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The objective of this study will be to investigate the safety and tolerability of olaparib tablet when given orally to Japanese patients with advanced solid malignancies. In addition, the pharmacokinetic profile, MTD (if possible) and efficacy of olaparib will be investigated.
MTD - maximum tolerated dose
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| olaparib tablet monotherapy | Experimental | olaparib tablet |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| olaparib | Drug | tablet oral |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Adverse Events | An adverse event is the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. This was recorded if it happend from the start dose to 30 days after the last of study drug. | From the start dose to 30 days after the last dose of study drug |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Dose Limiting Toxicities | Dose Limiting Toxicities were defined as study specific events that is determined to be possibly or probably related to olaparib (as determined by the investigator) and occurring during the first cycle of treatment (28 days after the first dose), irrespective of whether the toxicity resolved. | From the start dose to 28 days after the first dose of study drug |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Thomas Morris, M.D. | Global Medicines Development | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | Chūōku | 104-0045 | Japan | |||
| Research Site |
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| Label | URL |
|---|---|
| D081BC00001\_Study\_Report\_Synopsis | View source |
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A total of 28 participants gave informed consent to join this study. Five participants were screen failures so that 23 participants were assigned and received study treatment
First patient enrolled on 25 March 2013. Last patient enrolled on 31 October 2013. Data cut off on 31 July 2014.
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| ID | Title | Description |
|---|---|---|
| FG000 | 200 mg Bid, Dose Escalation Part | Olaparib tablet 200 mg bid, 400 mg/day, dose escalation part |
| FG001 | 300 mg Bid, Dose Escalation Part | Olaparib table 300 mg bid, 600 mg/day, dose escalation part |
| FG002 | 300 mg Bid, Expansion Part | Olaparib tablet 300 mg bid, 600 mg/day, expansion part |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 200 mg Bid, Dose Escalation Part | Olaparib tablet 200 mg bid, 400 mg/day, dose escalation part |
| BG001 | 300 mg Bid, Dose Escalation Part | Olaparib table 300 mg bid, 600 mg/day, dose escalation part |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With Adverse Events | An adverse event is the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. This was recorded if it happend from the start dose to 30 days after the last of study drug. | Posted | Number | Participants | From the start dose to 30 days after the last dose of study drug |
|
Through treatment and 30-day follow-up period, an average of about 4 months.
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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 | 200 mg Bid, Dose Escalation Part | Olaparib tablet 200 mg bid, 400 mg/day, dose escalation part |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Ileus | Gastrointestinal disorders | MedDRA Version 16.0 | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nasopharyngitis | Infections and infestations | MedDRA Version 16.0 | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Director | AstraZeneca | ClinicalTrialTransparency@astrazeneca.com |
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| ID | Term |
|---|---|
| D009369 | Neoplasms |
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| ID | Term |
|---|---|
| C531550 | olaparib |
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| Cmax Following Single Dosing | Day 1: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hours at post-dose |
| Cmax Following Multiple Dosing | Day 15: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours at post-dose |
| Tmax Following Single Dosing | Day 1: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hours at post-dose |
| Tmax Following Multiple Dosing | Day 15: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours at post-dose |
| AUC Following Single Dosing | Day 1: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hours at post-dose |
| AUC at Steady State Following Multiple Dosing | Day 15: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours at post-dose |
| Fukuoka |
| 811-1395 |
| Japan |
| Research Site | Sapporo | 003-0804 | Japan |
| Lack of Efficacy |
|
| Death |
|
| BG002 | 300 mg Bid, Expansion Part | Olaparib tablet 300 mg bid, 600 mg/day, expansion part |
| BG003 | Total | Total of all reporting groups |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Primary tumour location | Count of Participants | Participants |
|
| OG002 | 300 mg Bid, Expansion Part | Olaparib tablet 300 mg bid, 600 mg/day, expansion part |
|
|
| Secondary | Number of Participants With Dose Limiting Toxicities | Dose Limiting Toxicities were defined as study specific events that is determined to be possibly or probably related to olaparib (as determined by the investigator) and occurring during the first cycle of treatment (28 days after the first dose), irrespective of whether the toxicity resolved. | All patients in only the dose escalation part who received olaparib and completed the safety follow-up through the dose-limiting toxicity (DLT) evaluation period (28 days), or who experienced a DLT. | Posted | Number | Participants | From the start dose to 28 days after the first dose of study drug |
|
|
|
| Secondary | Cmax Following Single Dosing | Dose escalation part only | Posted | Geometric Mean | Geometric Coefficient of Variation | μg/mL | Day 1: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hours at post-dose |
|
|
|
| Secondary | Cmax Following Multiple Dosing | Dose escalation part only. Two participants (1 in 200 mg bid and 1 in 300 mg bid) had no PK data due to early discontinuation prior to Day 15. | Posted | Geometric Mean | Geometric Coefficient of Variation | μg/mL | Day 15: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours at post-dose |
|
|
|
| Secondary | Tmax Following Single Dosing | Dose escalation part only | Posted | Median | Full Range | hour | Day 1: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hours at post-dose |
|
|
|
| Secondary | Tmax Following Multiple Dosing | Dose escalation part only. Two participants (1 in 200 mg bid and 1 in 300 mg bid) had no PK data due to early discontinuation prior to Day 15. | Posted | Median | Full Range | hour | Day 15: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours at post-dose |
|
|
|
| Secondary | AUC Following Single Dosing | Dose escalation part only. One participant in 200 mg bid had no AUC data because AUC was not calculable for this participant. | Posted | Geometric Mean | Geometric Coefficient of Variation | μg*h/mL | Day 1: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hours at post-dose |
|
|
|
