Study to Investigate Idelalisib in Combination With Chemotherapeutic Agents, Immunomodulatory Agents and Anti-CD20 Monoclonal Antibody (mAb) in Participants With Relapsed or Refractory Indolent B-cell Non-Hodgkin's Lymphoma, Mantle Cell Lymphoma or Chronic Lymphocytic Leukemia

Sponsor
Gilead Sciences (Industry)
Overall Status
Completed
CT.gov ID
NCT01088048
Collaborator
(none)
241
11
10
61.1
21.9
0.4

Study Details

Study Description

Brief Summary

The primary objective of the study is to evaluate the safety of idelalisib in combination with an anti-CD20 monoclonal antibody (mAb), a chemotherapeutic agent, a mammalian target of rapamycin (mTOR) inhibitor, a protease inhibitor, an antiangiogenic agent, and/or an immunomodulatory agent in participants with relapsed or refractory indolent B-cell non-Hodgkin lymphoma (NHL), mantle cell lymphoma (MCL), or chronic lymphocytic leukemia (CLL).

Study Design

Study Type:
Interventional
Actual Enrollment :
241 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase I Study to Investigate the Safety and Clinical Activity of Idelalisib in Combination With Chemotherapeutic Agents, Immunomodulatory Agents and Anti-CD20 mAb in Subjects With Relapsed or Refractory Indolent B-cell Non-Hodgkin Lymphoma, Mantle Cell Lymphoma or Chronic Lymphocytic Leukemia
Actual Study Start Date :
Mar 25, 2010
Actual Primary Completion Date :
Apr 28, 2015
Actual Study Completion Date :
Apr 28, 2015

Arms and Interventions

Arm Intervention/Treatment
Experimental: Idelalisib + Rituximab

Participants with chronic lymphocytic leukemia (CLL) and indolent non-Hodgkin lymphoma (iNHL) will receive treatments as follows: Cohort 1a: Idelalisib (IDELA) 100 mg orally twice daily (BID) on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 intravenously (IV) on Days 1, 8, 15 & 22, Cycles 1 & 2 Cohort 2a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Days 1, 8, 15, & 22, Cycles 1 & 2 Cohort 3e: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Days 1, 8, 15, & 22, Cycles 1 & 2 Cohort 4a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle, starting Cycle 2 Day 1 with the 5th dose of rituximab + rituximab 375 mg/m^2 IV on Days 1, 8, 15, & 22, Cycles 1 & 2

Drug: Idelalisib
Idelalisib tablet administered orally
Other Names:
  • GS-1101
  • CAL-101
  • Zydelig®
  • Drug: Rituximab
    Rituximab administered intravenously
    Other Names:
  • Rituxan
  • Experimental: Idelalisib + Rituximab + Bendamustine

    Participants with CLL, iNHL and mantle cell lymphoma (MCL) will receive treatments as follows: Cohort 3a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6 Cohort 3b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + bendamustine 70 mg/m^2 IV on Days 1 & 2 of each 28-day cycle from Cycles 1 - 6 Cohort 5c: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6

    Drug: Idelalisib
    Idelalisib tablet administered orally
    Other Names:
  • GS-1101
  • CAL-101
  • Zydelig®
  • Drug: Rituximab
    Rituximab administered intravenously
    Other Names:
  • Rituxan
  • Drug: Bendamustine
    Bendamustine administered intravenously
    Other Names:
  • Treanda
  • Experimental: Idelalisib + Bendamustine

    Participants with CLL and iNHL will receive treatments as follows: Cohort 1b: IDELA 100 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6 Cohort 2b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6 Cohort 3f: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6 Cohort 3g: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 70 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6 Cohort 4b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle starting Cycle 2, Day 3 (after the Cycle 2 bendamustine dosing) + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6

    Drug: Idelalisib
    Idelalisib tablet administered orally
    Other Names:
  • GS-1101
  • CAL-101
  • Zydelig®
  • Drug: Bendamustine
    Bendamustine administered intravenously
    Other Names:
  • Treanda
  • Experimental: Idelalisib + Ofatumumab

    Participants with CLL will receive treatments as follows: Cohort 3c: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + ofatumumab 12 doses (300 mg (Day 1 or Day 2, Dose 1), followed 1 week later by 1,000 mg weekly for 7 doses (Doses 2 - 8), followed 5 weeks later by 1,000 mg every 4 weeks for 4 doses (Doses 9 - 12))

    Drug: Idelalisib
    Idelalisib tablet administered orally
    Other Names:
  • GS-1101
  • CAL-101
  • Zydelig®
  • Drug: Ofatumumab
    Ofatumumab administered intravenously
    Other Names:
  • Arzerra
  • Experimental: Idelalisib + Fludarabine

    Participants with CLL will receive treatments as follows: Cohort 3d: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + fludarabine 40 mg/m^2 orally on Days 1 - 5 of each 28-day cycle, Cycles 1 - 6

    Drug: Idelalisib
    Idelalisib tablet administered orally
    Other Names:
  • GS-1101
  • CAL-101
  • Zydelig®
  • Drug: Fludarabine
    Fludarabine administered orally
    Other Names:
  • Fludara
  • Experimental: Idelalisib + Everolimus

    Participants with MCL will receive treatments as follows: Cohort 5a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + everolimus 10 mg orally once daily on Days 1 - 28 of each 28-day cycle

    Drug: Idelalisib
    Idelalisib tablet administered orally
    Other Names:
  • GS-1101
  • CAL-101
  • Zydelig®
  • Drug: Everolimus
    Everolimus administered orally twice daily until disease progression
    Other Names:
  • Afinitor
  • RAD-001
  • Experimental: Idelalisib + Bortezomib

    Participants with MCL will receive treatments as follows: Cohort 5b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bortezomib 1.3 mg/m^2 subcutaneously on Days 1, 8 & 15 of each 28-day cycle

    Drug: Idelalisib
    Idelalisib tablet administered orally
    Other Names:
  • GS-1101
  • CAL-101
  • Zydelig®
  • Drug: Bortezomib
    Bortezomib administered as a subcutaneous injection
    Other Names:
  • Velcade
  • codenamed PS-341
  • Experimental: Idelalisib + Chlorambucil

    Participants with CLL will receive treatments as follows: Cohort 6a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + chlorambucil 10 mg/m^2 orally once daily for 7 days every 28 days, Cycles 1 - 12

    Drug: Idelalisib
    Idelalisib tablet administered orally
    Other Names:
  • GS-1101
  • CAL-101
  • Zydelig®
  • Drug: Chlorambucil
    Chlorambucil administered on Days 1-7 every 28 days to allow appropriate therapy for participants with CLL and to coordinate into a cycle period equivalent to other study treatment regimens.
    Other Names:
  • Leukeran
  • Experimental: Idelalisib + Rituximab + Chlorambucil

    Participants with CLL will receive treatments as follows: Cohort 6b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + chlorambucil 10 mg/m^2 orally once daily for 7 days every 28 days, Cycles 1 - 12

    Drug: Idelalisib
    Idelalisib tablet administered orally
    Other Names:
  • GS-1101
  • CAL-101
  • Zydelig®
  • Drug: Rituximab
    Rituximab administered intravenously
    Other Names:
  • Rituxan
  • Drug: Chlorambucil
    Chlorambucil administered on Days 1-7 every 28 days to allow appropriate therapy for participants with CLL and to coordinate into a cycle period equivalent to other study treatment regimens.
    Other Names:
  • Leukeran
  • Experimental: Idelalisib + Rituximab + Lenalidomide

    Participants with CLL and iNHL will receive treatments as follows: Cohort 7a: IDELA 150 mg orally BID on Days 1 - 35 of Cycle 1 (35 days) & Days 1 - 28 of all subsequent 28-day cycles + rituximab 375 mg/m^2 IV on Days 1 & 8 of Cycle 1 & Day 1 of Cycles 2 - 6 + lenalidomide 5 mg orally once daily on Days 8 - 28 of Cycle 1 (35 days) & Days 1 - 21 of next five 28-day cycles Cohort 7b: IDELA 150 mg orally BID on Days 1 - 35 of Cycle 1 (35 days) & Days 1 - 28 of all subsequent 28-day cycles + rituximab 375 mg/m^2 IV on Days 1 & 8 of Cycle 1 & Day 1 of Cycles 2 - 6 + lenalidomide 10 mg orally once daily on Days 8 - 28 of Cycle 1 (35 days) & Days 1 - 21 of next five 28-day cycles Cohort 7c: IDELA 150 mg orally BID on Days 1 - 35 of Cycle 1 (35 days) & Days 1 - 28 of all subsequent 28-day cycles + rituximab 375 mg/m^2 IV on Days 1 & 8 of Cycle 1 & Day 1 of Cycles 2 - 6 + lenalidomide 20 mg orally once daily on Days 8 - 28 of Cycle 1 (35 days) & Days 1 - 21 of next five 28-day cycles

    Drug: Idelalisib
    Idelalisib tablet administered orally
    Other Names:
  • GS-1101
  • CAL-101
  • Zydelig®
  • Drug: Rituximab
    Rituximab administered intravenously
    Other Names:
  • Rituxan
  • Drug: Lenalidomide
    Lenalidomide administered orally
    Other Names:
  • Revlimid
  • Outcome Measures

    Primary Outcome Measures

    1. Duration of Exposure to IDELA [First dose date up to 12 months]

      Duration of exposure to IDELA was summarized using descriptive statistics.

    2. Toxicity of Administration of IDELA [First dose date up to 5 years]

      Percentage of participants experiencing toxicities of administration of IDELA were measured according to the Common Terminology Criteria for Adverse Events v4.02

    Secondary Outcome Measures

    1. Overall Response Rate [Up to 5 years]

      Overall Response Rate (ORR) was defined as the percentage of participants achieving a complete response (CR) or partial response (PR). The response definitions were based on the following standard criteria established for each indication: CLL: International Workshop on chronic lymphocytic leukemia (IWCLL),2008 iNHL & MCL: Cheson, 2007

    2. Duration of Response [Up to 5 years]

      Duration of response (DOR) was defined as the interval from the first documentation of CR or PR to the earlier of the first documentation of disease progression or death from any cause.

    3. Time to Response [Up to 5 years]

      Time to response (TTR) was defined as the interval from the start of study drug to the first documentation of CR or PR.

    4. Progression-free Survival [Up to 5 years]

      Progression free survival (PFS) was defined as the interval from the start of study drug to the earlier of the first documentation of disease progression or death from any cause. The response definitions were based on the following standard criteria established for each indication: CLL: International Workshop on chronic lymphocytic leukemia (IWCLL), 2008 iNHL & MCL: Cheson, 2007

    5. Overall Survival [Up to 5 years]

      Overall Survival (OS) was defined as the interval from the start of study drug to death from any cause.

    6. Plasma Concentration of IDELA (Cohort 1, Cohorts 2 and 3, Cohort 5) [Predose, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0 hours postdose at Week 0; predose, 1.5 hours postdose at Weeks 4, 12, and 24]

    7. Plasma Concentration of IDELA (Cohort 4) [Predose at Week 0; predose, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0 hours postdose at Week 4; predose, 1.5 hours postdose at Week 12; and predose, 1.5 hours postdose at Week 24]

    8. Plasma Concentration of IDELA (Cohort 6) [Predose, 1.5 hours postdose at Weeks 0, 4, 12 and 24]

    9. Plasma Concentration of IDELA (Cohort 7) [Predose, 1.5 hours postdose at Weeks 0, 5 and 13]

    10. Sub-study: Plasma Concentration of IDELA (Cohorts 1-4) [pre dose and 0.5, 1, 1.5, 2.0, 3.0, 4.0, and 6.0 hours post dose]

    11. Plasma Concentration of Bendamustine [Predose, 0.25, 0.5, 0.75, 1.0, 1.25, 1.5, 2.0, 3.0, 4.0, 5.0, 6.0 hours postdose at Week 0]

    12. Plasma Concentration of Everolimus [Predose, 1.5 hours postdose at Weeks 0 and 4]

    13. Plasma Concentration of Lenalidomide [Predose, 1.5 hours postdose at Week 1 and predose at Week 5]

    Eligibility Criteria

    Criteria

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

    • Previously treated with relapsed or refractory disease (refractory defined as not responding to a standard regimen or progressing within 6 months of the last course of a standard regimen)

    • Disease status requirement:

    • For CLL patients, symptomatic disease that mandates treatment as defined by the International Workshop on Chronic Lymphocytic Lymphoma (IWCLL) 2008 criteria

    • For indolent NHL and MCL patients, measurable disease by CT scan defined as at least 1 lesion that measures > 2 cm in a single dimension

    • WHO performance status of ≤ 2

    • For men and women of child-bearing potential, willing to use adequate contraception (ie, latex condom, cervical cap, diaphragm, abstinence, etc.) for the entire duration of the study.

    • For Cohort 7 only: Women of child bearing potential must have 2 negative pregnancy tests prior to starting lenalidomide.

    • Able to provide written informed consent

    Key Exclusion Criteria:
    • Is not a good candidate to receive any of the drugs administered in the study for a given disease (idelalisib, bendamustine, rituximab, ofatumumab, fludarabine, everolimus, bortezomib, or chlorambucil), according to the clinical judgment of the investigator

    • Patients with atypical immunophenotype with t(11:14) translocation or cyclin D1 over-expression (CLL patients only)

    • Had radiotherapy, radioimmunotherapy, biological therapy, chemotherapy, or treatment with an investigational product within 4-weeks prior to the baseline disease status tests

    • Had treatment with a short course of corticosteroids for symptom relief within 1-week prior to the baseline disease status tests

    • Has had an allogeneic hematopoietic stem cell transplant

    • Has known active central nervous system involvement of the malignancy

    • Is pregnant or nursing

    • Has active, serious infection requiring systemic therapy. Patients may receive prophylactic antibiotics and antiviral therapy at the discretion of the investigator

    • Has absolute neutrophil count (ANC) < 1000/µL, unless it is related to underlying CLL, MCL or indolent NHL, the latter documented by > 50% infiltration of bone marrow by tumor cells

    • Has platelet count < 75000/µL, unless it is related to underlying CLL, MCL, or iNHL, the latter documented by > 50% infiltration of bone marrow by tumor cells

    • Has serum creatinine ≥ 2.0 mg/dL

    • For Cohort 7 only: Has creatinine clearance < 60 mL/min

    • Has serum bilirubin ≥ 2 mg/dL (unless due to Gilbert's syndrome) for patients with iNHL or CLL; for patients with MCL, serum bilirubin ≥ 1.5 x upper limit of normal

    • Has serum aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≥ 2 x upper limit of normal

    • Has Child-Pugh Class B or C hepatic impairment

    • Has a positive test for HIV antibodies

    • Has active hepatitis B or C (confirmed by RNA test). Patients with serologic evidence of prior exposure are eligible.

    • Prior treatment with idelalisib

    Note: Other protocol defined Inclusion/Exclusion criteria may apply.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Clearview Cancer Institute Huntsville Alabama United States 35805
    2 UCLA Los Angeles California United States 90024
    3 Stanford Cancer Center Palo Alto California United States 94304-5548
    4 Center for Cancer and Blood Disorders Bethesda Maryland United States 20817
    5 Washington University School of Medicine Saint Louis Missouri United States 63110
    6 Long Island Jewish Medical Center New Hyde Park New York United States 11040
    7 Weill Medical College of Cornell New York New York United States 10021
    8 Willamette Valley Cancer Institute and Research Center Springfield Oregon United States 97477
    9 Sarah Cannon Research Institute Nashville Tennessee United States 37203
    10 MD Anderson Cancer Houston Texas United States 77030
    11 North Star Lodge Cancer Center Yakima Washington United States 98902

