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A Study to Evaluate the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of Idasanutlin Monotherapy in Participants With Hydroxyurea-Resistant/Intolerant Polycythemia Vera

Sponsor
Hoffmann-La Roche (Industry)
Overall Status
Terminated
CT.gov ID
NCT03287245
Collaborator
(none)
27
Enrollment
11
Locations
1
Arm
24.3
Actual Duration (Months)
2.5
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is an open-label, single-arm study of idasanutlin monotherapy in participants with hydroxyurea (HU)-resistant/intolerant Polycythemia vera (PV). The study will include two phases: initial phase and expansion phase. The initial phase will assess the safety and efficacy of idasanutlin monotherapy in ruxolitinib naïve and ruxolitinib-resistant or intolerant patients, respectively. If the initial phase shows promising results for ruxolitinib-resistant or intolerant patients, an expansion phase will be opened to further characterize the efficacy of idasanutlin.

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
27 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase II, Single-Arm, Open-Label Study to Evaluate the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of Idasanutlin Monotherapy in Patients With Hydroxyurea-Resistant/Intolerant Polycythemia Vera
Actual Study Start Date :
Feb 21, 2018
Actual Primary Completion Date :
Mar 3, 2020
Actual Study Completion Date :
Mar 3, 2020

Arms and Interventions

Arm Intervention/Treatment
Experimental: Idasanutlin

Two cohorts of ruxolitinib-naïve and ruxolitinib-resitant or intolerant participants will be enrolled to receive idasanutlin once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years).

Drug: Idasanutlin
All participants will receive 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years). Intra-participant dose-escalation to 200 mg daily for 5 days may be permitted after Cycle 3 for those who demonstrate no hematocrit (Hct) control and/or for those with inadequately controlled leukocytosis and/or thrombocytosis in which the investigator judges that better control is important.
Other Names:
  • RO5503781
  • RG7388

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    Outcome Measures

    Primary Outcome Measures

    1. Percentage of Ruxolitinib-Naïve Participants With Splenomegaly at Baseline Who Achieved Composite Response at Week 32 [Week 32]

      Composite response is defined as hematocrit (Hct) control without phlebotomy and ≥35% decrease in spleen size by imaging at Week 32. Hct control is defined as protocol-specified ineligibility for phlebotomy between Weeks 8 to 32 and ≤1 instance of phlebotomy eligibility between first dose and Week 8. Eligibility for phlebotomy is defined as a Hct of ≥45% that was ≥3% higher than baseline level or a Hct of >48%. One Cycle is 28 Days.

    2. Percentage of Ruxolitinib-Naïve Participants Without Splenomegaly at Baseline Who Achieved Hematocrit (Hct) Control Without Phlebotomy at Week 32 [Week 32]

      Hct control is defined as protocol-specified ineligibility for phlebotomy between Weeks 8 to 32 and ≤1 instance of phlebotomy eligibility between first dose and Week 8. Eligibility for phlebotomy is defined as a Hct level ≥45% that was ≥3% higher than baseline level or a Hct level of >48%.

    3. Percentage of All Ruxolitinib-Naïve Participants (Irrespective of Spleen Size) Who Achieved Hct Control Without Phlebotomy at Week 32 [Week 32]

      Hct control is defined as protocol-specified ineligibility for phlebotomy between Weeks 8 to 32 and ≤1 instance of phlebotomy eligibility between first dose and Week 8. Eligibility for phlebotomy is defined as a Hct level ≥45% that was ≥3% higher than baseline level or a Hct level of >48%.

    4. Percentage of All Ruxolitinib-Resistant or Intolerant Participants Who Achieved Hct Control Without Phlebotomy at Week 32 [From Baseline to Week 32 (Cycle 8 Day 28)]

      Hct control is defined as protocol-specified ineligibility for phlebotomy between Weeks 8 to 32 and ≤1 instance of phlebotomy eligibility between first dose and Week 8. Eligibility for phlebotomy is defined as a Hct level ≥45% that was ≥3% higher than baseline level or a Hct level of >48%.

    Secondary Outcome Measures

    1. Percentage of All Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Participants Who Achieved Complete Hematologic Response at Week 32 [Week 32 (Cycle 8 Day 28)]

      Complete hematologic response requires all of the following: Hct control without phlebotomy; White blood cell (WBC) count ≤10 × 10^9/Liter (L) at Week 32; and Platelet count ≤400 × 10^9/L at Week 32. Hct control is defined as protocol-specified ineligibility for phlebotomy between Weeks 8 to 32 and ≤1 instance of phlebotomy eligibility between first dose and Week 8. Eligibility for phlebotomy is defined as a Hct level ≥45% that was ≥3% higher than baseline level or a Hct level of >48%.

    2. Percentage of All Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Participants Who Achieved Complete Hematologic Remission at Cycle 11 Day 28 [Cycle 11 Day 28]

      Complete hematologic remission requires all of the following: Hct control without phlebotomy between Weeks 32 and Cycle 11 Day 28; WBC count ≤10 × 10^9/L at Cycle 11 Day 28; and Platelet count ≤400 × 10^9/L at Week 32. Hct control is defined as protocol-specified ineligibility for phlebotomy. Eligibility for phlebotomy is defined as a Hct level ≥45% that was ≥3% higher than baseline level or a Hct level of >48%.

    3. Duration of Complete Hematologic Remission, With a Durable Responder Defined as a Participant in Remission at Week 32 and Cycle 11 Day 28 [Week 32 (Cycle 8 Day 28), Cycle 11 Day 28]

      Complete hematologic remission requires all of the following: Hct control without phlebotomy between Week 32 (Cycle 8 Day 28) and Cycle 11 Day 28; WBC count ≤10 × 10^9/L at Cycle 11 Day 28; and Platelet count ≤400 × 10^9/L at Week 32. Hct control is defined as protocol-specified ineligibility for phlebotomy. Eligibility for phlebotomy is defined as a Hct level ≥45% that was ≥3% higher than baseline level or a Hct level of >48%

    4. Percentage of Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Participants With Splenomegaly at Baseline by Response Per Modified European Leukemia Net (ELN) Criteria [Baseline, Day 28 of Cycles 3, 5, 8, 11, 12, 14, 17, 20 and Final visit (28 days after post-last dose)]

      Complete response (CR) includes all of the following: Hct <45% without phlebotomy; Platelet count ≤400 × 10^9/L; WBC count ≤10 × 10^9/L; Normal spleen size on imaging; and No disease-related symptoms. Partial response (PR): in participants who do not fulfill the criteria for CR: Hct <45% without phlebotomy or response in 3 or more of the other criteria. No response (NR): any response that does not satisfy partial response. Progressive disease (PD): increased bone marrow fibrosis from baseline, and/or transformation to myelofibrosis (MF), myelodysplastic syndrome (MDS) or acute leukemia. All responders of each category grouped per timepoint include all categories mentioned above. There were no PD responses at any timepoint. The study was pre-maturely terminated by the sponsor's decision due to non-transformative efficacy and poor long-term tolerability of the dosing schedule as well as due to chronic gastrointestinal toxicity, therefore did not reach the end of study.

    5. Percentage of Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Participants Without Splenomegaly at Baseline by Response Per Modified ELN Criteria [Baseline, Day 28 of Cycles 3, 5, 8, 11, 12, 14, 17, 20 and Final visit (28 days after post-last dose)]

      Complete response (CR) includes all of the following: Hct <45% without phlebotomy; Platelet count ≤400 × 10^9/L; WBC count ≤10 × 10^9/L; Normal spleen size on imaging; and No disease-related symptoms. Partial response (PR): in participants who do not fulfill the criteria for CR: Hct <45% without phlebotomy or response in 3 or more of the other criteria. No response (NR): any response that does not satisfy partial response. Progressive disease (PD): increased bone marrow fibrosis from baseline, and/or transformation to myelofibrosis (MF), myelodysplastic syndrome (MDS) or acute leukemia. All responders of each category grouped per timepoint include all categories mentioned above. There were no PD responses at any timepoint. The study was pre-maturely terminated by the sponsor's decision due to non-transformative efficacy and poor long-term tolerability of the dosing schedule as well as due to chronic gastrointestinal toxicity, therefore did not reach the end of study.

    6. Percentage of All Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Participants (Irrespective of Spleen Size) by Response Per Modified ELN Criteria [Baseline, Day 28 of Cycles 3, 5, 8, 11, 12, 14, 17, 20 and Final visit (28 days after post-last dose)]

      Complete response (CR) includes all of the following: Hct <45% without phlebotomy; Platelet count ≤400 × 10^9/L; WBC count ≤10 × 10^9/L; Normal spleen size on imaging; and No disease-related symptoms. Partial response (PR): in participants who do not fulfill the criteria for CR: Hct <45% without phlebotomy or response in 3 or more of the other criteria. No response (NR): any response that does not satisfy partial response. Progressive disease (PD): increased bone marrow fibrosis from baseline, and/or transformation to myelofibrosis (MF), myelodysplastic syndrome (MDS) or acute leukemia. All responders of each category grouped per timepoint include all categories mentioned above. There were no PD responses at any timepoint. The study was pre-maturely terminated by the sponsor's decision due to non-transformative efficacy and poor long-term tolerability of the dosing schedule as well as due to chronic gastrointestinal toxicity, therefore did not reach the end of study.

    7. Percentage of Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Participants With Splenomegaly at Baseline With Durable Response Lasting at Least 12 Weeks From Week 32 [From Week 32 (Cycle 8 Day 28) and at least 12 Weeks after until end of study (up to 2 years)]

      The percentage of participants with a durable response lasting at least 12 weeks from Week 32 are analyzed by the type of response achieved: Hct control, complete hematologic response, ELN 2009 response criteria, and composite response, if applicable. Reported result data start from Cycle 11 Day 28 which is 12 weeks after Week 32 (Cycle 8 Day 28). There was one timepoint for which the participants qualify. The study was pre-maturely terminated by the sponsor decision, therefore did not reach the end of study.

    8. Number of Participants With a Durable Response, in Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Participants With Splenomegaly at Baseline With Durable Response Lasting at Least 12 Weeks From Week 32 [From Week 32 (Cycle 8 Day 28) and at least 12 weeks after until end of study (up to 2 years)]

      The number of participants with a durable response lasting at least 12 weeks from Week 32 is analyzed by the type of response achieved: Hct control, complete hematologic response, ELN 2009 response criteria, and composite response, if applicable. Reported result data start from Cycle 11 Day 28 which is 12 weeks after Week 32 (Cycle 8 Day 28). There was one timepoint for which the participants qualify. The study was pre-maturely terminated by the sponsor's decision due to non-transformative efficacy and poor long-term tolerability of the dosing schedule as well as due to chronic gastrointestinal toxicity, therefore did not reach the planned end of study.

    9. Percentage of Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Participants Without Splenomegaly at Baseline With Durable Response Lasting at Least 12 Weeks From Week 32 [From Week 32 (Cycle 8 Day 28) and at least 12 Weeks after until end of study (up to 2 years)]

      The percentage of participants with a durable response lasting at least 12 weeks from Week 32 is analyzed by the type of response achieved: Hct control, complete hematologic response, ELN 2009 response criteria, and composite response, if applicable. Reported result data start from Cycle 11 Day 28 which is 12 weeks after Week 32 (Cycle 8 Day 28). There was one timepoint for which the participants qualify. The study was pre-maturely terminated by the sponsor decision, therefore did not reach the end of study.

    10. Number of Participants With a Durable Response, in Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Participants Without Splenomegaly at Baseline With Durable Response Lasting at Least 12 Weeks From Week 32 [From Week 32 (Cycle 8 Day 28) and at least 12 weeks after until end of study (up to 2 years)]

      The number of participants with a durable response lasting at least 12 weeks from Week 32 is analyzed by the type of response achieved: Hct control, complete hematologic response, ELN 2009 response criteria, and composite response, if applicable. Reported result data start from Cycle 11 Day 28 which is 12 weeks after Week 32 (Cycle 8 Day 28). There was one timepoint for which the participants qualify. The study was pre-maturely terminated by the sponsor's decision due to non-transformative efficacy and poor long-term tolerability of the dosing schedule as well as due to chronic gastrointestinal toxicity, therefore did not reach the planned end of study.

    11. Percentage of All Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Participants (Irrespective of Spleen Size) With Durable Response Lasting at Least 12 Weeks From Week 32 [From Week 32 (Cycle 8 Day 28) and at least 12 Weeks after until end of study (up to 2 years)]

      The percentage of participants with a durable response lasting at least 12 weeks from Week 32 is analyzed by the type of response achieved: Hct control, complete hematologic response, ELN 2009 response criteria, and composite response, if applicable. Reported result data start from Cycle 11 Day 28 which is 12 weeks after Week 32 (Cycle 8 Day 28). There was one timepoint for which the participants qualify. The study was pre-maturely terminated by the sponsor decision, therefore did not reach the end of study.

    12. Number of Participants With a Duration Response, in All Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Participants (Irrespective of Spleen Size) With Durable Response Lasting at Least 12 Weeks From Week 32 [From Week 32 (Cycle 8 Day 28) and at least 12 weeks after until end of study (up to 2 years)]

      The number of participants with a durable response lasting at least 12 weeks from Week 32 is analyzed by the type of response achieved: Hct control, complete hematologic response, ELN 2009 response criteria, and composite response, if applicable. Reported result data start from Cycle 11 Day 28 which is 12 weeks after Week 32 (Cycle 8 Day 28). There was one timepoint for which the participants qualify. The study was pre-maturely terminated by the sponsor's decision due to non-transformative efficacy and poor long-term tolerability of the dosing schedule as well as due to chronic gastrointestinal toxicity, therefore did not reach the planned end of study.

    13. Total Number of Participants With Adverse Events by Severity, Graded According to NCI CTCAE v4.0 [Baseline to end of study (up to 2 years)]

      An adverse event is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study drug, whether or not considered related to the study drug. The adverse event severity grading scale for the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (NCI CTCAE v4.0) will be used for assessing adverse event severity. During the final analyses, the focus was on the Adverse Events of severity grades >/=3 as shown below. The extensive listings of all grade AEs are available at request. The study was pre-maturely terminated by the sponsor's decision due to non-transformative efficacy and poor long-term tolerability of the dosing schedule as well as due to chronic gastrointestinal toxicity, therefore did not reach the planned end of study.

    14. Percentage of Participants With Clinical Laboratory Abnormalities: Hematology Parameters. [Baseline to end of study (up to 2 years)]

      Hematology parameter laboratory values falling outside the standard reference range were planned to be recorded as either high or low. There was no clinical laboratory abnormalities identified. The study was pre-maturely terminated by the sponsor's decision, therefore did not reach the end of study.

    15. Percentage of Participants With Clinical Laboratory Abnormalities: Clinical Chemistry Parameters [Baseline to end of study (up to 2 years)]

      Clinical chemistry parameter laboratory values falling outside the standard reference range were to be recorded as either high or low. There was no clinical chemistry abnormalities identified. The study was pre-maturely terminated by the sponsor's decision, therefore did not reach the end of study.

    16. Percentage of Participants With Clinical Laboratory Abnormalities: Urinalysis Parameters [Baseline to end of study (up to 2 years)]

      Urinalysis parameter laboratory values falling outside the standard reference range were planned to be recorded as either high or low. There was no clinical laboratory (urinalysis) abnormalities identified. The study was pre-maturely terminated by the sponsor's decision, therefore did not reach the end of study.

    17. Change From Baseline in Electrocardiogram Parameters: PQ(PR), QRS, QT, QTcB, QTcF, and RR Durations [Baseline, Cycle 1 (Day 1, hours 4 and 6, Day 2 pre-dose and 24 Hour, Day 5 pre-dose, 4 and 6 Hour), Cycle 2 (Day 1 pre-dose only), Cycle 3 (Day 1 pre-dose, 4 and 6 Hour), Cycle 4 (Day 1 pre-dose and 4 Hour)]

      Single 12-lead ECGs was obtained using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTc intervals. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The study was pre-maturely terminated by the sponsor's decision due to non-transformative efficacy and poor long-term tolerability of the dosing schedule as well as due to chronic gastrointestinal toxicity, therefore did not reach the planned end of study.

    18. Change From Baseline in Heart Rate, as Measured by Electrocardiogram [Baseline, Cycle 1 (Day 1, hours 4 and 6, Day 2 pre-dose and 24 Hour, Day 5 pre-dose, 4 and 6 Hour), Cycle 2 (Day 1 pre-dose only), Cycle 3 (Day 1 pre-dose, 4 and 6 Hour), Cycle 4 (Day 1 pre-dose and 4 Hour)]

      Single 12-lead ECGs was obtained using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTc intervals. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The study was pre-maturely terminated by the sponsor's decision due to non-transformative efficacy and poor long-term tolerability of the dosing schedule as well as due to chronic gastrointestinal toxicity, therefore did not reach the planned end of study.

    19. Change From Baseline in Oral Temperature [Baseline, Cycle 1 (Days 15 and 22), Cycle 2 and 3 (Days 1 and 15), Each Cycle 4-23 (Day 1 only) and Final Visit]

      Vital signs were measured prior to the infusion while the participant was in a seated position. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The study was pre-maturely terminated by the sponsor's decision, therefore did not reach the end of study.

    20. Change From Baseline in Pulse Rate [Baseline, Cycle 1 (Days 15 and 22), Cycle 2 and 3 (Days 1 and 15), Each Cycle 4-23 (Day 1 only) and Final Visit]

      Vital signs were measured prior to the infusion while the participant was in a seated position. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The study was pre-maturely terminated by the sponsor's decision due to non-transformative efficacy and poor long-term tolerability of the dosing schedule as well as due to chronic gastrointestinal toxicity, therefore did not reach the planned end of study.

    21. Change From Baseline in Respiratory Rate [Baseline, Cycle 1 (Days 15 and 22), Cycle 2 and 3 (Days 1 and 15), Each Cycle 4-23 (Day 1 only) and Final Visit]

      Vital signs were measured prior to the infusion while the participant was in a seated position. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The study was pre-maturely terminated by the sponsor's decision due to non-transformative efficacy and poor long-term tolerability of the dosing schedule as well as due to chronic gastrointestinal toxicity, therefore did not reach the planned end of study.

    22. Change From Baseline in Systolic Blood Pressure [Baseline, Cycle 1 (Days 15 and 22), Cycle 2 and 3 (Days 1 and 15), Each Cycle 4-23 (Day 1 only) and Final Visit]

      Vital signs were measured prior to the infusion while the participant was in a seated position. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The study was pre-maturely terminated by the sponsor's decision due to non-transformative efficacy and poor long-term tolerability of the dosing schedule as well as due to chronic gastrointestinal toxicity, therefore did not reach the planned end of study.

    23. Change From Baseline in Diastolic Blood Pressure [Baseline, Cycle 1 (Days 15 and 22), Cycle 2 and 3 (Days 1 and 15), Each Cycle 4-23 (Day 1 only) and Final Visit]

      Vital signs were measured prior to the infusion while the participant was in a seated position. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The study was pre-maturely terminated by the sponsor's decision due to non-transformative efficacy and poor long-term tolerability of the dosing schedule as well as due to chronic gastrointestinal toxicity, therefore did not reach the planned end of study.

    24. Eastern Cooperative Oncology Group (ECOG) Performance Status Over Time [Baseline]

      The ECOG performance status is a scale used to quantify cancer patients' general well-being and activities of daily life. The scale ranges from 0 to 5, with 0 denoting perfect health and 5 indicating death. The 6 categories are 0=Asymptomatic (Fully active, able to carry on all pre-disease activities without restriction), 1=Symptomatic but completely ambulatory, 2=Symptomatic, < 50% in bed during the day (Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours), 3=Symptomatic, > 50% in bed, but not bedbound (Capable of only limited self-care, confined to bed or chair 50% or more of waking hours), 4=Bedbound (Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair), 5=Death. Only baseline data were collectable. The study was pre-maturely terminated by the sponsor's decision, therefore did not reach the planned end of study.

