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| ID | Type | Description | Link |
|---|---|---|---|
| 2012-004090-16 | EudraCT Number | EudraCT |
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To evaluate the safety and tolerability of multiple doses of BI 655064 administered subcutaneously in healthy volunteers (HVs) and in rheumatoid arthritis (RA) patients. To explore the pharmacokinetic (PK) and pharmacodynamic (PD) parameters of multiple doses of BI 655064 in healthy volunteers (HVs) and rheumatoid arthritis (RA) patients. To assess clinical effect of BI 655064 in RA patients with prior inadequate response to methotrexate (MTX) after 12 weeks of treatment
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part 1, Placebo BI 655064 80/120mg (HV) | Placebo Comparator | Part 1, Healthy volunteers (HV): Placebo matching BI 655064 80 or 120 milligram (mg) injected subcutaneous on days 1, 8, 15, and 22 (once weekly, for 4 weeks) followed by 6 weeks follow-up period. |
|
| Part 1, Placebo BI 655064 180/240mg (HV) | Placebo Comparator | Part 1, Healthy volunteers (HV): Placebo matching BI 655064 180 or 240 mg injected subcutaneous on days 1, 8, 15, and 22 (once weekly, for 4 weeks) followed by 6 weeks (180mg dosing group) or 8 weeks (240mg dosing group) follow-up period. |
|
| Part 1, BI 655064 80mg (HV) | Experimental | Part 1, Healthy volunteers (HV): 80 mg of BI 655064 injected subcutaneous on days 1, 8, 15, and 22 (once weekly, for 4 weeks) followed by 6 weeks follow-up period. |
|
| Part 1, BI 655064 120mg (HV) | Experimental | Part 1, Healthy volunteers (HV): 120 mg of BI 655064 injected subcutaneous on days 1, 8, 15, and 22 (once weekly, for 4 weeks) followed by 6 weeks follow-up period. |
|
| Part 1, BI 655064 180mg (HV) | Experimental |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Placebo matching BI 655064 | Drug | Placebo matching BI 655064 injected subcutaneous. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Part 1: Cmax After the First and Last Dose | Part 1: This outcome measure presents the maximum measured concentration of BI 655064 in plasma (Cmax) after the first and last (fourth) dose. More detailed time frame: Pharmacokinetic (PK) sample times: 0:30 hour (h) prior first administration of BI 655064 and 1 h, 8 h, 12 h, 24 h, 48 h, 72 h, 84 h, 96 h, 108 h, 120 h, 144 h, 167:30 h, 335:30 h, 503:30 h, 505 h, 516 h, 528 h, 552 h, 576 h, 600 h, 624 h, 648 h, 672 h, 696 h, 744 h, 816 h, 912 h, 1008 h, 1176 h, 1344 h, 1512 h, 1848 h thereafter; further administration times for BI 655064: 168 h, 336 h, and 504 h after first administration. | From first day of drug administration till end of trial, up to 77 days. Detailed PK can be found in the endpoint description. |
| Part 1: AUC 0-infinity After the Last Dose | Part 1: Area under the concentration-time curve of BI 655064 in plasma over the time interval from 0 extrapolated to infinite (AUC 0-infinity). | PK sample times: 1 h, 12 h, 24 h, 48 h, 72 h, 96 h, 120 h, 144 h, 168 h, 192 h, 240 h, 312 h, 408 h, 504 h, 672 h, 840 h, 1008 h, 1344 h after the last administration of BI 655064 on day 22 |
| Part 1: AUCtau After the Last Dose | Area under the concentration-time curve of BI 655064 in plasma after the 4th dose over a uniform dosing interval t (AUC t,4) after the first and 4th dose. AUCtau is synonymous with AUC0-168. | PK sample times: 1 h, 12 h, 24 h, 48 h, 72 h, 96 h, 120 h, 144 h, 168 h, 192 h, 240 h, 312 h, 408 h, 504 h, 672 h, 840 h, 1008 h, 1344 h after the last administration of trial drug on day 22 |
| Part 1: Percentage of Subjects With Drug Related Adverse Events | In Part 1 (Phase Ib): The primary safety endpoint was the percentage of subjects with AEs related to treatment with trial medication. | from first administration of study medication (day 1) up to day 64 (dosing groups 80, 120, 180mg) or up to day 78 post-treatment (dosing group 240mg) |
| Measure | Description | Time Frame |
|---|---|---|
| Part 2: ACR50 Response Rates at Week 12 | ACR 50 criteria at week 12 relative to the patient's status at baseline: that is, at least 50 % improvement in swollen joint count, at least 50% improvement in tender joint count, and at least 50% improvement in ≥3 of the following 5 variables: 1) patient's assessment of pain on the visual analogue scale (VAS), rated on a scale of 1 to 10; 2) patient's global assessment of disease on the VAS, rated on a scale of 1 to 10; 3) investigator's global assessment of disease on the VAS; 4) patient's assessment of disability on the health assessment questionnaire (HAQ), rated on a scale of 1 to 3; and 5) concentrations of acute phase reactants. For all scales (1-4): smaller values better. The percentage of subjects with ACR50 response is presented. |
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Inclusion criteria:
Part 1 (phase Ib) (HVs):
Healthy males and females according to the investigators assessment, as based on the following criteria: a complete medical history including a physical examination, vital signs (BP, PR), 12-lead ECG, and clinical laboratory tests
Age >= 18 and <= 60 years
Body Mass Index >= 18.5 and <= 29.9 kg/m2
Signed and dated written informed consent prior to admission to the study in accordance with GCP and the local legislation
Female subjects who meet any of the following criteria from at least 30 days before the first study drug administration and until 30 days after trial completion:
Part 2 (phase IIa) (RA Patients):
Age >= 18 and <= 70 years
Patients classified as having RA according to the 1987 ACR Classification Criteria
Inadequate clinical response to methotrexate monotherapy defined as moderate/high active disease after oral or s.c. MTX treatment given continuously for at least 3 months and for the last 6 weeks before screening at a stable weekly dose >=15mg. For patients who do not tolerate the minimum weekly dose of at least 15 mg due to side effects, a stable weekly dose as low as 7.5 mg is also permitted.