    Sponsors and Collaborators

    • Gilead Sciences

    Investigators

    • Study Director: Gilead Study Director, Gilead Sciences

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Gilead Sciences
    ClinicalTrials.gov Identifier:
    NCT01088048
    Other Study ID Numbers:
    • 101-07
    First Posted:
    Mar 17, 2010
    Last Update Posted:
    Mar 18, 2021
    Last Verified:
    Feb 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Gilead Sciences
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details Participants were enrolled at study sites in United States. The first participant was screened on 25 March 2010. The last study visit occurred on 28 April 2015.
    Pre-assignment Detail 277 participants were screened. Per prespecified analysis, participants were grouped by disease (chronic lymphocytic leukemia, indolent non-Hodgkin lymphoma, mantle cell lymphoma) and by treatment regimen (cohort).
    Arm/Group Title Idelalisib + Rituximab Idelalisib + Bendamustine Idelalisib + Everolimus Idelalisib + Bortezomib Idelalisib + Rituximab + Bendamustine Idelalisib + Ofatumumab Idelalisib + Fludarabine Idelalisib + Chlorambucil Idelalisib + Rituximab + Chlorambucil Idelalisib + Rituximab + Lenalidomide
    Arm/Group Description Participants with chronic lymphocytic leukemia (CLL) and indolent non-Hodgkin lymphoma (iNHL) received treatments as follows: Cohort 1a: Idelalisib (IDELA) 100 mg orally twice daily (BID) on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 intravenously (IV) on Days 1, 8, 15 & 22, Cycles 1 & 2 Cohort 2a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Days 1, 8, 15, & 22, Cycles 1 & 2 Cohort 3e: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Days 1, 8, 15, & 22, Cycles 1 & 2 Cohort 4a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle, starting Cycle 2 Day 1 with the 5th dose of rituximab + rituximab 375 mg/m^2 IV on Days 1, 8, 15, & 22, Cycles 1 & 2 Participants with CLL and iNHL received treatments as follows: Cohort 1b: IDELA 100 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6 Cohort 2b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6 Cohort 3f: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6 Cohort 3g: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 70 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6 Cohort 4b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle starting Cycle 2, Day 3 (after the Cycle 2 bendamustine dosing) + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6 Participants with mantle cell lymphoma (MCL) received treatments as follows: Cohort 5a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + everolimus 10 mg orally once daily on Days 1 - 28 of each 28-day cycle Participants with MCL received treatments as follows: Cohort 5b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bortezomib 1.3 mg/m^2 subcutaneously on Days 1, 8 & 15 of each 28-day cycle Participants with CLL, iNHL and MCL received treatments as follows: Cohort 3a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6 Cohort 3b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + bendamustine 70 mg/m^2 IV on Days 1 & 2 of each 28-day cycle from Cycles 1 - 6 Cohort 5c: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6 Participants with CLL received treatments as follows: Cohort 3c: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + ofatumumab 12 doses (300 mg (Day 1 or Day 2, Dose 1), followed 1 week later by 1,000 mg weekly for 7 doses (Doses 2 - 8), followed 5 weeks later by 1,000 mg every 4 weeks for 4 doses (Doses 9 - 12)) Participants with CLL received treatments as follows: Cohort 3d: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + fludarabine 40 mg/m^2 orally on Days 1 - 5 of each 28-day cycle, Cycles 1 - 6 Participants with CLL received treatments as follows: Cohort 6a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + chlorambucil 10 mg/m^2 orally once daily for 7 days every 28 days, Cycles 1 - 12 Participants with CLL received treatments as follows: Cohort 6b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + chlorambucil 10 mg/m^2 orally once daily for 7 days every 28 days, Cycles 1 - 12 Participants with CLL and iNHL received treatments as follows: Cohort 7a: IDELA 150 mg orally BID on Days 1 - 35 of Cycle 1 (35 days) and Days 1 - 28 of all subsequent 28-day cycles + rituximab 375 mg/m^2 IV on Days 1 & 8 of the first cycle and Day 1 of Cycles 2 - 6 + lenalidomide 5 mg orally once daily starting on Days 8 - 28 of Cycle 1 (35 days) and Days 1 - 21 of the next five 28-day cycles Cohort 7b: IDELA 150 mg orally BID on Days 1 - 35 of Cycle 1 (35 days) and Days 1 - 28 of all subsequent 28-day cycles + rituximab 375 mg/m^2 IV on Days 1 & 8 of the first cycle and Day 1 of Cycles 2 - 6 + lenalidomide 10 mg orally once daily starting on Days 8 - 28 of Cycle 1 (35 days) and Days 1 - 21 of the next five 28-day cycles Cohort 7c: IDELA 150 mg orally BID on Days 1 - 35 of Cycle 1 (35 days) and Days 1 - 28 of all subsequent 28-day cycles + rituximab 375 mg/m^2 IV on Days 1 & 8 of the first cycle and Day 1 of Cycles 2 - 6 + lenalidomide 20 mg orally once daily starting on Days 8 - 28 of Cycle 1 (35 days) and Days 1 - 21 of the next five 28-day cycles
    Period Title: Overall Study
    STARTED 51 51 18 18 33 21 12 15 15 7
    Participants With CLL 19 18 0 0 15 21 12 15 14 1
    Participants With Indolent NHL 32 33 0 0 14 0 0 0 1 6
    Participants With MCL 0 0 18 18 4 0 0 0 0 0
    COMPLETED 29 24 4 4 16 10 6 10 8 3
    NOT COMPLETED 22 27 14 14 17 11 6 5 7 4

    Baseline Characteristics

    Arm/Group Title Idelalisib + Rituximab Idelalisib + Bendamustine Idelalisib + Everolimus Idelalisib + Bortezomib Idelalisib + Rituximab + Bendamustine Idelalisib + Ofatumumab Idelalisib + Fludarabine Idelalisib + Chlorambucil Idelalisib + Rituximab + Chlorambucil Idelalisib + Rituximab + Lenalidomide Total
    Arm/Group Description Participants with CLL and iNHL received treatments as follows: Cohort 1a: IDELA 100 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Days 1, 8, 15 & 22, Cycles 1 & 2 Cohort 2a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Days 1, 8, 15, & 22, Cycles 1 & 2 Cohort 3e: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Days 1, 8, 15, & 22, Cycles 1 & 2 Cohort 4a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle, starting Cycle 2 Day 1 with the 5th dose of rituximab + rituximab 375 mg/m^2 IV on Days 1, 8, 15, & 22, Cycles 1 & 2 Participants with CLL and iNHL received treatments as follows: Cohort 1b: IDELA 100 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6 Cohort 2b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6 Cohort 3f: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6 Cohort 3g: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 70 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6 Cohort 4b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle starting Cycle 2, Day 3 (after the Cycle 2 bendamustine dosing) + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6 Participants with MCL received treatments as follows: Cohort 5a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + everolimus 10 mg orally once daily on Days 1 - 28 of each 28-day cycle Participants with MCL received treatments as follows: Cohort 5b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bortezomib 1.3 mg/m^2 subcutaneously on Days 1, 8 & 15 of each 28-day cycle Participants with CLL, iNHL and MCL received treatments as follows: Cohort 3a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6 Cohort 3b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + bendamustine 70 mg/m^2 IV on Days 1 & 2 of each 28-day cycle from Cycles 1 - 6 Cohort 5c: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6 Participants with CLL received treatments as follows: Cohort 3c: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + ofatumumab 12 doses (300 mg (Day 1 or Day 2, Dose 1), followed 1 week later by 1,000 mg weekly for 7 doses (Doses 2 - 8), followed 5 weeks later by 1,000 mg every 4 weeks for 4 doses (Doses 9 - 12)) Participants with CLL received treatments as follows: Cohort 3d: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + fludarabine 40 mg/m^2 orally on Days 1 - 5 of each 28-day cycle, Cycles 1 - 6 Participants with CLL received treatments as follows: Cohort 6a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + chlorambucil 10 mg/m^2 orally once daily for 7 days every 28 days, Cycles 1 - 12 Participants with CLL received treatments as follows: Cohort 6b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + chlorambucil 10 mg/m^2 orally once daily for 7 days every 28 days, Cycles 1 - 12 Participants with CLL and iNHL received treatments as follows: Cohort 7a: IDELA 150 mg orally BID on Days 1 - 35 of Cycle 1 (35 days) and Days 1 - 28 of all subsequent 28-day cycles + rituximab 375 mg/m^2 IV on Days 1 & 8 of the first cycle and Day 1 of Cycles 2 - 6 + lenalidomide 5 mg orally once daily starting on Days 8 - 28 of Cycle 1 (35 days) and Days 1 - 21 of the next five 28-day cycles Cohort 7b: IDELA 150 mg orally BID on Days 1 - 35 of Cycle 1 (35 days) and Days 1 - 28 of all subsequent 28-day cycles + rituximab 375 mg/m^2 IV on Days 1 & 8 of the first cycle and Day 1 of Cycles 2 - 6 + lenalidomide 10 mg orally once daily starting on Days 8 - 28 of Cycle 1 (35 days) and Days 1 - 21 of the next five 28-day cycles Cohort 7c: IDELA 150 mg orally BID on Days 1 - 35 of Cycle 1 (35 days) and Days 1 - 28 of all subsequent 28-day cycles + rituximab 375 mg/m^2 IV on Days 1 & 8 of the first cycle and Day 1 of Cycles 2 - 6 + lenalidomide 20 mg orally once daily starting on Days 8 - 28 of Cycle 1 (35 days) and Days 1 - 21 of the next five 28-day cycles Total of all reporting groups
    Overall Participants 51 51 18 18 33 21 12 15 15 7 241
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    65
    (10.1)
    61
    (11.2)
    69
    (7.1)
    72
    (6.0)
    60
    (8.3)
    66
    (9.7)
    69
    (7.1)
    63
    (7.8)
    68
    (10.0)
    61
    (8.3)
    64
    (9.9)
    Sex: Female, Male (Count of Participants)
    Female
    16
    31.4%
    21
    41.2%
    7
    38.9%
    3
    16.7%
    12
    36.4%
    6
    28.6%
    4
    33.3%
    1
    6.7%
    4
    26.7%
    2
    28.6%
    76
    31.5%
    Male
    35
    68.6%
    30
    58.8%
    11
    61.1%
    15
    83.3%
    21
    63.6%
    15
    71.4%
    8
    66.7%
    14
    93.3%
    11
    73.3%
    5
    71.4%
    165
    68.5%
    Race/Ethnicity, Customized (Count of Participants)
    White/Caucasian
    42
    82.4%
    45
    88.2%
    16
    88.9%
    14
    77.8%
    29
    87.9%
    20
    95.2%
    8
    66.7%
    14
    93.3%
    15
    100%
    6
    85.7%
    209
    86.7%
    Black or African American
    2
    3.9%
    3
    5.9%
    0
    0%
    0
    0%
    1
    3%
    0
    0%
    1
    8.3%
    1
    6.7%
    0
    0%
    1
    14.3%
    9
    3.7%
    Asian
    5
    9.8%
    1
    2%
    1
    5.6%
    2
    11.1%
    1
    3%
    0
    0%
    1
    8.3%
    0
    0%
    0
    0%
    0
    0%
    11
    4.6%
    Other
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    4.8%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    0.4%
    Not Reported
    2
    3.9%
    2
    3.9%
    1
    5.6%
    2
    11.1%
    2
    6.1%
    0
    0%
    2
    16.7%
    0
    0%
    0
    0%
    0
    0%
    11
    4.6%
    Race/Ethnicity, Customized (Count of Participants)
    Hispanic or Latino
    0
    0%
    2
    3.9%
    0
    0%
    1
    5.6%
    0
    0%
    0
    0%
    0
    0%
    1
    6.7%
    0
    0%
    0
    0%
    4
    1.7%
    Not Hispanic or Latino
    51
    100%
    49
    96.1%
    18
    100%
    17
    94.4%
    31
    93.9%
    21
    100%
    11
    91.7%
    14
    93.3%
    15
    100%
    7
    100%
    234
    97.1%
    Missing
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    2
    6.1%
    0
    0%
    1
    8.3%
    0
    0%
    0
    0%
    0
    0%
    3
    1.2%

    Outcome Measures

    1. Primary Outcome
    Title Duration of Exposure to IDELA
    Description Duration of exposure to IDELA was summarized using descriptive statistics.
    Time Frame First dose date up to 12 months

    Outcome Measure Data

    Analysis Population Description
    The ITT analysis set included participants who received at least 1 dose of study drug (idelalisib or combination drugs). Per prespecified analysis, participants for this outcome measure were grouped by disease and treatment regimen (cohort).
    Arm/Group Title Idelalisib + Rituximab Idelalisib + Bendamustine Idelalisib + Everolimus Idelalisib + Bortezomib Idelalisib + Rituximab + Bendamustine Idelalisib + Ofatumumab Idelalisib + Fludarabine Idelalisib + Chlorambucil Idelalisib + Rituximab + Chlorambucil Idelalisib + Rituximab + Lenalidomide
    Arm/Group Description Participants with chronic CLL and iNHL received treatments as follows: Cohort 1a: IDELA 100 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Days 1, 8, 15 & 22, Cycles 1 & 2 Cohort 2a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Days 1, 8, 15, & 22, Cycles 1 & 2 Cohort 3e: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Days 1, 8, 15, & 22, Cycles 1 & 2 Cohort 4a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle, starting Cycle 2 Day 1 with the 5th dose of rituximab + rituximab 375 mg/m^2 IV on Days 1, 8, 15, & 22, Cycles 1 & 2 Participants with CLL and iNHL received treatments as follows: Cohort 1b: IDELA 100 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6 Cohort 2b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6 Cohort 3f: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6 Cohort 3g: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 70 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6 Cohort 4b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle starting Cycle 2, Day 3 (after the Cycle 2 bendamustine dosing) + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6 Participants with MCL received treatments as follows: Cohort 5a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + everolimus 10 mg orally once daily on Days 1 - 28 of each 28-day cycle Participants with MCL received treatments as follows: Cohort 5b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bortezomib 1.3 mg/m^2 subcutaneously on Days 1, 8 & 15 of each 28-day cycle Participants with CLL, iNHL and MCL received treatments as follows: Cohort 3a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6 Cohort 3b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + bendamustine 70 mg/m^2 IV on Days 1 & 2 of each 28-day cycle from Cycles 1 - 6 Cohort 5c: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6 Participants with CLL received treatments as follows: Cohort 3c: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + ofatumumab 12 doses (300 mg (Day 1 or Day 2, Dose 1), followed 1 week later by 1,000 mg weekly for 7 doses (Doses 2 - 8), followed 5 weeks later by 1,000 mg every 4 weeks for 4 doses (Doses 9 - 12)) Participants with CLL received treatments as follows: Cohort 3d: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + fludarabine 40 mg/m^2 orally on Days 1 - 5 of each 28-day cycle, Cycles 1 - 6 Participants with CLL received treatments as follows: Cohort 6a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + chlorambucil 10 mg/m^2 orally once daily for 7 days every 28 days, Cycles 1 - 12 Participants with CLL received treatments as follows: Cohort 6b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + chlorambucil 10 mg/m^2 orally once daily for 7 days every 28 days, Cycles 1 - 12 Participants with CLL and iNHL received treatments as follows: Cohort 7a: IDELA 150 mg orally BID on Days 1 - 35 of Cycle 1 (35 days) and Days 1 - 28 of all subsequent 28-day cycles + rituximab 375 mg/m^2 IV on Days 1 & 8 of the first cycle and Day 1 of Cycles 2 - 6 + lenalidomide 5 mg orally once daily starting on Days 8 - 28 of Cycle 1 (35 days) and Days 1 - 21 of the next five 28-day cycles Cohort 7b: IDELA 150 mg orally BID on Days 1 - 35 of Cycle 1 (35 days) and Days 1 - 28 of all subsequent 28-day cycles + rituximab 375 mg/m^2 IV on Days 1 & 8 of the first cycle and Day 1 of Cycles 2 - 6 + lenalidomide 10 mg orally once daily starting on Days 8 - 28 of Cycle 1 (35 days) and Days 1 - 21 of the next five 28-day cycles Cohort 7c: IDELA 150 mg orally BID on Days 1 - 35 of Cycle 1 (35 days) and Days 1 - 28 of all subsequent 28-day cycles + rituximab 375 mg/m^2 IV on Days 1 & 8 of the first cycle and Day 1 of Cycles 2 - 6 + lenalidomide 20 mg orally once daily starting on Days 8 - 28 of Cycle 1 (35 days) and Days 1 - 21 of the next five 28-day cycles
    Measure Participants 51 51 18 18 33 21 12 15 15 7
    Mean (Standard Deviation) [months]
    8.1
    (3.74)
    7.6
    (3.96)
    4.2
    (3.92)
    5.1
    (3.90)
    8.0
    (4.16)
    8.3
    (4.03)
    8.9
    (3.57)
    8.8
    (3.76)
    8.7
    (3.01)
    7.7
    (4.78)
    2. Primary Outcome
    Title Toxicity of Administration of IDELA
    Description Percentage of participants experiencing toxicities of administration of IDELA were measured according to the Common Terminology Criteria for Adverse Events v4.02
    Time Frame First dose date up to 5 years

