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| Name | Class |
|---|---|
| University of Texas | OTHER |
| New York City Hoffman Center | UNKNOWN |
| Gustave Roussy, Cancer Campus, Grand Paris | OTHER |
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This study is being conducted to test study drug AZD1480 to see how it may work to treat myeloproliferative diseases. The main purpose of this study is to determine the safety and tolerability of AZD1480. This is the first time the drug has been given to humans and is classed as a first time in man study. Its main purpose is to establish a safe dosage of the drug and provide additional information on any potential side effects this drug may cause. The study will also assess the blood levels and action of AZD1480 in the body over a period of time and will indicate whether the drug has a therapeutic effect on myeloproliferative diseases.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 1 | Experimental | AZD1480 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| AZD1480 | Drug | Oral capsule 2.5 mg, 10 mg and 40 mg |
|
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacokinetic Parameters Following Single Dosing: AUC0-12 | Single dose AUC0-12 (ug*h/L) | 0 to 12 hour sampling (Day 1: 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hours post dose) |
| Pharmacokinetic Parameters Following Single Dosing: AUC0-24 | Single dose AUC0-24 (ug*h/L) | 0 to 24 hour sampling (Day 1: 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post dose) |
| Pharmacokinetic Parameters Following Single Dosing:AUC0-inf | Single dose AUC(0 to infinity) (ug*h/L) | 0 to 24 hour sampling (Day 1: 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post dose) |
| Pharmacokinetic Parameters Following Multiple Dosing: Cmax,ss | Multiple dose Cmax,ss (ug/L) | On Days 1 and 28 at 0, 0,5, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post dose, and at 0, 2, 4 hours post dose on Days 4 and 10 |
| Pharmacokinetic Parameters Following Multiple Dosing: Cmin,ss | Multiple dose Cmin,ss (ug/L) | On Days 1 and 28 at 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose and at 0, 2, 4 hours post-dose on Days 4 and 10. |
| Pharmacokinetic Parameters Following Single Dosing: Cmax | Single dose Cmax (ug/L) | 0 to 24 hour sampling (Day 1: 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post dose) |
| Pharmacokinetic Parameters Following Single Dosing: Vz/F | Single dose Vz/F (L) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Srdan Verstovsek, MD | MDACC | Principal Investigator |
| Ronald Hoffman, MD | Mt. Sinai | Principal Investigator |
| Vincent Ribrag, MD | Gustave Roussy, Cancer Campus, Grand Paris | Principal Investigator |
| Becker Hewes, MD | AstraZeneca | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | New York | New York | United States | |||
| Research Site |
Patients ≥25 years of age with primary myelofibrosis (MF) and post-polycythaemia vera/essential thrombocythaemia MF who had relapsed, were intolerant of, or were refractory to MF-directed therapy were enrolled.
Commenced 19MAY2009. All subjects recruited to Part A only (based on emerging data). 65 patients were enrolled of which 35 recieved at least 1 dose of AZD1480.
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| ID | Title | Description |
|---|---|---|
| FG000 | 2.5 mg QD | AZD1480 may be administered orally in capsules |
| FG001 | 5.0 mg QD | AZD1480 may be administered orally in capsules |
| FG002 | 10 mg QD | AZD1480 may be administered orally in capsules |
| FG003 | 30 mg QD | AZD1480 may be administered orally in capsules |
| FG004 | 50 mg QD | AZD1480 may be administered orally in capsules |
| FG005 | 70 mg QD | AZD1480 may be administered orally in capsules |
| FG006 | 10 mg BID | AZD1480 may be administered orally in capsules |
| FG007 | 15 mg BID | AZD1480 may be administered orally in capsules |
| FG008 | 20 mg QD | AZD1480 may be administered orally in capsules |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 2.5 mg QD | AZD1480 may be administered orally in capsules |
| BG001 | 5.0 mg QD | AZD1480 may be administered orally in capsules |
| 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 | Pharmacokinetic Parameters Following Single Dosing: AUC0-12 | Single dose AUC0-12 (ug*h/L) | Pharmacokinetic. Note - no GeoCV(%) was captured in the TFL. Hence the geometric mean was still presented as applicable but with the SD (since only available). | Posted | Geometric Mean | Standard Deviation | ug*h/L | 0 to 12 hour sampling (Day 1: 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hours post dose) |
