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| Name | Class |
|---|---|
| Acerta Pharma, LLC | OTHER |
Not provided
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To characterize the safety profile of acalabrutinib with and without dexamethasone in subjects with relapsed or refractory Multiple Myeloma (MM)
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1 | Experimental | Acalabrutinib 100 mg twice daily (bid) continuously |
|
| Cohort 2 | Experimental | Acalabrutinib 100 mg bid continuously and 40 mg dexamethasone once weekly |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| acalabrutinib | Drug |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Safety Profile of Acalabrutinib With and Without Dexamethasone | AEs and SAEs were coded by system organ class (SOC) and preferred term (PT) based on the Medical Dictionary for Regulatory Activities (MedDRA) reporting system. All AEs summarized were treatment-emergent. Summaries were also presented by the severity of the AE (per Common Toxicity Criteria for Adverse Events [CTCAE]) and by relationship to study drug as assessed by the investigator. Events of clinical interest (ECIs) selected for dedicated analysis were evaluated using Standardized MedDRA Queries, where available, by SOC, or by Sponsor-defined baskets of MedDRA Adverse Event Grouped Terms (AEGTs). The following ECIs were summarized: Cardiac events (including a subset of atrial fibrillation), cytopenias (anemia, leukopenia, neutropenia, and thrombocytopenia), hemorrhage (including a subset of major hemorrhage), hepatic events, hypertension, infection, interstitial lung disease/pneumonitis, second primary malignancies (second primary malignancies excluding skin), tumor lysis syndrome. | From first dose of study drug up to Cycle 12 (48 weeks). Subjects who showed benefit from study drugs were allowed to continue until disease progression. |
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacokinetic (PK) Parameters Calculated for Acalabrutinib: AUC0-4, AUClast, AUCINF, Cmax, Tmax, λz, t1/2, CL/F, and Vz/F. PK Parameters Calculated for Dexamethasone: Tmax, Cmax, AUC0-4 and AUClast. | The plasma PK of study drug was characterized using noncompartmental analysis. PK parameters were calculated whenever possible, from plasma concentrations of acalabrutinib. Missing dates or times could have been imputed for PK and pharmacodynamic (PD) samples if the missing values could be established with an acceptable level of accuracy based on other information obtained during the visit in question. If PK and PD sampling for a 33 Final Clinical Study Report Drug Substance Acalabrutinib Study Code ACE-MY-001 Edition Number 2 Date 31 October 2018 given subject was not performed according to protocol, the subject could have been excluded from the PK and PD analyses. The PK parameters were tabulated and summarized using descriptive statistics. For each PD variable, the concentration at each assessment was described. The change from baseline to each assessment was summarized. As appropriate the on treatment values were compared with the pretreatment baseline values using paired t-tests. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Acerta Clinical Trials | 1-888-292-9613 | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Baltimore | Maryland | United States | ||||
| United Kingdom |
Not provided
Multicenter, open-label, randomized, parallel-group study to evaluate the safety, pharmacokinetics, pharmacodynamics and activity of acalabrutinib with/without dexamethasone in subjects with relapsed/refractory multiple myeloma in US and United Kingdom. 27 subjects enrolled into 2 cohorts. Enrollment was discontinued because of lack of efficacy.
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| ID | Title | Description |
|---|---|---|
| FG000 | Cohort 1 | Acalabrutinib 100 mg twice daily (bid) continuously |
| FG001 | Cohort 2 | Acalabrutinib 100 mg bid continuously and 40 mg dexamethasone once weekly |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Not provided
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| ID | Title | Description |
|---|---|---|
| BG000 | Cohort 1 | Acalabrutinib 100 mg twice daily (bid) continuously |
| BG001 | Cohort 2 | Acalabrutinib 100 mg bid continuously and 40 mg dexamethasone once weekly |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of 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 | Safety Profile of Acalabrutinib With and Without Dexamethasone | AEs and SAEs were coded by system organ class (SOC) and preferred term (PT) based on the Medical Dictionary for Regulatory Activities (MedDRA) reporting system. All AEs summarized were treatment-emergent. Summaries were also presented by the severity of the AE (per Common Toxicity Criteria for Adverse Events [CTCAE]) and by relationship to study drug as assessed by the investigator. Events of clinical interest (ECIs) selected for dedicated analysis were evaluated using Standardized MedDRA Queries, where available, by SOC, or by Sponsor-defined baskets of MedDRA Adverse Event Grouped Terms (AEGTs). The following ECIs were summarized: Cardiac events (including a subset of atrial fibrillation), cytopenias (anemia, leukopenia, neutropenia, and thrombocytopenia), hemorrhage (including a subset of major hemorrhage), hepatic events, hypertension, infection, interstitial lung disease/pneumonitis, second primary malignancies (second primary malignancies excluding skin), tumor lysis syndrome. | Posted | Count of Participants | Participants | From first dose of study drug up to Cycle 12 (48 weeks). Subjects who showed benefit from study drugs were allowed to continue until disease progression. |
Reported Adverse Events (AEs) include events starting on or after Day 0 and on or before Day 1210.