DAS28 4v-CRP >= 3.5 with >= 6 tender and >= 6 swollen joints out of 68/66 joint count at screening and confirmed by >= 6 tender and >= 6 swollen joints out of 68/66 joint count only at randomisation visit (Visit 2)
Serum CRP level >= 0.8 mg/dL or ESR >= 28 mm/1h at screening
Anti-CCP2 or Rheumatoid Factor positivity as per the limits of used assay at screening
Female patients who meet any of the following criteria from at least 30 days before the first study drug administration and until at least 6 months after last dose of MTX taken in the current trial:
using adequate contraception, e.g. any of the following methods plus condom: implants, injectables, combined oral contraceptives, intrauterine device (IUD)
OR
Male patients who:
Signed and dated written informed consent prior to admission to the study in accordance with GCP and local legislation
Exclusion criteria:
Part 1 (phase Ib in HVs):
9. Within 10 days prior to administration of trial medication, use of drugs that might reasonably influence the results of the trial 12. Alcohol abuse (consumption of more than 140 g/week in females and 210 g/week in males) 13. Drug abuse or positive drug screen 17. Chronic or relevant acute infections, including but not limited to HIV, Hepatitis B and C and tuberculosis (including a history of clinical TB and/or a positive QuantiFERON TB-Gold test) 18. Subject is assessed by the investigator as unsuitable for inclusion e.g. considered not able to understand and comply with study requirements or has a condition that would not allow safe participation in the study 19. Positive pregnancy test, pregnancy or plans to become pregnant within 30 days after study completion 20. Lactation
Further exclusion criteria applicable for part 1 only are given in the CTP.
Part 2 (phase IIa in RA patients):
Part 1 (phase Ib) exclusion criteria 7, 9, 12, 13 and 17-20 plus:
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| Name | Affiliation | Role |
|---|---|---|
| Boehringer Ingelheim | Boehringer Ingelheim | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| 1293.2.00049 Boehringer Ingelheim Investigational Site | Olomouc | Czechia | ||||
| 1293.2.00024 Boehringer Ingelheim Investigational Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30902820 | Derived | Visvanathan S, Daniluk S, Ptaszynski R, Muller-Ladner U, Ramanujam M, Rosenstock B, Eleftheraki AG, Vinisko R, Petrikova A, Kellner H, Dokoupilova E, Kwiatkowska B, Alten R, Schwabe C, Baum P, Joseph D, Fine JS, Padula SJ, Steffgen J. Effects of BI 655064, an antagonistic anti-CD40 antibody, on clinical and biomarker variables in patients with active rheumatoid arthritis: a randomised, double-blind, placebo-controlled, phase IIa study. Ann Rheum Dis. 2019 Jun;78(6):754-760. doi: 10.1136/annrheumdis-2018-214729. Epub 2019 Mar 22. |
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All subjects were screened for eligibility to participate in trial. Subjects attended specialist sites to ensure that they (the subjects) met all implemented inclusion/exclusion criteria. Subjects were not to be randomised to trial drug if any of the specific entry criteria was violated.
Part 1 (Phase Ib multiple rising dose): 40 healthy volunteers were recruited, in 4 sequential groups of 10 subjects (8 of them received active drug, 2 placebo) each. Thereafter, part 2 (Phase 2a): 67 patients with Rheumatoid Arthritis(RA), who had prior inadequate response to Methotrexate (MTX)treatment, were randomised into 2 arms.
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| ID | Title | Description |
|---|---|---|
| FG000 | Part 1, Placebo BI 655064 80/120mg (HV) | Part 1, Healthy volunteers (HV): Placebo matching BI 655064 80 or 120 milligram (mg) injected subcutaneous on days 1, 8, 15, and 22 (once weekly, for 4 weeks) followed by 6 weeks follow-up period. |
| FG001 | Part 1, Placebo BI 655064 180/240mg (HV) |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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Part 1, Healthy volunteers (HV): 180 mg of BI 655064 injected subcutaneous on days 1, 8, 15, and 22 (once weekly, for 4 weeks) followed by 6 weeks follow-up period.
