FUSION NHL 001: A Study to Determine Dose, Safety, and Efficacy of Durvalumab as Monotherapy and in Combination Therapy in Subjects With Lymphoma or Chronic Lymphocytic Leukemia

Sponsor
Celgene (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT02733042
Collaborator
(none)
106
Enrollment
54
Locations
4
Arms
75.3
Anticipated Duration (Months)
2
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study is designed to determine the recommended phase 2 dose (RP2D), and the safety, and efficacy of durvalumab as monotherapy and when given in combination with lenalidomide and rituximab; ibrutinib; or bendamustine and rituximab at the RP2D in adults with lymphoma or chronic lymphocytic leukemia (CLL).

Detailed Description

The study was to consist of 3 parts: dose-finding, dose-confirmation, and dose-expansion. In this study, 4 treatment arms were to be investigated:

  • Arm A: durvalumab and lenalidomide ± rituximab

  • Arm B: durvalumab and ibrutinib

  • Arm C: durvalumab and rituximab ± bendamustine

  • Arm D: durvalumab (monotherapy)

The study was to start with 3 dose-finding cohorts (Arms A, B, and C) and 1 dose-confirmation cohort (Arm D) in parallel. All treatment arms were to be open for enrollment at study start except in the US, where Arm D was to enroll depending on the availability of treatment slots and following the completion of assessment of responses from the combination therapy arms. For Arms A and C, prior to enrolling participants to receive all 3 drugs, the doublet combinations were to be evaluated. Once the doublet combinations were deemed tolerable, the eventual triplet combinations were to be tested.

On 05 September 2017, the US FDA issued a Partial Clinical Hold on the study Arm A. Following this Partial Clinical Hold no more participants were enrolled into study Arm A. Participants already enrolled and treated in Arm A who were receiving clinical benefit, based on the discretion of the investigator, could continue study treatment after being reconsented. Arm B and C completed dose confirmation. The dose expansion part of the study was not opened.

Study Design

Study Type:
Interventional
Actual Enrollment :
106 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Intervention Model Description:
Within Arms A, B, and C participants on the dose-finding part were enrolled sequentially according to a 3+3 design. All treatment arms were to be open for enrollment at study start except in the US, where Arm D was to enroll depending on the availability of treatment slots and following the completion of assessment of responses from the combination therapy arms.Within Arms A, B, and C participants on the dose-finding part were enrolled sequentially according to a 3+3 design. All treatment arms were to be open for enrollment at study start except in the US, where Arm D was to enroll depending on the availability of treatment slots and following the completion of assessment of responses from the combination therapy arms.
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1/2, Open-label, Multi-center Study to Assess the Safety and Tolerability of Durvalumab (Anti-PDL1 Antibody) as Monotherapy and in Combination Therapy in Subjects With Lymphoma or Chronic Lymphocitic Leukemia
Actual Study Start Date :
May 11, 2016
Actual Primary Completion Date :
Mar 6, 2019
Anticipated Study Completion Date :
Aug 21, 2022

Arms and Interventions

ArmIntervention/Treatment
Experimental: Arm A: Durvalumab + Lenalidomide ± Rituximab

Participants assigned to Arm A will receive: Durvalumab 1500 mg intravenous (IV) infusion on Day 1 of Cycles 1 through 13 (ie, 12 months) and Lenalidomide orally at assigned dose levels (10 mg, 15 mg or 20 mg) once daily on Days 1 to 21 of: Cycles 1 through 13 in indolent non-Hodgkin's lymphoma (NHL) or All cycles of treatment period until disease progression, unacceptable toxicity, or discontinuation for any other reason in aggressive NHL Rituximab 375 mg/m² IV infusion every week in Cycle 1 (Days 2, 8, 15, 22) and on Day 1 of Cycles 2 through 5. All treatment cycles were 28 days.

Drug: Durvalumab
Administered as an IV infusion (250 mL) over approximately 1 hour in duration
Other Names:
  • MEDI4736
  • IMFINZI®
  • Drug: Lenalidomide
    Administered orally
    Other Names:
  • Revlimid®
  • Drug: Rituximab
    Administered by intravenous infusion
    Other Names:
  • Rituxan®
  • MabThera®
  • Experimental: Arm B: Durvalumab + Ibrutinib

    Participants assigned to Arm B will receive: Durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13 Ibrutinib orally at assigned dose levels (280 mg, 420 mg, or 560 mg) once daily until disease progression, unacceptable toxicity or discontinuation for any other reason. All treatment cycles were 28 days.

    Drug: Durvalumab
    Administered as an IV infusion (250 mL) over approximately 1 hour in duration
    Other Names:
  • MEDI4736
  • IMFINZI®
  • Drug: Ibrutinib
    Administered orally
    Other Names:
  • Imbruvica®
  • Experimental: Arm C: Durvalumab + Rituximab ± Bendamustine

    Participants assigned to Arm C will receive: Durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13 Rituximab 375 mg/m² IV infusion on Day 2 of Cycles 1 through 6 (for CLL the rituximab dose will be 375 mg/m² Cycle 1 first dose and 500 mg/m² for each subsequent dose) Bendamustine IV infusion at assigned dose levels (70 mg/m² or 90 mg/m²) on Days 1 and 2 of Cycles 1 through 6. All treatment cycles were 28 days.

    Drug: Durvalumab
    Administered as an IV infusion (250 mL) over approximately 1 hour in duration
    Other Names:
  • MEDI4736
  • IMFINZI®
  • Drug: Rituximab
    Administered by intravenous infusion
    Other Names:
  • Rituxan®
  • MabThera®
  • Drug: Bendamustine
    Administered as a 30-minute intravenous infusion
    Other Names:
  • Treanda®
  • Bendeka®
  • Levact®
  • Experimental: Arm D: Durvalumab Monotherapy

    Participants assigned to Arm D will receive durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13. All treatment cycles were 28 days.

    Drug: Durvalumab
    Administered as an IV infusion (250 mL) over approximately 1 hour in duration
    Other Names:
  • MEDI4736
  • IMFINZI®
  • Outcome Measures

    Primary Outcome Measures

    1. Part 1: Number of Participants With Dose Limiting Toxicities (DLTs) [Cycle 1 (28 days)]

      Dose limiting toxicities were evaluated during the DLT evaluation period for participants in the dose finding cohorts. The severity grading was determined according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03. A DLT is defined as below: Hematologic DLT Grade 4 neutropenia observed for greater than 5 days duration Grade 3 neutropenia associated with fever (≥ 38.5 °C) of any duration Grade 4 thrombocytopenia or Grade 3 thrombocytopenia with bleeding, or any requirement for platelets transfusion Grade 4 anemia, unexplained by underlying disease Any other grade 4 hematologic toxicity that does not resolve to participant's pretreatment baseline level within 72 hours. Non-Hematologic DLT Any non-hematological toxicity ≥ Grade 3 except for alopecia and nausea controlled by medical management Any treatment interruption greater than 2 weeks due to adverse event.

    2. Number of Participants With Treatment-emergent Adverse Events [From first dose of any study drug to 90 days after last dose of durvalumab or 28 days after last dose of other study drugs, up to the data cut-off date of 6 March 2019. Maximum time on treatment was 55.4 weeks for DUR and 130 weeks for other study drugs.]

      Treatment-emergent adverse events (TEAEs) are defined as adverse events (AEs) occurring or worsening on or after the first dose of any study treatment (durvalumab, lenalidomide, ibrutinib, bendamustine or rituximab) and within 90 days after last dose of durvalumab or 28 days after the last dose of other study drugs, whichever was later, as well as those serious adverse events made known to the investigator at any time thereafter that were suspected of being related to study treatment. The intensity of AEs was graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03. For all other AEs not described in the CTCAE criteria, the intensity was assessed by the investigator as mild (Grade 1), moderate (Grade 2), severe (Grade 3), life-threatening (Grade 4), or death (Grade 5).

    Secondary Outcome Measures

    1. Overall Response Rate (ORR) During Durvalumab Treatment [Up to 13 cycles (12 months)]

      For lymphoma participants, response evaluation was based on International Working Group (IWG) response criteria for malignant lymphoma (the Lugano Classification). Overall response rate is defined as the percent of participants with best response of complete response (CR) or partial response (PR). For chronic lymphocytic leukemia participants, response evaluation was based on International Workshop on Chronic Lymphocytic Leukemia (IWCLL) guidelines for diagnosis and treatment of CLL. The ORR is defined as the percent of participants with best response of CR, complete response with incomplete marrow recovery (CRi), nodular partial response (nPR), PR, or partial response with lymphocytosis (PRL).

    2. Overall Response Rate During the Entire Study [From first dose of any study drug to the end of follow-up, up to the data cutoff date of March 6, 2019; median (minimum, maximum) time on study was 16.7 (0.9, 32.9) months.]

      For lymphoma participants, response evaluation was based on International Working Group (IWG) response criteria for malignant lymphoma (the Lugano Classification) (Cheson, 2014). Overall response rate is defined as the percent of participants with best response of complete response (CR) or partial response (PR). For chronic lymphocytic leukemia participants, response evaluation was based on International Workshop on Chronic Lymphocytic Leukemia (IWCLL) guidelines for diagnosis and treatment of CLL. The ORR is defined as the percentage of participants with best response of CR, complete response with incomplete marrow recovery (CRi), nodular partial response (nPR), PR, or partial response with lymphocytosis (PRL).

    3. Time to First Response [From first dose of any study drug to the end of follow-up, up to the data cutoff date of March 6, 2019; median (minimum, maximum) time on study was 16.7 (0.9, 32.9) months.]

      Time to response was calculated as the time from first dose of study drug to the first response date (CR or PR for lymphoma participants and CR, CRi, nPR, PR, or PRL for CLL participants).

    4. Kaplan-Meier Estimate of Duration of Response [From first dose of any study drug to the end of follow-up, up to the data cutoff date of March 6, 2019; median (minimum, maximum) time on study was 16.7 (0.9, 32.9) months.]

      Duration of response is defined for responders only as the time from the first documented response (CR or PR for lymphoma participants or CR, CRi, nPR, PR, or PRL for CLL participants) to disease progression or death (from any cause). For participants with response but no progression, or death, duration of response was censored at the last date that the participant was known to be progression-free.

    5. Kaplan-Meier Estimate of Progression-free Survival (PFS) [From first dose of any study drug to the end of follow-up, up to the data cutoff date of March 6, 2019; median (minimum, maximum) time on study was 16.7 (0.9, 32.9) months.]

      Progression-free survival was calculated as the time from first dose of study drug to the first documented progression or death (from any cause) during the entire efficacy evaluation period. For participants with no progression or death, PFS was censored at the last assessment date the participant was known to be progression-free.

    6. Maximum Observed Plasma Concentration (Cmax) of Durvalumab [Cycle 1, Day 1 (pre-dose and at end of infusion), and 4, 24, 48, 168 (Day 8), 336 (Day 15), and 508 (Day 22) hours after the end of infusion.]

    7. Time to Maximum Plasma Concentration (Tmax) of Durvalumab [Cycle 1, Day 1 (pre-dose and at end of infusion), and 4, 24, 48, 168 (Day 8), 336 (Day 15), and 508 (Day 22) hours after the end of infusion.]

    8. Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUClast) of Durvalumab [Cycle 1, Day 1 (pre-dose and at end of infusion), and 4, 24, 48, 168 (Day 8), 336 (Day 15), and 508 (Day 22) hours after the end of infusion.]

    9. Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUCinf) of Durvalumab [Cycle 1, Day 1 (pre-dose and at end of infusion), and 4, 24, 48, 168 (Day 8), 336 (Day 15), and 508 (Day 22) hours after the end of infusion.]

    10. Terminal Elimination Phase Half-Life (t½) of Durvalumab [Cycle 1, Day 1 (pre-dose and at end of infusion), and 4, 24, 48, 168 (Day 8), 336 (Day 15), and 508 (Day 22) hours after the end of infusion.]

    11. Clearance (CL) of Durvalumab [Cycle 1, Day 1 (pre-dose and at end of infusion), and 4, 24, 48, 168 (Day 8), 336 (Day 15), and 508 (Day 22) hours after the end of infusion.]

    12. Volume of Distribution (Vz) of Durvalumab [Cycle 1, Day 1 (pre-dose and at end of infusion), and 4, 24, 48, 168 (Day 8), 336 (Day 15), and 508 (Day 22) hours after the end of infusion.]

    13. Maximum Observed Plasma Concentration (Cmax) of Lenalidomide [Cycle 1 Day 1 at predose and 1, 2, 4, and 24 hours post-dose, and Cycle 1 Day 15 at pre-dose, 1, 2, and 4 hours post-dose.]

    14. Time to Maximum Observed Plasma Concentration (Tmax) of Lenalidomide [Cycle 1 Day 1 at predose and 1, 2, 4, and 24 hours post-dose, and Cycle 1 Day 15 at pre-dose, 1, 2, and 4 hours post-dose.]

    15. Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUClast) of Lenalidomide [Cycle 1 Day 1 at predose and 1, 2, 4, and 24 hours post-dose]

    16. Maximum Observed Plasma Concentration (Cmax) of Ibrutinib [Cycle 1 Day 1 at predose and 1, 2, 4, and 24 hours post-dose, and Cycle 1 Day 15 at pre-dose, 1, 2, and 4 hours post-dose.]

    17. Time to Maximum Observed Plasma Concentration (Tmax) of Ibrutinib [Cycle 1 Day 1 at predose and 1, 2, 4, and 24 hours post-dose, and Cycle 1 Day 15 at pre-dose, 1, 2, and 4 hours post-dose.]

    18. Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUClast) of Ibrutinib [Cycle 1 Day 1 at predose and 1, 2, 4, and 24 hours post-dose]

    19. Change From Baseline in Soluble Programmed Cell Death Ligand-1 (sPD-L1) Concentration [Baseline (Cycle 1 Day 1 predose) and Day 1 of Cycles 2 to 13]

      Change from baseline in sPD-L1 could not be calculated as all post-baseline samples were below the lower limit of quantification (<15.60 pg/mL).

