Volasertib + Decitabine in Patients With Acute Myeloid Leukemia (AML)
Study Details
Study Description
Brief Summary
Dose Escalation (MTD Finding) Phase: To investigate the maximum tolerated dose (MTD), safety and pharmacokinetics of different volasertib administration schedules in combination with decitabine in previously untreated AML patients >= 65 years of age who are considered ineligible for standard intensive therapy, or patients with relapsed or refractory AML regardless of prior treatment status.
MTD Extension Phase: To collect additional data on safety, efficacy and pharmacokinetics of volasertib in combination with decitabine in previously untreated patients with AML >= 65 years of age and considered ineligible for standard intensive therapy.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: volasertib + decitabine dose escalation and MTD (Maximum Tolerated Dose) Extension (Note: Decitabine is a Backbone Treatment and Volasertib is Investigational Medicinal Product (IMP)) |
Drug: decitabine iv
decitabine iv fixed dose
Drug: volasertib iv infusion
volasertib iv infusion (Body Surface Area (BSA) based dosing)
|
Outcome Measures
Primary Outcome Measures
- Determination of the Maximum Tolerated Dose (MTD) Based on the Occurrence of Dose-limiting Toxicity (DLT) in Cycle 1 [4 weeks]
The primary objective of the dose-escalation part of this study was to determine the MTD of volasertib in combination with decitabine. The MTD was to be identified based on the DLT information collected during the first treatment cycle of each dosing schedule. DLT was defined as a non-haematological drug-related toxicity of Common Terminology Criteria for Adverse Events (CTCAE) grade ≥3. The MTD corresponded to the highest dose of volasertib and decitabine at which the incidence of DLT was ≤17% (i.e. 1/6 patients) during Cycle 1.
- Number of Subjects With Dose Limiting Toxicities (DLT) in Cycle 1 [4 weeks]
Number of subjects with Dose Limiting Toxicities (DLT) in Cycle 1 is presented
Eligibility Criteria
Criteria
Inclusion criteria:
-
Dose Escalation Phase: patients with previously untreated AML, relapsed or refractory AML regardless of prior treatment status.
-
MTD Extension Phase: previously untreated AML (prior treatment for Myelodysplastic Syndrome(MDS) is allowed).
-
Age >= 65 years.
-
Previously untreated patients must be ineligible for receiving standard intensive therapy at the time of enrolment, in the opinion of the investigator and based on documented medical reasons.
-
Histologically or cytologically confirmed AML (except for APL, FAB (French-American-British)subtype M3) according to the World Health Organisation classification.
-
Eastern co-operative oncology group (ECOG) performance score =< 1 at screening.
-
Signed and dated written informed consent by start date of Screening Visit in accordance with Good Clinical Practice and local legislation.
Exclusion criteria:
-
MTD Extension Phase: Prior chemotherapy for AML (except for hydroxyurea). Patients can receive treatment with hydroxyurea in order to reduce high White Blood Cells count for no more than 28 days (cumulative); discontinuation of hydroxyurea at least one day prior to the study treatment is required. Please note that any prior therapy for MDS is allowed.
-
Acute promyelocytic leukemia (APL, FAB subtype M3), according to World Health Organisation classification.
-
Hypersensitivity to the trial drugs.
-
Other malignancy currently requiring active therapy (except for hormonal/anti-hormonal treatment, e.g. in prostate or breast cancer).
-
Known clinical central nervous system (CNS) symptoms deemed by the investigator to be related to leukemic CNS involvement.
-
QTcF (QT interval corrected for heart rate by the Fridericia formula) > 470 ms, calculated as the mean value of the triplicates taken at least 2 minutes apart at baseline or QTcF prolongation deemed clinically relevant by the investigator.
-
Baseline Left Ventricular Ejection Fraction of < 45% or below the lower limit of institutional normal range.
-
Aspartate amino transferase (AST) or alanine amino transferase (ALT) > 2.5 x the upper limit of normal (ULN). Patients with elevated liver enzyme(s) due to leukemic involvement are allowed up to = 5 x the ULN.
-
Total bilirubin > 1.5 x ULN. For patients with Gilbert's syndrome or elevation due to hepatic infiltrate, total bilirubin must be <4 x ULN.
-
Creatinine clearance (CLcr) < 30 ml/min (estimated creatinine clearance by the Cockcroft-Gault (C-G) equation.