|
| Part 1, BI 655064 240mg (HV) | Experimental | Part 1, Healthy volunteers (HV): 240mg of BI 655064 injected subcutaneous on days 1, 8, 15, and 22 (once weekly, for 4 weeks) followed by 8 weeks follow-up period. |
|
| Part 2, Placebo BI 655064 120mg (RA) | Placebo Comparator | Part 2, patients with Rheumatoid arthritis (RA) who had prior inadequate response to Methotrexat (MTX) therapy: Placebo matching BI 655064 120 milligram (mg) injected subcutaneous on days 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78 (once weekly for 12 weeks) followed by 8 weeks follow-up period. |
|
| Part 2, BI 655064 120mg (RA) | Experimental | Part 2, patients with RA who had prior inadequate response to MTX therapy: 120 milligram (mg) of BI 655064 injected subcutaneous on days 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78 (once weekly for 12 weeks) followed by 8 weeks follow-up period. |
|
| BI 655064 | Drug | BI 655064 injected subcutaneous |
|
| Part 2: American College of Rheumatology (ACR)20 Response Rate at Week 12 | ACR 20 criteria at week 12 relative to the patient's status at baseline: that is, at least 20 percent (%) improvement in swollen joint count, at least 20% improvement in tender joint count, and at least 20% improvement in ≥3 of the following 5 variables: 1) patient's assessment of pain on the visual analogue scale (VAS), rated on a scale of 1 to 10; 2) patient's global assessment of disease on the VAS, rated on a scale of 1 to 10; 3) investigator's global assessment of disease on the VAS; 4) patient's assessment of disability on the health assessment questionnaire (HAQ), rated on a scale of 1 to 3; and 5) concentrations of acute phase reactants. For all scales (1-4): smaller values better. The ACR20 were evaluated descriptively. The data were analysed with a Bayesian approach using an informative prior for the placebo treatment group; predictive probability that the treatment difference was larger than 0%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40% or 45% was to be evaluated. | at week 12 (day 85) from the initiation of study treatment |
| at week 12 (day 85) |
| Part 2: ACR70 Response Rates at Week 12 | ACR70 criteria at week 12 relative to the patient's status at baseline: that is, at least 70 % improvement in swollen joint count, at least 70% improvement in tender joint count, and at least 70% improvement in ≥3 of the following 5 variables: 1) patient's assessment of pain on the visual analogue scale (VAS), rated on a scale of 1 to 10; 2) patient's global assessment of disease on the VAS, rated on a scale of 1 to 10; 3) investigator's global assessment of disease on the VAS; 4) patient's assessment of disability on the health assessment questionnaire (HAQ), rated on a scale of 1 to 3; and 5) concentrations of acute phase reactants. For all scales (1-4): smaller values better). The percentage of subjects with ACR50 response is presented. | at week 12 (day 85) |
| Part 2: EULAR Disease Activity Score in 28 Joints and C-reactive Protein (DAS28-CRP) at Week 12 | Assessed by European League Against Rheumatism (EULAR) categorization as good, moderate, or nonresponders based on improvement from baseline using the DAS28-CRP at week 12. In this outcome measure the frequency of EULAR response rates (change from the day of first dose to the day of visit 14 in week 12) are presented. DAS28-CRP is calculated as 0.56*√(TJC) + 0.28*√(SJC) + 0.36*Ln(CRP+1) + 0.014*VAS + 0.96. The total score ranges from 1.0 to 9.4, where a higher score indicates a better outcome. EULAR response states were classified as follows: good responders were patients with an improvement of >1.2 and a present score of ⩽3.2; moderate responders were patients with an improvement of >0.6 to ⩽1.2 and a present score of ⩽5.1, or an improvement of >1.2 and a present score of >3.2; non-responders were any patients with an improvement of ⩽0.6, or patients with an improvement of >0.6 to ⩽1.2 and a present score of >5.1. Improvement (impr.) is abbreviated in the category names. | baseline (day 1) and week 12 (day 85) |
| Part 2: EULAR DAS28-ESR at Week 12 | Response as assessed by European League Against Rheumatism (EULAR) using Disease activity score in 28 joints and the erythrocyte sedimentation rate (DAS28-ESR) at week 12. In this outcome measure the frequency of EULAR response rates (change from the day of first dose to the day of visit 14 in week 12) are presented. DAS28-ESR is calculated as 0.56*√(TJC) + 0.28*√(SJC) + 0.70 *Ln(ESR) + 0.014*VAS. The total score ranges from 0 to 9.4, where a higher score indicates a better outcome. EULAR response states were classified as follows: good responders were patients with an improvement of >1.2 and a present score of ⩽3.2; moderate responders were patients with an improvement of >0.6 to ⩽1.2 and a present score of ⩽5.1, or an improvement of >1.2 and a present score of >3.2; non-responders were any patients with an improvement of ⩽0.6, or patients with an improvement of >0.6 to ⩽1.2 and a present score of >5.1. Improvement (impr.) is abbreviated in the category names. | baseline (day 1) and week 12 (day 85) |
| Part 2: Percentage of Patients With a Decrease in DAS28-CRP of >1.2 at Week 12 | Percentage of patients who had a decrease of >1.2 on the Disease activity score in 28 joints and C-reactive protein (DAS28-CRP) at week 12 (day 85) compared to baseline. The adjusted absolute risk difference was adjusted for treatment, region and anti-TNF history. DAS28-CRP is calculated using Tender Joint Count 28 (TJC28), Swollen Joint Count 28 (SJC28), C-reactive protein (CRP) (in mg/L), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst), where the total score is calculated as follows: 0.56*√(TJC) + 0.28*√(SJC) + 0.36*Ln(CRP+1) + 0.014*VAS + 0.96. The total score ranges from 1.0 to 9.4, where a higher score indicates a better outcome. | baseline (day 1) and week 12 (day 85) |
