycle.
The patients were administered Volasertib 300 mg/m2 (solution for infusion) by intravenous infusion over approximately 1 hour on Day 1 of 14-day cycle.
Overall Number of Participants Analyzed 3 3 6 6 4 0
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*h/mL/mg
41.7
(40.1%)
51.2
(69.8%)
36.4
(28.2%)
28.6
(19.0%)
22.1
(37.9%)
12.Secondary Outcome
Title Half-Life (t1/2) of Volasertib
Hide Description This outcome measure presents half-life of Volasertib.
Time Frame Cycle 1: -0:05 (hour/s: minute/s) before drug administration and 1:00, 1:30, 3:00, 24:00, 96:00, 216:00 after drug administration. Cycle >=2: -0:05 (hour/s: minute/s) before drug administration and 1:00 after drug administration.
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic Set: All evaluable patients were included in the PK analysis. A patient was considered to be not evaluable, if the patient had an important protocol violation relevant to the evaluation of PK or had insufficient data.
Arm/Group Title 2 to <12 Years: Volasertib 200 mg/m2 2 to <12 Years: Volasertib 250 mg/m2 2 to <12 Years: Volasertib 300 mg/m2 12 to <18 Years: Volasertib 200 mg/m2 12 to <18 Years: Volasertib 250 mg/m2 12 to <18 Years: Volasertib 300 mg/m2
Hide Arm/Group Description:
The patients were administered Volasertib 200 mg/m2 (solution for infusion) by intravenous infusion over approximately 1 hour on Day 1 of 14-day cycle.
The patients were administered Volasertib 250 mg/m2 (solution for infusion) by intravenous infusion over approximately 1 hour on Day 1 of 14-day cycle.
The patients were administered Volasertib 300 mg/m2 (solution for infusion) by intravenous infusion over approximately 1 hour on Day 1 of 14-day cycle.
The patients were administered Volasertib 200 mg/m2 (solution for infusion) by intravenous infusion over approximately 1 hour on Day 1 of 14-day cycle.
The patients were administered Volasertib 250 mg/m2 (solution for infusion) by intravenous infusion over approximately 1 hour on Day 1 of 14-day cycle.
The patients were administered Volasertib 300 mg/m2 (solution for infusion) by intravenous infusion over approximately 1 hour on Day 1 of 14-day cycle.
Overall Number of Participants Analyzed 3 3 6 6 4 0
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: h
102
(28.6%)
130
(14.1%)
54.8
(27.2%)
78.6
(27.3%)
52.7
(17.7%)
Time Frame From the first drug administration until 30 days after the last drug administration.
Adverse Event Reporting Description Treated Set
 
Arm/Group Title 2 to <12 Years: Volasertib 200 mg/m2 2 to <12 Years: Volasertib 250 mg/m2 2 to <12 Years: Volasertib 300 mg/m2 2 to <12 Years: Volasertib Pooled Total 12 to <18 Years: Volasertib 200 mg/m2 12 to <18 Years: Volasertib 250 mg/m2 12 to <18 Years: Volasertib Pooled Total
Hide Arm/Group Description The patients were administered Volasertib 200 mg/m2 (solution for infusion) by intravenous infusion over approximately 1 hour on Day 1 of 14-day cycle. The patients were administered Volasertib 250 mg/m2 (solution for infusion) by intravenous infusion over approximately 1 hour on Day 1 of 14-day cycle. The patients were administered Volasertib 300 mg/m2 (solution for infusion) by intravenous infusion over approximately 1 hour on Day 1 of 14-day cycle. The pooled total of patients administered Volasertib 200 mg/m2/250 mg/m2/300 mg/m2 (solution for infusion) by intravenous infusion over approximately 1 hour on Day 1 of 14-day cycle. The patients were administered Volasertib 200 mg/m2 (solution for infusion) by intravenous infusion over approximately 1 hour on Day 1 of 14-day cycle. The patients were administered Volasertib 250 mg/m2 (solution for infusion) by intravenous infusion over approximately 1 hour on Day 1 of 1-day cycle. The pooled total of patients administered Volasertib 200 mg/m2/250 mg/m2 (solution for infusion) by intravenous infusion over approximately 1 hour on Day 1 of 14-day cycle.
