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Enrollment issues
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The purpose of this study is to evaluate the efficacy and safety of ruxolitinib versus anagrelide in subjects with essential thrombocythemia who are resistant to or intolerant of hydroxyurea.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Group A : Ruxolitinib and anagrelide placebo | Experimental | Ruxolitinib or placebo will be administered orally twice a day at a starting dose of 10 mg. |
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| Group B : Anagrelide and Ruxolitinib PLacebo | Active Comparator | Anagrelide or placebo will be administered orally twice a day at a starting dose of 1 mg. Use of anagrelide will be consistent with approved prescribing information. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ruxolitinib | Drug | Ruxolitinib administered orally twice daily (BID) at the protocol-defined starting dose. |
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| Measure | Description | Time Frame |
|---|---|---|
| Proportion of Subjects Who Achieve Platelet and White Blood Cell (WBC) Control | Defined as proportion of subjects who achieve a simultaneous reduction of platelet counts to < 600 × 10^9/L with a reduction of WBC counts to < 10 × 10^9/L for at least 80% of biweekly measurements for a consecutive 12-week period between Weeks 32 and 52. | 52 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug/treatment. | Baseline through the end of randomized period -up to 14 months per participant |
| Proportion of Subjects Who Achieve Complete Remission or Partial Remission |
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Inclusion Criteria:
Diagnosis of essential thrombocythemia according to revised World Health Organization (WHO) 2016 criteria.
Resistant to or intolerant of hydroxyurea, that is, fulfilling at least 1 of the following criteria:
Platelet count ≥ 650 × 10^9/L at screening.
WBC ≥ 11.0 × 10^9/L at screening.
Exclusion Criteria:
Subjects previously treated with anagrelide or Hydroxyurea (HU).
Inadequate liver function at screening and Day 1 (before drug administration) as demonstrated by:
Inadequate renal function at screening as demonstrated by creatinine clearance < 40 mL/min calculated by Cockcroft-Gault equation.
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| Name | Affiliation | Role |
|---|---|---|
| Albert Assad, MD | Incyte Corporation | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Mayo Clinic | Phoenix | Arizona | 85054 | United States | ||
| Pacific Shores Medical Group |
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Twelve participants were enrolled and randomized. One participant in the ruxolitinib group was enrolled in error and withdrawn from the study before receiving any dose of study drug.
Approximately 120 participants were planned for enrollment and 12 participants were enrolled (6 in the ruxolitinib group and 6 in the anagrelide group). The first participant was dosed on 14 Nov 2017 and Last participant completed study on 03 Aug 2020
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| ID | Title | Description |
|---|---|---|
| FG000 | Group A : Ruxolitinib and Anagrelide Placebo | Ruxolitinib or placebo will be administered orally twice a day at a starting dose of 10 mg. |
| FG001 | Group B : Anagrelide and Ruxolitinib Placebo |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Aug 2, 2019 | Aug 2, 2021 |
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| Anagrelide | Drug | Anagrelide administered orally at a starting dose of 1 mg BID. |
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| Placebo | Drug | Anagrelide-placebo administered orally BID |
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| Placebo | Drug | Ruxolitinib-placebo administered orally BID. |
