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| ID | Type | Description | Link |
|---|---|---|---|
| ISIS 481464 | Other Identifier | ISIS Pharmaceuticals Inc |
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| Name | Class |
|---|---|
| Ionis Pharmaceuticals, Inc. | INDUSTRY |
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This is a phase I/Ib open-label, multicentre study to assess the safety, tolerability, pharmacokinetics and preliminary anti-tumour activity of AZD9150 in patients with advanced/metastatic hepatocellular carcinoma.
A Phase I/Ib, Open-Label, Multicentre Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Anti-tumour Activity of AZD9150 in Patients with Advanced/Metastatic Hepatocellular Carcinoma.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| AZD9150 | Experimental | There are two parts, dose escalation phase (Part A) and dose expansion phase (Part B). |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| AZD9150 | Drug | Intravenous infusion over 3 hours. |
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| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Dose Limiting Toxicities During Cycle 1 | Cycle 1 was defined as 3 loading doses given on Days 1, 3, and 5 followed by 3 weekly doses given on Days 8, 15, and 22. | DLT assessment window - Cycle 1 (22 days) |
| Measure | Description | Time Frame |
|---|---|---|
| Evaluation of Pharmacokinetics (PK) of AZD9150 (Following Single Administrations in Patients With HCC) by Determining Cmax, Using the Plasma Concentration Data. | 8 times (pre-dose, 1.5, 3, 3.5, 4, 6, 8, 24 hours post-dose) on Day1 of Cycle1. For additional 6 patients in Japan, 8 times (pre-dose, 1.5, 3, 3.5, 4, 6, 8, 24 hours post-dose) on Day1 of Cycle1. From the multiple samples a timecourse is obtained of treatment conc in the plasma over time. From this curve the associated PK parameters e.g. Cmax are obtained. For n patients we obtain up to n parameters which can then be averaged. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Frank Neumann, MD | AstraZeneca | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | Hong Kong | Hong Kong | ||||
| Research Site |
Note that 39 patients is the number of patients who were actually assigned to treatment out of the total enrolled. The ecpansion phase consisted of the 3mg/kg group only.
The first patient entered the study on 03 May 2013, and the last patient last visit before the DCO was 31 December 2014. The DCO date was 05 January 2015.
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| ID | Title | Description |
|---|---|---|
| FG000 | AZD9150 1mg/kg | Intravenous. Part A. |
| FG001 | AZD9150 1.5 mg/kg | Intravenous dosing Part A |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| 8 times of PK sampling on Day1 of Cycle1. Additional 6 patients in Japan; 8 times of PK sampling on Day1 of Cycle1. |
| Preliminary Assessment of the Anti-tumour Activity of AZD9150 by Evaluation of Tumour Response. | Tumour response assessment by modified Response Evaluation Criteria in Solid Tumours (RECIST). Overall tumour response: assessed by mRECIST for HCC overall visit response of CR (disappearance of baseline TLs and NTLs), PR (>=30% decrease in sum of TLs), SD (neither PR nor PD), PD (sum TLs increased >20%), or NE . | Every 6 weeks, assessed up to 12 months. |
| Evaluation of Pharmacokinetics (PK) of AZD9150 (Following Single Administrations in Patients With HCC) by Determining Tmax, Using the Plasma Concentration Data. | 8 times (pre-dose, 1.5, 3, 3.5, 4, 6, 8, 24 hours post-dose) on Day1 of Cycle1. For additional 6 patients in Japan, 8 times (pre-dose, 1.5, 3, 3.5, 4, 6, 8, 24 hours post-dose) on Day1 of Cycle1. | 8 times of PK sampling on Day1 of Cycle1. Additional 6 patients in Japan; 8 times of PK sampling on Day 1 of Cycle 1. |
| Chūōku |
| Japan |