| Part 2: Change in DAS28-CRP Score at Week 12 | Change at week 12 in the Disease activity score in 28 joints and C-reactive protein (DAS28-CRP) compared with the score at baseline. The mean was adjusted for region, anti-TNF history and baseline DAS28-CRP. DAS28-CRP is calculated using Tender Joint Count 28 (TJC28), Swollen Joint Count 28 (SJC28), C-reactive protein (CRP) (in mg/L), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst), where the total score is calculated as follows: 0.56*√(TJC) + 0.28*√(SJC) + 0.36*Ln(CRP+1) + 0.014*VAS + 0.96. The total score ranges from 1.0 to 9.4, where a higher score indicates a better outcome. | baseline (day 1) and week 12 (day 85) |
| Uherské Hradiště |
| Czechia |
| 1293.2.00028 Boehringer Ingelheim Investigational Site | ZlÃn | Czechia |
| 1293.2.00015 Boehringer Ingelheim Investigational Site | Bad Kreuznach | Germany |
| 1293.2.00010 Boehringer Ingelheim Investigational Site | Berlin | Germany |
| 1293.2.00013 Boehringer Ingelheim Investigational Site | Berlin | Germany |
| 1293.2.00043 Boehringer Ingelheim Investigational Site | München | Germany |
| 1293.2.00012 Boehringer Ingelheim Investigational Site | Zerbst | Germany |
| 1293.2.00031 Boehringer Ingelheim Investigational Site | Amsterdam | Netherlands |
| 1293.2.00032 Boehringer Ingelheim Investigational Site | Leeuwarden | Netherlands |
| 1293.2.00038 Boehringer Ingelheim Investigational Site | Leiden | Netherlands |
| 1293.2.00040 Boehringer Ingelheim Investigational Site | Sneek | Netherlands |
| 1293.2.00001 Boehringer Ingelheim Investigational Site | Grafton Auckland NZ | New Zealand |
| 1293.2.00039 Boehringer Ingelheim Investigational Site | Bialystok | Poland |
| 1293.2.00034 Boehringer Ingelheim Investigational Site | Bydgoszcz | Poland |
| 1293.2.00041 Boehringer Ingelheim Investigational Site | Bydgoszcz | Poland |
| 1293.2.00025 Boehringer Ingelheim Investigational Site | Lublin | Poland |
| 1293.2.00050 Boehringer Ingelheim Investigational Site | Poznan | Poland |
| 1293.2.00023 Boehringer Ingelheim Investigational Site | Warsaw | Poland |
| 1293.2.00026 Boehringer Ingelheim Investigational Site | Warsaw | Poland |
| 1293.2.00021 Boehringer Ingelheim Investigational Site | A Coruña | Spain |
| 1293.2.00017 Boehringer Ingelheim Investigational Site | Barcelona | Spain |
| 1293.2.00022 Boehringer Ingelheim Investigational Site | Granada | Spain |
| 1293.2.00016 Boehringer Ingelheim Investigational Site | La Laguna (Sta Cruz Tenerife) | Spain |
| 1293.2.00020 Boehringer Ingelheim Investigational Site | Santiago de Compostela | Spain |
Part 1, Healthy volunteers (HV): Placebo matching BI 655064 180 or 240 mg injected subcutaneous on days 1, 8, 15, and 22 (once weekly, for 4 weeks) followed by 6 weeks (180mg dosing group) or 8 weeks (240mg dosing group) follow-up period. |
| FG002 | Part 1, BI 655064 80mg (HV) | Part 1, Healthy volunteers (HV): 80 mg of BI 655064 injected subcutaneous on days 1, 8, 15, and 22 (once weekly, for 4 weeks) followed by 6 weeks follow-up period. |
| FG003 | Part 1, BI 655064 120mg (HV) | Part 1, Healthy volunteers (HV): 120 mg of BI 655064 injected subcutaneous on days 1, 8, 15, and 22 (once weekly, for 4 weeks) followed by 6 weeks follow-up period. |
| FG004 | Part 1, BI 655064 180mg (HV) | Part 1, Healthy volunteers (HV): 180 mg of BI 655064 injected subcutaneous on days 1, 8, 15, and 22 (once weekly, for 4 weeks) followed by 6 weeks follow-up period. |
| FG005 | Part 1, BI 655064 240mg (HV) | Part 1, Healthy volunteers (HV): 240mg of BI 655064 injected subcutaneous on days 1, 8, 15, and 22 (once weekly, for 4 weeks) followed by 8 weeks follow-up period. |
| FG006 | Part 2, Placebo BI 655064 120mg (RA) | Part 2, patients with Rheumatoid arthritis (RA) who had prior inadequate response to Methotrexat (MTX) therapy: Placebo matching BI 655064 120 milligram (mg) injected subcutaneous on days 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78 (once weekly for 12 weeks) followed by 8 weeks follow-up period. |
| FG007 | Part 2, BI 655064 120mg (RA) | Part 2, patients with RA who had prior inadequate response to MTX therapy: 120 milligram (mg) of BI 655064 injected subcutaneous on days 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78 (once weekly for 12 weeks) followed by 8 weeks follow-up period. |
| COMPLETED |
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| NOT COMPLETED |
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|
Treated set (TS): This patient set includes all subjects who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
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| ID | Title | Description |
|---|---|---|
| BG000 | Part 1, Placebo BI 655064 80/120mg (HV) | Part 1, Healthy volunteers (HV): Placebo matching BI 655064 80 or 120 milligram (mg) injected subcutaneous on days 1, 8, 15, and 22 (once weekly, for 4 weeks) followed by 6 weeks follow-up period. |
| BG001 | Part 1, Placebo BI 655064 180/240mg (HV) | Part 1, Healthy volunteers (HV): Placebo matching BI 655064 180 or 240 mg injected subcutaneous on days 1, 8, 15, and 22 (once weekly, for 4 weeks) followed by 6 weeks (180mg dosing group) or 8 weeks (240mg dosing group) follow-up period. |
| BG002 | Part 1, BI 655064 80mg (HV) | Part 1, Healthy volunteers (HV): 80 mg of BI 655064 injected subcutaneous on days 1, 8, 15, and 22 (once weekly, for 4 weeks) followed by 6 weeks follow-up period. |
| BG003 | Part 1, BI 655064 120mg (HV) | Part 1, Healthy volunteers (HV): 120 mg of BI 655064 injected subcutaneous on days 1, 8, 15, and 22 (once weekly, for 4 weeks) followed by 6 weeks follow-up period. |
| BG004 | Part 1, BI 655064 180mg (HV) | Part 1, Healthy volunteers (HV): 180 mg of BI 655064 injected subcutaneous on days 1, 8, 15, and 22 (once weekly, for 4 weeks) followed by 6 weeks follow-up period. |