    Outcome Measure Data

    Analysis Population Description
    Participants in the ITT analysis set were analyzed. Per prespecified analysis, participants for this outcome measure were grouped by disease and treatment regimen (cohort).
    Arm/Group Title Idelalisib + Rituximab Idelalisib + Bendamustine Idelalisib + Everolimus Idelalisib + Bortezomib Idelalisib + Rituximab + Bendamustine Idelalisib + Ofatumumab Idelalisib + Fludarabine Idelalisib + Chlorambucil Idelalisib + Rituximab + Chlorambucil Idelalisib + Rituximab + Lenalidomide
    Arm/Group Description Participants with chronic CLL and iNHL received treatments as follows: Cohort 1a: IDELA 100 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Days 1, 8, 15 & 22, Cycles 1 & 2 Cohort 2a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Days 1, 8, 15, & 22, Cycles 1 & 2 Cohort 3e: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Days 1, 8, 15, & 22, Cycles 1 & 2 Cohort 4a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle, starting Cycle 2 Day 1 with the 5th dose of rituximab + rituximab 375 mg/m^2 IV on Days 1, 8, 15, & 22, Cycles 1 & 2 Participants with CLL and iNHL received treatments as follows: Cohort 1b: IDELA 100 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6 Cohort 2b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6 Cohort 3f: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6 Cohort 3g: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 70 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6 Cohort 4b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle starting Cycle 2, Day 3 (after the Cycle 2 bendamustine dosing) + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6 Participants with MCL received treatments as follows: Cohort 5a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + everolimus 10 mg orally once daily on Days 1 - 28 of each 28-day cycle Participants with MCL received treatments as follows: Cohort 5b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bortezomib 1.3 mg/m^2 subcutaneously on Days 1, 8 & 15 of each 28-day cycle Participants with CLL, iNHL and MCL received treatments as follows: Cohort 3a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6 Cohort 3b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + bendamustine 70 mg/m^2 IV on Days 1 & 2 of each 28-day cycle from Cycles 1 - 6 Cohort 5c: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6 Participants with CLL received treatments as follows: Cohort 3c: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + ofatumumab 12 doses (300 mg (Day 1 or Day 2, Dose 1), followed 1 week later by 1,000 mg weekly for 7 doses (Doses 2 - 8), followed 5 weeks later by 1,000 mg every 4 weeks for 4 doses (Doses 9 - 12)) Participants with CLL received treatments as follows: Cohort 3d: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + fludarabine 40 mg/m^2 orally on Days 1 - 5 of each 28-day cycle, Cycles 1 - 6 Participants with CLL received treatments as follows: Cohort 6a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + chlorambucil 10 mg/m^2 orally once daily for 7 days every 28 days, Cycles 1 - 12 Participants with CLL received treatments as follows: Cohort 6b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + chlorambucil 10 mg/m^2 orally once daily for 7 days every 28 days, Cycles 1 - 12 Participants with CLL and iNHL received treatments as follows: Cohort 7a: IDELA 150 mg orally BID on Days 1 - 35 of Cycle 1 (35 days) and Days 1 - 28 of all subsequent 28-day cycles + rituximab 375 mg/m^2 IV on Days 1 & 8 of the first cycle and Day 1 of Cycles 2 - 6 + lenalidomide 5 mg orally once daily starting on Days 8 - 28 of Cycle 1 (35 days) and Days 1 - 21 of the next five 28-day cycles Cohort 7b: IDELA 150 mg orally BID on Days 1 - 35 of Cycle 1 (35 days) and Days 1 - 28 of all subsequent 28-day cycles + rituximab 375 mg/m^2 IV on Days 1 & 8 of the first cycle and Day 1 of Cycles 2 - 6 + lenalidomide 10 mg orally once daily starting on Days 8 - 28 of Cycle 1 (35 days) and Days 1 - 21 of the next five 28-day cycles Cohort 7c: IDELA 150 mg orally BID on Days 1 - 35 of Cycle 1 (35 days) and Days 1 - 28 of all subsequent 28-day cycles + rituximab 375 mg/m^2 IV on Days 1 & 8 of the first cycle and Day 1 of Cycles 2 - 6 + lenalidomide 20 mg orally once daily starting on Days 8 - 28 of Cycle 1 (35 days) and Days 1 - 21 of the next five 28-day cycles
    Measure Participants 51 51 18 18 33 21 12 15 15 7
    Number [percentage of participants]
    100.0
    196.1%
    100.0
    196.1%
    100.0
    555.6%
    83.33
    462.9%
    100.0
    303%
    100.0
    476.2%
    100.0
    833.3%
    100.0
    666.7%
    100.0
    666.7%
    100.0
    1428.6%
    3. Secondary Outcome
    Title Overall Response Rate
    Description Overall Response Rate (ORR) was defined as the percentage of participants achieving a complete response (CR) or partial response (PR). The response definitions were based on the following standard criteria established for each indication: CLL: International Workshop on chronic lymphocytic leukemia (IWCLL),2008 iNHL & MCL: Cheson, 2007
    Time Frame Up to 5 years

    Outcome Measure Data

    Analysis Population Description
    Participants in the ITT analysis set were analyzed. Per prespecified analysis, participants for this outcome measure were grouped by disease and treatment regimen (cohort).
    Arm/Group Title Idelalisib + Rituximab Idelalisib + Bendamustine Idelalisib + Everolimus Idelalisib + Bortezomib Idelalisib + Rituximab + Bendamustine Idelalisib + Ofatumumab Idelalisib + Fludarabine Idelalisib + Chlorambucil Idelalisib + Rituximab + Chlorambucil Idelalisib + Rituximab + Lenalidomide
    Arm/Group Description Participants with chronic CLL and iNHL received treatments as follows: Cohort 1a: IDELA 100 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Days 1, 8, 15 & 22, Cycles 1 & 2 Cohort 2a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Days 1, 8, 15, & 22, Cycles 1 & 2 Cohort 3e: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Days 1, 8, 15, & 22, Cycles 1 & 2 Cohort 4a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle, starting Cycle 2 Day 1 with the 5th dose of rituximab + rituximab 375 mg/m^2 IV on Days 1, 8, 15, & 22, Cycles 1 & 2 Participants with CLL and iNHL received treatments as follows: Cohort 1b: IDELA 100 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6 Cohort 2b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6 Cohort 3f: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6 Cohort 3g: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 70 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6 Cohort 4b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle starting Cycle 2, Day 3 (after the Cycle 2 bendamustine dosing) + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6 Participants with MCL received treatments as follows: Cohort 5a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + everolimus 10 mg orally once daily on Days 1 - 28 of each 28-day cycle Participants with MCL received treatments as follows: Cohort 5b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bortezomib 1.3 mg/m^2 subcutaneously on Days 1, 8 & 15 of each 28-day cycle Participants with CLL, iNHL and MCL received treatments as follows: Cohort 3a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6 Cohort 3b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + bendamustine 70 mg/m^2 IV on Days 1 & 2 of each 28-day cycle from Cycles 1 - 6 Cohort 5c: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6 Participants with CLL received treatments as follows: Cohort 3c: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + ofatumumab 12 doses (300 mg (Day 1 or Day 2, Dose 1), followed 1 week later by 1,000 mg weekly for 7 doses (Doses 2 - 8), followed 5 weeks later by 1,000 mg every 4 weeks for 4 doses (Doses 9 - 12)) Participants with CLL received treatments as follows: Cohort 3d: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + fludarabine 40 mg/m^2 orally on Days 1 - 5 of each 28-day cycle, Cycles 1 - 6 Participants with CLL received treatments as follows: Cohort 6a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + chlorambucil 10 mg/m^2 orally once daily for 7 days every 28 days, Cycles 1 - 12 Participants with CLL received treatments as follows: Cohort 6b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + chlorambucil 10 mg/m^2 orally once daily for 7 days every 28 days, Cycles 1 - 12 Participants with CLL and iNHL received treatments as follows: Cohort 7a: IDELA 150 mg orally BID on Days 1 - 35 of Cycle 1 (35 days) and Days 1 - 28 of all subsequent 28-day cycles + rituximab 375 mg/m^2 IV on Days 1 & 8 of the first cycle and Day 1 of Cycles 2 - 6 + lenalidomide 5 mg orally once daily starting on Days 8 - 28 of Cycle 1 (35 days) and Days 1 - 21 of the next five 28-day cycles Cohort 7b: IDELA 150 mg orally BID on Days 1 - 35 of Cycle 1 (35 days) and Days 1 - 28 of all subsequent 28-day cycles + rituximab 375 mg/m^2 IV on Days 1 & 8 of the first cycle and Day 1 of Cycles 2 - 6 + lenalidomide 10 mg orally once daily starting on Days 8 - 28 of Cycle 1 (35 days) and Days 1 - 21 of the next five 28-day cycles Cohort 7c: IDELA 150 mg orally BID on Days 1 - 35 of Cycle 1 (35 days) and Days 1 - 28 of all subsequent 28-day cycles + rituximab 375 mg/m^2 IV on Days 1 & 8 of the first cycle and Day 1 of Cycles 2 - 6 + lenalidomide 20 mg orally once daily starting on Days 8 - 28 of Cycle 1 (35 days) and Days 1 - 21 of the next five 28-day cycles
    Measure Participants 51 51 18 18 33 21 12 15 15 7
    Number (95% Confidence Interval) [percentage of participants]
    78.4
    153.7%
    84.3
    165.3%
    44.4
    246.7%
    61.1
    339.4%
    81.8
    247.9%
    71.4
    340%
    91.7
    764.2%
    66.7
    444.7%
    93.3
    622%
    71.4
    1020%
    4. Secondary Outcome
    Title Duration of Response
    Description Duration of response (DOR) was defined as the interval from the first documentation of CR or PR to the earlier of the first documentation of disease progression or death from any cause.
    Time Frame Up to 5 years

    Outcome Measure Data

    Analysis Population Description
    Participants in the ITT analysis set with available data were analyzed. Per prespecified analysis, participants for this outcome measure were grouped by disease and treatment regimen (cohort).
    Arm/Group Title Idelalisib + Rituximab Idelalisib + Bendamustine Idelalisib + Everolimus Idelalisib + Bortezomib Idelalisib + Rituximab + Bendamustine Idelalisib + Ofatumumab Idelalisib + Fludarabine Idelalisib + Chlorambucil Idelalisib + Rituximab + Chlorambucil Idelalisib + Rituximab + Lenalidomide
    Arm/Group Description Participants with chronic CLL and iNHL received treatments as follows: Cohort 1a: IDELA 100 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Days 1, 8, 15 & 22, Cycles 1 & 2 Cohort 2a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Days 1, 8, 15, & 22, Cycles 1 & 2 Cohort 3e: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Days 1, 8, 15, & 22, Cycles 1 & 2 Cohort 4a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle, starting Cycle 2 Day 1 with the 5th dose of rituximab + rituximab 375 mg/m^2 IV on Days 1, 8, 15, & 22, Cycles 1 & 2 Participants with CLL and iNHL received treatments as follows: Cohort 1b: IDELA 100 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6 Cohort 2b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6 Cohort 3f: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6 Cohort 3g: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 70 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6 Cohort 4b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle starting Cycle 2, Day 3 (after the Cycle 2 bendamustine dosing) + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6 Participants with MCL received treatments as follows: Cohort 5a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + everolimus 10 mg orally once daily on Days 1 - 28 of each 28-day cycle Participants with MCL received treatments as follows: Cohort 5b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bortezomib 1.3 mg/m^2 subcutaneously on Days 1, 8 & 15 of each 28-day cycle Participants with CLL, iNHL and MCL received treatments as follows: Cohort 3a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6 Cohort 3b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + bendamustine 70 mg/m^2 IV on Days 1 & 2 of each 28-day cycle from Cycles 1 - 6 Cohort 5c: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6 Participants with CLL received treatments as follows: Cohort 3c: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + ofatumumab 12 doses (300 mg (Day 1 or Day 2, Dose 1), followed 1 week later by 1,000 mg weekly for 7 doses (Doses 2 - 8), followed 5 weeks later by 1,000 mg every 4 weeks for 4 doses (Doses 9 - 12)) Participants with CLL received treatments as follows: Cohort 3d: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + fludarabine 40 mg/m^2 orally on Days 1 - 5 of each 28-day cycle, Cycles 1 - 6 Participants with CLL received treatments as follows: Cohort 6a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + chlorambucil 10 mg/m^2 orally once daily for 7 days every 28 days, Cycles 1 - 12 Participants with CLL received treatments as follows: Cohort 6b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + chlorambucil 10 mg/m^2 orally once daily for 7 days every 28 days, Cycles 1 - 12 Participants with CLL and iNHL received treatments as follows: Cohort 7a: IDELA 150 mg orally BID on Days 1 - 35 of Cycle 1 (35 days) and Days 1 - 28 of all subsequent 28-day cycles + rituximab 375 mg/m^2 IV on Days 1 & 8 of the first cycle and Day 1 of Cycles 2 - 6 + lenalidomide 5 mg orally once daily starting on Days 8 - 28 of Cycle 1 (35 days) and Days 1 - 21 of the next five 28-day cycles Cohort 7b: IDELA 150 mg orally BID on Days 1 - 35 of Cycle 1 (35 days) and Days 1 - 28 of all subsequent 28-day cycles + rituximab 375 mg/m^2 IV on Days 1 & 8 of the first cycle and Day 1 of Cycles 2 - 6 + lenalidomide 10 mg orally once daily starting on Days 8 - 28 of Cycle 1 (35 days) and Days 1 - 21 of the next five 28-day cycles Cohort 7c: IDELA 150 mg orally BID on Days 1 - 35 of Cycle 1 (35 days) and Days 1 - 28 of all subsequent 28-day cycles + rituximab 375 mg/m^2 IV on Days 1 & 8 of the first cycle and Day 1 of Cycles 2 - 6 + lenalidomide 20 mg orally once daily starting on Days 8 - 28 of Cycle 1 (35 days) and Days 1 - 21 of the next five 28-day cycles
    Measure Participants 40 43 8 11 27 15 11 10 14 5
    Median (95% Confidence Interval) [months]
    NA
    NA
    5.6
    9.3
    NA
    NA
    NA
    NA
    NA
    NA
    5. Secondary Outcome
    Title Time to Response
    Description Time to response (TTR) was defined as the interval from the start of study drug to the first documentation of CR or PR.
    Time Frame Up to 5 years

    Outcome Measure Data

    Analysis Population Description
    Participants in the ITT analysis set with available data were analyzed. Per prespecified analysis, participants for this outcome measure were grouped by disease and treatment regimen (cohort).
    Arm/Group Title Idelalisib + Rituximab Idelalisib + Bendamustine Idelalisib + Everolimus Idelalisib + Bortezomib Idelalisib + Rituximab + Bendamustine Idelalisib + Ofatumumab Idelalisib + Fludarabine Idelalisib + Chlorambucil Idelalisib + Rituximab + Chlorambucil Idelalisib + Rituximab + Lenalidomide
    Arm/Group Description Participants with chronic CLL and iNHL received treatments as follows: Cohort 1a: IDELA 100 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Days 1, 8, 15 & 22, Cycles 1 & 2 Cohort 2a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Days 1, 8, 15, & 22, Cycles 1 & 2 Cohort 3e: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Days 1, 8, 15, & 22, Cycles 1 & 2 Cohort 4a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle, starting Cycle 2 Day 1 with the 5th dose of rituximab + rituximab 375 mg/m^2 IV on Days 1, 8, 15, & 22, Cycles 1 & 2 Participants with CLL and iNHL received treatments as follows: Cohort 1b: IDELA 100 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6 Cohort 2b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6 Cohort 3f: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6 Cohort 3g: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 70 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6 Cohort 4b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle starting Cycle 2, Day 3 (after the Cycle 2 bendamustine dosing) + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6 Participants with MCL received treatments as follows: Cohort 5a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + everolimus 10 mg orally once daily on Days 1 - 28 of each 28-day cycle Participants with MCL received treatments as follows: Cohort 5b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bortezomib 1.3 mg/m^2 subcutaneously on Days 1, 8 & 15 of each 28-day cycle Participants with CLL, iNHL and MCL received treatments as follows: Cohort 3a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6 Cohort 3b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + bendamustine 70 mg/m^2 IV on Days 1 & 2 of each 28-day cycle from Cycles 1 - 6 Cohort 5c: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6 Participants with CLL received treatments as follows: Cohort 3c: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + ofatumumab 12 doses (300 mg (Day 1 or Day 2, Dose 1), followed 1 week later by 1,000 mg weekly for 7 doses (Doses 2 - 8), followed 5 weeks later by 1,000 mg every 4 weeks for 4 doses (Doses 9 - 12)) Participants with CLL received treatments as follows: Cohort 3d: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + fludarabine 40 mg/m^2 orally on Days 1 - 5 of each 28-day cycle, Cycles 1 - 6 Participants with CLL received treatments as follows: Cohort 6a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + chlorambucil 10 mg/m^2 orally once daily for 7 days every 28 days, Cycles 1 - 12 Participants with CLL received treatments as follows: Cohort 6b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + chlorambucil 10 mg/m^2 orally once daily for 7 days every 28 days, Cycles 1 - 12 Participants with CLL and iNHL received treatments as follows: Cohort 7a: IDELA 150 mg orally BID on Days 1 - 35 of Cycle 1 (35 days) and Days 1 - 28 of all subsequent 28-day cycles + rituximab 375 mg/m^2 IV on Days 1 & 8 of the first cycle and Day 1 of Cycles 2 - 6 + lenalidomide 5 mg orally once daily starting on Days 8 - 28 of Cycle 1 (35 days) and Days 1 - 21 of the next five 28-day cycles Cohort 7b: IDELA 150 mg orally BID on Days 1 - 35 of Cycle 1 (35 days) and Days 1 - 28 of all subsequent 28-day cycles + rituximab 375 mg/m^2 IV on Days 1 & 8 of the first cycle and Day 1 of Cycles 2 - 6 + lenalidomide 10 mg orally once daily starting on Days 8 - 28 of Cycle 1 (35 days) and Days 1 - 21 of the next five 28-day cycles Cohort 7c: IDELA 150 mg orally BID on Days 1 - 35 of Cycle 1 (35 days) and Days 1 - 28 of all subsequent 28-day cycles + rituximab 375 mg/m^2 IV on Days 1 & 8 of the first cycle and Day 1 of Cycles 2 - 6 + lenalidomide 20 mg orally once daily starting on Days 8 - 28 of Cycle 1 (35 days) and Days 1 - 21 of the next five 28-day cycles
    Measure Participants 40 43 8 11 27 15 11 10 14 5
    Median (Inter-Quartile Range) [months]
    1.9
    1.9
    1.9
    1.9
    1.9
    1.9
    1.9
    1.9
    1.9
    3.0
    6. Secondary Outcome
    Title Progression-free Survival
    Description Progression free survival (PFS) was defined as the interval from the start of study drug to the earlier of the first documentation of disease progression or death from any cause. The response definitions were based on the following standard criteria established for each indication: CLL: International Workshop on chronic lymphocytic leukemia (IWCLL), 2008 iNHL & MCL: Cheson, 2007
    Time Frame Up to 5 years

