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Study to Determine the Safety and Efficacy of INCB018424 in Patients With Polycythemia Vera or Essential Thrombocythemia

Sponsor
Incyte Corporation (Industry)
Overall Status
Terminated
CT.gov ID
NCT00726232
Collaborator
(none)
73
Enrollment
4
Locations
3
Arms
120
Actual Duration (Months)
18.3
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

To evaluate the safety and efficacy profile of different treatment regimens of Ruxolitinib (INCB018424) administered to two groups of patients; those with polycythemia vera (PV) and those with essential thrombocythemia (ET). Patients in each group were refractory to hydroxyurea or for whom hydroxyurea is contraindicated.

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

The study consisted of a 2-stage design, which included a dose-ranging phase (during which patients received treatment at their randomized dose) and an expansion phase (after adjustment of dose/regimen to achieve an optimal balance of efficacy and safety). During the dose-ranging phase, patients in each disease group (PV or ET) were randomly assigned in a 1:1:1 ratio independent of each other to receive 1 of 3 treatment regimens with Ruxolitinib, 10 mg twice daily (bid), 25 mg bid, or 50 mg once daily (qd). After patients completed 2 cycles of treatment with Ruxolitinib at the randomized dose, Investigators were permitted to adjust the dose/regimen on an individual basis using their discretion in order to achieve an optimal balance of efficacy and safety. During the expansion phase (ie, after optimization of dose), additional patients with PV or ET were enrolled to receive Ruxolitinib at the dose that was selected upon review of data from the dose-ranging phase. Treatment continued until a patient met a withdrawal criterion, had intolerable toxicity, progression of disease, or withdrew consent.

Study Design

Study Type:
Interventional
Actual Enrollment :
73 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 2, Open Label, Dose Regimen Ranging Clinical Study to Determine the Safety and Efficacy of INCB018424 in Patients With Advanced Polycythemia Vera or Essential Thrombocythemia Refractory to Hydroxyurea
Actual Study Start Date :
Aug 20, 2008
Actual Primary Completion Date :
Jun 20, 2010
Actual Study Completion Date :
Aug 20, 2018

Arms and Interventions

Arm Intervention/Treatment
Experimental: Ruxolitinib 10 mg BID

Participants received 10 mg Ruxolitinib orally twice a day (BID) for 56 days (two 28-day cycles) during the dose-ranging phase. After patients completed 2 cycles of treatment at the randomized dose, Investigators were permitted to adjust the dose/regimen on an individual basis to achieve an optimal balance of efficacy and safety. Treatment continued until a patient met a withdrawal criterion, had intolerable toxicity, progression of disease, or withdrew consent.

Drug: Ruxolitinib
Ruxolitinib was administered orally and supplied as 5 mg and 25 mg tablets.
Other Names:
  • INCB018424

    		•
    Experimental: Ruxolitinib 25 mg BID

    Participants received 25 mg Ruxolitinib orally twice a day (BID) for 56 days (two 28-day cycles) during the dose-ranging phase. After patients completed 2 cycles of treatment at the randomized dose, Investigators were permitted to adjust the dose/regimen on an individual basis to achieve an optimal balance of efficacy and safety. Treatment continued until a patient met a withdrawal criterion, had intolerable toxicity, progression of disease, or withdrew consent.

    Drug: Ruxolitinib
    Ruxolitinib was administered orally and supplied as 5 mg and 25 mg tablets.
    Other Names:
  • INCB018424

    		•
    Experimental: Ruxolitinib 50 mg QD

    Participants received 50 mg Ruxolitinib orally once a day (QD) for 56 days (two 28-day cycles) during the dose-ranging phase. After patients completed 2 cycles of treatment at the randomized dose, Investigators were permitted to adjust the dose/regimen on an individual basis to achieve an optimal balance of efficacy and safety. Treatment continued until a patient met a withdrawal criterion, had intolerable toxicity, progression of disease, or withdrew consent.

    Drug: Ruxolitinib
    Ruxolitinib was administered orally and supplied as 5 mg and 25 mg tablets.
    Other Names:
  • INCB018424

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Percentage of Polycythemia Vera Participants With a Confirmed Clinical Partial Response (PR) or Complete Response (CR) [Assessed after 2 cycles (56 days) of treatment on Day 1 of Cycle 3]

      For a confirmed response all criteria must have been sustained for at least 2 months. CR: Hematocrit < 45% in men and < 42% in women No phlebotomy for 1 month No palpable splenomegaly White blood cells < 10 x 10^9/L with normal differential and platelets < 400 x 10^9/L No sustained leucopenia or thrombocytopenia (>2 weeks) No systemic PV symptoms (pruritus, night sweats, bone pain, fever, weight loss) PR: Hematocrit < 45% in men and < 42% in women 50% reduction in phlebotomy requirements from 6 months before treatment started 50% reduction in palpable splenomegaly

    2. Percentage of Essential Thrombocythemia (ET) Participants With a Confirmed Clinical Partial Response (PR) or Complete Response (CR) [Assessed after 2 cycles (56 days) of treatment on Day 1 of Cycle 3.]

      For a confirmed response all criteria must have been sustained for at least 2 months. Complete Clinical Response: Platelet count < 400 x 10^9/L White blood cell count < 10 x 10^9/L with normal differential and Hematocrit ≤ upper limit of normal Absence of sustained (> 2 weeks) anemia or leucopenia based on institutional normal ranges Absence of systemic ET symptoms (pruritus, bone pain, weakness, night sweats, paresthesias) Absence of palpable splenomegaly Partial Clinical Response: Platelet count < 400 x 10^9/L 50% reduction in palpable splenomegaly

    Secondary Outcome Measures

    1. Percentage of Polycythemia Vera Participants Who Achieved Individual Components of Clinical Response at 12 Weeks [Baseline and Week 12 (Cycle 4, Day 1)]

      The individual components of clinical response included: Hematocrit (Hct) < 45% without phlebotomy Absence of palpable splenomegaly 50% reduction in spleen size Platelet count ≤ 400 x 10^9/L White blood cell (WBC) count ≤ 10 x 10^9/L

    2. Percentage of Polycythemia Vera Participants Who Achieved Individual Components of Clinical Response at 24 Weeks [Baseline and Week 24 (Cycle 7, Day 1)]

      The individual components of clinical response included: Hematocrit (Hct) < 45% without phlebotomy Absence of palpable splenomegaly 50% reduction in spleen size Platelet count ≤ 400 x 10^9/L White blood cell (WBC) count ≤ 10 x 10^9/L

    3. Percentage of Polycythemia Vera Participants Who Achieved Individual Components of Clinical Response at 36 Weeks [Baseline and Week 36 (Cycle 10, Day 1)]

      The individual components of clinical response included: Hematocrit (Hct) < 45% without phlebotomy Absence of palpable splenomegaly 50% reduction in spleen size Platelet count ≤ 400 x 10^9/L White blood cell (WBC) count ≤ 10 x 10^9/L

    4. Percentage of Essential Thrombocythemia Participants Who Achieved Individual Components of Clinical Response at 4 Weeks [Baseline and 4 weeks (Cycle 2, Day 1)]

      The individual components of clinical response included: Platelet count ≤ 400 x 10^9/L White blood cell (WBC) count ≤ 10 x 10^9/L 50% reduction in spleen size Absence of palpable splenomegaly

    5. Percentage of Essential Thrombocythemia Participants Who Achieved Individual Components of Clinical Response at 24 Weeks [Baseline and 24 weeks (Cycle 7, Day 1)]

      The individual components of clinical response included: Platelet count ≤ 400 x 10^9/L White blood cell (WBC) count ≤ 10 x 10^9/L 50% reduction in spleen size Absence of palpable splenomegaly

    6. Percentage of Essential Thrombocythemia Participants Who Achieved Individual Components of Clinical Response at 36 Weeks [Baseline and 36 weeks (Cycle 10, Day 1)]

      The individual components of clinical response included: Platelet count ≤ 400 x 10^9/L White blood cell (WBC) count ≤ 10 x 10^9/L 50% reduction in spleen size Absence of palpable splenomegaly

    7. Change From Baseline to Week 4 in Polycythemia Vera Symptoms [Baseline and Week 4 (Cycle 2, Day 1)]

      Patients were asked to rate their symptoms on a scale of 0 (none) to 10 (worse possible) for the prior week giving the worst level of symptoms experienced during the preceding 7 days. A negative change from baseline score indicates improvement in symptoms. For patients with Polycythemia Vera, queried symptoms included fever, itching/pruritus, bone pain and night sweats.

    8. Change From Baseline to Week 4 in Essential Thrombocythemia Symptoms [Baseline and Week 4 (Cycle 2, Day 1)]

      Patients were asked to rate their symptoms on a scale of 0 (none) to 10 (worse possible) for the prior week giving the worst level of symptoms experienced during the preceding 7 days. A negative change from baseline score indicates improvement in symptoms. For patients with essential thrombocythemia, queried symptoms included itching/pruritus, bone pain, night sweats, paresthesias (tingling or numbness), and weakness.

    9. Change From Baseline to Week 4 in Health-related Quality of Life [Baseline and Week 4 (Cycle 2, Day 1)]

      Health-related Quality of Life was assessed using the Global Health Status/Quality of Life Scale of the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). This scale ranges from 0 to 100, with higher scores indicating higher quality of life.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Confirmed diagnosis of polycythemia vera or essential thrombocythemia as determined by treating physician

    • Disease refractory to hydroxyurea or for whom treatment with hydroxyurea is contraindicated or have refused further treatment with hydroxyurea due to side effects.

    • Patient meets baseline clinical lab parameters

    Exclusion Criteria:

    • Treatment with interferon alpha or anagrelide within 7 days and hydroxyurea within 1 day of starting INCB018424.