All-Cause Mortality
2 to <12 Years: Volasertib 200 mg/m2 2 to <12 Years: Volasertib 250 mg/m2 2 to <12 Years: Volasertib 300 mg/m2 2 to <12 Years: Volasertib Pooled Total 12 to <18 Years: Volasertib 200 mg/m2 12 to <18 Years: Volasertib 250 mg/m2 12 to <18 Years: Volasertib Pooled Total
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/--   --/--   --/-- 
Hide Serious Adverse Events
2 to <12 Years: Volasertib 200 mg/m2 2 to <12 Years: Volasertib 250 mg/m2 2 to <12 Years: Volasertib 300 mg/m2 2 to <12 Years: Volasertib Pooled Total 12 to <18 Years: Volasertib 200 mg/m2 12 to <18 Years: Volasertib 250 mg/m2 12 to <18 Years: Volasertib Pooled Total
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   1/3 (33.33%)   1/3 (33.33%)   5/6 (83.33%)   7/12 (58.33%)   6/6 (100.00%)   4/4 (100.00%)   10/10 (100.00%) 
Blood and lymphatic system disorders               
Febrile neutropenia  1  1/3 (33.33%)  1/3 (33.33%)  3/6 (50.00%)  5/12 (41.67%)  2/6 (33.33%)  2/4 (50.00%)  4/10 (40.00%) 
Anaemia  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  1/4 (25.00%)  1/10 (10.00%) 
Bone marrow toxicity  1  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  1/12 (8.33%)  0/6 (0.00%)  0/4 (0.00%)  0/10 (0.00%) 
Leukopenia  1  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  1/12 (8.33%)  0/6 (0.00%)  1/4 (25.00%)  1/10 (10.00%) 
Neutropenia  1  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  1/12 (8.33%)  0/6 (0.00%)  0/4 (0.00%)  0/10 (0.00%) 
Thrombocytopenia  1  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  1/12 (8.33%)  0/6 (0.00%)  1/4 (25.00%)  1/10 (10.00%) 
Gastrointestinal disorders               
Mouth haemorrhage  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  1/10 (10.00%) 
Abdominal pain  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  1/4 (25.00%)  1/10 (10.00%) 
Diarrhoea  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  1/4 (25.00%)  1/10 (10.00%) 
Gastrointestinal haemorrhage  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  1/4 (25.00%)  1/10 (10.00%) 
Vomiting  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/6 (16.67%)  1/4 (25.00%)  2/10 (20.00%) 
Nausea  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  1/10 (10.00%) 
General disorders               
Asthenia  1  0/3 (0.00%)  1/3 (33.33%)  0/6 (0.00%)  1/12 (8.33%)  0/6 (0.00%)  1/4 (25.00%)  1/10 (10.00%) 
Pyrexia  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  1/4 (25.00%)  1/10 (10.00%) 
Infections and infestations               
Abscess neck  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  1/10 (10.00%) 
Pharyngitis  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  1/4 (25.00%)  1/10 (10.00%) 
Soft tissue infection  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  1/10 (10.00%) 
Viral infection  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  1/4 (25.00%)  1/10 (10.00%) 
Injury, poisoning and procedural complications               
Lower limb fracture  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  1/4 (25.00%)  1/10 (10.00%) 
Tongue injury  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  1/4 (25.00%)  1/10 (10.00%) 
Investigations               
Electrocardiogram QT prolonged  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/6 (16.67%)  1/4 (25.00%)  2/10 (20.00%) 
Musculoskeletal and connective tissue disorders               
Myalgia  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  1/4 (25.00%)  1/10 (10.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)               
Malignant neoplasm progression  1  0/3 (0.00%)  0/3 (0.00%)  2/6 (33.33%)  2/12 (16.67%)  1/6 (16.67%)  0/4 (0.00%)  1/10 (10.00%) 