    Outcome Measure Data

    Analysis Population Description
    Participants in the ITT analysis set were analyzed. Per prespecified analysis, participants for this outcome measure were grouped by disease and treatment regimen (cohort).
    Arm/Group Title Idelalisib + Rituximab Idelalisib + Bendamustine Idelalisib + Everolimus Idelalisib + Bortezomib Idelalisib + Rituximab + Bendamustine Idelalisib + Ofatumumab Idelalisib + Fludarabine Idelalisib + Chlorambucil Idelalisib + Rituximab + Chlorambucil Idelalisib + Rituximab + Lenalidomide
    Arm/Group Description Participants with chronic CLL and iNHL received treatments as follows: Cohort 1a: IDELA 100 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Days 1, 8, 15 & 22, Cycles 1 & 2 Cohort 2a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Days 1, 8, 15, & 22, Cycles 1 & 2 Cohort 3e: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Days 1, 8, 15, & 22, Cycles 1 & 2 Cohort 4a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle, starting Cycle 2 Day 1 with the 5th dose of rituximab + rituximab 375 mg/m^2 IV on Days 1, 8, 15, & 22, Cycles 1 & 2 Participants with CLL and iNHL received treatments as follows: Cohort 1b: IDELA 100 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6 Cohort 2b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6 Cohort 3f: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6 Cohort 3g: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 70 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6 Cohort 4b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle starting Cycle 2, Day 3 (after the Cycle 2 bendamustine dosing) + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6 Participants with MCL received treatments as follows: Cohort 5a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + everolimus 10 mg orally once daily on Days 1 - 28 of each 28-day cycle Participants with MCL received treatments as follows: Cohort 5b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bortezomib 1.3 mg/m^2 subcutaneously on Days 1, 8 & 15 of each 28-day cycle Participants with CLL, iNHL and MCL received treatments as follows: Cohort 3a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6 Cohort 3b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + bendamustine 70 mg/m^2 IV on Days 1 & 2 of each 28-day cycle from Cycles 1 - 6 Cohort 5c: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6 Participants with CLL received treatments as follows: Cohort 3c: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + ofatumumab 12 doses (300 mg (Day 1 or Day 2, Dose 1), followed 1 week later by 1,000 mg weekly for 7 doses (Doses 2 - 8), followed 5 weeks later by 1,000 mg every 4 weeks for 4 doses (Doses 9 - 12)) Participants with CLL received treatments as follows: Cohort 3d: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + fludarabine 40 mg/m^2 orally on Days 1 - 5 of each 28-day cycle, Cycles 1 - 6 Participants with CLL received treatments as follows: Cohort 6a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + chlorambucil 10 mg/m^2 orally once daily for 7 days every 28 days, Cycles 1 - 12 Participants with CLL received treatments as follows: Cohort 6b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + chlorambucil 10 mg/m^2 orally once daily for 7 days every 28 days, Cycles 1 - 12 Participants with CLL and iNHL received treatments as follows: Cohort 7a: IDELA 150 mg orally BID on Days 1 - 35 of Cycle 1 (35 days) and Days 1 - 28 of all subsequent 28-day cycles + rituximab 375 mg/m^2 IV on Days 1 & 8 of the first cycle and Day 1 of Cycles 2 - 6 + lenalidomide 5 mg orally once daily starting on Days 8 - 28 of Cycle 1 (35 days) and Days 1 - 21 of the next five 28-day cycles Cohort 7b: IDELA 150 mg orally BID on Days 1 - 35 of Cycle 1 (35 days) and Days 1 - 28 of all subsequent 28-day cycles + rituximab 375 mg/m^2 IV on Days 1 & 8 of the first cycle and Day 1 of Cycles 2 - 6 + lenalidomide 10 mg orally once daily starting on Days 8 - 28 of Cycle 1 (35 days) and Days 1 - 21 of the next five 28-day cycles Cohort 7c: IDELA 150 mg orally BID on Days 1 - 35 of Cycle 1 (35 days) and Days 1 - 28 of all subsequent 28-day cycles + rituximab 375 mg/m^2 IV on Days 1 & 8 of the first cycle and Day 1 of Cycles 2 - 6 + lenalidomide 20 mg orally once daily starting on Days 8 - 28 of Cycle 1 (35 days) and Days 1 - 21 of the next five 28-day cycles
    Measure Participants 51 51 18 18 33 21 12 15 15 7
    Median (95% Confidence Interval) [months]
    NA
    NA
    4.3
    8.1
    NA
    NA
    NA
    NA
    NA
    NA
    7. Secondary Outcome
    Title Overall Survival
    Description Overall Survival (OS) was defined as the interval from the start of study drug to death from any cause.
    Time Frame Up to 5 years

    Outcome Measure Data

    Analysis Population Description
    Participants in the ITT analysis set were analyzed. Per prespecified analysis, participants for this outcome measure were grouped by disease and treatment regimen (cohort).
    Arm/Group Title Idelalisib + Rituximab Idelalisib + Bendamustine Idelalisib + Everolimus Idelalisib + Bortezomib Idelalisib + Rituximab + Bendamustine Idelalisib + Ofatumumab Idelalisib + Fludarabine Idelalisib + Chlorambucil Idelalisib + Rituximab + Chlorambucil Idelalisib + Rituximab + Lenalidomide
    Arm/Group Description Participants with chronic CLL and iNHL received treatments as follows: Cohort 1a: IDELA 100 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Days 1, 8, 15 & 22, Cycles 1 & 2 Cohort 2a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Days 1, 8, 15, & 22, Cycles 1 & 2 Cohort 3e: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Days 1, 8, 15, & 22, Cycles 1 & 2 Cohort 4a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle, starting Cycle 2 Day 1 with the 5th dose of rituximab + rituximab 375 mg/m^2 IV on Days 1, 8, 15, & 22, Cycles 1 & 2 Participants with CLL and iNHL received treatments as follows: Cohort 1b: IDELA 100 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6 Cohort 2b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6 Cohort 3f: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6 Cohort 3g: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 70 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6 Cohort 4b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle starting Cycle 2, Day 3 (after the Cycle 2 bendamustine dosing) + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6 Participants with MCL received treatments as follows: Cohort 5a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + everolimus 10 mg orally once daily on Days 1 - 28 of each 28-day cycle Participants with MCL received treatments as follows: Cohort 5b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bortezomib 1.3 mg/m^2 subcutaneously on Days 1, 8 & 15 of each 28-day cycle Participants with CLL, iNHL and MCL received treatments as follows: Cohort 3a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6 Cohort 3b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + bendamustine 70 mg/m^2 IV on Days 1 & 2 of each 28-day cycle from Cycles 1 - 6 Cohort 5c: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6 Participants with CLL received treatments as follows: Cohort 3c: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + ofatumumab 12 doses (300 mg (Day 1 or Day 2, Dose 1), followed 1 week later by 1,000 mg weekly for 7 doses (Doses 2 - 8), followed 5 weeks later by 1,000 mg every 4 weeks for 4 doses (Doses 9 - 12)) Participants with CLL received treatments as follows: Cohort 3d: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + fludarabine 40 mg/m^2 orally on Days 1 - 5 of each 28-day cycle, Cycles 1 - 6 Participants with CLL received treatments as follows: Cohort 6a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + chlorambucil 10 mg/m^2 orally once daily for 7 days every 28 days, Cycles 1 - 12 Participants with CLL received treatments as follows: Cohort 6b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + chlorambucil 10 mg/m^2 orally once daily for 7 days every 28 days, Cycles 1 - 12 Participants with CLL and iNHL received treatments as follows: Cohort 7a: IDELA 150 mg orally BID on Days 1 - 35 of Cycle 1 (35 days) and Days 1 - 28 of all subsequent 28-day cycles + rituximab 375 mg/m^2 IV on Days 1 & 8 of the first cycle and Day 1 of Cycles 2 - 6 + lenalidomide 5 mg orally once daily starting on Days 8 - 28 of Cycle 1 (35 days) and Days 1 - 21 of the next five 28-day cycles Cohort 7b: IDELA 150 mg orally BID on Days 1 - 35 of Cycle 1 (35 days) and Days 1 - 28 of all subsequent 28-day cycles + rituximab 375 mg/m^2 IV on Days 1 & 8 of the first cycle and Day 1 of Cycles 2 - 6 + lenalidomide 10 mg orally once daily starting on Days 8 - 28 of Cycle 1 (35 days) and Days 1 - 21 of the next five 28-day cycles Cohort 7c: IDELA 150 mg orally BID on Days 1 - 35 of Cycle 1 (35 days) and Days 1 - 28 of all subsequent 28-day cycles + rituximab 375 mg/m^2 IV on Days 1 & 8 of the first cycle and Day 1 of Cycles 2 - 6 + lenalidomide 20 mg orally once daily starting on Days 8 - 28 of Cycle 1 (35 days) and Days 1 - 21 of the next five 28-day cycles
    Measure Participants 51 51 18 18 33 21 12 15 15 7
    Median (95% Confidence Interval) [months]
    NA
    NA
    NA
    NA
    NA
    NA
    NA
    NA
    NA
    NA
    8. Secondary Outcome
    Title Plasma Concentration of IDELA (Cohort 1, Cohorts 2 and 3, Cohort 5)
    Description
    Time Frame Predose, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0 hours postdose at Week 0; predose, 1.5 hours postdose at Weeks 4, 12, and 24

    Outcome Measure Data

    Analysis Population Description
    The pharmacokinetic (PK) analysis set included data from participants in the ITT analysis set who had the necessary baseline and on-study measurements to provide interpretable results for the specific parameters of interest. Per prespecified analysis, data were summarized for participants in Cohort 1a 1b, who received idelalisib 100 mg and for participants in Cohorts 2a, 2b, 3a, 3b, 3c, 3d, 3e, 3f, 3g 5a, 5b, and 5c who received idelalisib 150 mg.
    Arm/Group Title Idelalisib 100 mg (Cohort 1) Idelalisib 150 mg (Cohorts 2 and 3) Idelalisib 150 mg (Cohort 5)
    Arm/Group Description Participants analyzed for this group included participants from Cohort 1 (subcohort 1a and 1b) who received the treatments as follows: Cohort 1a: IDELA 100 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Days 1, 8, 15 & 22, Cycles 1 & 2 Cohort 1b: IDELA 100 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycle 1 - 6 Participants analyzed for this group included participants from Cohort 2a, 2b, 3a, 3b, 3c, 3e, 3f, 3g who received the treatments as follows: Cohort 2a: IDELA 150 mg orally (po) BID, D1 - D28 of each cycle + rituximab 375 mg/m^2 IV on D1, D8, D15, & D22, C1 & C2 Cohort 2b: IDELA 150 mg po BID, D1 - D28 of each cycle + bendamustine 90 mg/m^2 IV, D1 & D2, C1 - C6 Cohorts 3a and 3b: IDELA 150 mg po BID, D1 - D28 of each cycle + rituximab 375 mg/m^2 IV on D1, C1 - C6 + bendamustine 90 mg/m^2 (Cohort 3a only) IV, D1 & D2, C1 - C6 + bendamustine 70 mg/m^2 (Cohort 3b only) IV on D1 & D2, C1 - C6 Cohort 3c: IDELA 150 mg po BID, D1 - D28 of each cycle + ofatumumab 12 doses (300 mg (D1 or D2, Dose 1), followed 1 week later by 1,000 mg weekly for 7 doses (Doses 2 - 8), followed 5 weeks later by 1,000 mg every 4 weeks for 4 doses (Doses 9 - 12)) Cohort 3d: IDELA 150 mg po BID, D1 - D28 of each cycle + fludarabine 40 mg/m^2 po D1 - D5, C1 - C6 Cohort 3e: IDELA 150 mg po BID, D1 - D28 of each cycle + rituximab 375 mg/m^2 IV on D1, D8, D15, & D22, C1 & C2 Cohorts 3f and 3g: IDELA 150 mg po BID, D1 - D28 of each cycle + bendamustine 90 mg/m^2 (cohort 3f only) IV, D1 & D2, C1 - C6 + bendamustine 70 mg/m^2 (Cohort 3g only) IV, D1 & D2, C1 - C6 C= Cycle D= Day Cycle length= 28 days Participants analyzed for this group included participants from Cohort 5 (subcohorts 5a, 5b, and 5c) who received the treatments as follows: Cohort 5a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + everolimus 10 mg orally once daily on Days 1 - 28 of each 28-day cycle Cohort 5b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bortezomib 1.3 mg/m^2 subcutaneously on Days 1, 8 & 15 of each 28-day cycle Cohort 5c: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6
    Measure Participants 24 123 45
    Pre-dose (Week 0)
    0.4
    (2.16)
    68.8
    (396.94)
    0.0
    (0.0)
    0.5 hr post-dose (Week 0)
    437.6
    (380.08)
    1231.4
    (1238.20)
    1380.0
    1.0 hr post-dose (Week 0)
    1022.4
    (652.92)
    1789.3
    (1162.31)
    1600.0
    1.5 hr post-dose (Week 0)
    1434.0
    (835.25)
    2017.3
    (1241.96)
    1564.7
    (983.46)
    2.0 hr post-dose (Week 0)
    1282.7
    (789.24)
    1732.8
    (744.87)
    1400.0
    3.0 hr post-dose (Week 0)
    1001.0
    (633.99)
    1296.1
    (509.80)
    1170.0
    4.0 hr post-dose (Week 0)
    788.4
    (629.67)
    910.0
    (420.79)
    795.0
    6.0 hr post-dose (Week 0)
    523.7
    (418.80)
    486.0
    (276.75)
    517.0
    Pre-dose (Week 4)
    416.5
    (636.01)
    364.1
    (341.84)
    408.0
    (699.35)
    1.5 hr post-dose (Week 4)
    1297.2
    (681.43)
    1808.1
    (931.67)
    1877.9
    (859.74)
    Pre-dose (Week 12)
    361.9
    (580.70)
    351.4
    (389.78)
    433.9
    (529.79)
    1.5 hr post-dose (Week 12)
    1309.5
    (750.50)
    1883.0
    (973.26)
    1426.8
    (917.02)
    Pre-dose (Week 24)
    369.9
    (461.67)
    419.7
    (359.03)
    549.1
    (622.95)
    1.5 hr post-dose (Week 24)
    1061.6
    (567.90)
    1840.1
    (1035.91)
    885.6
    (568.81)
    9. Secondary Outcome
    Title Plasma Concentration of IDELA (Cohort 4)
    Description
    Time Frame Predose at Week 0; predose, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0 hours postdose at Week 4; predose, 1.5 hours postdose at Week 12; and predose, 1.5 hours postdose at Week 24

    Outcome Measure Data

    Analysis Population Description
    Participants in the PK analysis set with available data were analyzed. Per prespecified analysis, data were summarized for participants in Cohort 4a, 4b who received idelalisib 150mg.
    Arm/Group Title Idelalisib 150 mg (Cohort 4)
    Arm/Group Description Participants analyzed for this group included participants from Cohort 4 (subcohorts 4a and 4b) who received the treatments as follows: Cohort 4a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle, starting Cycle 2 Day 1 with the 5th dose of rituximab + rituximab 375 mg/m^2 IV on Days 1, 8, 15, & 22, Cycles 1 & 2 Cohort 4b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle starting Cycle 2, Day 3 (after the Cycle 2 bendamustine dosing) + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6
    Measure Participants 18
    Pre-dose (Week 0)
    0.0
    (0.0)
    Pre-dose (Week 4)
    0.0
    (0.0)
    0.5 hr post-dose (Week 4)
    1119.5
    (1513.99)
    1.0 hr post-dose (Week 4)
    994.5
    (601.75)
    1.5 hr post-dose (Week 4)
    1758.2
    (1414.07)
    2.0 hr post-dose (Week 4)
    737.0
    (108.89)
    3.0 hr post-dose (Week 4)
    605.0
    (18.38)
    4.0 hr post-dose (Week 4)
    547.0
    (158.39)
    6.0 hr post-dose (Week 4)
    524.0
    (404.47)
    Pre-dose (Week 12)
    401.9
    (344.93)
    1.5 hr post-dose (Week 12)
    2018.2
    (1703.98)
    Pre-dose (Week 24)
    752.5
    (967.91)
    1.5 hr post-dose (Week 24)
    2251.1
    (1744.44)
    10. Secondary Outcome
    Title Plasma Concentration of IDELA (Cohort 6)
    Description
    Time Frame Predose, 1.5 hours postdose at Weeks 0, 4, 12 and 24

    Outcome Measure Data

    Analysis Population Description
    Participants in the PK analysis set with available data were analyzed. Per prespecified analysis, data were summarized for participants in Cohort 6a, 6b who received idelalisib 150mg.
    Arm/Group Title Idelalisib 150 mg (Cohort 6)
    Arm/Group Description Participants analyzed for this group included participants from Cohort 6 (subcohorts 6a and 6b) who received the treatments as follows Cohort 6a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + chlorambucil 10 mg/m^2 orally once daily for 7 days every 28 days, Cycles 1 - 12 Cohort 6b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + chlorambucil 10 mg/m^2 orally once daily for 7 days every 28 days, Cycles 1 - 12
    Measure Participants 30
    Pre-dose (Week 0)
    0.0
    (0.0)
    1.5 hr post-dose (Week 0)
    1930.7
    (1220.87)
    Pre-dose (Week 4)
    530.8
    (563.59)
    1.5 hr post-dose (Week 4)
    1869.8
    (1001.39)
    Pre-dose (Week 12)
    677.9
    (940.94)
    1.5 hr post-dose (Week 12)
    1733.0
    (941.94)
    Pre-dose (Week 24)
    346.8
    (377.84)
    1.5 hr post-dose (Week 24)
    1710.7
    (1235.08)
    11. Secondary Outcome
    Title Plasma Concentration of IDELA (Cohort 7)
    Description
    Time Frame Predose, 1.5 hours postdose at Weeks 0, 5 and 13

