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The purpose of the RELIEF study is to compare symptoms in polycythemia vera (PV) subjects treated with ruxolitinib versus subjects treated with hydroxyurea (HU) as measured by the percent of subjects who achieve a clinically meaningful symptom improvement (ie, total symptom score reduction of ≥ 50% reduction) at Week 16 compared to Baseline. The study is also designed to demonstrate that these responses are durable with continued treatment.
This is a Phase 3 multicenter, double-blind, double-dummy, randomized study. Only subjects with PV who have received HU for at least 12 weeks, have been receiving a stable dose before screening, and still have symptoms related to PV will be enrolled.
Subjects will be randomized (1:1) to 1 of 2 treatment arms:
A: ruxolitinib and HU-placebo B: HU and ruxolitinib-placebo
Subjects randomized to either arm may be eligible to transition to open-label ruxolitinib after Week 16.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| ruxolitinib and hydroxyurea (HU)-placebo | Experimental |
| |
| HU and ruxolitinib-placebo | Active Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ruxolitinib | Drug | Ruxolitinib will be orally self-administered at a starting dose of 10 mg (two 5 mg tablets) twice a day. Dose increases of 5 mg (1 tablet) in twice-daily increments are permitted after 4 weeks and again after 8 weeks of therapy for subjects who meet prespecified criteria for inadequate efficacy. |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Subjects Achieving a ≥ 50% Improvement From Baseline in Total Symptom Score-Cytokine (TSS-C) at Week 16, as Measured by the Modified Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) Diary | Symptoms of polycythemia vera were assessed using a modified Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) electronic diary. Using the diary, patients rated the following symptoms on a scale from 0 (absent) to 10 (worst imaginable): tiredness, itching, muscle aches, night sweats, and sweats while awake. The total symptom score ranged from 0-50 and was calculated as the sum of the 5 symptom scores. A higher score indicates worse symptoms. | From Baseline to Week 16 |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Subjects Achieving ≥ 50% Improvement From Baseline in the Individual Symptom Scores for TSS-C at Week 16 | The TSS-C cluster includes tiredness, itching, muscle aches, night sweats, and sweats while awake. | From Baseline to Week 16 |
| Proportion of Subjects Randomized to Ruxolitinib Who Achieved ≥ 50% Improvement From Baseline in Total Symptom Score-Cytokine and the Individual Symptom Scores at Week 16 That Were Maintained at Week 48 |
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Inclusion Criteria:
Subjects must currently be reporting symptoms while on a stable dose of HU monotherapy and be eligible to continue HU on study after randomization.
Before screening, the subject must have been receiving HU for at least 12 weeks AND be receiving a stable dose.
Subjects must meet baseline symptom criteria
Subjects should meet at least 1 of the following criteria:
Subjects must have a hematocrit that can be controlled within 35% to 48% (inclusive) before randomization.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Mark Jones, M.D. | Incyte Corporation | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Scottsdale | Arizona | United States | ||||
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| ID | Title | Description |
|---|---|---|
| FG000 | Ruxolitinib | Ruxolitinib will be orally self-administered at a starting dose of 10 mg (two 5 mg tablets) twice a day. Dose increases of 5 mg (1 tablet) in twice-daily increments are permitted after 4 weeks and again after 8 weeks of therapy for subjects who meet prespecified criteria for inadequate efficacy. HU-placebo All placebo will be self-administered, and dosing will be the same as with the blinded dose. When adjustments are made to the ruxolitinib dose, the dose of HU-placebo will be adjusted concurrently. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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|
| Hydroxyurea (HU) | Drug | Hydroxyurea (500 mg capsules) will be orally self-administered at the dose that the subject was receiving previously. The dose may be increased after 4 weeks and again after 8 weeks of therapy to optimize efficacy for subjects meeting prespecified criteria. |
|
| HU-placebo | Drug | All placebo will be self-administered, and dosing will be the same as with the blinded dose. When adjustments are made to the ruxolitinib dose, the dose of HU-placebo will be adjusted concurrently. |
|
| Ruxolitinib-placebo | Drug | All placebo will be self-administered, and dosing will be the same as with the blinded dose. When adjustments are made to the HU dose, the dose of ruxolitinib-placebo will be adjusted concurrently. |
|
Durable Response on TSS-C/individual symptoms defined as a ≥ 50% reduction in TSS-C/individual symptoms at Week 16 that were maintained at Week 48 |
| Week 48 |
| Fayetteville |
| Arkansas |
| United States |
| Burbank | California | United States |
| Glendale | California | United States |
| La Jolla | California | United States |
| Los Angeles | California | United States |
| San Diego | California | United States |
| Aurora | Colorado | United States |
| Stamford | Connecticut | United States |
| Washington D.C. | District of Columbia | United States |
| Boynton Beach | Florida | United States |
| Orlando | Florida | United States |
| Atlanta | Georgia | United States |
| Chicago | Illinois | United States |
| Niles | Illinois | United States |
| Springfield | Illinois | United States |
| Ames | Iowa | United States |
| Westwood | Kansas | United States |
| Alexandria | Louisiana | United States |
| Baltimore | Maryland | United States |
| Southfield | Michigan | United States |
