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| ID | Type | Description | Link |
|---|---|---|---|
| 2018-002177-21 | EudraCT Number |
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Phase I: To investigate maximum tolerated dose (MTD), safety and tolerability, pharmacokinetics, exploratory biomarker and efficacy of BI 836858 monotherapy in patients with low or intermediate-1 risk myelodysplastic syndromes (MDS) with symptomatic anemia. Phase II: To investigate safety and efficacy of BI 836858 plus Best Supportive Care compared to Best Supportive Care alone in low or intermediate-1 risk MDS patients with symptomatic anemia.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm B | Active Comparator | Best Supportive Care Alone |
|
| Arm A | Experimental | BI 836858 plus Best Supportive Care |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Best Supportive Care | Procedure | At Discretion of the Investigator (Transfusions) |
|
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Tolerated Dose (MTD) (Phase I) | The MTD is defined as the highest dose of BI 836858 with less than 25% risk of the true dose-limiting toxicity (DLT) rate being above 33% during the MTD evaluation period. MTD determination will be based on a Bayesian logistic regression model with overdose control. For any dose-escalation cohort, at least 3 patients (pts) will be required. However, in the case that only 2 pts are evaluable and neither has experienced a DLT within the first cycle (2 administrations - 28 days), then dose-escalation can occur based on these 2 pts. After all pts in a cohort have either experienced a DLT or have been observed for at least one cycle (2 administrations - 28 days) without experiencing a DLT, the Bayesian model will be updated with the newly accumulated data. The MTD may be considered reached if either the posterior probability of the true DLT rate in the target interval (16%-33%) is above 50%, or at least 12 pts have been treated at MTD, including the two expansion cohorts. | From the first administration of BI 836858 to start of the third administration of BI 836858, excluding the day of the third administration of BI 836858, up to 28 days |
| Number of Patients With Dose Limiting Toxicity (DLT) (Phase I) | Dose Limiting Toxicity (DLT):
| From the first administration of BI 836858 to start of the third administration of BI 836858, excluding the day of the third administration of BI 836858, up to 28 days |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Patients With Red Blood Cell (RBC) Transfusion Independency (Phase I) | Number of patients with red blood cell (RBC) Transfusion Independency is presented. Red blood cell (RBC) transfusion independence and platelet transfusion independence will be evaluated in patients who are transfusion dependent at baseline. Percentages will be calculated using all treated patients as the denominator. A patient is considered transfusion independent at baseline if the patient has had no transfusions during the 56 days prior to and including the first day of treatment. Otherwise, the patient is considered to be transfusion dependent. A patient is considered transfusion independent if the patient has had no transfusions over the course of ≥ 56 consecutive days. |
Not provided
Inclusion criteria:
Documented diagnosis of Myelodysplastic Syndromes (MDS) according to World Health Organization (WHO) criteria that meets International Prognostic Scoring System (IPSS) classification of low or intermediate-1 risk disease at screening as determined by microscopic and standard cytogenetic analyses of the bone marrow and peripheral complete blood count (CBC).
Phase I dose escalation: patients who experienced Erythropoiesis-Stimulating Agents (ESA) treatment failure or do not qualify (serum erythropoietin level > 500 U) for ESA treatment, and are refractory to or not amenable or eligible for established MDS therapy (Hypomethylating Agents (HMA), lenalidomide)
Phase I expansion:
Phase II: patients who experienced ESA treatment failure or do not qualify (serum erythropoietin level > 500 U) for ESA treatment. For definition of further details of the phase II patients to be included the protocol will be amended based on Phase I results
Patient is non-responsive to, refractory to, or intolerant of ESAs, or ESAs are contraindicated or unavailable, or a documented serum erythropoietin level of > 500 U/L.
Eastern Cooperative Oncology Group (ECOG) Performance Status <=2.
Age >= 18 years.
Written informed consent which is consistent with International Conference on Harmonization - Good Clinical Practice (ICH-GCP) guidelines and local legislation.
Exclusion criteria:
Women of childbearing potential are defined as females who:
Have experienced menarche and
Are not postmenopausal (12 months with no menses without an alternative medical cause) and
Are not permanently sterilized (e.g. hysterectomy, bilateral oophorectomy or bilateral salpingectomy
Within two weeks (4 weeks for biologics) of first administration of BI 836858, or if the half-life of the previous product is known, within 5 times the half-life, whichever is longer.
Patient has persistent toxicities from prior MDS therapies which are determined to be relevant by the Investigator.
Concomitant treatment with another investigational agent while participating this trial.
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| Name | Affiliation | Role |
|---|---|---|
| Boehringer Ingelheim | Boehringer Ingelheim | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Mayo Clinic Cancer Center | Jacksonville | Florida | 32224 | United States | ||
| H. Lee Moffitt Cancer Center and Research Institute |
Not provided
| Label | URL |
|---|---|
| Related Info | View source |
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Subjects were screened for eligibility prior to participation. They attended a specialist site which ensured that they strictly met all eligibility criteria. Subjects were not to be allocated to a treatment group if any of the entry criteria were violated.
This is a phase I/II, multicenter, open-label, dose escalation and randomized trial of BI 836858 in patients with low or intermediate-1 risk myelodysplastic syndromes.