| BG005 | Part 1, BI 655064 240mg (HV) | Part 1, Healthy volunteers (HV): 240mg of BI 655064 injected subcutaneous on days 1, 8, 15, and 22 (once weekly, for 4 weeks) followed by 8 weeks follow-up period. |
| BG006 | Part 2, Placebo BI 655064 120mg (RA) | Part 2, patients with Rheumatoid arthritis (RA) who had prior inadequate response to Methotrexat (MTX) therapy: Placebo matching BI 655064 120 milligram (mg) injected subcutaneous on days 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78 (once weekly for 12 weeks) followed by 8 weeks follow-up period. |
| BG007 | Part 2, BI 655064 120mg (RA) | Part 2, patients with RA who had prior inadequate response to MTX therapy: 120 milligram (mg) of BI 655064 injected subcutaneous on days 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78 (once weekly for 12 weeks) followed by 8 weeks follow-up period. |
| BG008 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | As pre-specified in the protocol, subjects in part 1 and part 2 were analyzed separately. | Mean | Standard Deviation | years |
| |||||||||
| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
|
| 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 | Part 1: Cmax After the First and Last Dose | Part 1: This outcome measure presents the maximum measured concentration of BI 655064 in plasma (Cmax) after the first and last (fourth) dose. More detailed time frame: Pharmacokinetic (PK) sample times: 0:30 hour (h) prior first administration of BI 655064 and 1 h, 8 h, 12 h, 24 h, 48 h, 72 h, 84 h, 96 h, 108 h, 120 h, 144 h, 167:30 h, 335:30 h, 503:30 h, 505 h, 516 h, 528 h, 552 h, 576 h, 600 h, 624 h, 648 h, 672 h, 696 h, 744 h, 816 h, 912 h, 1008 h, 1176 h, 1344 h, 1512 h, 1848 h thereafter; further administration times for BI 655064: 168 h, 336 h, and 504 h after first administration. | All subjects were treated and and provided data for at least 1 primary pharmacokinetic (PK) endpoint and therefore all subjects were also included in the PK set (PKS). | Posted | Geometric Mean | Geometric Coefficient of Variation | microgram (µg)/ millilitre (mL) | From first day of drug administration till end of trial, up to 77 days. Detailed PK can be found in the endpoint description. |
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| Primary | Part 1: AUC 0-infinity After the Last Dose | Part 1: Area under the concentration-time curve of BI 655064 in plasma over the time interval from 0 extrapolated to infinite (AUC 0-infinity). | PKS | Posted | Geometric Mean | Geometric Coefficient of Variation | µg* hours (h)/mL | PK sample times: 1 h, 12 h, 24 h, 48 h, 72 h, 96 h, 120 h, 144 h, 168 h, 192 h, 240 h, 312 h, 408 h, 504 h, 672 h, 840 h, 1008 h, 1344 h after the last administration of BI 655064 on day 22 |
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| Primary | Part 1: AUCtau After the Last Dose | Area under the concentration-time curve of BI 655064 in plasma after the 4th dose over a uniform dosing interval t (AUC t,4) after the first and 4th dose. AUCtau is synonymous with AUC0-168. | PKS | Posted | Geometric Mean | Geometric Coefficient of Variation | µg*h/mL | PK sample times: 1 h, 12 h, 24 h, 48 h, 72 h, 96 h, 120 h, 144 h, 168 h, 192 h, 240 h, 312 h, 408 h, 504 h, 672 h, 840 h, 1008 h, 1344 h after the last administration of trial drug on day 22 |
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| Primary | Part 1: Percentage of Subjects With Drug Related Adverse Events | In Part 1 (Phase Ib): The primary safety endpoint was the percentage of subjects with AEs related to treatment with trial medication. | TS | Posted | Number | Percentage of participants | from first administration of study medication (day 1) up to day 64 (dosing groups 80, 120, 180mg) or up to day 78 post-treatment (dosing group 240mg) |
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| Primary | Part 2: American College of Rheumatology (ACR)20 Response Rate at Week 12 | ACR 20 criteria at week 12 relative to the patient's status at baseline: that is, at least 20 percent (%) improvement in swollen joint count, at least 20% improvement in tender joint count, and at least 20% improvement in ≥3 of the following 5 variables: 1) patient's assessment of pain on the visual analogue scale (VAS), rated on a scale of 1 to 10; 2) patient's global assessment of disease on the VAS, rated on a scale of 1 to 10; 3) investigator's global assessment of disease on the VAS; 4) patient's assessment of disability on the health assessment questionnaire (HAQ), rated on a scale of 1 to 3; and 5) concentrations of acute phase reactants. For all scales (1-4): smaller values better. The ACR20 were evaluated descriptively. The data were analysed with a Bayesian approach using an informative prior for the placebo treatment group; predictive probability that the treatment difference was larger than 0%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40% or 45% was to be evaluated. | The full analysis set (FAS) included 66 of 67 randomised and treated patients; 1 patient (placebo group) was excluded due to insufficient efficacy data (excluded due to important protocol violations). Noncompleters were assumed to be failures (NCF). | Posted | Number | Percentage of participants | at week 12 (day 85) from the initiation of study treatment |
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| Secondary | Part 2: ACR50 Response Rates at Week 12 | ACR 50 criteria at week 12 relative to the patient's status at baseline: that is, at least 50 % improvement in swollen joint count, at least 50% improvement in tender joint count, and at least 50% improvement in ≥3 of the following 5 variables: 1) patient's assessment of pain on the visual analogue scale (VAS), rated on a scale of 1 to 10; 2) patient's global assessment of disease on the VAS, rated on a scale of 1 to 10; 3) investigator's global assessment of disease on the VAS; 4) patient's assessment of disability on the health assessment questionnaire (HAQ), rated on a scale of 1 to 3; and 5) concentrations of acute phase reactants. For all scales (1-4): smaller values better. The percentage of subjects with ACR50 response is presented. | FAS (NCF) | Posted | Number | 95% Confidence Interval | Percentage of participants | at week 12 (day 85) |