Nervous system disorders               
Haemorrhage intracranial  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  1/4 (25.00%)  1/10 (10.00%) 
Headache  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  2/4 (50.00%)  2/10 (20.00%) 
Paraplegia  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  1/10 (10.00%) 
Renal and urinary disorders               
Haematuria  1  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  1/12 (8.33%)  0/6 (0.00%)  0/4 (0.00%)  0/10 (0.00%) 
Hydronephrosis  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  1/10 (10.00%) 
Renal impairment  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  1/10 (10.00%) 
Respiratory, thoracic and mediastinal disorders               
Pneumonia  1  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  1/12 (8.33%)  0/6 (0.00%)  0/4 (0.00%)  0/10 (0.00%) 
Dyspnoea  1  0/3 (0.00%)  1/3 (33.33%)  0/6 (0.00%)  1/12 (8.33%)  0/6 (0.00%)  0/4 (0.00%)  0/10 (0.00%) 
Pneumonitis  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  1/10 (10.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 18.1
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
2 to <12 Years: Volasertib 200 mg/m2 2 to <12 Years: Volasertib 250 mg/m2 2 to <12 Years: Volasertib 300 mg/m2 2 to <12 Years: Volasertib Pooled Total 12 to <18 Years: Volasertib 200 mg/m2 12 to <18 Years: Volasertib 250 mg/m2 12 to <18 Years: Volasertib Pooled Total
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   3/3 (100.00%)   3/3 (100.00%)   6/6 (100.00%)   12/12 (100.00%)   6/6 (100.00%)   3/4 (75.00%)   9/10 (90.00%) 
Blood and lymphatic system disorders               
Anaemia  1  1/3 (33.33%)  2/3 (66.67%)  3/6 (50.00%)  6/12 (50.00%)  2/6 (33.33%)  1/4 (25.00%)  3/10 (30.00%) 
Leukopenia  1  0/3 (0.00%)  1/3 (33.33%)  0/6 (0.00%)  1/12 (8.33%)  0/6 (0.00%)  0/4 (0.00%)  1/10 (10.00%) 
Lymphadenopathy  1  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  1/12 (8.33%)  0/6 (0.00%)  0/4 (0.00%)  0/10 (0.00%) 
Neutropenia  1  1/3 (33.33%)  0/3 (0.00%)  3/6 (50.00%)  4/12 (33.33%)  3/6 (50.00%)  1/4 (25.00%)  4/10 (40.00%) 
Thrombocytopenia  1  0/3 (0.00%)  2/3 (66.67%)  1/6 (16.67%)  3/12 (25.00%)  3/6 (50.00%)  1/4 (25.00%)  4/10 (40.00%) 
Cardiac disorders               
Conduction disorder  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  1/10 (10.00%) 
Sinus tachycardia  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  1/10 (10.00%) 
Eye disorders               
Visual impairment  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  1/10 (10.00%) 
Gastrointestinal disorders               
Abdominal pain  1  0/3 (0.00%)  1/3 (33.33%)  2/6 (33.33%)  3/12 (25.00%)  2/6 (33.33%)  0/4 (0.00%)  2/10 (20.00%) 
Abdominal pain upper  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  1/10 (10.00%) 
Anal inflammation  1  1/3 (33.33%)  0/3 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  0/6 (0.00%)  0/4 (0.00%)  0/10 (0.00%) 
Aphthous ulcer  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  1/4 (25.00%)  1/10 (10.00%) 
Constipation  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  2/6 (33.33%)  0/4 (0.00%)  2/10 (20.00%) 
Diarrhoea  1  0/3 (0.00%)  1/3 (33.33%)  1/6 (16.67%)  2/12 (16.67%)  0/6 (0.00%)  0/4 (0.00%)  0/10 (0.00%) 
Dyspepsia  1  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  1/12 (8.33%)  0/6 (0.00%)  0/4 (0.00%)  0/10 (0.00%) 
Glossodynia  1  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  1/12 (8.33%)  0/6 (0.00%)  0/4 (0.00%)  0/10 (0.00%) 
Nausea  1  1/3 (33.33%)  0/3 (0.00%)  1/6 (16.67%)  2/12 (16.67%)  2/6 (33.33%)  2/4 (50.00%)  4/10 (40.00%) 