-
Severe illness or organ dysfunction involving the kidneys, liver or other organ system, including active uncontrolled infection, which in the opinion of the investigator precludes treatment with decitabine or would interfere with the evaluation of the safety of the study treatment.
-
Presence of clinically relevant cardiovascular abnormalities such as uncontrolled hypertension, congestive heart failure New York Heart Association (NYHA) Classification of 3, unstable angina or poorly controlled arrhythmia as determined by the investigator. Myocardial infarction within 6 months prior to study entry.
-
Significant concurrent psychiatric disorder or social situation that according to the investigator's judgment would compromise patient's safety or compliance, interfere with consent, study participation, or interpretation of study results.
-
Patients with a systemic fungal, bacterial, viral, or other infection that is not controlled.
-
Contraindications for decitabine treatment according to the manufacturer's prescribing information provided in the Investigator Site File
-
Female patients of childbearing potential who are sexually active and unwilling to use a medically acceptable method of contraception during the trial and for a minimum of 6 months after completion of study treatment.
-
Male patients with partners of childbearing potential who are unwilling to use condoms in combination with a second medically acceptable method of contraception during the trial and for a minimum of 6 months after completion of study treatment.
-
Pregnant or breast feeding patients.
-
Treatment with any investigational drug within 2 weeks of administration of first study medication dose or within less than five half -lives of the investigational drug before treatment with the present trial drug, whichever is shorter, and / or persistence of toxicities of prior anti-leukemic therapies which are deemed clinically relevant.
-
Prior treatment with a Plk inhibitor such as volasertib or treatment in a clinical trial using a Plk inhibitory compound.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Yale Cancer Center | New Haven | Connecticut | United States | 06510 |
| 2 | Washington School of Medicine | Saint Louis | Missouri | United States | 63110 |
| 3 | The University of Texas MD Anderson Cancer Center | Houston | Texas | United States | 77030 |
Sponsors and Collaborators
- Boehringer Ingelheim
Investigators
- Study Chair: Boehringer Ingelheim, Boehringer Ingelheim
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- 1230.30
- 2013-001752-36
Study Results
Participant Flow
| Recruitment Details | It was originally planned to enter 127 patients into this trial; however, the development of volasertib was discontinued during the conduct of the study. |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Volasertib 300 mg + Decitabine | Volasertib 350 mg + Decitabine | Volasertib 400 mg + Decitabine |
|---|---|---|---|
| Arm/Group Description | Patients were treated according to dosing Schedule A in which decitabine (Dacogen®; solution for infusion) 20 mg/m2 was to be administered (Intravenous infusion) for the first 5 consecutive days of the treatment cycle (Day 1 to Day 5). Volasertib 300 mg (solution for infusion) was administered (Intravenous infusion) on Days 1 and 15 of the treatment cycle. The duration of a treatment cycle was 28 days. Number of treatment cycles was unlimited until the patient met criteria for stopping study medication. | Patients were treated according to dosing Schedule A in which decitabine (Dacogen®; solution for infusion) 20 mg/m2 was to be administered (Intravenous infusion) for the first 5 consecutive days of the treatment cycle (Day 1 to Day 5). Volasertib 350 mg (solution