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    1. Subject who has histologically confirmed and documented B-cell lymphoma (eg, follicular, diffuse large B-cell, mantle cell, small lymphocytic, or Hodgkin lymphoma) and chronic lymphocytic leukemia.

    2. Subject who has high-risk chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL).

    3. Subject who was previously treated with at least one prior systemic chemotherapy, immunotherapy, or chemoimmunotherapy.

    4. Subject who has the Eastern Cooperative Oncology Group performance status of 0, 1, or

    5. Subject who is willing and able to undergo biopsy.

    6. Subject who has documented active relapsed or refractory disease requiring therapeutic intervention.

    7. Subject with lymphoma who has measurable disease (≥ 2.0 cm in its longest dimension by computed tomography) or chronic lymphocytic leukemia in need of treatment.

    8. Subject who fulfills the laboratory requirements as per protocol

    Exclusion Criteria

    1. Subject who has central nervous system (CNS) or meningeal involvement by lymphoma.

    2. Subject who has any histopathologic finding consistent with myelodysplastic syndrome on bone marrow studies.

    3. Subject who received any prior monoclonal antibodies against programmed cell death-1 (PD-1) or programmed cell death ligand-1 (PD-L1) and/or any prior:

    4. Arm A only: drugs with immunomodulatory and other properties (eg, lenalidomide, thalidomide);

    5. Arm B only: ibrutinib or other Bruton's tyrosine kinase (BTK) inhibitor;

    6. Arms C only: bendamustine

    7. Subject who has active auto-immune disease.

    8. Subject who has history of organ transplant or allogeneic hematopoietic stem cell transplantation.

    9. Subject who is seropositive for or active viral infection with hepatitis B virus (HBV) (hepatitis B surface antigen [HBsAg] positive and/or detectable viral DNA)

    10. Subject who has known seropositivity for or active infection for human immunodeficiency virus (HIV) or hepatitis C virus (HCV).

    11. Subject who has history of primary immunodeficiency or tuberculosis.

    12. Subject who other invasive malignancy within 2 years (5 years for Arm A) except for noninvasive malignancies such as cervical carcinoma in situ, non-melanomatous carcinoma of the skin, ductal carcinoma in situ of the breast, or incidental histologic finding of prostate cancer (T1a or T1b using the TNM [tumor, nodes, metastasis] clinical staging system) that has/have been surgically cured.

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1Banner MD Anderson Cancer CenterGilbertArizonaUnited States85234
    2Pinnacle Oncology HematologyScottsdaleArizonaUnited States85258
    3University of Colorado Cancer CenterAuroraColoradoUnited States80045
    4Shands Cancer Center University of FloridaGainesvilleFloridaUnited States32610
    5Moffitt Cancer CenterTampaFloridaUnited States33612
    6Emory UniversityAtlantaGeorgiaUnited States30322
    7Northwestern University Feinberg School of MedicineChicagoIllinoisUnited States60611
    8Mayo ClinicRochesterMinnesotaUnited States55905
    9Washington University School of MedicineSaint LouisMissouriUnited States63110
    10John Theurer Cancer Center at Hackensack University Medical CenterHackensackNew JerseyUnited States07601
    11Weill Cornell Medical CollegeNew YorkNew YorkUnited States10065
    12University of RochesterRochesterNew YorkUnited States14642
    13The Ohio State UniversityColumbusOhioUnited States43210
    14University of Oklahoma Peggy and Charles Stephenson Cancer CenterOklahoma CityOklahomaUnited States73104
    15Jefferson Medical Oncology AssociatesPhiladelphiaPennsylvaniaUnited States19107
    16MD Anderson Cancer CenterHoustonTexasUnited States77030-4009
    17Houston Methodist Cancer CenterHoustonTexasUnited States77030
    18MD Anderson Cancer CenterHoustonTexasUnited States77030
    19Centre Hospitalier Universitaire d'AvicennesBobigny CedexFrance93009
    20Hopital Henri MondorCreteilFrance94010
    21Centre HospitalierDijon CedexFrance21079
    22Institut Paoli CalmettesMarseille Cedex 9France13273
    23CHU MontpellierMontpellier Cedex 5France34295
    24Centre Hospitalier Universitaire de NantesNantesFrance44093
    25Hopital Haut LevequePessac CedexFrance33604
    26Centre Hospitalier Lyon-SudPierre-Benite CEDEXFrance69495
    27CHRU RennesRennesFrance35033
    28Centre Henri BecquerelRouen CedexFrance76038
    29Universitatsklinikum EssenEssenGermany45122
    30UKG Universitatsklinikum GottingenGöttingenGermany37099
    31Universitatsklinikum des SaarlandesHomburg-SaarGermany66421
    32Universitatsklinik KolnKölnGermany50924
    33Medizinische Klinik III Klinikum der Universität München-GroßhadernMünchenGermany81377
    34University of BolognaBolognaItaly40138
    35Spedali Civili Di BresciaBresciaItaly25123
    36IEO- Istituto Europeo di OncologiaMilanoItaly20144
    37A.O. Ospedale Ca Granda - NiguardaMilanoItaly20162
    38Istituto Nazionale Per Lo Studio E La Cura Dei Tumori Fondazione Giovanni PascaleNapoli, CampaniaItaly80131
    39I.R.C.C.S. Policlinico San MatteoPaviaItaly27100
    40IRCCS Humanitas Clinical InstituteRozzano (milano)Italy20089
    41National Cancer Center HospitalChuo-kuJapan104-0045
    42Tokai University HospitalIsehara City, KanagawaJapan259-1193
    43Aichi Cancer CenterNagoyaJapan464-8681
    44VU Academic Medical Center, AmsterdamAmsterdamNetherlands1081 HV
    45UMC GroningenGroningenNetherlands9713 GZ
    46Leids Universitair Medisch CentrumLeidenNetherlands2333 ZA
    47Erasmus Medical CenterRotterdamNetherlands3015 CN
    48St James University HospitalLeedsUnited KingdomLS9 7TF
    49UCL Cancer InstituteLondonUnited KingdomWC1E 6BT
    50Christie Hospital NHS TrustManchesterUnited KingdomM20 4BX
    51Nottingham University Hospitals NHS TrustNottinghamUnited KingdomNg5 1PB
    52Oxford University Hospitals NHS Trust- Churchill Hospital-Oxford Centre for Respiratory MedicineOxfordUnited Kingdom0X3 7LE
    53Derriford HospitalPlymouthUnited KingdomPL6 8DH
    54Southampton University Hospitals NHS TrustSouthamptonUnited KingdomSO16 6YD

    Sponsors and Collaborators

    • Celgene

    Investigators

    • Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Celgene
    ClinicalTrials.gov Identifier:
    NCT02733042
    Other Study ID Numbers:
    • MEDI4736-NHL-001
    • 2015-003516-21
    First Posted:
    Apr 11, 2016
    Last Update Posted:
    Feb 1, 2022
    Last Verified:
    Jan 1, 2022

    Study Results

    Participant Flow

    Recruitment DetailsThe study was conducted at 32 sites in 6 countries: France, Italy, Japan, the Netherlands, the United Kingdom, and the US. The study was to consist of 3 parts: dose-finding (Part 1) dose-confirmation (Part 2), and dose-expansion (Part 3). Part 3 was not opened. The study is ongoing; results are based on a data cut-off date of March 6, 2019.
    Pre-assignment DetailParticipants were assigned to 1 of 4 treatment arms based on the investigator's choice led by the participant's eligibility status per the inclusion/exclusion criteria for each treatment arm, prior antilymphoma/chronic lymphocytic leukemia (CLL) therapy, response to prior therapy, medical history, and the availability of open treatment slots.
    Arm/Group TitlePart 1, Arm A: DUR 1500 mg + LEN 20 mgPart 1, Arm A: DUR 1500 mg + LEN 20 mg + RIT 375 mg/m²Part 1, Arm A: DUR 1500 mg + LEN 10 mg + RIT 375 mg/m²Part 1, Arm B: DUR 1500 mg + IBR 420 mgPart 1, Arm B: DUR 1500 mg + IBR 560 mgPart 1, Arm C: DUR 1500 mg + RIT 375 mg/m²Part 1, Arm C: DUR 1500 mg + BEN 70 mg/m²Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m²Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 90 mg/m²Part 2, Arm B CLL/SLL: DUR 1500 mg + IBR 420 mgPart 2, Arm B MCL: DUR 1500 mg + IBR 560 mgPart 2, Arm C FL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m²Part 2 Arm C DLBCL: DUR mg + RIT 375 mg/m² + BEN 70 mg/m²Part 2, Arm C CLL/SLL: DUR + RIT 375 mg/m² + BEN 70 mg/m²Part 2, Arm D FL: DUR 1500 mgPart 2, Arm D DLBCL: DUR 1500 mgPart 2, Arm D CLL/SLL: DUR 1500 mgPart 2, Arm D MCL: DUR 1500 mgPart 2 Arm D HL: DUR 1500 mg
    Arm/Group DescriptionParticipants received durvalumab (DUR) 1500 mg intravenous (IV) infusion on Day 1 of Cycles 1 through 13 (ie, 12 months) and lenalidomide (LEN) 20 mg orally once daily on Days 1 to 21 of Cycles 1 through 13 for participants with indolent non-Hodgkin's lymphoma (NHL) or for all cycles of treatment period until disease progression, unacceptable toxicity, or discontinuation for any other reason in participants with aggressive NHL.Participants received durvalumab (DUR) 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and lenalidomide (LEN) 20 mg orally once daily on Days 1 to 21 of Cycles 1 through 13 for participants with indolent NHL or until disease progression, unacceptable toxicity, or discontinuation for any other reason in participants with aggressive NHL, and rituximab (RIT) 375 mg/m² IV infusion on Days 2, 8, 15, and 22 of Cycle 1 and on Day 1 of every 28-day cycle from Cycles 2 through 5.Participants received durvalumab (DUR) 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and lenalidomide (LEN) 10 mg orally once daily on Days 1 to 21 of Cycles 1 through 13 for participants with indolent NHL or until disease progression, unacceptable toxicity, or discontinuation for any other reason in participants with aggressive NHL, and rituximab 375 mg/m² IV infusion on Days 2, 8, 15, 22 of Cycle 1 and on Day 1 of every 28-day cycle from Cycles 2 through 5.Participants received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and ibrutinib (IBR) 420 mg orally once daily until disease progression, unacceptable toxicity or discontinuation for any other reason.Participants received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and ibrutinib 560 mg orally once daily until disease progression, unacceptable toxicity or discontinuation for any other reason.Participants received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13, and rituximab 375 mg/m² IV infusion on Day 2 of Cycles 1 through 6 (for participants with CLL the rituximab dose was 375 mg/m² Cycle 1 first dose and 500 mg/m² for each subsequent dose).Participants received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and bendamustine (BEN) 70 mg/m² IV infusion on Days 1 and 2 of Cycles 1 through 6.Participants received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13, bendamustine 70 mg/m² IV infusion on Days 1 and 2 of Cycles 1 through 6, and rituximab 375 mg/m² IV infusion on Day 2 of Cycles 1 through 6 (for CLL the rituximab dose was 375 mg/m² Cycle 1 first dose and 500 mg/m² for each subsequent dose).Participants received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13, bendamustine 90 mg/m² IV infusion on Days 1 and 2 of Cycles 1 through 6, and rituximab 375 mg/m² IV infusion on Day 2 of Cycles 1 through 6 (for CLL the rituximab dose was 375 mg/m² Cycle 1 first dose and 500 mg/m² for each subsequent dose).Participants with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and ibrutinib 420 mg orally once daily until disease progression, unacceptable toxicity or discontinuation for any other reason.Participants with mantle cell lymphoma (MCL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and ibrutinib 560 mg orally once daily until disease progression, unacceptable toxicity or discontinuation for any other reason.Participants with follicular lymphoma (FL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13, bendamustine 70 mg/m² IV infusion on Days 1 and 2 of Cycles 1 through 6, and rituximab 375 mg/m² IV infusion on Day 2 of Cycles 1 through 6.Participants with diffuse large B-cell lymphoma (DLBCL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13, bendamustine 70 mg/m² IV infusion on Days 1 and 2 of Cycles 1 through 6, and rituximab 375 mg/m² IV infusion on Day 2 of Cycles 1 through 6.Participants with CLL or SLL received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13, bendamustine 70 mg/m² IV infusion on Days 1 and 2 of Cycles 1 through 6, and rituximab 375 mg/m² IV infusion on Day 2 of Cycles 1 through 6 (for CLL the rituximab dose was 375 mg/m² Cycle 1 first dose and 500 mg/m² for each subsequent dose).Participants with follicular lymphoma received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13.Participants with diffuse large B-cell lymphoma (DLBCL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13.Participants with CLL or SLL received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13.Participants with mantle cell lymphoma (MCL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13.Participants with Hodgkin lymphoma (HL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13.
    Period Title: Treatment Period
    STARTED338343145101010105510255
    COMPLETED0110000100041100000
    NOT COMPLETED3273431351010694510255
    Period Title: Treatment Period
    STARTED3363120442599415032
    COMPLETED0000000000000000010
    NOT COMPLETED3363120442599415022