|
Throughout study continuously and 30 days post discontinuation of treatment
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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 | 2.5 mg QD | AZD1480 may be administered orally in capsules |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| APHASIA | Nervous system disorders | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| ANAEMIA | Blood and lymphatic system disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr Gregory Curt, MD | AstraZeneca | +1 301 398 0109 | Gregory.Curt@astrazeneca.com |
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| ID | Term |
|---|---|
| D055728 | Primary Myelofibrosis |
| ID | Term |
|---|---|
| D009196 | Myeloproliferative Disorders |
| D001855 | Bone Marrow Diseases |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
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| ID | Term |
|---|---|
| C545606 | AZD 1480 |
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| 0 to 24 hour sampling (Day 1: 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post dose) |
| Pharmacokinetic Parameters Following Single Dosing: CL/F | Single dose CL/F (L/h) | 0 to 24 hour sampling (Day 1: 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post dose) |
| Pharmacokinetic Parameters Following Multiple Dosing: CLss/F | Multiple dose CLss/F (L/h) | On Days 1 and 28 at 0, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24 hours post dose and at 0, 2, 4 hours post-dose |
| Pharamcokinetic Parameters Following Single Dosing: Tmax | Single dose Tmax (h) | 0 to 24 hour sampling (Day 1: 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post dose) |
| Pharamcokinetic Parameters Following Multiple Dosing: Tmax,ss | Multiple dose Tmax,ss (h) | On Days 1 and 28 at 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post dose and at 0, 2, 4 hours post-dose on Days 4 and 10 |
| Inhibition of PSTAT3 (Count) | PSTAT3 inhinition | 2hrs and 4 hrs post dose |
| Houston |
| Texas |
| United States |
| Research Site | Villejuif | France |
| Withdrawal by Subject |
|
| (not specified) |
|
| Adverse Event |
|
| BG002 | 10 mg QD | AZD1480 may be administered orally in capsules |
| BG003 | 70 mg QD | AZD1480 may be administered orally in capsules |
| BG004 | 15 mg BID | AZD1480 may be administered orally in capsules |
| BG005 | 30 mg QD | AZD1480 may be administered orally in capsules |
| BG006 | 50 mg QD | AZD1480 may be administered orally in capsules |
| BG007 | 10 mg BID | AZD1480 may be administered orally in capsules |
| BG008 | 20 mg QD | AZD1480 may be administered orally in capsules |
| BG009 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| 10 mg QD |
AZD1480 may be administered orally in capsules |
| OG003 | 30 mg QD | AZD1480 may be administered orally in capsules |
| OG004 | 70 mg QD | AZD1480 may be administered orally in capsules |
| OG005 | 10 mg BID | AZD1480 may be administered orally in capsules |
| OG006 | 15 mg BID | AZD1480 may be administered orally in capsules |
| OG007 | 50 mg QD | AZD1480 may be administered orally in capsules |
| OG008 | 20 mg QD | AZD1480 may be administered orally in capsules |
|
|
| Primary | Pharmacokinetic Parameters Following Single Dosing: AUC0-24 | Single dose AUC0-24 (ug*h/L) | Pharmacokinetic. Note - no GeoCV(%) was captured in the TFL. Hence the geometric mean was still presented as applicable but with the SD (since only available). From the BID schedule we can not derive the single dosing AUC0_24 and hence this is not presented/calculated. | Posted | Geometric Mean | Standard Deviation | ug*h/L | 0 to 24 hour sampling (Day 1: 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post dose) |
|
|
|
| Primary | Pharmacokinetic Parameters Following Single Dosing:AUC0-inf | Single dose AUC(0 to infinity) (ug*h/L) | Pharmacokinetic. Note - no GeoCV(%) was captured in the TFL. Hence the geometric mean was still presented as applicable but with the SD (since only available). From the BID (twice a day dosing schedules) we can not derive the PK parameter AUC0_inf following single dosing. With that these do not contribute. | Posted | Geometric Mean | Standard Deviation | ug*h/L | 0 to 24 hour sampling (Day 1: 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post dose) |
