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The purpose of this study is to determine the effect of AZD0530 on subjects with breast cancer or prostate cancer with metastatic bone disease in comparison to zoledronic acid.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| AZD0530 175 mg | Experimental | AZD0530 (saracatinib) 175 mg once daily |
|
| Zoledronic Acid 4 mg | Experimental | Zoledronic Acid 4 mg on Day 1 of the 4-week treatment period |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| AZD0530 | Drug | Daily oral dose |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Percentage Change From Baseline in Serum Beta C-terminal Cross-linking Telopeptide of Type I Collagen (betaCTX) at Week 4 | Result at Week 4 minus result at baseline as a percentage of the result at baseline, based on log transformed data. Back transformation of the least squares (LS) mean. | Baseline to Week 4 |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage Change From Baseline in Serum Bone-specific Alkaline Phosphatase (bALP) at Week 4 | Result at Week 4 minus result at baseline as a percentage of the result at baseline, based on log transformed data. Back transformation of the least squares (LS) mean. | Baseline to Week 4 |
| Percentage Change From Baseline in Serum Cross-linked C-terminal Telopeptide of Type I Collagen (ICTP) at Week 4 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Richard Finkelman, DDS, PhD | AstraZeneca | Study Director |
| Meabe Aklilu, MD | Wake Forest University Health Sciences | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | Pleasant Hill | California | United States | |||
| Research Site |
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Randomised=full analysis set: AZD0530 175mg=69, Zoledronic acid 4mg=70; safety set: AZD0530 175mg=68, Zoledronic acid 4mg=69
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| ID | Title | Description |
|---|---|---|
| FG000 | AZD0530 175 mg | AZD0530 (saracatinib) 175 mg once daily |
| FG001 | Zoledronic Acid 4 mg | Zoledronic Acid 4 mg on Day 1 of the 4-week treatment period |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Zoledronic Acid | Drug |
|
|
Result at Week 4 minus result at baseline as a percentage of the result at baseline, based on log transformed data. Back transformation of the least squares (LS) mean. |
| Baseline to Week 4 |
| Percentage Change From Baseline in Serum N-terminal Propeptide of Type I Procollagen (PINP) at Week 4 | Result at Week 4 minus result at baseline as a percentage of the result at baseline, based on log transformed data. Back transformation of the least squares (LS) mean. | Baseline to Week 4 |
| Percentage Change From Baseline in Serum Tartrate-resistant Acid Phosphatase 5b (TRAP5b) at Week 4 | Result at Week 4 minus result at baseline as a percentage of the result at baseline, based on log transformed data. Back transformation of the least squares (LS) mean. | Baseline to Week 4 |
| Percentage Change From Baseline in Urine N-terminal Cross-linking Telopeptide of Type I Collagen Normalised to Creatinine (NTx/Cr) at Week 4 | Result at Week 4 minus result at baseline as a percentage of the result at baseline, based on log transformed data. Back transformation of the least squares (LS) mean. | Baseline to Week 4 |
| Percentage Change From Baseline in Urine Alpha-alpha C-terminal Cross-linking Telopeptide of Type I Collagen Normalised to Creatinine (aaCTx/Cr) at Week 4 | Result at Week 4 minus result at baseline as a percentage of the result at baseline, based on log transformed data. Back transformation of the least squares (LS) mean. | Baseline to Week 4 |
| Saracatinib: Area Under the Curve at Steady State (AUCss) | Previous studies have shown that saracatinib reduces osteoclast function and bone resorption. Bone turnover, the combined result of bone formation and bone resorption, can be assessed in real time by measuring specific markers of bone turnover in serum and in urine. These markers were assessed in a study of patients with metastatic bone disease treated with saracatinib. Specific assays are available to quantitate these markers in serum and urine. In this study the effects of saracatinib on bone turnover were compared with the effects of zoledronic acid, a marketed drug known to inhibit bone resorption in cancer patients with bone metastatses. | Pre-dose on days 8, 15, 29; 2 hours, 4 hours, 6 hours, 9 hours post dose on day 29 |