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| ID | Title | Description |
|---|---|---|
| FG000 | BI 836858 20 mg (Phase I) | All patients were administered doses of BI 836858, 20 milligrams (mg) by a rate-controlled intravenous infusion on day 1 and on day 15 of a 28-day cycle for a duration of 4 cycles. All infusions were to be started at a rate of 10 mL/h. The infusion rate was to be increased every 30 (+/-10) minutes by 10 mL/h to a maximum of 80 mL/h as long as tolerated by the patient. |
| FG001 | BI 836858 40 mg (Phase I) | All patients were administered doses of BI 836858, 40 milligrams (mg) by a rate-controlled intravenous infusion on day 1 and on day 15 of a 28-day cycle for a duration of 4 cycles. All infusions were to be started at a rate of 10 mL/h. The infusion rate was to be increased every 30 (+/-10) minutes by 10 mL/h to a maximum of 80 mL/h as long as tolerated by the patient. |
| FG002 | BI 836858 80 mg (Phase I) | All patients were administered doses of BI 836858, 80 milligrams (mg) by a rate-controlled intravenous infusion on day 1 and on day 15 of a 28-day cycle for a duration of 4 cycles. All infusions were to be started at a rate of 10 mL/h. The infusion rate was to be increased every 30 (+/-10) minutes by 10 mL/h to a maximum of 80 mL/h as long as tolerated by the patient. |
| FG003 | BI 836858 160 mg (Phase I) | All patients were administered doses of BI 836858, 160 milligrams (mg) by a rate-controlled intravenous infusion on day 1 and on day 15 of a 28-day cycle for a duration of 4 cycles. All infusions were to be started at a rate of 10 mL/h. The infusion rate was to be increased every 30 (+/-10) minutes by 10 mL/h to a maximum of 80 mL/h as long as tolerated by the patient. |
| FG004 | BI 836858 320 mg (Phase I) | All patients were administered doses of BI 836858, 320 milligrams (mg) by a rate-controlled intravenous infusion on day 1 and on day 15 of a 28-day cycle for a duration of 4 cycles. All infusions were to be started at a rate of 10 mL/h. The infusion rate was to be increased every 30 (+/-10) minutes by 10 mL/h to a maximum of 80 mL/h as long as tolerated by the patient. |
| FG005 | BI 836858 + Best Supportive Care (BSC) (Phase II) | All patients were planned to be administered doses of BI 836858, recommended phase 2 dose (RP2D) together with best supportive care (BSC) by a rate-controlled intravenous infusion on day 1 and on day 15 of a 28-day cycle for a duration of 4 cycles. All infusions were to be started at a rate of 10 mL/h. The infusion rate was to be increased every 30 (+/-10) minutes by 10 mL/h to a maximum of 80 mL/h as long as tolerated by the patient. |
| FG006 | Best Supportive Care (BSC) Only (Phase II) | All patients were planned to be administered best supportive care (BSC) including red blood cell transfusion, platelet transfusion and iron chelation therapy. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Treated set (TS): The TS included all subjects who had been enrolled and treated with at least 1 dose of study drug. The treated set was used for safety analyses.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | BI 836858 20 mg (Phase I) | All patients were administered doses of BI 836858, 20 milligrams (mg) by a rate-controlled intravenous infusion on day 1 and on day 15 of a 28-day cycle for a duration of 4 cycles. All infusions were to be started at a rate of 10 mL/h. The infusion rate was to be increased every 30 (+/-10) minutes by 10 mL/h to a maximum of 80 mL/h as long as tolerated by the patient. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Maximum Tolerated Dose (MTD) (Phase I) | The MTD is defined as the highest dose of BI 836858 with less than 25% risk of the true dose-limiting toxicity (DLT) rate being above 33% during the MTD evaluation period. MTD determination will be based on a Bayesian logistic regression model with overdose control. For any dose-escalation cohort, at least 3 patients (pts) will be required. However, in the case that only 2 pts are evaluable and neither has experienced a DLT within the first cycle (2 administrations - 28 days), then dose-escalation can occur based on these 2 pts. After all pts in a cohort have either experienced a DLT or have been observed for at least one cycle (2 administrations - 28 days) without experiencing a DLT, the Bayesian model will be updated with the newly accumulated data. The MTD may be considered reached if either the posterior probability of the true DLT rate in the target interval (16%-33%) is above 50%, or at least 12 pts have been treated at MTD, including the two expansion cohorts. | As the study was prematurely discontinued, recruitment of participants into the dose escalation part was not fully completed. No formal MTD was determined. | Posted | From the first administration of BI 836858 to start of the third administration of BI 836858, excluding the day of the third administration of BI 836858, up to 28 days |
From first administration of BI 836858 until end of residual effect period (REP), up to 198 days. For all-cause mortality from first administration of BI 836858 until end of follow-up, up to 198 days + 6 months follow-up.