    25. Percentage of Participants With Concomitant Medications [Overall Study Period]

      Participants with Concomitant Medications used from 28 days prior to screening until the final visit or end of study (EOS) were reported. The result data not derived due to early termination of the study by the sponsor's decision and did not reach the end of study.

    26. Maximum Serum Concentration Observed (Cmax) of Idasanutlin [Days 1, 2, and 5 of Cycles 1 and 4]

      Cmax is the maximum observed concentration of drug in blood. The result data not derived due to early termination of the study by the sponsor's decision and did not reach the end of study.

    27. Trough Concentration (Ctrough) of Idasanutlin [Days 1, 2, and 5 of Cycles 1 and 4]

      Ctrough is the measured concentration of a drug at the end of a dosing interval at steady state. The result data not derived due to early termination of the study by the sponsor's decision and did not reach the end of study.

    28. Time of Maximum Concentration Observed (Tmax) of Idasanutlin [Days 1, 2, and 5 of Cycles 1 and 4]

      Tmax is the time elapsed from the time of drug administration to maximum plasma concentration. The result data not derived due to early termination of the study by the sponsor's decision and did not reach the end of study.

    29. Clearance (CL) of Idasanutlin [Days 1, 2, and 5 of Cycles 1 and 4]

      CL is a measure of the body's elimination of a drug from plasma over time. The result data not derived due to early termination of the study by the sponsor's decision and did not reach the end of study.

    30. Apparent Clearance (CL/F) of Idasanutlin [Days 1, 2, and 5 of Cycles 1 and 4]

      CL/F is a measure of the body's elimination of a drug from plasma over time, after oral administration. The result data not derived due to early termination of the study by the sponsor's decision and did not reach the end of study.

    31. Volume or Apparent Volume of Distribution (Vdss/F) of Idasanutlin [Days 1, 2, and 5 of Cycles 1 and 4]

      Vdss/F is the theoretical volume that would be necessary to contain the total amount of an administered drug at the same concentration that it is observed in the plasma. The result data not derived due to early termination of the study by the sponsor's decision and did not reach the end of study.

    32. Area Under the Concentration-Time Curve (AUC) of Idasanutlin [Days 1, 2, and 5 of Cycles 1 and 4]

      AUC (from zero to infinity) represents the total drug exposure over time. The result data not derived due to early termination of the study by the sponsor's decision and did not reach the end of study.

    33. Half-life (t1/2) of Idasanutlin [Days 1, 2, and 5 of Cycles 1 and 4]

      t1/2 is defined as the time required for the drug plasma concentration to be reduced to half. The result data not derived due to early termination of the study by the sponsor's decision and did not reach the end of study.

    34. Baseline and Mean Change From Baseline Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS) Over Time [Baseline (Cycle 1 Day 1), Cycle 2 Day 1, Days 28 of Cycles 3, 5, 8 (Week 32), 11, 14, 17 ) Day 28, Cycle 5 Day 28, End of Cycle 8 (Week 32), and Final Visit]

      MPN-SAF Total Symptom Score is the sum of the following 10 items: early satiety, abdominal discomfort, inactivity, concentration issues, night sweats, Itching, Bone pain, Fever and Unintentional weight loss last 6 months and fatigue. The participant provides a severity score for each symptom on a scale of 0 as a minimum score (none/absent) to 10 (worst imaginable) as a maximum score. Baseline (Cycle 1, Day 1) MPN-SAF total symptom score and the mean change from baseline score at each timepoint are reported. The change from baseline score was calculated by subtracting the post-baseline score from the baseline score. The study was pre-maturely terminated by the sponsor's decision due to non-transformative efficacy and poor long-term tolerability of the dosing schedule as well as due to chronic gastrointestinal toxicity, therefore did not reach the end of study.

    35. Baseline and Mean Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores Over Time [Baseline (Cycle 1 Day 1), Cycle 2 Day 1, Cycles 3, 5, 8, 11, 14, 17, 20 Day 28 and Final Visit]

      Reported EORTC QLQ-C30 Scores include: Cognitive function, Diarrhea Emotional functioning, Nausea and vomiting, Social functioning, Physical functioning, Global health status/QoL and Role functioning. The questions use a 4-point scale (1 'Not at all' to 4 'Very much'; 2 questions used 7-point scale [1 'very poor' to 7 'Excellent']). Scores are averaged and transformed to 0-100 scale; higher score=better level of functioning or greater degree of symptoms. The study was pre-maturely terminated by the sponsor's decision due to non-transformative efficacy and poor long-term tolerability of the dosing schedule as well as due to chronic gastrointestinal toxicity, therefore did not reach the end of study.

    36. Frequency Count of Participant Responses to the Patient Global Impression of Change (PGIC) Question Over Time [Cycle 2 Day 1, Cycle 3 Day 28, Cycle 5 Day 28, End of Cycle 8 (Week 32), and every 3 cycles thereafter (1 cycle is 28 days) until end of study (up to 2 years)]

      The PGIC is a one-item measure used to assess perceived treatment benefit. Participants were asked "Since the start of the treatment you've received in this study, your polycythemia vera (PV) symptoms are: 'very much improved', 'much improved', 'minimally improved', 'no change', 'minimally worse', 'much worse', and 'very much worse'. The study was pre-maturely terminated by the sponsor's decision, therefore did not reach the end of study.

    Eligibility Criteria

    Criteria

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

    • Documentation that the participant has met the revised 2016 World Health Organization (WHO) criteria for the diagnosis of polycythemia vera (PV)

    • Hematocrit at screening and at initiation of idasanutlin greater than (>)40%

    • Phlebotomy-dependent participants with splenomegaly by magnetic resonance imaging (MRI) or computerized tomography (CT) imaging (greater than or equal to [≥]450 cubic centimeters [cm3]) or without splenomegaly (less than [<]450 cm3 or prior splenectomy)

    • Resistance to/intolerance to hydroxyurea according to modified European Leukemia Net (ELN) criteria

    • For participants in the ruxolitinib intolerant or resistant group, in addition to previous hydroxyurea intolerance/resistance: Therapy-resistant PV after at least 6 months of treatment with ruxolitinib, as defined in the protocol; Ruxolitinib intolerance, as defined in the protocol; and Documentation of adverse events likely caused by ruxolitinib (assessment of attending physician) and that are of a severity that preclude further treatment with ruxolitinib (as per judgment of the attending physician and the patient)

    • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1

    • Participants must be willing to submit the blood sampling and bone marrow sampling for the pharmacokinetic (PK) and pharmacodynamic analyses and exploratory biomarkers

    • Adequate hepatic and renal function

    • Ability and willingness to comply with the study protocol procedures, including clinical outcome assessment measures

    • For women of childbearing potential: agreement to use contraceptive methods that result in a failure rate of less than (<)1% per year during the treatment period and for at least 6 weeks after the last dose of idasanutlin

    • For men: Agreement to use contraceptive measures, and agreement to refrain from donating sperm during the treatment period and for at least 90 days after the last dose of idasanutlin

    Exclusion Criteria:

    • Meets the criteria for post-PV myelofibrosis as defined by the International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT)

    • Blast phase disease (>20% blasts in the marrow or peripheral blood)

    • Clinically-significant thrombosis within 3 months of screening

    • Participants who must receive CYP2C8 inhibitors, substrates and inducers, strong CYP3A4 inducers, or OATP1B1/3 substrates while on study. These must be discontinued 7 days (inhibitors and substrates) or 14 days (inducers) prior to start of study medication

    • Previously treated with murine double minute 2 (MDM2) antagonist therapies or receiving interferon-alpha, anagrelide, or ruxolitinib within 28 days or 5 half-lives (whichever is shorter), or hydroxyurea within 1 day, or receiving any other cytoreductive or investigational agents within 28 days or 5 half-lives (whichever is shorter) of initial dose. Aspirin is permitted per treatment guidelines for PV unless medically contraindicated

    • Patients with evidence of electrolyte imbalance such as hypokalemia, hyperkalemia, hypocalcemia, hypercalcemia, hypomagnesemia, and hypermagnesemia of Grade >1 intensity, as per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.0, prior to dosing on Cycle 1 Day 1. Treatment for correction of electrolyte imbalances is permitted to meet eligibility

    • Neutrophil count <1.5 × 10^9/Liter (L) prior to dosing on Cycle 1 Day 1

    • Platelet count less than or equal to (≤)150 × 10^9/L prior to dosing on Cycle 1 Day 1

    • Women who are pregnant or breastfeeding

    • Ongoing serious non-healing wound, ulcer, or bone fracture

    • History of major organ transplant

    • Uncontrolled intercurrent illness including, but not limited to hepatitis, concurrent malignancy that could affect compliance with the protocol or interpretation of results, hepatitis A, B, and C, human immunodeficiency virus (HIV)-positive, ongoing or active infection, clinically significant cardiac disease (New York Heart Association Class III or IV), symptomatic congestive heart failure, unstable angina pectoris, ventricular arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. Concurrent malignancy exceptions include: Curatively treated carcinoma in situ of the cervix, good-prognosis ductal carcinoma in situ of the breast, basal- or squamous-cell skin cancer, Stage I melanoma, or low-grade, early-stage localized prostate cancer. Any previously treated early-stage non-hematological malignancy that has been in remission for at least 2 years is also permitted.

    • Patients with active gastrointestinal conditions (Crohn's disease, ulcerative colitis, diverticulosis associated colitis, and Behçet's disease)

    • Clinically significant toxicity (other than alopecia) from prior therapy that has not resolved to Grade ≤1 (according to the NCI CTCAE, v4.0) prior to Cycle 1 Day 1

    • Cardiovascular disease, such as: uncontrolled arterial hypertension; symptomatic congestive heart failure or ejection fraction below 55% at screening, or left ventricular hypertrophy; any significant structural abnormality of the heart at screening echocardiogram; unstable angina pectoris; presence or history of any type of supraventricular and ventricular arrhythmias, including lone atrial fibrillation or flutter

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Mayo Clinic - Arizona Phoenix Arizona United States 85054
    2 University of Kansas Cancer Center; Westwood Cancer Center/BMT Output Clinic Kansas City Kansas United States 66205
    3 Icahn School of Medicine at Mount Sinai New York New York United States 10029
    4 Cleveland Clinic Cancer Center Independence Ohio United States 44131
    5 University of Texas Health Sciences Center in San Antonio San Antonio Texas United States 78229
    6 Royal Adelaide Hospital; Haematology Clinical Trials Adelaide South Australia Australia 5000
    7 Peter MacCallum Cancer Centre; Department of Haematology Melbourne Victoria Australia 3002
    8 Princess Margaret Cancer Center Toronto Ontario Canada M5G 1Z5
    9 ASST PAPA GIOVANNI XXIII; Ematologia Bergamo Lombardia Italy 24127
    10 Ospedale Di Circolo E Fondazione Macchi; Ematologia Varese Lombardia Italy 21100
    11 Az. Ospedaliero-Universitaria Careggi; CRIMM Firenze Toscana Italy 50134

    Sponsors and Collaborators

    • Hoffmann-La Roche

    Investigators

    • Study Director: Clinical Trials, Hoffmann-La Roche

    Study Documents (Full-Text)

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Hoffmann-La Roche
    ClinicalTrials.gov Identifier:
    NCT03287245
    Other Study ID Numbers:
    • NP39761
    • 2017-000861-58
    First Posted:
    Sep 19, 2017
    Last Update Posted:
    Dec 8, 2021
    Last Verified:
    Dec 1, 2021
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Hoffmann-La Roche
    polycythemia vera
    PV
    P vera
    myeloproliferative diseases
    hematologic diseases
    myeloproliferative neoplasm
    MPN
    Additional relevant MeSH terms:
    Polycythemia Vera
    Polycythemia

    Study Results

    Participant Flow

    Recruitment Details A total of 48 participants were screened for enrollment; 21 were failed screening. 27 were enrolled and received study treatment. All 27 patients were discontinued from study before the planned date of follow-up.
    Pre-assignment Detail
    Arm/Group Title Ruxolitinib-naïve Participants With Splenomegaly Ruxolitinib-naïve Participants Without Splenomegaly Ruxolitinib-Resistant or Intolerant Participants With Splenomegaly Ruxolitinib-Resistant or Intolerant Participants Without Splenomegaly
    Arm/Group Description Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years). Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years). Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years) Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years)
    Period Title: Overall Study
    STARTED 15 5 6 1
    COMPLETED 0 0 0 0
    NOT COMPLETED 15 5 6 1

    Baseline Characteristics

    Arm/Group Title Ruxolitinib-naïve Participants With Splenomegaly Ruxolitinib-naïve Participants Without Splenomegaly Ruxolitinib-Resistant or Intolerant Participants With Splenomegaly Ruxolitinib-Resistant or Intolerant Participants Without Splenomegaly Total
    Arm/Group Description Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years). Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years). Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years) Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years) Total of all reporting groups
    Overall Participants 15 5 6 1 27
    Age (Years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Years]
    54.5
    (10.7)
    56.8
    (8.8)
    60.3
    (8.4)
    55
    (0)
    56.3
    (9.6)
    Sex: Female, Male (Count of Participants)
    Female
    2
    13.3%
    5
    100%
    4
    66.7%
    0
    0%
    11
    40.7%
    Male
    13
    86.7%
    0
    0%
    2
    33.3%
    1
    100%
    16
    59.3%
    Race/Ethnicity, Customized (Count of Participants)
    Hispanic or Latino
    1
    6.7%
    0
    0%
    0
    0%
    0
    0%
    1
    3.7%
    Not Hispanic or Latino
    14
    93.3%
    5
    100%
    6
    100%
    1
    100%
    26
    96.3%
    Race/Ethnicity, Customized (Count of Participants)
    Asian
    1
    6.7%
    0
    0%
    0
    0%
    0
    0%
    1
    3.7%
    White
    14
    93.3%
    5
    100%
    6
    100%
    1
    100%
    26
    96.3%

    Outcome Measures

    1. Primary Outcome
    Title Percentage of Ruxolitinib-Naïve Participants With Splenomegaly at Baseline Who Achieved Composite Response at Week 32
    Description Composite response is defined as hematocrit (Hct) control without phlebotomy and ≥35% decrease in spleen size by imaging at Week 32. Hct control is defined as protocol-specified ineligibility for phlebotomy between Weeks 8 to 32 and ≤1 instance of phlebotomy eligibility between first dose and Week 8. Eligibility for phlebotomy is defined as a Hct of ≥45% that was ≥3% higher than baseline level or a Hct of >48%. One Cycle is 28 Days.
    Time Frame Week 32

    Outcome Measure Data

    Analysis Population Description
    ITT Population
    Arm/Group Title Ruxolitinib-Naïve Participants With Splenomegaly
    Arm/Group Description Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years).
    Measure Participants 9
    Number [Percentage of Participants]
    44.4
    296%
    2. Primary Outcome
    Title Percentage of Ruxolitinib-Naïve Participants Without Splenomegaly at Baseline Who Achieved Hematocrit (Hct) Control Without Phlebotomy at Week 32
    Description Hct control is defined as protocol-specified ineligibility for phlebotomy between Weeks 8 to 32 and ≤1 instance of phlebotomy eligibility between first dose and Week 8. Eligibility for phlebotomy is defined as a Hct level ≥45% that was ≥3% higher than baseline level or a Hct level of >48%.
    Time Frame Week 32

    Outcome Measure Data

    Analysis Population Description
    ITT Population
    Arm/Group Title Ruxolitinib-Naïve Participants Without Splenomegaly
    Arm/Group Description Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years).
    Measure Participants 2
    Number [Percentage of Participants]
    100
    666.7%
    3. Primary Outcome
    Title Percentage of All Ruxolitinib-Naïve Participants (Irrespective of Spleen Size) Who Achieved Hct Control Without Phlebotomy at Week 32
    Description Hct control is defined as protocol-specified ineligibility for phlebotomy between Weeks 8 to 32 and ≤1 instance of phlebotomy eligibility between first dose and Week 8. Eligibility for phlebotomy is defined as a Hct level ≥45% that was ≥3% higher than baseline level or a Hct level of >48%.
    Time Frame Week 32

    Outcome Measure Data

    Analysis Population Description
    ITT population
    Arm/Group Title Ruxolitinib-Naïve Participants With Splenomegaly Ruxolitinib-Naïve Participants Without Splenomegaly Total Ruxolitinib-Naïve Participants
    Arm/Group Description Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years). Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years). Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years).
    Measure Participants 9 2 11
    Number [Percentage of Participants]
    44.4
    296%
    100
    2000%
    54.5
    908.3%
    4. Primary Outcome
    Title Percentage of All Ruxolitinib-Resistant or Intolerant Participants Who Achieved Hct Control Without Phlebotomy at Week 32
    Description Hct control is defined as protocol-specified ineligibility for phlebotomy between Weeks 8 to 32 and ≤1 instance of phlebotomy eligibility between first dose and Week 8. Eligibility for phlebotomy is defined as a Hct level ≥45% that was ≥3% higher than baseline level or a Hct level of >48%.
    Time Frame From Baseline to Week 32 (Cycle 8 Day 28)

    Outcome Measure Data

    Analysis Population Description
    ITT population. The number analyzed includes participants who were evaluable at each timepoint.
    Arm/Group Title Ruxolitinib-Resistant or Intolerant Participants With Splenomegaly Ruxolitinib-Resistant or Intolerant Participants Without Splenomegaly Total Ruxolitinib-Resistant or Intolerant Participants
    Arm/Group Description Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years) Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years) Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years)
    Measure Participants 4 1 5
    Number [Percentage of Participants]
    75.0
    500%
    0
    0%
    60
    1000%
    5. Secondary Outcome
    Title Percentage of All Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Participants Who Achieved Complete Hematologic Response at Week 32
    Description Complete hematologic response requires all of the following: Hct control without phlebotomy; White blood cell (WBC) count ≤10 × 10^9/Liter (L) at Week 32; and Platelet count ≤400 × 10^9/L at Week 32. Hct control is defined as protocol-specified ineligibility for phlebotomy between Weeks 8 to 32 and ≤1 instance of phlebotomy eligibility between first dose and Week 8. Eligibility for phlebotomy is defined as a Hct level ≥45% that was ≥3% higher than baseline level or a Hct level of >48%.
    Time Frame Week 32 (Cycle 8 Day 28)

    Outcome Measure Data

    Analysis Population Description
    ITT population. The number analyzed includes participants who were evaluable at each timepoint.
    Arm/Group Title Ruxolitinib-naïve Participants With Splenomegaly Ruxolitinib-naïve Participants Without Splenomegaly Ruxolitinib-Resistant or Intolerant Participants With Splenomegaly Ruxolitinib-Resistant or Intolerant Participants Without Splenomegaly
    Arm/Group Description Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years). Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years). Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years). Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years).
    Measure Participants 9 2 4 1
    Number [Percentage of Participants]
    33.3
    222%
    100
    2000%
    75.0
    1250%
    0
    0%
    6. Secondary Outcome
    Title Percentage of All Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Participants Who Achieved Complete Hematologic Remission at Cycle 11 Day 28
    Description Complete hematologic remission requires all of the following: Hct control without phlebotomy between Weeks 32 and Cycle 11 Day 28; WBC count ≤10 × 10^9/L at Cycle 11 Day 28; and Platelet count ≤400 × 10^9/L at Week 32. Hct control is defined as protocol-specified ineligibility for phlebotomy. Eligibility for phlebotomy is defined as a Hct level ≥45% that was ≥3% higher than baseline level or a Hct level of >48%.
    Time Frame Cycle 11 Day 28