Oral pain  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  1/4 (25.00%)  1/10 (10.00%) 
Stomatitis  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  1/10 (10.00%) 
Vomiting  1  1/3 (33.33%)  0/3 (0.00%)  2/6 (33.33%)  3/12 (25.00%)  2/6 (33.33%)  2/4 (50.00%)  4/10 (40.00%) 
General disorders               
Asthenia  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  1/4 (25.00%)  1/10 (10.00%) 
Chest pain  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/6 (16.67%)  1/4 (25.00%)  2/10 (20.00%) 
Chills  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  1/10 (10.00%) 
Fatigue  1  1/3 (33.33%)  0/3 (0.00%)  1/6 (16.67%)  2/12 (16.67%)  1/6 (16.67%)  2/4 (50.00%)  3/10 (30.00%) 
Influenza like illness  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  1/10 (10.00%) 
Malaise  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  1/4 (25.00%)  1/10 (10.00%) 
Mucosal inflammation  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  1/10 (10.00%) 
Pain  1  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  1/12 (8.33%)  0/6 (0.00%)  0/4 (0.00%)  0/10 (0.00%) 
Pyrexia  1  2/3 (66.67%)  0/3 (0.00%)  0/6 (0.00%)  2/12 (16.67%)  1/6 (16.67%)  1/4 (25.00%)  2/10 (20.00%) 
Hepatobiliary disorders               
Hyperbilirubinaemia  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  1/10 (10.00%) 
Infections and infestations               
Anal abscess  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  1/4 (25.00%)  1/10 (10.00%) 
Conjunctivitis  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  1/10 (10.00%) 
Nasopharyngitis  1  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  1/12 (8.33%)  0/6 (0.00%)  0/4 (0.00%)  0/10 (0.00%) 
Oropharyngeal candidiasis  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  1/10 (10.00%) 
Stoma site infection  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  1/10 (10.00%) 
Injury, poisoning and procedural complications               
Allergic transfusion reaction  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  1/10 (10.00%) 
Investigations               
Activated partial thromboplastin time prolonged  1  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  1/12 (8.33%)  0/6 (0.00%)  0/4 (0.00%)  0/10 (0.00%) 
Alanine aminotransferase decreased  1  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  1/12 (8.33%)  0/6 (0.00%)  0/4 (0.00%)  0/10 (0.00%) 
Alanine aminotransferase increased  1  0/3 (0.00%)  1/3 (33.33%)  0/6 (0.00%)  1/12 (8.33%)  2/6 (33.33%)  0/4 (0.00%)  2/10 (20.00%) 
Antithrombin III decreased  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  1/10 (10.00%) 
Aspartate aminotransferase increased  1  0/3 (0.00%)  1/3 (33.33%)  0/6 (0.00%)  1/12 (8.33%)  0/6 (0.00%)  0/4 (0.00%)  0/10 (0.00%) 
Blood alkaline phosphatase increased  1  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  1/12 (8.33%)  0/6 (0.00%)  0/4 (0.00%)  0/10 (0.00%) 
Blood bilirubin increased  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  1/10 (10.00%) 
Blood creatine increased  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  1/10 (10.00%) 
Blood creatine phosphokinase MB increased  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  1/10 (10.00%) 
Blood creatine phosphokinase increased  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  1/4 (25.00%)  1/10 (10.00%) 
Blood creatinine increased  1  1/3 (33.33%)  0/3 (0.00%)  1/6 (16.67%)  2/12 (16.67%)  1/6 (16.67%)  0/4 (0.00%)  1/10 (10.00%) 
Blood lactate dehydrogenase increased  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  1/10 (10.00%) 
Blood phosphorus decreased  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/6 (16.67%)  1/4 (25.00%)  2/10 (20.00%) 