Not provided
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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 | Cohort 1 | Acalabrutinib 100 mg twice daily (bid) continuously | 2 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hypercalcaemia | Metabolism and nutrition disorders | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Acerta Clinical Trials | Acerta Pharma B.V. | 1-888-292-9613 | acertamc@dlss.com |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jan 13, 2016 | Apr 22, 2020 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Sep 20, 2018 | Apr 22, 2020 | SAP_001.pdf |
Not provided
| ID | Term |
|---|---|
| D009101 | Multiple Myeloma |
| ID | Term |
|---|---|
| D054219 | Neoplasms, Plasma Cell |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D020141 | Hemostatic Disorders |
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| ID | Term |
|---|---|
| C000604908 | acalabrutinib |
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| On Days 1 and 22: pre-dose, and at 0.5, 0.75, 1, 2, 4, and 6 hours after the morning dose. On Days 8, 15, and 28: pre-dose and 1 hour after the morning dose. |
| Bruton Tyrosine Kinase (BTK) Occupancy | The percent occupied BTK was calculated in each subject's peripheral blood mononuclear cells (PBMC) sample for each assessment timepoint using an ELISA-based method. Samples from 17 subjects met the criteria for data inclusion, having a dynamic range (signal to noise) of ≥5 for the Day 1 pre-dose timepoint. Acalabrutinib administered at 100 mg bid resulted in a median steady-state (Day 8) BTK target occupancy level of 95% and 98% for Cohort 1 and Cohort 2, respectively. The Days 28 and 56 assessments, both taken at pre-dose, were >97% occupancy for each cohort. Intersubject variability was low, with 6 of 7 (86%) subjects in Cohort 1 and 4 of 5 (80%) subjects in Cohort 2 having >90% BTK occupancy at steady-state trough (12h post-dose). The single subject in Cohort 2 with <90% occupancy at Day 8 pre-dose did not take their Day 7 doses. | On Days 1 and 8: pre-dose and at 4 hours after the morning dose. On Days 28 and 56: morning pre-dose only. |
| Response Assessed According to Guidelines Proposed by the International Myeloma Workshop Consensus Panel and European Group for Blood and Marrow Transplant | Per EBMT: CR, negative immunofixation of serum and urine, disappearance of plasmacytomas and < 5% plasma cells; Stringent complete response (SCR), CR + normal flow cytometry and absence of clonal plasma cells; Very good partial response (VGPR), Serum and urine M-protein detectable on immunofixation but not on electrophoresis or > 90% reduction is serum and urine M protein; Partial response (PR), > 50% reduction in serum M-protein and > 90% reduction in 24 hour urine M-protein, > 50% reduction in baseline soft tissue plasmacytoma; Minimal response (MR), 25-49% reduction of serum M-protein and 50-59% reduction in 24 hour urine M-protein, 25-49% reduction in plasmacytomas and no increase in lytic bone lesions; Stable disease (SD), not meeting criteria for CR, VGPR, MR, PR or progressive disease (PD); PD, increase of 25% or more from nadir in serum M-protein, urine M-protein, new or increased bone lesions or plasmacytomas, or hypercalcemia solely attributed to multiple myeloma. | From first dose of study drug up to Cycle 12 (48 weeks). Subjects who showed benefit from study drugs were allowed to continue until disease progression |
| Leicester |
| United Kingdom |
| Guys and St Thomas' Hospital NHS Foundation Trust | London | United Kingdom |
| Started another cancer therapy |
|
| Withdrawal by Subject |
|
| In agreement with patient, no benefit |
|
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Median | Full Range | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| ID | Title | Description |
|---|
| OG000 | Cohort 1 | Acalabrutinib 100 mg twice daily (bid) continuously |
| OG001 | Cohort 2 | Acalabrutinib 100 mg bid continuously and 40 mg dexamethasone once weekly |
|
|