Treated set (TS): The TS included all subjects who had been enrolled and treated with at least 1 dose of study drug. The treated set was used for safety analyses.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | BI 836858 20mg | All patients were administered doses of BI 836858, 20 milligrams (mg) by a rate-controlled intravenous infusion on day 1 and on day 15 of a 28-day cycle for a duration of 4 cycles. All infusions were to be started at a rate of 10 mL/h. The infusion rate was to be increased every 30 (+/-10) minutes by 10 mL/h to a maximum of 80 mL/h as long as tolerated by the patient. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Acute coronary syndrome | Cardiac disorders | MedDRA 22.1 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 22.1 | Systematic Assessment |
Development of BI 836858 was discontinued (strategic decision) during the Phase I Expansion cohort stage. No patients were enrolled in the Phase II part.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Boehringer Ingelheim, Call Center | Boehringer Ingelheim | 1-800-243-0127 | clintriage.rdg@boehringer-ingelheim.com |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| SAP | No | Yes | No | Statistical Analysis Plan | Jan 7, 2020 | Oct 12, 2020 | SAP_000.pdf |
| Prot | Yes | No | No | Study Protocol | Sep 11, 2019 | Dec 17, 2020 | Prot_001.pdf |
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| ID | Term |
|---|---|
| D009190 | Myelodysplastic Syndromes |
| ID | Term |
|---|---|
| D001855 | Bone Marrow Diseases |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
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| ID | Term |
|---|---|
| C000621731 | BI 836858 |
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| BI 836858 | Drug | Monotherapy with BI 836858 |
|
| Number of Patients With Red Blood Cell (RBC) Transfusion Independency (Phase II) | Red blood cell (RBC) transfusion independence and platelet transfusion independence will be evaluated in patients who are transfusion dependent at baseline. Percentages will be calculated using all treated patients as the denominator. A patient is considered transfusion independent at baseline if the patient has had no transfusions during the 56 days prior to and including the first day of treatment. Otherwise, the patient is considered to be transfusion dependent. A patient is considered transfusion independent if the patient has had no transfusions over the course of ≥ 56 consecutive days. | From first administration of BI 836858 until discontinuation of the treatment. Up to 168 days (6 cycles, each of 28 days) |
| From first administration of BI 836858 until discontinuation of the treatment. Up to 168 days (6 cycles, each of 28 days) |
| Number of Patients With Hematologic Improvement Neutrophils (HI-N) (Phase I) | Number of patients with hematologic improvement neutrophils (HI-N) is presented. The HI will be evaluated in patients with abnormal pretreatment values defined as follows: Neutrophil response (HI-N) - Patients with a pretreatment neutrophil count <1 x 10^9/liters (L) demonstrate a neutrophil response if they have an at least 100 percent increase and an absolute increase >0.5 x 10^9/L. | From first administration of BI 836858 until HI-N, up to 168 days (6 cycles, each of 28 days) |
| Number of Patients With Hematologic Improvement Platelets (HI-P) (Phase I) | Number of patients with hematologic improvement platelets (HI-P) is presented. The HI will be evaluated in patients with abnormal pretreatment values defined as follows: Platelet response (HI-P) - Patients with a pretreatment platelet count <100 x 109/Liters (L) demonstrate a platelet response if there is an absolute platelet increase of ≥30 x 109/L for patients starting with >20 x 109/L platelets. For those with an increase from 10 x 109/L to >20 x 109/L must have an increase of at least 100 percent. | From first administration of BI 836858 until HI-P, up to 168 days (6 cycles, each of 28 days) |
| Number of Patients With Hematologic Improvement Erythroid (HI-E) (Phase I) | Number of patients with hematologic improvement erythroid (HI-E) is presented. The HI will be evaluated in patients with abnormal pretreatment values defined as follows: Erythroid response (HI-E): Patients with a pretreatment hemoglobin <11 grams per deciliters (g/dL) demonstrate erythroid response if their hemoglobin increases by ≥1.5 g/dL for at least eight weeks, and there is a reduction in the units of red cell transfusions by an absolute number of at least four red cell transfusions per eight weeks compared with the pretreatment transfusion number in the previous eight weeks. Only red cell transfusions given for a hemoglobin ≤9 g/dL pretreatment will count in the red cell transfusion response evaluation. | From first administration of BI 836858 until HI-E, up to 168 days (6 cycles, each of 28 days) |
| Time to HI-E Response (Phase I) | Time to HI-E response is defined only for patients who achieve a HI-E response as follows: Time to HI-E response [days] = date of first assessment indicating HI-E response - date of first administration of trial medication + 1. | From first administration of BI 836858 until HI-E response, up to 168 days (6 cycles, each of 28 days) |
| Number of Patients With Mean Hemoglobin Increase ≥ 1.5 g/dL (Phase I) | Number of patients with mean hemoglobin increase ≥ 1.5 grams per deciliters (g/dL) is presented. Mean hemoglobin increase ≥ 1.5 g/dL - Proportion of subjects achieving hemoglobin (Hgb) increase from baseline ≥ 1.5 g/dL over any consecutive 56-day period in absence of Red blood cell (RBC) transfusions. | Up to 48 weeks |
| Duration of Response (RBC Transfusion Independency, HI-N, HI-P, HI-E or Objective Response) (Phase I) | Defined only for patients who achieve complete Response (CR) or marrow complete response (mCR) or RBC Transfusion independency (TI), measured from first date of achieving response until date of relapse. Date of relapse will be earliest of dates of disease assessment (blood sample, bone marrow sample, or clinical assessment) in which relapse was observed. For patients who die or are lost to follow-up without documented relapse, response duration will be censored, respectively, on date of death, regardless of cause, or on date of last disease assessment for patients who are alive when lost to follow-up. Duration of Response [days] = date of outcome - date of first assessment indicating CR or mCR or RBC TI after first administration of trial medication + 1. | From the first date of achieving a response until the date of relapse, up to 168 days (6 cycles, each of 28 days) |