    Outcome Measure Data

    Analysis Population Description
    ITT Population. The number analyzed includes participants who were evaluable at each timepoint.
    Arm/Group Title Ruxolitinib-Naïve Participants With Splenomegaly Ruxolitinib-Naïve Participants Without Splenomegaly Ruxolitinib-Resistant or Intolerant Participants With Splenomegaly Ruxolitinib-Resistant or Intolerant Participants Without Splenomegaly
    Arm/Group Description Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years). Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years). Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years). Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years).
    Measure Participants 5 1 1 1
    Number [Percentage of Participants]
    40
    266.7%
    100
    2000%
    0
    0%
    0
    0%
    7. Secondary Outcome
    Title Duration of Complete Hematologic Remission, With a Durable Responder Defined as a Participant in Remission at Week 32 and Cycle 11 Day 28
    Description Complete hematologic remission requires all of the following: Hct control without phlebotomy between Week 32 (Cycle 8 Day 28) and Cycle 11 Day 28; WBC count ≤10 × 10^9/L at Cycle 11 Day 28; and Platelet count ≤400 × 10^9/L at Week 32. Hct control is defined as protocol-specified ineligibility for phlebotomy. Eligibility for phlebotomy is defined as a Hct level ≥45% that was ≥3% higher than baseline level or a Hct level of >48%
    Time Frame Week 32 (Cycle 8 Day 28), Cycle 11 Day 28

    Outcome Measure Data

    Analysis Population Description
    ITT population. The "number of participants analyzed" is the number of patients (total n) per arm. "The number analyzed" was the number of patients evaluable at that specific timepoint. Not all participants of each arm were evaluable at each time point.
    Arm/Group Title Ruxolitinib-naïve Participants With Splenomegaly Ruxolitinib-naïve Participants Without Splenomegaly Ruxolitinib-Resistant or Intolerant Participants With Splenomegaly Ruxolitinib-Resistant or Intolerant Participants Without Splenomegaly
    Arm/Group Description Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years). Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years). Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years). Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years).
    Measure Participants 15 5 6 1
    Cycle 11, Day 28
    2
    13.3%
    1
    20%
    0
    0%
    0
    0%
    Week 32
    3
    20%
    2
    40%
    3
    50%
    0
    0%
    8. Secondary Outcome
    Title Percentage of Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Participants With Splenomegaly at Baseline by Response Per Modified European Leukemia Net (ELN) Criteria
    Description Complete response (CR) includes all of the following: Hct <45% without phlebotomy; Platelet count ≤400 × 10^9/L; WBC count ≤10 × 10^9/L; Normal spleen size on imaging; and No disease-related symptoms. Partial response (PR): in participants who do not fulfill the criteria for CR: Hct <45% without phlebotomy or response in 3 or more of the other criteria. No response (NR): any response that does not satisfy partial response. Progressive disease (PD): increased bone marrow fibrosis from baseline, and/or transformation to myelofibrosis (MF), myelodysplastic syndrome (MDS) or acute leukemia. All responders of each category grouped per timepoint include all categories mentioned above. There were no PD responses at any timepoint. The study was pre-maturely terminated by the sponsor's decision due to non-transformative efficacy and poor long-term tolerability of the dosing schedule as well as due to chronic gastrointestinal toxicity, therefore did not reach the end of study.
    Time Frame Baseline, Day 28 of Cycles 3, 5, 8, 11, 12, 14, 17, 20 and Final visit (28 days after post-last dose)

    Outcome Measure Data

    Analysis Population Description
    ITT population. The "number of participants analyzed" is the number of patients (total n) per arm. "The number analyzed" was the number of patients evaluable at that specific timepoint. Not all participants of each arm were evaluable at each time point.
    Arm/Group Title Ruxolitinib-naïve Participants With Splenomegaly Ruxolitinib-Resistant or Intolerant Participants With Splenomegaly
    Arm/Group Description Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years). Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years).
    Measure Participants 15 6
    Baseline Complete Response
    0
    0%
    0
    0%
    Baseline Partial Response
    0
    0%
    0
    0%
    Baseline Progressive Disease
    0
    0%
    0
    0%
    Baseline No Response
    0
    0%
    0
    0%
    Cycle 3, Day 28 Complete Response
    0
    0%
    33.3
    666%
    Cycle 3, Day 28 Partial Response
    73.3
    488.7%
    50.0
    1000%
    Cycle 3, Day 28 Progressive Disease
    0
    0%
    0
    0%
    Cycle 3, Day 28 No Response
    26.7
    178%
    16.7
    334%
    Cycle 5, Day 28 Complete Response
    0
    0%
    0
    0%
    Cycle 5, Day 28 Partial Response
    76.9
    512.7%
    80.0
    1600%
    Cycle 5, Day 28 Progressive Disease
    0
    0%
    0
    0%
    Cycle 5, Day 28 No Response
    23.1
    154%
    20.0
    400%
    Cycle 8, Day 28 (Week 32) Complete Response
    0
    0%
    25.0
    500%
    Cycle 8, Day 28 (Week 32) Partial Response
    66.7
    444.7%
    50.0
    1000%
    Cycle 8, Day 28 (Week 32) Progressive Disease
    0
    0%
    0
    0%
    Cycle 8, Day 28 (Week 32) No Response
    33.3
    222%
    25.0
    500%
    Cycle 11, Day 28 Complete Response
    0
    0%
    0
    0%
    Cycle 11, Day 28 Partial Response
    80.0
    533.3%
    100.0
    2000%
    Cycle 11, Day 28 Progressive Disease
    0
    0%
    0
    0%
    Cycle 11, Day 28 No Response
    20.0
    133.3%
    0
    0%
    Cycle 12, Day 28 Complete Response
    0
    0%
    Cycle 12, Day 28 Partial Response
    0
    0%
    Cycle 12, Day 28 Progressive Disease
    0
    0%
    Cycle 12, Day 28 No Response
    0
    0%
    Cycle 14, Day 28 Complete Response
    0
    0%
    0
    0%
    Cycle 14, Day 28 Partial Response
    80
    533.3%
    100
    2000%
    Cycle 14, Day 28 Progressive Disease
    0
    0%
    0
    0%
    Cycle 14, Day 28 No Response
    20
    133.3%
    0
    0%
    Cycle 17, Day 28 Complete Response
    0
    0%
    0
    0%
    Cycle 17, Day 28 Partial Response
    33.3
    222%
    0
    0%
    Cycle 17, Day 28 Progressive Disease
    0
    0%
    0
    0%
    Cycle 17, Day 28 No Response
    66.7
    444.7%
    100
    2000%
    Cycle 20, Day 28 Complete Response
    0
    0%
    Cycle 20, Day 28 Partial Response
    100
    666.7%
    Cycle 20, Day 28 Progressive Disease
    0
    0%
    Cycle 20, Day 28 No Response
    0
    0%
    Final Visit (28 Days post-last dose) Complete Response
    0
    0%
    0
    0%
    Final Visit (28 Days post-last dose) Partial Response
    20.0
    133.3%
    33.3
    666%
    Final Visit (28 Days post-last dose) Progressive Disease
    0
    0%
    0
    0%
    Final Visit (28 Days post-last dose) No Response
    80
    533.3%
    66.7
    1334%
    9. Secondary Outcome
    Title Percentage of Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Participants Without Splenomegaly at Baseline by Response Per Modified ELN Criteria
    Description Complete response (CR) includes all of the following: Hct <45% without phlebotomy; Platelet count ≤400 × 10^9/L; WBC count ≤10 × 10^9/L; Normal spleen size on imaging; and No disease-related symptoms. Partial response (PR): in participants who do not fulfill the criteria for CR: Hct <45% without phlebotomy or response in 3 or more of the other criteria. No response (NR): any response that does not satisfy partial response. Progressive disease (PD): increased bone marrow fibrosis from baseline, and/or transformation to myelofibrosis (MF), myelodysplastic syndrome (MDS) or acute leukemia. All responders of each category grouped per timepoint include all categories mentioned above. There were no PD responses at any timepoint. The study was pre-maturely terminated by the sponsor's decision due to non-transformative efficacy and poor long-term tolerability of the dosing schedule as well as due to chronic gastrointestinal toxicity, therefore did not reach the end of study.
    Time Frame Baseline, Day 28 of Cycles 3, 5, 8, 11, 12, 14, 17, 20 and Final visit (28 days after post-last dose)

    Outcome Measure Data

    Analysis Population Description
    ITT population. The "number of participants analyzed" is the number of patients (total n) per arm. "The number analyzed" was the number of patients evaluable at that specific timepoint. Not all participants of each arm were evaluable at each time point.
    Arm/Group Title Ruxolitinib-naïve Participants Without Splenomegaly Ruxolitinib-Resistant or Intolerant Participants Without Splenomegaly
    Arm/Group Description Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years). Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years).
    Measure Participants 5 1
    Baseline Complete Response
    0
    0%
    0
    0%
    Baseline Partial Response
    0
    0%
    0
    0%
    Baseline Progressive Disease
    0
    0%
    0
    0%
    Baseline No Response
    0
    0%
    0
    0%
    Cycle 3, Day 28 Complete Response
    50
    333.3%
    0
    0%
    Cycle 3, Day 28 Partial Response
    50
    333.3%
    0
    0%
    Cycle 3, Day 28 Progressive Disease
    0
    0%
    0
    0%
    Cycle 3, Day 28 No Response
    0
    0%
    100
    2000%
    Cycle 5 Day 28 Complete Response
    66.7
    444.7%
    0
    0%
    Cycle 5 Day 28 Partial Response
    33.3
    222%
    0
    0%
    Cycle 5 Day 28 Progressive Disease
    0
    0%
    0
    0%
    Cycle 5 Day 28 No Response
    0
    0%
    100
    2000%
    Cycle 8, Day 28 (Week 32) Complete Response
    100
    666.7%
    0
    0%
    Cycle 8, Day 28 (Week 32) Partial Response
    0
    0%
    0
    0%
    Cycle 8, Day 28 (Week 32) Progressive Disease
    0
    0%
    0
    0%
    Cycle 8, Day 28 (Week 32) No Response
    0
    0%
    100
    2000%
    Cycle 11, day 28 Complete Response
    100
    666.7%
    0
    0%
    Cycle 11, day 28 Partial Response
    0
    0%
    0
    0%
    Cycle 11, day 28 Progressive Disease
    0
    0%
    0
    0%
    Cycle 11, day 28 No Response
    0
    0%
    100
    2000%
    Cycle 14, Day 28 Complete Response
    100
    666.7%
    0
    0%
    Cycle 14, Day 28 Partial Response
    0
    0%
    0
    0%
    Cycle 14, Day 28 Progressive Disease
    0
    0%
    0
    0%
    Cycle 14, Day 28 No Response
    0
    0%
    100
    2000%
    Cycle 17, Day 28 Complete Response
    100
    666.7%
    0
    0%
    Cycle 17, Day 28 Partial Response
    0
    0%
    0
    0%
    Cycle 17, Day 28 Progressive Disease
    0
    0%
    0
    0%
    Cycle 17, Day 28 No Response
    0
    0%
    100
    2000%
    Cycle 20, Day 28 Complete Response
    0
    0%
    Cycle 20, Day 28 Partial Response
    0
    0%
    Cycle 20, Day 28 Progressive Disease
    0
    0%
    Cycle 20, Day 28 No Response
    100
    666.7%
    Final (28 Days post-last dose) Complete Response
    50.0
    333.3%
    0
    0%
    Final (28 Days post-last dose) Partial Response
    25.0
    166.7%
    0
    0%
    Final (28 Days post-last dose) Progressive Disease
    0.0
    0%
    0
    0%
    Final (28 Days post-last dose) No Response
    25.0
    166.7%
    100
    2000%
    10. Secondary Outcome
    Title Percentage of All Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Participants (Irrespective of Spleen Size) by Response Per Modified ELN Criteria
    Description Complete response (CR) includes all of the following: Hct <45% without phlebotomy; Platelet count ≤400 × 10^9/L; WBC count ≤10 × 10^9/L; Normal spleen size on imaging; and No disease-related symptoms. Partial response (PR): in participants who do not fulfill the criteria for CR: Hct <45% without phlebotomy or response in 3 or more of the other criteria. No response (NR): any response that does not satisfy partial response. Progressive disease (PD): increased bone marrow fibrosis from baseline, and/or transformation to myelofibrosis (MF), myelodysplastic syndrome (MDS) or acute leukemia. All responders of each category grouped per timepoint include all categories mentioned above. There were no PD responses at any timepoint. The study was pre-maturely terminated by the sponsor's decision due to non-transformative efficacy and poor long-term tolerability of the dosing schedule as well as due to chronic gastrointestinal toxicity, therefore did not reach the end of study.
    Time Frame Baseline, Day 28 of Cycles 3, 5, 8, 11, 12, 14, 17, 20 and Final visit (28 days after post-last dose)

    Outcome Measure Data

    Analysis Population Description
    ITT population. The "number of participants analyzed" is the number of patients (total n) per arm. "The number analyzed" was the number of patients evaluable at that specific timepoint. Not all participants of each arm were evaluable at each time point.
    Arm/Group Title All Ruxolitinib-Naïve Participants All Ruxolitinib-Resistant or Intolerant Participants
    Arm/Group Description Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years). Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years).
    Measure Participants 20 7
    Baseline Complete Response
    0
    0%
    0
    0%
    Baseline Partial Response
    0
    0%
    0
    0%
    Baseline Progressive Disease
    0
    0%
    0
    0%
    Baseline No Response
    0
    0%
    0
    0%
    Cycle 3, Day 28 Complete Response
    10.5
    70%
    28.6
    572%
    Cycle 3, Day 28 Partial Response
    68.4
    456%
    42.9
    858%
    Cycle 3, Day 28 Progressive Disease
    0
    0%
    0
    0%
    Cycle 3, Day 28 No Response
    21.1
    140.7%
    28.6
    572%
    Cycle 5, Day 28 Complete Response
    12.5
    83.3%
    0
    0%
    Cycle 5, Day 28 Partial Response
    68.8
    458.7%
    66.7
    1334%
    Cycle 5, Day 28 Progressive Disease
    0
    0%
    0
    0%
    Cycle 5, Day 28 No Response
    18.8
    125.3%
    33.3
    666%
    Cycle 8, Day 28 (Week 32) Complete Response
    18.2
    121.3%
    20.0
    400%
    Cycle 8, Day 28 (Week 32) Partial Response
    54.5
    363.3%
    40.0
    800%
    Cycle 8, Day 28 (Week 32) Progressive Disease
    0
    0%
    0
    0%
    Cycle 8, Day 28 (Week 32) No Response
    27.3
    182%
    40.0
    800%
    Cycle 11 Day 28 Complete Response
    16.7
    111.3%
    0
    0%
    Cycle 11 Day 28 Partial Response
    66.7
    444.7%
    50.0
    1000%
    Cycle 11 Day 28 Progressive Disease
    0
    0%
    0
    0%
    Cycle 11 Day 28 No Response
    16.7
    111.3%
    50.0
    1000%
    Cycle 12 Day 28 Complete Response
    0
    0%
    Cycle 12 Day 28 Partial Response
    100
    666.7%
    Cycle 12 Day 28 Progressive Disease
    0
    0%
    Cycle 12 Day 28 No Response
    0
    0%
    Cycle 14, Day 28 Complete Response
    16.7
    111.3%
    0
    0%
    Cycle 14, Day 28 Partial Response
    66.7
    444.7%
    50
    1000%
    Cycle 14, Day 28 Progressive Disease
    0
    0%
    0
    0%
    Cycle 14, Day 28 No Response
    16.7
    111.3%
    50.0
    1000%
    Cycle 17, Day 28 Complete Response
    25.0
    166.7%
    0
    0%
    Cycle 17, Day 28 Partial Response
    25.0
    166.7%
    0
    0%
    Cycle 17, Day 28 Progressive Disease
    0
    0%
    0
    0%
    Cycle 17, Day 28 No Response
    50.0
    333.3%
    100
    2000%
    Cycle 20, Day 28 Complete Response
    0
    0%
    0
    0%
    Cycle 20, Day 28 Partial Response
    100
    666.7%
    0
    0%
    Cycle 20, Day 28 Progressive Disease
    0
    0%
    0
    0%
    Cycle 20, Day 28 No Response
    0
    0%
    100
    2000%
    Final Visit Complete Response
    14.3
    95.3%
    0
    0%
    Final Visit Partial Response
    21.4
    142.7%
    25.0
    500%
    Final Visit Progressive Disease
    0
    0%
    0
    0%
    Final Visit No Response
    64.3
    428.7%
    75.0
    1500%
    11. Secondary Outcome
    Title Percentage of Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Participants With Splenomegaly at Baseline With Durable Response Lasting at Least 12 Weeks From Week 32
    Description The percentage of participants with a durable response lasting at least 12 weeks from Week 32 are analyzed by the type of response achieved: Hct control, complete hematologic response, ELN 2009 response criteria, and composite response, if applicable. Reported result data start from Cycle 11 Day 28 which is 12 weeks after Week 32 (Cycle 8 Day 28). There was one timepoint for which the participants qualify. The study was pre-maturely terminated by the sponsor decision, therefore did not reach the end of study.
    Time Frame From Week 32 (Cycle 8 Day 28) and at least 12 Weeks after until end of study (up to 2 years)

    Outcome Measure Data

    Analysis Population Description
    ITT population. The number analyzed includes participants who were evaluable at each timepoint.
    Arm/Group Title Ruxolitinib-Naïve Participants With Splenomegaly Ruxolitinib-Resistant or Intolerant Participants With Splenomegaly
    Arm/Group Description Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years). Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years).
    Measure Participants 15 6
    HCT Control
    42.9
    286%
    100
    2000%
    Composite Response
    0
    0%
    0
    0%
    ELN Response
    50
    333.3%
    75
    1500%
    Complete Hematologic Response
    28.6
    190.7%
    66.7
    1334%
    12. Secondary Outcome
    Title Number of Participants With a Durable Response, in Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Participants With Splenomegaly at Baseline With Durable Response Lasting at Least 12 Weeks From Week 32
    Description The number of participants with a durable response lasting at least 12 weeks from Week 32 is analyzed by the type of response achieved: Hct control, complete hematologic response, ELN 2009 response criteria, and composite response, if applicable. Reported result data start from Cycle 11 Day 28 which is 12 weeks after Week 32 (Cycle 8 Day 28). There was one timepoint for which the participants qualify. The study was pre-maturely terminated by the sponsor's decision due to non-transformative efficacy and poor long-term tolerability of the dosing schedule as well as due to chronic gastrointestinal toxicity, therefore did not reach the planned end of study.
    Time Frame From Week 32 (Cycle 8 Day 28) and at least 12 weeks after until end of study (up to 2 years)

    Outcome Measure Data

    Analysis Population Description
    ITT population. The number analyzed includes participants who were evaluable at each timepoint.
    Arm/Group Title Ruxolitinib-Naïve Participants With Splenomegaly Ruxolitinib-Resistant or Intolerant Participants With Splenomegaly
    Arm/Group Description Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years). Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years).
    Measure Participants 15 6
    HCT Control
    3
    20%
    3
    60%
    Composite Response
    0
    0%
    0
    0%
    ELN Response
    4
    26.7%
    3
    60%
    Complete Hematologic Response
    2
    13.3%
    2
    40%
    13. Secondary Outcome
    Title Percentage of Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Participants Without Splenomegaly at Baseline With Durable Response Lasting at Least 12 Weeks From Week 32
    Description The percentage of participants with a durable response lasting at least 12 weeks from Week 32 is analyzed by the type of response achieved: Hct control, complete hematologic response, ELN 2009 response criteria, and composite response, if applicable. Reported result data start from Cycle 11 Day 28 which is 12 weeks after Week 32 (Cycle 8 Day 28). There was one timepoint for which the participants qualify. The study was pre-maturely terminated by the sponsor decision, therefore did not reach the end of study.
    Time Frame From Week 32 (Cycle 8 Day 28) and at least 12 Weeks after until end of study (up to 2 years)