| Secondary | AUC at Steady State Following Multiple Dosing | Dose escalation part only. Two participants (1 in 200 mg bid and 1 in 300 mg bid) had no PK data due to early discontinuation prior to Day 15. | Posted | Geometric Mean | Geometric Coefficient of Variation | μg*h/mL | Day 15: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours at post-dose |
|
|
|
| 1 |
| 4 |
| 4 |
| 4 |
| EG001 | 300 mg Bid, Dose Escalation Part | Olaparib table 300 mg bid, 600 mg/day, dose escalation part | 0 | 7 | 7 | 7 |
| EG002 | 300 mg Bid, Expansion Part | Olaparib tablet 300 mg bid, 600 mg/day, expansion part | 0 | 12 | 10 | 12 |
| Paronychia | Infections and infestations | MedDRA Version 16.0 | Non-systematic Assessment |
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| Pneumonia | Infections and infestations | MedDRA Version 16.0 | Non-systematic Assessment |
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| Pyelonephritis | Infections and infestations | MedDRA Version 16.0 | Non-systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA Version 16.0 | Non-systematic Assessment |
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| Anaemia | Blood and lymphatic system disorders | MedDRA Version 16.0 | Non-systematic Assessment |
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| Neutropenia | Blood and lymphatic system disorders | MedDRA Version 16.0 | Non-systematic Assessment |
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| Decreased appetite | Metabolism and nutrition disorders | MedDRA Version 16.0 | Non-systematic Assessment |
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| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA Version 16.0 | Non-systematic Assessment |
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| Anxiety | Psychiatric disorders | MedDRA Version 16.0 | Non-systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA Version 16.0 | Non-systematic Assessment |
|
| Dysgeusia | Nervous system disorders | MedDRA Version 16.0 | Non-systematic Assessment |
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| Headache | Nervous system disorders | MedDRA Version 16.0 | Non-systematic Assessment |
|
| Erythema of eyelid | Eye disorders | MedDRA Version 16.0 | Non-systematic Assessment |
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| Eye pruritus | Eye disorders | MedDRA Version 16.0 | Non-systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA Version 16.0 | Non-systematic Assessment |
|
| Dysaesthesia pharynx | Respiratory, thoracic and mediastinal disorders | MedDRA Version 16.0 | Non-systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA Version 16.0 | Non-systematic Assessment |
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| Abdominal pain upper | Gastrointestinal disorders | MedDRA Version 16.0 | Non-systematic Assessment |
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| Constipation | Gastrointestinal disorders | MedDRA Version 16.0 | Non-systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA Version 16.0 | Non-systematic Assessment |
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| Duodenitis | Gastrointestinal disorders | MedDRA Version 16.0 | Non-systematic Assessment |
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| Dyspepsia | Gastrointestinal disorders | MedDRA Version 16.0 | Non-systematic Assessment |
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| Gastritis | Gastrointestinal disorders | MedDRA Version 16.0 | Non-systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA Version 16.0 | Non-systematic Assessment |
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| Stomatitis | Gastrointestinal disorders | MedDRA Version 16.0 | Non-systematic Assessment |
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| Toothache | Gastrointestinal disorders | MedDRA Version 16.0 | Non-systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA Version 16.0 | Non-systematic Assessment |
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| Hepatic function abnormal | Hepatobiliary disorders | MedDRA Version 16.0 | Non-systematic Assessment |
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| Palmar-plantar erythrodysaesthesia syndrome | Skin and subcutaneous tissue disorders | MedDRA Version 16.0 | Non-systematic Assessment |
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| Pruritus | Skin and subcutaneous tissue disorders | MedDRA Version 16.0 | Non-systematic Assessment |
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| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA Version 16.0 | Non-systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA Version 16.0 | Non-systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA Version 16.0 | Non-systematic Assessment |
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| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA Version 16.0 | Non-systematic Assessment |
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| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA Version 16.0 | Non-systematic Assessment |
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| Proteinuria | Renal and urinary disorders | MedDRA Version 16.0 | Non-systematic Assessment |
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| Fatigue | General disorders | MedDRA Version 16.0 | Non-systematic Assessment |
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| Malaise | General disorders | MedDRA Version 16.0 | Non-systematic Assessment |
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| Oedema | General disorders | MedDRA Version 16.0 | Non-systematic Assessment |
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| Pyrexia | General disorders | MedDRA Version 16.0 | Non-systematic Assessment |
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| Alanine aminotransferase increased | Investigations | MedDRA Version 16.0 | Non-systematic Assessment |
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| Aspartate aminotransferase increased | Investigations | MedDRA Version 16.0 | Non-systematic Assessment |
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| Blood creatinine increased | Investigations | MedDRA Version 16.0 | Non-systematic Assessment |
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| Grip strength decreased | Investigations | MedDRA Version 16.0 | Non-systematic Assessment |
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| Lymphocyte count decreased | Investigations | MedDRA Version 16.0 | Non-systematic Assessment |
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| Neutrophil count decreased | Investigations | MedDRA Version 16.0 | Non-systematic Assessment |
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| Platelet count decreased | Investigations | MedDRA Version 16.0 | Non-systematic Assessment |
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| White blood cell count decreased | Investigations | MedDRA Version 16.0 | Non-systematic Assessment |
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| Contusion | Injury, poisoning and procedural complications | MedDRA Version 16.0 | Non-systematic Assessment |
|
| Procedural pain | Injury, poisoning and procedural complications | MedDRA Version 16.0 | Non-systematic Assessment |
|
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