| Secondary | Pharmacokinetic (PK) Parameters Calculated for Acalabrutinib: AUC0-4, AUClast, AUCINF, Cmax, Tmax, λz, t1/2, CL/F, and Vz/F. PK Parameters Calculated for Dexamethasone: Tmax, Cmax, AUC0-4 and AUClast. | The plasma PK of study drug was characterized using noncompartmental analysis. PK parameters were calculated whenever possible, from plasma concentrations of acalabrutinib. Missing dates or times could have been imputed for PK and pharmacodynamic (PD) samples if the missing values could be established with an acceptable level of accuracy based on other information obtained during the visit in question. If PK and PD sampling for a 33 Final Clinical Study Report Drug Substance Acalabrutinib Study Code ACE-MY-001 Edition Number 2 Date 31 October 2018 given subject was not performed according to protocol, the subject could have been excluded from the PK and PD analyses. The PK parameters were tabulated and summarized using descriptive statistics. For each PD variable, the concentration at each assessment was described. The change from baseline to each assessment was summarized. As appropriate the on treatment values were compared with the pretreatment baseline values using paired t-tests. | Day 1: 24 (of 27 subjects enrolled) were equally randomized (1:1 ratio) into two cohorts to receive Acalabrutinib (12 in Cohort 1), or with dexamethasone (12 in Cohort 2). Day 22: 17 (of 24) subjects with PK data were remaining: 9 in Cohort 1 and 8 in Cohort 2. Seven subjects discontinued the study prior to Day 22. | Posted | Mean | Standard Deviation | percentage of CV | On Days 1 and 22: pre-dose, and at 0.5, 0.75, 1, 2, 4, and 6 hours after the morning dose. On Days 8, 15, and 28: pre-dose and 1 hour after the morning dose. |
|
|
|
| Secondary | Bruton Tyrosine Kinase (BTK) Occupancy | The percent occupied BTK was calculated in each subject's peripheral blood mononuclear cells (PBMC) sample for each assessment timepoint using an ELISA-based method. Samples from 17 subjects met the criteria for data inclusion, having a dynamic range (signal to noise) of ≥5 for the Day 1 pre-dose timepoint. Acalabrutinib administered at 100 mg bid resulted in a median steady-state (Day 8) BTK target occupancy level of 95% and 98% for Cohort 1 and Cohort 2, respectively. The Days 28 and 56 assessments, both taken at pre-dose, were >97% occupancy for each cohort. Intersubject variability was low, with 6 of 7 (86%) subjects in Cohort 1 and 4 of 5 (80%) subjects in Cohort 2 having >90% BTK occupancy at steady-state trough (12h post-dose). The single subject in Cohort 2 with <90% occupancy at Day 8 pre-dose did not take their Day 7 doses. | 17 (of 27) subjects with evaluable data. For 10 subjects the data was excluded due to: no Day 1 sample received, low cells events or parent populations, or other deviation. Day 1 post and additional time points, further decrease of evaluable data due to: subject discontinuation, low cells events or parent populations, or other deviation. | Posted | Mean | Standard Deviation | percentage of occupied BTK | On Days 1 and 8: pre-dose and at 4 hours after the morning dose. On Days 28 and 56: morning pre-dose only. |
|
|
|
| Secondary | Response Assessed According to Guidelines Proposed by the International Myeloma Workshop Consensus Panel and European Group for Blood and Marrow Transplant | Per EBMT: CR, negative immunofixation of serum and urine, disappearance of plasmacytomas and < 5% plasma cells; Stringent complete response (SCR), CR + normal flow cytometry and absence of clonal plasma cells; Very good partial response (VGPR), Serum and urine M-protein detectable on immunofixation but not on electrophoresis or > 90% reduction is serum and urine M protein; Partial response (PR), > 50% reduction in serum M-protein and > 90% reduction in 24 hour urine M-protein, > 50% reduction in baseline soft tissue plasmacytoma; Minimal response (MR), 25-49% reduction of serum M-protein and 50-59% reduction in 24 hour urine M-protein, 25-49% reduction in plasmacytomas and no increase in lytic bone lesions; Stable disease (SD), not meeting criteria for CR, VGPR, MR, PR or progressive disease (PD); PD, increase of 25% or more from nadir in serum M-protein, urine M-protein, new or increased bone lesions or plasmacytomas, or hypercalcemia solely attributed to multiple myeloma. | Posted | Count of Participants | Participants | From first dose of study drug up to Cycle 12 (48 weeks). Subjects who showed benefit from study drugs were allowed to continue until disease progression |