    Baseline Characteristics

    Arm/Group TitlePart 1, Arm A: DUR 1500 mg + LEN 20 mgPart 1, Arm A: DUR 1500 mg + LEN 20 mg + RIT 375 mg/m²Part 1, Arm A: DUR 1500 mg + LEN 10 mg + RIT 375 mg/m²Part 1, Arm B: DUR 1500 mg + IBR 420 mgPart 1, Arm B: DUR 1500 mg + IBR 560 mgPart 1, Arm C: DUR 1500 mg + RIT 375 mg/m²Part 1, Arm C: DUR 1500 mg + BEN 70 mg/m²Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m²Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 90 mg/m²Part 2, Arm B CLL/SLL: DUR 1500 mg + IBR 420 mGPart 2, Arm B MCL: DUR 1500 mg + IBR 560 mgPart 2, Arm C FL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m²Part 2 Arm C DLBCL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m²Part 2, Arm C CLL/SLL: DUR + RIT 375 mg/m² + BEN 70 mg/m²Part 2, Arm D FL: DUR 1500 mgPart 2, Arm D DLBCL: DUR 1500 mgPart 2, Arm D CLL/SLL: DUR 1500 mgPart 2, Arm D MCL: DUR 1500 mgPart 2 Arm D HL: DUR 1500 mgTotal
    Arm/Group DescriptionParticipants received durvalumab (DUR) 1500 mg intravenous (IV) infusion on Day 1 of Cycles 1 through 13 (ie, 12 months) and lenalidomide (LEN) 20 mg orally once daily on Days 1 to 21 of Cycles 1 through 13 for participants with indolent non-Hodgkin's lymphoma (NHL) or for all cycles of treatment period until disease progression, unacceptable toxicity, or discontinuation for any other reason in participants with aggressive NHL.Participants received durvalumab (DUR) 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and lenalidomide (LEN) 20 mg orally once daily on Days 1 to 21 of Cycles 1 through 13 for participants with indolent NHL or until disease progression, unacceptable toxicity, or discontinuation for any other reason in participants with aggressive NHL, and rituximab 375 mg/m² IV infusion on Days 2, 8, 15, 22 of Cycle 1 and on Day 1 of every 28-day cycle from Cycles 2 through 5.Participants received durvalumab (DUR) 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and lenalidomide (LEN) 10 mg orally once daily on Days 1 to 21 of Cycles 1 through 13 for participants with indolent NHL or until disease progression, unacceptable toxicity, or discontinuation for any other reason in participants with aggressive NHL, and rituximab 375 mg/m² IV infusion on Days 2, 8, 15, 22 of Cycle 1 and on Day 1 of every 28-day cycle from Cycles 2 through 5.Participants received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and ibrutinib 420 mg orally once daily until disease progression, unacceptable toxicity or discontinuation for any other reason.Participants received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and ibrutinib 560 mg orally once daily until disease progression, unacceptable toxicity or discontinuation for any other reason.Participants received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13, and rituximab 375 mg/m² IV infusion on Day 2 of Cycles 1 through 6 (for participants with CLL the rituximab dose was 375 mg/m² Cycle 1 first dose and 500 mg/m² for each subsequent dose).Participants received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and bendamustine 70 mg/m² IV infusion on Days 1 and 2 of Cycles 1 through 6.Participants received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13, bendamustine 70 mg/m² IV infusion on Days 1 and 2 of Cycles 1 through 6, and rituximab 375 mg/m² IV infusion on Day 2 of Cycles 1 through 6 (for CLL the rituximab dose was 375 mg/m² Cycle 1 first dose and 500 mg/m² for each subsequent dose).Participants received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13, bendamustine 90 mg/m² IV infusion on Days 1 and 2 of Cycles 1 through 6, and rituximab 375 mg/m² IV infusion on Day 2 of Cycles 1 through 6 (for CLL the rituximab dose was 375 mg/m² Cycle 1 first dose and 500 mg/m² for each subsequent dose).Participants with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and ibrutinib 420 mg orally once daily until disease progression, unacceptable toxicity or discontinuation for any other reason.Participants with mantle cell lymphoma (MCL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and ibrutinib 560 mg orally once daily until disease progression, unacceptable toxicity or discontinuation for any other reason.Participants with follicular lymphoma (FL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13, bendamustine 70 mg/m² IV infusion on Days 1 and 2 of Cycles 1 through 6, and rituximab 375 mg/m² IV infusion on Day 2 of Cycles 1 through 6.Participants with diffuse large B-cell lymphoma (DLBCL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13, bendamustine 70 mg/m² IV infusion on Days 1 and 2 of Cycles 1 through 6, and rituximab 375 mg/m² IV infusion on Day 2 of Cycles 1 through 6.Participants with CLL or SLL received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13, bendamustine 70 mg/m² IV infusion on Days 1 and 2 of Cycles 1 through 6, and rituximab 375 mg/m² IV infusion on Day 2 of Cycles 1 through 6 (for CLL the rituximab dose was 375 mg/m² Cycle 1 first dose and 500 mg/m² for each subsequent dose).Participants with follicular lymphoma received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13.Participants with diffuse large B-cell lymphoma (DLBCL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13.Participants with CLL or SLL received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13.Participants with mantle cell lymphoma (MCL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13.Participants with Hodgkin lymphoma (HL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13.Total of all reporting groups
    Overall Participants338343145101010105510255106
    Age (years) [Median (Full Range) ]
    Median (Full Range) [years]
    71.0
    66.0
    77.0
    58.0
    68.0
    79.0
    70.0
    68.0
    38.0
    68.0
    73.5
    64.5
    60.0
    68.0
    52.0
    61.5
    62.0
    77.0
    51.0
    67.0
    Age, Customized (Count of Participants)
    < 65 Years
    1
    33.3%
    1
    33.3%
    2
    25%
    2
    66.7%
    1
    25%
    0
    0%
    0
    0%
    1
    25%
    3
    60%
    4
    40%
    2
    20%
    5
    50%
    7
    70%
    2
    40%
    3
    60%
    5
    50%
    1
    50%
    0
    0%
    4
    80%
    44
    41.5%
    ≥ 65 Years
    2
    66.7%
    2
    66.7%
    6
    75%
    1
    33.3%
    3
    75%
    3
    100%
    1
    100%
    3
    75%
    2
    40%
    6
    60%
    8
    80%
    5
    50%
    3
    30%
    3
    60%
    2
    40%
    5
    50%
    1
    50%
    5
    100%
    1
    20%
    62
    58.5%
    Sex: Female, Male (Count of Participants)
    Female
    1
    33.3%
    0
    0%
    2
    25%
    0
    0%
    2
    50%
    2
    66.7%
    0
    0%
    1
    25%
    3
    60%
    3
    30%
    1
    10%
    3
    30%
    4
    40%
    2
    40%
    2
    40%
    4
    40%
    1
    50%
    2
    40%
    2
    40%
    35
    33%
    Male
    2
    66.7%
    3
    100%
    6
    75%
    3
    100%
    2
    50%
    1
    33.3%
    1
    100%
    3
    75%
    2
    40%
    7
    70%
    9
    90%
    7
    70%
    6
    60%
    3
    60%
    3
    60%
    6
    60%
    1
    50%
    3
    60%
    3
    60%
    71
    67%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    25%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    20%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    2
    1.9%
    Not Hispanic or Latino
    2
    66.7%
    2
    66.7%
    7
    87.5%
    2
    66.7%
    3
    75%
    1
    33.3%
    1
    100%
    3
    75%
    3
    60%
    5
    50%
    7
    70%
    6
    60%
    8
    80%
    3
    60%
    2
    40%
    9
    90%
    2
    100%
    5
    100%
    5
    100%
    76
    71.7%
    Unknown or Not Reported
    1
    33.3%
    1
    33.3%
    1
    12.5%
    1
    33.3%
    0
    0%
    2
    66.7%
    0
    0%
    1
    25%
    2
    40%
    5
    50%
    3
    30%
    4
    40%
    2
    20%
    1
    20%
    3
    60%
    1
    10%
    0
    0%
    0
    0%
    0
    0%
    28
    26.4%
    Race/Ethnicity, Customized (Count of Participants)
    White
    2
    66.7%
    2
    66.7%
    3
    37.5%
    2
    66.7%
    4
    100%
    0
    0%
    1
    100%
    0
    0%
    4
    80%
    5
    50%
    6
    60%
    4
    40%
    4
    40%
    4
    80%
    2
    40%
    9
    90%
    2
    100%
    4
    80%
    5
    100%
    63
    59.4%
    Asian
    0
    0%
    0
    0%
    3
    37.5%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    3
    75%
    1
    20%
    0
    0%
    1
    10%
    1
    10%
    3
    30%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    20%
    0
    0%
    13
    12.3%
    Black or African American
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    10%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    0.9%
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Other
    0
    0%
    0
    0%
    1
    12.5%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    10%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    2
    1.9%
    Not Collected or Reported
    1
    33.3%
    1
    33.3%
    1
    12.5%
    1
    33.3%
    0
    0%
    3
    100%
    0
    0%
    1
    25%
    0
    0%
    5
    50%
    3
    30%
    4
    40%
    2
    20%
    1
    20%
    3
    60%
    1
    10%
    0
    0%
    0
    0%
    0
    0%
    27
    25.5%
    Histology (Count of Participants)
    Follicular lymphoma
    1
    33.3%
    3
    100%
    1
    12.5%
    1
    33.3%
    0
    0%
    1
    33.3%
    0
    0%
    1
    25%
    0
    0%
    0
    0%
    0
    0%
    10
    100%
    0
    0%
    0
    0%
    5
    100%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    23
    21.7%
    Diffuse large B-cell lymphoma
    2
    66.7%
    0
    0%
    4
    50%
    0
    0%
    0
    0%
    2
    66.7%
    1
    100%
    3
    75%
    5
    100%
    0
    0%
    0
    0%
    0
    0%
    10
    100%
    0
    0%
    0
    0%
    10
    100%
    0
    0%
    0
    0%
    0
    0%
    37
    34.9%
    Marginal zone lymphoma
    0
    0%
    0
    0%
    2
    25%
    0
    0%
    3
    75%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    5
    4.7%
    Transformed follicular lymphoma
    0
    0%
    0
    0%
    1
    12.5%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    0.9%
    Mantle cell lymphoma
    0
    0%
    0
    0%
    0
    0%
    1
    33.3%
    1
    25%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    10
    100%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    5
    100%
    0
    0%
    17
    16%
    CLL / SLL
    0
    0%
    0
    0%
    0
    0%
    1
    33.3%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    10
    100%
    0
    0%
    0
    0%
    0
    0%
    5
    100%
    0
    0%
    0
    0%
    2
    100%
    0
    0%
    0
    0%
    18
    17%
    Hodgkin lymphoma
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    5
    100%
    5
    4.7%
    Eastern Cooperative Oncology Group ECOG) Performance Status (Count of Participants)
    0 - Fully Active
    0
    0%
    2
    66.7%
    2
    25%
    0
    0%
    1
    25%
    1
    33.3%
    0
    0%
    3
    75%
    2
    40%
    8
    80%
    6
    60%
    6
    60%
    7
    70%
    0
    0%
    2
    40%
    3
    30%
    1
    50%
    4
    80%
    5
    100%
    53
    50%
    1 - Restricted but ambulatory
    3
    100%
    1
    33.3%
    4
    50%
    3
    100%
    3
    75%
    2
    66.7%
    0
    0%
    0
    0%
    2
    40%
    2
    20%
    3
    30%
    3
    30%
    1
    10%
    4
    80%
    2
    40%
    4
    40%
    1
    50%
    1
    20%
    0
    0%
    39
    36.8%
    2 - Ambulatory but unable to work
    0
    0%
    0
    0%
    2
    25%
    0
    0%
    0
    0%
    0
    0%
    1
    100%
    1
    25%
    1
    20%
    0
    0%
    1
    10%
    1
    10%
    2
    20%
    1
    20%
    1
    20%
    2
    20%
    0
    0%
    0
    0%
    0
    0%
    13
    12.3%
    3 - Limited self-care
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    10%
    0
    0%
    0
    0%
    0
    0%
    1
    0.9%

    Outcome Measures

    1. Primary Outcome
    TitlePart 1: Number of Participants With Dose Limiting Toxicities (DLTs)
    DescriptionDose limiting toxicities were evaluated during the DLT evaluation period for participants in the dose finding cohorts. The severity grading was determined according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03. A DLT is defined as below: Hematologic DLT Grade 4 neutropenia observed for greater than 5 days duration Grade 3 neutropenia associated with fever (≥ 38.5 °C) of any duration Grade 4 thrombocytopenia or Grade 3 thrombocytopenia with bleeding, or any requirement for platelets transfusion Grade 4 anemia, unexplained by underlying disease Any other grade 4 hematologic toxicity that does not resolve to participant's pretreatment baseline level within 72 hours. Non-Hematologic DLT Any non-hematological toxicity ≥ Grade 3 except for alopecia and nausea controlled by medical management Any treatment interruption greater than 2 weeks due to adverse event.
    Time FrameCycle 1 (28 days)