    Outcome Measure Data

    Analysis Population Description
    Participants in the PK analysis set with available data were analyzed. Per prespecified analysis, data were summarized for participants in Cohort 7a, 7b, 7c who received idelalisib 150mg.
    Arm/Group Title Idelalisib 150 mg (Cohort 7)
    Arm/Group Description Participants analyzed for this group included participants from Cohort 7 (subcohorts 7a, 7b, and 7c) who received the treatments as follows: Cohort 7a: IDELA 150 mg orally BID on Days 1 - 35 of Cycle 1 (35 days) and Days 1 - 28 of all subsequent 28-day cycles + rituximab 375 mg/m^2 IV on Days 1 & 8 of the first cycle and Day 1 of Cycles 2 - 6 + lenalidomide 5 mg orally once daily starting on Days 8 - 28 of Cycle 1 (35 days) and Days 1 - 21 of the next five 28-day cycles Cohort 7b: IDELA 150 mg orally BID on Days 1 - 35 of Cycle 1 (35 days) and Days 1 - 28 of all subsequent 28-day cycles + rituximab 375 mg/m^2 IV on Days 1 & 8 of the first cycle and Day 1 of Cycles 2 - 6 + lenalidomide 10 mg orally once daily starting on Days 8 - 28 of Cycle 1 (35 days) and Days 1 - 21 of the next five 28-day cycles Cohort 7c: IDELA 150 mg orally BID on Days 1 - 35 of Cycle 1 (35 days) and Days 1 - 28 of all subsequent 28-day cycles + rituximab 375 mg/m^2 IV on Days 1 & 8 of the first cycle and Day 1 of Cycles 2 - 6 + lenalidomide 20 mg orally once daily starting on Days 8 - 28 of Cycle 1 (35 days) and Days 1 - 21 of the next five 28-day cycles
    Measure Participants 7
    Pre-dose (Week 0)
    NA
    (NA)
    1.5 hr post-dose (Week 0)
    1603.1
    (1196.78)
    Pre-dose (Week 5)
    20.7
    (50.13)
    1.5 hr post-dose (Week 5)
    1621.3
    (663.80)
    Pre-dose (Week 13)
    354.8
    (278.62)
    1.5 hr post-dose (Week 13)
    592.7
    (597.52)
    12. Secondary Outcome
    Title Sub-study: Plasma Concentration of IDELA (Cohorts 1-4)
    Description
    Time Frame pre dose and 0.5, 1, 1.5, 2.0, 3.0, 4.0, and 6.0 hours post dose

    Outcome Measure Data

    Analysis Population Description
    Participants with CLL or iNHL from the PK Analysis Set in Cohorts 1, 2, 3, and 4 who participated in the PK substudy were analyzed. Per prespecified analysis, data were summarized for participants in Cohort 1a, 1b who received idelalisib 100mg and Cohorts 2a, 2b, 3a, 3c, 3d, 3e, 3f, 3g, 4a, 4b who received idelalisib 150 mg in the PK substudy.
    Arm/Group Title Idelalisib 100 mg (Cohort 1a, 1b) Idelalisib 150 mg (Cohorts 2a, 2b, 3a, 3c, 3d, 3e, 3f, 3g, 4a, 4b)
    Arm/Group Description Participants analyzed for this group included participants from Cohort 1 who received the treatments as follows: Cohort 1a: IDELA 100 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Days 1, 8, 15 & 22, Cycles 1 & 2 Cohort 1b: IDELA 100 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6 Participants included for analysis received treatments as follows: Cohort 2a: IDELA 150 mg po BID, D1 - D28 of each cycle + rituximab 375 mg/m^2 IV on D1, D8, D15, & D22, C1 & C2 Cohort 2b: IDELA 150 mg po BID, D1 - D28 of each cycle + bendamustine 90 mg/m^2 IV, D1 & D2, C1 - C6 Cohorts 3a and 3b: IDELA 150 mg po BID, D1 - D28 of each cycle + rituximab 375 mg/m^2 IV on D1, C1 - C6 + bendamustine 90 mg/m^2 (Cohort 3a only) IV, D1 & D2, C1 - C6 + bendamustine 70 mg/m^2 (Cohort 3b only) IV on D1 & D2, C1 - C6 Cohort 3c: IDELA 150 mg po BID, D1 - D28 of each cycle + ofatumumab 12 doses (300 mg (D1 or D2, Dose 1), followed 1 week later by 1,000 mg weekly for 7 doses (Doses 2 - 8), followed 5 weeks later by 1,000 mg every 4 weeks for 4 doses (Doses 9 - 12)) Cohort 3d: IDELA 150 mg po BID, D1 - D28 of each cycle + fludarabine 40 mg/m^2 po D1 - D5, C1 - C6 Cohort 3e: IDELA 150 mg po BID, D1 - D28 of each cycle + rituximab 375 mg/m^2 IV on D1, D8, D15, & D22, C1 & C2 Cohorts 3f and 3g: IDELA 150 mg po BID, D1 - D28 of each cycle + bendamustine 90 mg/m^2 (Cohort 3f only) IV, D1 & D2, C1 - C6 + bendamustine 70 mg/m^2 (Cohort 3g only) IV, D1 & D2, C1 - C6 Cohort 4a: IDELA 150 mg po BID, D1 - D28 of each cycle (starting C2 D1) + rituximab 375 mg/m^2 IV, D1, D8, D15, & D22, C1 & C2 Cohort 4b: IDELA 150 mg po BID, D1 - D28 of each cycle (starting C2, D3) + bendamustine 90 mg/m^2 IV, D1 & D2, C1 - C6 C= Cycle D= Day Cycle length= 28 days
    Measure Participants 7 24
    Pre-dose
    1.5
    (4.01)
    0.0
    (0.0)
    0.5 hr post-dose
    437.6
    (380.08)
    1222.1
    (1224.95)
    1.0 hr post-dose
    1022.4
    (652.92)
    1723.1
    (1140.00)
    1.5 hr post-dose
    1264.7
    (868.41)
    1599.2
    (746.58)
    2.0 hr post-dose
    1282.7
    (789.24)
    1646.2
    (766.31)
    3.0 hr post-dose
    1001.0
    (633.99)
    1238.5
    (524.77)
    4.0 hr post-dose
    788.4
    (629.67)
    879.8
    (416.25)
    6.0 hr post-dose
    523.7
    (418.80)
    489.3
    (277.82)
    13. Secondary Outcome
    Title Plasma Concentration of Bendamustine
    Description
    Time Frame Predose, 0.25, 0.5, 0.75, 1.0, 1.25, 1.5, 2.0, 3.0, 4.0, 5.0, 6.0 hours postdose at Week 0

    Outcome Measure Data

    Analysis Population Description
    Participants in the PK analysis set with available data were analyzed. Per prespecified analysis, data were summarized for participants in Cohorts 1b, 2b, 3a, 3b, 3f, 3g, 4b, 5c who received bendamustine.
    Arm/Group Title Bendamustine (Cohorts 1b, 2b, 3a, 3b, 3f, 3g, 4b, 5c)
    Arm/Group Description Participants included for analysis received treatments as follows: Cohort 1b: IDELA 100 mg po BID on Days 1 - 28 of each 28-day cycle + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6 Cohort 2b: IDELA 150 mg po BID on Days 1 - 28 of each 28-day cycle + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6 Cohort 3a: IDELA 150 mg po BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6 Cohort 3b: IDELA 150 mg po BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + bendamustine 70 mg/m^2 IV on Days 1 & 2 of each 28-day cycle from Cycles 1 - 6 Cohort 3f: IDELA 150 mg po BID on Days 1 - 28 of each 28-day cycle + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6 Cohort 3g: IDELA 150 mg po BID on Days 1 - 28 of each 28-day cycle + bendamustine 70 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6 Cohort 4b: IDELA 150 mg po BID on Days 1 - 28 of each 28-day cycle starting Cycle 2, Day 3 (after the Cycle 2 bendamustine dosing) + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6 Cohort 5c: IDELA 150 mg po BID on Days 1 - 28 + rituximab 375 mg/m^2 IV on Day 1, Cycles 1 - 6 + bendamustine 90 mg/m^2 IV on Days 1 & 2, Cycles 1 - 6 (Cycle length= 28 days)
    Measure Participants 19
    Pre-dose (Week 0)
    NA
    (NA)
    0.25 hr post-dose (Week 0)
    3484.1
    (2617.17)
    0.5 hr post-dose (Week 0)
    4694.7
    (3570.78)
    0.75 hr post-dose (Week 0)
    3433.2
    (2991.15)
    1.0 hr post-dose (Week 0)
    2847.2
    (2462.90)
    1.25 hr post-dose (Week 0)
    1916.4
    (1551.50)
    1.5 hr post-dose (Week 0)
    1211.2
    (1093.74)
    2.0 hr post-dose (Week 0)
    514.0
    (489.76)
    3.0 hr post-dose (Week 0)
    463.4
    (1529.30)
    4.0 hr post-dose (Week 0)
    78.5
    (238.30)
    5.0 hr post-dose (Week 0)
    15.3
    (36.79)
    6.0 hr post-dose (Week 0)
    4.4
    (6.58)
    14. Secondary Outcome
    Title Plasma Concentration of Everolimus
    Description
    Time Frame Predose, 1.5 hours postdose at Weeks 0 and 4

    Outcome Measure Data

    Analysis Population Description
    Participants in the PK analysis set with available data were analyzed. Data were summarized for participants in Cohort 5a who received everolimus.
    Arm/Group Title Everolimus (Cohort 5a)
    Arm/Group Description Participants analyzed for this group included participants from Cohort 5 (subcohort 5a) who received the treatments as follows: Cohort 5a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + everolimus 10 mg orally once daily on Days 1 - 28 of each 28-day cycle
    Measure Participants 6
    Pre-dose (Week 0)
    NA
    (NA)
    1.5 hr post-dose (Week 0)
    93.0
    (63.50)
    Pre-dose (Week 4)
    3.0
    (3.79)
    1.5 hr post-dose (Week 4)
    56.3
    (67.48)
    15. Secondary Outcome
    Title Plasma Concentration of Lenalidomide
    Description
    Time Frame Predose, 1.5 hours postdose at Week 1 and predose at Week 5

    Outcome Measure Data

    Analysis Population Description
    Participants in the PK analysis set with available data were analyzed. Per prespecified analysis, data were summarized for participants in Cohort 7a, 7b, 7c who received lenalidomide.
    Arm/Group Title Lenalidomide (Cohort 7a, 7b, 7c)
    Arm/Group Description Participants analyzed for this group included participants from Cohort 7 (subcohorts 7a, 7b, and 7c) who received the treatments as follows: Cohort 7a: IDELA 150 mg orally BID on Days 1 - 35 of Cycle 1 (35 days) and Days 1 - 28 of all subsequent 28-day cycles + rituximab 375 mg/m^2 IV on Days 1 & 8 of the first cycle and Day 1 of Cycles 2 - 6 + lenalidomide 5 mg orally once daily starting on Days 8 - 28 of Cycle 1 (35 days) and Days 1 - 21 of the next five 28-day cycles Cohort 7b: IDELA 150 mg orally BID on Days 1 - 35 of Cycle 1 (35 days) and Days 1 - 28 of all subsequent 28-day cycles + rituximab 375 mg/m^2 IV on Days 1 & 8 of the first cycle and Day 1 of Cycles 2 - 6 + lenalidomide 10 mg orally once daily starting on Days 8 - 28 of Cycle 1 (35 days) and Days 1 - 21 of the next five 28-day cycles Cohort 7c: IDELA 150 mg orally BID on Days 1 - 35 of Cycle 1 (35 days) and Days 1 - 28 of all subsequent 28-day cycles + rituximab 375 mg/m^2 IV on Days 1 & 8 of the first cycle and Day 1 of Cycles 2 - 6 + lenalidomide 20 mg orally once daily starting on Days 8 - 28 of Cycle 1 (35 days) and Days 1 - 21 of the next five 28-day cycles
    Measure Participants 7
    Pre-dose (Week 1)
    NA
    (NA)
    1.5 hr post-dose (Week 1)
    51.6
    (31.77)
    Pre-dose (Week 5)
    NA
    (NA)