| Saracatinib: Plasma Clearance at Steady State (CLss/F) | Pre-dose on days 8, 15, 29; 2 hours, 4 hours, 6 hours, 9 hours post dose on day 29 |
| Saracatinib: Maximum Plasma Concentration at Steady State (Css,Max) | Pre-dose on days 8, 15, 29; 2 hours, 4 hours, 6 hours, 9 hours post dose on day 29 |
| Saracatinib: Minimum Plasma Concentration at Steady State (Css,Min) | Pre-dose on days 8, 15, 29; 2 hours, 4 hours, 6 hours, 9 hours post dose on day 29 |
| Saracatinib: Time to Cssmax (Tmax) | Pre-dose on days 8, 15, 29; 2 hours, 4 hours, 6 hours, 9 hours post dose on day 29 |
| N-desmethyl Metabolite of Saracatinib: Area Under the Curve at Steady State (AUCss) | Pre-dose on days 8, 15, 29; 2 hours, 4 hours, 6 hours, 9 hours post dose on day 29 |
| N-desmethyl Metabolite of Saracatinib: Maximum Plasma Concentration at Steady State (Css,Max) | Pre-dose on days 8, 15, 29; 2 hours, 4 hours, 6 hours, 9 hours post dose on day 29 |
| N-desmethyl Metabolite of Saracatinib: Minimum Plasma Concentration at Steady State (Css,Min) | Pre-dose on days 8, 15, 29; 2 hours, 4 hours, 6 hours, 9 hours post dose on day 29 |
| N-desmethyl Metabolite of Saracatinib: AUCss Metabolite to Parent Ratio | Pre-dose on days 8, 15, 29; 2 hours, 4 hours, 6 hours, 9 hours post dose on day 29 |
| N-desmethyl Metabolite of Saracatinib: Time to Cssmax (Tmax) | Pre-dose on days 8, 15, 29; 2 hours, 4 hours, 6 hours, 9 hours post dose on day 29 |
| Sacramento |
| California |
| United States |
| Research Site | Middlebury | Connecticut | United States |
| Research Site | Aventura | Florida | United States |
| Research Site | Baltimore | Maryland | United States |
| Research Site | Ann Arbor | Michigan | United States |
| Research Site | Poughkeepsie | New York | United States |
| Research Site | Winston-Salem | North Carolina | United States |
| Research Site | Hershey | Pennsylvania | United States |
| Research Site | Edmonton | Alberta | Canada |
| Research Site | Vancouver | British Columbia | Canada |
| Research Site | Toronto | Ontario | Canada |
| Research Site | Montreal | Quebec | Canada |
| Research Site | Québec | Quebec | Canada |
| Research Site | Arhus N | Denmark |
| Research Site | Frederica | Denmark |
| Research Site | Herlev | Denmark |
| Research Site | Holstebro | Denmark |
| Research Site | Kristiansand | Norway |
| Research Site | Oslo | Norway |
| Research Site | Lisbon | Portugal |
| Research Site | Barcelona | Catalonia | Spain |
| Research Site | Lleida | Catalonia | Spain |
| Research Site | Valencia | Valencia | Spain |
| Research Site | Uppsala | Sweden |
| Research Site | Cardiff | United Kingdom |
| Research Site | Glasgow | United Kingdom |
| Research Site | Manchester | United Kingdom |
| 30 Days Follow-up |
|
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | AZD0530 175 mg | AZD0530 (saracatinib) 175 mg once daily |
| BG001 | Zoledronic Acid 4 mg | Zoledronic Acid 4 mg on Day 1 of the 4-week treatment period |
| BG002 | 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 | Mean | Standard Deviation | Years |
| |||||||||||||||
| Sex: Female, Male | 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 | Percentage Change From Baseline in Serum Beta C-terminal Cross-linking Telopeptide of Type I Collagen (betaCTX) at Week 4 | Result at Week 4 minus result at baseline as a percentage of the result at baseline, based on log transformed data. Back transformation of the least squares (LS) mean. | The number of participants analyzed reflected the number of paired serum samples per participant that yielded valid assay results, not the total number of participants or completers. The number of evaluable paired serum samples will therefore be a subset of the total number of participants. | Posted | Geometric Mean | 95% Confidence Interval | Percentage change in betaCTX | Baseline to Week 4 |
|
|
| ||||||||||||||||||||||||||||
| Secondary | Percentage Change From Baseline in Serum Bone-specific Alkaline Phosphatase (bALP) at Week 4 | Result at Week 4 minus result at baseline as a percentage of the result at baseline, based on log transformed data. Back transformation of the least squares (LS) mean. | The number of participants analyzed reflected the number of paired serum samples per participant that yielded valid assay results, not the total number of participants or completers. The number of evaluable paired serum samples will therefore be a subset of the total number of participants. | Posted | Geometric Mean | 95% Confidence Interval | Percentage change in bALP | Baseline to Week 4 |