    Outcome Measure Data

    Analysis Population Description
    DLT Evaluable population included participants in Arms A, B, and C of Part 1, who took at least one dose of study drug and completed the DLT evaluation through the end of DLT evaluation period, or participants who took at least one dose of study drug and experienced at least one DLT prior to completion of the DLT evaluation period.
    Arm/Group TitlePart 1, Arm A: DUR 1500 mg + LEN 20 mgPart 1, Arm A: DUR 1500 mg + LEN 20 mg + RIT 375 mg/m²Part 1, Arm A: DUR 1500 mg + LEN 10 mg + RIT 375 mg/m²Part 1, Arm B: DUR 1500 mg + IBR 420 mgPart 1, Arm B: DUR 1500 mg + IBR 560 mgPart 1, Arm C: DUR 1500 mg + RIT 375 mg/m²Part 1, Arm C: DUR 1500 mg + BEN 70 mg/m²Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m²Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 90 mg/m²
    Arm/Group DescriptionParticipants received durvalumab (DUR) 1500 mg intravenous (IV) infusion on Day 1 of Cycles 1 through 13 (ie, 12 months) and lenalidomide (LEN) 20 mg orally once daily on Days 1 to 21 of Cycles 1 through 13 for participants with indolent non-Hodgkin's lymphoma (NHL) or for all cycles of treatment period until disease progression, unacceptable toxicity, or discontinuation for any other reason in participants with aggressive NHL.Participants received durvalumab (DUR) 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and lenalidomide (LEN) 20 mg orally once daily on Days 1 to 21 of Cycles 1 through 13 for participants with indolent NHL or until disease progression, unacceptable toxicity, or discontinuation for any other reason in participants with aggressive NHL, and rituximab 375 mg/m² IV infusion on Days 2, 8, 15, 22 of Cycle 1 and on Day 1 of every 28-day cycle from Cycles 2 through 5.Participants received durvalumab (DUR) 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and lenalidomide (LEN) 10 mg orally once daily on Days 1 to 21 of Cycles 1 through 13 for participants with indolent NHL or until disease progression, unacceptable toxicity, or discontinuation for any other reason in participants with aggressive NHL, and rituximab 375 mg/m² IV infusion on Days 2, 8, 15, 22 of Cycle 1 and on Day 1 of every 28-day cycle from Cycles 2 through 5.Participants received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and ibrutinib 420 mg orally once daily until disease progression, unacceptable toxicity or discontinuation for any other reason.Participants received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and ibrutinib 560 mg orally once daily until disease progression, unacceptable toxicity or discontinuation for any other reason.Participants received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13, and rituximab 375 mg/m² IV infusion on Day 2 of Cycles 1 through 6 (for participants with CLL the rituximab dose was 375 mg/m² Cycle 1 first dose and 500 mg/m² for each subsequent dose).Participants received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and bendamustine 70 mg/m² IV infusion on Days 1 and 2 of Cycles 1 through 6.Participants received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13, bendamustine 70 mg/m² IV infusion on Days 1 and 2 of Cycles 1 through 6, and rituximab 375 mg/m² IV infusion on Day 2 of Cycles 1 through 6 (for CLL the rituximab dose was 375 mg/m² Cycle 1 first dose and 500 mg/m² for each subsequent dose).Participants received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13, bendamustine 90 mg/m² IV infusion on Days 1 and 2 of Cycles 1 through 6, and rituximab 375 mg/m² IV infusion on Day 2 of Cycles 1 through 6 (for CLL the rituximab dose was 375 mg/m² Cycle 1 first dose and 500 mg/m² for each subsequent dose).
    Measure Participants336343045
    Count of Participants [Participants]
    0
    0%
    3
    100%
    1
    12.5%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    25%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Part 1, Arm B: DUR 1500 mg + IBR 420 mg, Part 1, Arm B: DUR 1500 mg + IBR 560 mg
    Comments The safety review committee identified a preliminary recommended Phase 2 dose (RP2D) for each dose finding cohort based on an integrated assessment of the safety, pharmacokinetic, pharmacodynamic, and preliminary efficacy (as available).
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesisp-Value
    Comments
    Method
    Comments
    Other Statistical AnalysisFor Arm B, ibrutinib 420 mg was confirmed as the RP2D for CLL/SLL participants and ibrutinib 560 mg was confirmed as the RP2D for MCL participants.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m², Part 1, Arm C: DUR 1500 mg + BEN 70 mg/m², Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m², Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 90 mg/m²
    Comments The safety review committee identified a preliminary recommended Phase 2 dose (RP2D) for each dose finding cohort based on an integrated assessment of the safety, pharmacokinetic, pharmacodynamic, and preliminary efficacy (as available).
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesisp-Value
    Comments
    Method
    Comments
    Other Statistical AnalysisFor Arm C the RP2D was confirmed as rituximab 375 mg/m² + bendamustine 70 mg/m².
    2. Primary Outcome
    TitleNumber of Participants With Treatment-emergent Adverse Events
    DescriptionTreatment-emergent adverse events (TEAEs) are defined as adverse events (AEs) occurring or worsening on or after the first dose of any study treatment (durvalumab, lenalidomide, ibrutinib, bendamustine or rituximab) and within 90 days after last dose of durvalumab or 28 days after the last dose of other study drugs, whichever was later, as well as those serious adverse events made known to the investigator at any time thereafter that were suspected of being related to study treatment. The intensity of AEs was graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03. For all other AEs not described in the CTCAE criteria, the intensity was assessed by the investigator as mild (Grade 1), moderate (Grade 2), severe (Grade 3), life-threatening (Grade 4), or death (Grade 5).
    Time FrameFrom first dose of any study drug to 90 days after last dose of durvalumab or 28 days after last dose of other study drugs, up to the data cut-off date of 6 March 2019. Maximum time on treatment was 55.4 weeks for DUR and 130 weeks for other study drugs.

    Outcome Measure Data

    Analysis Population Description
    The Safety population included all participants who received at least 1 dose of study drug.
    Arm/Group TitlePart 1, Arm A: DUR 1500 mg + LEN 20 mgPart 1, Arm A: DUR 1500 mg + LEN 20 mg + RIT 375 mg/m²Part 1, Arm A: DUR 1500 mg + LEN 10 mg + RIT 375 mg/m²Part 1, Arm B: DUR 1500 mg + IBR 420 mgPart 1, Arm B: DUR 1500 mg + IBR 560 mgPart 1, Arm C: DUR 1500 mg + RIT 375 mg/m²Part 1, Arm C: DUR 1500 mg + BEN 70 mg/m²Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m²Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 90 mg/m²Part 2, Arm B CLL/SLL: DUR 1500 mg + IBR 420 mgPart 2, Arm B MCL: DUR 1500 mg + IBR 560 mgPart 2, Arm C FL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m²Part 2 Arm C DLBCL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m²Part 2, Arm C CLL/SLL: DUR + RIT 375 mg/m² + BEN 70 mg/m²Part 2, Arm D FL: DUR 1500 mgPart 2, Arm D DLBCL: DUR 1500 mgPart 2, Arm D CLL/SLL: DUR 1500 mgPart 2, Arm D MCL: DUR 1500 mgPart 2 Arm D HL: DUR 1500 mg
    Arm/Group DescriptionParticipants received durvalumab (DUR) 1500 mg intravenous (IV) infusion on Day 1 of Cycles 1 through 13 (ie, 12 months) and lenalidomide (LEN) 20 mg orally once daily on Days 1 to 21 of Cycles 1 through 13 for participants with indolent non-Hodgkin's lymphoma (NHL) or for all cycles of treatment period until disease progression, unacceptable toxicity, or discontinuation for any other reason in participants with aggressive NHL.Participants received durvalumab (DUR) 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and lenalidomide (LEN) 20 mg orally once daily on Days 1 to 21 of Cycles 1 through 13 for participants with indolent NHL or until disease progression, unacceptable toxicity, or discontinuation for any other reason in participants with aggressive NHL, and rituximab 375 mg/m² IV infusion on Days 2, 8, 15, 22 of Cycle 1 and on Day 1 of every 28-day cycle from Cycles 2 through 5.Participants received durvalumab (DUR) 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and lenalidomide (LEN) 10 mg orally once daily on Days 1 to 21 of Cycles 1 through 13 for participants with indolent NHL or until disease progression, unacceptable toxicity, or discontinuation for any other reason in participants with aggressive NHL, and rituximab 375 mg/m² IV infusion on Days 2, 8, 15, 22 of Cycle 1 and on Day 1 of every 28-day cycle from Cycles 2 through 5.Participants received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and ibrutinib 420 mg orally once daily until disease progression, unacceptable toxicity or discontinuation for any other reason.Participants received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and ibrutinib 560 mg orally once daily until disease progression, unacceptable toxicity or discontinuation for any other reason.Participants received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13, and rituximab 375 mg/m² IV infusion on Day 2 of Cycles 1 through 6 (for participants with CLL the rituximab dose was 375 mg/m² Cycle 1 first dose and 500 mg/m² for each subsequent dose).Participants received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and bendamustine 70 mg/m² IV infusion on Days 1 and 2 of Cycles 1 through 6.Participants received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13, bendamustine 70 mg/m² IV infusion on Days 1 and 2 of Cycles 1 through 6, and rituximab 375 mg/m² IV infusion on Day 2 of Cycles 1 through 6 (for CLL the rituximab dose was 375 mg/m² Cycle 1 first dose and 500 mg/m² for each subsequent dose).Participants received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13, bendamustine 90 mg/m² IV infusion on Days 1 and 2 of Cycles 1 through 6, and rituximab 375 mg/m² IV infusion on Day 2 of Cycles 1 through 6 (for CLL the rituximab dose was 375 mg/m² Cycle 1 first dose and 500 mg/m² for each subsequent dose).Participants with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and ibrutinib 420 mg orally once daily until disease progression, unacceptable toxicity or discontinuation for any other reason.Participants with mantle cell lymphoma (MCL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and ibrutinib 560 mg orally once daily until disease progression, unacceptable toxicity or discontinuation for any other reason.Participants with follicular lymphoma (FL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13, bendamustine 70 mg/m² IV infusion on Days 1 and 2 of Cycles 1 through 6, and rituximab 375 mg/m² IV infusion on Day 2 of Cycles 1 through 6.Participants with diffuse large B-cell lymphoma (DLBCL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13, bendamustine 70 mg/m² IV infusion on Days 1 and 2 of Cycles 1 through 6, and rituximab 375 mg/m² IV infusion on Day 2 of Cycles 1 through 6.Participants with CLL or SLL received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13, bendamustine 70 mg/m² IV infusion on Days 1 and 2 of Cycles 1 through 6, and rituximab 375 mg/m² IV infusion on Day 2 of Cycles 1 through 6 (for CLL the rituximab dose was 375 mg/m² Cycle 1 first dose and 500 mg/m² for each subsequent dose).Participants with follicular lymphoma received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13.Participants with diffuse large B-cell lymphoma (DLBCL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13.Participants with CLL or SLL received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13.Participants with mantle cell lymphoma (MCL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13.Participants with Hodgkin lymphoma (HL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13.
    Measure Participants338343145101010105510255
    Any TEAE
    3
    100%
    3
    100%
    8
    100%
    3
    100%
    4
    100%
    3
    100%
    1
    100%
    4
    100%
    5
    100%
    10
    100%
    10
    100%
    10
    100%
    9
    90%
    5
    100%
    5
    100%
    9
    90%
    2
    100%
    5
    100%
    5
    100%
    TEAE Related to Any Study Drug
    3
    100%
    3
    100%
    8
    100%
    3
    100%
    4
    100%
    3
    100%
    0
    0%
    4
    100%
    5
    100%
    10
    100%
    9
    90%
    10
    100%
    9
    90%
    5
    100%
    4
    80%
    3
    30%
    0
    0%
    3
    60%
    2
    40%
    CTCAE Grade 3-4 TEAE
    1
    33.3%
    3
    100%
    7
    87.5%
    2
    66.7%
    3
    75%
    2
    66.7%
    1
    100%
    3
    75%
    4
    80%
    8
    80%
    10
    100%
    6
    60%
    9
    90%
    5
    100%
    4
    80%
    7
    70%
    1
    50%
    4
    80%
    3
    60%
    CTCAE Grade 3-4 TEAE Related to Any Study Drug
    1
    33.3%
    3
    100%
    7
    87.5%
    1
    33.3%
    1
    25%
    2
    66.7%
    0
    0%
    2
    50%
    2
    40%
    7
    70%
    6
    60%
    5
    50%
    7
    70%
    3
    60%
    3
    60%
    2
    20%
    0
    0%
    1
    20%
    1
    20%
    CTCAE Grade 5 TEAE
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    10%
    0
    0%
    0
    0%
    1
    20%
    1
    20%
    4
    40%
    0
    0%
    0
    0%
    0
    0%
    CTCAE Grade 5 TEAE Related to Any Study Drug
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    10%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Serious TEAE
    1
    33.3%
    2
    66.7%
    4
    50%
    2
    66.7%
    2
    50%
    2
    66.7%
    1
    100%
    1
    25%
    3
    60%
    6
    60%
    7
    70%
    5
    50%
    5
    50%
    2
    40%
    4
    80%
    7
    70%
    0
    0%
    3
    60%
    2
    40%
    Serious TEAE Related to Any Study Drug
    1
    33.3%
    2
    66.7%
    3
    37.5%
    1
    33.3%
    0
    0%
    1
    33.3%
    0
    0%
    0
    0%
    1
    20%
    2
    20%
    3
    30%
    3
    30%
    3
    30%
    1
    20%
    3
    60%
    1
    10%
    0
    0%
    0
    0%
    0
    0%
    TEAE Leading to Discontinuation of Any Study Drug
    1
    33.3%
    0
    0%
    3
    37.5%
    1
    33.3%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    2
    20%
    2
    20%
    1
    10%
    2
    40%
    1
    20%
    0
    0%
    0
    0%
    1
    20%
    0
    0%
    TEAE Leading to Dose Modifications of Study Drug
    1
    33.3%
    3
    100%
    3
    37.5%
    3
    100%
    4
    100%
    3
    100%
    1
    100%
    4
    100%
    4
    80%
    8
    80%
    9
    90%
    7
    70%
    4
    40%
    3
    60%
    2
    40%
    0
    0%
    0
    0%
    3
    60%
    3
    60%
    3. Secondary Outcome
    TitleOverall Response Rate (ORR) During Durvalumab Treatment
    DescriptionFor lymphoma participants, response evaluation was based on International Working Group (IWG) response criteria for malignant lymphoma (the Lugano Classification). Overall response rate is defined as the percent of participants with best response of complete response (CR) or partial response (PR). For chronic lymphocytic leukemia participants, response evaluation was based on International Workshop on Chronic Lymphocytic Leukemia (IWCLL) guidelines for diagnosis and treatment of CLL. The ORR is defined as the percent of participants with best response of CR, complete response with incomplete marrow recovery (CRi), nodular partial response (nPR), PR, or partial response with lymphocytosis (PRL).
    Time FrameUp to 13 cycles (12 months)