    Adverse Events

    Time Frame First dose date up to 5 years
    Adverse Event Reporting Description The ITT analysis set included participants who received at least 1 dose of study drug (IDELA or combination drugs). Per prespecified analysis, participants were grouped by disease (CLL, iNHL, MCL) and by treatment regimen (cohort).
    Arm/Group Title Idelalisib + Rituximab Idelalisib + Bendamustine Idelalisib + Everolimus Idelalisib + Bortezomib Idelalisib + Rituximab + Bendamustine Idelalisib + Ofatumumab Idelalisib + Fludarabine Idelalisib + Chlorambucil Idelalisib + Rituximab + Chlorambucil Idelalisib + Rituximab + Lenalidomide
    Arm/Group Description Participants with chronic CLL and iNHL received treatments as follows: Cohort 1a: IDELA 100 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Days 1, 8, 15 & 22, Cycles 1 & 2 Cohort 2a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Days 1, 8, 15, & 22, Cycles 1 & 2 Cohort 3e: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Days 1, 8, 15, & 22, Cycles 1 & 2 Cohort 4a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle, starting Cycle 2 Day 1 with the 5th dose of rituximab + rituximab 375 mg/m^2 IV on Days 1, 8, 15, & 22, Cycles 1 & 2 Participants with CLL and iNHL received treatments as follows: Cohort 1b: IDELA 100 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6 Cohort 2b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6 Cohort 3f: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6 Cohort 3g: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bendamustine 70 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6 Cohort 4b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle starting Cycle 2, Day 3 (after the Cycle 2 bendamustine dosing) + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6 Participants with MCL received treatments as follows: Cohort 5a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + everolimus 10 mg orally once daily on Days 1 - 28 of each 28-day cycle Participants with MCL received treatments as follows: Cohort 5b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + bortezomib 1.3 mg/m^2 subcutaneously on Days 1, 8 & 15 of each 28-day cycle Participants with CLL, iNHL and MCL received treatments as follows: Cohort 3a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6 Cohort 3b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + bendamustine 70 mg/m^2 IV on Days 1 & 2 of each 28-day cycle from Cycles 1 - 6 Cohort 5c: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + bendamustine 90 mg/m^2 IV on Days 1 & 2 of each 28-day cycle, Cycles 1 - 6 Participants with CLL received treatments as follows: Cohort 3c: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + ofatumumab 12 doses (300 mg (Day 1 or Day 2, Dose 1), followed 1 week later by 1,000 mg weekly for 7 doses (Doses 2 - 8), followed 5 weeks later by 1,000 mg every 4 weeks for 4 doses (Doses 9 - 12)) Participants with CLL received treatments as follows: Cohort 3d: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + fludarabine 40 mg/m^2 orally on Days 1 - 5 of each 28-day cycle, Cycles 1 - 6 Participants with CLL received treatments as follows: Cohort 6a: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + chlorambucil 10 mg/m^2 orally once daily for 7 days every 28 days, Cycles 1 - 12 Participants with CLL received treatments as follows: Cohort 6b: IDELA 150 mg orally BID on Days 1 - 28 of each 28-day cycle + rituximab 375 mg/m^2 IV on Day 1 of each 28-day cycle, Cycles 1 - 6 + chlorambucil 10 mg/m^2 orally once daily for 7 days every 28 days, Cycles 1 - 12 Participants with CLL and iNHL received treatments as follows: Cohort 7a: IDELA 150 mg orally BID on Days 1 - 35 of Cycle 1 (35 days) and Days 1 - 28 of all subsequent 28-day cycles + rituximab 375 mg/m^2 IV on Days 1 & 8 of the first cycle and Day 1 of Cycles 2 - 6 + lenalidomide 5 mg orally once daily starting on Days 8 - 28 of Cycle 1 (35 days) and Days 1 - 21 of the next five 28-day cycles Cohort 7b: IDELA 150 mg orally BID on Days 1 - 35 of Cycle 1 (35 days) and Days 1 - 28 of all subsequent 28-day cycles + rituximab 375 mg/m^2 IV on Days 1 & 8 of the first cycle and Day 1 of Cycles 2 - 6 + lenalidomide 10 mg orally once daily starting on Days 8 - 28 of Cycle 1 (35 days) and Days 1 - 21 of the next five 28-day cycles Cohort 7c: IDELA 150 mg orally BID on Days 1 - 35 of Cycle 1 (35 days) and Days 1 - 28 of all subsequent 28-day cycles + rituximab 375 mg/m^2 IV on Days 1 & 8 of the first cycle and Day 1 of Cycles 2 - 6 + lenalidomide 20 mg orally once daily starting on Days 8 - 28 of Cycle 1 (35 days) and Days 1 - 21 of the next five 28-day cycles
    All Cause Mortality
    Idelalisib + Rituximab Idelalisib + Bendamustine Idelalisib + Everolimus Idelalisib + Bortezomib Idelalisib + Rituximab + Bendamustine Idelalisib + Ofatumumab Idelalisib + Fludarabine Idelalisib + Chlorambucil Idelalisib + Rituximab + Chlorambucil Idelalisib + Rituximab + Lenalidomide
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 1/51 (2%) 6/51 (11.8%) 4/18 (22.2%) 3/18 (16.7%) 1/33 (3%) 4/21 (19%) 2/12 (16.7%) 0/15 (0%) 3/15 (20%) 2/7 (28.6%)
    Serious Adverse Events
    Idelalisib + Rituximab Idelalisib + Bendamustine Idelalisib + Everolimus Idelalisib + Bortezomib Idelalisib + Rituximab + Bendamustine Idelalisib + Ofatumumab Idelalisib + Fludarabine Idelalisib + Chlorambucil Idelalisib + Rituximab + Chlorambucil Idelalisib + Rituximab + Lenalidomide
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 20/51 (39.2%) 37/51 (72.5%) 14/18 (77.8%) 6/18 (33.3%) 17/33 (51.5%) 12/21 (57.1%) 9/12 (75%) 9/15 (60%) 8/15 (53.3%) 5/7 (71.4%)
    Blood and lymphatic system disorders
    Anaemia 0/51 (0%) 2/51 (3.9%) 1/18 (5.6%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 1/12 (8.3%) 0/15 (0%) 1/15 (6.7%) 0/7 (0%)
    Autoimmune haemolytic anaemia 0/51 (0%) 1/51 (2%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Coombs positive haemolytic anaemia 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 1/15 (6.7%) 0/15 (0%) 0/7 (0%)
    Febrile neutropenia 3/51 (5.9%) 5/51 (9.8%) 2/18 (11.1%) 0/18 (0%) 1/33 (3%) 1/21 (4.8%) 1/12 (8.3%) 4/15 (26.7%) 2/15 (13.3%) 0/7 (0%)
    Immune thrombocytopenic purpura 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 1/33 (3%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Neutropenia 0/51 (0%) 2/51 (3.9%) 0/18 (0%) 0/18 (0%) 1/33 (3%) 0/21 (0%) 1/12 (8.3%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Pancytopenia 0/51 (0%) 1/51 (2%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Thrombocytopenia 1/51 (2%) 2/51 (3.9%) 1/18 (5.6%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 1/12 (8.3%) 0/15 (0%) 0/15 (0%) 1/7 (14.3%)
    Cardiac disorders
    Atrial fibrillation 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 2/33 (6.1%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Cardiac arrest 1/51 (2%) 0/51 (0%) 0/18 (0%) 1/18 (5.6%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Cardiac failure 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 1/33 (3%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Supraventricular tachycardia 0/51 (0%) 1/51 (2%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Endocrine disorders
    Endocrine disorder 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 1/21 (4.8%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Eye disorders
    Retinal detachment 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 1/33 (3%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Uveitis 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 1/12 (8.3%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Gastrointestinal disorders
    Abdominal pain 2/51 (3.9%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Colitis 2/51 (3.9%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 1/33 (3%) 1/21 (4.8%) 0/12 (0%) 2/15 (13.3%) 1/15 (6.7%) 1/7 (14.3%)
    Colitis ischaemic 0/51 (0%) 1/51 (2%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Colitis microscopic 0/51 (0%) 0/51 (0%) 0/18 (0%) 1/18 (5.6%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Diarrhoea 2/51 (3.9%) 2/51 (3.9%) 0/18 (0%) 1/18 (5.6%) 2/33 (6.1%) 1/21 (4.8%) 0/12 (0%) 1/15 (6.7%) 2/15 (13.3%) 0/7 (0%)
    Dysphagia 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 1/33 (3%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Gastrointestinal haemorrhage 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 1/21 (4.8%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%) 0/7 (0%)
    Gingival bleeding 0/51 (0%) 1/51 (2%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Intestinal obstruction 0/51 (0%) 1/51 (2%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Large intestinal ulcer 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 1/33 (3%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Mouth haemorrhage 0/51 (0%) 1/51 (2%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Nausea 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 1/33 (3%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Neutropenic colitis 0/51 (0%) 1/51 (2%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Peptic ulcer 1/51 (2%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Rectal haemorrhage 0/51 (0%) 1/51 (2%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Stomatitis 0/51 (0%) 0/51 (0%) 1/18 (5.6%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Vomiting 0/51 (0%) 1/51 (2%) 0/18 (0%) 0/18 (0%) 1/33 (3%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    General disorders
    Asthenia 0/51 (0%) 1/51 (2%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Chest pain 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%) 0/7 (0%)
    Fatigue 0/51 (0%) 2/51 (3.9%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%) 0/7 (0%)
    Generalised oedema 1/51 (2%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Mucosal inflammation 0/51 (0%) 0/51 (0%) 1/18 (5.6%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Multi-organ failure 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 1/33 (3%) 1/21 (4.8%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Pyrexia 1/51 (2%) 10/51 (19.6%) 1/18 (5.6%) 1/18 (5.6%) 5/33 (15.2%) 2/21 (9.5%) 1/12 (8.3%) 1/15 (6.7%) 0/15 (0%) 2/7 (28.6%)
    Hepatobiliary disorders
    Cholecystitis 0/51 (0%) 1/51 (2%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Cholecystitis acute 1/51 (2%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Cholecystitis chronic 1/51 (2%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Hepatic failure 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 1/7 (14.3%)
    Hepatitis 1/51 (2%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Immune system disorders
    Hypersensitivity 0/51 (0%) 1/51 (2%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Infections and infestations
    Aspergillus infection 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 2/15 (13.3%) 0/7 (0%)
    Atypical pneumonia 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%) 0/7 (0%)
    Bacteraemia 0/51 (0%) 1/51 (2%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%) 0/7 (0%)
    Bacterial infection 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 1/21 (4.8%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Bronchiolitis 0/51 (0%) 0/51 (0%) 0/18 (0%) 1/18 (5.6%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Bronchitis 1/51 (2%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 1/21 (4.8%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Bronchopulmonary aspergillosis 0/51 (0%) 1/51 (2%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Candida infection 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 1/21 (4.8%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Cellulitis 1/51 (2%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%) 0/7 (0%)
    Clostridium difficile colitis 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 1/12 (8.3%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Clostridium difficile infection 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 1/12 (8.3%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Cytomegalovirus gastrointestinal infection 1/51 (2%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Cytomegalovirus infection 0/51 (0%) 1/51 (2%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Cytomegalovirus viraemia 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 1/15 (6.7%) 0/15 (0%) 0/7 (0%)
    Diverticulitis 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 1/12 (8.3%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Encephalitis 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 1/12 (8.3%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Enterococcal bacteraemia 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%) 0/7 (0%)
    Escherichia bacteraemia 0/51 (0%) 2/51 (3.9%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Escherichia sepsis 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%) 0/7 (0%)
    Folliculitis 0/51 (0%) 0/51 (0%) 1/18 (5.6%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Gastroenteritis 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 1/33 (3%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Gastroenteritis salmonella 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 1/15 (6.7%) 0/15 (0%) 0/7 (0%)
    Groin abscess 0/51 (0%) 1/51 (2%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Herpes zoster 1/51 (2%) 1/51 (2%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Herpes zoster disseminated 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%) 0/7 (0%)
    Herpes zoster pharyngitis 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 1/33 (3%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Human herpesvirus 6 infection 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 2/12 (16.7%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Listeria sepsis 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%) 0/7 (0%)
    Listeriosis 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%) 0/7 (0%)
    Lung infection 0/51 (0%) 0/51 (0%) 1/18 (5.6%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Mycobacterium avium complex infection 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%) 0/7 (0%)
    Neutropenic sepsis 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 1/21 (4.8%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Ophthalmic herpes zoster 0/51 (0%) 1/51 (2%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Perirectal abscess 0/51 (0%) 1/51 (2%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Pneumocystis jirovecii pneumonia 0/51 (0%) 2/51 (3.9%) 1/18 (5.6%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 1/12 (8.3%) 2/15 (13.3%) 1/15 (6.7%) 0/7 (0%)
    Pneumonia 4/51 (7.8%) 10/51 (19.6%) 2/18 (11.1%) 0/18 (0%) 1/33 (3%) 3/21 (14.3%) 1/12 (8.3%) 1/15 (6.7%) 1/15 (6.7%) 0/7 (0%)
    Pneumonia bacterial 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%) 0/7 (0%)
    Pneumonia fungal 0/51 (0%) 1/51 (2%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%) 1/7 (14.3%)
    Pneumonia haemophilus 0/51 (0%) 1/51 (2%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Pneumonia influenzal 0/51 (0%) 1/51 (2%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Pseudomonal bacteraemia 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%) 0/7 (0%)
    Sepsis 0/51 (0%) 4/51 (7.8%) 0/18 (0%) 1/18 (5.6%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 1/15 (6.7%) 1/15 (6.7%) 0/7 (0%)
    Septic shock 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 1/33 (3%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Staphylococcal bacteraemia 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 1/33 (3%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Streptococcal bacteraemia 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 1/12 (8.3%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Tooth infection 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 1/33 (3%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Upper respiratory tract infection 0/51 (0%) 1/51 (2%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 1/21 (4.8%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Urinary tract infection 0/51 (0%) 1/51 (2%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Vaginal infection 0/51 (0%) 1/51 (2%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Viral upper respiratory tract infection 0/51 (0%) 1/51 (2%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Injury, poisoning and procedural complications
    Fall 1/51 (2%) 0/51 (0%) 0/18 (0%) 1/18 (5.6%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Pelvic fracture 1/51 (2%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Subdural haematoma 1/51 (2%) 1/51 (2%) 0/18 (0%) 1/18 (5.6%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Investigations
    Alanine aminotransferase increased 1/51 (2%) 1/51 (2%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 2/7 (28.6%)
    Aspartate aminotransferase increased 0/51 (0%) 1/51 (2%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 2/7 (28.6%)
    Blood bilirubin increased 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 1/7 (14.3%)
    Blood lactate dehydrogenase increased 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 2/7 (28.6%)
    Hepatic enzyme increased 1/51 (2%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Transaminases increased 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 1/21 (4.8%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%) 0/7 (0%)
    Weight decreased 0/51 (0%) 1/51 (2%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Metabolism and nutrition disorders
    Decreased appetite 1/51 (2%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Failure to thrive 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%) 0/7 (0%)
    Hypercalcaemia 0/51 (0%) 0/51 (0%) 0/18 (0%) 1/18 (5.6%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Hyperglycaemia 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 1/12 (8.3%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Hyperkalaemia 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%) 0/7 (0%)
    Hyperuricaemia 1/51 (2%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Hypoglycaemia 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%) 0/7 (0%)