    • Patients diagnosed with another malignancy unless the malignancy was cervical intraepithelial neoplasia or basal or squamous cell skin cancer and the patient has been disease free for > 3 years

    • Patients receiving therapy with intermediate or high dose steroids greater than the equivalent of 10 mg prednisone per day

    • Clinically significant cardiac disease (New York Heart Association (NYHA) Class III or IV)

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Houston Texas United States 77030
    2 Bergamo Italy
    3 Firenze Italy
    4 Pavia Italy

    Sponsors and Collaborators

    • Incyte Corporation

    Investigators

    • Study Director: Albert Assad, MD, Incyte Corporation

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Incyte Corporation
    ClinicalTrials.gov Identifier:
    NCT00726232
    Other Study ID Numbers:
    • INCB 18424-256
    • Ruxolitinib
    First Posted:
    Jul 31, 2008
    Last Update Posted:
    Oct 28, 2019
    Last Verified:
    Oct 1, 2019
    Additional relevant MeSH terms:
    Polycythemia Vera
    Myeloproliferative Disorders
    Polycythemia
    Thrombocytosis
    Thrombocythemia, Essential

    Study Results

    Participant Flow

    Recruitment Details This was a multicenter study with 2 sites in the United States and 4 sites in Italy.
    Pre-assignment Detail
    Arm/Group Title Polycythemia Vera (PV): Ruxolitinib 10 mg BID PV: Ruxolitinib 25 mg BID PV: Ruxolitinib 50 mg QD Essential Thrombocythemia (ET): Ruxolitinib 10 mg BID ET: Ruxolitinib 25 mg BID ET: Ruxolitinib 50 mg QD PV: Ruxolitinib All Doses Combined- Expansion Phase ET: Ruxolitinib All Doses Combined-expansion Phase
    Arm/Group Description Participants with Polycythemia Vera received 10 mg Ruxolitinib orally twice a day (BID) for 56 days (two 28-day cycles) during the dose-ranging phase. After patients completed 2 cycles of treatment at the randomized dose, Investigators were permitted to adjust the dose/regimen on an individual basis to achieve an optimal balance of efficacy and safety. Treatment continued until a patient met a withdrawal criterion, had intolerable toxicity, progression of disease, or withdrew consent. Participants with Polycythemia Vera received 25 mg Ruxolitinib orally twice a day (BID) for 56 days (two 28-day cycles) during the dose-ranging phase. After patients completed 2 cycles of treatment at the randomized dose, Investigators were permitted to adjust the dose/regimen on an individual basis to achieve an optimal balance of efficacy and safety. Treatment continued until a patient met a withdrawal criterion, had intolerable toxicity, progression of disease, or withdrew consent. Participants with Polycythemia Vera received 50 mg Ruxolitinib orally once a day (QD) for 56 days (two 28-day cycles) during the dose-ranging phase. After patients completed 2 cycles of treatment at the randomized dose, Investigators were permitted to adjust the dose/regimen on an individual basis to achieve an optimal balance of efficacy and safety. Treatment continued until a patient met a withdrawal criterion, had intolerable toxicity, progression of disease, or withdrew consent. Participants with Essential Thrombocythemia received 10 mg Ruxolitinib orally twice a day (BID) for 56 days (two 28-day cycles) during the dose-ranging phase. After patients completed 2 cycles of treatment at the randomized dose, Investigators were permitted to adjust the dose/regimen on an individual basis to achieve an optimal balance of efficacy and safety. Treatment continued until a patient met a withdrawal criterion, had intolerable toxicity, progression of disease, or withdrew consent. Participants with Essential Thrombocythemia received 25 mg Ruxolitinib orally twice a day (BID) for 56 days (two 28-day cycles) during the dose-ranging phase. After patients completed 2 cycles of treatment at the randomized dose, Investigators were permitted to adjust the dose/regimen on an individual basis to achieve an optimal balance of efficacy and safety. Treatment continued until a patient met a withdrawal criterion, had intolerable toxicity, progression of disease, or withdrew consent. Participants with Essential Thrombocythemia received 50 mg Ruxolitinib orally once a day (QD) for 56 days (two 28-day cycles) during the dose-ranging phase. After patients completed 2 cycles of treatment at the randomized dose, Investigators were permitted to adjust the dose/regimen on an individual basis to achieve an optimal balance of efficacy and safety. Treatment continued until a patient met a withdrawal criterion, had intolerable toxicity, progression of disease, or withdrew consent. After the completion of the dose-finding phase of the study, the starting dose of ruxolitinib for the expansion phase was determined to be 10 mg BID for subjects with PV. After subjects completed 8 weeks of ruxolitinib treatment at the starting dose, investigators were permitted to adjust the dose regimen to a maximum total daily dose of 75 mg on an individual basis, using their discretion, in order to achieve an optimal balance of efficacy and safety. After the completion of the dose-finding phase of the study, the starting dose of ruxolitinib for the expansion phase was determined to be 25 mg BID for subjects with ET. After subjects completed 8 weeks of ruxolitinib treatment at the starting dose, investigators were permitted to adjust the dose regimen to a maximum total daily dose of 75 mg on an individual basis, using their discretion, in order to achieve an optimal balance of efficacy and safety.
    Period Title: Initial Phase (Dose-finding)
    STARTED 19 8 7 8 22 9 0 0
    Safety Evaluable Participants 19 8 7 8 22 9 0 0
    ITT Participants 19 8 7 8 22 9 0 0
    COMPLETED 6 2 2 0 1 0 0 0
    NOT COMPLETED 13 6 5 8 21 9 0 0
    Period Title: Initial Phase (Dose-finding)
    STARTED 0 0 0 0 0 0 34 39
    Safety Evaluable Participants 0 0 0 0 0 0 34 39
    ITT Participants 0 0 0 0 0 0 34 39
    COMPLETED 0 0 0 0 0 0 10 1
    NOT COMPLETED 0 0 0 0 0 0 24 38

    Baseline Characteristics

    Arm/Group Title PV: Ruxolitinib 10 mg BID PV: Ruxolitinib 25 mg BID PV: Ruxolitinib 50 mg QD ET: Ruxolitinib 10 mg BID ET: Ruxolitinib 25 mg BID ET: Ruxolitinib 50 mg QD Total
    Arm/Group Description Participants with Polycythemia Vera received 10 mg Ruxolitinib orally twice a day (BID) for 56 days (two 28-day cycles) during the dose-ranging phase. After patients completed 2 cycles of treatment at the randomized dose, Investigators were permitted to adjust the dose/regimen on an individual basis to achieve an optimal balance of efficacy and safety. Treatment continued until a patient met a withdrawal criterion, had intolerable toxicity, progression of disease, or withdrew consent. Participants with Polycythemia Vera received 25 mg Ruxolitinib orally twice a day (BID) for 56 days (two 28-day cycles) during the dose-ranging phase. After patients completed 2 cycles of treatment at the randomized dose, Investigators were permitted to adjust the dose/regimen on an individual basis to achieve an optimal balance of efficacy and safety. Treatment continued until a patient met a withdrawal criterion, had intolerable toxicity, progression of disease, or withdrew consent. Participants with Polycythemia Vera received 50 mg Ruxolitinib orally once a day (QD) for 56 days (two 28-day cycles) during the dose-ranging phase. After patients completed 2 cycles of treatment at the randomized dose, Investigators were permitted to adjust the dose/regimen on an individual basis to achieve an optimal balance of efficacy and safety. Treatment continued until a patient met a withdrawal criterion, had intolerable toxicity, progression of disease, or withdrew consent. Participants with Essential Thrombocythemia received 10 mg Ruxolitinib orally twice a day (BID) for 56 days (two 28-day cycles) during the dose-ranging phase. After patients completed 2 cycles of treatment at the randomized dose, Investigators were permitted to adjust the dose/regimen on an individual basis to achieve an optimal balance of efficacy and safety. Treatment continued until a patient met a withdrawal criterion, had intolerable toxicity, progression of disease, or withdrew consent. Participants with Essential Thrombocythemia received 25 mg Ruxolitinib orally twice a day (BID) for 56 days (two 28-day cycles) during the dose-ranging phase. After patients completed 2 cycles of treatment at the randomized dose, Investigators were permitted to adjust the dose/regimen on an individual basis to achieve an optimal balance of efficacy and safety. Treatment continued until a patient met a withdrawal criterion, had intolerable toxicity, progression of disease, or withdrew consent. Participants with Essential Thrombocythemia received 50 mg Ruxolitinib orally once a day (QD) for 56 days (two 28-day cycles) during the dose-ranging phase. After patients completed 2 cycles of treatment at the randomized dose, Investigators were permitted to adjust the dose/regimen on an individual basis to achieve an optimal balance of efficacy and safety. Treatment continued until a patient met a withdrawal criterion, had intolerable toxicity, progression of disease, or withdrew consent. Total of all reporting groups
    Overall Participants 19 8 7 8 22 9 73
    Age (years) [Mean (Standard Deviation) ]
    Polycythemia vera group
    56.3
    (10.98)
    57.0
    (11.26)
    51.0
    (20.49)
    NA
    (NA)
    NA
    (NA)
    NA
    (NA)
    55.4
    (13.20)
    Essential thrombocythemia group
    NA
    (NA)
    NA
    (NA)
    NA
    (NA)
    49.6
    (17.89)
    54.1
    (11.55)
    52.8
    (13.48)
    52.9
    (13.19)
    Age, Customized (participants) [Number]
    >= 65
    5
    26.3%
    3
    37.5%
    2
    28.6%
    1
    12.5%
    3
    13.6%
    3
    33.3%
    17
    23.3%
    < 65
    14
    73.7%
    5
    62.5%
    5
    71.4%
    7
    87.5%
    19
    86.4%
    6
    66.7%
    56
    76.7%
    Sex: Female, Male (Count of Participants)
    Female
    11
    57.9%
    2
    25%
    4
    57.1%
    3
    37.5%
    13
    59.1%
    9
    100%
    42
    57.5%
    Male
    8
    42.1%
    6
    75%
    3
    42.9%
    5
    62.5%
    9
    40.9%
    0
    0%
    31
    42.5%
    Hematocrit (participants) [Number]
    Hematocrit ≥ 45%
    10
    52.6%
    7
    87.5%
    6
    85.7%
    1
    12.5%
    4
    18.2%
    0
    0%
    28
    38.4%
    Hematocrit < 45%
    9
    47.4%
    1
    12.5%
    1
    14.3%
    7
    87.5%
    18
    81.8%
    9
    100%
    45
    61.6%
    Platelet count (participants) [Number]
    ≥400 x 10^9 per liter
    13
    68.4%
    4
    50%
    6
    85.7%
    7
    87.5%
    22
    100%
    9
    100%
    61
    83.6%
    < 400 x 10^9 per liter
    6
    31.6%
    4
    50%
    1
    14.3%
    1
    12.5%
    0
    0%
    0
    0%
    12
    16.4%
    White blood cell count (participants) [Number]
    ≥ 10 x 10^9 per liter
    12
    63.2%
    7
    87.5%
    6
    85.7%
    2
    25%
    7
    31.8%
    2
    22.2%
    36
    49.3%
    < 10 x 10^9 per liter
    7
    36.8%
    1
    12.5%
    1
    14.3%
    6
    75%
    15
    68.2%
    7
    77.8%
    37
    50.7%