for infusion) was administered (Intravenous infusion) on Days 1 and 15 of the treatment cycle. The duration of a treatment cycle was 28 days. Number of treatment cycles was unlimited until the patient met criteria for stopping study medication. | Patients were treated according to dosing Schedule A in which decitabine (Dacogen®; solution for infusion) 20 mg/m2 was to be administered (Intravenous infusion) for the first 5 consecutive days of the treatment cycle (Day 1 to Day 5). Volasertib 400 mg (solution for infusion) was administered (Intravenous infusion) on Days 1 and 15 of the treatment cycle. The duration of a treatment cycle was 28 days. Number of treatment cycles was unlimited until the patient met criteria for stopping study medication. |
| Period Title: Overall Study | |||
| STARTED | 3 | 4 | 6 |
| COMPLETED | 0 | 0 | 0 |
| NOT COMPLETED | 3 | 4 | 6 |
Baseline Characteristics
| Arm/Group Title | Volasertib 300 mg + Decitabine | Volasertib 350 mg + Decitabine | Volasertib 400 mg + Decitabine | Total |
|---|---|---|---|---|
| Arm/Group Description | Patients were treated according to dosing Schedule A in which decitabine (Dacogen®; solution for infusion) 20 mg/m2 was to be administered (Intravenous infusion) for the first 5 consecutive days of the treatment cycle (Day 1 to Day 5). Volasertib 300 mg (solution for infusion) was administered (Intravenous infusion) on Days 1 and 15 of the treatment cycle. The duration of a treatment cycle was 28 days. Number of treatment cycles was unlimited until the patient met criteria for stopping study medication. | Patients were treated according to dosing Schedule A in which decitabine (Dacogen®; solution for infusion) 20 mg/m2 was to be administered (Intravenous infusion) for the first 5 consecutive days of the treatment cycle (Day 1 to Day 5). Volasertib 350 mg (solution for infusion) was administered (Intravenous infusion) on Days 1 and 15 of the treatment cycle. The duration of a treatment cycle was 28 days. Number of treatment cycles was unlimited until the patient met criteria for stopping study medication. | Patients were treated according to dosing Schedule A in which decitabine (Dacogen®; solution for infusion) 20 mg/m2 was to be administered (Intravenous infusion) for the first 5 consecutive days of the treatment cycle (Day 1 to Day 5). Volasertib 400 mg (solution for infusion) was administered (Intravenous infusion) on Days 1 and 15 of the treatment cycle. The duration of a treatment cycle was 28 days. Number of treatment cycles was unlimited until the patient met criteria for stopping study medication. | Total of all reporting groups |
| Overall Participants | 3 | 4 | 6 | 13 |
| Age (years) [Median (Full Range) ] | ||||
| Median (Full Range) [years] |
71.0
|
76.0
|
69.5
|
73.0
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
3
100%
|
1
25%
|
2
33.3%
|
6
46.2%
|
| Male |
0
0%
|
3
75%
|
4
66.7%
|
7
53.8%
|
Outcome Measures
| Title | Determination of the Maximum Tolerated Dose (MTD) Based on the Occurrence of Dose-limiting Toxicity (DLT) in Cycle 1 |
|---|---|
| Description | The primary objective of the dose-escalation part of this study was to determine the MTD of volasertib in combination with decitabine. The MTD was to be identified based on the DLT information collected during the first treatment cycle of each dosing schedule. DLT was defined as a non-haematological drug-related toxicity of Common Terminology Criteria for Adverse Events (CTCAE) grade ≥3. The MTD corresponded to the highest dose of volasertib and decitabine at which the incidence of DLT was ≤17% (i.e. 1/6 patients) during Cycle 1. |