| Minneapolis | Minnesota | United States |
| Columbia | Missouri | United States |
| St Louis | Missouri | United States |
| Henderson | Nevada | United States |
| Las Vegas | Nevada | United States |
| East Orange | New Jersey | United States |
| Morristown | New Jersey | United States |
| Somerville | New Jersey | United States |
| Albany | New York | United States |
| Armonk | New York | United States |
| Mineola | New York | United States |
| New York | New York | United States |
| Canton | Ohio | United States |
| Bethlehem | Pennsylvania | USA | United States |
| Charleston | South Carolina | United States |
| Chattanooga | Tennessee | United States |
| Amarillo | Texas | United States |
| Bedford | Texas | United States |
| Dallas | Texas | United States |
| Garland | Texas | United States |
| Houston | Texas | United States |
| Longview | Texas | United States |
| Midland | Texas | United States |
| San Antonio | Texas | United States |
| Temple | Texas | United States |
| Tyler | Texas | United States |
| Salt Lake City | Utah | United States |
| Alexandria | Virginia | United States |
| Seattle | Washington | United States |
| Milwaukee | Wisconsin | United States |
| Antwerp | Belgium |
| Bruges | Belgium |
| Aachen | Germany |
| Berlin | Germany |
| Freiburg im Breisgau | Germany |
| Hamburg | Germany |
| Stuttgart | Germany |
| Ulm | Germany |
| Galway | Ireland |
| Florence | Italy |
| Reggio Calabria | Italy |
| Varese | Italy |
| Barcelona | Spain |
| Pamplona | Spain |
| Salamanca | Spain |
| Boston | United Kingdom |
| Leicester | United Kingdom |
| Nottingham | United Kingdom |
| West Bromwich | United Kingdom |
| FG001 | Hydroxyurea | Hydroxyurea (HU) (500 mg capsules) will be orally self-administered at the dose that the subject was receiving previously. The dose may be increased after 4 weeks and again after 8 weeks of therapy to optimize efficacy for subjects meeting prespecified criteria. Ruxolitinib-placebo All placebo will be self-administered, and dosing will be the same as with the blinded dose. When adjustments are made to the HU dose, the dose of ruxolitinib-placebo will be adjusted concurrently. |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Ruxolitinib | Ruxolitinib will be orally self-administered at a starting dose of 10 mg (two 5 mg tablets) twice a day. Dose increases of 5 mg (1 tablet) in twice-daily increments are permitted after 4 weeks and again after 8 weeks of therapy for subjects who meet prespecified criteria for inadequate efficacy. HU-placebo All placebo will be self-administered, and dosing will be the same as with the blinded dose. When adjustments are made to the ruxolitinib dose, the dose of HU-placebo will be adjusted concurrently. |
| BG001 | Hydroxyurea | Hydroxyurea (HU) (500 mg capsules) will be orally self-administered at the dose that the subject was receiving previously. The dose may be increased after 4 weeks and again after 8 weeks of therapy to optimize efficacy for subjects meeting prespecified criteria. Ruxolitinib-placebo All placebo will be self-administered, and dosing will be the same as with the blinded dose. When adjustments are made to the HU dose, the dose of ruxolitinib-placebo will be adjusted concurrently. |
| 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 |
| ||||||||||||||||
| Race/Ethnicity, Customized | Number | 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 of Subjects Achieving a ≥ 50% Improvement From Baseline in Total Symptom Score-Cytokine (TSS-C) at Week 16, as Measured by the Modified Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) Diary | Symptoms of polycythemia vera were assessed using a modified Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) electronic diary. Using the diary, patients rated the following symptoms on a scale from 0 (absent) to 10 (worst imaginable): tiredness, itching, muscle aches, night sweats, and sweats while awake. The total symptom score ranged from 0-50 and was calculated as the sum of the 5 symptom scores. A higher score indicates worse symptoms. | Intent-to-Treat (ITT); all subjects randomized in the study. For the overall TSS-C score, only those subjects with a baseline score of 0 and a Week 16 score of 0 or missing were excluded from the analysis. | Posted | Number | Percentage of participants | From Baseline to Week 16 |
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| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Percentage of Subjects Achieving ≥ 50% Improvement From Baseline in the Individual Symptom Scores for TSS-C at Week 16 | The TSS-C cluster includes tiredness, itching, muscle aches, night sweats, and sweats while awake. | Intent-to-Treat (ITT); all subjects randomized in the study. For individual symptom scores within the TSS-C cluster, only those subjects with a baseline score of 0 and a Week 16 score of 0 or missing were excluded from the analysis. | Posted | Number | Percentage of participants | From Baseline to Week 16 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Proportion of Subjects Randomized to Ruxolitinib Who Achieved ≥ 50% Improvement From Baseline in Total Symptom Score-Cytokine and the Individual Symptom Scores at Week 16 That Were Maintained at Week 48 | Durable Response on TSS-C/individual symptoms defined as a ≥ 50% reduction in TSS-C/individual symptoms at Week 16 that were maintained at Week 48 | Intent-to-Treat (ITT); all subjects randomized to Ruxolitinib in the study. For TSS-C/individual symptoms, subject without baseline value was excluded from the analysis. | Posted | Number | 95% Confidence Interval | percentage of participants | Week 48 |
|
|
The duration of the study up to Week 16. This time frame defines the blinded, comparative phase of the study where the majority of patients remained on their original randomized assignment and exposure between ruxolitinib and hydroxyurea was similar.