    Outcome Measure Data

    Analysis Population Description
    ITT population. The number analyzed includes participants who were evaluable at each timepoint.
    Arm/Group Title Ruxolitinib-Naïve Participants Without Splenomegaly Ruxolitinib-Resistant or Intolerant Participants Without Splenomegaly
    Arm/Group Description Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years). Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years).
    Measure Participants 5 1
    HCT Control
    100
    666.7%
    0
    0%
    Composite Response
    0
    0%
    0
    0%
    ELN Response
    100
    666.7%
    0
    0%
    Complete Hematologic Response
    100
    666.7%
    0
    0%
    14. Secondary Outcome
    Title Number of Participants With a Durable Response, in Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Participants Without Splenomegaly at Baseline With Durable Response Lasting at Least 12 Weeks From Week 32
    Description The number of participants with a durable response lasting at least 12 weeks from Week 32 is analyzed by the type of response achieved: Hct control, complete hematologic response, ELN 2009 response criteria, and composite response, if applicable. Reported result data start from Cycle 11 Day 28 which is 12 weeks after Week 32 (Cycle 8 Day 28). There was one timepoint for which the participants qualify. The study was pre-maturely terminated by the sponsor's decision due to non-transformative efficacy and poor long-term tolerability of the dosing schedule as well as due to chronic gastrointestinal toxicity, therefore did not reach the planned end of study.
    Time Frame From Week 32 (Cycle 8 Day 28) and at least 12 weeks after until end of study (up to 2 years)

    Outcome Measure Data

    Analysis Population Description
    ITT population. The number analyzed includes participants who were evaluable at each timepoint.
    Arm/Group Title Ruxolitinib-Naïve Participants Without Splenomegaly Ruxolitinib-Resistant or Intolerant Participants Without Splenomegaly
    Arm/Group Description Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years). Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years).
    Measure Participants 5 1
    HCT Control
    2
    13.3%
    0
    0%
    Composite Response
    0
    0%
    0
    0%
    ELN Response
    2
    13.3%
    0
    0%
    Complete Hematologic Response
    2
    13.3%
    0
    0%
    15. Secondary Outcome
    Title Percentage of All Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Participants (Irrespective of Spleen Size) With Durable Response Lasting at Least 12 Weeks From Week 32
    Description The percentage of participants with a durable response lasting at least 12 weeks from Week 32 is analyzed by the type of response achieved: Hct control, complete hematologic response, ELN 2009 response criteria, and composite response, if applicable. Reported result data start from Cycle 11 Day 28 which is 12 weeks after Week 32 (Cycle 8 Day 28). There was one timepoint for which the participants qualify. The study was pre-maturely terminated by the sponsor decision, therefore did not reach the end of study.
    Time Frame From Week 32 (Cycle 8 Day 28) and at least 12 Weeks after until end of study (up to 2 years)

    Outcome Measure Data

    Analysis Population Description
    ITT population. The number analyzed includes participants who were evaluable at each timepoint.
    Arm/Group Title All Ruxolitinib-Naïve Participants All Ruxolitinib-Resistant or Intolerant Participants
    Arm/Group Description Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years). Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years).
    Measure Participants 20 7
    After 12 Weeks from Week 32 HCT Control
    55.6
    370.7%
    75
    1500%
    After 12 Weeks from Week 32 Composite Response
    0
    0%
    0
    0%
    After 12 Weeks from Week 32 ELN Response
    60
    400%
    60
    1200%
    After 12 Weeks from Week 32 Complete Hematologic Response
    44.4
    296%
    50
    1000%
    16. Secondary Outcome
    Title Number of Participants With a Duration Response, in All Ruxolitinib-Naïve and Ruxolitinib-Resistant or Intolerant Participants (Irrespective of Spleen Size) With Durable Response Lasting at Least 12 Weeks From Week 32
    Description The number of participants with a durable response lasting at least 12 weeks from Week 32 is analyzed by the type of response achieved: Hct control, complete hematologic response, ELN 2009 response criteria, and composite response, if applicable. Reported result data start from Cycle 11 Day 28 which is 12 weeks after Week 32 (Cycle 8 Day 28). There was one timepoint for which the participants qualify. The study was pre-maturely terminated by the sponsor's decision due to non-transformative efficacy and poor long-term tolerability of the dosing schedule as well as due to chronic gastrointestinal toxicity, therefore did not reach the planned end of study.
    Time Frame From Week 32 (Cycle 8 Day 28) and at least 12 weeks after until end of study (up to 2 years)

    Outcome Measure Data

    Analysis Population Description
    ITT population. The number analyzed includes participants who were evaluable at each timepoint.
    Arm/Group Title All Ruxolitinib-Naïve Participants All Ruxolitinib-Resistant or Intolerant Participants
    Arm/Group Description Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years). Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years).
    Measure Participants 20 7
    HCT Control
    5
    33.3%
    3
    60%
    Composite Response
    0
    0%
    0
    0%
    ELN Response
    6
    40%
    3
    60%
    Complete Hematologic Response
    4
    26.7%
    2
    40%
    17. Secondary Outcome
    Title Total Number of Participants With Adverse Events by Severity, Graded According to NCI CTCAE v4.0
    Description An adverse event is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study drug, whether or not considered related to the study drug. The adverse event severity grading scale for the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (NCI CTCAE v4.0) will be used for assessing adverse event severity. During the final analyses, the focus was on the Adverse Events of severity grades >/=3 as shown below. The extensive listings of all grade AEs are available at request. The study was pre-maturely terminated by the sponsor's decision due to non-transformative efficacy and poor long-term tolerability of the dosing schedule as well as due to chronic gastrointestinal toxicity, therefore did not reach the planned end of study.
    Time Frame Baseline to end of study (up to 2 years)

    Outcome Measure Data

    Analysis Population Description
    ITT population. The number analyzed includes participants who were evaluable at each timepoint.
    Arm/Group Title Ruxolitinib-Naïve Participants With Splenomegaly Ruxolitinib-Naïve Participants Without Splenomegaly Ruxolitinib-Resistant or Intolerant Participants With Splenomegaly Ruxolitinib-Resistant or Intolerant Participants Without Splenomegaly
    Arm/Group Description Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years). Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years). Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years) Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years)
    Measure Participants 15 5 6 1
    Baseline
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Grade 3-5 AE
    5
    33.3%
    2
    40%
    3
    50%
    0
    0%
    18. Secondary Outcome
    Title Percentage of Participants With Clinical Laboratory Abnormalities: Hematology Parameters.
    Description Hematology parameter laboratory values falling outside the standard reference range were planned to be recorded as either high or low. There was no clinical laboratory abnormalities identified. The study was pre-maturely terminated by the sponsor's decision, therefore did not reach the end of study.
    Time Frame Baseline to end of study (up to 2 years)

    Outcome Measure Data

    Analysis Population Description
    Safety-Evaluable Patients.
    Arm/Group Title Ruxolitinib-Naïve Participants With Splenomegaly Ruxolitinib-Naïve Participants Without Splenomegaly Ruxolitinib-Resistant or Intolerant Participants With Splenomegaly Ruxolitinib-Resistant or Intolerant Participants Without Splenomegaly
    Arm/Group Description Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years). Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years). Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years). Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years).
    Measure Participants 15 5 6 1
    Number [Percentage of Participants]
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    19. Secondary Outcome
    Title Percentage of Participants With Clinical Laboratory Abnormalities: Clinical Chemistry Parameters
    Description Clinical chemistry parameter laboratory values falling outside the standard reference range were to be recorded as either high or low. There was no clinical chemistry abnormalities identified. The study was pre-maturely terminated by the sponsor's decision, therefore did not reach the end of study.
    Time Frame Baseline to end of study (up to 2 years)

    Outcome Measure Data

    Analysis Population Description
    Safety-Evaluable Participants
    Arm/Group Title Ruxolitinib-Naïve Participants With Splenomegaly Ruxolitinib-Naïve Participants Without Splenomegaly Ruxolitinib-Resistant or Intolerant Participants With Splenomegaly Ruxolitinib-Resistant or Intolerant Participants Without Splenomegaly
    Arm/Group Description Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years). Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years). Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years). Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years).
    Measure Participants 15 5 6 1
    Number [Percentage of Participants]
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    20. Secondary Outcome
    Title Percentage of Participants With Clinical Laboratory Abnormalities: Urinalysis Parameters
    Description Urinalysis parameter laboratory values falling outside the standard reference range were planned to be recorded as either high or low. There was no clinical laboratory (urinalysis) abnormalities identified. The study was pre-maturely terminated by the sponsor's decision, therefore did not reach the end of study.
    Time Frame Baseline to end of study (up to 2 years)

    Outcome Measure Data

    Analysis Population Description
    ITT population
    Arm/Group Title Ruxolitinib-naïve Participants With Splenomegaly Ruxolitinib-naïve Participants Without Splenomegaly Ruxolitinib-Resistant or Intolerant Participants With Splenomegaly Ruxolitinib-Resistant or Intolerant Participants Without Splenomegaly
    Arm/Group Description Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years). Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years). Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years). Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years).
    Measure Participants 15 5 6 1
    Number [Percentage of Participants]
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    21. Secondary Outcome
    Title Change From Baseline in Electrocardiogram Parameters: PQ(PR), QRS, QT, QTcB, QTcF, and RR Durations
    Description Single 12-lead ECGs was obtained using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTc intervals. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The study was pre-maturely terminated by the sponsor's decision due to non-transformative efficacy and poor long-term tolerability of the dosing schedule as well as due to chronic gastrointestinal toxicity, therefore did not reach the planned end of study.
    Time Frame Baseline, Cycle 1 (Day 1, hours 4 and 6, Day 2 pre-dose and 24 Hour, Day 5 pre-dose, 4 and 6 Hour), Cycle 2 (Day 1 pre-dose only), Cycle 3 (Day 1 pre-dose, 4 and 6 Hour), Cycle 4 (Day 1 pre-dose and 4 Hour)

    Outcome Measure Data

    Analysis Population Description
    Safety-Evaluable population. The number analyzed includes participants who were evaluable at each timepoint.
    Arm/Group Title Ruxolitinib-naïve Participants With Splenomegaly Ruxolitinib-naïve Participants Without Splenomegaly Ruxolitinib-Resistant or Intolerant Participants With Splenomegaly Ruxolitinib-Resistant or Intolerant Participants Without Splenomegaly
    Arm/Group Description Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years). Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years). Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years). Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years).
    Measure Participants 15 5 6 1
    PR Duration Baseline
    158.93
    (24.86)
    153.60
    (22.55)
    152.00
    (17.39)
    196.00
    (0)
    PQ(PR) Durations Cycle 1, Day 1, 4 hour
    0.60
    (10.89)
    -2.60
    (5.37)
    -2.00
    (9.72)
    4.00
    (0)
    PQ(PR) Durations Cycle 1, Day 1, 6 hour
    -2.80
    (8.10)
    -4.40
    (15.52)
    6.00
    (25.49)
    0.00
    (0)
    PQ(PR) Durations Cycle 1, Day 2, pre-dose
    -14.00
    (0)
    -6.00
    (0)
    PQ(PR) Durations Cycle 1, Day 2, 24 hour
    1.93
    (10.32)
    1.00
    (16.45)
    0.67
    (22.01)
    -12.00
    (0)
    PQ(PR) Durations Cycle ,1 Day 5, pre-dose
    -1.00
    (11.70)
    -12.00
    (9.38)
    0.40
    (26.59)
    -4.00
    (0)
    PQ(PR) Durations Cycle 1, Day 5, 4 hour
    -8.00
    (12.68)
    -6.25
    (15.59)
    -1.20
    (29.52)
    0
    (0)
    PQ(PR) Durations Cycle 1, Day 5, 6 hour
    -4.77
    (14.08)
    -2.75
    (10.81)
    7.60
    (27.29)
    0
    (0)
    PQ(PR) Durations Cycle 2, Day1, pre-dose
    1.43
    (14.26)
    -5.75
    (11.79)
    -2.33
    (11.89)
    -8.00
    (0)
    PQ(PR) Durations Cycle 3, Day 1, pre-dose
    -6.00
    (0)
    PQ(PR) Durations Cycle 3, Day 1, 4 hour
    -8.00
    (0)
    PQ(PR) Durations Cycle 3, Day 1, 6 hour
    -6.00
    (0)
    PQ(PR) Durations Cycle 4, Day 1, pre-dose
    -20.00
    (0)
    PQ(PR) Durations Cycle 4, Day 1, 4 hour
    -20.00
    (0)
    QRS Duration Baseline
    90.87
    (8.25)
    83.80
    (6.42)
    83.33
    (9.77)
    94.00
    (0)
    QRS Cycle 1 Day 1 (4 H)
    -1.47
    (5.83)
    4.60
    (6.69)
    1.33
    (1.03)
    0
    (0)
    QRS Cycle 1 Day 1 (6 H)
    -1.27
    (5.27)
    4.00
    (3.08)
    0.33
    (5.28)
    -2.00
    (0)
    QRS Cycle 1 Day 2 (PREDOSE)
    -4.00
    (0)
    2.00
    (0)
    QRS Cycle 1 Day 2 (24 H)
    1.07
    (3.77)
    1.75
    (6.55)
    3.00
    (11.64)
    -2.00
    (0)
    QRS Cycle 1 Day 5 (PREDOSE)
    0.13
    (4.63)
    4.00
    (9.09)
    0.00
    (2.00)
    2.00
    (0)
    QRS Cycle 1 Day 5 (4 H)
    -1.08
    (3.12)
    3.75
    (9.46)
    -0.40
    (2.61)
    0
    (0)
    QRS Cycle 1 Day 5 (6 H)
    -0.92
    (4.73)
    -0.25
    (5.19)
    2.00
    (5.83)
    0
    (0)
    QRS Cycle 2 Day 1 (PREDOSE)
    0.64
    (6.25)
    7.75
    (9.46)
    1.00
    (2.76)
    -4.00
    (0)
    QRS Cycle 3 Day 1 (PREDOSE)
    -4.00
    (0)
    QRS Cycle 3 Day 1 (4 H)
    -4.00
    (0)
    QRS Cycle 3 Day 1 (6 H)
    -4.00
    (0)
    QRS Cycle 4 Day 1 (PREDOSE)
    -2.00
    (0)
    QRS Cycle 4 Day 1 (4 H)
    -2.00
    (0)
    QT Duration Baseline
    396.67
    (31.96)
    392.60
    (38.74)
    386.00
    (16.78)
    392.00
    (0)
    QT Duration Cycle 1 Day 1 (4 H)
    -7.33
    (26.43)
    16.80
    (13.44)
    5.67
    (10.07)
    36.00
    (0)
    QT Duration Cycle 1 Day 1 (6 H)
    -9.40
    (23.70)
    11.00
    (29.14)
    -1.33
    (13.49)
    36.00
    (0)
    QT Duration Cycle 1 Day 2 (PREDOSE)
    -6.00
    (0)
    -18.00
    (0)
    QT Duration Cycle 1 Day 2 (24 H)
    -10.21
    (25.57)
    2.75
    (29.00)
    7.00
    (16.58)
    0
    (0)
    QT Duration Cycle 1 Day 5 (PREDOSE)
    -6.20
    (19.79)
    -8.75
    (21.00)
    8.00
    (19.54)
    4.00
    (0)
    QT Duration Cycle 1 Day 5 (4 H)
    -4.31
    (33.31)
    15.25
    (15.65)
    3.20
    (24.23)
    -12.00
    (0)
    QT Duration Cycle 1 Day 5 (6 H)
    -10.31
    (24.83)
    4.75
    (20.93)
    7.60
    (16.40)
    -4.00
    (0)
    QT Duration Cycle 2 Day 1 (PREDOSE)
    5.00
    (22.68)
    10.50
    (25.96)
    19.00
    (13.67)
    12.00
    (0)
    QT Durations Cycle 3 Day 1 (PREDOSE)
    -2.00
    (0)
    QT Durations Cycle 3 Day 1 (4 H)
    -10.00
    (0)
    QT Durations Cycle 3 Day 1 (6 H)
    -4.00
    (0)
    QT Durations Cycle 4 Day 1 (PREDOSE)
    -16.00
    (0)
    QT Durations Cycle 4 Day 1 (4 H)
    -16.00
    (0)
    QTcB baseline
    427.67
    (24.23)
    419.60
    (7.70)
    424.50
    (25.74)
    444.00
    (0)
    QTcB - Bazett's Correction Formula Cycle 1 Day 1 (4 H)
    3.80
    (12.82)
    21.00
    (11.14)
    13.83
    (14.05)
    -30.00
    (0)
    QTcB - Bazett's Correction Formula Cycle 1 Day 1 (6 H)
    8.00
    (10.54)
    8.40
    (22.40)
    6.33
    (5.50)
    5.00
    (0)
    QTcB - Bazett's Correction Formula Cycle 1 Day 2 (PREDOSE)
    -15.00
    (0)
    -410.00
    (0)
    QTcB - Bazett's Correction Formula Cycle 1 Day 2 (24 H)
    3.71
    (15.59)
    -0.75
    (16.40)
    4.50
    (14.47)
    -14.00
    (0)
    QTcB - Bazett's Correction Formula Cycle 1 Day 5 (PREDOSE)
    -11.07
    (15.21)
    -10.00
    (8.76)
    -9.20
    (15.25)
    -7.00
    (0)
    QTcB - Bazett's Correction Formula Cycle 4 Day 1 (4 H)
    -62.00
    (0)
    QTcB - Bazett's Correction FormulaCycle 1 Day 5 (4 H)
    -2.92
    (14.20)
    1.50
    (8.81)
    -4.60
    (18.70)
    0.00
    (0)
    QTcB - Bazett's Correction Formula Cycle 1 Day 5 (6 H)
    -4.54
    (16.10)
    -4.75
    (6.18)
    -1.60
    (15.44)
    -12.00
    (0)
    QTcB - Bazett's Correction Formula Cycle 2 Day 1 (PREDOSE)
    3.93
    (14.42)
    7.75
    (20.61)
    0.17
    (14.54)
    -23.00
    (0)
    QTcB - Bazett's Correction Formula Cycle 3 Day 1 (PREDOSE)
    -16.00
    (0)
    QTcB - Bazett's Correction Formula Cycle 3 Day 1 (4 H)
    6.00
    (0)
    QTcB - Bazett's Correction Formula Cycle 3 Day 1 (6 H)
    8.00
    (0)
    QTcB - Bazett's Correction Formula Cycle 4 Day 1 (PREDOSE)
    -62.00
    (0)
    QTcB - Bazett's Correction Formula Cycle 4 Day 1, 4 H
    -62.00
    (0)
    QTcF Durations Fridericia's Correction Formula Baseline
    417.93
    (22.41)
    410.00
    (17.62)
    411.17
    (17.90)
    426.00
    (0)
    QTcF Durations Fridericia's Correction Formula Cycle 1 Day 1 (4 H)
    -1.27
    (11.86)
    18.80
    (10.08)
    11.67
    (11.09)
    -8.00
    (0)
    QTcF Durations Fridericia's Correction Formula Cycle 1 Day 1 (6 H)
    1.00
    (8.78)
    10.00
    (21.64)
    3.50
    (7.37)
    16.00
    (0)
    QTcF Durations Fridericia's Correction Formula Cycle 1 Day 2 (PREDOSE)
    -12.00
    (0)
    -20.00
    (0)
    QTcF Durations Fridericia's Correction Formula Cycle 1 Day 2 (24 H)
    -2.36
    (13.32)
    0.00
    (20.46)
    5.33
    (14.81)
    -9.00
    (0)
    QTcF Durations Fridericia's Correction Formula Cycle 1 Day 5 (PREDOSE)
    -10.47
    (14.17)
    -9.25
    (8.96)
    -3.20
    (14.60)
    -3.00
    (0)
    QTcF Durations Fridericia's Correction Formula Cycle 1 Day 5 (4 H)
    -0.08
    (26.39)
    4.00
    (8.98)
    -2.00
    (17.36)
    -4.00
    (0)
    QTcF Durations Fridericia's Correction Formula Cycle 1 Day 5 (6 H)
    -7.85
    (13.44)
    -2.25
    (8.46)
    1.60
    (14.10)
    6.00
    (0)
    QTcF Durations Fridericia's Correction Formula Cycle 2 Day 1 (PREDOSE)
    3.36
    (10.49)
    8
    (20.51)
    6.83
    (12.45)
    -11.00
    (0)
    QTcF Durations Fridericia's Correction Formula Cycle 3 Day 1 (PREDOSE)
    -11.00
    (0)
    QTcF Durations Fridericia's Correction Formula Cycle 3 Day 1 (4 H)
    0.00
    (0)
    QTcF Durations Fridericia's Correction Formula Cycle 3 Day 1 (6 H)
    4.00
    (0)
    QTcF Durations Fridericia's Correction Formula Cycle 4 Day 1 (PREDOSE)
    -45.00
    (0)
    QTcF Durations Fridericia's Correction Formula Cycle 4 Day 1 (4 H)
    -45.00
    (0)
    RR Duration Baseline
    861.47
    (133.95)
    881.00
    (151.46)
    835.83
    (139.93)
    779.00
    (0)
    RR Duration Cycle 1 Day 1 4 H
    -38.87
    (130.21)
    -5.60
    (58.23)
    -36.50
    (66.76)
    292.00
    (0)
    RR Duration Cycle 1 Day 1 6 H
    -65.67
    (117.44)
    14.00
    (100.82)
    -31.17
    (49.04)
    130.00
    (0)
    RR Duration Cycle 1 Day 2 (PREDOSE)
    28.00
    (0)
    18.00
    (0)
    RR Duration Cycle 1 Day 2 (24 H)
    -51.50
    (121.75)
    17.25
    (65.17)
    8.83
    (29.78)
    54.00
    (0)
    RR Duration Cycle 1 Day 5 (PREDOSE)
    25.87
    (97.32)
    -0.75
    (104.53)
    67.80
    (78.89)
    43.00
    (0)
    RR Duration Cycle 1 Day 5 (4 H)
    -26.23
    (114.00)
    79.75
    (62.99)
    24.20
    (114.05)
    -47.00
    (0)
    RR Duration Cycle 1 Day 5 (6 H)
    -21.46
    (121.82)
    49.50
    (99.21)
    33.00
    (59.05)
    -56.00
    (0)
    RR Duration Cycle 2 Day 1 (PREDOSE)
    7.14
    (118.26)
    23.75
    (86.53)
    78.17
    (59.85)
    144.00
    (0)
    RR Duration Cycle 3 Day 1 (PREDOSE)
    48.00
    (0)
    RR Duration Cycle 3 Day 1 (4 H)
    -59.00
    (0)
    RR Duration Cycle 3 Day 1 (6 H)
    -43.00
    (0)
    RR Duration Cycle 4 Day 1 (PREDOSE)
    182.00
    (0)
    RR Duration Cycle 4 Day 1 (4 H)
    182.00
    (0)
    22. Secondary Outcome
    Title Change From Baseline in Heart Rate, as Measured by Electrocardiogram
    Description Single 12-lead ECGs was obtained using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTc intervals. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The study was pre-maturely terminated by the sponsor's decision due to non-transformative efficacy and poor long-term tolerability of the dosing schedule as well as due to chronic gastrointestinal toxicity, therefore did not reach the planned end of study.
    Time Frame Baseline, Cycle 1 (Day 1, hours 4 and 6, Day 2 pre-dose and 24 Hour, Day 5 pre-dose, 4 and 6 Hour), Cycle 2 (Day 1 pre-dose only), Cycle 3 (Day 1 pre-dose, 4 and 6 Hour), Cycle 4 (Day 1 pre-dose and 4 Hour)