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Defined as proportion of subjects who achieve CR or PR at Week 32 based on European LeukemiaNet (ELN) 2013 response criteria. Per ELN criteria: Complete Remission: durable resolution of disease related signs and symptoms, durable blood count normalization, absence of hemorrhagic or thrombotic events, absence of signs of progressive disease and bone marrow histological remission including disappearance of megakaryocyte hyperplasia and absence of reticulin fibrosis >Grade 1. Partial remission: durable resolution of disease related signs and symptoms, durable blood count normalization, absence of hemorrhagic or thrombotic events, absence of signs of progressive disease, persistance of megakaryocyte hyperplasia. No response: any response that does not satisfy partial remission. Progressive Disease: transformation in PET-MF, MDS or acute leukemia. |
| 32 weeks |
| Time to Treatment Discontinuation | Defined as the time when treatment is discontinued | 98 weeks |
| Duration of Response | Defined as measurement of response from the onset of response to the loss of response for responders. | 142 weeks |
| Proportion of Subjects Who Achieve Reduction of Platelet Counts to < 600 × 10^9/L | Defined as Proportion of subjects who achieve reduction of platelet counts to < 600 × 10^9/L for at least 80% of biweekly measurements for a consecutive 12-week period between Weeks 32 and 52. | Between 32 and 52 weeks |
| Proportion of Subjects Who Achieve a Reduction of WBC Counts to < 10 × 109/L | Defined as Proportion of subjects who achieve a reduction of WBC counts to < 10 × 109/L for at least 80% of biweekly measurements for a consecutive 12-week period between Weeks 32 and 52. | 52 weeks |
| Long Beach |
| California |
| 90813 |
| United States |
| University of Southern California | Los Angeles | California | 90033 | United States |
| Ventura County Hematology-Oncology Specialists | Oxnard | California | 93030 | United States |
| Compassionate Cancer Care Medical Group | Riverside | California | 92501 | United States |
| Innovative Clinical Research Institute | Whittier | California | 90603 | United States |
| Bond Clinic, PA | Winter Haven | Florida | 33880 | United States |
| Tift Regional | Tifton | Georgia | 31794 | United States |
| Edward Cancer Center | Naperville | Illinois | 60540 | United States |
| North Shore Cancer Research Association-Skokie | Skokie | Illinois | 60076 | United States |
| Southern Illinois University | Springfield | Illinois | 62702 | United States |
| Clinical Trials of SWLA LLC | Lake Charles | Louisiana | 70601 | United States |
| St. Agnes Hospital | Baltimore | Maryland | 21229 | United States |
| Washington University School of Medicine | St Louis | Missouri | 63110 | United States |
| Summit Medical Group | Morristown | New Jersey | 07960 | United States |
| Columbia Weill Cornell Cancer Centers - Herbert Irving Comprehensive Cancer Center (HICCC) | New York | New York | 10032 | United States |
| Montefiore Medical Center | The Bronx | New York | 10467 | United States |
| Waverly Hem Onc | Cary | North Carolina | 27518 | United States |
| Vidant Medical Center | Greenville | North Carolina | 27858 | United States |
| Gabrail Cancer Center- Canton Facility | Canton | Ohio | 44718 | United States |
| INTEGRIS Southwest Medical Center | Oklahoma City | Oklahoma | 73109 | United States |
| INTEGRIS Cancer Institute Proton Campus | Oklahoma City | Oklahoma | 73142 | United States |
| Kaiser Permanente Northwest | Portland | Oregon | 97227 | United States |
| Geisinger - Knapper Clinic | Danville | Pennsylvania | 17822 | United States |
| Prairie Lakes Health Care System Inc. | Watertown | South Dakota | 57201 | United States |
| Renovatio Clinical | The Woodlands | Texas | 77401 | United States |
Anagrelide or placebo will be administered orally twice a day at a starting dose of 1 mg. Use of anagrelide will be consistent with approved prescribing information.