    Outcome Measures

    1. Primary Outcome
    Title Percentage of Polycythemia Vera Participants With a Confirmed Clinical Partial Response (PR) or Complete Response (CR)
    Description For a confirmed response all criteria must have been sustained for at least 2 months. CR: Hematocrit < 45% in men and < 42% in women No phlebotomy for 1 month No palpable splenomegaly White blood cells < 10 x 10^9/L with normal differential and platelets < 400 x 10^9/L No sustained leucopenia or thrombocytopenia (>2 weeks) No systemic PV symptoms (pruritus, night sweats, bone pain, fever, weight loss) PR: Hematocrit < 45% in men and < 42% in women 50% reduction in phlebotomy requirements from 6 months before treatment started 50% reduction in palpable splenomegaly
    Time Frame Assessed after 2 cycles (56 days) of treatment on Day 1 of Cycle 3

    Outcome Measure Data

    Analysis Population Description
    Polycythemia Vera intent to treat population, including all patients who took at least 1 dose of study drug.
    Arm/Group Title PV: Ruxolitinib 10 mg BID PV: Ruxolitinib 25 mg BID PV: Ruxolitinib 50 mg QD
    Arm/Group Description Participants with Polycythemia Vera received 10 mg Ruxolitinib orally twice a day (BID) for 56 days (two 28-day cycles) during the dose-ranging phase. After patients completed 2 cycles of treatment at the randomized dose, Investigators were permitted to adjust the dose/regimen on an individual basis to achieve an optimal balance of efficacy and safety. Treatment continued until a patient met a withdrawal criterion, had intolerable toxicity, progression of disease, or withdrew consent. Participants with Polycythemia Vera received 25 mg Ruxolitinib orally twice a day (BID) for 56 days (two 28-day cycles) during the dose-ranging phase. After patients completed 2 cycles of treatment at the randomized dose, Investigators were permitted to adjust the dose/regimen on an individual basis to achieve an optimal balance of efficacy and safety. Treatment continued until a patient met a withdrawal criterion, had intolerable toxicity, progression of disease, or withdrew consent. Participants with Polycythemia Vera received 50 mg Ruxolitinib orally once a day (QD) for 56 days (two 28-day cycles) during the dose-ranging phase. After patients completed 2 cycles of treatment at the randomized dose, Investigators were permitted to adjust the dose/regimen on an individual basis to achieve an optimal balance of efficacy and safety. Treatment continued until a patient met a withdrawal criterion, had intolerable toxicity, progression of disease, or withdrew consent.
    Measure Participants 19 8 7
    Number [percentage of participants]
    58
    305.3%
    50
    625%
    57
    814.3%
    2. Secondary Outcome
    Title Percentage of Polycythemia Vera Participants Who Achieved Individual Components of Clinical Response at 12 Weeks
    Description The individual components of clinical response included: Hematocrit (Hct) < 45% without phlebotomy Absence of palpable splenomegaly 50% reduction in spleen size Platelet count ≤ 400 x 10^9/L White blood cell (WBC) count ≤ 10 x 10^9/L
    Time Frame Baseline and Week 12 (Cycle 4, Day 1)

    Outcome Measure Data

    Analysis Population Description
    Polycythemia Vera intent to treat population for whom data was available.
    Arm/Group Title PV: Ruxolitinib 10 mg BID PV: Ruxolitinib 25 mg BID PV: Ruxolitinib 50 mg QD
    Arm/Group Description Participants with Polycythemia Vera received 10 mg Ruxolitinib orally twice a day (BID) for 56 days (two 28-day cycles) during the dose-ranging phase. After patients completed 2 cycles of treatment at the randomized dose, Investigators were permitted to adjust the dose/regimen on an individual basis to achieve an optimal balance of efficacy and safety. Treatment continued until a patient met a withdrawal criterion, had intolerable toxicity, progression of disease, or withdrew consent. Participants with Polycythemia Vera received 25 mg Ruxolitinib orally twice a day (BID) for 56 days (two 28-day cycles) during the dose-ranging phase. After patients completed 2 cycles of treatment at the randomized dose, Investigators were permitted to adjust the dose/regimen on an individual basis to achieve an optimal balance of efficacy and safety. Treatment continued until a patient met a withdrawal criterion, had intolerable toxicity, progression of disease, or withdrew consent. Participants with Polycythemia Vera received 50 mg Ruxolitinib orally once a day (QD) for 56 days (two 28-day cycles) during the dose-ranging phase. After patients completed 2 cycles of treatment at the randomized dose, Investigators were permitted to adjust the dose/regimen on an individual basis to achieve an optimal balance of efficacy and safety. Treatment continued until a patient met a withdrawal criterion, had intolerable toxicity, progression of disease, or withdrew consent.
    Measure Participants 19 8 7
    Hematocrit <45% Without Phlebotomy
    95
    500%
    88
    1100%
    86
    1228.6%
    Absence of palpable splenomegaly
    68
    357.9%
    50
    625%
    57
    814.3%
    50% reduction in spleen size
    74
    389.5%
    63
    787.5%
    86
    1228.6%
    Platelet count ≤ 400 x 10^9/L
    58
    305.3%
    50
    625%
    57
    814.3%
    WBC count ≤ 10 x 10^9/L
    68
    357.9%
    63
    787.5%
    43
    614.3%
    3. Primary Outcome
    Title Percentage of Essential Thrombocythemia (ET) Participants With a Confirmed Clinical Partial Response (PR) or Complete Response (CR)
    Description For a confirmed response all criteria must have been sustained for at least 2 months. Complete Clinical Response: Platelet count < 400 x 10^9/L White blood cell count < 10 x 10^9/L with normal differential and Hematocrit ≤ upper limit of normal Absence of sustained (> 2 weeks) anemia or leucopenia based on institutional normal ranges Absence of systemic ET symptoms (pruritus, bone pain, weakness, night sweats, paresthesias) Absence of palpable splenomegaly Partial Clinical Response: Platelet count < 400 x 10^9/L 50% reduction in palpable splenomegaly
    Time Frame Assessed after 2 cycles (56 days) of treatment on Day 1 of Cycle 3.

    Outcome Measure Data

    Analysis Population Description
    Essential thrombocythemia intent to treat population, including all patients who took at least 1 dose of study drug. One patient in the 50 mg QD group did not have a response assessment at Cycle 3, Day 1.
    Arm/Group Title ET: Ruxolitinib 10 mg BID ET: Ruxolitinib 25 mg BID ET: Ruxolitinib 50 mg QD
    Arm/Group Description Participants with Essential Thrombocythemia received 10 mg Ruxolitinib orally twice a day (BID) for 56 days (two 28-day cycles) during the dose-ranging phase. After patients completed 2 cycles of treatment at the randomized dose, Investigators were permitted to adjust the dose/regimen on an individual basis to achieve an optimal balance of efficacy and safety. Treatment continued until a patient met a withdrawal criterion, had intolerable toxicity, progression of disease, or withdrew consent. Participants with Essential Thrombocythemia received 25 mg Ruxolitinib orally twice a day (BID) for 56 days (two 28-day cycles) during the dose-ranging phase. After patients completed 2 cycles of treatment at the randomized dose, Investigators were permitted to adjust the dose/regimen on an individual basis to achieve an optimal balance of efficacy and safety. Treatment continued until a patient met a withdrawal criterion, had intolerable toxicity, progression of disease, or withdrew consent. Participants with Essential Thrombocythemia received 50 mg Ruxolitinib orally once a day (QD) for 56 days (two 28-day cycles) during the dose-ranging phase. After patients completed 2 cycles of treatment at the randomized dose, Investigators were permitted to adjust the dose/regimen on an individual basis to achieve an optimal balance of efficacy and safety. Treatment continued until a patient met a withdrawal criterion, had intolerable toxicity, progression of disease, or withdrew consent.
    Measure Participants 8 22 8
    Number [percentage of participants]
    13
    68.4%
    0
    0%
    0
    0%
    4. Secondary Outcome
    Title Percentage of Polycythemia Vera Participants Who Achieved Individual Components of Clinical Response at 24 Weeks
    Description The individual components of clinical response included: Hematocrit (Hct) < 45% without phlebotomy Absence of palpable splenomegaly 50% reduction in spleen size Platelet count ≤ 400 x 10^9/L White blood cell (WBC) count ≤ 10 x 10^9/L
    Time Frame Baseline and Week 24 (Cycle 7, Day 1)

    Outcome Measure Data

    Analysis Population Description
    Polycythemia Vera intent to treat population for whom data was available. 'N' indicates the number of patients for whom data was available for each component.
    Arm/Group Title PV: Ruxolitinib 10 mg BID PV: Ruxolitinib 25 mg BID PV: Ruxolitinib 50 mg QD
    Arm/Group Description Participants with Polycythemia Vera received 10 mg Ruxolitinib orally twice a day (BID) for 56 days (two 28-day cycles) during the dose-ranging phase. After patients completed 2 cycles of treatment at the randomized dose, Investigators were permitted to adjust the dose/regimen on an individual basis to achieve an optimal balance of efficacy and safety. Treatment continued until a patient met a withdrawal criterion, had intolerable toxicity, progression of disease, or withdrew consent. Participants with Polycythemia Vera received 25 mg Ruxolitinib orally twice a day (BID) for 56 days (two 28-day cycles) during the dose-ranging phase. After patients completed 2 cycles of treatment at the randomized dose, Investigators were permitted to adjust the dose/regimen on an individual basis to achieve an optimal balance of efficacy and safety. Treatment continued until a patient met a withdrawal criterion, had intolerable toxicity, progression of disease, or withdrew consent. Participants with Polycythemia Vera received 50 mg Ruxolitinib orally once a day (QD) for 56 days (two 28-day cycles) during the dose-ranging phase. After patients completed 2 cycles of treatment at the randomized dose, Investigators were permitted to adjust the dose/regimen on an individual basis to achieve an optimal balance of efficacy and safety. Treatment continued until a patient met a withdrawal criterion, had intolerable toxicity, progression of disease, or withdrew consent.
    Measure Participants 19 8 7
    Hematocrit <45% Without Phlebotomy
    100
    526.3%
    88
    1100%
    100
    1428.6%
    Absence of palpable splenomegaly
    61
    321.1%
    43
    537.5%
    71
    1014.3%
    50% reduction in spleen size
    78
    410.5%
    71
    887.5%
    100
    1428.6%
    Platelet count ≤ 400 x 10^9/L
    58
    305.3%
    88
    1100%
    86
    1228.6%
    WBC count ≤ 10 x 10^9/L
    74
    389.5%
    25
    312.5%
    86
    1228.6%
    5. Secondary Outcome
    Title Percentage of Polycythemia Vera Participants Who Achieved Individual Components of Clinical Response at 36 Weeks
    Description The individual components of clinical response included: Hematocrit (Hct) < 45% without phlebotomy Absence of palpable splenomegaly 50% reduction in spleen size Platelet count ≤ 400 x 10^9/L White blood cell (WBC) count ≤ 10 x 10^9/L
    Time Frame Baseline and Week 36 (Cycle 10, Day 1)