| Time Frame | 4 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| TS. One patient treated with volasertib 350 mg + decitabine had to be excluded because they did not receive all planned doses of volasertib and could therefore not be included in the calculation of MTD. Thus overall 12 patients were analysed instead of 13 patients. |
| Arm/Group Title | Volasertib + Decitabine |
|---|---|
| Arm/Group Description | Patients were treated according to dosing Schedule A in which decitabine (Dacogen®; solution for infusion) was to be administered (Intravenous infusion) for the first 5 consecutive days of the treatment cycle (Day 1 to Day 5). Volasertib (solution for infusion) was administered (Intravenous infusion) on Days 1 and 15 of the treatment cycle. The duration of a treatment cycle was 28 days. Number of treatment cycles was unlimited until the patient met criteria for stopping study medication. |
| Measure Participants | 12 |
| Number [Milligram (mg)] |
400
|
| Title | Number of Subjects With Dose Limiting Toxicities (DLT) in Cycle 1 |
|---|---|
| Description | Number of subjects with Dose Limiting Toxicities (DLT) in Cycle 1 is presented |
| Time Frame | 4 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| TS. One patient treated with volasertib 350 mg + decitabine had to be excluded because they did not receive all planned doses of volasertib and could therefore not be included in the calculation of MTD. Thus 3 patients were analysed instead of 4 patients for volasertib 350 mg + decitabine arm. |
| Arm/Group Title | Volasertib 300 mg + Decitabine | Volasertib 350 mg + Decitabine | Volasertib 400 mg + Decitabine |
|---|---|---|---|
| Arm/Group Description | Patients were treated according to dosing Schedule A in which decitabine (Dacogen®; solution for infusion) 20 mg/m2 was to be administered (Intravenous infusion) for the first 5 consecutive days of the treatment cycle (Day 1 to Day 5). Volasertib 300 mg (solution for infusion) was administered (Intravenous infusion) on Days 1 and 15 of the treatment cycle. The duration of a treatment cycle was 28 days. Number of treatment cycles was unlimited until the patient met criteria for stopping study medication. | Patients were treated according to dosing Schedule A in which decitabine (Dacogen®; solution for infusion) 20 mg/m2 was to be administered (Intravenous infusion) for the first 5 consecutive days of the treatment cycle (Day 1 to Day 5). Volasertib 350 mg (solution for infusion) was administered (Intravenous infusion) on Days 1 and 15 of the treatment cycle. The duration of a treatment cycle was 28 days. Number of treatment cycles was unlimited until the patient met criteria for stopping study medication. | Patients were treated according to dosing Schedule A in which decitabine (Dacogen®; solution for infusion) 20 mg/m2 was to be administered (Intravenous infusion) for the first 5 consecutive days of the treatment cycle (Day 1 to Day 5). Volasertib 400 mg (solution for infusion) was administered (Intravenous infusion) on Days 1 and 15 of the treatment cycle. The duration of a treatment cycle was 28 days. Number of treatment cycles was unlimited until the patient met criteria for stopping study medication. |
| Measure Participants | 3 | 3 | 6 |
| Number [participant] |
0
|
0
|
1
|
Adverse Events
| Time Frame | All Adverse events with an onset after the first dose of study medication up to a period of 30 days after the last administration of study medication; up to 333 days | |||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||
| Arm/Group Title | Volasertib 300 mg + Decitabine | Volasertib 350 mg + Decitabine | Volasertib 400 mg + Decitabine | Total | ||||