    Outcome Measure Data

    Analysis Population Description
    Safety-Evaluable Participants. The number analyzed includes participants who were evaluable at each timepoint.
    Arm/Group Title Ruxolitinib-naïve Participants With Splenomegaly Ruxolitinib-naïve Participants Without Splenomegaly Ruxolitinib-Resistant or Intolerant Participants With Splenomegaly Ruxolitinib-Resistant or Intolerant Participants Without Splenomegaly
    Arm/Group Description Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years). Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years). Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years). Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years).
    Measure Participants 15 5 6 1
    Baseline
    71.47
    (12.74)
    69.80
    (12.28)
    73.17
    (10.07)
    77.00
    (0)
    Cycle 1, Day 1, 4 Hour
    4.40
    (10.58)
    0.60
    (5.32)
    2.50
    (4.23)
    -21.00
    (0)
    Cycle 1, Day 1, 6 Hour
    6.20
    (10.35)
    -0.60
    (8.65)
    3.00
    (5.44)
    -11.00
    (0)
    Cycle 1 Day 2, pre-dose
    -3.00
    (0)
    -1.00
    (0)
    Cycle 1 Day 2, 24 Hour
    4.71
    (10.31)
    -1.75
    (5.32)
    -0.67
    (2.50)
    -5.00
    (0)
    Cycle 1 Day 5, pre-dose
    -1.47
    (6.56)
    -0.75
    (8.14)
    -5.60
    (5.27)
    -4.00
    (0)
    Cycle 1 Day 5, 4 hour
    2.69
    (8.61)
    -5.00
    (2.94)
    -2.20
    (7.92)
    5.00
    (0)
    Cycle 1 Day 5, 6 hour
    2.23
    (9.39)
    -3.75
    (7.76)
    -2.80
    (4.92)
    6.00
    (0)
    Cycle 2, Day 1, pre-dose
    -1.43
    (9.83)
    -1.50
    (8.39)
    -6.17
    (5.19)
    -12.00
    (0)
    Cycle 3 Day 1, pre-dose
    -5.00
    (0)
    Cycle 3 Day 1, 4 hour
    7.00
    (0)
    Cycle 3 Day 1, 6 hour
    5.00
    (0)
    Cycle 4 Day 1, pre-dose
    -16.00
    (0)
    Cycle 4 Day 1, 4 hour
    -16.00
    (0)
    23. Secondary Outcome
    Title Change From Baseline in Oral Temperature
    Description Vital signs were measured prior to the infusion while the participant was in a seated position. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The study was pre-maturely terminated by the sponsor's decision, therefore did not reach the end of study.
    Time Frame Baseline, Cycle 1 (Days 15 and 22), Cycle 2 and 3 (Days 1 and 15), Each Cycle 4-23 (Day 1 only) and Final Visit

    Outcome Measure Data

    Analysis Population Description
    Safety-Evaluable Participants. The number analyzed includes participants who were evaluable at each timepoint.
    Arm/Group Title Ruxolitinib-naïve Participants With Splenomegaly Ruxolitinib-naïve Participants Without Splenomegaly Ruxolitinib-Resistant or Intolerant Participants With Splenomegaly Ruxolitinib-Resistant or Intolerant Participants Without Splenomegaly
    Arm/Group Description Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years). Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years). Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years). Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years).
    Measure Participants 15 5 6 1
    Baseline
    36.50
    (0.37)
    36.40
    (0.25)
    36.47
    (0.28)
    37.10
    (0)
    Cycle 1 Day 15
    0.13
    (0.33)
    0.42
    (0.50)
    0.18
    (0.32)
    -0.30
    (0)
    Cycle 1 Day 22
    0.03
    (0.18)
    0.04
    (0.29)
    0.15
    (0.21)
    -0.50
    (0)
    Cycle 2 Day 1
    -0.05
    (0.28)
    0.05
    (0.30)
    0.17
    (0.34)
    -0.60
    (0)
    Cycle 2 Day 15
    0.04
    (0.27)
    0.18
    (0.24)
    0.23
    (0.38)
    -0.30
    (0)
    Cycle 3 Day 1
    -0.09
    (0.36)
    0.13
    (0.45)
    0.17
    (0.43)
    0.10
    (0)
    Cycle 3 Day 15
    -0.04
    (0.31)
    -0.03
    (0.06)
    0.10
    (0.26)
    -0.20
    (0)
    Cycle 4 Day 1
    -0.05
    (0.26)
    -0.17
    (0.15)
    0.06
    (0.37)
    -0.50
    (0)
    Cycle 5 Day 1
    0.05
    (0.16)
    -0.10
    (0.36)
    0.10
    (0.32)
    -0.80
    (0)
    Cycle 6 Day 1
    -0.03
    (0.16)
    -0.10
    (0.45)
    0.12
    (0.16)
    -0.40
    (0)
    Cycle 7 Day 1
    0.01
    (0.30)
    -0.20
    (0.28)
    0.20
    (0.26)
    -0.60
    (0)
    Cycle 8 Day 1
    -0.01
    (0.20)
    -0.05
    (0.64)
    0.20
    (0.36)
    -0.30
    (0)
    Cycle 9 Day 1
    0.03
    (0.13)
    0.05
    (0.35)
    -0.07
    (0.42)
    -0.40
    (0)
    Cycle 10 Day 1
    -0.08
    (0.10)
    0.30
    (0.42)
    0.10
    (0.35)
    -0.60
    (0)
    Cycle 11 Day 1
    -0.07
    (0.19)
    -0.20
    (0)
    -0.10
    (0.14)
    -0.40
    (0)
    Cycle 12 Day 1
    -0.10
    (0.16)
    0.30
    (0)
    -0.20
    (0.14)
    -0.70
    (0)
    Cycle 13 Day 1
    0.00
    (0.19)
    -0.70
    (0)
    0
    -0.70
    (0)
    Cycle 14 Day 1
    0.00
    (0.41)
    -0.10
    (0)
    -0.30
    (0)
    -0.70
    (0)
    Cycle 15 Day 1
    -0.10
    (0.14)
    -0.30
    (0)
    -0.40
    (0)
    -0.50
    (0)
    Cycle 16 Day 1
    0.03
    (0.30)
    -0.80
    (0)
    -0.10
    (0)
    -0.50
    (0)
    Cycle 17 Day 1
    0.03
    (0.12)
    0.60
    (0)
    0.00
    (60)
    -0.80
    (0)
    Cycle 18 Day 1
    0.07
    (0.15)
    -0.20
    (0)
    -0.80
    (0)
    Cycle 19 Day 1
    -0.15
    (0.21)
    0
    -0.50
    (0)
    Cycle 20 Day 1
    0.00
    (0.14)
    0
    -0.50
    (0)
    Cycle 21 Day 1
    0
    (0)
    -0.40
    (0)
    Cycle 22 Day 1
    -0.50
    (0)
    -0.70
    (0)
    Cycle 23 Day 1
    -0.80
    (0)
    Final Visit
    -0.08
    (0.15)
    0.26
    (0.26)
    0.08
    (0.37)
    -0.50
    (0)
    24. Secondary Outcome
    Title Change From Baseline in Pulse Rate
    Description Vital signs were measured prior to the infusion while the participant was in a seated position. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The study was pre-maturely terminated by the sponsor's decision due to non-transformative efficacy and poor long-term tolerability of the dosing schedule as well as due to chronic gastrointestinal toxicity, therefore did not reach the planned end of study.
    Time Frame Baseline, Cycle 1 (Days 15 and 22), Cycle 2 and 3 (Days 1 and 15), Each Cycle 4-23 (Day 1 only) and Final Visit

    Outcome Measure Data

    Analysis Population Description
    Safety-Evaluable Participants. The number analyzed includes participants who were evaluable at each timepoint.
    Arm/Group Title Ruxolitinib-naïve Participants With Splenomegaly Ruxolitinib-naïve Participants Without Splenomegaly Ruxolitinib-Resistant or Intolerant Participants With Splenomegaly Ruxolitinib-Resistant or Intolerant Participants Without Splenomegaly
    Arm/Group Description Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years). Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years). Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years). Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years).
    Measure Participants 15 5 6 1
    Baseline
    74.7
    (12.3)
    71.6
    (9.2)
    76.7
    (14.1)
    68.0
    (0)
    Cycle 1 Day 15
    4.5
    (13.2)
    5.4
    (5.5)
    -0.7
    (4.8)
    7.0
    (0)
    Cycle 1 Day 22
    3.9
    (11.3)
    8.2
    (4.9)
    -5.8
    (3.9)
    8.0
    (0)
    Cycle 2 Day 1
    -1.1
    (8.6)
    1.8
    (8.7)
    -9.3
    (6.1)
    12.0
    (0)
    Cycle 2 Day 15
    0.1
    (11.0)
    1.8
    (8.5)
    -5.8
    (5.5)
    9.0
    (0)
    Cycle 3 Day 1
    -2.8
    (9.4)
    -2.0
    (8.6)
    -4.2
    (9.9)
    9.0
    (0)
    Cycle 3 Day 15
    -1.2
    (9.7)
    10.8
    (13.6)
    -2.2
    (11.0)
    21.0
    (0)
    Cycle 4 Day 1
    1.0
    (11.2)
    1.7
    (9.9)
    -6.6
    (9.8)
    24.0
    (0)
    Cycle 5 Day 1
    0.6
    (8.4)
    -4.0
    (9.3)
    -3.6
    (4.2)
    28.0
    (0)
    Cycle 6 Day 1
    0.4
    (9.1)
    -4.3
    (6.8)
    -1.6
    (6.8)
    14.0
    (0)
    Cycle 7 Day 1
    1.4
    (14.6)
    1.5
    (16.3)
    -1.0
    (9.8)
    21.0
    (0)
    Cycle 8 Day 1
    -3.9
    (13.3)
    -1.0
    (12.7)
    0.5
    (3.1)
    11.0
    (0)
    Cycle 9 Day 1
    -5.4
    (6.4)
    0.0
    (5.7)
    0.3
    (2.5)
    0
    (0)
    Cycle 10 Day 1
    -0.3
    (9.9)
    8.5
    (19.1)
    2.3
    (8.5)
    20.0
    (0)
    Cycle 11 Day 1
    -2.5
    (11.5)
    -2.0
    (0)
    2.5
    (0.7)
    37.0
    (0)
    Cycle 12, Day 1
    -0.2
    (11.6)
    -6.0
    (0)
    -1.0
    (4.2)
    21.0
    (0)
    Cycle 13, Day 1
    -2.8
    (7.8)
    -5.0
    (0)
    -1.0
    (0)
    16.0
    (0)
    Cycle 14, Day 1
    -3.8
    (11.1)
    -2.0
    (0)
    -4.0
    (0)
    12.0
    (0)
    Cycle 15 Day 1
    -0.8
    (10.4)
    10.0
    (0)
    -2.0
    (0)
    14.0
    (0)
    Cycle 16 Day 1
    -1.3
    (15.6)
    -2.0
    (0)
    -2.0
    (0)
    16.0
    (0)
    Cycle 17, Day 1
    -12.7
    (9.5)
    9.0
    (0)
    1.0
    (0)
    22.0
    (0)
    Cycle 18, Day 1
    -4.3
    (3.5)
    -3.0
    (0)
    16.0
    (0)
    Cycle 19, Day 1
    -9.0
    (5.7)
    6.0
    (0)
    15.0
    (0)
    Cycle 20, Day 1
    -5.0
    (9.9)
    4.0
    (0)
    5.0
    (0)
    Cycle 21, Day 1
    2.0
    (0)
    17.0
    (0)
    Cycle 22, Day 1
    -8.0
    (0)
    14
    (0)
    Cycle 23, Day 1
    19.0
    (0)
    Final Visit
    -1.7
    (12.2)
    0.2
    (11.6)
    0.2
    (10.1)
    16.0
    (0)
    25. Secondary Outcome
    Title Change From Baseline in Respiratory Rate
    Description Vital signs were measured prior to the infusion while the participant was in a seated position. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The study was pre-maturely terminated by the sponsor's decision due to non-transformative efficacy and poor long-term tolerability of the dosing schedule as well as due to chronic gastrointestinal toxicity, therefore did not reach the planned end of study.
    Time Frame Baseline, Cycle 1 (Days 15 and 22), Cycle 2 and 3 (Days 1 and 15), Each Cycle 4-23 (Day 1 only) and Final Visit

    Outcome Measure Data

    Analysis Population Description
    Safety-Evaluable Participants. The number analyzed includes participants who were evaluable at each timepoint.
    Arm/Group Title Ruxolitinib-naïve Participants With Splenomegaly Ruxolitinib-naïve Participants Without Splenomegaly Ruxolitinib-Resistant or Intolerant Participants With Splenomegaly Ruxolitinib-Resistant or Intolerant Participants Without Splenomegaly
    Arm/Group Description Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years). Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years). Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years). Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years).
    Measure Participants 15 5 6 1
    Baseline
    17.4
    (2.0)
    17.4
    (1.9)
    18.2
    (2.6)
    16.0
    (0)
    Cycle 1 Day 15
    -0.3
    (1.0)
    -0.2
    (1.8)
    -0.2
    (1.8)
    0
    (0)
    Cycle 1 Day 22
    -0.5
    (0.8)
    0.2
    (0.4)
    -0.5
    (2.2)
    0
    (0)
    Cycle 2 Day 1
    -0.3
    (1.5)
    -0.3
    (1.7)
    -0.4
    (1.7)
    0
    (0)
    Cycle 2 Day 15
    -0.2
    (1.0)
    0.0
    (0.8)
    -1.2
    (1.8)
    2.0
    (0)
    Cycle 3 Day 1
    -0.7
    (1.3)
    -1.5
    (3.1)
    -1.8
    (1.8)
    0
    (0)
    Cycle 3 Day 15
    -0.7
    (1.3)
    0.0
    (1.0)
    -1.0
    (1.0)
    0
    (0)
    Cycle 4 Day 1
    -0.3
    (1.3)
    -3.3
    (4.2)
    -1.0
    (1.0)
    2.0
    (0)
    Cycle 5 Day 1
    -0.4
    (1.9)
    -0.3
    (0.6)
    1.0
    (2.2)
    0
    (0)
    Cycle 6 Day 1
    -0.5
    (1.3)
    -0.5
    (1.9)
    -0.6
    (1.3)
    2.0
    (0)
    Cycle 7 Day 1
    -0.2
    (1.7)
    0
    (0)
    -2.3
    (1.5)
    2.0
    (0)
    Cycle 8 Day 1
    0.1
    (1.5)
    -0.5
    (2.1)
    -0.8
    (3.8)
    0
    (0)
    Cycle 9 Day 1
    0.4
    (1.8)
    0.5
    (0.7)
    -1.7
    (6.0)
    -2.0
    (0)
    Cycle 10 Day 1
    -0.2
    (1.6)
    -0.5
    (2.1)
    -0.3
    (5.5)
    0
    (0)
    Cycle 11 Day 1
    -0.8
    (1.0)
    1.0
    (0)
    -0.5
    (0.7)
    2.0
    (0)
    Cycle 12 Day 1
    -0.4
    (1.5)
    1.0
    (0)
    1.5
    (0.7)
    0
    (0)
    Cycle 13 Day 1
    -1.4
    (2.8)
    1.0
    (0)
    -1.0
    (0)
    2.0
    (0)
    Cycle 14 Day 1
    0.8
    (2.3)
    1.0
    (0)
    1.0
    (0)
    0
    (0)
    Cycle 15 Day 1
    0.0
    (1.4)
    1.0
    (0)
    -1.0
    (0)
    0
    (0)
    Cycle 16 Day 1
    -0.3
    (1.3)
    1.0
    (0)
    -2.0
    (0)
    0
    (0)
    Cycle 17 Day 1
    1.3
    (2.3)
    1.0
    (0)
    -2.0
    (0)
    0
    (0)
    Cycle 18 Day 1
    1.3
    (2.3)
    -1.0
    (0)
    2.0
    (0)
    Cycle 19 Day 1
    1.5
    (2.1)
    -3.0
    (0)
    2.0
    (0)
    Cycle 20 Day 1
    2.0
    (2.8)
    -3.0
    (0)
    2.0
    (0)
    Cycle 21 Day 1
    2.0
    (0)
    0
    (0)
    Cycle 22 Day 1
    0.0
    (0)
    0
    (0)
    Cycle 23 Day 1
    0
    (0)
    Final visit
    -0.3
    (1.5)
    -1.2
    (1.5)
    -1.8
    (1.8)
    0
    (0)
    26. Secondary Outcome
    Title Change From Baseline in Systolic Blood Pressure
    Description Vital signs were measured prior to the infusion while the participant was in a seated position. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The study was pre-maturely terminated by the sponsor's decision due to non-transformative efficacy and poor long-term tolerability of the dosing schedule as well as due to chronic gastrointestinal toxicity, therefore did not reach the planned end of study.
    Time Frame Baseline, Cycle 1 (Days 15 and 22), Cycle 2 and 3 (Days 1 and 15), Each Cycle 4-23 (Day 1 only) and Final Visit