|
| |||||||||||||||||||||||||||||
| Secondary | Percentage Change From Baseline in Serum Cross-linked C-terminal Telopeptide of Type I Collagen (ICTP) at Week 4 | Result at Week 4 minus result at baseline as a percentage of the result at baseline, based on log transformed data. Back transformation of the least squares (LS) mean. | The number of participants analyzed reflected the number of paired serum samples per participant that yielded valid assay results, not the total number of participants or completers. The number of evaluable paired serum samples will therefore be a subset of the total number of participants. | Posted | Geometric Mean | 95% Confidence Interval | Percentage change in ICTP | Baseline to Week 4 |
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| |||||||||||||||||||||||||||||
| Secondary | Percentage Change From Baseline in Serum N-terminal Propeptide of Type I Procollagen (PINP) at Week 4 | Result at Week 4 minus result at baseline as a percentage of the result at baseline, based on log transformed data. Back transformation of the least squares (LS) mean. | The number of participants analyzed reflected the number of paired serum samples per participant that yielded valid assay results, not the total number of participants or completers. The number of evaluable paired serum samples will therefore be a subset of the total number of participants. | Posted | Geometric Mean | 95% Confidence Interval | Percentage change in PINP | Baseline to Week 4 |
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| |||||||||||||||||||||||||||||
| Secondary | Percentage Change From Baseline in Serum Tartrate-resistant Acid Phosphatase 5b (TRAP5b) at Week 4 | Result at Week 4 minus result at baseline as a percentage of the result at baseline, based on log transformed data. Back transformation of the least squares (LS) mean. | The number of participants analyzed reflected the number of paired serum samples per participant that yielded valid assay results, not the total number of participants or completers. The number of evaluable paired serum samples will therefore be a subset of the total number of participants. | Posted | Geometric Mean | 95% Confidence Interval | Percentage change in TRAP5b | Baseline to Week 4 |
|
| |||||||||||||||||||||||||||||
| Secondary | Percentage Change From Baseline in Urine N-terminal Cross-linking Telopeptide of Type I Collagen Normalised to Creatinine (NTx/Cr) at Week 4 | Result at Week 4 minus result at baseline as a percentage of the result at baseline, based on log transformed data. Back transformation of the least squares (LS) mean. | The number of participants analyzed reflected the number of paired serum samples per participant that yielded valid assay results, not the total number of participants or completers. The number of evaluable paired serum samples will therefore be a subset of the total number of participants. | Posted | Geometric Mean | 95% Confidence Interval | Percentage change in NTx/Cr | Baseline to Week 4 |
|
| |||||||||||||||||||||||||||||
| Secondary | Percentage Change From Baseline in Urine Alpha-alpha C-terminal Cross-linking Telopeptide of Type I Collagen Normalised to Creatinine (aaCTx/Cr) at Week 4 | Result at Week 4 minus result at baseline as a percentage of the result at baseline, based on log transformed data. Back transformation of the least squares (LS) mean. | The number of participants analyzed reflected the number of paired serum samples per participant that yielded valid assay results, not the total number of participants or completers. The number of evaluable paired serum samples will therefore be a subset of the total number of participants. | Posted | Geometric Mean | 95% Confidence Interval | Percentage change in aaCTx/Cr | Baseline to Week 4 |
|
| |||||||||||||||||||||||||||||