|
|
|
| Primary | Pharmacokinetic Parameters Following Multiple Dosing: Cmax,ss | Multiple dose Cmax,ss (ug/L) | Pharmacokinetic. Note - no GeoCV(%) was captured in the TFL. Hence the geometric mean was still presented as applicable but with the SD (since only available). | Posted | Geometric Mean | Standard Deviation | ug/L | On Days 1 and 28 at 0, 0,5, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post dose, and at 0, 2, 4 hours post dose on Days 4 and 10 |
|
|
|
| Primary | Pharmacokinetic Parameters Following Multiple Dosing: Cmin,ss | Multiple dose Cmin,ss (ug/L) | Pharmacokinetic. Note - no GeoCV(%) was captured in the TFL. Hence the geometric mean was still presented as applicable but with the SD (since only available). | Posted | Geometric Mean | Standard Deviation | ug/L | On Days 1 and 28 at 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose and at 0, 2, 4 hours post-dose on Days 4 and 10. |
|
|
|
| Primary | Pharmacokinetic Parameters Following Single Dosing: Cmax | Single dose Cmax (ug/L) | Pharmacokinetic. Note - no GeoCV(%) was captured in the TFL. Hence the geometric mean was still presented as applicable but with the SD (since only available). | Posted | Geometric Mean | Standard Deviation | ug/L | 0 to 24 hour sampling (Day 1: 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post dose) |
|
|
|
| Primary | Pharmacokinetic Parameters Following Single Dosing: Vz/F | Single dose Vz/F (L) | Pharmacokinetic. Note - no GeoCV(%) was captured in the TFL. Hence the geometric mean was still presented as applicable but with the SD (since only available). Due to the nature of the dosing schedule this PK parameter was not reported for the BID (twice daily dosing) groups. | Posted | Geometric Mean | Standard Deviation | L | 0 to 24 hour sampling (Day 1: 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post dose) |
|
|
|
| Primary | Pharmacokinetic Parameters Following Single Dosing: CL/F | Single dose CL/F (L/h) | Pharmacokinetic. Note - no GeoCV(%) was captured in the TFL. Hence the geometric mean was still presented as applicable but with the SD (since only available). | Posted | Geometric Mean | Standard Deviation | L/h | 0 to 24 hour sampling (Day 1: 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post dose) |
|
|
|
| Primary | Pharmacokinetic Parameters Following Multiple Dosing: CLss/F | Multiple dose CLss/F (L/h) | Pharmacokinetic. Note - no GeoCV(%) was captured in the TFL. Hence the geometric mean was still presented as applicable but with the SD (since only available). | Posted | Geometric Mean | Standard Deviation | L/h | On Days 1 and 28 at 0, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24 hours post dose and at 0, 2, 4 hours post-dose |
|
|
|
| Primary | Pharamcokinetic Parameters Following Single Dosing: Tmax | Single dose Tmax (h) | Posted | Median | Full Range | h | 0 to 24 hour sampling (Day 1: 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post dose) |
|
|
|
| Primary | Pharamcokinetic Parameters Following Multiple Dosing: Tmax,ss | Multiple dose Tmax,ss (h) | Posted | Median | Full Range | h | On Days 1 and 28 at 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post dose and at 0, 2, 4 hours post-dose on Days 4 and 10 |
|
|
|
| Primary | Inhibition of PSTAT3 (Count) | PSTAT3 inhinition | Posted | Number | # patients with 50% reduction in PSTAT3 | 2hrs and 4 hrs post dose |
|
|
|
| 2 |
| 6 |
| 6 |
| 6 |
| EG001 | 5.0 mg QD | AZD1480 may be administered orally in capsules | 2 | 3 | 3 | 3 |
| EG002 | 10 mg QD | AZD1480 may be administered orally in capsules | 0 | 3 | 3 | 3 |
| EG003 | 70 mg QD | AZD1480 may be administered orally in capsules | 0 | 1 | 1 | 1 |
| EG004 | 15 mg BID | AZD1480 may be administered orally in capsules | 1 | 4 | 4 | 4 |
| EG005 | 20 mg QD | AZD1480 may be administered orally in capsules | 3 | 3 | 3 | 3 |
| EG006 | 30 mg QD | AZD1480 may be administered orally in capsules | 0 | 3 | 3 | 3 |
| EG007 | 50 mg QD | AZD1480 may be administered orally in capsules | 4 | 6 | 6 | 6 |
| EG008 | 10 mg BID | AZD1480 may be administered orally in capsules | 3 | 6 | 6 | 6 |
| AMNESIA | Nervous system disorders | Systematic Assessment |
|
| ATAXIA | Nervous system disorders | Systematic Assessment |
|
| DYSARTHRIA | Nervous system disorders | Systematic Assessment |
|
| CONFUSIONAL STATE | Psychiatric disorders | Systematic Assessment |