    Outcome Measure Data

    Analysis Population Description
    Polycythemia Vera intent to treat population for whom data was available. 'N' indicates the number of patients for whom data was available for each component.
    Arm/Group Title PV: Ruxolitinib 10 mg BID PV: Ruxolitinib 25 mg BID PV: Ruxolitinib 50 mg QD
    Arm/Group Description Participants with Polycythemia Vera received 10 mg Ruxolitinib orally twice a day (BID) for 56 days (two 28-day cycles) during the dose-ranging phase. After patients completed 2 cycles of treatment at the randomized dose, Investigators were permitted to adjust the dose/regimen on an individual basis to achieve an optimal balance of efficacy and safety. Treatment continued until a patient met a withdrawal criterion, had intolerable toxicity, progression of disease, or withdrew consent. Participants with Polycythemia Vera received 25 mg Ruxolitinib orally twice a day (BID) for 56 days (two 28-day cycles) during the dose-ranging phase. After patients completed 2 cycles of treatment at the randomized dose, Investigators were permitted to adjust the dose/regimen on an individual basis to achieve an optimal balance of efficacy and safety. Treatment continued until a patient met a withdrawal criterion, had intolerable toxicity, progression of disease, or withdrew consent. Participants with Polycythemia Vera received 50 mg Ruxolitinib orally once a day (QD) for 56 days (two 28-day cycles) during the dose-ranging phase. After patients completed 2 cycles of treatment at the randomized dose, Investigators were permitted to adjust the dose/regimen on an individual basis to achieve an optimal balance of efficacy and safety. Treatment continued until a patient met a withdrawal criterion, had intolerable toxicity, progression of disease, or withdrew consent.
    Measure Participants 18 8 7
    Hematocrit <45% Without Phlebotomy
    100
    526.3%
    88
    1100%
    100
    1428.6%
    Absence of palpable splenomegaly
    71
    373.7%
    57
    712.5%
    86
    1228.6%
    50% reduction in spleen size
    76
    400%
    71
    887.5%
    100
    1428.6%
    Platelet count ≤ 400 x 10^9/L
    67
    352.6%
    75
    937.5%
    86
    1228.6%
    WBC count ≤ 10 x 10^9/L
    67
    352.6%
    25
    312.5%
    71
    1014.3%
    6. Secondary Outcome
    Title Percentage of Essential Thrombocythemia Participants Who Achieved Individual Components of Clinical Response at 4 Weeks
    Description The individual components of clinical response included: Platelet count ≤ 400 x 10^9/L White blood cell (WBC) count ≤ 10 x 10^9/L 50% reduction in spleen size Absence of palpable splenomegaly
    Time Frame Baseline and 4 weeks (Cycle 2, Day 1)

    Outcome Measure Data

    Analysis Population Description
    Essential thrombocythemia intent to treat population. 'N' indicates the number of patients for whom data was available for each component.
    Arm/Group Title ET: Ruxolitinib 10 mg BID ET: Ruxolitinib 25 mg BID ET: Ruxolitinib 50 mg QD
    Arm/Group Description Participants with Essential Thrombocythemia received 10 mg Ruxolitinib orally twice a day (BID) for 56 days (two 28-day cycles) during the dose-ranging phase. After patients completed 2 cycles of treatment at the randomized dose, Investigators were permitted to adjust the dose/regimen on an individual basis to achieve an optimal balance of efficacy and safety. Treatment continued until a patient met a withdrawal criterion, had intolerable toxicity, progression of disease, or withdrew consent. Participants with Essential Thrombocythemia received 25 mg Ruxolitinib orally twice a day (BID) for 56 days (two 28-day cycles) during the dose-ranging phase. After patients completed 2 cycles of treatment at the randomized dose, Investigators were permitted to adjust the dose/regimen on an individual basis to achieve an optimal balance of efficacy and safety. Treatment continued until a patient met a withdrawal criterion, had intolerable toxicity, progression of disease, or withdrew consent. Participants with Essential Thrombocythemia received 50 mg Ruxolitinib orally once a day (QD) for 56 days (two 28-day cycles) during the dose-ranging phase. After patients completed 2 cycles of treatment at the randomized dose, Investigators were permitted to adjust the dose/regimen on an individual basis to achieve an optimal balance of efficacy and safety. Treatment continued until a patient met a withdrawal criterion, had intolerable toxicity, progression of disease, or withdrew consent.
    Measure Participants 8 22 9
    Platelet count ≤ 400 x 10^9/L
    25
    131.6%
    41
    512.5%
    33
    471.4%
    WBC count ≤ 10 x 10^9/L
    100
    526.3%
    100
    1250%
    100
    1428.6%
    50% reduction in spleen size
    83
    436.8%
    95
    1187.5%
    100
    1428.6%
    Absence of palpable splenomegaly
    67
    352.6%
    89
    1112.5%
    100
    1428.6%
    7. Secondary Outcome
    Title Percentage of Essential Thrombocythemia Participants Who Achieved Individual Components of Clinical Response at 24 Weeks
    Description The individual components of clinical response included: Platelet count ≤ 400 x 10^9/L White blood cell (WBC) count ≤ 10 x 10^9/L 50% reduction in spleen size Absence of palpable splenomegaly
    Time Frame Baseline and 24 weeks (Cycle 7, Day 1)

    Outcome Measure Data

    Analysis Population Description
    Essential thrombocythemia intent to treat population. 'N' indicates the number of patients for whom data was available for each component.
    Arm/Group Title ET: Ruxolitinib 10 mg BID ET: Ruxolitinib 25 mg BID ET: Ruxolitinib 50 mg QD
    Arm/Group Description Participants with Essential Thrombocythemia received 10 mg Ruxolitinib orally twice a day (BID) for 56 days (two 28-day cycles) during the dose-ranging phase. After patients completed 2 cycles of treatment at the randomized dose, Investigators were permitted to adjust the dose/regimen on an individual basis to achieve an optimal balance of efficacy and safety. Treatment continued until a patient met a withdrawal criterion, had intolerable toxicity, progression of disease, or withdrew consent. Participants with Essential Thrombocythemia received 25 mg Ruxolitinib orally twice a day (BID) for 56 days (two 28-day cycles) during the dose-ranging phase. After patients completed 2 cycles of treatment at the randomized dose, Investigators were permitted to adjust the dose/regimen on an individual basis to achieve an optimal balance of efficacy and safety. Treatment continued until a patient met a withdrawal criterion, had intolerable toxicity, progression of disease, or withdrew consent. Participants with Essential Thrombocythemia received 50 mg Ruxolitinib orally once a day (QD) for 56 days (two 28-day cycles) during the dose-ranging phase. After patients completed 2 cycles of treatment at the randomized dose, Investigators were permitted to adjust the dose/regimen on an individual basis to achieve an optimal balance of efficacy and safety. Treatment continued until a patient met a withdrawal criterion, had intolerable toxicity, progression of disease, or withdrew consent.
    Measure Participants 8 22 9
    Platelet count ≤ 400 x 10^9/L
    14
    73.7%
    5
    62.5%
    0
    0%
    WBC count ≤ 10 x 10^9/L
    100
    526.3%
    86
    1075%
    100
    1428.6%
    50% reduction in spleen size
    100
    526.3%
    100
    1250%
    100
    1428.6%
    Absence of palpable splenomegaly
    100
    526.3%
    95
    1187.5%
    100
    1428.6%
    8. Secondary Outcome
    Title Percentage of Essential Thrombocythemia Participants Who Achieved Individual Components of Clinical Response at 36 Weeks
    Description The individual components of clinical response included: Platelet count ≤ 400 x 10^9/L White blood cell (WBC) count ≤ 10 x 10^9/L 50% reduction in spleen size Absence of palpable splenomegaly
    Time Frame Baseline and 36 weeks (Cycle 10, Day 1)

    Outcome Measure Data

    Analysis Population Description
    Essential thrombocythemia intent to treat population. 'N' indicates the number of patients for whom data was available for each component.
    Arm/Group Title ET: Ruxolitinib 10 mg BID ET: Ruxolitinib 25 mg BID ET: Ruxolitinib 50 mg QD
    Arm/Group Description Participants with Essential Thrombocythemia received 10 mg Ruxolitinib orally twice a day (BID) for 56 days (two 28-day cycles) during the dose-ranging phase. After patients completed 2 cycles of treatment at the randomized dose, Investigators were permitted to adjust the dose/regimen on an individual basis to achieve an optimal balance of efficacy and safety. Treatment continued until a patient met a withdrawal criterion, had intolerable toxicity, progression of disease, or withdrew consent. Participants with Essential Thrombocythemia received 25 mg Ruxolitinib orally twice a day (BID) for 56 days (two 28-day cycles) during the dose-ranging phase. After patients completed 2 cycles of treatment at the randomized dose, Investigators were permitted to adjust the dose/regimen on an individual basis to achieve an optimal balance of efficacy and safety. Treatment continued until a patient met a withdrawal criterion, had intolerable toxicity, progression of disease, or withdrew consent. Participants with Essential Thrombocythemia received 50 mg Ruxolitinib orally once a day (QD) for 56 days (two 28-day cycles) during the dose-ranging phase. After patients completed 2 cycles of treatment at the randomized dose, Investigators were permitted to adjust the dose/regimen on an individual basis to achieve an optimal balance of efficacy and safety. Treatment continued until a patient met a withdrawal criterion, had intolerable toxicity, progression of disease, or withdrew consent.
    Measure Participants 8 22 9
    Platelet count ≤ 400 x 10^9/L
    14
    73.7%
    11
    137.5%
    14
    200%
    WBC count ≤ 10 x 10^9/L
    100
    526.3%
    79
    987.5%
    86
    1228.6%
    50% reduction in spleen size
    100
    526.3%
    100
    1250%
    100
    1428.6%
    Absence of palpable splenomegaly
    100
    526.3%
    94
    1175%
    100
    1428.6%
    9. Secondary Outcome
    Title Change From Baseline to Week 4 in Polycythemia Vera Symptoms
    Description Patients were asked to rate their symptoms on a scale of 0 (none) to 10 (worse possible) for the prior week giving the worst level of symptoms experienced during the preceding 7 days. A negative change from baseline score indicates improvement in symptoms. For patients with Polycythemia Vera, queried symptoms included fever, itching/pruritus, bone pain and night sweats.
    Time Frame Baseline and Week 4 (Cycle 2, Day 1)