    Outcome Measure Data

    Analysis Population Description
    The Efficacy Evaluable population includes all participants who completed at least 1 cycle of their assigned treatment, and have baseline and at least 1 post-baseline tumor response assessment.
    Arm/Group TitlePart 1, Arm A: DUR 1500 mg + LEN 20 mgPart 1, Arm A: DUR 1500 mg + LEN 20 mg + RIT 375 mg/m²Part 1, Arm A: DUR 1500 mg + LEN 10 mg + RIT 375 mg/m²Part 1, Arm B: DUR 1500 mg + IBR 420 mgPart 1, Arm B: DUR 1500 mg + IBR 560 mgPart 1, Arm C: DUR 1500 mg + RIT 375 mg/m²Part 1, Arm C: DUR 1500 mg + BEN 70 mg/m²Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m²Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 90 mg/m²Part 2, Arm B CLL/SLL: DUR 1500 mg + IBR 420 mgPart 2, Arm B MCL: DUR 1500 mg + IBR 560 mgPart 2, Arm C FL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m²Part 2 Arm C DLBCL: DUR + RIT 375 mg/m² + BEN 70 mg/m²Part 2, Arm C CLL/SLL: DUR + RIT 375 mg/m² + BEN 70 mg/m²Part 2, Arm D FL: DUR 1500 mgPart 2, Arm D DLBCL: DUR 1500 mgPart 2, Arm D CLL/SLL: DUR 1500 mgPart 2, Arm D MCL: DUR 1500 mgPart 2 Arm D HL: DUR 1500 mg
    Arm/Group DescriptionParticipants received durvalumab (DUR) 1500 mg intravenous (IV) infusion on Day 1 of Cycles 1 through 13 (ie, 12 months) and lenalidomide (LEN) 20 mg orally once daily on Days 1 to 21 of Cycles 1 through 13 for participants with indolent non-Hodgkin's lymphoma (NHL) or for all cycles of treatment period until disease progression, unacceptable toxicity, or discontinuation for any other reason in participants with aggressive NHL.Participants received durvalumab (DUR) 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and lenalidomide (LEN) 20 mg orally once daily on Days 1 to 21 of Cycles 1 through 13 for participants with indolent NHL or until disease progression, unacceptable toxicity, or discontinuation for any other reason in participants with aggressive NHL, and rituximab 375 mg/m² IV infusion on Days 2, 8, 15, 22 of Cycle 1 and on Day 1 of every 28-day cycle from Cycles 2 through 5.Participants received durvalumab (DUR) 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and lenalidomide (LEN) 10 mg orally once daily on Days 1 to 21 of Cycles 1 through 13 for participants with indolent NHL or until disease progression, unacceptable toxicity, or discontinuation for any other reason in participants with aggressive NHL, and rituximab 375 mg/m² IV infusion on Days 2, 8, 15, 22 of Cycle 1 and on Day 1 of every 28-day cycle from Cycles 2 through 5.Participants received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and ibrutinib 420 mg orally once daily until disease progression, unacceptable toxicity or discontinuation for any other reason.Participants received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and ibrutinib 560 mg orally once daily until disease progression, unacceptable toxicity or discontinuation for any other reason.Participants received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13, and rituximab 375 mg/m² IV infusion on Day 2 of Cycles 1 through 6 (for participants with CLL the rituximab dose was 375 mg/m² Cycle 1 first dose and 500 mg/m² for each subsequent dose).Participants received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and bendamustine 70 mg/m² IV infusion on Days 1 and 2 of Cycles 1 through 6.Participants received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13, bendamustine 70 mg/m² IV infusion on Days 1 and 2 of Cycles 1 through 6, and rituximab 375 mg/m² IV infusion on Day 2 of Cycles 1 through 6 (for CLL the rituximab dose was 375 mg/m² Cycle 1 first dose and 500 mg/m² for each subsequent dose).Participants received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13, bendamustine 90 mg/m² IV infusion on Days 1 and 2 of Cycles 1 through 6, and rituximab 375 mg/m² IV infusion on Day 2 of Cycles 1 through 6 (for CLL the rituximab dose was 375 mg/m² Cycle 1 first dose and 500 mg/m² for each subsequent dose).Participants with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and ibrutinib 420 mg orally once daily until disease progression, unacceptable toxicity or discontinuation for any other reason.Participants with mantle cell lymphoma (MCL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and ibrutinib 560 mg orally once daily until disease progression, unacceptable toxicity or discontinuation for any other reason.Participants with follicular lymphoma (FL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13, bendamustine 70 mg/m² IV infusion on Days 1 and 2 of Cycles 1 through 6, and rituximab 375 mg/m² IV infusion on Day 2 of Cycles 1 through 6.Participants with diffuse large B-cell lymphoma (DLBCL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13, bendamustine 70 mg/m² IV infusion on Days 1 and 2 of Cycles 1 through 6, and rituximab 375 mg/m² IV infusion on Day 2 of Cycles 1 through 6.Participants with CLL or SLL received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13, bendamustine 70 mg/m² IV infusion on Days 1 and 2 of Cycles 1 through 6, and rituximab 375 mg/m² IV infusion on Day 2 of Cycles 1 through 6 (for CLL the rituximab dose was 375 mg/m² Cycle 1 first dose and 500 mg/m² for each subsequent dose).Participants with follicular lymphoma received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13.Participants with diffuse large B-cell lymphoma (DLBCL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13.Participants with CLL or SLL received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13.Participants with mantle cell lymphoma (MCL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13.Participants with Hodgkin lymphoma (HL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13.
    Measure Participants3353430449109104510255
    Number (95% Confidence Interval) [percentage of participants]
    33.3
    1110%
    66.7
    2223.3%
    80.0
    1000%
    66.7
    2223.3%
    75.0
    1875%
    33.3
    1110%
    50.0
    5000%
    0
    0%
    88.9
    1778%
    60.0
    600%
    88.9
    889%
    30.0
    300%
    50.0
    500%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    20.0
    400%
    4. Secondary Outcome
    TitleOverall Response Rate During the Entire Study
    DescriptionFor lymphoma participants, response evaluation was based on International Working Group (IWG) response criteria for malignant lymphoma (the Lugano Classification) (Cheson, 2014). Overall response rate is defined as the percent of participants with best response of complete response (CR) or partial response (PR). For chronic lymphocytic leukemia participants, response evaluation was based on International Workshop on Chronic Lymphocytic Leukemia (IWCLL) guidelines for diagnosis and treatment of CLL. The ORR is defined as the percentage of participants with best response of CR, complete response with incomplete marrow recovery (CRi), nodular partial response (nPR), PR, or partial response with lymphocytosis (PRL).
    Time FrameFrom first dose of any study drug to the end of follow-up, up to the data cutoff date of March 6, 2019; median (minimum, maximum) time on study was 16.7 (0.9, 32.9) months.

    Outcome Measure Data

    Analysis Population Description
    The Efficacy Evaluable population includes all participants who completed at least 1 cycle of their assigned treatment, and have baseline and at least 1 post-baseline tumor response assessment.
    Arm/Group TitlePart 1, Arm A: DUR 1500 mg + LEN 20 mgPart 1, Arm A: DUR 1500 mg + LEN 20 mg + RIT 375 mg/m²Part 1, Arm A: DUR 1500 mg + LEN 10 mg + RIT 375 mg/m²Part 1, Arm B: DUR 1500 mg + IBR 420 mgPart 1, Arm B: DUR 1500 mg + IBR 560 mgPart 1, Arm C: DUR 1500 mg + RIT 375 mg/m²Part 1, Arm C: DUR 1500 mg + BEN 70 mg/m²Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m²Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 90 mg/m²Part 2, Arm B CLL/SLL: DUR 1500 mg + IBR 420 mgPart 2, Arm B MCL: DUR 1500 mg + IBR 560 mgPart 2, Arm C FL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m²Part 2 Arm C DLBCL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m²Part 2, Arm C CLL/SLL: DUR + RIT 375 mg/m² + BEN 70 mg/m²Part 2, Arm D FL: DUR 1500 mgPart 2, Arm D DLBCL: DUR 1500 mgPart 2, Arm D CLL/SLL: DUR 1500 mgPart 2, Arm D MCL: DUR 1500 mgPart 2 Arm D HL: DUR 1500 mg
    Arm/Group DescriptionParticipants received durvalumab (DUR) 1500 mg intravenous (IV) infusion on Day 1 of Cycles 1 through 13 (ie, 12 months) and lenalidomide (LEN) 20 mg orally once daily on Days 1 to 21 of Cycles 1 through 13 for participants with indolent non-Hodgkin's lymphoma (NHL) or for all cycles of treatment period until disease progression, unacceptable toxicity, or discontinuation for any other reason in participants with aggressive NHL.Participants received durvalumab (DUR) 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and lenalidomide (LEN) 20 mg orally once daily on Days 1 to 21 of Cycles 1 through 13 for participants with indolent NHL or until disease progression, unacceptable toxicity, or discontinuation for any other reason in participants with aggressive NHL, and rituximab 375 mg/m² IV infusion on Days 2, 8, 15, 22 of Cycle 1 and on Day 1 of every 28-day cycle from Cycles 2 through 5.Participants received durvalumab (DUR) 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and lenalidomide (LEN) 10 mg orally once daily on Days 1 to 21 of Cycles 1 through 13 for participants with indolent NHL or until disease progression, unacceptable toxicity, or discontinuation for any other reason in participants with aggressive NHL, and rituximab 375 mg/m² IV infusion on Days 2, 8, 15, 22 of Cycle 1 and on Day 1 of every 28-day cycle from Cycles 2 through 5.Participants received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and ibrutinib 420 mg orally once daily until disease progression, unacceptable toxicity or discontinuation for any other reason.Participants received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and ibrutinib 560 mg orally once daily until disease progression, unacceptable toxicity or discontinuation for any other reason.Participants received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13, and rituximab 375 mg/m² IV infusion on Day 2 of Cycles 1 through 6 (for participants with CLL the rituximab dose was 375 mg/m² Cycle 1 first dose and 500 mg/m² for each subsequent dose).Participants received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and bendamustine 70 mg/m² IV infusion on Days 1 and 2 of Cycles 1 through 6.Participants received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13, bendamustine 70 mg/m² IV infusion on Days 1 and 2 of Cycles 1 through 6, and rituximab 375 mg/m² IV infusion on Day 2 of Cycles 1 through 6 (for CLL the rituximab dose was 375 mg/m² Cycle 1 first dose and 500 mg/m² for each subsequent dose).Participants received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13, bendamustine 90 mg/m² IV infusion on Days 1 and 2 of Cycles 1 through 6, and rituximab 375 mg/m² IV infusion on Day 2 of Cycles 1 through 6 (for CLL the rituximab dose was 375 mg/m² Cycle 1 first dose and 500 mg/m² for each subsequent dose).Participants with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and ibrutinib 420 mg orally once daily until disease progression, unacceptable toxicity or discontinuation for any other reason.Participants with mantle cell lymphoma (MCL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and ibrutinib 560 mg orally once daily until disease progression, unacceptable toxicity or discontinuation for any other reason.Participants with follicular lymphoma (FL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13, bendamustine 70 mg/m² IV infusion on Days 1 and 2 of Cycles 1 through 6, and rituximab 375 mg/m² IV infusion on Day 2 of Cycles 1 through 6.Participants with diffuse large B-cell lymphoma (DLBCL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13, bendamustine 70 mg/m² IV infusion on Days 1 and 2 of Cycles 1 through 6, and rituximab 375 mg/m² IV infusion on Day 2 of Cycles 1 through 6.Participants with CLL or SLL received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13, bendamustine 70 mg/m² IV infusion on Days 1 and 2 of Cycles 1 through 6, and rituximab 375 mg/m² IV infusion on Day 2 of Cycles 1 through 6 (for CLL the rituximab dose was 375 mg/m² Cycle 1 first dose and 500 mg/m² for each subsequent dose).Participants with follicular lymphoma received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13.Participants with diffuse large B-cell lymphoma (DLBCL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13.Participants with CLL or SLL received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13.Participants with mantle cell lymphoma (MCL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13.Participants with Hodgkin lymphoma (HL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13.
    Measure Participants3353430449109104510255
    Number (95% Confidence Interval) [percentage of participants]
    66.7
    2223.3%
    66.7
    2223.3%
    80.0
    1000%
    66.7
    2223.3%
    75.0
    1875%
    33.3
    1110%
    50.0
    5000%
    0
    0%
    100.0
    2000%
    70.0
    700%
    88.9
    889%
    30.0
    300%
    50.0
    500%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    20.0
    400%
    5. Secondary Outcome
    TitleTime to First Response
    DescriptionTime to response was calculated as the time from first dose of study drug to the first response date (CR or PR for lymphoma participants and CR, CRi, nPR, PR, or PRL for CLL participants).
    Time FrameFrom first dose of any study drug to the end of follow-up, up to the data cutoff date of March 6, 2019; median (minimum, maximum) time on study was 16.7 (0.9, 32.9) months.