| Number of Patients With Overall Objective Response (OR) [Complete Response (CR), Partial Response (PR), and Hematologic Improvement (HI)] (Phase I) | Number of patients with overall Objective Response (OR) [Complete Response (CR), Partial Response (PR), and Hematologic Improvement (HI)] is presented. Overall Objective Response is defined as Complete Response (CR), Partial Response (PR), HI-N, HI-P, or HI-E. A patient's " Overall Objective Response " = "Yes" if one of these responses was reported at least once throughout the trial. CR defined as: -Bone marrow: <5 % blasts with normal maturation of all cell lines (Dysplastic changes should consider the normal range of dysplastic changes), persistent dysplasia will be noted; -Peripheral blood: Hgb > 11 grams per deciliters (g/dL), Platelets >100 x 109/liters (L), Neutrophils > 1.0 x 109/L, Blasts 0 % PR defined as: -All CR criteria if abnormal before treatment except: Bone marrow blasts decreased by >50 % to pre-treatment but still >5 %, Cellularity and morphology not relevant. HI Definition see other endpoints. | From first administration of BI 836858 until overall objective response, up to 168 days (6 cycles, each of 28 days) |
| Tampa |
| Florida |
| 33612 |
| United States |
| Cleveland Clinic | Cleveland | Ohio | 44195 | United States |
| Universitätsklinikum Carl Gustav Carus Dresden | Dresden | 01307 | Germany |
| Universitätsklinikum Düsseldorf | Düsseldorf | 40225 | Germany |
| Adverse Event |
|
| Progressive disease |
|
| Dose limiting toxicity |
|
| Refused to continue taking medication |
|
| Insurance billing concerns |
|
| BG001 | BI 836858 40 mg (Phase I) | All patients were administered doses of BI 836858, 40 milligrams (mg) by a rate-controlled intravenous infusion on day 1 and on day 15 of a 28-day cycle for a duration of 4 cycles. All infusions were to be started at a rate of 10 mL/h. The infusion rate was to be increased every 30 (+/-10) minutes by 10 mL/h to a maximum of 80 mL/h as long as tolerated by the patient. |
| BG002 | BI 836858 80 mg (Phase I) | All patients were administered doses of BI 836858, 80 milligrams (mg) by a rate-controlled intravenous infusion on day 1 and on day 15 of a 28-day cycle for a duration of 4 cycles. All infusions were to be started at a rate of 10 mL/h. The infusion rate was to be increased every 30 (+/-10) minutes by 10 mL/h to a maximum of 80 mL/h as long as tolerated by the patient. |
| BG003 | BI 836858 160 mg (Phase I) | All patients were administered doses of BI 836858, 160 milligrams (mg) by a rate-controlled intravenous infusion on day 1 and on day 15 of a 28-day cycle for a duration of 4 cycles. All infusions were to be started at a rate of 10 mL/h. The infusion rate was to be increased every 30 (+/-10) minutes by 10 mL/h to a maximum of 80 mL/h as long as tolerated by the patient. |
| BG004 | BI 836858 320 mg (Phase I) | All patients were administered doses of BI 836858, 320 milligrams (mg) by a rate-controlled intravenous infusion on day 1 and on day 15 of a 28-day cycle for a duration of 4 cycles. All infusions were to be started at a rate of 10 mL/h. The infusion rate was to be increased every 30 (+/-10) minutes by 10 mL/h to a maximum of 80 mL/h as long as tolerated by the patient. |
| BG005 | Total | Total of all reporting groups |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| ID | Title | Description |
|---|---|---|
| OG000 | BI 836858 | Treatment group "BI 836858" comprises all dose cohorts during the dose escalation phase, that is, "BI 836858 20 mg", "BI 836858 40 mg", "BI 836858 80 mg", "BI 836858 160 mg" and "BI 836858 320 mg". All patients were administered doses of BI 836858, by a rate-controlled intravenous infusion on day 1 and on day 15 of a 28-day cycle for a duration of 4 cycles. All infusions were to be started at a rate of 10 mL/h. The infusion rate was to be increased every 30 (+/-10) minutes by 10 mL/h to a maximum of 80 mL/h as long as tolerated by the patient. |
|
| Primary | Number of Patients With Dose Limiting Toxicity (DLT) (Phase I) | Dose Limiting Toxicity (DLT):
| MTD evaluation set: All patients who were documented to have initiated at least one dose of BI 836858 and who have not been replaced for the MTD evaluation. | Posted | Count of Participants | Participants | From the first administration of BI 836858 to start of the third administration of BI 836858, excluding the day of the third administration of BI 836858, up to 28 days |
|
|
|
| Secondary | Number of Patients With Red Blood Cell (RBC) Transfusion Independency (Phase I) | Number of patients with red blood cell (RBC) Transfusion Independency is presented. Red blood cell (RBC) transfusion independence and platelet transfusion independence will be evaluated in patients who are transfusion dependent at baseline. Percentages will be calculated using all treated patients as the denominator. A patient is considered transfusion independent at baseline if the patient has had no transfusions during the 56 days prior to and including the first day of treatment. Otherwise, the patient is considered to be transfusion dependent. A patient is considered transfusion independent if the patient has had no transfusions over the course of ≥ 56 consecutive days. | Treated set (TS): The TS included all patients who had been enrolled and treated with at least 1 dose of study drug. The treated set was used for safety analyses. | Posted | Count of Participants | Participants | From first administration of BI 836858 until discontinuation of the treatment. Up to 168 days (6 cycles, each of 28 days) |
|
|
|
| Secondary | Number of Patients With Hematologic Improvement Neutrophils (HI-N) (Phase I) | Number of patients with hematologic improvement neutrophils (HI-N) is presented. The HI will be evaluated in patients with abnormal pretreatment values defined as follows: Neutrophil response (HI-N) - Patients with a pretreatment neutrophil count <1 x 10^9/liters (L) demonstrate a neutrophil response if they have an at least 100 percent increase and an absolute increase >0.5 x 10^9/L. | Treated set (TS): The TS included all patients who had been enrolled and treated with at least 1 dose of study drug. The treated set was used for safety analyses. | Posted | Count of Participants | Participants | From first administration of BI 836858 until HI-N, up to 168 days (6 cycles, each of 28 days) |
|
|
|