    Outcome Measure Data

    Analysis Population Description
    Polycythemia Vera intent to treat population who had symptom scores > 0 at baseline for whom data was available.
    Arm/Group Title PV: Ruxolitinib 10 mg BID PV: Ruxolitinib 25 mg BID PV: Ruxolitinib 50 mg QD
    Arm/Group Description Participants with Polycythemia Vera received 10 mg Ruxolitinib orally twice a day (BID) for 56 days (two 28-day cycles) during the dose-ranging phase. After patients completed 2 cycles of treatment at the randomized dose, Investigators were permitted to adjust the dose/regimen on an individual basis to achieve an optimal balance of efficacy and safety. Treatment continued until a patient met a withdrawal criterion, had intolerable toxicity, progression of disease, or withdrew consent. Participants with Polycythemia Vera received 25 mg Ruxolitinib orally twice a day (BID) for 56 days (two 28-day cycles) during the dose-ranging phase. After patients completed 2 cycles of treatment at the randomized dose, Investigators were permitted to adjust the dose/regimen on an individual basis to achieve an optimal balance of efficacy and safety. Treatment continued until a patient met a withdrawal criterion, had intolerable toxicity, progression of disease, or withdrew consent. Participants with Polycythemia Vera received 50 mg Ruxolitinib orally once a day (QD) for 56 days (two 28-day cycles) during the dose-ranging phase. After patients completed 2 cycles of treatment at the randomized dose, Investigators were permitted to adjust the dose/regimen on an individual basis to achieve an optimal balance of efficacy and safety. Treatment continued until a patient met a withdrawal criterion, had intolerable toxicity, progression of disease, or withdrew consent.
    Measure Participants 19 8 7
    Itching (pruritus)
    -4.2
    (3.63)
    -4.6
    (1.85)
    -2.8
    (4.09)
    Bone pain
    -2.0
    (1.95)
    -2.5
    (0.71)
    -4.3
    (2.08)
    Fever
    -2.0
    (1.41)
    -2.0
    (1.41)
    Night sweats
    -1.9
    (2.52)
    -2.8
    (3.19)
    -3.3
    (1.15)
    10. Secondary Outcome
    Title Change From Baseline to Week 4 in Essential Thrombocythemia Symptoms
    Description Patients were asked to rate their symptoms on a scale of 0 (none) to 10 (worse possible) for the prior week giving the worst level of symptoms experienced during the preceding 7 days. A negative change from baseline score indicates improvement in symptoms. For patients with essential thrombocythemia, queried symptoms included itching/pruritus, bone pain, night sweats, paresthesias (tingling or numbness), and weakness.
    Time Frame Baseline and Week 4 (Cycle 2, Day 1)

    Outcome Measure Data

    Analysis Population Description
    Essential Thrombocythemia intent to treat population who had symptom scores > 0 at baseline and for whom data was available.
    Arm/Group Title ET: Ruxolitinib 10 mg BID ET: Ruxolitinib 25 mg BID ET: Ruxolitinib 50 mg QD
    Arm/Group Description Participants with Essential Thrombocythemia received 10 mg Ruxolitinib orally twice a day (BID) for 56 days (two 28-day cycles) during the dose-ranging phase. After patients completed 2 cycles of treatment at the randomized dose, Investigators were permitted to adjust the dose/regimen on an individual basis to achieve an optimal balance of efficacy and safety. Treatment continued until a patient met a withdrawal criterion, had intolerable toxicity, progression of disease, or withdrew consent. Participants with Essential Thrombocythemia received 25 mg Ruxolitinib orally twice a day (BID) for 56 days (two 28-day cycles) during the dose-ranging phase. After patients completed 2 cycles of treatment at the randomized dose, Investigators were permitted to adjust the dose/regimen on an individual basis to achieve an optimal balance of efficacy and safety. Treatment continued until a patient met a withdrawal criterion, had intolerable toxicity, progression of disease, or withdrew consent. Participants with Essential Thrombocythemia received 50 mg Ruxolitinib orally once a day (QD) for 56 days (two 28-day cycles) during the dose-ranging phase. After patients completed 2 cycles of treatment at the randomized dose, Investigators were permitted to adjust the dose/regimen on an individual basis to achieve an optimal balance of efficacy and safety. Treatment continued until a patient met a withdrawal criterion, had intolerable toxicity, progression of disease, or withdrew consent.
    Measure Participants 8 22 8
    Itching (pruritus)
    -2.7
    (2.89)
    -1.2
    (2.74)
    Night Sweats
    -5.0
    (NA)
    -1.3
    (2.49)
    -4.0
    (4.36)
    Weakness
    -1.0
    (1.00)
    -0.2
    (2.46)
    -1.7
    (2.52)
    Bone pain
    -3.5
    (2.12)
    -0.4
    (2.26)
    -2.3
    (4.93)
    Paresthesia
    -1.7
    (2.08)
    -1.6
    (1.50)
    -2.8
    (2.93)
    11. Secondary Outcome
    Title Change From Baseline to Week 4 in Health-related Quality of Life
    Description Health-related Quality of Life was assessed using the Global Health Status/Quality of Life Scale of the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). This scale ranges from 0 to 100, with higher scores indicating higher quality of life.
    Time Frame Baseline and Week 4 (Cycle 2, Day 1)

    Outcome Measure Data

    Analysis Population Description
    Intent to treat population. The intent-to-treat (ITT) population included all subjects who took at least 1 dose of study drug.
    Arm/Group Title PV: Ruxolitinib 10 mg BID PV: Ruxolitinib 25 mg BID PV: Ruxolitinib 50 mg QD ET: Ruxolitinib 10 mg BID ET: Ruxolitinib 25 mg BID ET: Ruxolitinib 50 mg QD
    Arm/Group Description Participants with Polycythemia Vera received 10 mg Ruxolitinib orally twice a day (BID) for 56 days (two 28-day cycles) during the dose-ranging phase. After patients completed 2 cycles of treatment at the randomized dose, Investigators were permitted to adjust the dose/regimen on an individual basis to achieve an optimal balance of efficacy and safety. Treatment continued until a patient met a withdrawal criterion, had intolerable toxicity, progression of disease, or withdrew consent. Participants with Polycythemia Vera received 25 mg Ruxolitinib orally twice a day (BID) for 56 days (two 28-day cycles) during the dose-ranging phase. After patients completed 2 cycles of treatment at the randomized dose, Investigators were permitted to adjust the dose/regimen on an individual basis to achieve an optimal balance of efficacy and safety. Treatment continued until a patient met a withdrawal criterion, had intolerable toxicity, progression of disease, or withdrew consent. Participants with Polycythemia Vera received 50 mg Ruxolitinib orally once a day (QD) for 56 days (two 28-day cycles) during the dose-ranging phase. After patients completed 2 cycles of treatment at the randomized dose, Investigators were permitted to adjust the dose/regimen on an individual basis to achieve an optimal balance of efficacy and safety. Treatment continued until a patient met a withdrawal criterion, had intolerable toxicity, progression of disease, or withdrew consent. Participants with Essential Thrombocythemia received 10 mg Ruxolitinib orally twice a day (BID) for 56 days (two 28-day cycles) during the dose-ranging phase. After patients completed 2 cycles of treatment at the randomized dose, Investigators were permitted to adjust the dose/regimen on an individual basis to achieve an optimal balance of efficacy and safety. Treatment continued until a patient met a withdrawal criterion, had intolerable toxicity, progression of disease, or withdrew consent. Participants with Essential Thrombocythemia received 25 mg Ruxolitinib orally twice a day (BID) for 56 days (two 28-day cycles) during the dose-ranging phase. After patients completed 2 cycles of treatment at the randomized dose, Investigators were permitted to adjust the dose/regimen on an individual basis to achieve an optimal balance of efficacy and safety. Treatment continued until a patient met a withdrawal criterion, had intolerable toxicity, progression of disease, or withdrew consent. Participants with Essential Thrombocythemia received 50 mg Ruxolitinib orally once a day (QD) for 56 days (two 28-day cycles) during the dose-ranging phase. After patients completed 2 cycles of treatment at the randomized dose, Investigators were permitted to adjust the dose/regimen on an individual basis to achieve an optimal balance of efficacy and safety. Treatment continued until a patient met a withdrawal criterion, had intolerable toxicity, progression of disease, or withdrew consent.
    Measure Participants 19 8 7 8 22 9
    Mean (Standard Deviation) [units on a scale]
    10.9
    (10.80)
    6.3
    (14.0)
    14.6
    (17.78)
    -2.1
    (10.5)
    3.0
    (27.6)
    11.2
    (23.4)