| Secondary | Saracatinib: Area Under the Curve at Steady State (AUCss) | Previous studies have shown that saracatinib reduces osteoclast function and bone resorption. Bone turnover, the combined result of bone formation and bone resorption, can be assessed in real time by measuring specific markers of bone turnover in serum and in urine. These markers were assessed in a study of patients with metastatic bone disease treated with saracatinib. Specific assays are available to quantitate these markers in serum and urine. In this study the effects of saracatinib on bone turnover were compared with the effects of zoledronic acid, a marketed drug known to inhibit bone resorption in cancer patients with bone metastatses. | Posted | Median | Full Range | ng•hr/ml | Pre-dose on days 8, 15, 29; 2 hours, 4 hours, 6 hours, 9 hours post dose on day 29 |
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| ||||||||||||||||||||||||||||||
| Secondary | Saracatinib: Plasma Clearance at Steady State (CLss/F) | Posted | Median | Full Range | L/h | Pre-dose on days 8, 15, 29; 2 hours, 4 hours, 6 hours, 9 hours post dose on day 29 |
|
| |||||||||||||||||||||||||||||||
| Secondary | Saracatinib: Maximum Plasma Concentration at Steady State (Css,Max) | Posted | Median | Full Range | ng/ml | Pre-dose on days 8, 15, 29; 2 hours, 4 hours, 6 hours, 9 hours post dose on day 29 |
|
| |||||||||||||||||||||||||||||||
| Secondary | Saracatinib: Minimum Plasma Concentration at Steady State (Css,Min) | Posted | Median | Full Range | ng/ml | Pre-dose on days 8, 15, 29; 2 hours, 4 hours, 6 hours, 9 hours post dose on day 29 |
|
| |||||||||||||||||||||||||||||||
| Secondary | Saracatinib: Time to Cssmax (Tmax) | Posted | Median | Full Range | h | Pre-dose on days 8, 15, 29; 2 hours, 4 hours, 6 hours, 9 hours post dose on day 29 |
|
| |||||||||||||||||||||||||||||||
| Secondary | N-desmethyl Metabolite of Saracatinib: Area Under the Curve at Steady State (AUCss) | Posted | Median | Full Range | ng.h/ml | Pre-dose on days 8, 15, 29; 2 hours, 4 hours, 6 hours, 9 hours post dose on day 29 |
|
| |||||||||||||||||||||||||||||||
| Secondary | N-desmethyl Metabolite of Saracatinib: Maximum Plasma Concentration at Steady State (Css,Max) | Posted | Median | Full Range | ng/ml | Pre-dose on days 8, 15, 29; 2 hours, 4 hours, 6 hours, 9 hours post dose on day 29 |
|
| |||||||||||||||||||||||||||||||
| Secondary | N-desmethyl Metabolite of Saracatinib: Minimum Plasma Concentration at Steady State (Css,Min) | Posted | Median | Full Range | ng/ml | Pre-dose on days 8, 15, 29; 2 hours, 4 hours, 6 hours, 9 hours post dose on day 29 |
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| Secondary | N-desmethyl Metabolite of Saracatinib: AUCss Metabolite to Parent Ratio | Posted | Median | Full Range | Ratio | Pre-dose on days 8, 15, 29; 2 hours, 4 hours, 6 hours, 9 hours post dose on day 29 |
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| Secondary | N-desmethyl Metabolite of Saracatinib: Time to Cssmax (Tmax) | Posted | Median | Full Range | h | Pre-dose on days 8, 15, 29; 2 hours, 4 hours, 6 hours, 9 hours post dose on day 29 |
|
|
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safety set: AZD0530 175mg=68, Zoledronic acid 4mg=69
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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 | AZD0530 175 mg | AZD0530 (saracatinib) 175 mg once daily | 11 | 68 | 51 | 68 | ||
| EG001 | Zoledronic Acid 4 mg | Zoledronic Acid 4 mg on Day 1 of the 4-week treatment period | 4 | 69 | 46 | 69 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Cardiac Arrest | Cardiac disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Myocardial Infarction | Cardiac disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
| |
| General Physical Health Deterioration | General disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 13.0 | Systematic Assessment |
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| Pneumonia | Infections and infestations | MedDRA 13.0 | Systematic Assessment |
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| Viral Infection | Infections and infestations | MedDRA 13.0 | Systematic Assessment |
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| Blood Creatinine Increased | Injury, poisoning and procedural complications | MedDRA 13.0 | Systematic Assessment |
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| Dehydration | Metabolism and nutrition disorders | MedDRA 13.0 | Systematic Assessment |
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| Bone Pain | Musculoskeletal and connective tissue disorders | MedDRA 13.0 | Systematic Assessment |
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| Muscle Spasms | Musculoskeletal and connective tissue disorders | MedDRA 13.0 | Systematic Assessment |