Blood pressure increased  1  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  1/12 (8.33%)  0/6 (0.00%)  0/4 (0.00%)  0/10 (0.00%) 
Body temperature increased  1  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  1/12 (8.33%)  0/6 (0.00%)  0/4 (0.00%)  0/10 (0.00%) 
Electrocardiogram QT prolonged  1  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  1/12 (8.33%)  0/6 (0.00%)  0/4 (0.00%)  0/10 (0.00%) 
Gamma-glutamyltransferase increased  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  1/10 (10.00%) 
Haemoglobin decreased  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  1/10 (10.00%) 
Lymphocyte count decreased  1  1/3 (33.33%)  0/3 (0.00%)  1/6 (16.67%)  2/12 (16.67%)  1/6 (16.67%)  1/4 (25.00%)  2/10 (20.00%) 
Neutrophil count decreased  1  1/3 (33.33%)  0/3 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  1/6 (16.67%)  1/4 (25.00%)  2/10 (20.00%) 
Platelet count decreased  1  1/3 (33.33%)  0/3 (0.00%)  1/6 (16.67%)  2/12 (16.67%)  1/6 (16.67%)  1/4 (25.00%)  2/10 (20.00%) 
Weight decreased  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  1/10 (10.00%) 
White blood cell count decreased  1  1/3 (33.33%)  0/3 (0.00%)  1/6 (16.67%)  2/12 (16.67%)  1/6 (16.67%)  1/4 (25.00%)  2/10 (20.00%) 
International normalised ration increased  1  0/3 (0.00%)  1/3 (33.33%)  0/6 (0.00%)  1/12 (8.33%)  0/6 (0.00%)  0/4 (0.00%)  0/10 (0.00%) 
Metabolism and nutrition disorders               
Decreased appetite  1  0/3 (0.00%)  1/3 (33.33%)  2/6 (33.33%)  3/12 (25.00%)  0/6 (0.00%)  0/4 (0.00%)  0/10 (0.00%) 
Hypercalcaemia  1  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  1/12 (8.33%)  2/6 (33.33%)  0/4 (0.00%)  2/10 (20.00%) 
Hyperglycaemia  1  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  1/12 (8.33%)  1/6 (16.67%)  1/4 (25.00%)  2/10 (20.00%) 
Hyperkalaemia  1  0/3 (0.00%)  1/3 (33.33%)  0/6 (0.00%)  1/12 (8.33%)  0/6 (0.00%)  1/4 (25.00%)  1/10 (10.00%) 
Hyperuricaemia  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  1/10 (10.00%) 
Hypoalbuminaemia  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  1/4 (25.00%)  1/10 (10.00%) 
Hypoglycaemia  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  1/4 (25.00%)  1/10 (10.00%) 
Hypokalaemia  1  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  1/12 (8.33%)  0/6 (0.00%)  1/4 (25.00%)  1/10 (10.00%) 
Hyponatraemia  1  1/3 (33.33%)  0/3 (0.00%)  1/6 (16.67%)  2/12 (16.67%)  1/6 (16.67%)  1/4 (25.00%)  2/10 (20.00%) 
Hypophosphataemia  1  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  1/12 (8.33%)  0/6 (0.00%)  0/4 (0.00%)  0/10 (0.00%) 
Musculoskeletal and connective tissue disorders               
Arthralgia  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/6 (16.67%)  1/4 (25.00%)  2/10 (20.00%) 
Back pain  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  1/10 (10.00%) 
Groin pain  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  1/10 (10.00%) 
Pain in extremity  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  1/4 (25.00%)  1/10 (10.00%) 
Musculoskeletal chest pain  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  1/10 (10.00%) 
Myalgia  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  1/4 (25.00%)  1/10 (10.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)               
Leukaemia  1  0/3 (0.00%)  1/3 (33.33%)  0/6 (0.00%)  1/12 (8.33%)  0/6 (0.00%)  0/4 (0.00%)  0/10 (0.00%) 
Nervous system disorders               
Cranial nerve disorder  1  1/3 (33.33%)  0/3 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  0/6 (0.00%)  0/4 (0.00%)  0/10 (0.00%) 