| Research Site | Kashiwa-shi | Japan |
| Research Site | Matsuyama | Japan |
| Research Site | Seoul | South Korea |
| Research Site | Tainan | Taiwan |
| Research Site | Taipei | Taiwan |
| FG002 |
| AZD9150 2mg/kg |
Intravenous dosing Part A |
| FG003 | AZD9150 2.5mg/kg | Intravenous dosing Part A |
| FG004 | AZD9150 3mg/kg | Pooled over parts A & B |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | AZD9150 1mg/kg | Intravenous. Part A. |
| BG001 | 1.5 mg/kg | given intravenously. Part A |
| BG002 | 2 mg/kg | given intravenously Part A |
| BG003 | 2.5 mg/kg | given intravenously Part A |
| BG004 | 3 mg/kg | given intravenously (Part A & B pooled) |
| BG005 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Gender | Count of Participants | Participants |
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| 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 | Number of Participants With Dose Limiting Toxicities During Cycle 1 | Cycle 1 was defined as 3 loading doses given on Days 1, 3, and 5 followed by 3 weekly doses given on Days 8, 15, and 22. | Safety: All patients who received at least 1 dose of AZD9150 | Posted | Number | participants with DLT | DLT assessment window - Cycle 1 (22 days) |
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| Secondary | Evaluation of Pharmacokinetics (PK) of AZD9150 (Following Single Administrations in Patients With HCC) by Determining Cmax, Using the Plasma Concentration Data. | 8 times (pre-dose, 1.5, 3, 3.5, 4, 6, 8, 24 hours post-dose) on Day1 of Cycle1. For additional 6 patients in Japan, 8 times (pre-dose, 1.5, 3, 3.5, 4, 6, 8, 24 hours post-dose) on Day1 of Cycle1. From the multiple samples a timecourse is obtained of treatment conc in the plasma over time. From this curve the associated PK parameters e.g. Cmax are obtained. For n patients we obtain up to n parameters which can then be averaged. | PK: All dosed patients with reportable AZD9150 plasma concentrations and no important adverse events or protocol deviations that may impact PK | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | 8 times of PK sampling on Day1 of Cycle1. Additional 6 patients in Japan; 8 times of PK sampling on Day1 of Cycle1. |
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| Secondary | Preliminary Assessment of the Anti-tumour Activity of AZD9150 by Evaluation of Tumour Response. | Tumour response assessment by modified Response Evaluation Criteria in Solid Tumours (RECIST). Overall tumour response: assessed by mRECIST for HCC overall visit response of CR (disappearance of baseline TLs and NTLs), PR (>=30% decrease in sum of TLs), SD (neither PR nor PD), PD (sum TLs increased >20%), or NE . | Evaluable for response: Dosed patients with measurable disease at baseline | Posted | Number | participants with Partial Response | Every 6 weeks, assessed up to 12 months. |
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| Secondary | Evaluation of Pharmacokinetics (PK) of AZD9150 (Following Single Administrations in Patients With HCC) by Determining Tmax, Using the Plasma Concentration Data. | 8 times (pre-dose, 1.5, 3, 3.5, 4, 6, 8, 24 hours post-dose) on Day1 of Cycle1. For additional 6 patients in Japan, 8 times (pre-dose, 1.5, 3, 3.5, 4, 6, 8, 24 hours post-dose) on Day1 of Cycle1. | PK: All dosed patients with reportable AZD9150 plasma concentrations and no important adverse events or protocol deviations that may impact PK | Posted | Median | Full Range | h | 8 times of PK sampling on Day1 of Cycle1. Additional 6 patients in Japan; 8 times of PK sampling on Day 1 of Cycle 1. |
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AEs will be collected throughout the study, from informed consent until the end of the follow up period. The follow-up period is defined as 28 +/-7 days after study treatment is discontinued.