    Outcome Measure Data

    Analysis Population Description
    Safety-Evaluable Participants. The number analyzed includes participants who were evaluable at each timepoint.
    Arm/Group Title Ruxolitinib-naïve Participants With Splenomegaly Ruxolitinib-naïve Participants Without Splenomegaly Ruxolitinib-Resistant or Intolerant Participants With Splenomegaly Ruxolitinib-Resistant or Intolerant Participants Without Splenomegaly
    Arm/Group Description Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years). Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years). Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years). Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years).
    Measure Participants 15 5 6 1
    Baseline
    129.3
    (11.5)
    132.0
    (17.2)
    122.3
    (16.9)
    106.0
    (0)
    Cycle 1, Day 15
    4.4
    (9.9)
    3.6
    (13.6)
    3.8
    (15.1)
    5.0
    (0)
    Cycle 1, Days 22
    3.3
    (9.4)
    -5.6
    (11.8)
    4.8
    (10.1)
    -5.0
    (0)
    Cycle 2, Day 1
    3.0
    (10.3)
    2.8
    (8.4)
    -4.3
    (7.9)
    10.0
    (0)
    Cycle 2 , Day 15
    5.2
    (9.8)
    -2.0
    (13.6)
    -7.2
    (9.6)
    30.0
    (0)
    Cycle 3, Day 1
    5.5
    (10.8)
    -3.0
    (9.8)
    7.3
    (18.3)
    0
    (0)
    Cycle 3, Day 15
    1.2
    (11.2)
    -3.5
    (14.2)
    -3.8
    (16.7)
    6.0
    (0)
    Cycle 4, Day 1
    2.2
    (9.1)
    -7.3
    (9.3)
    9.8
    (8.1)
    13.0
    (0)
    Cycle 5, Day 1
    4.2
    (10.5)
    -2.5
    (6.8)
    3.3
    (6.9)
    16.0
    (0)
    Cycle 6 Day 1
    11.2
    (13.0)
    2.5
    (9.7)
    8.6
    (10.8)
    8.0
    (0)
    Cycle 7 Day 1
    4.7
    (4.2)
    -4.0
    (15.6)
    10.0
    (5.0)
    29.0
    (0)
    Cycle 8 Day 1
    8.8
    (9.0)
    5.0
    (7.1)
    14.0
    (18.8)
    9.0
    (0)
    Cycle 9 Day 1
    12.6
    (8.3)
    3.0
    (9.9)
    -4.3
    (4.9)
    26.0
    (0)
    Cycle 10 Day 1
    11.8
    (9.9)
    -3.0
    (2.8)
    11.0
    (13.2)
    30.0
    (0)
    Cycle 11 Day 1
    8.5
    (12.3)
    14.0
    (0)
    11.0
    (12.7)
    34.0
    (0)
    Cycle 12 Day 1
    10.8
    (11.5)
    -8.0
    (0)
    6.5
    (3.5)
    6.0
    (0)
    Cycle 13 Day 1
    13.4
    (5.1)
    -8.0
    (0)
    8.0
    (0)
    14.0
    (0)
    Cycle 14 Day 1
    4.4
    (14.7)
    18.0
    (0)
    3.0
    (0)
    14.0
    (0)
    Cycle 15 Day 1
    13.6
    (7.5)
    14.0
    (0)
    4.0
    (0)
    5.0
    (0)
    Cycle 16 Day 1
    7.5
    (8.6)
    8.0
    (0)
    9.0
    (0)
    4.0
    (0)
    Cycle 17 Day 1
    9.3
    (5.8)
    24.0
    (0)
    7.0
    (0)
    6.0
    (0)
    Cycle 18 Day 1
    5.7
    (4.2)
    9.0
    (0)
    13.0
    (0)
    Cycle 19 Day 1
    2.5
    (3.5)
    9.0
    (0)
    13.0
    (0)
    Cycle 20 Day 1
    11.5
    (9.2)
    9.0
    (0)
    13.0
    (0)
    Cycle 21 Day 1
    -18.0
    (0)
    7.0
    (0)
    Cycle 22 Day 1
    24.0
    (0)
    6.0
    (0)
    Cycle 23 Day 1
    11.0
    (0)
    Final Visit
    1.3
    (9.7)
    7.6
    (16.2)
    12.8
    (23.9)
    19.0
    (0)
    27. Secondary Outcome
    Title Change From Baseline in Diastolic Blood Pressure
    Description Vital signs were measured prior to the infusion while the participant was in a seated position. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. The study was pre-maturely terminated by the sponsor's decision due to non-transformative efficacy and poor long-term tolerability of the dosing schedule as well as due to chronic gastrointestinal toxicity, therefore did not reach the planned end of study.
    Time Frame Baseline, Cycle 1 (Days 15 and 22), Cycle 2 and 3 (Days 1 and 15), Each Cycle 4-23 (Day 1 only) and Final Visit

    Outcome Measure Data

    Analysis Population Description
    Safety-Evaluable Participants. The number analyzed includes participants who were evaluable at each timepoint.
    Arm/Group Title Ruxolitinib-naïve Participants With Splenomegaly Ruxolitinib-naïve Participants Without Splenomegaly Ruxolitinib-Resistant or Intolerant Participants With Splenomegaly Ruxolitinib-Resistant or Intolerant Participants Without Splenomegaly
    Arm/Group Description Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years). Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years). Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years). Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years).
    Measure Participants 15 5 6 1
    Baseline
    76.3
    (7.8)
    73.2
    (5.2)
    72.3
    (9.0)
    65.0
    (0)
    Cycle1, Day 15
    5.1
    (8.7)
    10.0
    (8.7)
    -1.8
    (3.4)
    0.0
    (0)
    Cycle 1, Day 22
    3.6
    (6.1)
    2.4
    (3.2)
    -2.2
    (5.8)
    -1.0
    (0)
    Cycle 2, Day 1
    6.1
    (8.3)
    3.0
    (2.9)
    -0.2
    (9.3)
    3.0
    (0)
    Cycle 2, Day 15
    4.1
    (6.3)
    2.5
    (9.7)
    -5.5
    (3.4)
    16.0
    (0)
    Cycle 3 Day 1
    6.2
    (8.1)
    5.8
    (10.0)
    -4.0
    (12.4)
    5.0
    (0)
    Cycle 3, Day 15
    1.8
    (10.5)
    2.0
    (10.1)
    -7.5
    (7.0)
    8.0
    (0)
    Cycle 4, Day 1
    5.5
    (5.7)
    2.7
    (6.8)
    -0.4
    (5.0)
    1.0
    (0)
    Cycle 5, Day 1
    1.7
    (6.1)
    5.0
    (5.8)
    -5.0
    (4.5)
    1.0
    (0)
    Cycle 6, Day 1
    5.9
    (4.5)
    3.3
    (11.1)
    -2.0
    (9.5)
    12.0
    (0)
    Cycle 7, Day 1
    2.9
    (4.8)
    4.5
    (13.4)
    -5.3
    (9.0)
    30.0
    (0)
    Cycle 8, Day 1
    7.8
    (5.4)
    5.0
    (7.1)
    0.5
    (12.3)
    10.0
    (0)
    Cycle 9, Day 1
    4.1
    (8.4)
    4.0
    (5.7)
    -2.7
    (1.5)
    4.0
    (0)
    Cycle 10, Day 1
    3.7
    (5.9)
    5.0
    (0)
    -2.3
    (10.1)
    3.0
    (0)
    Cycle 11, Day 1
    9.7
    (14.1)
    10.0
    (0)
    1.0
    (7.1)
    24.0
    (0)
    Cycle 12, Day 1
    9.8
    (8.6)
    6.0
    (0)
    2.0
    (4.2)
    8.0
    (0)
    Cycle 13, Day 1
    9.0
    (7.6)
    4.0
    (0)
    2.0
    (0)
    10.0
    (0)
    Cycle 14, Day 1
    5.6
    (5.1)
    19.0
    (0)
    -9.0
    (0)
    11.0
    (0)
    Cycle 15, Day 1
    7.0
    (8.0)
    10.0
    (0)
    -2.0
    (0)
    7.0
    (0)
    Cycle 16, Day 1
    9.8
    (7.8)
    11.0
    (0)
    7.0
    (0)
    6.0
    (0)
    Cycle 17, Day 1
    11.3
    (3.5)
    11.0
    (0)
    3.0
    (0)
    7.0
    (0)
    Cycle 18, Day 1
    5.0
    (1.7)
    -2.0
    (0)
    3.0
    (0)
    Cycle 19, Day 1
    4.0
    (5.7)
    5.0
    (0)
    8.0
    (0)
    Cycle 20, Day 1
    12.5
    (3.5)
    -1.0
    (0)
    2.0
    (0)
    Cycle 21, Day 1
    -3.0
    (0)
    7.0
    (0)
    Cycle 22, Day 1
    22.0
    (0)
    8.0
    (0)
    Cycle 23, Day 1
    7.0
    (0)
    Final visit
    5.8
    (9.0)
    3.8
    (14.0)
    -2.0
    (12.6)
    11.0
    (0)
    28. Secondary Outcome
    Title Eastern Cooperative Oncology Group (ECOG) Performance Status Over Time
    Description The ECOG performance status is a scale used to quantify cancer patients' general well-being and activities of daily life. The scale ranges from 0 to 5, with 0 denoting perfect health and 5 indicating death. The 6 categories are 0=Asymptomatic (Fully active, able to carry on all pre-disease activities without restriction), 1=Symptomatic but completely ambulatory, 2=Symptomatic, < 50% in bed during the day (Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours), 3=Symptomatic, > 50% in bed, but not bedbound (Capable of only limited self-care, confined to bed or chair 50% or more of waking hours), 4=Bedbound (Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair), 5=Death. Only baseline data were collectable. The study was pre-maturely terminated by the sponsor's decision, therefore did not reach the planned end of study.
    Time Frame Baseline

    Outcome Measure Data

    Analysis Population Description
    Safety-Evaluable Patients. The number analyzed includes participants who were evaluable at each timepoint.
    Arm/Group Title Ruxolitinib-naïve Participants With Splenomegaly Ruxolitinib-naïve Participants Without Splenomegaly Ruxolitinib-Resistant or Intolerant Participants With Splenomegaly Ruxolitinib-Resistant or Intolerant Participants Without Splenomegaly
    Arm/Group Description Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years). Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years). Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years). Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years).
    Measure Participants 15 5 6 1
    Baseline 0
    66.7
    60.0
    50.0
    100.0
    Baseline 1
    33.3
    40.0
    50.0
    0
    29. Secondary Outcome
    Title Percentage of Participants With Concomitant Medications
    Description Participants with Concomitant Medications used from 28 days prior to screening until the final visit or end of study (EOS) were reported. The result data not derived due to early termination of the study by the sponsor's decision and did not reach the end of study.
    Time Frame Overall Study Period

    Outcome Measure Data

    Analysis Population Description
    Safety-Evaluable Population. The number analyzed includes participants who were evaluable at each timepoint.
    Arm/Group Title Ruxolitinib-naïve Participants With Splenomegaly Ruxolitinib-naïve Participants Without SplenomegalyEdit Ruxolitinib-Resistant or Intolerant Participants With Splenomegaly Ruxolitinib-Resistant or Intolerant Participants Without Splenomegaly
    Arm/Group Description Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years). Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years). t Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years). Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years).
    Measure Participants 15 5 6 1
    Number [Percentage of Participants]
    100
    666.7%
    100
    2000%
    100
    1666.7%
    100
    10000%
    30. Secondary Outcome
    Title Maximum Serum Concentration Observed (Cmax) of Idasanutlin
    Description Cmax is the maximum observed concentration of drug in blood. The result data not derived due to early termination of the study by the sponsor's decision and did not reach the end of study.
    Time Frame Days 1, 2, and 5 of Cycles 1 and 4

    Outcome Measure Data

    Analysis Population Description
    The study plan was to determine Cmax as part of the pharmacokinetics, however study was terminated prematurely in the initial phase after 27 patients were recruited due to non-transformative efficacy and poor long-term tolerability of the dosing schedule as well as due to chronic gastrointestinal toxicity leading to high dropout rate in participants. Therefore, no participants were available for this endpoint and result data were not collected.
    Arm/Group Title Ruxolitinib-Naïve ParticipantsEditEdit Ruxolitinib-Resistant or Intolerant Participants
    Arm/Group Description Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years). Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years)
    Measure Participants 0 0
    31. Secondary Outcome
    Title Trough Concentration (Ctrough) of Idasanutlin
    Description Ctrough is the measured concentration of a drug at the end of a dosing interval at steady state. The result data not derived due to early termination of the study by the sponsor's decision and did not reach the end of study.
    Time Frame Days 1, 2, and 5 of Cycles 1 and 4

    Outcome Measure Data

    Analysis Population Description
    The study plan was to determine Ctrough as part of the pharmacokinetics, however study was terminated prematurely in the initial phase after 27 patients were recruited due to non-transformative efficacy and poor long-term tolerability of the dosing schedule as well as due to chronic gastrointestinal toxicity leading to high dropout rate in participants. Therefore, no participants were available for this endpoint and result data were not collected.
    Arm/Group Title Ruxolitinib-Naïve Participants Ruxolitinib-Resistant or Intolerant Participants
    Arm/Group Description Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years). Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years)
    Measure Participants 0 0
    32. Secondary Outcome
    Title Time of Maximum Concentration Observed (Tmax) of Idasanutlin
    Description Tmax is the time elapsed from the time of drug administration to maximum plasma concentration. The result data not derived due to early termination of the study by the sponsor's decision and did not reach the end of study.
    Time Frame Days 1, 2, and 5 of Cycles 1 and 4

    Outcome Measure Data

    Analysis Population Description
    The study plan was to determine tmax as part of the pharmacokinetics, however study was terminated prematurely in the initial phase after 27 patients were recruited due to non-transformative efficacy and poor long-term tolerability of the dosing schedule as well as due to chronic gastrointestinal toxicity leading to high dropout rate in participants. Therefore, no participants were available for this endpoint and result data were not collected.
    Arm/Group Title Ruxolitinib-Naïve Participants Ruxolitinib-Resistant or Intolerant Participants
    Arm/Group Description Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years). Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years)
    Measure Participants 0 0
    33. Secondary Outcome
    Title Clearance (CL) of Idasanutlin
    Description CL is a measure of the body's elimination of a drug from plasma over time. The result data not derived due to early termination of the study by the sponsor's decision and did not reach the end of study.
    Time Frame Days 1, 2, and 5 of Cycles 1 and 4

    Outcome Measure Data

    Analysis Population Description
    The study plan was to determine CL as part of the pharmacokinetics, however study was terminated prematurely in the initial phase after 27 patients were recruited due to non-transformative efficacy and poor long-term tolerability of the dosing schedule as well as due to chronic gastrointestinal toxicity leading to high dropout rate in participants. Therefore, no participants were available for this endpoint and result data were not collected.
    Arm/Group Title Ruxolitinib-Naïve Participants Ruxolitinib-Resistant or Intolerant Participants
    Arm/Group Description Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years). Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years)
    Measure Participants 0 0
    34. Secondary Outcome
    Title Apparent Clearance (CL/F) of Idasanutlin
    Description CL/F is a measure of the body's elimination of a drug from plasma over time, after oral administration. The result data not derived due to early termination of the study by the sponsor's decision and did not reach the end of study.
    Time Frame Days 1, 2, and 5 of Cycles 1 and 4

    Outcome Measure Data

    Analysis Population Description
    The study plan was to determine CL/F as part of the pharmacokinetics, however study was terminated prematurely in the initial phase after 27 patients were recruited due to non-transformative efficacy and poor long-term tolerability of the dosing schedule as well as due to chronic gastrointestinal toxicity leading to high dropout rate in participants. Therefore, no participants were available for this endpoint and result data were not collected.
    Arm/Group Title Ruxolitinib-Naïve Participants Ruxolitinib-Resistant or Intolerant Participants
    Arm/Group Description Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years). Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years)
    Measure Participants 0 0
    35. Secondary Outcome
    Title Volume or Apparent Volume of Distribution (Vdss/F) of Idasanutlin
    Description Vdss/F is the theoretical volume that would be necessary to contain the total amount of an administered drug at the same concentration that it is observed in the plasma. The result data not derived due to early termination of the study by the sponsor's decision and did not reach the end of study.
    Time Frame Days 1, 2, and 5 of Cycles 1 and 4

    Outcome Measure Data

    Analysis Population Description
    The study plan was to determine Vdss/F as part of the pharmacokinetics, however study was terminated prematurely in the initial phase after 27 patients were recruited due to non-transformative efficacy and poor long-term tolerability of the dosing schedule as well as due to chronic gastrointestinal toxicity leading to high dropout rate in participants. Therefore, no participants were available for this endpoint and result data were not collected.
    Arm/Group Title Ruxolitinib-Naïve Participants Ruxolitinib-Resistant or Intolerant Participants
    Arm/Group Description Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years). Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years)
    Measure Participants 0 0
    36. Secondary Outcome
    Title Area Under the Concentration-Time Curve (AUC) of Idasanutlin
    Description AUC (from zero to infinity) represents the total drug exposure over time. The result data not derived due to early termination of the study by the sponsor's decision and did not reach the end of study.
    Time Frame Days 1, 2, and 5 of Cycles 1 and 4

    Outcome Measure Data

    Analysis Population Description
    The study plan was to determine AUC as part of the pharmacokinetics, however study was terminated prematurely in the initial phase after 27 patients were recruited due to non-transformative efficacy and poor long-term tolerability of the dosing schedule as well as due to chronic gastrointestinal toxicity leading to high dropout rate in participants. Therefore, no participants were available for this endpoint and result data were not collected.
    Arm/Group Title Ruxolitinib-Naïve Participants Ruxolitinib-Resistant or Intolerant Participants
    Arm/Group Description Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years). Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years)
    Measure Participants 0 0
    37. Secondary Outcome
    Title Half-life (t1/2) of Idasanutlin
    Description t1/2 is defined as the time required for the drug plasma concentration to be reduced to half. The result data not derived due to early termination of the study by the sponsor's decision and did not reach the end of study.
    Time Frame Days 1, 2, and 5 of Cycles 1 and 4