    Adverse Events

    Time Frame From start of study up to data cutoff at 20 June 2018; approximately 9 years.
    Adverse Event Reporting Description Safety evaluable PV and ET participants.The safety evaluable population included all enrolled participants who received at lease 1 dose of study drug.
    Arm/Group Title PV: Ruxolitinib 10 mg BID PV: Ruxolitinib 25 mg BID PV: Ruxolitinib 50 mg QD ET: Ruxolitinib 10 mg BID ET: Ruxolitinib 25 mg BID ET: Ruxolitinib 50 mg QD PV: Ruxolitinib All Doses Combined- Expansion Phase ET: Ruxolitinib All Doses Combined-expansion Phase
    Arm/Group Description Participants with Polycythemia Vera received 10 mg Ruxolitinib orally twice a day (BID) for 56 days (two 28-day cycles) during the dose-ranging phase. After patients completed 2 cycles of treatment at the randomized dose, Investigators were permitted to adjust the dose/regimen on an individual basis to achieve an optimal balance of efficacy and safety. Treatment continued until a patient met a withdrawal criterion, had intolerable toxicity, progression of disease, or withdrew consent. Participants with Polycythemia Vera received 25 mg Ruxolitinib orally twice a day (BID) for 56 days (two 28-day cycles) during the dose-ranging phase. After patients completed 2 cycles of treatment at the randomized dose, Investigators were permitted to adjust the dose/regimen on an individual basis to achieve an optimal balance of efficacy and safety. Treatment continued until a patient met a withdrawal criterion, had intolerable toxicity, progression of disease, or withdrew consent. Participants with Polycythemia Vera received 50 mg Ruxolitinib orally once a day (QD) for 56 days (two 28-day cycles) during the dose-ranging phase. After patients completed 2 cycles of treatment at the randomized dose, Investigators were permitted to adjust the dose/regimen on an individual basis to achieve an optimal balance of efficacy and safety. Treatment continued until a patient met a withdrawal criterion, had intolerable toxicity, progression of disease, or withdrew consent. Participants with Essential Thrombocythemia received 10 mg Ruxolitinib orally twice a day (BID) for 56 days (two 28-day cycles) during the dose-ranging phase. After patients completed 2 cycles of treatment at the randomized dose, Investigators were permitted to adjust the dose/regimen on an individual basis to achieve an optimal balance of efficacy and safety. Treatment continued until a patient met a withdrawal criterion, had intolerable toxicity, progression of disease, or withdrew consent. Participants with Essential Thrombocythemia received 25 mg Ruxolitinib orally twice a day (BID) for 56 days (two 28-day cycles) during the dose-ranging phase. After patients completed 2 cycles of treatment at the randomized dose, Investigators were permitted to adjust the dose/regimen on an individual basis to achieve an optimal balance of efficacy and safety. Treatment continued until a patient met a withdrawal criterion, had intolerable toxicity, progression of disease, or withdrew consent. Participants with Essential Thrombocythemia received 50 mg Ruxolitinib orally once a day (QD) for 56 days (two 28-day cycles) during the dose-ranging phase. After patients completed 2 cycles of treatment at the randomized dose, Investigators were permitted to adjust the dose/regimen on an individual basis to achieve an optimal balance of efficacy and safety. Treatment continued until a patient met a withdrawal criterion, had intolerable toxicity, progression of disease, or withdrew consent. After the completion of the dose-finding phase of the study, the starting dose of ruxolitinib for the expansion phase was determined to be 10 mg BID for subjects with PV. After subjects completed 8 weeks of ruxolitinib treatment at the starting dose, investigators were permitted to adjust the dose regimen to a maximum total daily dose of 75 mg on an individual basis, using their discretion, in order to achieve an optimal balance of efficacy and safety. After the completion of the dose-finding phase of the study, the starting dose of ruxolitinib for the expansion phase was determined to be 25 mg BID for subjects with ET. After subjects completed 8 weeks of ruxolitinib treatment at the starting dose, investigators were permitted to adjust the dose regimen to a maximum total daily dose of 75 mg on an individual basis, using their discretion, in order to achieve an optimal balance of efficacy and safety.
    All Cause Mortality
    PV: Ruxolitinib 10 mg BID PV: Ruxolitinib 25 mg BID PV: Ruxolitinib 50 mg QD ET: Ruxolitinib 10 mg BID ET: Ruxolitinib 25 mg BID ET: Ruxolitinib 50 mg QD PV: Ruxolitinib All Doses Combined- Expansion Phase ET: Ruxolitinib All Doses Combined-expansion Phase
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    PV: Ruxolitinib 10 mg BID PV: Ruxolitinib 25 mg BID PV: Ruxolitinib 50 mg QD ET: Ruxolitinib 10 mg BID ET: Ruxolitinib 25 mg BID ET: Ruxolitinib 50 mg QD PV: Ruxolitinib All Doses Combined- Expansion Phase ET: Ruxolitinib All Doses Combined-expansion Phase
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 2/19 (10.5%) 2/8 (25%) 1/7 (14.3%) 1/8 (12.5%) 1/22 (4.5%) 3/9 (33.3%) 17/34 (50%) 17/39 (43.6%)
    Blood and lymphatic system disorders
    Anaemia 1/19 (5.3%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 1/34 (2.9%) 0/39 (0%)
    Thrombocytopenia 1/19 (5.3%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 1/34 (2.9%) 0/39 (0%)
    Cardiac disorders
    Atrial flutter 1/19 (5.3%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 1/34 (2.9%) 0/39 (0%)
    Cardiac failure congestive 0/19 (0%) 0/8 (0%) 1/7 (14.3%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 1/34 (2.9%) 1/39 (2.6%)
    Atrial fibrillation 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 1/34 (2.9%) 0/39 (0%)
    Mitral valve incompetence 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 1/34 (2.9%) 0/39 (0%)
    Cardiac failure 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 1/39 (2.6%)
    Ventricular tachycardia 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 1/39 (2.6%)
    Gastrointestinal disorders
    Gastric varices haemorrhage 1/19 (5.3%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 1/34 (2.9%) 0/39 (0%)
    Gastrointestinal haemorrhage 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 1/9 (11.1%) 0/34 (0%) 1/39 (2.6%)
    Haematemesis 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 1/34 (2.9%) 0/39 (0%)
    Ileus 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 1/34 (2.9%) 0/39 (0%)
    Inguinal hernia 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 1/34 (2.9%) 0/39 (0%)
    Varices oesophageal 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 1/34 (2.9%) 1/39 (2.6%)
    Erosive oesophagitis 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 1/39 (2.6%)
    Gastric haemorrhage 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 1/39 (2.6%)
    Retroperitoneal haematoma 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 1/39 (2.6%)
    Small intestine ulcer 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 1/39 (2.6%)
    General disorders
    Non-cardiac chest pain 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 1/34 (2.9%) 0/39 (0%)
    Drug withdrawal syndrome 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 1/39 (2.6%)
    Multiple organ dysfunction syndrome 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 1/39 (2.6%)
    Oedema peripheral 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 1/39 (2.6%)
    Hepatobiliary disorders
    Cholecystitis 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 1/22 (4.5%) 0/9 (0%) 0/34 (0%) 1/39 (2.6%)
    Infections and infestations
    Pneumonia 0/19 (0%) 1/8 (12.5%) 1/7 (14.3%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 3/34 (8.8%) 2/39 (5.1%)
    Bronchitis 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 1/9 (11.1%) 0/34 (0%) 1/39 (2.6%)
    Abdominal abscess 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 1/34 (2.9%) 0/39 (0%)
    Gastroenteritis 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 1/34 (2.9%) 0/39 (0%)
    Postoperative wound infection 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 1/34 (2.9%) 0/39 (0%)
    Progressive multifocal leukoencephalopathy 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 1/34 (2.9%) 0/39 (0%)
    Urinary tract infection 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 1/34 (2.9%) 0/39 (0%)
    Erysipelas 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 1/39 (2.6%)
    Lung infection 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 1/39 (2.6%)
    Pneumococcal bacteraemia 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 1/39 (2.6%)
    Injury, poisoning and procedural complications
    Accidental overdose 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 1/34 (2.9%) 0/39 (0%)
    Road traffic accident 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 1/34 (2.9%) 0/39 (0%)
    Traumatic intracranial haemorrhage 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 1/34 (2.9%) 0/39 (0%)
    Upper limb fracture 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 1/39 (2.6%)
    Metabolism and nutrition disorders
    Hyperuricaemia 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 1/39 (2.6%)
    Musculoskeletal and connective tissue disorders
    Osteoarthritis 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 2/34 (5.9%) 1/39 (2.6%)
    Arthralgia 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 1/39 (2.6%)
    Osteitis deformans 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 1/39 (2.6%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Renal neoplasm 0/19 (0%) 1/8 (12.5%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 1/34 (2.9%) 0/39 (0%)
    Squamous cell carcinoma 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 1/34 (2.9%) 0/39 (0%)
    Squamous cell carcinoma of the oral cavity 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 1/34 (2.9%) 0/39 (0%)
    Squamous cell carcinoma of the tongue 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 1/34 (2.9%) 0/39 (0%)
    Tongue cancer recurrent 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 1/34 (2.9%) 0/39 (0%)
    Acute leukaemia 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 1/39 (2.6%)
    Basal cell carcinoma 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 1/39 (2.6%)
    Chronic myeloid leukaemia 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 1/39 (2.6%)
    Kaposi's sarcoma 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 1/39 (2.6%)