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| Secondary | Part 2: ACR70 Response Rates at Week 12 | ACR70 criteria at week 12 relative to the patient's status at baseline: that is, at least 70 % improvement in swollen joint count, at least 70% improvement in tender joint count, and at least 70% improvement in ≥3 of the following 5 variables: 1) patient's assessment of pain on the visual analogue scale (VAS), rated on a scale of 1 to 10; 2) patient's global assessment of disease on the VAS, rated on a scale of 1 to 10; 3) investigator's global assessment of disease on the VAS; 4) patient's assessment of disability on the health assessment questionnaire (HAQ), rated on a scale of 1 to 3; and 5) concentrations of acute phase reactants. For all scales (1-4): smaller values better). The percentage of subjects with ACR50 response is presented. | FAS (NCF) | Posted | Number | 95% Confidence Interval | Percentage of participants | at week 12 (day 85) |
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| Secondary | Part 2: EULAR Disease Activity Score in 28 Joints and C-reactive Protein (DAS28-CRP) at Week 12 | Assessed by European League Against Rheumatism (EULAR) categorization as good, moderate, or nonresponders based on improvement from baseline using the DAS28-CRP at week 12. In this outcome measure the frequency of EULAR response rates (change from the day of first dose to the day of visit 14 in week 12) are presented. DAS28-CRP is calculated as 0.56*√(TJC) + 0.28*√(SJC) + 0.36*Ln(CRP+1) + 0.014*VAS + 0.96. The total score ranges from 1.0 to 9.4, where a higher score indicates a better outcome. EULAR response states were classified as follows: good responders were patients with an improvement of >1.2 and a present score of ⩽3.2; moderate responders were patients with an improvement of >0.6 to ⩽1.2 and a present score of ⩽5.1, or an improvement of >1.2 and a present score of >3.2; non-responders were any patients with an improvement of ⩽0.6, or patients with an improvement of >0.6 to ⩽1.2 and a present score of >5.1. Improvement (impr.) is abbreviated in the category names. | FAS (observed cases) | Posted | Number | Percentage of participants | baseline (day 1) and week 12 (day 85) |
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| Secondary | Part 2: EULAR DAS28-ESR at Week 12 | Response as assessed by European League Against Rheumatism (EULAR) using Disease activity score in 28 joints and the erythrocyte sedimentation rate (DAS28-ESR) at week 12. In this outcome measure the frequency of EULAR response rates (change from the day of first dose to the day of visit 14 in week 12) are presented. DAS28-ESR is calculated as 0.56*√(TJC) + 0.28*√(SJC) + 0.70 *Ln(ESR) + 0.014*VAS. The total score ranges from 0 to 9.4, where a higher score indicates a better outcome. EULAR response states were classified as follows: good responders were patients with an improvement of >1.2 and a present score of ⩽3.2; moderate responders were patients with an improvement of >0.6 to ⩽1.2 and a present score of ⩽5.1, or an improvement of >1.2 and a present score of >3.2; non-responders were any patients with an improvement of ⩽0.6, or patients with an improvement of >0.6 to ⩽1.2 and a present score of >5.1. Improvement (impr.) is abbreviated in the category names. | FAS (observed cases) | Posted | Number | Percentage of participants | baseline (day 1) and week 12 (day 85) |
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| Secondary | Part 2: Percentage of Patients With a Decrease in DAS28-CRP of >1.2 at Week 12 | Percentage of patients who had a decrease of >1.2 on the Disease activity score in 28 joints and C-reactive protein (DAS28-CRP) at week 12 (day 85) compared to baseline. The adjusted absolute risk difference was adjusted for treatment, region and anti-TNF history. DAS28-CRP is calculated using Tender Joint Count 28 (TJC28), Swollen Joint Count 28 (SJC28), C-reactive protein (CRP) (in mg/L), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst), where the total score is calculated as follows: 0.56*√(TJC) + 0.28*√(SJC) + 0.36*Ln(CRP+1) + 0.014*VAS + 0.96. The total score ranges from 1.0 to 9.4, where a higher score indicates a better outcome. | FAS (Last observation carried forward) | Posted | Number | 95% Confidence Interval | Percentage of participants | baseline (day 1) and week 12 (day 85) |
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| Secondary | Part 2: Change in DAS28-CRP Score at Week 12 | Change at week 12 in the Disease activity score in 28 joints and C-reactive protein (DAS28-CRP) compared with the score at baseline. The mean was adjusted for region, anti-TNF history and baseline DAS28-CRP. DAS28-CRP is calculated using Tender Joint Count 28 (TJC28), Swollen Joint Count 28 (SJC28), C-reactive protein (CRP) (in mg/L), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst), where the total score is calculated as follows: 0.56*√(TJC) + 0.28*√(SJC) + 0.36*Ln(CRP+1) + 0.014*VAS + 0.96. The total score ranges from 1.0 to 9.4, where a higher score indicates a better outcome. | FAS (last observation carried forward) | Posted | Mean | Standard Error | units on a scale | baseline (day 1) and week 12 (day 85) |
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from first administration of study medication (day 1) up to day 64 (dosing groups 80, 120, 180mg) or up to day 78 post-treatment (dosing group 240mg) in part 1 and up to 141 days in part 2.