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Group A : Ruxolitinib and Anagrelide Placebo | Ruxolitinib or placebo will be administered orally twice a day at a starting dose of 10 mg. |
| BG001 | Group B : Anagrelide and Ruxolitinib Placebo | Anagrelide or placebo will be administered orally twice a day at a starting dose of 1 mg. Use of anagrelide will be consistent with approved prescribing information. |
| BG002 | 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 |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| Race/Ethnicity, Customized | 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 | Proportion of Subjects Who Achieve Platelet and White Blood Cell (WBC) Control | Defined as proportion of subjects who achieve a simultaneous reduction of platelet counts to < 600 × 10^9/L with a reduction of WBC counts to < 10 × 10^9/L for at least 80% of biweekly measurements for a consecutive 12-week period between Weeks 32 and 52. | The intent-to-treat (ITT) population will include subjects randomized in the study | Posted | Number | proportion of participants | 52 weeks |
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| Secondary | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug/treatment. | The safety population includes all randomized subjects who received at least 1 dose of study drug. AE has been summarized only in randomized period. End of randomized period is defined as the earliest of discontinuation or the individual unblinding date. | Posted | Number | participants | Baseline through the end of randomized period -up to 14 months per participant |
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| Secondary | Proportion of Subjects Who Achieve Complete Remission or Partial Remission | Defined as proportion of subjects who achieve CR or PR at Week 32 based on European LeukemiaNet (ELN) 2013 response criteria. Per ELN criteria: Complete Remission: durable resolution of disease related signs and symptoms, durable blood count normalization, absence of hemorrhagic or thrombotic events, absence of signs of progressive disease and bone marrow histological remission including disappearance of megakaryocyte hyperplasia and absence of reticulin fibrosis >Grade 1. Partial remission: durable resolution of disease related signs and symptoms, durable blood count normalization, absence of hemorrhagic or thrombotic events, absence of signs of progressive disease, persistance of megakaryocyte hyperplasia. No response: any response that does not satisfy partial remission. Progressive Disease: transformation in PET-MF, MDS or acute leukemia. | The intent-to-treat (ITT) population will include subjects randomized in the study | Posted | Number | proportion of participants | 32 weeks |
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| Secondary | Time to Treatment Discontinuation | Defined as the time when treatment is discontinued | The intent-to-treat (ITT) population will include subjects randomized in the study | Posted | Mean | Standard Deviation | Days | 98 weeks |
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| Secondary | Duration of Response | Defined as measurement of response from the onset of response to the loss of response for responders. | The intent-to-treat (ITT) population who are responders | Posted | Number | Days | 142 weeks |
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| Secondary | Proportion of Subjects Who Achieve Reduction of Platelet Counts to < 600 × 10^9/L | Defined as Proportion of subjects who achieve reduction of platelet counts to < 600 × 10^9/L for at least 80% of biweekly measurements for a consecutive 12-week period between Weeks 32 and 52. | The intent-to-treat (ITT) population will include subjects randomized in the study | Posted | Number | Proportion of participants | Between 32 and 52 weeks |
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| Secondary | Proportion of Subjects Who Achieve a Reduction of WBC Counts to < 10 × 109/L | Defined as Proportion of subjects who achieve a reduction of WBC counts to < 10 × 109/L for at least 80% of biweekly measurements for a consecutive 12-week period between Weeks 32 and 52. | The intent-to-treat (ITT) population will include subjects randomized in the study | Posted | Number | Proportion of participants | 52 weeks |
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Baseline through the end of randomized period -up to 14 months per participant
The safety population includes all randomized subjects who received at least 1 dose of study drug. AE has been summarized only in randomized period. End of randomized period is defined as the earliest of discontinuation or the individual unblinding date.