| Arm/Group Description | Patients were treated according to dosing Schedule A in which decitabine (Dacogen®; solution for infusion) 20 mg/m2 was to be administered (Intravenous infusion) for the first 5 consecutive days of the treatment cycle (Day 1 to Day 5). Volasertib 300 mg (solution for infusion) was administered (Intravenous infusion) on Days 1 and 15 of the treatment cycle. The duration of a treatment cycle was 28 days. Number of treatment cycles was unlimited until the patient met criteria for stopping study medication. | Patients were treated according to dosing Schedule A in which decitabine (Dacogen®; solution for infusion) 20 mg/m2 was to be administered (Intravenous infusion) for the first 5 consecutive days of the treatment cycle (Day 1 to Day 5). Volasertib 350 mg (solution for infusion) was administered (Intravenous infusion) on Days 1 and 15 of the treatment cycle. The duration of a treatment cycle was 28 days. Number of treatment cycles was unlimited until the patient met criteria for stopping study medication. | Patients were treated according to dosing Schedule A in which decitabine (Dacogen®; solution for infusion) 20 mg/m2 was to be administered (Intravenous infusion) for the first 5 consecutive days of the treatment cycle (Day 1 to Day 5). Volasertib 400 mg (solution for infusion) was administered (Intravenous infusion) on Days 1 and 15 of the treatment cycle. The duration of a treatment cycle was 28 days. Number of treatment cycles was unlimited until the patient met criteria for stopping study medication. | Total of all arms | ||||
All Cause Mortality |
||||||||
| Volasertib 300 mg + Decitabine | Volasertib 350 mg + Decitabine | Volasertib 400 mg + Decitabine | Total | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||
Serious Adverse Events |
||||||||
| Volasertib 300 mg + Decitabine | Volasertib 350 mg + Decitabine | Volasertib 400 mg + Decitabine | Total | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 3/3 (100%) | 4/4 (100%) | 6/6 (100%) | 13/13 (100%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Anaemia | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 1/13 (7.7%) | ||||
| Febrile neutropenia | 3/3 (100%) | 1/4 (25%) | 4/6 (66.7%) | 8/13 (61.5%) | ||||
| Neutropenia | 0/3 (0%) | 1/4 (25%) | 0/6 (0%) | 1/13 (7.7%) | ||||
| Pancytopenia | 2/3 (66.7%) | 0/4 (0%) | 0/6 (0%) | 2/13 (15.4%) | ||||
| Cardiac disorders | ||||||||
| Acute myocardial infarction | 0/3 (0%) | 1/4 (25%) | 0/6 (0%) | 1/13 (7.7%) | ||||
| Cardiac failure congestive | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 1/13 (7.7%) | ||||
| Supraventricular tachycardia | 0/3 (0%) | 1/4 (25%) | 0/6 (0%) | 1/13 (7.7%) | ||||
| Tachycardia | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 1/13 (7.7%) | ||||
| Gastrointestinal disorders | ||||||||
| Peritoneal haemorrhage | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 1/13 (7.7%) | ||||
| General disorders | ||||||||
| Asthenia | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 1/13 (7.7%) | ||||
| Chills | 0/3 (0%) | 1/4 (25%) | 0/6 (0%) | 1/13 (7.7%) | ||||
| Fatigue | 0/3 (0%) | 2/4 (50%) | 0/6 (0%) | 2/13 (15.4%) | ||||
| Mucosal inflammation | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 1/13 (7.7%) | ||||
| Pyrexia | 0/3 (0%) | 1/4 (25%) | 0/6 (0%) | 1/13 (7.7%) | ||||
| Infections and infestations | ||||||||
| Lung infection | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 1/13 (7.7%) | ||||
| Neutropenic infection | 0/3 (0%) | 1/4 (25%) | 0/6 (0%) | 1/13 (7.7%) | ||||
| Pneumonia | 1/3 (33.3%) | 3/4 (75%) | 2/6 (33.3%) | 6/13 (46.2%) | ||||
| Pneumonia fungal | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 1/13 (7.7%) | ||||
| Sepsis | 1/3 (33.3%) | 0/4 (0%) | 1/6 (16.7%) | 2/13 (15.4%) | ||||
| Skin infection | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 1/13 (7.7%) | ||||
| Urinary tract infection | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 1/13 (7.7%) | ||||