    Outcome Measure Data

    Analysis Population Description
    Efficacy evaluable population (all participants who completed at least 1 cycle of their assigned treatment, and have baseline and at least 1 post-baseline tumor response assessment) who had an objective response
    Arm/Group TitlePart 1, Arm A: DUR 1500 mg + LEN 20 mgPart 1, Arm A: DUR 1500 mg + LEN 20 mg + RIT 375 mg/m²Part 1, Arm A: DUR 1500 mg + LEN 10 mg + RIT 375 mg/m²Part 1, Arm B: DUR 1500 mg + IBR 420 mgPart 1, Arm B: DUR 1500 mg + IBR 560 mgPart 1, Arm C: DUR 1500 mg + RIT 375 mg/m²Part 1, Arm C: DUR 1500 mg + BEN 70 mg/m²Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m²Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 90 mg/m²Part 2, Arm B CLL/SLL: DUR 1500 mg + IBR 420 mgPart 2, Arm B MCL: DUR 1500 mg + IBR 560 mgPart 2, Arm C FL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m²Part 2 Arm C DLBCL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m²Part 2, Arm C CLL/SLL: DUR + RIT 375 mg/m² + BEN 70 mg/m²Part 2, Arm D FL: DUR 1500 mgPart 2, Arm D DLBCL: DUR 1500 mgPart 2, Arm D CLL/SLL: DUR 1500 mgPart 2, Arm D MCL: DUR 1500 mgPart 2 Arm D HL: DUR 1500 mg
    Arm/Group DescriptionParticipants received durvalumab (DUR) 1500 mg intravenous (IV) infusion on Day 1 of Cycles 1 through 13 (ie, 12 months) and lenalidomide (LEN) 20 mg orally once daily on Days 1 to 21 of Cycles 1 through 13 for participants with indolent non-Hodgkin's lymphoma (NHL) or for all cycles of treatment period until disease progression, unacceptable toxicity, or discontinuation for any other reason in participants with aggressive NHL.Participants received durvalumab (DUR) 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and lenalidomide (LEN) 20 mg orally once daily on Days 1 to 21 of Cycles 1 through 13 for participants with indolent NHL or until disease progression, unacceptable toxicity, or discontinuation for any other reason in participants with aggressive NHL, and rituximab 375 mg/m² IV infusion on Days 2, 8, 15, 22 of Cycle 1 and on Day 1 of every 28-day cycle from Cycles 2 through 5.Participants received durvalumab (DUR) 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and lenalidomide (LEN) 10 mg orally once daily on Days 1 to 21 of Cycles 1 through 13 for participants with indolent NHL or until disease progression, unacceptable toxicity, or discontinuation for any other reason in participants with aggressive NHL, and rituximab 375 mg/m² IV infusion on Days 2, 8, 15, 22 of Cycle 1 and on Day 1 of every 28-day cycle from Cycles 2 through 5.Participants received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and ibrutinib 420 mg orally once daily until disease progression, unacceptable toxicity or discontinuation for any other reason.Participants received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and ibrutinib 560 mg orally once daily until disease progression, unacceptable toxicity or discontinuation for any other reason.Participants received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13, and rituximab 375 mg/m² IV infusion on Day 2 of Cycles 1 through 6 (for participants with CLL the rituximab dose was 375 mg/m² Cycle 1 first dose and 500 mg/m² for each subsequent dose).Participants received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and bendamustine 70 mg/m² IV infusion on Days 1 and 2 of Cycles 1 through 6.Participants received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13, bendamustine 70 mg/m² IV infusion on Days 1 and 2 of Cycles 1 through 6, and rituximab 375 mg/m² IV infusion on Day 2 of Cycles 1 through 6 (for CLL the rituximab dose was 375 mg/m² Cycle 1 first dose and 500 mg/m² for each subsequent dose).Participants received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13, bendamustine 90 mg/m² IV infusion on Days 1 and 2 of Cycles 1 through 6, and rituximab 375 mg/m² IV infusion on Day 2 of Cycles 1 through 6 (for CLL the rituximab dose was 375 mg/m² Cycle 1 first dose and 500 mg/m² for each subsequent dose).Participants with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and ibrutinib 420 mg orally once daily until disease progression, unacceptable toxicity or discontinuation for any other reason.Participants with mantle cell lymphoma (MCL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and ibrutinib 560 mg orally once daily until disease progression, unacceptable toxicity or discontinuation for any other reason.Participants with follicular lymphoma (FL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13, bendamustine 70 mg/m² IV infusion on Days 1 and 2 of Cycles 1 through 6, and rituximab 375 mg/m² IV infusion on Day 2 of Cycles 1 through 6.Participants with diffuse large B-cell lymphoma (DLBCL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13, bendamustine 70 mg/m² IV infusion on Days 1 and 2 of Cycles 1 through 6, and rituximab 375 mg/m² IV infusion on Day 2 of Cycles 1 through 6.Participants with CLL or SLL received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13, bendamustine 70 mg/m² IV infusion on Days 1 and 2 of Cycles 1 through 6, and rituximab 375 mg/m² IV infusion on Day 2 of Cycles 1 through 6 (for CLL the rituximab dose was 375 mg/m² Cycle 1 first dose and 500 mg/m² for each subsequent dose).Participants with follicular lymphoma received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13.Participants with diffuse large B-cell lymphoma (DLBCL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13.Participants with CLL or SLL received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13.Participants with mantle cell lymphoma (MCL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13.Participants with Hodgkin lymphoma (HL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13.
    Measure Participants2242310209783200001
    Median (Full Range) [weeks]
    70.85
    12.60
    18.20
    11.85
    13.40
    13.00
    13.10
    12.10
    12.10
    12.35
    12.00
    12.10
    13.10
    6. Secondary Outcome
    TitleKaplan-Meier Estimate of Duration of Response
    DescriptionDuration of response is defined for responders only as the time from the first documented response (CR or PR for lymphoma participants or CR, CRi, nPR, PR, or PRL for CLL participants) to disease progression or death (from any cause). For participants with response but no progression, or death, duration of response was censored at the last date that the participant was known to be progression-free.
    Time FrameFrom first dose of any study drug to the end of follow-up, up to the data cutoff date of March 6, 2019; median (minimum, maximum) time on study was 16.7 (0.9, 32.9) months.

    Outcome Measure Data

    Analysis Population Description
    Efficacy evaluable population (all participants who completed at least 1 cycle of their assigned treatment, and have baseline and at least 1 post-baseline tumor response assessment) who had an objective response
    Arm/Group TitlePart 1, Arm A: DUR 1500 mg + LEN 20 mgPart 1, Arm A: DUR 1500 mg + LEN 20 mg + RIT 375 mg/m²Part 1, Arm A: DUR 1500 mg + LEN 10 mg + RIT 375 mg/m²Part 1, Arm B: DUR 1500 mg + IBR 420 mgPart 1, Arm B: DUR 1500 mg + IBR 560 mgPart 1, Arm C: DUR 1500 mg + RIT 375 mg/m²Part 1, Arm C: DUR 1500 mg + BEN 70 mg/m²Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m²Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 90 mg/m²Part 2, Arm B CLL/SLL: DUR 1500 mg + IBR 420 mgPart 2, Arm B MCL: DUR 1500 mg + IBR 560 mgPart 2, Arm C FL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m²Part 2 Arm C DLBCL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m²Part 2, Arm C CLL/SLL: DUR + RIT 375 mg/m² + BEN 70 mg/m²Part 2, Arm D FL: DUR 1500 mgPart 2, Arm D DLBCL: DUR 1500 mgPart 2, Arm D CLL/SLL: DUR 1500 mgPart 2, Arm D MCL: DUR 1500 mgPart 2 Arm D HL: DUR 1500 mg
    Arm/Group DescriptionParticipants received durvalumab (DUR) 1500 mg intravenous (IV) infusion on Day 1 of Cycles 1 through 13 (ie, 12 months) and lenalidomide (LEN) 20 mg orally once daily on Days 1 to 21 of Cycles 1 through 13 for participants with indolent non-Hodgkin's lymphoma (NHL) or for all cycles of treatment period until disease progression, unacceptable toxicity, or discontinuation for any other reason in participants with aggressive NHL.Participants received durvalumab (DUR) 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and lenalidomide (LEN) 20 mg orally once daily on Days 1 to 21 of Cycles 1 through 13 for participants with indolent NHL or until disease progression, unacceptable toxicity, or discontinuation for any other reason in participants with aggressive NHL, and rituximab 375 mg/m² IV infusion on Days 2, 8, 15, 22 of Cycle 1 and on Day 1 of every 28-day cycle from Cycles 2 through 5.Participants received durvalumab (DUR) 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and lenalidomide (LEN) 10 mg orally once daily on Days 1 to 21 of Cycles 1 through 13 for participants with indolent NHL or until disease progression, unacceptable toxicity, or discontinuation for any other reason in participants with aggressive NHL, and rituximab 375 mg/m² IV infusion on Days 2, 8, 15, 22 of Cycle 1 and on Day 1 of every 28-day cycle from Cycles 2 through 5.Participants received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and ibrutinib 420 mg orally once daily until disease progression, unacceptable toxicity or discontinuation for any other reason.Participants received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and ibrutinib 560 mg orally once daily until disease progression, unacceptable toxicity or discontinuation for any other reason.Participants received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13, and rituximab 375 mg/m² IV infusion on Day 2 of Cycles 1 through 6 (for participants with CLL the rituximab dose was 375 mg/m² Cycle 1 first dose and 500 mg/m² for each subsequent dose).Participants received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and bendamustine 70 mg/m² IV infusion on Days 1 and 2 of Cycles 1 through 6.Participants received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13, bendamustine 70 mg/m² IV infusion on Days 1 and 2 of Cycles 1 through 6, and rituximab 375 mg/m² IV infusion on Day 2 of Cycles 1 through 6 (for CLL the rituximab dose was 375 mg/m² Cycle 1 first dose and 500 mg/m² for each subsequent dose).Participants received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13, bendamustine 90 mg/m² IV infusion on Days 1 and 2 of Cycles 1 through 6, and rituximab 375 mg/m² IV infusion on Day 2 of Cycles 1 through 6 (for CLL the rituximab dose was 375 mg/m² Cycle 1 first dose and 500 mg/m² for each subsequent dose).Participants with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and ibrutinib 420 mg orally once daily until disease progression, unacceptable toxicity or discontinuation for any other reason.Participants with mantle cell lymphoma (MCL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and ibrutinib 560 mg orally once daily until disease progression, unacceptable toxicity or discontinuation for any other reason.Participants with follicular lymphoma (FL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13, bendamustine 70 mg/m² IV infusion on Days 1 and 2 of Cycles 1 through 6, and rituximab 375 mg/m² IV infusion on Day 2 of Cycles 1 through 6.Participants with diffuse large B-cell lymphoma (DLBCL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13, bendamustine 70 mg/m² IV infusion on Days 1 and 2 of Cycles 1 through 6, and rituximab 375 mg/m² IV infusion on Day 2 of Cycles 1 through 6.Participants with CLL or SLL received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13, bendamustine 70 mg/m² IV infusion on Days 1 and 2 of Cycles 1 through 6, and rituximab 375 mg/m² IV infusion on Day 2 of Cycles 1 through 6 (for CLL the rituximab dose was 375 mg/m² Cycle 1 first dose and 500 mg/m² for each subsequent dose).Participants with follicular lymphoma received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13.Participants with diffuse large B-cell lymphoma (DLBCL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13.Participants with CLL or SLL received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13.Participants with mantle cell lymphoma (MCL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13.Participants with Hodgkin lymphoma (HL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13.
    Measure Participants2242310209783200001
    Median (95% Confidence Interval) [weeks]
    10.14
    NA
    NA
    NA
    NA
    29.29
    NA
    NA
    NA
    NA
    24.14
    NA
    11.14
    7. Secondary Outcome
    TitleKaplan-Meier Estimate of Progression-free Survival (PFS)
    DescriptionProgression-free survival was calculated as the time from first dose of study drug to the first documented progression or death (from any cause) during the entire efficacy evaluation period. For participants with no progression or death, PFS was censored at the last assessment date the participant was known to be progression-free.
    Time FrameFrom first dose of any study drug to the end of follow-up, up to the data cutoff date of March 6, 2019; median (minimum, maximum) time on study was 16.7 (0.9, 32.9) months.

    Outcome Measure Data

    Analysis Population Description
    Safety population
    Arm/Group TitlePart 1, Arm A: DUR 1500 mg + LEN 20 mgPart 1, Arm A: DUR 1500 mg + LEN 20 mg + RIT 375 mg/m²Part 1, Arm A: DUR 1500 mg + LEN 10 mg + RIT 375 mg/m²Part 1, Arm B: DUR 1500 mg + IBR 420 mgPart 1, Arm B: DUR 1500 mg + IBR 560 mgPart 1, Arm C: DUR 1500 mg + RIT 375 mg/m²Part 1, Arm C: DUR 1500 mg + BEN 70 mg/m²Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m²Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 90 mg/m²Part 2, Arm B CLL/SLL: DUR 1500 mg + IBR 420 mgPart 2, Arm B MCL: DUR 1500 mg + IBR 560 mgPart 2, Arm C FL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m²Part 2 Arm C DLBCL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m²Part 2, Arm C CLL/SLL: DUR + RIT 375 mg/m² + BEN 70 mg/m²Part 2, Arm D FL: DUR 1500 mgPart 2, Arm D DLBCL: DUR 1500 mgPart 2, Arm D CLL/SLL: DUR 1500 mgPart 2, Arm D MCL: DUR 1500 mgPart 2 Arm D HL: DUR 1500 mg
    Arm/Group DescriptionParticipants received durvalumab (DUR) 1500 mg intravenous (IV) infusion on Day 1 of Cycles 1 through 13 (ie, 12 months) and lenalidomide (LEN) 20 mg orally once daily on Days 1 to 21 of Cycles 1 through 13 for participants with indolent non-Hodgkin's lymphoma (NHL) or for all cycles of treatment period until disease progression, unacceptable toxicity, or discontinuation for any other reason in participants with aggressive NHL.Participants received durvalumab (DUR) 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and lenalidomide (LEN) 20 mg orally once daily on Days 1 to 21 of Cycles 1 through 13 for participants with indolent NHL or until disease progression, unacceptable toxicity, or discontinuation for any other reason in participants with aggressive NHL, and rituximab 375 mg/m² IV infusion on Days 2, 8, 15, 22 of Cycle 1 and on Day 1 of every 28-day cycle from Cycles 2 through 5.Participants received durvalumab (DUR) 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and lenalidomide (LEN) 10 mg orally once daily on Days 1 to 21 of Cycles 1 through 13 for participants with indolent NHL or until disease progression, unacceptable toxicity, or discontinuation for any other reason in participants with aggressive NHL, and rituximab 375 mg/m² IV infusion on Days 2, 8, 15, 22 of Cycle 1 and on Day 1 of every 28-day cycle from Cycles 2 through 5.Participants received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and ibrutinib 420 mg orally once daily until disease progression, unacceptable toxicity or discontinuation for any other reason.Participants received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and ibrutinib 560 mg orally once daily until disease progression, unacceptable toxicity or discontinuation for any other reason.Participants received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13, and rituximab 375 mg/m² IV infusion on Day 2 of Cycles 1 through 6 (for participants with CLL the rituximab dose was 375 mg/m² Cycle 1 first dose and 500 mg/m² for each subsequent dose).Participants received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and bendamustine 70 mg/m² IV infusion on Days 1 and 2 of Cycles 1 through 6.Participants received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13, bendamustine 70 mg/m² IV infusion on Days 1 and 2 of Cycles 1 through 6, and rituximab 375 mg/m² IV infusion on Day 2 of Cycles 1 through 6 (for CLL the rituximab dose was 375 mg/m² Cycle 1 first dose and 500 mg/m² for each subsequent dose).Participants received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13, bendamustine 90 mg/m² IV infusion on Days 1 and 2 of Cycles 1 through 6, and rituximab 375 mg/m² IV infusion on Day 2 of Cycles 1 through 6 (for CLL the rituximab dose was 375 mg/m² Cycle 1 first dose and 500 mg/m² for each subsequent dose).Participants with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and ibrutinib 420 mg orally once daily until disease progression, unacceptable toxicity or discontinuation for any other reason.Participants with mantle cell lymphoma (MCL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and ibrutinib 560 mg orally once daily until disease progression, unacceptable toxicity or discontinuation for any other reason.Participants with follicular lymphoma (FL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13, bendamustine 70 mg/m² IV infusion on Days 1 and 2 of Cycles 1 through 6, and rituximab 375 mg/m² IV infusion on Day 2 of Cycles 1 through 6.Participants with diffuse large B-cell lymphoma (DLBCL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13, bendamustine 70 mg/m² IV infusion on Days 1 and 2 of Cycles 1 through 6, and rituximab 375 mg/m² IV infusion on Day 2 of Cycles 1 through 6.Participants with CLL or SLL received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13, bendamustine 70 mg/m² IV infusion on Days 1 and 2 of Cycles 1 through 6, and rituximab 375 mg/m² IV infusion on Day 2 of Cycles 1 through 6 (for CLL the rituximab dose was 375 mg/m² Cycle 1 first dose and 500 mg/m² for each subsequent dose).Participants with follicular lymphoma received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13.Participants with diffuse large B-cell lymphoma (DLBCL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13.Participants with CLL or SLL received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13.Participants with mantle cell lymphoma (MCL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13.Participants with Hodgkin lymphoma (HL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13.
    Measure Participants338343145101010105510255
    Median (95% Confidence Interval) [months]
    8.41
    NA
    NA
    NA
    28.71
    9.69
    1.25
    3.82
    2.48
    NA
    NA
    14.65
    2.06
    NA
    1.68
    1.17
    2.76
    2.33
    2.66
    8. Secondary Outcome
    TitleMaximum Observed Plasma Concentration (Cmax) of Durvalumab
    Description
    Time FrameCycle 1, Day 1 (pre-dose and at end of infusion), and 4, 24, 48, 168 (Day 8), 336 (Day 15), and 508 (Day 22) hours after the end of infusion.