    Hypokalaemia 0/51 (0%) 2/51 (3.9%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Hyponatraemia 0/51 (0%) 0/51 (0%) 1/18 (5.6%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Lactic acidosis 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 1/12 (8.3%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Tumour lysis syndrome 0/51 (0%) 2/51 (3.9%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 2/12 (16.7%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 0/51 (0%) 1/51 (2%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Myalgia 0/51 (0%) 1/51 (2%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Rhabdomyolysis 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 1/33 (3%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Acute myeloid leukaemia 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 1/21 (4.8%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Renal cell carcinoma 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 1/7 (14.3%)
    Nervous system disorders
    Cerebral ischaemia 1/51 (2%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Cerebrovascular accident 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 1/12 (8.3%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Dizziness 0/51 (0%) 1/51 (2%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Lethargy 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%) 0/7 (0%)
    Normal pressure hydrocephalus 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 1/12 (8.3%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Syncope 0/51 (0%) 1/51 (2%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 1/21 (4.8%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Psychiatric disorders
    Depression 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 1/12 (8.3%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Suicidal ideation 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 1/33 (3%) 0/21 (0%) 1/12 (8.3%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Renal and urinary disorders
    Acute kidney injury 2/51 (3.9%) 0/51 (0%) 3/18 (16.7%) 1/18 (5.6%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 1/7 (14.3%)
    Hydronephrosis 0/51 (0%) 0/51 (0%) 1/18 (5.6%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Obstructive uropathy 0/51 (0%) 0/51 (0%) 1/18 (5.6%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Urinary tract obstruction 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 1/33 (3%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Reproductive system and breast disorders
    Pelvic pain 0/51 (0%) 1/51 (2%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Vaginal haemorrhage 0/51 (0%) 1/51 (2%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory failure 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 2/15 (13.3%) 0/7 (0%)
    Bronchial secretion retention 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%) 0/7 (0%)
    Bronchiectasis 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%) 0/7 (0%)
    Epistaxis 0/51 (0%) 1/51 (2%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Hypoxia 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 1/12 (8.3%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Organising pneumonia 0/51 (0%) 0/51 (0%) 1/18 (5.6%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Pleural effusion 0/51 (0%) 0/51 (0%) 0/18 (0%) 1/18 (5.6%) 0/33 (0%) 1/21 (4.8%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Pleuritic pain 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%) 0/7 (0%)
    Pneumonitis 1/51 (2%) 2/51 (3.9%) 1/18 (5.6%) 1/18 (5.6%) 0/33 (0%) 1/21 (4.8%) 1/12 (8.3%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Pulmonary embolism 0/51 (0%) 0/51 (0%) 1/18 (5.6%) 0/18 (0%) 1/33 (3%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Pulmonary haemorrhage 0/51 (0%) 1/51 (2%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Respiratory distress 0/51 (0%) 0/51 (0%) 1/18 (5.6%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Respiratory failure 0/51 (0%) 0/51 (0%) 0/18 (0%) 1/18 (5.6%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 1/7 (14.3%)
    Skin and subcutaneous tissue disorders
    Angioedema 0/51 (0%) 0/51 (0%) 1/18 (5.6%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Drug eruption 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 1/33 (3%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Erythema multiforme 0/51 (0%) 1/51 (2%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Rash 1/51 (2%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 3/33 (9.1%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Rash erythematous 0/51 (0%) 1/51 (2%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Rash maculo-papular 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 1/33 (3%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Skin ulcer 0/51 (0%) 0/51 (0%) 1/18 (5.6%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Vascular disorders
    Deep vein thrombosis 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 1/33 (3%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Haemorrhage 0/51 (0%) 1/51 (2%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Hypotension 0/51 (0%) 0/51 (0%) 1/18 (5.6%) 0/18 (0%) 1/33 (3%) 0/21 (0%) 0/12 (0%) 1/15 (6.7%) 0/15 (0%) 0/7 (0%)
    Orthostatic hypotension 0/51 (0%) 1/51 (2%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Other (Not Including Serious) Adverse Events
    Idelalisib + Rituximab Idelalisib + Bendamustine Idelalisib + Everolimus Idelalisib + Bortezomib Idelalisib + Rituximab + Bendamustine Idelalisib + Ofatumumab Idelalisib + Fludarabine Idelalisib + Chlorambucil Idelalisib + Rituximab + Chlorambucil Idelalisib + Rituximab + Lenalidomide
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 51/51 (100%) 51/51 (100%) 18/18 (100%) 15/18 (83.3%) 33/33 (100%) 21/21 (100%) 12/12 (100%) 15/15 (100%) 15/15 (100%) 7/7 (100%)
    Blood and lymphatic system disorders
    Anaemia 6/51 (11.8%) 13/51 (25.5%) 5/18 (27.8%) 5/18 (27.8%) 4/33 (12.1%) 3/21 (14.3%) 3/12 (25%) 3/15 (20%) 4/15 (26.7%) 0/7 (0%)
    Coombs positive haemolytic anaemia 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 1/15 (6.7%) 0/15 (0%) 0/7 (0%)
    Eosinophilia 0/51 (0%) 0/51 (0%) 1/18 (5.6%) 0/18 (0%) 1/33 (3%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Febrile neutropenia 0/51 (0%) 3/51 (5.9%) 1/18 (5.6%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 1/15 (6.7%) 0/15 (0%) 0/7 (0%)
    Hypoglobulinaemia 1/51 (2%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%) 0/7 (0%)
    Iron deficiency anaemia 1/51 (2%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 2/21 (9.5%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Leukopenia 3/51 (5.9%) 6/51 (11.8%) 2/18 (11.1%) 2/18 (11.1%) 4/33 (12.1%) 0/21 (0%) 0/12 (0%) 4/15 (26.7%) 0/15 (0%) 0/7 (0%)
    Lymphadenopathy 1/51 (2%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 1/15 (6.7%) 0/15 (0%) 0/7 (0%)
    Lymphocytosis 1/51 (2%) 1/51 (2%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%) 0/7 (0%)
    Lymphopenia 0/51 (0%) 2/51 (3.9%) 1/18 (5.6%) 0/18 (0%) 1/33 (3%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Neutropenia 15/51 (29.4%) 27/51 (52.9%) 7/18 (38.9%) 4/18 (22.2%) 13/33 (39.4%) 6/21 (28.6%) 6/12 (50%) 9/15 (60%) 7/15 (46.7%) 2/7 (28.6%)
    Pancytopenia 0/51 (0%) 1/51 (2%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 1/12 (8.3%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Thrombocytopenia 4/51 (7.8%) 14/51 (27.5%) 11/18 (61.1%) 4/18 (22.2%) 3/33 (9.1%) 3/21 (14.3%) 1/12 (8.3%) 5/15 (33.3%) 3/15 (20%) 0/7 (0%)
    Cardiac disorders
    Angina pectoris 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 1/12 (8.3%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Atrial fibrillation 1/51 (2%) 1/51 (2%) 3/18 (16.7%) 0/18 (0%) 0/33 (0%) 1/21 (4.8%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%) 0/7 (0%)
    Cardiac failure congestive 0/51 (0%) 2/51 (3.9%) 1/18 (5.6%) 1/18 (5.6%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%) 0/7 (0%)
    Cardiomyopathy 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%) 0/7 (0%)
    Palpitations 1/51 (2%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 1/33 (3%) 0/21 (0%) 3/12 (25%) 0/15 (0%) 0/15 (0%) 1/7 (14.3%)
    Pulseless electrical activity 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 1/12 (8.3%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Sinus tachycardia 0/51 (0%) 3/51 (5.9%) 1/18 (5.6%) 0/18 (0%) 1/33 (3%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Tachycardia 0/51 (0%) 0/51 (0%) 1/18 (5.6%) 0/18 (0%) 0/33 (0%) 1/21 (4.8%) 0/12 (0%) 0/15 (0%) 2/15 (13.3%) 0/7 (0%)
    Ear and labyrinth disorders
    Ear pain 2/51 (3.9%) 3/51 (5.9%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Vertigo 5/51 (9.8%) 1/51 (2%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%) 0/7 (0%)
    Eye disorders
    Cataract 1/51 (2%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 1/33 (3%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%) 0/7 (0%)
    Dry eye 1/51 (2%) 0/51 (0%) 2/18 (11.1%) 1/18 (5.6%) 3/33 (9.1%) 1/21 (4.8%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 2/7 (28.6%)
    Eye irritation 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 1/33 (3%) 0/21 (0%) 1/12 (8.3%) 0/15 (0%) 1/15 (6.7%) 0/7 (0%)
    Eyelid thickening 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%) 0/7 (0%)
    Lacrimation increased 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 3/7 (42.9%)
    Periorbital oedema 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 1/33 (3%) 0/21 (0%) 1/12 (8.3%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Vision blurred 3/51 (5.9%) 1/51 (2%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 2/12 (16.7%) 0/15 (0%) 0/15 (0%) 1/7 (14.3%)
    Visual impairment 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 1/33 (3%) 0/21 (0%) 1/12 (8.3%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Vitreous floaters 0/51 (0%) 0/51 (0%) 1/18 (5.6%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Gastrointestinal disorders
    Abdominal discomfort 1/51 (2%) 1/51 (2%) 1/18 (5.6%) 0/18 (0%) 1/33 (3%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Abdominal distension 2/51 (3.9%) 1/51 (2%) 2/18 (11.1%) 2/18 (11.1%) 1/33 (3%) 1/21 (4.8%) 0/12 (0%) 1/15 (6.7%) 0/15 (0%) 0/7 (0%)
    Abdominal hernia 0/51 (0%) 0/51 (0%) 0/18 (0%) 1/18 (5.6%) 1/33 (3%) 1/21 (4.8%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Abdominal pain 10/51 (19.6%) 6/51 (11.8%) 1/18 (5.6%) 3/18 (16.7%) 3/33 (9.1%) 2/21 (9.5%) 1/12 (8.3%) 1/15 (6.7%) 3/15 (20%) 1/7 (14.3%)
    Abdominal pain lower 0/51 (0%) 1/51 (2%) 1/18 (5.6%) 1/18 (5.6%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 1/15 (6.7%) 0/15 (0%) 0/7 (0%)
    Abdominal pain upper 3/51 (5.9%) 1/51 (2%) 1/18 (5.6%) 0/18 (0%) 1/33 (3%) 0/21 (0%) 1/12 (8.3%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Abdominal tenderness 0/51 (0%) 0/51 (0%) 0/18 (0%) 1/18 (5.6%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Anal haemorrhage 0/51 (0%) 0/51 (0%) 0/18 (0%) 1/18 (5.6%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Anal pruritus 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%) 0/7 (0%)
    Aphthous stomatitis 0/51 (0%) 0/51 (0%) 0/18 (0%) 1/18 (5.6%) 2/33 (6.1%) 0/21 (0%) 0/12 (0%) 1/15 (6.7%) 0/15 (0%) 0/7 (0%)
    Colitis 1/51 (2%) 1/51 (2%) 0/18 (0%) 0/18 (0%) 1/33 (3%) 0/21 (0%) 1/12 (8.3%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Constipation 5/51 (9.8%) 11/51 (21.6%) 2/18 (11.1%) 3/18 (16.7%) 8/33 (24.2%) 4/21 (19%) 2/12 (16.7%) 2/15 (13.3%) 6/15 (40%) 6/7 (85.7%)
    Diarrhoea 20/51 (39.2%) 14/51 (27.5%) 9/18 (50%) 7/18 (38.9%) 12/33 (36.4%) 11/21 (52.4%) 6/12 (50%) 6/15 (40%) 8/15 (53.3%) 2/7 (28.6%)
    Dry mouth 1/51 (2%) 2/51 (3.9%) 1/18 (5.6%) 0/18 (0%) 0/33 (0%) 1/21 (4.8%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Dyspepsia 1/51 (2%) 9/51 (17.6%) 1/18 (5.6%) 0/18 (0%) 2/33 (6.1%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 2/15 (13.3%) 0/7 (0%)
    Dysphagia 3/51 (5.9%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Faeces soft 1/51 (2%) 2/51 (3.9%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 1/12 (8.3%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Flatulence 3/51 (5.9%) 2/51 (3.9%) 0/18 (0%) 1/18 (5.6%) 0/33 (0%) 1/21 (4.8%) 1/12 (8.3%) 0/15 (0%) 1/15 (6.7%) 0/7 (0%)
    Gastritis 1/51 (2%) 1/51 (2%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 1/12 (8.3%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Gastrooesophageal reflux disease 1/51 (2%) 5/51 (9.8%) 0/18 (0%) 0/18 (0%) 2/33 (6.1%) 0/21 (0%) 1/12 (8.3%) 0/15 (0%) 1/15 (6.7%) 1/7 (14.3%)
    Gingival bleeding 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 1/15 (6.7%) 0/15 (0%) 0/7 (0%)
    Gingival pain 1/51 (2%) 0/51 (0%) 1/18 (5.6%) 0/18 (0%) 1/33 (3%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%) 0/7 (0%)
    Glossitis 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 1/15 (6.7%) 0/15 (0%) 0/7 (0%)
    Glossodynia 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 2/21 (9.5%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Haematochezia 0/51 (0%) 0/51 (0%) 1/18 (5.6%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 2/12 (16.7%) 0/15 (0%) 0/15 (0%) 1/7 (14.3%)
    Large intestine polyp 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%) 0/7 (0%)
    Lip blister 0/51 (0%) 0/51 (0%) 1/18 (5.6%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 1/12 (8.3%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Mouth ulceration 1/51 (2%) 1/51 (2%) 1/18 (5.6%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 2/12 (16.7%) 0/15 (0%) 1/15 (6.7%) 0/7 (0%)
    Nausea 17/51 (33.3%) 19/51 (37.3%) 2/18 (11.1%) 3/18 (16.7%) 14/33 (42.4%) 6/21 (28.6%) 4/12 (33.3%) 4/15 (26.7%) 6/15 (40%) 4/7 (57.1%)
    Noninfective gingivitis 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%) 0/7 (0%)
    Oesophagitis 1/51 (2%) 1/51 (2%) 0/18 (0%) 0/18 (0%) 1/33 (3%) 1/21 (4.8%) 0/12 (0%) 1/15 (6.7%) 0/15 (0%) 0/7 (0%)
    Oral dysaesthesia 1/51 (2%) 0/51 (0%) 1/18 (5.6%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Oral pain 1/51 (2%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 2/33 (6.1%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Proctitis 0/51 (0%) 0/51 (0%) 1/18 (5.6%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Retching 2/51 (3.9%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%) 0/7 (0%)
    Stomatitis 4/51 (7.8%) 4/51 (7.8%) 2/18 (11.1%) 1/18 (5.6%) 2/33 (6.1%) 1/21 (4.8%) 0/12 (0%) 2/15 (13.3%) 0/15 (0%) 2/7 (28.6%)
    Toothache 0/51 (0%) 1/51 (2%) 0/18 (0%) 0/18 (0%) 1/33 (3%) 0/21 (0%) 0/12 (0%) 2/15 (13.3%) 0/15 (0%) 0/7 (0%)
    Vomiting 5/51 (9.8%) 6/51 (11.8%) 2/18 (11.1%) 1/18 (5.6%) 6/33 (18.2%) 3/21 (14.3%) 3/12 (25%) 4/15 (26.7%) 1/15 (6.7%) 2/7 (28.6%)
    General disorders
    Asthenia 5/51 (9.8%) 4/51 (7.8%) 3/18 (16.7%) 2/18 (11.1%) 2/33 (6.1%) 1/21 (4.8%) 2/12 (16.7%) 0/15 (0%) 2/15 (13.3%) 0/7 (0%)
    Catheter site pain 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 1/33 (3%) 0/21 (0%) 1/12 (8.3%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Chest discomfort 0/51 (0%) 1/51 (2%) 0/18 (0%) 0/18 (0%) 1/33 (3%) 0/21 (0%) 0/12 (0%) 1/15 (6.7%) 2/15 (13.3%) 0/7 (0%)
    Chest pain 1/51 (2%) 1/51 (2%) 1/18 (5.6%) 1/18 (5.6%) 1/33 (3%) 1/21 (4.8%) 1/12 (8.3%) 1/15 (6.7%) 1/15 (6.7%) 0/7 (0%)
    Chills 8/51 (15.7%) 11/51 (21.6%) 4/18 (22.2%) 2/18 (11.1%) 4/33 (12.1%) 3/21 (14.3%) 0/12 (0%) 6/15 (40%) 1/15 (6.7%) 1/7 (14.3%)
    Face oedema 0/51 (0%) 1/51 (2%) 1/18 (5.6%) 0/18 (0%) 1/33 (3%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Fatigue 18/51 (35.3%) 24/51 (47.1%) 5/18 (27.8%) 4/18 (22.2%) 12/33 (36.4%) 4/21 (19%) 5/12 (41.7%) 4/15 (26.7%) 5/15 (33.3%) 4/7 (57.1%)
    Gait disturbance 1/51 (2%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 1/12 (8.3%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Inflammation 0/51 (0%) 0/51 (0%) 0/18 (0%) 1/18 (5.6%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Influenza like illness 0/51 (0%) 0/51 (0%) 0/18 (0%) 1/18 (5.6%) 0/33 (0%) 1/21 (4.8%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Infusion site pain 0/51 (0%) 1/51 (2%) 0/18 (0%) 0/18 (0%) 3/33 (9.1%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Injection site discomfort 0/51 (0%) 0/51 (0%) 0/18 (0%) 1/18 (5.6%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Injection site erythema 0/51 (0%) 0/51 (0%) 0/18 (0%) 1/18 (5.6%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Injection site reaction 0/51 (0%) 0/51 (0%) 0/18 (0%) 1/18 (5.6%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Malaise 0/51 (0%) 1/51 (2%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 1/21 (4.8%) 0/12 (0%) 1/15 (6.7%) 0/15 (0%) 0/7 (0%)
    Mucosal inflammation 2/51 (3.9%) 3/51 (5.9%) 3/18 (16.7%) 0/18 (0%) 2/33 (6.1%) 1/21 (4.8%) 2/12 (16.7%) 0/15 (0%) 1/15 (6.7%) 1/7 (14.3%)
    Oedema 1/51 (2%) 2/51 (3.9%) 2/18 (11.1%) 0/18 (0%) 2/33 (6.1%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%) 0/7 (0%)
    Oedema peripheral 4/51 (7.8%) 4/51 (7.8%) 3/18 (16.7%) 3/18 (16.7%) 4/33 (12.1%) 3/21 (14.3%) 2/12 (16.7%) 3/15 (20%) 2/15 (13.3%) 1/7 (14.3%)
    Pain 5/51 (9.8%) 4/51 (7.8%) 3/18 (16.7%) 2/18 (11.1%) 3/33 (9.1%) 0/21 (0%) 2/12 (16.7%) 3/15 (20%) 2/15 (13.3%) 0/7 (0%)
    Peripheral swelling 1/51 (2%) 0/51 (0%) 1/18 (5.6%) 0/18 (0%) 1/33 (3%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%) 0/7 (0%)
    Pyrexia 18/51 (35.3%) 26/51 (51%) 4/18 (22.2%) 3/18 (16.7%) 18/33 (54.5%) 6/21 (28.6%) 4/12 (33.3%) 3/15 (20%) 8/15 (53.3%) 1/7 (14.3%)
    Hepatobiliary disorders
    Cholecystitis acute 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 1/15 (6.7%) 0/15 (0%) 0/7 (0%)
    Immune system disorders
    Anaphylactic reaction 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 1/12 (8.3%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Drug hypersensitivity 0/51 (0%) 1/51 (2%) 0/18 (0%) 0/18 (0%) 1/33 (3%) 0/21 (0%) 1/12 (8.3%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Hypersensitivity 2/51 (3.9%) 1/51 (2%) 1/18 (5.6%) 1/18 (5.6%) 0/33 (0%) 1/21 (4.8%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%) 1/7 (14.3%)
    Hypogammaglobulinaemia 1/51 (2%) 0/51 (0%) 1/18 (5.6%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 1/12 (8.3%) 0/15 (0%) 2/15 (13.3%) 0/7 (0%)
    Seasonal allergy 2/51 (3.9%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 1/33 (3%) 0/21 (0%) 1/12 (8.3%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Infections and infestations
    Aspergillus infection 0/51 (0%) 1/51 (2%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%) 0/7 (0%)
    Bacteraemia 0/51 (0%) 0/51 (0%) 1/18 (5.6%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Bronchitis 3/51 (5.9%) 2/51 (3.9%) 0/18 (0%) 1/18 (5.6%) 1/33 (3%) 0/21 (0%) 0/12 (0%) 1/15 (6.7%) 1/15 (6.7%) 0/7 (0%)
    Campylobacter infection 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%) 0/7 (0%)