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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 | Ruxolitinib | Ruxolitinib will be orally self-administered at a starting dose of 10 mg (two 5 mg tablets) twice a day. Dose increases of 5 mg (1 tablet) in twice-daily increments are permitted after 4 weeks and again after 8 weeks of therapy for subjects who meet prespecified criteria for inadequate efficacy. HU-placebo All placebo will be self-administered, and dosing will be the same as with the blinded dose. When adjustments are made to the ruxolitinib dose, the dose of HU-placebo will be adjusted concurrently. | 5 | 54 | 50 | 54 | ||
| EG001 | Hydroxyurea | Hydroxyurea (HU) (500 mg capsules) will be orally self-administered at the dose that the subject was receiving previously. The dose may be increased after 4 weeks and again after 8 weeks of therapy to optimize efficacy for subjects meeting prespecified criteria. Ruxolitinib-placebo All placebo will be self-administered, and dosing will be the same as with the blinded dose. When adjustments are made to the HU dose, the dose of ruxolitinib-placebo will be adjusted concurrently. | 4 | 56 | 45 | 56 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Angina unstable | Cardiac disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Arterial occlusive disease | Vascular disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Cerebral ischemia | Nervous system disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Chest discomfort | General disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Platelet count increased | Investigations | MedDRA (15.1) | Systematic Assessment |
| |
| Spondylolisthesis | Musculoskeletal and connective tissue disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Deep vein thrombosis | Vascular disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Hematuria | Renal and urinary disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Hemoglobin decreased | Investigations | MedDRA (15.1) | Systematic Assessment |
| |
| Hydronephrosis | Renal and urinary disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Hyperkalemia | Metabolism and nutrition disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Renal failure acute | Renal and urinary disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Urosepsis | Infections and infestations | MedDRA (15.1) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Headache | Nervous system disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Anemia | Blood and lymphatic system disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA (15.1) | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Contusion | Injury, poisoning and procedural complications | MedDRA (15.1) | Systematic Assessment |
| |
| Vision blurred | Eye disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Weight increased | Investigations | MedDRA (15.1) | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Dyspnea | Respiratory, thoracic and mediastinal disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Night sweats | Skin and subcutaneous tissue disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Edema peripheral | General disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Blood lactate dehydrogenase increased | Investigations | MedDRA (15.1) | Systematic Assessment |
| |
| Dry mouth | Gastrointestinal disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Thrombocytosis | Blood and lymphatic system disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Abdominal distension | Gastrointestinal disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA (15.1) | Systematic Assessment |
| |
| Disturbance in attention | Psychiatric disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Palpitations | Cardiac disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Tinnitus | Ear and labyrinth disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Paresthesia | Nervous system disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA (15.1) | Systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Erythema | Skin and subcutaneous tissue disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Leukopenia | Blood and lymphatic system disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA (15.1) | Systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Depression | Psychiatric disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Gout | Metabolism and nutrition disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Atrial fibrillation | Cardiac disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Benign prostatic hyperplasia | Reproductive system and breast disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Hydronephrosis | Renal and urinary disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Hyperkalemia | Metabolism and nutrition disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Hyperuricemia | Metabolism and nutrition disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Lymphadenopathy | Blood and lymphatic system disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Neutrophil count decreased | Investigations | MedDRA (15.1) | Systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA (15.1) | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Platelet count decreased | Investigations | MedDRA (15.1) | Systematic Assessment |
| |
| Diarrhea | Gastrointestinal disorders | MedDRA (15.1) | Systematic Assessment |
| |
| Chest pain | General disorders | MedDRA (15.1) | Systematic Assessment |
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Following the first publication, the Institution and/or Principal Investigator may publish data or results from the Study, provided, however, that the Institution and/or Principal Investigator submits the proposed publication to the Sponsor for review at least sixty (60) days prior to the date of the proposed publication. Sponsor may remove from the proposed publication any information that is considered confidential and/or proprietary other than Study data and results.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Incyte Corporation | 855 463-3463 |
| ID | Term |
|---|---|
| D011087 | Polycythemia Vera |
| ID | Term |
|---|---|
| D019046 | Bone Marrow Neoplasms |
| D019337 | Hematologic Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001855 | Bone Marrow Diseases |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D009196 | Myeloproliferative Disorders |
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| ID | Term |
|---|---|
| C540383 | ruxolitinib |
| D006918 | Hydroxyurea |
| ID | Term |
|---|---|
| D014508 | Urea |
| D000577 | Amides |
| D009930 | Organic Chemicals |
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| Male |
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| Asian |
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