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| Musculoskeletal Pain | Musculoskeletal and connective tissue disorders | MedDRA 13.0 | Systematic Assessment |
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| Cerebral Haemorrhage | Nervous system disorders | MedDRA 13.0 | Systematic Assessment |
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| Renal Failure | Renal and urinary disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Renal Failure Acute | Renal and urinary disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Pulmonary Oedema | Respiratory, thoracic and mediastinal disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Deep Vein Thrombosis | Vascular disorders | MedDRA 13.0 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
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| Influenza Like Illness | General disorders | MedDRA 13.0 | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA 13.0 | Systematic Assessment |
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| Fatigue | General disorders | MedDRA 13.0 | Systematic Assessment |
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| Asthenia | General disorders | MedDRA 13.0 | Systematic Assessment |
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| Oedema Peripheral | General disorders | MedDRA 13.0 | Systematic Assessment |
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| Influenza | Infections and infestations | MedDRA 13.0 | Systematic Assessment |
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| Urinary Tract Infection | Infections and infestations | MedDRA 13.0 | Systematic Assessment |
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| Decreased Appetite | Metabolism and nutrition disorders | MedDRA 13.0 | Systematic Assessment |
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| Pain In Extremity | Musculoskeletal and connective tissue disorders | MedDRA 13.0 | Systematic Assessment |
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| Back Pain | Musculoskeletal and connective tissue disorders | MedDRA 13.0 | Systematic Assessment |
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| Musculoskeletal Pain | Musculoskeletal and connective tissue disorders | MedDRA 13.0 | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 13.0 | Systematic Assessment |
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| Bone Pain | Musculoskeletal and connective tissue disorders | MedDRA 13.0 | Systematic Assessment |
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| Neck Pain | Musculoskeletal and connective tissue disorders | MedDRA 13.0 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 13.0 | Systematic Assessment |
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| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 13.0 | Systematic Assessment |
|
Non-compliant patients were excluded from the biomarker analysis, in order to accurately assess effects due to treatment. The compliance criteria did not apply to the zoledronic acid arm, which led to an imbalance in the number of subjects analysed.
If a Study Site, or an investigator, requests permission to publish data from this study, any such publication (including oral presentations) is to be agreed with AstraZeneca prior to publication.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Gerard Lynch | AstraZeneca | aztrial_results_posting@astrazeneca.com |
| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| D011471 | Prostatic Neoplasms |
| D001859 | Bone Neoplasms |
| D001847 | Bone Diseases |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D005834 | Genital Neoplasms, Male |
| D014565 | Urogenital Neoplasms |
| D005832 | Genital Diseases, Male |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D011469 | Prostatic Diseases |
| D052801 | Male Urogenital Diseases |
| D009140 | Musculoskeletal Diseases |
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| ID | Term |
|---|---|
| C515233 | saracatinib |
| D000077211 | Zoledronic Acid |
| ID | Term |
|---|---|
| D004164 | Diphosphonates |
| D063065 | Organophosphonates |
| D009943 | Organophosphorus Compounds |
| D009930 | Organic Chemicals |
| D007093 | Imidazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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| Male |
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