|
|
|
| 13 |
| 5 |
| 13 |
| 13 |
| 13 |
| EG001 | Cohort 2 | Acalabrutinib 100 mg bid continuously and 40 mg dexamethasone once weekly | 4 | 14 | 9 | 14 | 14 | 14 |
| Acute kidney injury | Renal and urinary disorders | Systematic Assessment |
|
| Angina pectoris | Cardiac disorders | Systematic Assessment |
|
| Bacteraemia | Infections and infestations | Systematic Assessment |
|
| Cellulitis | Infections and infestations | Systematic Assessment |
|
| Fatigue | General disorders | Systematic Assessment |
|
| Headache | Nervous system disorders | Systematic Assessment |
|
| Hyperviscosity syndrome | Blood and lymphatic system disorders | Systematic Assessment |
|
| Lower gastrointestinal haemorrhage | Gastrointestinal disorders | Systematic Assessment |
|
| Muscular weakness | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Norovirus test positive | Investigations | Systematic Assessment |
|
| Pain | General disorders | Systematic Assessment |
|
| Pneumonia | Infections and infestations | Systematic Assessment |
|
| Pneumonia influenzal | Infections and infestations | Systematic Assessment |
|
| Renail impairment | Renal and urinary disorders | Systematic Assessment |
|
| Sepsis | Infections and infestations | Systematic Assessment |
|
| Skin mass | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Syncope | Nervous system disorders | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | Systematic Assessment |
|
| Headache | Nervous system disorders | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Fatigue | General disorders | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Confusional state | Psychiatric disorders | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | Systematic Assessment |
|
| Contusion | Psychiatric disorders | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | Systematic Assessment |
|
| Hypercalcaemia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Pyrexia | General disorders | Systematic Assessment |
|
| Rhinitis | Infections and infestations | Systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | Systematic Assessment |
|
| Abdominal distension | Gastrointestinal disorders | Systematic Assessment |
|
| Acute kidney injury | Renal and urinary disorders | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Cardiac murmur | Investigations | Systematic Assessment |
|
| Dizziness | Nervous system disorders | Systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | Systematic Assessment |
|
| Ear pain | Ear and labyrinth disorders | Systematic Assessment |
|
| Haemoptysis | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Lethargy | Nervous system disorders | Systematic Assessment |
|
| Lower respiratory tract infection | Infections and infestations | Systematic Assessment |
|
| Muscular weakness | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Oedema peripheral | General disorders | Systematic Assessment |
|
| Pain | General disorders | Systematic Assessment |
|
| Platelet count decreased | Investigations | Systematic Assessment |
|
| Sepsis | Infections and infestations | Systematic Assessment |
|
| White blood cell count decreased | Investigations | Systematic Assessment |
|
Site and PI can publish/publicly present the results of the study only with prior written consent of Sponsor or otherwise after expiry of 12 months following completion of the study.
Site and PI agree to provide 30 days written notice to Sponsor prior to submission for publication or presentation."
| D014652 |
| Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D010265 | Paraproteinemias |
| D001796 | Blood Protein Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D006474 | Hemorrhagic Disorders |
| D008232 | Lymphoproliferative Disorders |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| AUC (area under the curve)_0-4 (hr*ng/mL) |
|
| AUC_last (hr*ng/mL) |
|
| AUC_INF (infinity) (hr*ng/mL) |
|
| VGPR |
|
| PR |
|
| MR |
|
| SD |
|
| PD |
|
| NE (not evaluable) |
|