| Viral infection | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 1/13 (7.7%) | ||||
| Injury, poisoning and procedural complications | ||||||||
| Subdural haematoma | 0/3 (0%) | 1/4 (25%) | 0/6 (0%) | 1/13 (7.7%) | ||||
| Investigations | ||||||||
| Alanine aminotransferase increased | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 1/13 (7.7%) | ||||
| Ejection fraction decreased | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 1/13 (7.7%) | ||||
| Electrocardiogram QT prolonged | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 1/13 (7.7%) | ||||
| Neutrophil count decreased | 0/3 (0%) | 1/4 (25%) | 0/6 (0%) | 1/13 (7.7%) | ||||
| Platelet count decreased | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 1/13 (7.7%) | ||||
| Metabolism and nutrition disorders | ||||||||
| Decreased appetite | 0/3 (0%) | 1/4 (25%) | 0/6 (0%) | 1/13 (7.7%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| Muscular weakness | 2/3 (66.7%) | 0/4 (0%) | 0/6 (0%) | 2/13 (15.4%) | ||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
| Malignant neoplasm progression | 1/3 (33.3%) | 0/4 (0%) | 0/6 (0%) | 1/13 (7.7%) | ||||
| Psychiatric disorders | ||||||||
| Delirium | 1/3 (33.3%) | 0/4 (0%) | 0/6 (0%) | 1/13 (7.7%) | ||||
| Mental status changes | 0/3 (0%) | 1/4 (25%) | 0/6 (0%) | 1/13 (7.7%) | ||||
| Renal and urinary disorders | ||||||||
| Acute kidney injury | 1/3 (33.3%) | 0/4 (0%) | 1/6 (16.7%) | 2/13 (15.4%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Acute respiratory failure | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 1/13 (7.7%) | ||||
| Atelectasis | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 1/13 (7.7%) | ||||
| Pleural effusion | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 1/13 (7.7%) | ||||
| Respiratory failure | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 1/13 (7.7%) | ||||
Other (Not Including Serious) Adverse Events |
||||||||
| Volasertib 300 mg + Decitabine | Volasertib 350 mg + Decitabine | Volasertib 400 mg + Decitabine | Total | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 3/3 (100%) | 4/4 (100%) | 6/6 (100%) | 13/13 (100%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Anaemia | 0/3 (0%) | 2/4 (50%) | 0/6 (0%) | 2/13 (15.4%) | ||||
| Leukopenia | 0/3 (0%) | 1/4 (25%) | 0/6 (0%) | 1/13 (7.7%) | ||||
| Thrombocytopenia | 1/3 (33.3%) | 0/4 (0%) | 0/6 (0%) | 1/13 (7.7%) | ||||
| Cardiac disorders | ||||||||
| Sinus tachycardia | 1/3 (33.3%) | 0/4 (0%) | 1/6 (16.7%) | 2/13 (15.4%) | ||||
| Eye disorders | ||||||||
| Conjunctival haemorrhage | 0/3 (0%) | 1/4 (25%) | 0/6 (0%) | 1/13 (7.7%) | ||||
| Dry eye | 0/3 (0%) | 1/4 (25%) | 0/6 (0%) | 1/13 (7.7%) | ||||
| Retinal haemorrhage | 0/3 (0%) | 1/4 (25%) | 0/6 (0%) | 1/13 (7.7%) | ||||
| Gastrointestinal disorders | ||||||||
| Abdominal tenderness | 1/3 (33.3%) | 0/4 (0%) | 0/6 (0%) | 1/13 (7.7%) | ||||
| Constipation | 0/3 (0%) | 1/4 (25%) | 2/6 (33.3%) | 3/13 (23.1%) | ||||
| Diarrhoea | 1/3 (33.3%) | 1/4 (25%) | 2/6 (33.3%) | 4/13 (30.8%) | ||||
| Dyspepsia | 0/3 (0%) | 1/4 (25%) | 1/6 (16.7%) | 2/13 (15.4%) | ||||
| Dysphagia | 0/3 (0%) | 2/4 (50%) | 0/6 (0%) | 2/13 (15.4%) | ||||
| Flatulence | 0/3 (0%) | 1/4 (25%) | 0/6 (0%) | 1/13 (7.7%) | ||||
| Gastrointestinal haemorrhage | 0/3 (0%) | 1/4 (25%) | 0/6 (0%) | 1/13 (7.7%) | ||||
| Gastrooesophageal reflux disease | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 1/13 (7.7%) | ||||
| Gingival bleeding | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 1/13 (7.7%) | ||||
| Gingival pain | 0/3 (0%) | 1/4 (25%) | 0/6 (0%) | 1/13 (7.7%) | ||||
| Melaena | 0/3 (0%) | 1/4 (25%) | 0/6 (0%) | 1/13 (7.7%) | ||||
| Mouth haemorrhage | 1/3 (33.3%) | 1/4 (25%) | 0/6 (0%) | 2/13 (15.4%) | ||||