    Candida infection 1/51 (2%) 3/51 (5.9%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 1/12 (8.3%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Cellulitis 1/51 (2%) 2/51 (3.9%) 0/18 (0%) 0/18 (0%) 1/33 (3%) 2/21 (9.5%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Chronic sinusitis 1/51 (2%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 2/33 (6.1%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Clostridium difficile colitis 0/51 (0%) 0/51 (0%) 1/18 (5.6%) 1/18 (5.6%) 0/33 (0%) 0/21 (0%) 1/12 (8.3%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Clostridium difficile infection 0/51 (0%) 0/51 (0%) 0/18 (0%) 1/18 (5.6%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Conjunctivitis 1/51 (2%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 1/33 (3%) 0/21 (0%) 0/12 (0%) 1/15 (6.7%) 1/15 (6.7%) 0/7 (0%)
    Diverticulitis 0/51 (0%) 0/51 (0%) 0/18 (0%) 1/18 (5.6%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 1/15 (6.7%) 0/15 (0%) 0/7 (0%)
    Ear infection 2/51 (3.9%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%) 0/7 (0%)
    Fungal infection 0/51 (0%) 1/51 (2%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 1/7 (14.3%)
    Fungal skin infection 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%) 0/7 (0%)
    Gastroenteritis viral 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 1/33 (3%) 0/21 (0%) 0/12 (0%) 1/15 (6.7%) 1/15 (6.7%) 0/7 (0%)
    Gingivitis 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 1/15 (6.7%) 0/15 (0%) 0/7 (0%)
    Herpes simplex 0/51 (0%) 1/51 (2%) 0/18 (0%) 1/18 (5.6%) 1/33 (3%) 1/21 (4.8%) 1/12 (8.3%) 2/15 (13.3%) 0/15 (0%) 0/7 (0%)
    Herpes virus infection 1/51 (2%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 1/33 (3%) 0/21 (0%) 0/12 (0%) 1/15 (6.7%) 0/15 (0%) 0/7 (0%)
    Herpes zoster 3/51 (5.9%) 3/51 (5.9%) 0/18 (0%) 1/18 (5.6%) 2/33 (6.1%) 1/21 (4.8%) 0/12 (0%) 1/15 (6.7%) 0/15 (0%) 0/7 (0%)
    Human herpesvirus 6 infection 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 1/12 (8.3%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Infected cyst 0/51 (0%) 0/51 (0%) 1/18 (5.6%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Mycobacterium avium complex infection 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%) 0/7 (0%)
    Nasopharyngitis 5/51 (9.8%) 1/51 (2%) 0/18 (0%) 0/18 (0%) 1/33 (3%) 1/21 (4.8%) 1/12 (8.3%) 2/15 (13.3%) 0/15 (0%) 0/7 (0%)
    Onychomycosis 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 1/12 (8.3%) 1/15 (6.7%) 0/15 (0%) 0/7 (0%)
    Oral candidiasis 5/51 (9.8%) 2/51 (3.9%) 1/18 (5.6%) 1/18 (5.6%) 0/33 (0%) 1/21 (4.8%) 1/12 (8.3%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Oral herpes 3/51 (5.9%) 3/51 (5.9%) 0/18 (0%) 0/18 (0%) 1/33 (3%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Osteomyelitis 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 1/12 (8.3%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Parvovirus infection 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%) 0/7 (0%)
    Pneumocystis jirovecii pneumonia 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%) 0/7 (0%)
    Pneumonia 3/51 (5.9%) 2/51 (3.9%) 0/18 (0%) 2/18 (11.1%) 5/33 (15.2%) 1/21 (4.8%) 0/12 (0%) 2/15 (13.3%) 3/15 (20%) 0/7 (0%)
    Pseudomonas infection 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 1/15 (6.7%) 0/15 (0%) 0/7 (0%)
    Rhinitis 2/51 (3.9%) 2/51 (3.9%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 1/15 (6.7%) 0/15 (0%) 0/7 (0%)
    Sinusitis 4/51 (7.8%) 6/51 (11.8%) 0/18 (0%) 1/18 (5.6%) 4/33 (12.1%) 4/21 (19%) 0/12 (0%) 2/15 (13.3%) 0/15 (0%) 0/7 (0%)
    Sinusitis bacterial 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 1/12 (8.3%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Skin infection 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%) 0/7 (0%)
    Upper respiratory tract infection 10/51 (19.6%) 10/51 (19.6%) 1/18 (5.6%) 2/18 (11.1%) 3/33 (9.1%) 4/21 (19%) 1/12 (8.3%) 1/15 (6.7%) 3/15 (20%) 0/7 (0%)
    Urinary tract infection 3/51 (5.9%) 3/51 (5.9%) 2/18 (11.1%) 1/18 (5.6%) 2/33 (6.1%) 3/21 (14.3%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%) 0/7 (0%)
    Vulvovaginal mycotic infection 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 1/33 (3%) 0/21 (0%) 1/12 (8.3%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Injury, poisoning and procedural complications
    Contusion 1/51 (2%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 1/12 (8.3%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Fall 1/51 (2%) 0/51 (0%) 2/18 (11.1%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 2/12 (16.7%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Humerus fracture 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 1/15 (6.7%) 0/15 (0%) 0/7 (0%)
    Infusion related reaction 3/51 (5.9%) 1/51 (2%) 0/18 (0%) 0/18 (0%) 5/33 (15.2%) 3/21 (14.3%) 0/12 (0%) 0/15 (0%) 2/15 (13.3%) 0/7 (0%)
    Procedural pain 2/51 (3.9%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 1/7 (14.3%)
    Pubis fracture 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 1/12 (8.3%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Rib fracture 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 2/12 (16.7%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Skin abrasion 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 1/21 (4.8%) 1/12 (8.3%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Traumatic ulcer 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 1/12 (8.3%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Investigations
    Alanine aminotransferase increased 8/51 (15.7%) 17/51 (33.3%) 2/18 (11.1%) 5/18 (27.8%) 5/33 (15.2%) 2/21 (9.5%) 3/12 (25%) 1/15 (6.7%) 4/15 (26.7%) 5/7 (71.4%)
    Aspartate aminotransferase increased 8/51 (15.7%) 14/51 (27.5%) 2/18 (11.1%) 5/18 (27.8%) 3/33 (9.1%) 2/21 (9.5%) 3/12 (25%) 1/15 (6.7%) 3/15 (20%) 5/7 (71.4%)
    Blood albumin decreased 0/51 (0%) 0/51 (0%) 1/18 (5.6%) 0/18 (0%) 0/33 (0%) 1/21 (4.8%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Blood alkaline phosphatase increased 3/51 (5.9%) 6/51 (11.8%) 0/18 (0%) 0/18 (0%) 1/33 (3%) 1/21 (4.8%) 0/12 (0%) 1/15 (6.7%) 1/15 (6.7%) 0/7 (0%)
    Blood bilirubin increased 0/51 (0%) 1/51 (2%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 1/21 (4.8%) 1/12 (8.3%) 0/15 (0%) 1/15 (6.7%) 2/7 (28.6%)
    Blood creatinine increased 1/51 (2%) 1/51 (2%) 4/18 (22.2%) 2/18 (11.1%) 1/33 (3%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Blood glucose increased 1/51 (2%) 0/51 (0%) 0/18 (0%) 1/18 (5.6%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Blood immunoglobulin A decreased 0/51 (0%) 3/51 (5.9%) 1/18 (5.6%) 1/18 (5.6%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Blood immunoglobulin G decreased 1/51 (2%) 3/51 (5.9%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 2/21 (9.5%) 0/12 (0%) 1/15 (6.7%) 0/15 (0%) 0/7 (0%)
    Blood immunoglobulin M decreased 0/51 (0%) 3/51 (5.9%) 1/18 (5.6%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Blood lactate dehydrogenase increased 1/51 (2%) 4/51 (7.8%) 2/18 (11.1%) 2/18 (11.1%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 5/7 (71.4%)
    Blood phosphorus decreased 0/51 (0%) 0/51 (0%) 0/18 (0%) 1/18 (5.6%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Blood pressure increased 0/51 (0%) 1/51 (2%) 0/18 (0%) 1/18 (5.6%) 1/33 (3%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Blood sodium decreased 0/51 (0%) 0/51 (0%) 0/18 (0%) 1/18 (5.6%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Blood triglycerides increased 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 3/33 (9.1%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Blood urea increased 0/51 (0%) 0/51 (0%) 1/18 (5.6%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 1/12 (8.3%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Carbon dioxide decreased 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 2/21 (9.5%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Electrocardiogram QT prolonged 0/51 (0%) 1/51 (2%) 1/18 (5.6%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Gamma-glutamyltransferase increased 4/51 (7.8%) 1/51 (2%) 0/18 (0%) 0/18 (0%) 1/33 (3%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Glucose tolerance increased 0/51 (0%) 3/51 (5.9%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Liver function test abnormal 1/51 (2%) 3/51 (5.9%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%) 0/7 (0%)
    Lymphocyte count increased 0/51 (0%) 1/51 (2%) 0/18 (0%) 1/18 (5.6%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 1/15 (6.7%) 0/15 (0%) 0/7 (0%)
    Neutrophil count decreased 0/51 (0%) 1/51 (2%) 0/18 (0%) 0/18 (0%) 3/33 (9.1%) 2/21 (9.5%) 0/12 (0%) 0/15 (0%) 2/15 (13.3%) 0/7 (0%)
    Neutrophil count increased 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 1/21 (4.8%) 0/12 (0%) 1/15 (6.7%) 0/15 (0%) 0/7 (0%)
    Protein total decreased 0/51 (0%) 0/51 (0%) 1/18 (5.6%) 0/18 (0%) 0/33 (0%) 2/21 (9.5%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Transaminases increased 1/51 (2%) 1/51 (2%) 0/18 (0%) 1/18 (5.6%) 1/33 (3%) 0/21 (0%) 0/12 (0%) 1/15 (6.7%) 0/15 (0%) 0/7 (0%)
    Weight decreased 3/51 (5.9%) 6/51 (11.8%) 1/18 (5.6%) 2/18 (11.1%) 3/33 (9.1%) 1/21 (4.8%) 2/12 (16.7%) 1/15 (6.7%) 2/15 (13.3%) 0/7 (0%)
    White blood cell count decreased 0/51 (0%) 1/51 (2%) 1/18 (5.6%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    White blood cell count increased 0/51 (0%) 0/51 (0%) 0/18 (0%) 2/18 (11.1%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Metabolism and nutrition disorders
    Decreased appetite 7/51 (13.7%) 7/51 (13.7%) 6/18 (33.3%) 3/18 (16.7%) 2/33 (6.1%) 5/21 (23.8%) 5/12 (41.7%) 2/15 (13.3%) 3/15 (20%) 0/7 (0%)
    Dehydration 2/51 (3.9%) 3/51 (5.9%) 2/18 (11.1%) 1/18 (5.6%) 1/33 (3%) 0/21 (0%) 0/12 (0%) 1/15 (6.7%) 0/15 (0%) 0/7 (0%)
    Diabetes mellitus 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%) 0/7 (0%)
    Fluid overload 0/51 (0%) 0/51 (0%) 1/18 (5.6%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 1/12 (8.3%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Fluid retention 1/51 (2%) 1/51 (2%) 1/18 (5.6%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 2/15 (13.3%) 0/7 (0%)
    Gout 0/51 (0%) 1/51 (2%) 0/18 (0%) 1/18 (5.6%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Hypercholesterolaemia 2/51 (3.9%) 2/51 (3.9%) 0/18 (0%) 1/18 (5.6%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Hyperglycaemia 3/51 (5.9%) 1/51 (2%) 1/18 (5.6%) 0/18 (0%) 1/33 (3%) 2/21 (9.5%) 2/12 (16.7%) 0/15 (0%) 1/15 (6.7%) 1/7 (14.3%)
    Hyperkalaemia 1/51 (2%) 1/51 (2%) 0/18 (0%) 1/18 (5.6%) 0/33 (0%) 1/21 (4.8%) 1/12 (8.3%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Hyperlipidaemia 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 1/33 (3%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%) 0/7 (0%)
    Hypertriglyceridaemia 0/51 (0%) 2/51 (3.9%) 2/18 (11.1%) 0/18 (0%) 1/33 (3%) 1/21 (4.8%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Hyperuricaemia 4/51 (7.8%) 0/51 (0%) 1/18 (5.6%) 2/18 (11.1%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 2/15 (13.3%) 1/15 (6.7%) 0/7 (0%)
    Hypocalcaemia 0/51 (0%) 1/51 (2%) 2/18 (11.1%) 2/18 (11.1%) 0/33 (0%) 3/21 (14.3%) 2/12 (16.7%) 0/15 (0%) 2/15 (13.3%) 0/7 (0%)
    Hypoglycaemia 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 2/21 (9.5%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%) 0/7 (0%)
    Hypokalaemia 4/51 (7.8%) 5/51 (9.8%) 6/18 (33.3%) 4/18 (22.2%) 4/33 (12.1%) 2/21 (9.5%) 1/12 (8.3%) 2/15 (13.3%) 5/15 (33.3%) 1/7 (14.3%)
    Hypomagnesaemia 1/51 (2%) 3/51 (5.9%) 0/18 (0%) 0/18 (0%) 2/33 (6.1%) 0/21 (0%) 2/12 (16.7%) 0/15 (0%) 3/15 (20%) 0/7 (0%)
    Hyponatraemia 1/51 (2%) 0/51 (0%) 0/18 (0%) 1/18 (5.6%) 0/33 (0%) 3/21 (14.3%) 0/12 (0%) 1/15 (6.7%) 1/15 (6.7%) 0/7 (0%)
    Hypophosphataemia 0/51 (0%) 0/51 (0%) 6/18 (33.3%) 1/18 (5.6%) 0/33 (0%) 1/21 (4.8%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%) 0/7 (0%)
    Metabolic acidosis 0/51 (0%) 0/51 (0%) 1/18 (5.6%) 1/18 (5.6%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Tumour lysis syndrome 0/51 (0%) 0/51 (0%) 0/18 (0%) 1/18 (5.6%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Type 2 diabetes mellitus 0/51 (0%) 0/51 (0%) 1/18 (5.6%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 1/15 (6.7%) 0/15 (0%) 0/7 (0%)
    Vitamin D deficiency 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 1/21 (4.8%) 1/12 (8.3%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 6/51 (11.8%) 4/51 (7.8%) 0/18 (0%) 0/18 (0%) 1/33 (3%) 1/21 (4.8%) 1/12 (8.3%) 0/15 (0%) 2/15 (13.3%) 0/7 (0%)
    Arthritis 0/51 (0%) 0/51 (0%) 1/18 (5.6%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Back pain 7/51 (13.7%) 5/51 (9.8%) 3/18 (16.7%) 0/18 (0%) 1/33 (3%) 3/21 (14.3%) 1/12 (8.3%) 1/15 (6.7%) 2/15 (13.3%) 0/7 (0%)
    Bone pain 2/51 (3.9%) 2/51 (3.9%) 0/18 (0%) 0/18 (0%) 2/33 (6.1%) 1/21 (4.8%) 0/12 (0%) 1/15 (6.7%) 0/15 (0%) 0/7 (0%)
    Flank pain 0/51 (0%) 0/51 (0%) 1/18 (5.6%) 1/18 (5.6%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%) 0/7 (0%)
    Groin pain 3/51 (5.9%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Muscle spasms 1/51 (2%) 1/51 (2%) 0/18 (0%) 0/18 (0%) 1/33 (3%) 2/21 (9.5%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Muscular weakness 3/51 (5.9%) 0/51 (0%) 0/18 (0%) 1/18 (5.6%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Musculoskeletal chest pain 0/51 (0%) 0/51 (0%) 1/18 (5.6%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 1/12 (8.3%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Musculoskeletal discomfort 0/51 (0%) 0/51 (0%) 1/18 (5.6%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Musculoskeletal pain 1/51 (2%) 1/51 (2%) 1/18 (5.6%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 1/12 (8.3%) 0/15 (0%) 1/15 (6.7%) 0/7 (0%)
    Myalgia 3/51 (5.9%) 1/51 (2%) 0/18 (0%) 1/18 (5.6%) 1/33 (3%) 2/21 (9.5%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 2/7 (28.6%)
    Neck pain 0/51 (0%) 1/51 (2%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 1/21 (4.8%) 0/12 (0%) 1/15 (6.7%) 0/15 (0%) 0/7 (0%)
    Pain in extremity 4/51 (7.8%) 2/51 (3.9%) 0/18 (0%) 0/18 (0%) 1/33 (3%) 4/21 (19%) 1/12 (8.3%) 1/15 (6.7%) 0/15 (0%) 0/7 (0%)
    Spinal column stenosis 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 1/12 (8.3%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Tendonitis 1/51 (2%) 0/51 (0%) 0/18 (0%) 1/18 (5.6%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Basal cell carcinoma 1/51 (2%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 1/21 (4.8%) 1/12 (8.3%) 0/15 (0%) 1/15 (6.7%) 0/7 (0%)
    Malignant melanoma in situ 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 1/12 (8.3%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Seborrhoeic keratosis 0/51 (0%) 0/51 (0%) 0/18 (0%) 1/18 (5.6%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Squamous cell carcinoma 0/51 (0%) 1/51 (2%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%) 0/7 (0%)
    Nervous system disorders
    Dizziness 8/51 (15.7%) 4/51 (7.8%) 1/18 (5.6%) 4/18 (22.2%) 3/33 (9.1%) 4/21 (19%) 2/12 (16.7%) 2/15 (13.3%) 2/15 (13.3%) 2/7 (28.6%)
    Dysarthria 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 1/15 (6.7%) 0/15 (0%) 0/7 (0%)
    Dysgeusia 4/51 (7.8%) 7/51 (13.7%) 2/18 (11.1%) 2/18 (11.1%) 1/33 (3%) 2/21 (9.5%) 2/12 (16.7%) 1/15 (6.7%) 3/15 (20%) 0/7 (0%)
    Headache 12/51 (23.5%) 4/51 (7.8%) 3/18 (16.7%) 0/18 (0%) 3/33 (9.1%) 2/21 (9.5%) 2/12 (16.7%) 2/15 (13.3%) 1/15 (6.7%) 2/7 (28.6%)
    Hyperaesthesia 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%) 0/7 (0%)
    Hypoaesthesia 0/51 (0%) 0/51 (0%) 0/18 (0%) 1/18 (5.6%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Lethargy 0/51 (0%) 0/51 (0%) 1/18 (5.6%) 0/18 (0%) 1/33 (3%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Migraine 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 1/15 (6.7%) 0/15 (0%) 0/7 (0%)
    Neuralgia 0/51 (0%) 0/51 (0%) 1/18 (5.6%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Neuropathy peripheral 2/51 (3.9%) 1/51 (2%) 0/18 (0%) 2/18 (11.1%) 1/33 (3%) 1/21 (4.8%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%) 0/7 (0%)
    Normal pressure hydrocephalus 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 1/12 (8.3%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Paraesthesia 2/51 (3.9%) 3/51 (5.9%) 0/18 (0%) 1/18 (5.6%) 1/33 (3%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Peripheral sensory neuropathy 0/51 (0%) 0/51 (0%) 0/18 (0%) 1/18 (5.6%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%) 0/7 (0%)
    Post herpetic neuralgia 0/51 (0%) 1/51 (2%) 0/18 (0%) 1/18 (5.6%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 1/15 (6.7%) 0/15 (0%) 0/7 (0%)
    Presyncope 0/51 (0%) 0/51 (0%) 2/18 (11.1%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Seizure 0/51 (0%) 0/51 (0%) 1/18 (5.6%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Trigeminal neuralgia 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%) 0/7 (0%)
    Psychiatric disorders
    Agitation 0/51 (0%) 0/51 (0%) 2/18 (11.1%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Anxiety 3/51 (5.9%) 0/51 (0%) 3/18 (16.7%) 0/18 (0%) 2/33 (6.1%) 1/21 (4.8%) 3/12 (25%) 3/15 (20%) 1/15 (6.7%) 0/7 (0%)
    Confusional state 0/51 (0%) 0/51 (0%) 1/18 (5.6%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 2/12 (16.7%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Delirium 0/51 (0%) 0/51 (0%) 1/18 (5.6%) 1/18 (5.6%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Depression 2/51 (3.9%) 1/51 (2%) 1/18 (5.6%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Hallucination 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 1/12 (8.3%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Insomnia 7/51 (13.7%) 11/51 (21.6%) 3/18 (16.7%) 0/18 (0%) 6/33 (18.2%) 2/21 (9.5%) 1/12 (8.3%) 4/15 (26.7%) 3/15 (20%) 0/7 (0%)
    Irritability 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 1/15 (6.7%) 0/15 (0%) 0/7 (0%)
    Sleep disorder 0/51 (0%) 1/51 (2%) 0/18 (0%) 0/18 (0%) 2/33 (6.1%) 1/21 (4.8%) 1/12 (8.3%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Stress 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 1/15 (6.7%) 0/15 (0%) 0/7 (0%)
    Renal and urinary disorders
    Acute kidney injury 0/51 (0%) 0/51 (0%) 1/18 (5.6%) 1/18 (5.6%) 2/33 (6.1%) 1/21 (4.8%) 1/12 (8.3%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Dysuria 3/51 (5.9%) 1/51 (2%) 2/18 (11.1%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 1/12 (8.3%) 0/15 (0%) 0/15 (0%) 0/7 (0%)
    Haematuria 0/51 (0%) 1/51 (2%) 1/18 (5.6%) 1/18 (5.6%) 1/33 (3%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%) 0/7 (0%)
    Incontinence 0/51 (0%) 0/51 (0%) 0/18 (0%) 0/18 (0%) 0/33 (0%) 0/21 (0%) 0/12 (0%) 0/15 (0%) 0/15 (0%) 1/7 (14.3%)
    Nephrolithiasis 0/51 (0%) 0/51 (0%) 0/18 (0%) 1/18 (5.6%) 0/33 (0%)