    Outcome Measure Data

    Analysis Population Description
    The study plan was to determine t1/2 as part of the pharmacokinetics, however study was terminated prematurely in the initial phase after 27 patients were recruited due to non-transformative efficacy and poor long-term tolerability of the dosing schedule as well as due to chronic gastrointestinal toxicity leading to high dropout rate in participants. Therefore, no participants were available for this endpoint and result data were not collected.
    Arm/Group Title Ruxolitinib-Naïve Participants Ruxolitinib-Resistant or Intolerant Participants
    Arm/Group Description Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years). Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years)
    Measure Participants 0 0
    38. Secondary Outcome
    Title Baseline and Mean Change From Baseline Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS) Over Time
    Description MPN-SAF Total Symptom Score is the sum of the following 10 items: early satiety, abdominal discomfort, inactivity, concentration issues, night sweats, Itching, Bone pain, Fever and Unintentional weight loss last 6 months and fatigue. The participant provides a severity score for each symptom on a scale of 0 as a minimum score (none/absent) to 10 (worst imaginable) as a maximum score. Baseline (Cycle 1, Day 1) MPN-SAF total symptom score and the mean change from baseline score at each timepoint are reported. The change from baseline score was calculated by subtracting the post-baseline score from the baseline score. The study was pre-maturely terminated by the sponsor's decision due to non-transformative efficacy and poor long-term tolerability of the dosing schedule as well as due to chronic gastrointestinal toxicity, therefore did not reach the end of study.
    Time Frame Baseline (Cycle 1 Day 1), Cycle 2 Day 1, Days 28 of Cycles 3, 5, 8 (Week 32), 11, 14, 17 ) Day 28, Cycle 5 Day 28, End of Cycle 8 (Week 32), and Final Visit

    Outcome Measure Data

    Analysis Population Description
    ITT Population. The number analyzed includes participants who were evaluable at each timepoint.
    Arm/Group Title Ruxolitinib-Naïve Participants Ruxolitinib-Resistant or Intolerant Participants
    Arm/Group Description Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years). Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years).
    Measure Participants 20 7
    Baseline (Cycle 1 Day 1)
    31.95
    (19.95)
    26.00
    (11.83)
    Cycle 2 Day 1
    -5.06
    (12.91)
    0.80
    (26.37)
    Cycle 3 Day 28
    -6.38
    (12.71)
    -8.00
    (15.08)
    Cycle 5 Day 28,
    -7.00
    (12.72)
    -9.50
    (10.56)
    Week 32
    -8.20
    (12.79)
    -5.00
    (15.26)
    Cycle 11 Day 28
    -4.60
    (3.71)
    -7.50
    (3.54)
    Cycle 14 Day 28
    -4.67
    (5.54)
    -10.50
    (4.95)
    Cycle 17 Day 28
    -3.25
    (5.38)
    -12.00
    (1.41)
    Cycle 20 Day 28
    -12.00
    (0)
    -8.00
    (0)
    Final Visit
    -5.92
    (9.96)
    -7.20
    (5.63)
    39. Secondary Outcome
    Title Baseline and Mean Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores Over Time
    Description Reported EORTC QLQ-C30 Scores include: Cognitive function, Diarrhea Emotional functioning, Nausea and vomiting, Social functioning, Physical functioning, Global health status/QoL and Role functioning. The questions use a 4-point scale (1 'Not at all' to 4 'Very much'; 2 questions used 7-point scale [1 'very poor' to 7 'Excellent']). Scores are averaged and transformed to 0-100 scale; higher score=better level of functioning or greater degree of symptoms. The study was pre-maturely terminated by the sponsor's decision due to non-transformative efficacy and poor long-term tolerability of the dosing schedule as well as due to chronic gastrointestinal toxicity, therefore did not reach the end of study.
    Time Frame Baseline (Cycle 1 Day 1), Cycle 2 Day 1, Cycles 3, 5, 8, 11, 14, 17, 20 Day 28 and Final Visit

    Outcome Measure Data

    Analysis Population Description
    ITT Population. The number analyzed includes participants who were evaluable at each timepoint.
    Arm/Group Title Ruxolitinib-Naïve Participants Ruxolitinib-Resistant or Intolerant Participants
    Arm/Group Description Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years). Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years).
    Measure Participants 20 7
    EORTC QLQ-C30 Scores: Cognitive function Baseline
    65.83
    (32.21)
    76.19
    (30.21)
    EORTC QLQ-C30 Scores: Cognitive function Cycle 2, Day 1
    11.11
    (11.43)
    8.33
    (13.94)
    EORTC QLQ-C30 Scores: Cognitive function Cycle 3 Day 28
    7.02
    (16.02)
    6.67
    (19.00)
    EORTC QLQ-C30 Scores: Cognitive function Cycle 5 Day 28
    1.19
    (22.13)
    11.11
    (25.09)
    EORTC QLQ-C30 Scores: Cognitive function Cycle 8 (Week 32)
    6.06
    (18.67)
    -3.33
    (21.73)
    EORTC QLQ-C30 Scores: Cognitive function Cycle 11 Day 28
    8.33
    (13.94)
    0
    (0)
    EORTC QLQ-C30 Scores: Cognitive function Cycle 14 Day 28
    5.56
    (17.21)
    0
    (0)
    EORTC QLQ-C30 Scores: Cognitive function Cycle 17 Day 28
    0.00
    (13.61)
    -8.33
    (11.79)
    EORTC QLQ-C30 Scores: Cognitive function Cycle 20 Day 28
    0
    (0)
    0
    (0)
    EORTC QLQ-C30 Scores: Cognitive function Final Visit
    4.44
    (18.33)
    6.67
    (9.13)
    EORTC QLQ-C30 Scores: Diarrhea Baseline
    8.33
    (18.34)
    14.29
    (17.82)
    EORTC QLQ-C30 Scores: Diarrhea Cycle 2 Day 1
    -5.56
    (17.15)
    5.56
    (13.61)
    EORTC QLQ-C30 Scores: Diarrhea Cycle 3 Day 28
    1.75
    (17.48)
    0
    (0)
    EORTC QLQ-C30 Scores: Diarrhea Cycle 5 Day 28
    7.14
    (19.30)
    5.56
    (13.61)
    EORTC QLQ-C30 Scores: Diarrhea Cycle 8 (Week 32)
    9.09
    (26.21)
    20.00
    (18.26)
    EORTC QLQ-C30 Scores: Diarrhea Cycle 11 Day 28
    5.56
    (13.61)
    0
    (0)
    EORTC QLQ-C30 Scores: Diarrhea Cycle 14 Day 28
    5.56
    (13.61)
    0
    (0)
    EORTC QLQ-C30 Scores: Diarrhea Cycle 17 Day 28
    25.00
    (31.91)
    0
    (0)
    EORTC QLQ-C30 Scores: Diarrhea Cycle 20 Day 28
    0
    (0)
    0
    (0)
    EORTC QLQ-C30 Scores: Diarrhea Final visit
    13.33
    (32.85)
    6.67
    (14.91)
    EORTC QLQ-C30 Scores: Emotional functioning Baseline
    65.83
    (28.34)
    64.29
    (21.36)
    EORTC QLQ-C30 Scores: Emotional functioning Cycle 1 Day 28
    13.43
    (20.24)
    15.28
    (13.35)
    EORTC QLQ-C30 Scores: Emotional functioning Cycle 3 Day 28
    14.04
    (21.88)
    8.33
    (10.21)
    EORTC QLQ-C30 Scores: Emotional functioning Cycle 5 Day 28
    16.07
    (20.53)
    6.94
    (16.17)
    EORTC QLQ-C30 Scores: Emotional functioning Cycle 8 (Week 32)
    14.39
    (18.29)
    5.00
    (27.39)
    EORTC QLQ-C30 Scores: Emotional functioning Cycle 11 Day 28
    6.94
    (11.08)
    16.67
    (0)
    EORTC QLQ-C30 Scores: Emotional functioning Cycle 14 Day 28
    5.56
    (10.09)
    -4.17
    (5.89)
    EORTC QLQ-C30 Scores: Emotional functioning Cycle 17 Day 28
    -8.33
    (16.67)
    0
    (0)
    EORTC QLQ-C30 Scores: Emotional functioning Cycle 20 Day 28
    0
    (0)
    8.33
    (0)
    EORTC QLQ-C30 Scores: Emotional functioning Final visit
    3.33
    (18.31)
    16.67
    (18.63)
    EORTC QLQ-C30 Scores: Nausea and vomiting Baseline
    10.00
    (16.58)
    2.38
    (6.30)
    EORTC QLQ-C30 Scores: Nausea and vomiting Cycle 2 Day 1
    -4.63
    (12.53)
    8.33
    (22.97)
    EORTC QLQ-C30 Scores: Nausea and vomiting Cycle 3 Day 28
    -1.75
    (17.48)
    3.33
    (13.94)
    EORTC QLQ-C30 Scores: Nausea and vomiting Cycle 5 Day 28
    -2.38
    (11.05)
    8.33
    (17.48)
    EORTC QLQ-C30 Scores: Nausea and vomiting Cycle 8 (Week 32)
    7.58
    (23.99)
    16.67
    (16.67)
    EORTC QLQ-C30 Scores: Nausea and vomiting Cycle 11 Day 28
    2.78
    (12.55)
    0.00
    (23.57)
    EORTC QLQ-C30 Scores: Nausea and vomiting Cycle 14 Day 28
    -2.78
    (6.80)
    -8.33
    (11.79)
    EORTC QLQ-C30 Scores: Nausea and vomiting Cycle 20 Day 28
    0
    (0)
    0
    (0)
    EORTC QLQ-C30 Scores: Nausea and vomiting Final visit
    11.11
    (33.73)
    6.67
    (19.00)
    EORTC QLQ-C30 Scores: Social functioning Baseline
    67.50
    (35.24)
    76.19
    (13.11)
    EORTC QLQ-C30 Scores: Social functioning Cycle 2 Day 1
    4.63
    (12.53)
    0.00
    (10.54)
    EORTC QLQ-C30 Scores: Social functioning Cycle 3 Day 28
    -1.75
    (22.15)
    3.33
    (13.94)
    EORTC QLQ-C30 Scores: Social functioning Cycle 5 Day 28
    5.95
    (24.98)
    -2.78
    (26.70)
    EORTC QLQ-C30 Scores: Social functioning Cycle 8 (Week 32)
    0.00
    (18.26)
    -6.67
    (19.00)
    EORTC QLQ-C30 Scores: Social functioning Cycle 11 Day 28
    0.00
    (18.26)
    0
    (0)
    EORTC QLQ-C30 Scores: Social functioning Cycle 14 Day 28
    0.00
    (10.54)
    0
    (0)
    EORTC QLQ-C30 Scores: Social functioning Cycle 17 Day 28
    -4.17
    (8.33)
    0
    (0)
    EORTC QLQ-C30 Scores: Social functioning Cycle 20 Day 28
    0
    (0)
    0
    (0)
    EORTC QLQ-C30 Scores: Social functioning Final visit
    0.00
    (30.86)
    -6.67
    (25.28)
    EORTC QLQ-C30 Scores: Physical functioning Baseline
    86.33
    (18.92)
    81.90
    (11.36)
    EORTC QLQ-C30 Scores: Physical functioning Cycle 2 Day 1
    1.48
    (9.02)
    2.22
    (6.89)
    EORTC QLQ-C30 Scores: Physical functioning Cycle 3 Day 28
    -2.81
    (15.45)
    2.67
    (5.96)
    EORTC QLQ-C30 Scores: Physical functioning Cycle 5 Day 28
    1.43
    (16.16)
    -2.22
    (5.44)
    EORTC QLQ-C30 Scores: Physical functioning Cycle 8 (Week 32)
    5.45
    (15.72)
    -4.00
    (7.60)
    EORTC QLQ-C30 Scores: Physical functioning Cycle 11 Day 28
    -1.11
    (6.55)
    -10.00
    (14.14)
    EORTC QLQ-C30 Scores: Physical functioning Cycle 14 Day 28
    -1.11
    (2.72)
    0.00
    (9.43)
    EORTC QLQ-C30 Scores: Physical functioning Cycle 17 Day 28
    1.67
    (3.33)
    0
    (0)
    EORTC QLQ-C30 Scores: Physical functioning Cycle 20 Day 28
    0
    (0)
    0
    (0)
    EORTC QLQ-C30 Scores: Physical functioning Final visit
    -4.44
    (9.65)
    -2.67
    (7.60)
    EORTC QLQ-C30 Scores: Global health status/QoL Baseline
    61.25
    (20.28)
    60.71
    (7.93)
    EORTC QLQ-C30 Scores: Global health status/QoL Cycle 2 Day 1
    2.31
    (18.92)
    1.39
    (8.19)
    EORTC QLQ-C30 Scores: Global health status/QoL Cycle 3 Day 28
    7.89
    (14.56)
    11.67
    (9.50)
    EORTC QLQ-C30 Scores: Global health status/QoL Cycle 5 Day 28
    7.14
    (19.84)
    0.00
    (17.48)
    EORTC QLQ-C30 Scores: Global health status/QoL Cycle 8 (Week 32)
    9.09
    (23.41)
    -8.33
    (13.18)
    EORTC QLQ-C30 Scores: Global health status/QoL Cycle 11 Day 28
    1.39
    (23.81)
    8.33
    (11.79)
    EORTC QLQ-C30 Scores: Global health status/QoL Cycle 14 Day 28
    2.78
    (21.52)
    8.33
    (0)
    EORTC QLQ-C30 Scores: Global health status/QoL Cycle 17 Day 28
    10.42
    (20.83)
    16.67
    (0)
    EORTC QLQ-C30 Scores: Global health status/QoL Cycle 20 Day 28
    25.00
    (0)
    25.00
    (0)
    EORTC QLQ-C30 Scores: Global health status/QoL Final visit
    -3.33
    (23.32)
    13.33
    (17.28)
    EORTC QLQ-C30 Scores: Role functioning Baseline
    74.17
    (28.85)
    76.19
    (16.27)
    EORTC QLQ-C30 Scores: Role functioning Cycle 2 Day 1
    7.41
    (17.36)
    -8.33
    (17.48)
    EORTC QLQ-C30 Scores: Role functioning Cycle 3 Day 28
    2.63
    (17.80)
    0.00
    (11.79)
    EORTC QLQ-C30 Scores: Role functioning Cycle 5 Day 28
    7.14
    (15.63)
    -2.78
    (22.15)
    EORTC QLQ-C30 Scores: Role functioning Cycle 8 (Week 32)
    15.15
    (21.67)
    0.00
    (20.41)
    EORTC QLQ-C30 Scores: Role functioning Cycle 11 Day 28
    -2.78
    (19.48)
    -8.33
    (11.79)
    EORTC QLQ-C30 Scores: Role functioning Cycle 14 Day 28
    5.56
    (8.61)
    0
    (0)
    EORTC QLQ-C30 Scores: Role functioning Cycle 17 Day 28
    8.33
    (9.62)
    0
    (0)
    EORTC QLQ-C30 Scores: Role functioning Cycle 20 Day 28
    16.67
    (0)
    0
    (0)
    EORTC QLQ-C30 Scores: Role functioning Final Visit
    -13.33
    (32.24)
    6.67
    (9.13)
    40. Secondary Outcome
    Title Frequency Count of Participant Responses to the Patient Global Impression of Change (PGIC) Question Over Time
    Description The PGIC is a one-item measure used to assess perceived treatment benefit. Participants were asked "Since the start of the treatment you've received in this study, your polycythemia vera (PV) symptoms are: 'very much improved', 'much improved', 'minimally improved', 'no change', 'minimally worse', 'much worse', and 'very much worse'. The study was pre-maturely terminated by the sponsor's decision, therefore did not reach the end of study.
    Time Frame Cycle 2 Day 1, Cycle 3 Day 28, Cycle 5 Day 28, End of Cycle 8 (Week 32), and every 3 cycles thereafter (1 cycle is 28 days) until end of study (up to 2 years)

    Outcome Measure Data

    Analysis Population Description
    ITT Population. The number analyzed includes participants who were evaluable at each timepoint.
    Arm/Group Title Ruxolitinib-Naïve Participants Ruxolitinib-Resistant or Intolerant Participants
    Arm/Group Description Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years). Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years).
    Measure Participants 20 7
    Cycle 2, Day 1 Very Much Improved
    0
    0%
    0
    0%
    Cycle 2, Day 1 Much Improved
    4
    26.7%
    1
    20%
    Cycle 2, Day 1 Minimally Improved
    5
    33.3%
    3
    60%
    Cycle 2, Day 1 No Change
    6
    40%
    1
    20%
    Cycle 2, Day 1 Minimally Worse
    1
    6.7%
    1
    20%
    Cycle 2, Day 1 Much Worse
    0
    0%
    0
    0%
    Cycle 2, Day 1 Very Much Worse
    0
    0%
    0
    0%
    Cycle 2, Day 1 Not Assessed
    0
    0%
    1
    20%
    Cycle 3 Day 28 Very Much Improved
    4
    26.7%
    1
    20%
    Cycle 3 Day 28 Much Improved
    4
    26.7%
    1
    20%
    Cycle 3 Day 28 Minimally Improved
    6
    40%
    3
    60%
    Cycle 3 Day 28 No Change
    3
    20%
    0
    0%
    Cycle 3 Day 28 Minimally Worse
    0
    0%
    0
    0%
    Cycle 3 Day 28 Much Worse
    0
    0%
    0
    0%
    Cycle 3 Day 28 Very Much Worse
    0
    0%
    0
    0%
    Cycle 3 Day 28 Not Assessed
    0
    0%
    1
    20%
    Cycle 5 Day 28 Very Much Improved
    2
    13.3%
    1
    20%
    Cycle 5 Day 28 Much Improved
    6
    40%
    1
    20%
    Cycle 5 Day 28 Minimally Improved
    2
    13.3%
    4
    80%
    Cycle 5 Day 28 No Change
    1
    6.7%
    0
    0%
    Cycle 5 Day 28 Minimally Worse
    0
    0%
    0
    0%
    Cycle 5 Day 28 Much Worse
    0
    0%
    0
    0%
    Cycle 5 Day 28 Very Much Worse
    0
    0%
    0
    0%
    Cycle 5 Day 28 Not Assessed
    4
    26.7%
    0
    0%
    Week 32 Very Much Improved
    3
    20%
    0
    0%
    Week 32 Much Improved
    3
    20%
    1
    20%
    Week 32 Minimally Improved
    3
    20%
    3
    60%
    Week 32 No Change
    1
    6.7%
    1
    20%
    Week 32 Minimally Worse
    1
    6.7%
    0
    0%
    Week 32 Much Worse
    0
    0%
    0
    0%
    Week 32 Very Much Worse
    0
    0%
    0
    0%
    Week 32 Not Assessed
    0
    0%
    0
    0%
    Cycle 11 Day 28 Very Much Improved
    1
    6.7%
    0
    0%
    Cycle 11 Day 28 Much Improved
    3
    20%
    2
    40%
    Cycle 11 Day 28 Minimally Improved
    0
    0%
    0
    0%
    Cycle 11 Day 28 No Change
    0
    0%
    0
    0%
    Cycle 11 Day 28 Minimally Worse
    1
    6.7%
    0
    0%
    Cycle 11 Day 28 Much Worse
    0
    0%
    0
    0%
    Cycle 11 Day 28 Very Much Worse
    0
    0%
    0
    0%
    Cycle 11 Day 28 Not Assessed
    0
    0%
    0
    0%
    Cycle 14 Day 28 Very Much Improved
    2
    13.3%
    0
    0%
    Cycle 14 Day 28 Much Improved
    2
    13.3%
    2
    40%
    Cycle 14 Day 28 Minimally Improved
    0
    0%
    0
    0%
    Cycle 14 Day 28 No change
    1
    6.7%
    0
    0%
    Cycle 14 Day 28 Minimally Worse
    1
    6.7%
    0
    0%
    Cycle 14 Day 28 Much Worse
    0
    0%
    0
    0%
    Cycle 14 Day 28 Very Much Worse
    0
    0%
    0
    0%
    Cycle 14 Day 28 Not Assessed
    0
    0%
    0
    0%
    Cycle 17 Day 28 Very Much Improved
    1
    6.7%
    0
    0%
    Cycle 17 Day 28 Much Improved
    1
    6.7%
    2
    40%
    Cycle 17 Day 28 Minimally Improved
    1
    6.7%
    0
    0%
    Cycle 17 Day 28 No Change
    1
    6.7%
    0
    0%
    Cycle 17 Day 28 Minimally Worse
    0
    0%
    0
    0%
    Cycle 17 Day 28 Much Worse
    0
    0%
    0
    0%
    Cycle 17 Day 28 Very Much Worse
    0
    0%
    0
    0%
    Cycle 17 Day 28 Not Assessed
    0
    0%
    0
    0%
    Cycle 20 Day 28 Very Much Improved
    0
    0%
    0
    0%
    Cycle 20 Day 28 Much Improved
    0
    0%
    0
    0%
    Cycle 20 Day 28 Minimally Improved
    1
    6.7%
    0
    0%
    Cycle 20 Day 28 No Change
    0
    0%
    0
    0%
    Cycle 20 Day 28 Minimally Worse
    0
    0%
    0
    0%
    Cycle 20 Day 28 Much Worse
    0
    0%
    0
    0%
    Cycle 20 Day 28 Very Much Worse
    0
    0%
    0
    0%
    Cycle 20 Day 28 Not Assessed
    0
    0%
    0
    0%
    Final Visit Very Much Improved
    3
    20%
    1
    20%
    Final Visit Much Improved
    3
    20%
    3
    60%
    Final Visit Minimally Improved
    2
    13.3%
    1
    20%
    Final Visit No Change
    6
    40%
    0
    0%
    Final Visit Minimally Worse
    1
    6.7%
    0
    0%
    Final Visit Much Worse
    0
    0%
    0
    0%
    Final Visit Very Much Worse
    0
    0%
    0
    0%
    Final Visit Not Assessed
    2
    13.3%
    0
    0%