| Secondary | Number of Patients With Hematologic Improvement Platelets (HI-P) (Phase I) | Number of patients with hematologic improvement platelets (HI-P) is presented. The HI will be evaluated in patients with abnormal pretreatment values defined as follows: Platelet response (HI-P) - Patients with a pretreatment platelet count <100 x 109/Liters (L) demonstrate a platelet response if there is an absolute platelet increase of ≥30 x 109/L for patients starting with >20 x 109/L platelets. For those with an increase from 10 x 109/L to >20 x 109/L must have an increase of at least 100 percent. | Treated set (TS): The TS included all patients who had been enrolled and treated with at least 1 dose of study drug. The treated set was used for safety analyses. | Posted | Count of Participants | Participants | From first administration of BI 836858 until HI-P, up to 168 days (6 cycles, each of 28 days) |
|
|
|
| Secondary | Number of Patients With Hematologic Improvement Erythroid (HI-E) (Phase I) | Number of patients with hematologic improvement erythroid (HI-E) is presented. The HI will be evaluated in patients with abnormal pretreatment values defined as follows: Erythroid response (HI-E): Patients with a pretreatment hemoglobin <11 grams per deciliters (g/dL) demonstrate erythroid response if their hemoglobin increases by ≥1.5 g/dL for at least eight weeks, and there is a reduction in the units of red cell transfusions by an absolute number of at least four red cell transfusions per eight weeks compared with the pretreatment transfusion number in the previous eight weeks. Only red cell transfusions given for a hemoglobin ≤9 g/dL pretreatment will count in the red cell transfusion response evaluation. | Treated set (TS): The TS included all patients who had been enrolled and treated with at least 1 dose of study drug. The treated set was used for safety analyses. | Posted | Count of Participants | Participants | From first administration of BI 836858 until HI-E, up to 168 days (6 cycles, each of 28 days) |
|
|
|
| Secondary | Time to HI-E Response (Phase I) | Time to HI-E response is defined only for patients who achieve a HI-E response as follows: Time to HI-E response [days] = date of first assessment indicating HI-E response - date of first administration of trial medication + 1. | Treated set (TS): The TS included all patients who had been enrolled and treated with at least 1 dose of study drug. The treated set was used for safety analyses. Only patients who showed a HI-E response were included. | Posted | From first administration of BI 836858 until HI-E response, up to 168 days (6 cycles, each of 28 days) |
|
|
| Secondary | Number of Patients With Mean Hemoglobin Increase ≥ 1.5 g/dL (Phase I) | Number of patients with mean hemoglobin increase ≥ 1.5 grams per deciliters (g/dL) is presented. Mean hemoglobin increase ≥ 1.5 g/dL - Proportion of subjects achieving hemoglobin (Hgb) increase from baseline ≥ 1.5 g/dL over any consecutive 56-day period in absence of Red blood cell (RBC) transfusions. | Treated set (TS): The TS included all patients who had been enrolled and treated with at least 1 dose of study drug. The treated set was used for safety analyses. | Posted | Count of Participants | Participants | Up to 48 weeks |
|
|
|
| Secondary | Duration of Response (RBC Transfusion Independency, HI-N, HI-P, HI-E or Objective Response) (Phase I) | Defined only for patients who achieve complete Response (CR) or marrow complete response (mCR) or RBC Transfusion independency (TI), measured from first date of achieving response until date of relapse. Date of relapse will be earliest of dates of disease assessment (blood sample, bone marrow sample, or clinical assessment) in which relapse was observed. For patients who die or are lost to follow-up without documented relapse, response duration will be censored, respectively, on date of death, regardless of cause, or on date of last disease assessment for patients who are alive when lost to follow-up. Duration of Response [days] = date of outcome - date of first assessment indicating CR or mCR or RBC TI after first administration of trial medication + 1. | Treated set (TS): The TS included all patients who had been enrolled and treated with at least 1 dose of study drug. The treated set was used for safety analyses. Only patients who had achieved complete response (CR) or marrow complete response (mCR) or RBC Transfusion independency (TI) were included. | Posted | From the first date of achieving a response until the date of relapse, up to 168 days (6 cycles, each of 28 days) |
|
|
| Secondary | Number of Patients With Overall Objective Response (OR) [Complete Response (CR), Partial Response (PR), and Hematologic Improvement (HI)] (Phase I) | Number of patients with overall Objective Response (OR) [Complete Response (CR), Partial Response (PR), and Hematologic Improvement (HI)] is presented. Overall Objective Response is defined as Complete Response (CR), Partial Response (PR), HI-N, HI-P, or HI-E. A patient's " Overall Objective Response " = "Yes" if one of these responses was reported at least once throughout the trial. CR defined as: -Bone marrow: <5 % blasts with normal maturation of all cell lines (Dysplastic changes should consider the normal range of dysplastic changes), persistent dysplasia will be noted; -Peripheral blood: Hgb > 11 grams per deciliters (g/dL), Platelets >100 x 109/liters (L), Neutrophils > 1.0 x 109/L, Blasts 0 % PR defined as: -All CR criteria if abnormal before treatment except: Bone marrow blasts decreased by >50 % to pre-treatment but still >5 %, Cellularity and morphology not relevant. HI Definition see other endpoints. | Treated set (TS): The TS included all patients who had been enrolled and treated with at least 1 dose of study drug. The treated set was used for safety analyses. | Posted | Count of Participants | Participants | From first administration of BI 836858 until overall objective response, up to 168 days (6 cycles, each of 28 days) |
|
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| Primary | Number of Patients With Red Blood Cell (RBC) Transfusion Independency (Phase II) | Red blood cell (RBC) transfusion independence and platelet transfusion independence will be evaluated in patients who are transfusion dependent at baseline. Percentages will be calculated using all treated patients as the denominator. A patient is considered transfusion independent at baseline if the patient has had no transfusions during the 56 days prior to and including the first day of treatment. Otherwise, the patient is considered to be transfusion dependent. A patient is considered transfusion independent if the patient has had no transfusions over the course of ≥ 56 consecutive days. | No patients were enrolled in the Phase II part. The company decided to stop the clinical development of BI 836858 prematurely during the Phase I expansion cohort stage for strategic reasons. | Posted | From first administration of BI 836858 until discontinuation of the treatment. Up to 168 days (6 cycles, each of 28 days) |