| Nausea | 1/3 (33.3%) | 2/4 (50%) | 1/6 (16.7%) | 4/13 (30.8%) | ||||
| Oral mucosa haematoma | 0/3 (0%) | 1/4 (25%) | 0/6 (0%) | 1/13 (7.7%) | ||||
| Oral pain | 0/3 (0%) | 1/4 (25%) | 0/6 (0%) | 1/13 (7.7%) | ||||
| Vomiting | 0/3 (0%) | 1/4 (25%) | 2/6 (33.3%) | 3/13 (23.1%) | ||||
| General disorders | ||||||||
| Asthenia | 0/3 (0%) | 2/4 (50%) | 1/6 (16.7%) | 3/13 (23.1%) | ||||
| Chest pain | 0/3 (0%) | 1/4 (25%) | 1/6 (16.7%) | 2/13 (15.4%) | ||||
| Chills | 1/3 (33.3%) | 0/4 (0%) | 1/6 (16.7%) | 2/13 (15.4%) | ||||
| Face oedema | 0/3 (0%) | 1/4 (25%) | 0/6 (0%) | 1/13 (7.7%) | ||||
| Fatigue | 2/3 (66.7%) | 0/4 (0%) | 1/6 (16.7%) | 3/13 (23.1%) | ||||
| Mucosal inflammation | 1/3 (33.3%) | 0/4 (0%) | 0/6 (0%) | 1/13 (7.7%) | ||||
| Oedema | 1/3 (33.3%) | 0/4 (0%) | 0/6 (0%) | 1/13 (7.7%) | ||||
| Oedema peripheral | 2/3 (66.7%) | 0/4 (0%) | 0/6 (0%) | 2/13 (15.4%) | ||||
| Pain | 0/3 (0%) | 1/4 (25%) | 0/6 (0%) | 1/13 (7.7%) | ||||
| Pyrexia | 1/3 (33.3%) | 0/4 (0%) | 0/6 (0%) | 1/13 (7.7%) | ||||
| Hepatobiliary disorders | ||||||||
| Hyperbilirubinaemia | 0/3 (0%) | 1/4 (25%) | 1/6 (16.7%) | 2/13 (15.4%) | ||||
| Infections and infestations | ||||||||
| Anal infection | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 1/13 (7.7%) | ||||
| Bacteraemia | 2/3 (66.7%) | 0/4 (0%) | 0/6 (0%) | 2/13 (15.4%) | ||||
| Bacterial infection | 1/3 (33.3%) | 0/4 (0%) | 0/6 (0%) | 1/13 (7.7%) | ||||
| Enterococcal bacteraemia | 1/3 (33.3%) | 0/4 (0%) | 0/6 (0%) | 1/13 (7.7%) | ||||
| Hordeolum | 1/3 (33.3%) | 0/4 (0%) | 0/6 (0%) | 1/13 (7.7%) | ||||
| Klebsiella bacteraemia | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 1/13 (7.7%) | ||||
| Pneumonia | 1/3 (33.3%) | 0/4 (0%) | 0/6 (0%) | 1/13 (7.7%) | ||||
| Rash pustular | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 1/13 (7.7%) | ||||
| Upper respiratory tract infection | 1/3 (33.3%) | 0/4 (0%) | 0/6 (0%) | 1/13 (7.7%) | ||||
| Injury, poisoning and procedural complications | ||||||||
| Animal scratch | 0/3 (0%) | 1/4 (25%) | 0/6 (0%) | 1/13 (7.7%) | ||||
| Contusion | 1/3 (33.3%) | 0/4 (0%) | 1/6 (16.7%) | 2/13 (15.4%) | ||||
| Mouth injury | 1/3 (33.3%) | 0/4 (0%) | 0/6 (0%) | 1/13 (7.7%) | ||||
| Investigations | ||||||||
| Aspartate aminotransferase increased | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 1/13 (7.7%) | ||||
| Blood bilirubin increased | 0/3 (0%) | 1/4 (25%) | 1/6 (16.7%) | 2/13 (15.4%) | ||||
| Blood creatine phosphokinase increased | 1/3 (33.3%) | 0/4 (0%) | 0/6 (0%) | 1/13 (7.7%) | ||||
| Blood creatinine increased | 0/3 (0%) | 1/4 (25%) | 0/6 (0%) | 1/13 (7.7%) | ||||
| Electrocardiogram QT prolonged | 1/3 (33.3%) | 0/4 (0%) | 0/6 (0%) | 1/13 (7.7%) | ||||
| International normalised ratio increased | 0/3 (0%) | 1/4 (25%) | 0/6 (0%) | 1/13 (7.7%) | ||||
| Neutrophil count decreased | 0/3 (0%) | 1/4 (25%) | 0/6 (0%) | 1/13 (7.7%) | ||||
| Urinary casts present | 0/3 (0%) | 1/4 (25%) | 0/6 (0%) | 1/13 (7.7%) | ||||
| White blood cell count decreased | 0/3 (0%) | 1/4 (25%) | 0/6 (0%) | 1/13 (7.7%) | ||||
| Metabolism and nutrition disorders | ||||||||
| Decreased appetite | 1/3 (33.3%) | 1/4 (25%) | 3/6 (50%) | 5/13 (38.5%) | ||||
| Electrolyte imbalance | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 1/13 (7.7%) | ||||
| Failure to thrive | 0/3 (0%) | 1/4 (25%) | 0/6 (0%) | 1/13 (7.7%) | ||||
| Hyperalbuminaemia | 0/3 (0%) | 1/4 (25%) | 0/6 (0%) | 1/13 (7.7%) | ||||
| Hyperglycaemia | 0/3 (0%) | 1/4 (25%) | 0/6 (0%) | 1/13 (7.7%) | ||||
| Hypernatraemia | 0/3 (0%) | 1/4 (25%) | 0/6 (0%) | 1/13 (7.7%) | ||||
| Hypoalbuminaemia | 0/3 (0%) | 1/4 (25%) | 0/6 (0%) | 1/13 (7.7%) | ||||
| Hypocalcaemia | 0/3 (0%) | 2/4 (50%) | 0/6 (0%) | 2/13 (15.4%) | ||||