    Outcome Measure Data

    Analysis Population Description
    The Pharmacokinetic (PK) population included all participants who received at least 1 dose of study drug and had at least 1 measurable plasma concentration.
    Arm/Group TitleArm A: Durvalumab + Lenalidomide ± RituximabArm B: Durvalumab + IbrutinibArm C: Durvalumab + Bendamustine ± RituximabArm D: Durvalumab Monotherapy
    Arm/Group DescriptionParticipants assigned to Arm A received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 to 13, and 10 mg or 20 mg lenalidomide orally once daily on Days 1 to 21 of Cycles 1 to 13 in indolent NHL or until disease progression, unacceptable toxicity, or discontinuation for any other reason in aggressive NHL, and rituximab 375 mg/m² IV weekly in Cycle 1 and on Day 1 of Cycles 2 to 5.Participants assigned to Arm B received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 to 13, and 420 or 560 mg ibrutinib orally once daily until disease progression, unacceptable toxicity or discontinuation for any other reason.Participants assigned to Arm C received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 to 13, 70 or 90 mg/m² bendamustine IV on Days 1 and 2 of Cycles 1 to 6, and rituximab 375 mg/m² IV on Day 2 of Cycles 1 to 6 (for CLL the rituximab dose was 375 mg/m² Cycle 1 first dose and 500 mg/m² for each subsequent dose).Participants assigned to Arm D received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 to 13.
    Measure Participants14273826
    Geometric Mean (Geometric Coefficient of Variation) [μg/L]
    420264.066
    (22.7)
    361906.229
    (30.1)
    331572.478
    (33.4)
    392663.668
    (41.1)
    9. Secondary Outcome
    TitleTime to Maximum Plasma Concentration (Tmax) of Durvalumab
    Description
    Time FrameCycle 1, Day 1 (pre-dose and at end of infusion), and 4, 24, 48, 168 (Day 8), 336 (Day 15), and 508 (Day 22) hours after the end of infusion.

    Outcome Measure Data

    Analysis Population Description
    PK population
    Arm/Group TitleArm A: Durvalumab + Lenalidomide ± RituximabArm B: Durvalumab + IbrutinibArm C: Durvalumab + Bendamustine ± RituximabArm D: Durvalumab Monotherapy
    Arm/Group DescriptionParticipants assigned to Arm A received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 to 13, and 10 mg or 20 mg lenalidomide orally once daily on Days 1 to 21 of Cycles 1 to 13 in indolent NHL or until disease progression, unacceptable toxicity, or discontinuation for any other reason in aggressive NHL, and rituximab 375 mg/m² IV weekly in Cycle 1 and on Day 1 of Cycles 2 to 5.Participants assigned to Arm B received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 to 13, and 420 or 560 mg ibrutinib orally once daily until disease progression, unacceptable toxicity or discontinuation for any other reason.Participants assigned to Arm C received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 to 13, 70 or 90 mg/m² bendamustine IV on Days 1 and 2 of Cycles 1 to 6, and rituximab 375 mg/m² IV on Day 2 of Cycles 1 to 6 (for CLL the rituximab dose was 375 mg/m² Cycle 1 first dose and 500 mg/m² for each subsequent dose).Participants assigned to Arm D received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 to 13.
    Measure Participants14273826
    Median (Full Range) [days]
    0.0510
    0.0479
    0.0510
    0.0420
    10. Secondary Outcome
    TitleArea Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUClast) of Durvalumab
    Description
    Time FrameCycle 1, Day 1 (pre-dose and at end of infusion), and 4, 24, 48, 168 (Day 8), 336 (Day 15), and 508 (Day 22) hours after the end of infusion.

    Outcome Measure Data

    Analysis Population Description
    The PK population
    Arm/Group TitleArm A: Durvalumab + Lenalidomide ± RituximabArm B: Durvalumab + IbrutinibArm C: Durvalumab + Bendamustine ± RituximabArm D: Durvalumab Monotherapy
    Arm/Group DescriptionParticipants assigned to Arm A received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 to 13, and 10 mg or 20 mg lenalidomide orally once daily on Days 1 to 21 of Cycles 1 to 13 in indolent NHL or until disease progression, unacceptable toxicity, or discontinuation for any other reason in aggressive NHL, and rituximab 375 mg/m² IV weekly in Cycle 1 and on Day 1 of Cycles 2 to 5.Participants assigned to Arm B received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 to 13, and 420 or 560 mg ibrutinib orally once daily until disease progression, unacceptable toxicity or discontinuation for any other reason.Participants assigned to Arm C received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 to 13, 70 or 90 mg/m² bendamustine IV on Days 1 and 2 of Cycles 1 to 6, and rituximab 375 mg/m² IV on Day 2 of Cycles 1 to 6 (for CLL the rituximab dose was 375 mg/m² Cycle 1 first dose and 500 mg/m² for each subsequent dose).Participants assigned to Arm D received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 to 13.
    Measure Participants14273826
    Geometric Mean (Geometric Coefficient of Variation) [days*μg/L]
    3120149.759
    (29.5)
    3225869.344
    (31.9)
    2670168.397
    (46.7)
    3053060.746
    (37.8)
    11. Secondary Outcome
    TitleArea Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUCinf) of Durvalumab
    Description
    Time FrameCycle 1, Day 1 (pre-dose and at end of infusion), and 4, 24, 48, 168 (Day 8), 336 (Day 15), and 508 (Day 22) hours after the end of infusion.

    Outcome Measure Data

    Analysis Population Description
    The PK population
    Arm/Group TitleArm A: Durvalumab + Lenalidomide ± RituximabArm B: Durvalumab + IbrutinibArm C: Durvalumab + Bendamustine ± RituximabArm D: Durvalumab Monotherapy
    Arm/Group DescriptionParticipants assigned to Arm A received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 to 13, and 10 mg or 20 mg lenalidomide orally once daily on Days 1 to 21 of Cycles 1 to 13 in indolent NHL or until disease progression, unacceptable toxicity, or discontinuation for any other reason in aggressive NHL, and rituximab 375 mg/m² IV weekly in Cycle 1 and on Day 1 of Cycles 2 to 5.Participants assigned to Arm B received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 to 13, and 420 or 560 mg ibrutinib orally once daily until disease progression, unacceptable toxicity or discontinuation for any other reason.Participants assigned to Arm C received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 to 13, 70 or 90 mg/m² bendamustine IV on Days 1 and 2 of Cycles 1 to 6, and rituximab 375 mg/m² IV on Day 2 of Cycles 1 to 6 (for CLL the rituximab dose was 375 mg/m² Cycle 1 first dose and 500 mg/m² for each subsequent dose).Participants assigned to Arm D received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 to 13.
    Measure Participants14273825
    Geometric Mean (Geometric Coefficient of Variation) [days*μg/L]
    4867431.378
    (23.3)
    5818262.846
    (42.1)
    4762968.345
    (71.0)
    5593532.553
    (53.0)
    12. Secondary Outcome
    TitleTerminal Elimination Phase Half-Life (t½) of Durvalumab
    Description
    Time FrameCycle 1, Day 1 (pre-dose and at end of infusion), and 4, 24, 48, 168 (Day 8), 336 (Day 15), and 508 (Day 22) hours after the end of infusion.

    Outcome Measure Data

    Analysis Population Description
    The PK population
    Arm/Group TitleArm A: Durvalumab + Lenalidomide ± RituximabArm B: Durvalumab + IbrutinibArm C: Durvalumab + Bendamustine ± RituximabArm D: Durvalumab Monotherapy
    Arm/Group DescriptionParticipants assigned to Arm A received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 to 13, and 10 mg or 20 mg lenalidomide orally once daily on Days 1 to 21 of Cycles 1 to 13 in indolent NHL or until disease progression, unacceptable toxicity, or discontinuation for any other reason in aggressive NHL, and rituximab 375 mg/m² IV weekly in Cycle 1 and on Day 1 of Cycles 2 to 5.Participants assigned to Arm B received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 to 13, and 420 or 560 mg ibrutinib orally once daily until disease progression, unacceptable toxicity or discontinuation for any other reason.Participants assigned to Arm C received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 to 13, 70 or 90 mg/m² bendamustine IV on Days 1 and 2 of Cycles 1 to 6, and rituximab 375 mg/m² IV on Day 2 of Cycles 1 to 6 (for CLL the rituximab dose was 375 mg/m² Cycle 1 first dose and 500 mg/m² for each subsequent dose).Participants assigned to Arm D received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 to 13.
    Measure Participants14273825
    Geometric Least Squares Mean (Geometric Coefficient of Variation) [days]
    11.596
    (46.6)
    17.344
    (47.3)
    16.327
    (57.4)
    15.399
    (53.5)
    13. Secondary Outcome
    TitleClearance (CL) of Durvalumab
    Description
    Time FrameCycle 1, Day 1 (pre-dose and at end of infusion), and 4, 24, 48, 168 (Day 8), 336 (Day 15), and 508 (Day 22) hours after the end of infusion.

    Outcome Measure Data

    Analysis Population Description
    The PK population
    Arm/Group TitleArm A: Durvalumab + Lenalidomide ± RituximabArm B: Durvalumab + IbrutinibArm C: Durvalumab + Bendamustine ± RituximabArm D: Durvalumab Monotherapy
    Arm/Group DescriptionParticipants assigned to Arm A received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 to 13, and 10 mg or 20 mg lenalidomide orally once daily on Days 1 to 21 of Cycles 1 to 13 in indolent NHL or until disease progression, unacceptable toxicity, or discontinuation for any other reason in aggressive NHL, and rituximab 375 mg/m² IV weekly in Cycle 1 and on Day 1 of Cycles 2 to 5.Participants assigned to Arm B received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 to 13, and 420 or 560 mg ibrutinib orally once daily until disease progression, unacceptable toxicity or discontinuation for any other reason.Participants assigned to Arm C received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 to 13, 70 or 90 mg/m² bendamustine IV on Days 1 and 2 of Cycles 1 to 6, and rituximab 375 mg/m² IV on Day 2 of Cycles 1 to 6 (for CLL the rituximab dose was 375 mg/m² Cycle 1 first dose and 500 mg/m² for each subsequent dose).Participants assigned to Arm D received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 to 13.
    Measure Participants14273825
    Geometric Least Squares Mean (Geometric Coefficient of Variation) [L/day]
    0.3082
    (23.3)
    0.2578
    (42.1)
    0.3149
    (71.0)
    0.2682
    (53.0)
    14. Secondary Outcome
    TitleVolume of Distribution (Vz) of Durvalumab
    Description
    Time FrameCycle 1, Day 1 (pre-dose and at end of infusion), and 4, 24, 48, 168 (Day 8), 336 (Day 15), and 508 (Day 22) hours after the end of infusion.

    Outcome Measure Data

    Analysis Population Description
    The PK population
    Arm/Group TitleArm A: Durvalumab + Lenalidomide ± RituximabArm B: Durvalumab + IbrutinibArm C: Durvalumab + Bendamustine ± RituximabArm D: Durvalumab Monotherapy
    Arm/Group DescriptionParticipants assigned to Arm A received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 to 13, and 10 mg or 20 mg lenalidomide orally once daily on Days 1 to 21 of Cycles 1 to 13 in indolent NHL or until disease progression, unacceptable toxicity, or discontinuation for any other reason in aggressive NHL, and rituximab 375 mg/m² IV weekly in Cycle 1 and on Day 1 of Cycles 2 to 5.Participants assigned to Arm B received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 to 13, and 420 or 560 mg ibrutinib orally once daily until disease progression, unacceptable toxicity or discontinuation for any other reason.Participants assigned to Arm C received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 to 13, 70 or 90 mg/m² bendamustine IV on Days 1 and 2 of Cycles 1 to 6, and rituximab 375 mg/m² IV on Day 2 of Cycles 1 to 6 (for CLL the rituximab dose was 375 mg/m² Cycle 1 first dose and 500 mg/m² for each subsequent dose).Participants assigned to Arm D received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 to 13.
    Measure Participants14273825
    Geometric Least Squares Mean (Geometric Coefficient of Variation) [liters]
    5.155
    (41.9)
    6.451
    (38.3)
    7.418
    (33.7)
    5.957
    (33.0)
    15. Secondary Outcome
    TitleMaximum Observed Plasma Concentration (Cmax) of Lenalidomide
    Description
    Time FrameCycle 1 Day 1 at predose and 1, 2, 4, and 24 hours post-dose, and Cycle 1 Day 15 at pre-dose, 1, 2, and 4 hours post-dose.