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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 | Group A : Ruxolitinib and Anagrelide Placebo | Ruxolitinib or placebo will be administered orally twice a day at a starting dose of 10 mg. | 0 | 5 | 0 | 5 | 5 | 5 |
| EG001 | Group B : Anagrelide and Ruxolitinib Placebo | Anagrelide or placebo will be administered orally twice a day at a starting dose of 1 mg. Use of anagrelide will be consistent with approved prescribing information | 0 | 6 | 1 | 6 | 4 | 6 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Non-small cell lung cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 20 | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal pain | Gastrointestinal disorders | MedDRA 20 | Systematic Assessment |
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| Abdominal pain upper | Gastrointestinal disorders | MedDRA 20 | Systematic Assessment |
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| Anaemia | Blood and lymphatic system disorders | MedDRA 20 | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 20 | Systematic Assessment |
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| Aspartate aminotransferase increased | Investigations | MedDRA 20 | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 20 | Systematic Assessment |
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| Blood creatinine | Investigations | MedDRA 20 | Systematic Assessment |
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| Bronchitis | Infections and infestations | MedDRA 20 | Systematic Assessment |
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| Contusion | Injury, poisoning and procedural complications | MedDRA 20 | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 20 | Systematic Assessment |
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| Decreased appetite | Metabolism and nutrition disorders | MedDRA 20 | Systematic Assessment |
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| Depression | Psychiatric disorders | MedDRA 20 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA 20 | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA 20 | Systematic Assessment |
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| Ear discomfort | Ear and labyrinth disorders | MedDRA 20 | Systematic Assessment |
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| Fall | Injury, poisoning and procedural complications | MedDRA 20 | Systematic Assessment |
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| Fatigue | General disorders | MedDRA 20 | Systematic Assessment |
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| Fungal infection | Infections and infestations | MedDRA 20 | Systematic Assessment |
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| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA 20 | Systematic Assessment |
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| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA 20 | Systematic Assessment |
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| Hyperuricaemia | Metabolism and nutrition disorders | MedDRA 20 | Systematic Assessment |
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| Hypoaesthesia | Nervous system disorders | MedDRA 20 | Systematic Assessment |
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| Hyponatraemia | Metabolism and nutrition disorders | MedDRA 20 | Systematic Assessment |
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| Hypotension | Vascular disorders | MedDRA 20 | Systematic Assessment |
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| Insomnia | Psychiatric disorders | MedDRA 20 | Systematic Assessment |
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| Micturition urgency | Renal and urinary disorders | MedDRA 20 | Systematic Assessment |
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| Muscle strain | Injury, poisoning and procedural complications | MedDRA 20 | Systematic Assessment |
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| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA 20 | Systematic Assessment |
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| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 20 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 20 | Systematic Assessment |
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| Nephrolithiasis | Renal and urinary disorders | MedDRA 20 | Systematic Assessment |
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| Night sweats | Skin and subcutaneous tissue disorders | MedDRA 20 | Systematic Assessment |
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| Oedema peripheral | General disorders | MedDRA 20 | Systematic Assessment |
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| Onycholysis | Skin and subcutaneous tissue disorders | MedDRA 20 | Systematic Assessment |
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| Palpitations | Cardiac disorders | MedDRA 20 | Systematic Assessment |
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| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 20 | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA 20 | Systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | MedDRA 20 | Systematic Assessment |
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| Skin abrasion | Injury, poisoning and procedural complications | MedDRA 20 | Systematic Assessment |
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| Skin ulcer | Skin and subcutaneous tissue disorders | MedDRA 20 | Systematic Assessment |
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| Tachycardia paroxysmal | Cardiac disorders | MedDRA 20 | Systematic Assessment |
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| Tinnitus | Ear and labyrinth disorders | MedDRA 20 | Systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA 20 | Systematic Assessment |
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| Vitreous floaters | Eye disorders | MedDRA 20 | Systematic Assessment |
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| Weight decreased | Investigations | MedDRA 20 | Systematic Assessment |
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| Weight increased | Investigations | MedDRA 20 | Systematic Assessment |
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Clinical Study Agreement
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Call Center | Incyte Corporation | 1.855.463.3463 | medinfo@incyte.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Sep 24, 2019 | Aug 2, 2021 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D009196 | Myeloproliferative Disorders |
| D013920 | Thrombocythemia, Essential |
| ID | Term |
|---|---|
| D001855 | Bone Marrow Diseases |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D001778 | Blood Coagulation Disorders |
| D013922 | Thrombocytosis |
| D001791 | Blood Platelet Disorders |
| D006474 | Hemorrhagic Disorders |
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| ID | Term |
|---|---|
| C540383 | ruxolitinib |
| C021139 | anagrelide |
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| Male |
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| Not Hispanic or Latino |
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| Not Reported |
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| Asian |
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