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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 | AZD9150 1mg/kg | Intravenous. Part A. | 0 | 6 | 6 | 6 | ||
| EG001 | 1.5 mg/kg | given intravenously. Part A | 0 | 6 | 6 | 6 | ||
| EG002 | 2 mg/kg | given intravenously Part A | 2 | 7 | 7 | 7 | ||
| EG003 | 2.5 mg/kg | given intravenously Part A | 2 | 5 | 5 | 5 | ||
| EG004 | 3 mg/kg | given intravenously (Part A & B pooled) | 4 | 15 | 15 | 15 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cellulitis | Infections and infestations | Systematic Assessment |
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| Liver abscess | Infections and infestations | Systematic Assessment |
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| Anaemia | Blood and lymphatic system disorders | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | Systematic Assessment |
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| Abdominal pain upper | Gastrointestinal disorders | Systematic Assessment |
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| Peritoneal haemorrhage | Gastrointestinal disorders | Systematic Assessment |
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| Hepatorenal failure | Hepatobiliary disorders | Systematic Assessment |
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| Alanine amonitransferase increased | Investigations | Systematic Assessment |
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| Aspartate aminotransferase increased | Investigations | Systematic Assessment |
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| Platelet count decreased | Investigations | Systematic Assessment |
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| Prothrombin time prolonged | Investigations | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Aspartate aminotransferase increased | Investigations | Systematic Assessment |
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| Platelet count decreased | Investigations | Systematic Assessment |
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| Alanine aminotransferase increased | Investigations | Systematic Assessment |
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| Neutrophil count decreased | Investigations | Systematic Assessment |
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| Blood bilirubin increased | Investigations | Systematic Assessment |
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| Gamma-glutamylytransferase increased | Investigations | Systematic Assessment |
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| White blod cell count decreased | Investigations | Systematic Assessment |
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| Prothrombin time prolonged | Investigations | Systematic Assessment |
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| Dyspepsia | Gastrointestinal disorders | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | Systematic Assessment |
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| Abdominal distension | Gastrointestinal disorders | Systematic Assessment |
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| Haemoptysis | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Productive cough | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Dysphonia | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Dyspnoea | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Neutropenia | Blood and lymphatic system disorders | Systematic Assessment |
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| Anaemia | Blood and lymphatic system disorders | Systematic Assessment |
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| Thrombocytopenia | Blood and lymphatic system disorders | Systematic Assessment |
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| Fatigue | General disorders | Systematic Assessment |
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| Pyrexia | General disorders | Systematic Assessment |
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| Asthenia | General disorders | Systematic Assessment |
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| Malaise | General disorders | Systematic Assessment |
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| Decreased apetite | Metabolism and nutrition disorders | Systematic Assessment |
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| Hypoalbuminaemia | Metabolism and nutrition disorders | Systematic Assessment |
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| Hypophosphataemia | Metabolism and nutrition disorders | Systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | Systematic Assessment |
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| Flank Pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Headache | Nervous system disorders | Systematic Assessment |
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| Dizziness | Nervous system disorders | Systematic Assessment |
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| Hypertension | Vascular disorders | Systematic Assessment |
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| Hepatic function abnormal | Hepatobiliary disorders | Systematic Assessment |
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| Haematuria | Renal and urinary disorders | Systematic Assessment |
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| Insomnia | Psychiatric disorders | Systematic Assessment |
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| Pruritus | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Alopecia | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Urticaria | Skin and subcutaneous tissue disorders | Systematic Assessment |
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The overall study objectives were achieved earlier than anticipated, so recruitment was stopped and the study was considered complete. In turn multiple dose PK profiles were not obtained during the study expansion phase.
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Martin Scott, MD/PhD | AstraZeneca Pharmaceuticals LP | Martin.Scott@astrazeneca.com | Martin.Scott@astrazeneca.com |
| ID | Term |
|---|---|
| D006528 | Carcinoma, Hepatocellular |
| ID | Term |
|---|---|
| D000230 | Adenocarcinoma |
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D008113 | Liver Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D004066 | Digestive System Diseases |
| D008107 | Liver Diseases |
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| ID | Term |
|---|---|
| C000610954 | danvatirsen |
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| Male |
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| 2.5 mg/kg |
given intravenously Part A |
| OG004 | 3 mg/kg | given intravenously (Part A & B pooled) |
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| 3 mg/kg |
given intravenously (Part A & B pooled) |
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| OG004 |
| 3 mg/kg |
given intravenously (Part A & B pooled) |
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