| Hypokalaemia | 0/3 (0%) | 2/4 (50%) | 1/6 (16.7%) | 3/13 (23.1%) | ||||
| Hypomagnesaemia | 0/3 (0%) | 1/4 (25%) | 0/6 (0%) | 1/13 (7.7%) | ||||
| Hyponatraemia | 0/3 (0%) | 1/4 (25%) | 1/6 (16.7%) | 2/13 (15.4%) | ||||
| Hypophosphataemia | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 1/13 (7.7%) | ||||
| Tumour lysis syndrome | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 1/13 (7.7%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| Back pain | 1/3 (33.3%) | 0/4 (0%) | 1/6 (16.7%) | 2/13 (15.4%) | ||||
| Joint swelling | 1/3 (33.3%) | 0/4 (0%) | 1/6 (16.7%) | 2/13 (15.4%) | ||||
| Muscle spasms | 1/3 (33.3%) | 0/4 (0%) | 0/6 (0%) | 1/13 (7.7%) | ||||
| Musculoskeletal pain | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 1/13 (7.7%) | ||||
| Musculoskeletal stiffness | 1/3 (33.3%) | 0/4 (0%) | 0/6 (0%) | 1/13 (7.7%) | ||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
| Lipoma | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 1/13 (7.7%) | ||||
| Nervous system disorders | ||||||||
| Dizziness | 1/3 (33.3%) | 0/4 (0%) | 0/6 (0%) | 1/13 (7.7%) | ||||
| Hypoaesthesia | 1/3 (33.3%) | 0/4 (0%) | 0/6 (0%) | 1/13 (7.7%) | ||||
| Lethargy | 1/3 (33.3%) | 1/4 (25%) | 0/6 (0%) | 2/13 (15.4%) | ||||
| Psychiatric disorders | ||||||||
| Anxiety | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 1/13 (7.7%) | ||||
| Confusional state | 1/3 (33.3%) | 0/4 (0%) | 0/6 (0%) | 1/13 (7.7%) | ||||
| Delirium | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 1/13 (7.7%) | ||||
| Depression | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 1/13 (7.7%) | ||||
| Insomnia | 0/3 (0%) | 1/4 (25%) | 1/6 (16.7%) | 2/13 (15.4%) | ||||
| Renal and urinary disorders | ||||||||
| Chronic kidney disease | 0/3 (0%) | 1/4 (25%) | 0/6 (0%) | 1/13 (7.7%) | ||||
| Renal failure | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 1/13 (7.7%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Cough | 2/3 (66.7%) | 0/4 (0%) | 1/6 (16.7%) | 3/13 (23.1%) | ||||
| Dyspnoea | 0/3 (0%) | 3/4 (75%) | 2/6 (33.3%) | 5/13 (38.5%) | ||||
| Epistaxis | 0/3 (0%) | 1/4 (25%) | 1/6 (16.7%) | 2/13 (15.4%) | ||||
| Haemoptysis | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 1/13 (7.7%) | ||||
| Hiccups | 0/3 (0%) | 1/4 (25%) | 0/6 (0%) | 1/13 (7.7%) | ||||
| Nasal congestion | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 1/13 (7.7%) | ||||
| Pleurisy | 1/3 (33.3%) | 0/4 (0%) | 0/6 (0%) | 1/13 (7.7%) | ||||
| Pulmonary alveolar haemorrhage | 0/3 (0%) | 1/4 (25%) | 0/6 (0%) | 1/13 (7.7%) | ||||
| Rhinorrhoea | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 1/13 (7.7%) | ||||
| Skin and subcutaneous tissue disorders | ||||||||
| Erythema | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 1/13 (7.7%) | ||||
| Petechiae | 0/3 (0%) | 1/4 (25%) | 0/6 (0%) | 1/13 (7.7%) | ||||
| Pruritus | 0/3 (0%) | 1/4 (25%) | 0/6 (0%) | 1/13 (7.7%) | ||||
| Purpura | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 1/13 (7.7%) | ||||
| Rash | 2/3 (66.7%) | 1/4 (25%) | 0/6 (0%) | 3/13 (23.1%) | ||||
| Rash papular | 0/3 (0%) | 0/4 (0%) | 1/6 (16.7%) | 1/13 (7.7%) | ||||
| Skin lesion | 1/3 (33.3%) | 0/4 (0%) | 0/6 (0%) | 1/13 (7.7%) | ||||
| Urticaria | 0/3 (0%) | 1/4 (25%) | 0/6 (0%) | 1/13 (7.7%) | ||||
| Vascular disorders | ||||||||
| Haemorrhage | 0/3 (0%) | 1/4 (25%) | 0/6 (0%) | 1/13 (7.7%) | ||||
| Hypertension | 1/3 (33.3%) | 0/4 (0%) | 2/6 (33.3%) | 3/13 (23.1%) | ||||
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
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
| Name/Title | Boehringer Ingelheim, Call Center |
|---|---|
| Organization | Boehringer Ingelheim |
| Phone | 1-800-243-0127 |
| clintriage.rdg@boehringer-ingelheim.com |
- 1230.30
- 2013-001752-36