|
| ANAEMIA | Blood and lymphatic system disorders | Systematic Assessment |
|
| ATRIAL FLUTTER/FIBRILLATION | Cardiac disorders | Systematic Assessment |
|
| NEUTROPENIA | Blood and lymphatic system disorders | Systematic Assessment |
|
| SPLENIC INFARCTION | Blood and lymphatic system disorders | Systematic Assessment |
|
| CARDIAC FAILURE CHRONIC | Cardiac disorders | Systematic Assessment |
|
| CORONARY ARTERY DISEASE | Cardiac disorders | Systematic Assessment |
|
| TACHYCARDIA | Cardiac disorders | Systematic Assessment |
|
| PYREXIA | General disorders | Systematic Assessment |
|
| PNEUMONIA | Infections and infestations | Systematic Assessment |
|
| CRANIOCEREBRAL INJURY | Injury, poisoning and procedural complications | Systematic Assessment |
|
| UPPER LIMB FRACTURE | Injury, poisoning and procedural complications | Systematic Assessment |
|
| HAEMOGLOBIN DECREASED | Investigations | Systematic Assessment |
|
| DEHYDRATION | Metabolism and nutrition disorders | Systematic Assessment |
|
| GOUT | Metabolism and nutrition disorders | Systematic Assessment |
|
| BASAL CELL CARCINOMA | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Systematic Assessment |
|
| NEUTROPENIUA | Blood and lymphatic system disorders | Systematic Assessment |
|
| THROMBOCYTOPENIA | Blood and lymphatic system disorders | Systematic Assessment |
|
| DIARRHOEA | Gastrointestinal disorders | Systematic Assessment |
|
| VOMITING | Gastrointestinal disorders | Systematic Assessment |
|
| FATIGUE | General disorders | Systematic Assessment |
|
| ASTHENIA | General disorders | Systematic Assessment |
|
| MUCOSAL INFLAMMATION | General disorders | Systematic Assessment |
|
| WEIGHT INCREASE | Investigations | Systematic Assessment |
|
| DIZZINESS | Nervous system disorders | Systematic Assessment |
|
| CONFUSIONAL STATE | Psychiatric disorders | Systematic Assessment |
|
| DYSPNOEA | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| PYREXIA | General disorders | Systematic Assessment |
|
| HYPERTHERMIA | General disorders | Systematic Assessment |
|
| OEMEMA PERIPHERAL | General disorders | Systematic Assessment |
|
| OEDEMA | General disorders | Systematic Assessment |
|
| FOLLICULITIS | Infections and infestations | Systematic Assessment |
|
| PROTEINURIA | Renal and urinary disorders | Systematic Assessment |
|
| HAEMATURIA | Renal and urinary disorders | Systematic Assessment |
|
| ASCITES | Gastrointestinal disorders | Systematic Assessment |
|
| ABDOMINAL DISTENSION | Gastrointestinal disorders | Systematic Assessment |
|
| ABDOMINAL PAIN | Gastrointestinal disorders | Systematic Assessment |
|
| CONSTIPATION | Gastrointestinal disorders | Systematic Assessment |
|
| GASTROOESOPHAGEAL REFLUX DISEASE | Gastrointestinal disorders | Systematic Assessment |
|
| HAEMORRHOIDS | Gastrointestinal disorders | Systematic Assessment |
|
| NAUSEA | Gastrointestinal disorders | Systematic Assessment |
|
| MUSCLE SPASMS | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| BONE PAIN | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| MUSCULOSKELETAL PAIN | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| MYALGIA AGGRAVATED | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| PAIN | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| RETINAL HAEMORRHAGE | Eye disorders | Systematic Assessment |
|
| CATARAC | Eye disorders | Systematic Assessment |
|
| CONJUNCTIVAL HAEMORRHAGE | Eye disorders | Systematic Assessment |
|
| DRY EYE | Eye disorders | Systematic Assessment |
|
| HAEMORRHAGE | Eye disorders | Systematic Assessment |
|
| KERATITI | Eye disorders | Systematic Assessment |
|
| HYPERBILIRUBINAEMIA | Hepatobiliary disorders | Systematic Assessment |
|
| ECCHYMOSI | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| PETECHIAE | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| PRURITIS | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| RASH | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| EXCORIATION | Injury, poisoning and procedural complications | Systematic Assessment |
|
| CARDIAC MURMUR | Investigations | Systematic Assessment |
|
| HEADACHE | Nervous system disorders | Systematic Assessment |
|
| PARAESTHES | Nervous system disorders | Systematic Assessment |
|
| INSOMNIA | Psychiatric disorders | Systematic Assessment |
|
| EPITAXIS | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
Not provided
| 4 Hours post dose |
|