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| 1 |
| 3 |
| 2 |
| 3 |
| 3 |
| 3 |
| EG001 | BI 836858 40mg | All patients were administered doses of BI 836858, 40 milligrams (mg) by a rate-controlled intravenous infusion on day 1 and on day 15 of a 28-day cycle for a duration of 4 cycles. All infusions were to be started at a rate of 10 mL/h. The infusion rate was to be increased every 30 (+/-10) minutes by 10 mL/h to a maximum of 80 mL/h as long as tolerated by the patient. | 0 | 3 | 2 | 3 | 3 | 3 |
| EG002 | BI 836858 80mg | All patients were administered doses of BI 836858, 80 milligrams (mg) by a rate-controlled intravenous infusion on day 1 and on day 15 of a 28-day cycle for a duration of 4 cycles. All infusions were to be started at a rate of 10 mL/h. The infusion rate was to be increased every 30 (+/-10) minutes by 10 mL/h to a maximum of 80 mL/h as long as tolerated by the patient. | 1 | 6 | 3 | 6 | 6 | 6 |
| EG003 | BI 836858 160mg | All patients were administered doses of BI 836858, 160 milligrams (mg) by a rate-controlled intravenous infusion on day 1 and on day 15 of a 28-day cycle for a duration of 4 cycles. All infusions were to be started at a rate of 10 mL/h. The infusion rate was to be increased every 30 (+/-10) minutes by 10 mL/h to a maximum of 80 mL/h as long as tolerated by the patient. | 0 | 4 | 0 | 4 | 4 | 4 |
| EG004 | BI 836858 320mg | All patients were administered doses of BI 836858, 320 milligrams (mg) by a rate-controlled intravenous infusion on day 1 and on day 15 of a 28-day cycle for a duration of 4 cycles. All infusions were to be started at a rate of 10 mL/h. The infusion rate was to be increased every 30 (+/-10) minutes by 10 mL/h to a maximum of 80 mL/h as long as tolerated by the patient. | 3 | 11 | 6 | 11 | 9 | 11 |
| Ventricular tachycardia | Cardiac disorders | MedDRA 22.1 | Systematic Assessment |
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| Non-cardiac chest pain | General disorders | MedDRA 22.1 | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA 22.1 | Systematic Assessment |
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| Cellulitis | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
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| Enterocolitis infectious | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
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| Infection | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
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| Sepsis | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
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| Staphylococcal infection | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
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| Wound infection | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
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| Fall | Injury, poisoning and procedural complications | MedDRA 22.1 | Systematic Assessment |
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| Infusion related reaction | Injury, poisoning and procedural complications | MedDRA 22.1 | Systematic Assessment |
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| Spinal compression fracture | Injury, poisoning and procedural complications | MedDRA 22.1 | Systematic Assessment |
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| Subdural haematoma | Injury, poisoning and procedural complications | MedDRA 22.1 | Systematic Assessment |
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| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 22.1 | Systematic Assessment |
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| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA 22.1 | Systematic Assessment |
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| Basal cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 22.1 | Systematic Assessment |
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| Syncope | Nervous system disorders | MedDRA 22.1 | Systematic Assessment |
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| Delirium | Psychiatric disorders | MedDRA 22.1 | Systematic Assessment |
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| Renal cyst | Renal and urinary disorders | MedDRA 22.1 | Systematic Assessment |
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| Lung infiltration | Respiratory, thoracic and mediastinal disorders | MedDRA 22.1 | Systematic Assessment |
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| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA 22.1 | Systematic Assessment |
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| Hypotension | Vascular disorders | MedDRA 22.1 | Systematic Assessment |
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| Monocytopenia | Blood and lymphatic system disorders | MedDRA 22.1 | Systematic Assessment |
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| Neutropenia | Blood and lymphatic system disorders | MedDRA 22.1 | Systematic Assessment |
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| Angina pectoris | Cardiac disorders | MedDRA 22.1 | Systematic Assessment |
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| Atrial fibrillation | Cardiac disorders | MedDRA 22.1 | Systematic Assessment |
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| Atrioventricular block first degree | Cardiac disorders | MedDRA 22.1 | Systematic Assessment |
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| Palpitations | Cardiac disorders | MedDRA 22.1 | Systematic Assessment |
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| Tachycardia | Cardiac disorders | MedDRA 22.1 | Systematic Assessment |
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| Vision blurred | Eye disorders | MedDRA 22.1 | Systematic Assessment |
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| Abdominal discomfort | Gastrointestinal disorders | MedDRA 22.1 | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | MedDRA 22.1 | Systematic Assessment |
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| Anal incontinence | Gastrointestinal disorders | MedDRA 22.1 | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | MedDRA 22.1 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA 22.1 | Systematic Assessment |
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| Dyspepsia | Gastrointestinal disorders | MedDRA 22.1 | Systematic Assessment |
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| Faeces discoloured | Gastrointestinal disorders | MedDRA 22.1 | Systematic Assessment |