    Metastases to bone 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 1/39 (2.6%)
    Paget's disease of the vulva 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 1/39 (2.6%)
    Skin cancer 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 1/39 (2.6%)
    Nervous system disorders
    Headache 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 1/9 (11.1%) 0/34 (0%) 1/39 (2.6%)
    Ischaemic stroke 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 1/34 (2.9%) 0/39 (0%)
    Transient ischaemic attack 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 1/39 (2.6%)
    Cerebrovascular accident 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 1/39 (2.6%)
    Renal and urinary disorders
    Renal failure 0/19 (0%) 0/8 (0%) 0/7 (0%) 1/8 (12.5%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 1/39 (2.6%)
    Nephrolithiasis 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 1/39 (2.6%)
    Reproductive system and breast disorders
    Ovarian cyst 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 1/34 (2.9%) 0/39 (0%)
    Respiratory, thoracic and mediastinal disorders
    Pneumonitis 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 1/34 (2.9%) 0/39 (0%)
    Pulmonary embolism 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 2/34 (5.9%) 1/39 (2.6%)
    Dyspnoea 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 1/39 (2.6%)
    Vascular disorders
    Hypotension 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 1/39 (2.6%)
    Other (Not Including Serious) Adverse Events
    PV: Ruxolitinib 10 mg BID PV: Ruxolitinib 25 mg BID PV: Ruxolitinib 50 mg QD ET: Ruxolitinib 10 mg BID ET: Ruxolitinib 25 mg BID ET: Ruxolitinib 50 mg QD PV: Ruxolitinib All Doses Combined- Expansion Phase ET: Ruxolitinib All Doses Combined-expansion Phase
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 19/19 (100%) 8/8 (100%) 7/7 (100%) 8/8 (100%) 22/22 (100%) 8/9 (88.9%) 34/34 (100%) 39/39 (100%)
    Blood and lymphatic system disorders
    Anaemia 16/19 (84.2%) 6/8 (75%) 3/7 (42.9%) 5/8 (62.5%) 19/22 (86.4%) 6/9 (66.7%) 27/34 (79.4%) 32/39 (82.1%)
    Thrombocytopenia 6/19 (31.6%) 4/8 (50%) 1/7 (14.3%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 17/34 (50%) 0/39 (0%)
    Leukopenia 4/19 (21.1%) 1/8 (12.5%) 0/7 (0%) 0/8 (0%) 2/22 (9.1%) 0/9 (0%) 8/34 (23.5%) 2/39 (5.1%)
    Lymphadenitis 0/19 (0%) 0/8 (0%) 1/7 (14.3%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 0/39 (0%)
    Neutropenia 1/19 (5.3%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 2/34 (5.9%) 2/39 (5.1%)
    Increased tendency to bruise 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 2/39 (5.1%)
    Cardiac disorders
    Palpitations 2/19 (10.5%) 0/8 (0%) 1/7 (14.3%) 0/8 (0%) 4/22 (18.2%) 0/9 (0%) 4/34 (11.8%) 6/39 (15.4%)
    Arrhythmia supraventricular 1/19 (5.3%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 0/39 (0%)
    Atrial fibrillation 1/19 (5.3%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 3/34 (8.8%) 0/39 (0%)
    Supraventricular tachycardia 1/19 (5.3%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 0/39 (0%)
    Tachycardia 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 1/22 (4.5%) 1/9 (11.1%) 0/34 (0%) 3/39 (7.7%)
    Cardiac failure 0/19 (0%) 0/8 (0%) 0/7 (0%) 1/8 (12.5%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 0/39 (0%)
    Ear and labyrinth disorders
    Ear pain 0/19 (0%) 0/8 (0%) 1/7 (14.3%) 0/8 (0%) 0/22 (0%) 1/9 (11.1%) 2/34 (5.9%) 0/39 (0%)
    Tinnitus 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 2/34 (5.9%) 0/39 (0%)
    Vertigo 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 2/39 (5.1%)
    Endocrine disorders
    Goitre 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 2/39 (5.1%)
    thyroid mass 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 2/39 (5.1%)
    Eye disorders
    Conjunctivitis 1/19 (5.3%) 0/8 (0%) 1/7 (14.3%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 3/34 (8.8%) 0/39 (0%)
    Conjunctival haemorrhage 1/19 (5.3%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 2/34 (5.9%) 0/39 (0%)
    Eye pain 1/19 (5.3%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 0/39 (0%)
    Myodesopsia 1/19 (5.3%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 0/39 (0%)
    Photophobia 1/19 (5.3%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 0/39 (0%)
    Vision blurred 0/19 (0%) 1/8 (12.5%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 3/34 (8.8%) 0/39 (0%)
    Visual impairment 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 2/22 (9.1%) 0/9 (0%) 0/34 (0%) 0/39 (0%)
    Cataract 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 3/34 (8.8%) 2/39 (5.1%)
    Dry eye 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 2/34 (5.9%) 0/39 (0%)
    Vitreous floaters 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 2/34 (5.9%) 0/39 (0%)
    Photopsia 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 2/39 (5.1%)
    Gastrointestinal disorders
    Diarrhoea 4/19 (21.1%) 2/8 (25%) 1/7 (14.3%) 1/8 (12.5%) 4/22 (18.2%) 3/9 (33.3%) 12/34 (35.3%) 12/39 (30.8%)
    Vomiting 3/19 (15.8%) 1/8 (12.5%) 1/7 (14.3%) 0/8 (0%) 1/22 (4.5%) 3/9 (33.3%) 9/34 (26.5%) 7/39 (17.9%)
    Abdominal pain 2/19 (10.5%) 1/8 (12.5%) 1/7 (14.3%) 0/8 (0%) 2/22 (9.1%) 0/9 (0%) 6/34 (17.6%) 3/39 (7.7%)
    Constipation 0/19 (0%) 1/8 (12.5%) 1/7 (14.3%) 0/8 (0%) 4/22 (18.2%) 1/9 (11.1%) 4/34 (11.8%) 6/39 (15.4%)
    Abdominal pain upper 0/19 (0%) 1/8 (12.5%) 0/7 (0%) 1/8 (12.5%) 2/22 (9.1%) 0/9 (0%) 6/34 (17.6%) 5/39 (12.8%)
    Aphthous stomatitis 0/19 (0%) 1/8 (12.5%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 0/39 (0%)
    Dental discomfort 0/19 (0%) 0/8 (0%) 1/7 (14.3%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 0/39 (0%)
    Gastrointestinal disorder 1/19 (5.3%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 0/39 (0%)
    Gastrooesophageal reflux disease 1/19 (5.3%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 0/39 (0%)
    Nausea 0/19 (0%) 1/8 (12.5%) 0/7 (0%) 1/8 (12.5%) 2/22 (9.1%) 2/9 (22.2%) 4/34 (11.8%) 9/39 (23.1%)
    Toothache 0/19 (0%) 0/8 (0%) 1/7 (14.3%) 0/8 (0%) 0/22 (0%) 1/9 (11.1%) 4/34 (11.8%) 4/39 (10.3%)
    Abdominal pain lower 0/19 (0%) 0/8 (0%) 0/7 (0%) 1/8 (12.5%) 0/22 (0%) 1/9 (11.1%) 0/34 (0%) 2/39 (5.1%)
    Dyspepsia 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 2/22 (9.1%) 0/9 (0%) 3/34 (8.8%) 5/39 (12.8%)
    Diverticulum 0/19 (0%) 0/8 (0%) 0/7 (0%) 1/8 (12.5%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 0/39 (0%)
    Aphthous ulcer 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 2/34 (5.9%) 0/39 (0%)
    Gastrointestinal haemorrhage 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 2/34 (5.9%) 0/39 (0%)
    Abdominal distension 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 3/39 (7.7%)
    General disorders
    Pyrexia 4/19 (21.1%) 1/8 (12.5%) 1/7 (14.3%) 2/8 (25%) 4/22 (18.2%) 1/9 (11.1%) 13/34 (38.2%) 16/39 (41%)
    Asthenia 2/19 (10.5%) 2/8 (25%) 0/7 (0%) 0/8 (0%) 1/22 (4.5%) 1/9 (11.1%) 9/34 (26.5%) 7/39 (17.9%)
    Fatigue 1/19 (5.3%) 0/8 (0%) 1/7 (14.3%) 0/8 (0%) 2/22 (9.1%) 2/9 (22.2%) 5/34 (14.7%) 5/39 (12.8%)
    Oedema peripheral 1/19 (5.3%) 1/8 (12.5%) 0/7 (0%) 1/8 (12.5%) 0/22 (0%) 0/9 (0%) 4/34 (11.8%) 5/39 (12.8%)
    Chest pain 1/19 (5.3%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 2/34 (5.9%) 2/39 (5.1%)
    Mucosal inflammation 0/19 (0%) 0/8 (0%) 1/7 (14.3%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 0/39 (0%)
    Influenza like illness 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 4/34 (11.8%) 3/39 (7.7%)
    Non-cardiac chest pain 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 2/39 (5.1%)
    Peripheral swelling 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 3/39 (7.7%)
    Hepatobiliary disorders
    Hyperbilirubinaemia 0/19 (0%) 0/8 (0%) 2/7 (28.6%) 1/8 (12.5%) 0/22 (0%) 0/9 (0%) 2/34 (5.9%) 0/39 (0%)
    Infections and infestations
    Herpes zoster 2/19 (10.5%) 1/8 (12.5%) 1/7 (14.3%) 1/8 (12.5%) 1/22 (4.5%) 1/9 (11.1%) 8/34 (23.5%) 8/39 (20.5%)
    Upper respiratory tract infection 1/19 (5.3%) 1/8 (12.5%) 2/7 (28.6%) 0/8 (0%) 2/22 (9.1%) 0/9 (0%) 9/34 (26.5%) 4/39 (10.3%)
    Influenza 0/19 (0%) 2/8 (25%) 1/7 (14.3%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 8/34 (23.5%) 4/39 (10.3%)
    Cystitis 1/19 (5.3%) 1/8 (12.5%) 0/7 (0%) 1/8 (12.5%) 1/22 (4.5%) 1/9 (11.1%) 7/34 (20.6%) 6/39 (15.4%)
    Gastroenteritis 1/19 (5.3%) 0/8 (0%) 1/7 (14.3%) 0/8 (0%) 1/22 (4.5%) 1/9 (11.1%) 4/34 (11.8%) 4/39 (10.3%)
    Oral herpes 1/19 (5.3%) 0/8 (0%) 1/7 (14.3%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 5/34 (14.7%) 0/39 (0%)
    Pharyngitis 2/19 (10.5%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 3/34 (8.8%) 5/39 (12.8%)
    Bronchitis 0/19 (0%) 1/8 (12.5%) 0/7 (0%) 2/8 (25%) 1/22 (4.5%) 0/9 (0%) 9/34 (26.5%) 11/39 (28.2%)
    Ear infection 0/19 (0%) 0/8 (0%) 1/7 (14.3%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 3/34 (8.8%) 3/39 (7.7%)
    Epstein-Barr virus infection 1/19 (5.3%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 0/39 (0%)
    Respiratory tract infection 0/19 (0%) 1/8 (12.5%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 1/9 (11.1%) 0/34 (0%) 0/39 (0%)
    Rhinitis 0/19 (0%) 1/8 (12.5%) 0/7 (0%) 1/8 (12.5%) 0/22 (0%) 0/9 (0%) 2/34 (5.9%) 0/39 (0%)
    Sinusitis 1/19 (5.3%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 1/9 (11.1%) 2/34 (5.9%) 3/39 (7.7%)
    Tooth infection 1/19 (5.3%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 0/39 (0%)
    Vulvovaginal mycotic infection 1/19 (5.3%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 0/39 (0%)
    Tooth abscess 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 1/9 (11.1%) 3/34 (8.8%) 0/39 (0%)
    Folliculitis 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 2/34 (5.9%) 0/39 (0%)
    Nasopharyngitis 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 3/34 (8.8%) 2/39 (5.1%)
    Urinary tract infection 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 3/34 (8.8%) 4/39 (10.3%)
    Vulvovaginal candidiasis 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 2/34 (5.9%) 0/39 (0%)
    Onychomycosis 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 2/39 (5.1%)
    Pneumonia 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 3/39 (7.7%)
    Tracheitis 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 2/39 (5.1%)
    Injury, poisoning and procedural complications
    Foot fracture 0/19 (0%) 0/8 (0%) 1/7 (14.3%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 2/34 (5.9%) 0/39 (0%)