Treated set (TS): This patient set includes all subjects who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Part 1, BI 655064 80mg (HV) | Part 1, HV: 80 mg of BI 655064 injected subcutaneous on days 1, 8, 15, and 22 (once weekly, for 4 weeks) followed by 6 weeks follow-up period. | 0 | 8 | 7 | 8 | ||
| EG001 | Part 1, BI 655064 120mg (HV) | Part 1, HV: 120 mg of BI 655064 injected subcutaneous on days 1, 8, 15, and 22 (once weekly, for 4 weeks) followed by 6 weeks follow-up period. | 0 | 8 | 6 | 8 | ||
| EG002 | Part 1, BI 655064 180mg (HV) | Part 1, HV: 180 mg of BI 655064 injected subcutaneous on days 1, 8, 15, and 22 (once weekly, for 4 weeks) followed by 6 weeks follow-up period. | 0 | 8 | 6 | 8 | ||
| EG003 | Part 1, BI 655064 240mg (HV) | Part 1, HV: 240mg of BI 655064 injected subcutaneous on days 1, 8, 15, and 22 (once weekly, for 4 weeks) followed by 8 weeks follow-up period. | 0 | 8 | 6 | 8 | ||
| EG004 | Part 1, Placebo (HV) | Part 1, HV: Placebo injected subcutaneous on days 1, 8, 15, and 22 (once weekly, for 4 weeks) followed by 6 weeks (80, 120, and 180mg dosing group) or 8 weeks (240mg dosing group) follow-up period. | 0 | 8 | 7 | 8 | ||
| EG005 | Part 2, BI 655064 120mg (RA) | Part 2, patients with RA who had prior inadequate response to MTX therapy: 120 milligram (mg) of BI 655064 injected subcutaneous on days 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78 (once weekly for 12 weeks) followed by 8 weeks follow-up period. | 2 | 44 | 29 | 44 | ||
| EG006 | Part 2, Placebo BI 655064 120mg (RA) | Part 2, patients with Rheumatoid arthritis (RA) who had prior inadequate response to Methotrexat (MTX) therapy: Placebo matching BI 655064 120 milligram (mg) injected subcutaneous on days 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78 (once weekly for 12 weeks) followed by 8 weeks follow-up period. | 2 | 23 | 17 | 23 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | 18.0 | Systematic Assessment |
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| Acute myocardial infarction | Cardiac disorders | 18.0 | Systematic Assessment |
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| Cardiopulmonary failure | Cardiac disorders | 18.0 | Systematic Assessment |
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| Cerebral haemorrhage | Nervous system disorders | 18.0 | Systematic Assessment |
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| Pleural effusion | Respiratory, thoracic and mediastinal disorders | 18.0 | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Ear pain | Ear and labyrinth disorders | 18.0 | Systematic Assessment |
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| Eye pain | Eye disorders | 18.0 | Systematic Assessment |
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| Photophobia | Eye disorders | 18.0 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | 18.0 | Systematic Assessment |
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| Food poisoning | Gastrointestinal disorders | 18.0 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | 18.0 | Systematic Assessment |
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| Toothache | Gastrointestinal disorders | 18.0 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | 18.0 | Systematic Assessment |
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| Catheter site oedema | General disorders | 18.0 | Systematic Assessment |
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| Chest pain | General disorders | 18.0 | Systematic Assessment |
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| Fatigue | General disorders | 18.0 | Systematic Assessment |
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| Injection site bruising | General disorders | 18.0 | Systematic Assessment |
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| Injection site pain | General disorders | 18.0 | Systematic Assessment |
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| Injection site rash | General disorders | 18.0 | Systematic Assessment |
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| Malaise | General disorders | 18.0 | Systematic Assessment |
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| Pyrexia | General disorders | 18.0 | Systematic Assessment |
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| Vessel puncture site bruise | General disorders | 18.0 | Systematic Assessment |
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| Liver disorder | Hepatobiliary disorders | 18.0 | Systematic Assessment |
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| Chlamydial infection | Infections and infestations | 18.0 | Systematic Assessment |
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| Fungal infection | Infections and infestations | 18.0 | Systematic Assessment |
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| Gastroenteritis | Infections and infestations | 18.0 | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | 18.0 | Systematic Assessment |
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| Pharyngitis | Infections and infestations | 18.0 | Systematic Assessment |
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| Rhinitis | Infections and infestations | 18.0 | Systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | 18.0 | Systematic Assessment |
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| Urinary tract infection | Infections and infestations | 18.0 | Systematic Assessment |
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| Viral infection | Infections and infestations | 18.0 | Systematic Assessment |
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| Viral upper respiratory tract infection | Infections and infestations | 18.0 | Systematic Assessment |
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| Contusion | Injury, poisoning and procedural complications | 18.0 | Systematic Assessment |
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| Head injury | Injury, poisoning and procedural complications | 18.0 | Systematic Assessment |