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| Gastric ulcer | Gastrointestinal disorders | MedDRA 22.1 | Systematic Assessment |
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| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA 22.1 | Systematic Assessment |
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| Hiatus hernia | Gastrointestinal disorders | MedDRA 22.1 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 22.1 | Systematic Assessment |
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| Proctalgia | Gastrointestinal disorders | MedDRA 22.1 | Systematic Assessment |
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| Rectal haemorrhage | Gastrointestinal disorders | MedDRA 22.1 | Systematic Assessment |
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| Stomatitis | Gastrointestinal disorders | MedDRA 22.1 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA 22.1 | Systematic Assessment |
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| Catheter site pain | General disorders | MedDRA 22.1 | Systematic Assessment |
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| Chest pain | General disorders | MedDRA 22.1 | Systematic Assessment |
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| Chills | General disorders | MedDRA 22.1 | Systematic Assessment |
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| Face oedema | General disorders | MedDRA 22.1 | Systematic Assessment |
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| Fatigue | General disorders | MedDRA 22.1 | Systematic Assessment |
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| Influenza like illness | General disorders | MedDRA 22.1 | Systematic Assessment |
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| Infusion site pain | General disorders | MedDRA 22.1 | Systematic Assessment |
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| Localised oedema | General disorders | MedDRA 22.1 | Systematic Assessment |
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| Oedema peripheral | General disorders | MedDRA 22.1 | Systematic Assessment |
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| Pain | General disorders | MedDRA 22.1 | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA 22.1 | Systematic Assessment |
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| Swelling | General disorders | MedDRA 22.1 | Systematic Assessment |
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| Arthritis infective | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
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| Cellulitis | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
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| Cystitis | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
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| Diverticulitis | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
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| Enterococcal infection | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
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| Pneumonia | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
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| Postoperative wound infection | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
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| Staphylococcal infection | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
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| Tinea cruris | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
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| Tinea pedis | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
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| Urinary tract infection | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
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| Wound infection | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
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| Contusion | Injury, poisoning and procedural complications | MedDRA 22.1 | Systematic Assessment |
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| Fall | Injury, poisoning and procedural complications | MedDRA 22.1 | Systematic Assessment |
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| Infusion related reaction | Injury, poisoning and procedural complications | MedDRA 22.1 | Systematic Assessment |
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| Procedural haemorrhage | Injury, poisoning and procedural complications | MedDRA 22.1 | Systematic Assessment |
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| Scratch | Injury, poisoning and procedural complications | MedDRA 22.1 | Systematic Assessment |
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| Skin abrasion | Injury, poisoning and procedural complications | MedDRA 22.1 | Systematic Assessment |
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| Skin laceration | Injury, poisoning and procedural complications | MedDRA 22.1 | Systematic Assessment |
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| Spinal fracture | Injury, poisoning and procedural complications | MedDRA 22.1 | Systematic Assessment |
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| Alanine aminotransferase increased | Investigations | MedDRA 22.1 | Systematic Assessment |
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| Aspartate aminotransferase increased | Investigations | MedDRA 22.1 | Systematic Assessment |
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| Blood bilirubin increased | Investigations | MedDRA 22.1 | Systematic Assessment |
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| Blood creatinine increased | Investigations | MedDRA 22.1 | Systematic Assessment |
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| Blood pressure increased | Investigations | MedDRA 22.1 | Systematic Assessment |
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| Carotid bruit | Investigations | MedDRA 22.1 | Systematic Assessment |
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| Neutrophil count decreased | Investigations | MedDRA 22.1 | Systematic Assessment |
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| Platelet count decreased | Investigations | MedDRA 22.1 | Systematic Assessment |
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| QRS axis abnormal | Investigations | MedDRA 22.1 | Systematic Assessment |
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| Weight decreased | Investigations | MedDRA 22.1 | Systematic Assessment |
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| White blood cell count decreased | Investigations | MedDRA 22.1 | Systematic Assessment |