    Patella fracture 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 1/9 (11.1%) 0/34 (0%) 0/39 (0%)
    Fall 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 2/34 (5.9%) 6/39 (15.4%)
    Hand fracture 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 2/34 (5.9%) 0/39 (0%)
    Contusion 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 3/39 (7.7%)
    Limb injury 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 2/39 (5.1%)
    Investigations
    Weight increased 2/19 (10.5%) 1/8 (12.5%) 2/7 (28.6%) 2/8 (25%) 5/22 (22.7%) 3/9 (33.3%) 7/34 (20.6%) 14/39 (35.9%)
    Blood creatinine increased 1/19 (5.3%) 1/8 (12.5%) 1/7 (14.3%) 0/8 (0%) 0/22 (0%) 2/9 (22.2%) 3/34 (8.8%) 3/39 (7.7%)
    Alanine aminotransferase increased 1/19 (5.3%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 4/34 (11.8%) 3/39 (7.7%)
    Aspartate aminotransferase increased 1/19 (5.3%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 1/9 (11.1%) 4/34 (11.8%) 4/39 (10.3%)
    Gamma-glutamyltransferase increased 1/19 (5.3%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 6/34 (17.6%) 2/39 (5.1%)
    Transaminases increased 0/19 (0%) 1/8 (12.5%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 0/39 (0%)
    Blood creatine phosphokinase increased 0/19 (0%) 0/8 (0%) 0/7 (0%) 1/8 (12.5%) 1/22 (4.5%) 0/9 (0%) 4/34 (11.8%) 11/39 (28.2%)
    Haematocrit decreased 0/19 (0%) 0/8 (0%) 0/7 (0%) 1/8 (12.5%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 3/39 (7.7%)
    Blood glucose decreased 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 2/34 (5.9%) 0/39 (0%)
    Blood lactate dehydrogenase increased 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 2/34 (5.9%) 2/39 (5.1%)
    Cardiac murmur 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 2/39 (5.1%)
    Platelet count increased 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 2/39 (5.1%)
    Serum ferritin decreased 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 3/39 (7.7%)
    Metabolism and nutrition disorders
    Hyperuricaemia 2/19 (10.5%) 1/8 (12.5%) 0/7 (0%) 0/8 (0%) 3/22 (13.6%) 0/9 (0%) 6/34 (17.6%) 6/39 (15.4%)
    Hypertriglyceridaemia 1/19 (5.3%) 1/8 (12.5%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 8/34 (23.5%) 6/39 (15.4%)
    Diabetes mellitus 1/19 (5.3%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 3/34 (8.8%) 0/39 (0%)
    Hypoalbuminaemia 1/19 (5.3%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 0/39 (0%)
    Increased appetite 0/19 (0%) 0/8 (0%) 0/7 (0%) 1/8 (12.5%) 1/22 (4.5%) 0/9 (0%) 0/34 (0%) 2/39 (5.1%)
    Hypophosphataemia 0/19 (0%) 0/8 (0%) 0/7 (0%) 1/8 (12.5%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 2/39 (5.1%)
    Hypercholesterolaemia 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 6/34 (17.6%) 10/39 (25.6%)
    Hyperglycaemia 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 2/34 (5.9%) 0/39 (0%)
    Hypokalaemia 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 4/34 (11.8%) 0/39 (0%)
    Decreased appetite 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 3/39 (7.7%)
    Iron deficiency 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 2/39 (5.1%)
    Musculoskeletal and connective tissue disorders
    Back pain 3/19 (15.8%) 1/8 (12.5%) 1/7 (14.3%) 1/8 (12.5%) 1/22 (4.5%) 1/9 (11.1%) 11/34 (32.4%) 8/39 (20.5%)
    Arthralgia 2/19 (10.5%) 0/8 (0%) 1/7 (14.3%) 0/8 (0%) 1/22 (4.5%) 1/9 (11.1%) 8/34 (23.5%) 11/39 (28.2%)
    Neck pain 1/19 (5.3%) 1/8 (12.5%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 2/34 (5.9%) 2/39 (5.1%)
    Joint stiffness 1/19 (5.3%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 0/39 (0%)
    Muscle spasms 0/19 (0%) 1/8 (12.5%) 0/7 (0%) 1/8 (12.5%) 1/22 (4.5%) 1/9 (11.1%) 5/34 (14.7%) 4/39 (10.3%)
    Musculoskeletal pain 1/19 (5.3%) 0/8 (0%) 0/7 (0%) 1/8 (12.5%) 1/22 (4.5%) 1/9 (11.1%) 4/34 (11.8%) 4/39 (10.3%)
    Myalgia 0/19 (0%) 0/8 (0%) 1/7 (14.3%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 2/34 (5.9%) 7/39 (17.9%)
    Pain in extremity 0/19 (0%) 0/8 (0%) 0/7 (0%) 1/8 (12.5%) 4/22 (18.2%) 1/9 (11.1%) 6/34 (17.6%) 11/39 (28.2%)
    Bone pain 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 1/22 (4.5%) 1/9 (11.1%) 3/34 (8.8%) 3/39 (7.7%)
    Muscular weakness 0/19 (0%) 0/8 (0%) 0/7 (0%) 1/8 (12.5%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 2/39 (5.1%)
    Osteoarthritis 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 3/34 (8.8%) 3/39 (7.7%)
    Intervertebral disc protrusion 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 3/39 (7.7%)
    Osteoporosis 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 2/39 (5.1%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Basal cell carcinoma 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 4/39 (10.3%)
    Squamous cell carcinoma of skin 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 2/39 (5.1%)
    Uterine leiomyoma 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 2/39 (5.1%)
    Nervous system disorders
    Dizziness 2/19 (10.5%) 1/8 (12.5%) 1/7 (14.3%) 0/8 (0%) 3/22 (13.6%) 0/9 (0%) 6/34 (17.6%) 5/39 (12.8%)
    Headache 2/19 (10.5%) 0/8 (0%) 1/7 (14.3%) 0/8 (0%) 6/22 (27.3%) 2/9 (22.2%) 4/34 (11.8%) 10/39 (25.6%)
    Dysgeusia 1/19 (5.3%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 0/39 (0%)
    Neuropathy peripheral 1/19 (5.3%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 0/39 (0%)
    Perineurial cyst 1/19 (5.3%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 0/39 (0%)
    Peripheral sensory neuropathy 0/19 (0%) 1/8 (12.5%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 0/39 (0%)
    Post herpetic neuralgia 0/19 (0%) 1/8 (12.5%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 0/39 (0%)
    Restless legs syndrome 1/19 (5.3%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 0/39 (0%)
    Paraesthesia 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 1/9 (11.1%) 2/34 (5.9%) 2/39 (5.1%)
    Peripheral sensorimotor neuropathy 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 1/9 (11.1%) 0/34 (0%) 0/39 (0%)
    Memory impairment 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 2/34 (5.9%) 2/39 (5.1%)
    Trigeminal neuralgia 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 2/34 (5.9%) 0/39 (0%)
    Dysaesthesia 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 2/39 (5.1%)
    Hypoaesthesia 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 2/39 (5.1%)
    Presyncope 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 2/39 (5.1%)
    Tremor 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 2/39 (5.1%)
    Psychiatric disorders
    Insomnia 1/19 (5.3%) 0/8 (0%) 2/7 (28.6%) 0/8 (0%) 1/22 (4.5%) 1/9 (11.1%) 5/34 (14.7%) 4/39 (10.3%)
    Anxiety 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 4/39 (10.3%)
    Depression 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 3/39 (7.7%)
    Renal and urinary disorders
    Dysuria 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 2/34 (5.9%) 2/39 (5.1%)
    Nephrolithiasis 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 3/39 (7.7%)
    Reproductive system and breast disorders
    Benign prostatic hyperplasia 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 2/34 (5.9%) 0/39 (0%)
    Amenorrhoea 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 2/39 (5.1%)
    Menstruation irregular 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 2/39 (5.1%)
    Respiratory, thoracic and mediastinal disorders
    Cough 2/19 (10.5%) 1/8 (12.5%) 1/7 (14.3%) 0/8 (0%) 4/22 (18.2%) 1/9 (11.1%) 12/34 (35.3%) 12/39 (30.8%)
    Dyspnoea 2/19 (10.5%) 0/8 (0%) 1/7 (14.3%) 0/8 (0%) 1/22 (4.5%) 1/9 (11.1%) 4/34 (11.8%) 4/39 (10.3%)
    Oropharyngeal pain 0/19 (0%) 1/8 (12.5%) 2/7 (28.6%) 0/8 (0%) 1/22 (4.5%) 1/9 (11.1%) 3/34 (8.8%) 3/39 (7.7%)
    Dyspnoea exertional 0/19 (0%) 0/8 (0%) 1/7 (14.3%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 2/34 (5.9%) 2/39 (5.1%)
    Rhinorrhoea 0/19 (0%) 0/8 (0%) 1/7 (14.3%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 0/39 (0%)
    Sleep apnoea syndrome 0/19 (0%) 0/8 (0%) 1/7 (14.3%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 0/39 (0%)
    Epistaxis 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 3/39 (7.7%)
    Skin and subcutaneous tissue disorders
    Pruritus 2/19 (10.5%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 2/22 (9.1%) 0/9 (0%) 5/34 (14.7%) 4/39 (10.3%)
    Erythema nodosum 0/19 (0%) 1/8 (12.5%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 0/39 (0%)
    Mucocutaneous rash 1/19 (5.3%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 0/39 (0%)
    Rash pruritic 0/19 (0%) 1/8 (12.5%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 0/39 (0%)
    Skin lesion 0/19 (0%) 0/8 (0%) 1/7 (14.3%) 0/8 (0%) 1/22 (4.5%) 1/9 (11.1%) 6/34 (17.6%) 6/39 (15.4%)
    Urticaria 0/19 (0%) 0/8 (0%) 1/7 (14.3%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 0/39 (0%)
    Actinic keratosis 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 4/34 (11.8%) 2/39 (5.1%)
    Ecchymosis 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 2/34 (5.9%) 2/39 (5.1%)
    Night sweats 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 5/34 (14.7%) 2/39 (5.1%)
    Skin ulcer 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 2/34 (5.9%) 0/39 (0%)
    Hyperhidrosis 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 2/39 (5.1%)
    Rash 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 2/39 (5.1%)
    Surgical and medical procedures
    Cataract operation 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 2/34 (5.9%) 0/39 (0%)
    Tooth extraction 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 0/9 (0%) 0/34 (0%) 2/39 (5.1%)
    Vascular disorders
    Hypertension 1/19 (5.3%) 0/8 (0%) 0/7 (0%) 2/8 (25%) 0/22 (0%) 0/9 (0%) 5/34 (14.7%) 8/39 (20.5%)
    Hot flush 0/19 (0%) 0/8 (0%) 0/7 (0%) 1/8 (12.5%) 0/22 (0%) 1/9 (11.1%) 0/34 (0%) 2/39 (5.1%)
    Hypertensive crisis 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 1/9 (11.1%) 0/34 (0%) 0/39 (0%)
    Venous thrombosis limb 0/19 (0%) 0/8 (0%) 0/7 (0%) 0/8 (0%) 0/22 (0%) 1/9 (11.1%) 0/34 (0%) 0/39 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    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.

    Results Point of Contact

    Name/Title Study Director
    Organization Incyte Corporation
    Phone 1-855-463-3463
    Email medinfo@incyte.com
    Responsible Party:
    Incyte Corporation
    ClinicalTrials.gov Identifier:
    NCT00726232
    Other Study ID Numbers:
    • INCB 18424-256
    • Ruxolitinib
    First Posted:
    Jul 31, 2008
    Last Update Posted:
    Oct 28, 2019
    Last Verified:
    Oct 1, 2019