    Adverse Events

    Time Frame From Baseline to end of study (up to 2 years) post initial dose or until subject discontinued. Safety follow-up: Until 28 days after the last dose of study treatment or until initiating another anti-cancer therapy.
    Adverse Event Reporting Description Reported: Safety Population. During the Safety Follow-up Period, non-Serious Adverse Events occurred at the 5% frequency threshold.
    Arm/Group Title Ruxolitinib Naive-With Splenomegaly Ruxolitinib Naive-Without Splenomegaly Ruxolitinib-Resistant or Intolerant Participants With Splenomegaly Ruxolitinib-Resistant or Intolerant Participants Without Splenomegaly
    Arm/Group Description Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years). Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years). Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years). Participants received 150 milligrams (mg) idasanutlin orally, once daily for 5 days, every 28 days, until treatment discontinuation or end of study (up to 2 years).
    All Cause Mortality
    Ruxolitinib Naive-With Splenomegaly Ruxolitinib Naive-Without Splenomegaly Ruxolitinib-Resistant or Intolerant Participants With Splenomegaly Ruxolitinib-Resistant or Intolerant Participants Without Splenomegaly
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/15 (0%) 0/5 (0%) 0/6 (0%) 0/1 (0%)
    Serious Adverse Events
    Ruxolitinib Naive-With Splenomegaly Ruxolitinib Naive-Without Splenomegaly Ruxolitinib-Resistant or Intolerant Participants With Splenomegaly Ruxolitinib-Resistant or Intolerant Participants Without Splenomegaly
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 2/15 (13.3%) 1/5 (20%) 0/6 (0%) 0/1 (0%)
    Cardiac disorders
    Atrial fibrillation 1/15 (6.7%) 1 0/5 (0%) 0 0/6 (0%) 0 0/1 (0%) 0
    Atrial flutter 1/15 (6.7%) 2 0/5 (0%) 0 0/6 (0%) 0 0/1 (0%) 0
    Gastrointestinal disorders
    Nausea 0/15 (0%) 0 1/5 (20%) 1 0/6 (0%) 0 0/1 (0%) 0
    Other (Not Including Serious) Adverse Events
    Ruxolitinib Naive-With Splenomegaly Ruxolitinib Naive-Without Splenomegaly Ruxolitinib-Resistant or Intolerant Participants With Splenomegaly Ruxolitinib-Resistant or Intolerant Participants Without Splenomegaly
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 15/15 (100%) 5/5 (100%) 6/6 (100%) 1/1 (100%)
    Blood and lymphatic system disorders
    Anaemia 3/15 (20%) 3 0/5 (0%) 0 2/6 (33.3%) 3 0/1 (0%) 0
    Lymphadenopathy 1/15 (6.7%) 1 0/5 (0%) 0 0/6 (0%) 0 0/1 (0%) 0
    Neutropenia 0/15 (0%) 0 1/5 (20%) 3 1/6 (16.7%) 1 0/1 (0%) 0
    Thrombocytopenia 0/15 (0%) 0 1/5 (20%) 1 2/6 (33.3%) 2 0/1 (0%) 0
    Cardiac disorders
    Extrasystoles 1/15 (6.7%) 1 0/5 (0%) 0 0/6 (0%) 0 0/1 (0%) 0
    Palpitations 1/15 (6.7%) 1 0/5 (0%) 0 0/6 (0%) 0 0/1 (0%) 0
    Ear and labyrinth disorders
    Ear pain 0/15 (0%) 0 1/5 (20%) 1 0/6 (0%) 0 0/1 (0%) 0
    Middle ear inflammation 0/15 (0%) 0 0/5 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0
    Tinnitus 0/15 (0%) 0 0/5 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0
    Eye disorders
    Dry eye 1/15 (6.7%) 1 0/5 (0%) 0 1/6 (16.7%) 1 1/1 (100%) 1
    Ocular hyperaemia 1/15 (6.7%) 1 0/5 (0%) 0 0/6 (0%) 0 0/1 (0%) 0
    Photophobia 1/15 (6.7%) 1 0/5 (0%) 0 0/6 (0%) 0 0/1 (0%) 0
    Gastrointestinal disorders
    Abdominal discomfort 1/15 (6.7%) 3 1/5 (20%) 2 1/6 (16.7%) 2 0/1 (0%) 0
    Abdominal distension 3/15 (20%) 5 0/5 (0%) 0 0/6 (0%) 0 0/1 (0%) 0
    Abdominal pain 3/15 (20%) 4 1/5 (20%) 2 2/6 (33.3%) 3 0/1 (0%) 0
    Abdominal pain upper 1/15 (6.7%) 1 1/5 (20%) 2 0/6 (0%) 0 0/1 (0%) 0
    Constipation 5/15 (33.3%) 7 0/5 (0%) 0 3/6 (50%) 5 1/1 (100%) 6
    Diarrhoea 11/15 (73.3%) 38 3/5 (60%) 11 6/6 (100%) 9 1/1 (100%) 2
    Dry mouth 1/15 (6.7%) 1 0/5 (0%) 0 0/6 (0%) 0 0/1 (0%) 0
    Dyspepsia 3/15 (20%) 3 0/5 (0%) 0 0/6 (0%) 0 0/1 (0%) 0
    Flatulence 2/15 (13.3%) 2 0/5 (0%) 0 0/6 (0%) 0 0/1 (0%) 0
    Gastritis 1/15 (6.7%) 1 0/5 (0%) 0 0/6 (0%) 0 0/1 (0%) 0
    Gastrointestinal pain 1/15 (6.7%) 1 0/5 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0
    Gastrointestinal tract irritation 0/15 (0%) 0 0/5 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0
    Gastrooesophageal reflux disease 1/15 (6.7%) 1 0/5 (0%) 0 0/6 (0%) 0 0/1 (0%) 0
    Glossitis 0/15 (0%) 0 1/5 (20%) 1 0/6 (0%) 0 0/1 (0%) 0
    Hypoaesthesia oral 1/15 (6.7%) 3 0/5 (0%) 0 0/6 (0%) 0 0/1 (0%) 0
    Irritable bowel syndrome 0/15 (0%) 0 1/5 (20%) 1 0/6 (0%) 0 0/1 (0%) 0
    Mouth ulceration 0/15 (0%) 0 0/5 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0
    Nausea 13/15 (86.7%) 60 5/5 (100%) 15 6/6 (100%) 25 1/1 (100%) 5
    Oral pain 0/15 (0%) 0 0/5 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0
    Paraesthesia oral 1/15 (6.7%) 3 0/5 (0%) 0 0/6 (0%) 0 0/1 (0%) 0
    Stomatitis 0/15 (0%) 0 0/5 (0%) 0 3/6 (50%) 3 0/1 (0%) 0
    Vomiting 6/15 (40%) 12 3/5 (60%) 4 1/6 (16.7%) 2 1/1 (100%) 1
    General disorders
    Asthenia 2/15 (13.3%) 6 1/5 (20%) 2 1/6 (16.7%) 4 0/1 (0%) 0
    Chest discomfort 1/15 (6.7%) 1 0/5 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0
    Chest pain 0/15 (0%) 0 0/5 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0
    Early satiety 1/15 (6.7%) 1 0/5 (0%) 0 0/6 (0%) 0 0/1 (0%) 0
    Fatigue 5/15 (33.3%) 27 0/5 (0%) 0 4/6 (66.7%) 13 1/1 (100%) 3
    Feeling abnormal 1/15 (6.7%) 1 0/5 (0%) 0 0/6 (0%) 0 0/1 (0%) 0
    Malaise 0/15 (0%) 0 0/5 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0
    Mucosal inflammation 1/15 (6.7%) 1 0/5 (0%) 0 0/6 (0%) 0 0/1 (0%) 0
    Oedema peripheral 0/15 (0%) 0 0/5 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0
    Pyrexia 1/15 (6.7%) 1 0/5 (0%) 0 0/6 (0%) 0 0/1 (0%) 0
    Infections and infestations
    Bronchitis 0/15 (0%) 0 1/5 (20%) 2 0/6 (0%) 0 0/1 (0%) 0
    Cellulitis 0/15 (0%) 0 0/5 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0
    Conjunctivitis 0/15 (0%) 0 0/5 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0
    Gastroenteritis 1/15 (6.7%) 1 0/5 (0%) 0 0/6 (0%) 0 0/1 (0%) 0
    Sinusitis 0/15 (0%) 0 0/5 (0%) 0 2/6 (33.3%) 2 0/1 (0%) 0
    Upper respiratory tract infection 0/15 (0%) 0 1/5 (20%) 1 1/6 (16.7%) 1 1/1 (100%) 2
    Urinary tract infection 1/15 (6.7%) 1 0/5 (0%) 0 0/6 (0%) 0 0/1 (0%) 0
    Varicella zoster virus infection 0/15 (0%) 0 1/5 (20%) 1 0/6 (0%) 0 0/1 (0%) 0
    Injury, poisoning and procedural complications
    Contusion 1/15 (6.7%) 1 1/5 (20%) 1 0/6 (0%) 0 0/1 (0%) 0
    Limb injury 0/15 (0%) 0 0/5 (0%) 0 1/6 (16.7%) 2 0/1 (0%) 0
    Rib fracture 0/15 (0%) 0 1/5 (20%) 1 0/6 (0%) 0 0/1 (0%) 0
    Upper limb fracture 0/15 (0%) 0 0/5 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0
    Wrist fracture 0/15 (0%) 0 1/5 (20%) 1 0/6 (0%) 0 0/1 (0%) 0
    Investigations
    Blood creatine phosphokinase increased 1/15 (6.7%) 1 0/5 (0%) 0 0/6 (0%) 0 0/1 (0%) 0
    Blood creatinine increased 3/15 (20%) 4 0/5 (0%) 0 1/6 (16.7%) 2 0/1 (0%) 0
    Blood urea increased 1/15 (6.7%) 1 0/5 (0%) 0 0/6 (0%) 0 0/1 (0%) 0
    Platelet count decreased 1/15 (6.7%) 2 0/5 (0%) 0 1/6 (16.7%) 5 0/1 (0%) 0
    White blood cell count decreased 1/15 (6.7%) 1 0/5 (0%) 0 0/6 (0%) 0 0/1 (0%) 0
    Metabolism and nutrition disorders
    Appetite disorder 0/15 (0%) 0 0/5 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0
    Decreased appetite 3/15 (20%) 3 1/5 (20%) 1 2/6 (33.3%) 2 0/1 (0%) 0
    Dehydration 0/15 (0%) 0 0/5 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0
    Gout 0/15 (0%) 0 0/5 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0
    Hyperglycaemia 1/15 (6.7%) 4 0/5 (0%) 0 0/6 (0%) 0 0/1 (0%) 0
    Hyperkalaemia 1/15 (6.7%) 1 1/5 (20%) 1 0/6 (0%) 0 0/1 (0%) 0
    Hyperphosphataemia 1/15 (6.7%) 1 0/5 (0%) 0 1/6 (16.7%) 2 0/1 (0%) 0
    Hyperuricaemia 2/15 (13.3%) 2 0/5 (0%) 0 0/6 (0%) 0 0/1 (0%) 0
    Musculoskeletal and connective tissue disorders
    Arthralgia 0/15 (0%) 0 0/5 (0%) 0 2/6 (33.3%) 2 0/1 (0%) 0
    Back pain 1/15 (6.7%) 2 0/5 (0%) 0 3/6 (50%) 3 0/1 (0%) 0
    Bone pain 1/15 (6.7%) 1 0/5 (0%) 0 0/6 (0%) 0 0/1 (0%) 0
    Flank pain 1/15 (6.7%) 1 0/5 (0%) 0 0/6 (0%) 0 0/1 (0%) 0
    Musculoskeletal pain 0/15 (0%) 0 0/5 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0
    Pain in extremity 0/15 (0%) 0 0/5 (0%) 0 2/6 (33.3%) 4 0/1 (0%) 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Skin papilloma 0/15 (0%) 0 0/5 (0%) 0 1/6 (16.7%) 1 1/1 (100%) 1
    Solitary fibrous tumour 1/15 (6.7%) 1 0/5 (0%) 0 0/6 (0%) 0 0/1 (0%) 0
    Squamous cell carcinoma of skin 0/15 (0%) 0 0/5 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0
    Nervous system disorders
    Disturbance in attention 1/15 (6.7%) 1 0/5 (0%) 0 0/6 (0%) 0 0/1 (0%) 0
    Dizziness 3/15 (20%) 3 1/5 (20%) 1 3/6 (50%) 3 0/1 (0%) 0
    Dysgeusia 3/15 (20%) 9 0/5 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0
    Headache 3/15 (20%) 4 1/5 (20%) 4 3/6 (50%) 4 1/1 (100%) 1
    Migraine 2/15 (13.3%) 8 0/5 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0
    Paraesthesia 0/15 (0%) 0 0/5 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0
    Parosmia 0/15 (0%) 0 0/5 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0
    Peripheral sensory neuropathy 1/15 (6.7%) 1 0/5 (0%) 0 0/6 (0%) 0 0/1 (0%) 0
    Seizure 0/15 (0%) 0 1/5 (20%) 1 0/6 (0%) 0 0/1 (0%) 0
    Somnolence 0/15 (0%) 0 1/5 (20%) 1 0/6 (0%) 0 0/1 (0%) 0
    Taste disorder 5/15 (33.3%) 14 0/5 (0%) 0 0/6 (0%) 0 1/1 (100%) 4
    Psychiatric disorders
    Agitation 0/15 (0%) 0 1/5 (20%) 1 1/6 (16.7%) 1 0/1 (0%) 0
    Anxiety 0/15 (0%) 0 1/5 (20%) 1 1/6 (16.7%) 1 0/1 (0%) 0
    Confusional state 0/15 (0%) 0 0/5 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0
    Depressed mood 1/15 (6.7%) 1 0/5 (0%) 0 0/6 (0%) 0 0/1 (0%) 0
    Depression 0/15 (0%) 0 0/5 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0
    Disorientation 1/15 (6.7%) 1 0/5 (0%) 0 0/6 (0%) 0 0/1 (0%) 0
    Hallucination 1/15 (6.7%) 1 0/5 (0%) 0 0/6 (0%) 0 0/1 (0%) 0
    Insomnia 2/15 (13.3%) 2 1/5 (20%) 1 2/6 (33.3%) 3 1/1 (100%) 2
    Irritability 1/15 (6.7%) 1 0/5 (0%) 0 0/6 (0%) 0 0/1 (0%) 0
    Libido decreased 1/15 (6.7%) 1 0/5 (0%) 0 0/6 (0%) 0 0/1 (0%) 0
    Mood altered 1/15 (6.7%) 1 0/5 (0%) 0 0/6 (0%) 0 0/1 (0%) 0
    Thinking abnormal 0/15 (0%) 0 0/5 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0
    Renal and urinary disorders
    Pollakiuria 1/15 (6.7%) 1 0/5 (0%) 0 0/6 (0%) 0 0/1 (0%) 0
    Reproductive system and breast disorders
    Benign prostatic hyperplasia 0/15 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 1/1 (100%) 1
    Breast mass 0/15 (0%) 0 0/5 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Asthma 0/15 (0%) 0 1/5 (20%) 1 0/6 (0%) 0 0/1 (0%) 0
    Cough 1/15 (6.7%) 1 0/5 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0
    Dyspnoea 0/15 (0%) 0 0/5 (0%) 0 3/6 (50%) 3 0/1 (0%) 0
    Dyspnoea at rest 0/15 (0%) 0 0/5 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0
    Hiccups 0/15 (0%) 0 0/5 (0%) 0 0/6 (0%) 0 1/1 (100%) 3
    Nasal congestion 1/15 (6.7%) 1 0/5 (0%) 0 0/6 (0%) 0 0/1 (0%) 0
    Oropharyngeal pain 1/15 (6.7%) 1 1/5 (20%) 1 1/6 (16.7%) 1 0/1 (0%) 0
    Wheezing 0/15 (0%) 0 1/5 (20%) 1 0/6 (0%) 0 0/1 (0%) 0
    Skin and subcutaneous tissue disorders
    Alopecia 0/15 (0%) 0 0/5 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0
    Blister 1/15 (6.7%) 1 0/5 (0%) 0 0/6 (0%) 0 0/1 (0%) 0
    Erythema 0/15 (0%) 0 0/5 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0
    Night sweats 1/15 (6.7%) 1 0/5 (0%) 0 0/6 (0%) 0 0/1 (0%) 0
    Pruritus 1/15 (6.7%) 1 1/5 (20%) 1 1/6 (16.7%) 2 1/1 (100%) 1
    Rash 0/15 (0%) 0 0/5 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0
    Rash maculo-papular 1/15 (6.7%) 1 0/5 (0%) 0 0/6 (0%) 0 1/1 (100%) 1
    Xeroderma 1/15 (6.7%) 1 0/5 (0%) 0 0/6 (0%) 0 0/1 (0%) 0
    Vascular disorders
    Flushing 0/15 (0%) 0 0/5 (0%) 0 1/6 (16.7%) 3 0/1 (0%) 0
    Hot flush 1/15 (6.7%) 1 0/5 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

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

    The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.

    Results Point of Contact

    Name/Title Medical Communications
    Organization Hoffmann-La Roche
    Phone 800 821-8590
    Email genentech@druginfo.com
    Responsible Party:
    Hoffmann-La Roche
    ClinicalTrials.gov Identifier:
    NCT03287245
    Other Study ID Numbers:
    • NP39761
    • 2017-000861-58
    First Posted:
    Sep 19, 2017
    Last Update Posted:
    Dec 8, 2021
    Last Verified:
    Dec 1, 2021