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| Decreased appetite | Metabolism and nutrition disorders | MedDRA 22.1 | Systematic Assessment |
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| Dehydration | Metabolism and nutrition disorders | MedDRA 22.1 | Systematic Assessment |
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| Diabetes mellitus | Metabolism and nutrition disorders | MedDRA 22.1 | Systematic Assessment |
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| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 22.1 | Systematic Assessment |
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| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA 22.1 | Systematic Assessment |
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| Hyperuricaemia | Metabolism and nutrition disorders | MedDRA 22.1 | Systematic Assessment |
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| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA 22.1 | Systematic Assessment |
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| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA 22.1 | Systematic Assessment |
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| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA 22.1 | Systematic Assessment |
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| Hyponatraemia | Metabolism and nutrition disorders | MedDRA 22.1 | Systematic Assessment |
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| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA 22.1 | Systematic Assessment |
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| Iron overload | Metabolism and nutrition disorders | MedDRA 22.1 | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 22.1 | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 22.1 | Systematic Assessment |
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| Bone pain | Musculoskeletal and connective tissue disorders | MedDRA 22.1 | Systematic Assessment |
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| Flank pain | Musculoskeletal and connective tissue disorders | MedDRA 22.1 | Systematic Assessment |
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| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 22.1 | Systematic Assessment |
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| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA 22.1 | Systematic Assessment |
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| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 22.1 | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA 22.1 | Systematic Assessment |
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| Dysarthria | Nervous system disorders | MedDRA 22.1 | Systematic Assessment |
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| Dysgeusia | Nervous system disorders | MedDRA 22.1 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 22.1 | Systematic Assessment |
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| Memory impairment | Nervous system disorders | MedDRA 22.1 | Systematic Assessment |
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| Paraesthesia | Nervous system disorders | MedDRA 22.1 | Systematic Assessment |
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| Agitation | Psychiatric disorders | MedDRA 22.1 | Systematic Assessment |
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| Anxiety | Psychiatric disorders | MedDRA 22.1 | Systematic Assessment |
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| Insomnia | Psychiatric disorders | MedDRA 22.1 | Systematic Assessment |
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| Urinary incontinence | Renal and urinary disorders | MedDRA 22.1 | Systematic Assessment |
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| Vaginal haemorrhage | Reproductive system and breast disorders | MedDRA 22.1 | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 22.1 | Systematic Assessment |
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| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 22.1 | Systematic Assessment |
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| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 22.1 | Systematic Assessment |
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| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 22.1 | Systematic Assessment |
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| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA 22.1 | Systematic Assessment |
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| Upper-airway cough syndrome | Respiratory, thoracic and mediastinal disorders | MedDRA 22.1 | Systematic Assessment |
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| Wheezing | Respiratory, thoracic and mediastinal disorders | MedDRA 22.1 | Systematic Assessment |
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| Alopecia | Skin and subcutaneous tissue disorders | MedDRA 22.1 | Systematic Assessment |
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| Dry skin | Skin and subcutaneous tissue disorders | MedDRA 22.1 | Systematic Assessment |
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| Pain of skin | Skin and subcutaneous tissue disorders | MedDRA 22.1 | Systematic Assessment |
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| Petechiae | Skin and subcutaneous tissue disorders | MedDRA 22.1 | Systematic Assessment |
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| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 22.1 | Systematic Assessment |
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| Purpura | Skin and subcutaneous tissue disorders | MedDRA 22.1 | Systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | MedDRA 22.1 | Systematic Assessment |
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| Skin burning sensation | Skin and subcutaneous tissue disorders | MedDRA 22.1 | Systematic Assessment |
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| Skin induration | Skin and subcutaneous tissue disorders | MedDRA 22.1 | Systematic Assessment |
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| Flushing | Vascular disorders | MedDRA 22.1 | Systematic Assessment |
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| Haematoma | Vascular disorders | MedDRA 22.1 | Systematic Assessment |
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| Hot flush | Vascular disorders | MedDRA 22.1 | Systematic Assessment |
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| Hypotension | Vascular disorders | MedDRA 22.1 | Systematic Assessment |
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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.