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| Laceration | Injury, poisoning and procedural complications | 18.0 | Systematic Assessment |
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| Skin abrasion | Injury, poisoning and procedural complications | 18.0 | Systematic Assessment |
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| Sunburn | Injury, poisoning and procedural complications | 18.0 | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | 18.0 | Systematic Assessment |
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| Joint laxity | Musculoskeletal and connective tissue disorders | 18.0 | Systematic Assessment |
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| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | 18.0 | Systematic Assessment |
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| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | 18.0 | Systematic Assessment |
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| Myalgia | Musculoskeletal and connective tissue disorders | 18.0 | Systematic Assessment |
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| Headache | Nervous system disorders | 18.0 | Systematic Assessment |
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| Lethargy | Nervous system disorders | 18.0 | Systematic Assessment |
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| Depression | Psychiatric disorders | 18.0 | Systematic Assessment |
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| Dyspareunia | Reproductive system and breast disorders | 18.0 | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | 18.0 | Systematic Assessment |
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| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | 18.0 | Systematic Assessment |
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| Throat irritation | Respiratory, thoracic and mediastinal disorders | 18.0 | Systematic Assessment |
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| Acne | Skin and subcutaneous tissue disorders | 18.0 | Systematic Assessment |
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| Dermatitis contact | Skin and subcutaneous tissue disorders | 18.0 | Systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | 18.0 | Systematic Assessment |
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| Rash erythematous | Skin and subcutaneous tissue disorders | 18.0 | Systematic Assessment |
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| Rash macular | Skin and subcutaneous tissue disorders | 18.0 | Systematic Assessment |
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| Rash pruritic | Skin and subcutaneous tissue disorders | 18.0 | Systematic Assessment |
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| Xeroderma | Skin and subcutaneous tissue disorders | 18.0 | 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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Boehringer Ingelheim, Call Center | Boehringer Ingelheim | 1-800-243-0127 | clintriage.rdg@boehringer-ingelheim.com |
| ID | Term |
|---|---|
| D001172 | Arthritis, Rheumatoid |
| ID | Term |
|---|---|
| D001168 | Arthritis |
| D007592 | Joint Diseases |
| D009140 | Musculoskeletal Diseases |
| D012216 | Rheumatic Diseases |
| D003240 | Connective Tissue Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C000627991 | BI 655064 |
Not provided
Not provided
Not provided
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| Part 2 |
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| after the last (fourth) dose |
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| Dose proportionality for Cmax was explored after the last (fourth) adminstration of BI 65564 on Day 22. | Slope | 1.4227 | Standard Error of the Mean | 0.1644 | 2-Sided | 95 | 1.0869 | 1.7584 | Dose proportionality was explored using a regression model. Based on the estimate for the slope parameter, a 2-sided 95% CI was computed. Perfect dose proportionality would correspond to a slope of 1. PK endpoints on the log-transformed scale. | Superiority or Other (legacy) |
| Part 1, BI 655064 240mg (HV) |
Part 1, Healthy volunteers (HV): 240mg of BI 655064 injected subcutaneous on days 1, 8, 15, and 22 (once weekly, for 4 weeks) followed by 8 weeks follow-up period. |
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| OG003 |
| Part 1, BI 655064 240mg (HV) |
Part 1, Healthy volunteers (HV): 240mg of BI 655064 injected subcutaneous on days 1, 8, 15, and 22 (once weekly, for 4 weeks) followed by 8 weeks follow-up period. |
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| OG003 | Part 1, BI 655064 180mg (HV) | Part 1, Healthy volunteers (HV): 180 mg of BI 655064 injected subcutaneous on days 1, 8, 15, and 22 (once weekly, for 4 weeks) followed by 6 weeks follow-up period. |
| OG004 | Part 1, BI 655064 240mg (HV) | Part 1, Healthy volunteers (HV): 240mg of BI 655064 injected subcutaneous on days 1, 8, 15, and 22 (once weekly, for 4 weeks) followed by 8 weeks follow-up period. |
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| OG001 | Part 2, BI 655064 120mg (RA) | Part 2, patients with RA who had prior inadequate response to MTX therapy: 120 milligram (mg) of BI 655064 injected subcutaneous on days 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78 (once weekly for 12 weeks) followed by 8 weeks follow-up period. |
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Part 2, patients with RA who had prior inadequate response to MTX therapy: 120 milligram (mg) of BI 655064 injected subcutaneous on days 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78 (once weekly for 12 weeks) followed by 8 weeks follow-up period. |
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Part 2, patients with RA who had prior inadequate response to MTX therapy: 120 milligram (mg) of BI 655064 injected subcutaneous on days 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78 (once weekly for 12 weeks) followed by 8 weeks follow-up period. |
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