Dysaesthesia  1  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  1/12 (8.33%)  0/6 (0.00%)  0/4 (0.00%)  0/10 (0.00%) 
Headache  1  1/3 (33.33%)  0/3 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  1/6 (16.67%)  1/4 (25.00%)  2/10 (20.00%) 
IIIrd nerve disorder  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  1/10 (10.00%) 
Paraesthesia  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  1/4 (25.00%)  1/10 (10.00%) 
Peripheral sensory neuropathy  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  1/10 (10.00%) 
Psychiatric disorders               
Agitation  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  1/10 (10.00%) 
Insomnia  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  1/4 (25.00%)  1/10 (10.00%) 
Renal and urinary disorders               
Oliguria  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  1/10 (10.00%) 
Urinary retention  1  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  1/12 (8.33%)  0/6 (0.00%)  0/4 (0.00%)  0/10 (0.00%) 
Respiratory, thoracic and mediastinal disorders               
Cough  1  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  1/12 (8.33%)  0/6 (0.00%)  1/4 (25.00%)  1/10 (10.00%) 
Epistaxis  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  2/4 (50.00%)  2/10 (20.00%) 
Oropharyngeal pain  1  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  1/12 (8.33%)  0/6 (0.00%)  0/4 (0.00%)  0/10 (0.00%) 
Respiratory disorder  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  1/4 (25.00%)  1/10 (10.00%) 
Respiratory failure  1  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  1/12 (8.33%)  0/6 (0.00%)  0/4 (0.00%)  0/10 (0.00%) 
Rhinorrhoea  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  1/4 (25.00%)  1/10 (10.00%) 
Skin and subcutaneous tissue disorders               
Dermatitis acneiform  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  1/4 (25.00%)  1/10 (10.00%) 
Erythema  1  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  1/12 (8.33%)  0/6 (0.00%)  0/4 (0.00%)  0/10 (0.00%) 
Exfoliative rash  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/6 (16.67%)  0/4 (0.00%)  1/10 (10.00%) 
Ingrowing nail  1  1/3 (33.33%)  0/3 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  0/6 (0.00%)  0/4 (0.00%)  0/10 (0.00%) 
Mechanical urticaria  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  1/4 (25.00%)  1/10 (10.00%) 
Petechiae  1  1/3 (33.33%)  0/3 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  0/6 (0.00%)  1/4 (25.00%)  1/10 (10.00%) 
Pruritus  1  0/3 (0.00%)  1/3 (33.33%)  0/6 (0.00%)  1/12 (8.33%)  1/6 (16.67%)  1/4 (25.00%)  2/10 (20.00%) 
Rash  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  1/4 (25.00%)  1/10 (10.00%) 
Scar pain  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  1/4 (25.00%)  1/10 (10.00%) 
Skin ulcer  1  0/3 (0.00%)  0/3 (0.00%)  1/6 (16.67%)  1/12 (8.33%)  0/6 (0.00%)  0/4 (0.00%)  0/10 (0.00%) 
Vascular disorders               
Hypotension  1  0/3 (0.00%)  0/3 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  0/6 (0.00%)  1/4 (25.00%)  1/10 (10.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 18.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Boehringer Ingelheim Call Center
Organization: Boehringer Ingelheim
Phone: 1-800-243-0127
EMail: clintriage.rdg@boehringer-ingelheim.com
Layout table for additonal information
Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01971476    
Other Study ID Numbers: 1230.27
2013-001291-38 ( EudraCT Number )
First Submitted: October 10, 2013
First Posted: October 29, 2013
Results First Submitted: October 24, 2017
Results First Posted: July 30, 2018
Last Update Posted: July 30, 2018