    Outcome Measure Data

    Analysis Population Description
    PK population with available data at each time point
    Arm/Group TitleArm A: Lenalidomide 10 mgArm A: Lenalidomide 20 mg
    Arm/Group DescriptionParticipants in Arm A received lenalidomide 10 mg orally once daily on Days 1 to 21 of Cycles 1 to 13 for participants with indolent NHL or until disease progression, unacceptable toxicity, or discontinuation for any other reason in participants with aggressive NHL, and durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 to 13, and rituximab 375 mg/m² IV weekly in Cycle 1 and on Day 1 of Cycles 2 to 5.Participants in Arm A received lenalidomide 20 mg orally once daily on Days 1 to 21 of Cycles 1 to 13 for participants with indolent NHL or until disease progression, unacceptable toxicity, or discontinuation for any other reason in participants with aggressive NHL, and durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 to 13, and rituximab 375 mg/m² IV weekly in Cycle 1 and on Day 1 of Cycles 2 to 5.
    Measure Participants54
    Cycle 1 Day 1
    141.881
    (22.0)
    309.917
    (6.9)
    Cycle 1 Day 15
    107.635
    (40.9)
    174.090
    16. Secondary Outcome
    TitleTime to Maximum Observed Plasma Concentration (Tmax) of Lenalidomide
    Description
    Time FrameCycle 1 Day 1 at predose and 1, 2, 4, and 24 hours post-dose, and Cycle 1 Day 15 at pre-dose, 1, 2, and 4 hours post-dose.

    Outcome Measure Data

    Analysis Population Description
    PK population with available data at each time point
    Arm/Group TitleArm A: Lenalidomide 10 mgArm A: Lenalidomide 20 mg
    Arm/Group DescriptionParticipants in Arm A received lenalidomide 10 mg orally once daily on Days 1 to 21 of Cycles 1 to 13 for participants with indolent NHL or until disease progression, unacceptable toxicity, or discontinuation for any other reason in participants with aggressive NHL, and durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 to 13, and rituximab 375 mg/m² IV weekly in Cycle 1 and on Day 1 of Cycles 2 to 5.Participants in Arm A received lenalidomide 20 mg orally once daily on Days 1 to 21 of Cycles 1 to 13 for participants with indolent NHL or until disease progression, unacceptable toxicity, or discontinuation for any other reason in participants with aggressive NHL, and durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 to 13, and rituximab 375 mg/m² IV weekly in Cycle 1 and on Day 1 of Cycles 2 to 5.
    Measure Participants54
    Cycle 1 Day 1
    1.9500
    1.1667
    Cycle 1 Day 15
    3.0333
    1.000
    17. Secondary Outcome
    TitleArea Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUClast) of Lenalidomide
    Description
    Time FrameCycle 1 Day 1 at predose and 1, 2, 4, and 24 hours post-dose

    Outcome Measure Data

    Analysis Population Description
    PK population with available data
    Arm/Group TitleArm A: Lenalidomide 10 mgArm A: Lenalidomide 20 mg
    Arm/Group DescriptionParticipants in Arm A received lenalidomide 10 mg orally once daily on Days 1 to 21 of Cycles 1 to 13 for participants with indolent NHL or until disease progression, unacceptable toxicity, or discontinuation for any other reason in participants with aggressive NHL, and durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 to 13, and rituximab 375 mg/m² IV weekly in Cycle 1 and on Day 1 of Cycles 2 to 5.Participants in Arm A received lenalidomide 20 mg orally once daily on Days 1 to 21 of Cycles 1 to 13 for participants with indolent NHL or until disease progression, unacceptable toxicity, or discontinuation for any other reason in participants with aggressive NHL, and durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 to 13, and rituximab 375 mg/m² IV weekly in Cycle 1 and on Day 1 of Cycles 2 to 5.
    Measure Participants54
    Geometric Least Squares Mean (Geometric Coefficient of Variation) [h*ng/mL]
    789.297
    (84.3)
    805.299
    (56.0)
    18. Secondary Outcome
    TitleMaximum Observed Plasma Concentration (Cmax) of Ibrutinib
    Description
    Time FrameCycle 1 Day 1 at predose and 1, 2, 4, and 24 hours post-dose, and Cycle 1 Day 15 at pre-dose, 1, 2, and 4 hours post-dose.

    Outcome Measure Data

    Analysis Population Description
    PK population with available data at each time point
    Arm/Group TitleArm B: Ibrutinib 420 mgArm B: Ibrutinib 560 mg
    Arm/Group DescriptionParticipants assigned to Arm B received 420 mg ibrutinib orally once daily until disease progression, unacceptable toxicity or discontinuation for any other reason, and durvalumab 1500 mg IV on Day 1 of Cycles 1 to 13.Participants assigned to Arm B received 560 mg ibrutinib orally once daily until disease progression, unacceptable toxicity or discontinuation for any other reason, and durvalumab 1500 mg IV on Day 1 of Cycles 1 to 13.
    Measure Participants1313
    Cycle 1 Day 1
    129.704
    (98.0)
    67.728
    (197.9)
    Cycle 1 Day 15
    86.840
    (136.9)
    72.436
    (166.3)
    19. Secondary Outcome
    TitleTime to Maximum Observed Plasma Concentration (Tmax) of Ibrutinib
    Description
    Time FrameCycle 1 Day 1 at predose and 1, 2, 4, and 24 hours post-dose, and Cycle 1 Day 15 at pre-dose, 1, 2, and 4 hours post-dose.

    Outcome Measure Data

    Analysis Population Description
    PK population with available data at each time point
    Arm/Group TitleArm B: Ibrutinib 420 mgArm B: Ibrutinib 560 mg
    Arm/Group DescriptionParticipants assigned to Arm B received 420 mg ibrutinib orally once daily until disease progression, unacceptable toxicity or discontinuation for any other reason, and durvalumab 1500 mg IV on Day 1 of Cycles 1 to 13.Participants assigned to Arm B received 560 mg ibrutinib orally once daily until disease progression, unacceptable toxicity or discontinuation for any other reason, and durvalumab 1500 mg IV on Day 1 of Cycles 1 to 13.
    Measure Participants1313
    Cycle 1 Day 1
    2.000
    1.9333
    Cycle 1 Day 15
    1.8833
    2.000
    20. Secondary Outcome
    TitleArea Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUClast) of Ibrutinib
    Description
    Time FrameCycle 1 Day 1 at predose and 1, 2, 4, and 24 hours post-dose

    Outcome Measure Data

    Analysis Population Description
    PK population with available data
    Arm/Group TitleArm B: Ibrutinib 420 mgArm B: Ibrutinib 560 mg
    Arm/Group DescriptionParticipants assigned to Arm B received 420 mg ibrutinib orally once daily until disease progression, unacceptable toxicity or discontinuation for any other reason, and durvalumab 1500 mg IV on Day 1 of Cycles 1 to 13.Participants assigned to Arm B received 560 mg ibrutinib orally once daily until disease progression, unacceptable toxicity or discontinuation for any other reason, and durvalumab 1500 mg IV on Day 1 of Cycles 1 to 13.
    Measure Participants1313
    Geometric Least Squares Mean (Geometric Coefficient of Variation) [h*ng/mL]
    586.396
    (117.2)
    436.855
    (246.5)
    21. Secondary Outcome
    TitleChange From Baseline in Soluble Programmed Cell Death Ligand-1 (sPD-L1) Concentration
    DescriptionChange from baseline in sPD-L1 could not be calculated as all post-baseline samples were below the lower limit of quantification (<15.60 pg/mL).
    Time FrameBaseline (Cycle 1 Day 1 predose) and Day 1 of Cycles 2 to 13

    Outcome Measure Data

    Analysis Population Description
    Biomarker Evaluable Population included all participants who received at least 1 dose of study drug and had at least 1 non-missing biomarker assessment. No participants had quantifiable sPD-L1 measurements post-baseline.
    Arm/Group TitlePart 1, Arm A: DUR 1500 mg + LEN 20 mgPart 1, Arm A: DUR 1500 mg + LEN 20 mg + RIT 375 mg/m²Part 1, Arm A: DUR 1500 mg + LEN 10 mg + RIT 375 mg/m²Part 1, Arm B: DUR 1500 mg + IBR 420 mgPart 1, Arm B: DUR 1500 mg + IBR 560 mgPart 1, Arm C: DUR 1500 mg + RIT 375 mg/m²Part 1, Arm C: DUR 1500 mg + BEN 70 mg/m²Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m²Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 90 mg/m²Part 2, Arm B CLL/SLL: DUR 1500 mg + IBR 420 mgPart 2, Arm B MCL: DUR 1500 mg + IBR 560 mgPart 2, Arm C FL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m²Part 2 Arm C DLBCL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m²Part 2, Arm C CLL/SLL: DUR + RIT 375 mg/m² + BEN 70 mg/m²Part 2, Arm D FL: DUR 1500 mgPart 2, Arm D DLBCL: DUR 1500 mgPart 2, Arm D CLL/SLL: DUR 1500 mgPart 2, Arm D MCL: DUR 1500 mgPart 2 Arm D HL: DUR 1500 mg
    Arm/Group DescriptionParticipants received durvalumab (DUR) 1500 mg intravenous (IV) infusion on Day 1 of Cycles 1 through 13 (ie, 12 months) and lenalidomide (LEN) 20 mg orally once daily on Days 1 to 21 of Cycles 1 through 13 for participants with indolent non-Hodgkin's lymphoma (NHL) or for all cycles of treatment period until disease progression, unacceptable toxicity, or discontinuation for any other reason in participants with aggressive NHL.Participants received durvalumab (DUR) 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and lenalidomide (LEN) 20 mg orally once daily on Days 1 to 21 of Cycles 1 through 13 for participants with indolent NHL or until disease progression, unacceptable toxicity, or discontinuation for any other reason in participants with aggressive NHL, and rituximab 375 mg/m² IV infusion on Days 2, 8, 15, 22 of Cycle 1 and on Day 1 of every 28-day cycle from Cycles 2 through 5.Participants received durvalumab (DUR) 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and lenalidomide (LEN) 10 mg orally once daily on Days 1 to 21 of Cycles 1 through 13 for participants with indolent NHL or until disease progression, unacceptable toxicity, or discontinuation for any other reason in participants with aggressive NHL, and rituximab 375 mg/m² IV infusion on Days 2, 8, 15, 22 of Cycle 1 and on Day 1 of every 28-day cycle from Cycles 2 through 5.Participants received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and ibrutinib 420 mg orally once daily until disease progression, unacceptable toxicity or discontinuation for any other reason.Participants received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and ibrutinib 560 mg orally once daily until disease progression, unacceptable toxicity or discontinuation for any other reason.Participants received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13, and rituximab 375 mg/m² IV infusion on Day 2 of Cycles 1 through 6 (for participants with CLL the rituximab dose was 375 mg/m² Cycle 1 first dose and 500 mg/m² for each subsequent dose).Participants received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and bendamustine 70 mg/m² IV infusion on Days 1 and 2 of Cycles 1 through 6.Participants received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13, bendamustine 70 mg/m² IV infusion on Days 1 and 2 of Cycles 1 through 6, and rituximab 375 mg/m² IV infusion on Day 2 of Cycles 1 through 6 (for CLL the rituximab dose was 375 mg/m² Cycle 1 first dose and 500 mg/m² for each subsequent dose).Participants received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13, bendamustine 90 mg/m² IV infusion on Days 1 and 2 of Cycles 1 through 6, and rituximab 375 mg/m² IV infusion on Day 2 of Cycles 1 through 6 (for CLL the rituximab dose was 375 mg/m² Cycle 1 first dose and 500 mg/m² for each subsequent dose).Participants with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and ibrutinib 420 mg orally once daily until disease progression, unacceptable toxicity or discontinuation for any other reason.Participants with mantle cell lymphoma (MCL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and ibrutinib 560 mg orally once daily until disease progression, unacceptable toxicity or discontinuation for any other reason.Participants with follicular lymphoma (FL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13, bendamustine 70 mg/m² IV infusion on Days 1 and 2 of Cycles 1 through 6, and rituximab 375 mg/m² IV infusion on Day 2 of Cycles 1 through 6.Participants with diffuse large B-cell lymphoma (DLBCL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13, bendamustine 70 mg/m² IV infusion on Days 1 and 2 of Cycles 1 through 6, and rituximab 375 mg/m² IV infusion on Day 2 of Cycles 1 through 6.Participants with CLL or SLL received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13, bendamustine 70 mg/m² IV infusion on Days 1 and 2 of Cycles 1 through 6, and rituximab 375 mg/m² IV infusion on Day 2 of Cycles 1 through 6 (for CLL the rituximab dose was 375 mg/m² Cycle 1 first dose and 500 mg/m² for each subsequent dose).Participants with follicular lymphoma received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13.Participants with diffuse large B-cell lymphoma (DLBCL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13.Participants with CLL or SLL received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13.Participants with mantle cell lymphoma (MCL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13.Participants with Hodgkin lymphoma (HL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13.
    Measure Participants0000000000000000000

    Adverse Events

    Time FrameFrom first dose of any study drug to 90 days after last dose of durvalumab or 28 days after last dose of other study drugs, up to the data cut-off date of 6 March 2019. Maximum time on treatment was 55.4 weeks for DUR and 130 weeks for other study drugs. All-cause mortality includes all deaths through the data cut-off date; median (minimum, maximum) time on study was 16.7 (0.9, 32.9) months.
    Adverse Event Reporting Description
    Arm/Group TitlePart 1, Arm A: DUR 1500 mg + LEN 20 mgPart 1, Arm A: DUR 1500 mg + LEN 20 mg + RIT 375 mg/m²Part 1, Arm A: DUR 1500 mg + LEN 10 mg + RIT 375 mg/m²Part 1, Arm B: DUR 1500 mg + IBR 420 mgPart 1, Arm B: DUR 1500 mg + IBR 560 mgPart 1, Arm C: DUR 1500 mg + RIT 375 mg/m²Part 1, Arm C: DUR 1500 mg + BEN 70 mg/m²Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m²Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 90 mg/m²Part 2, Arm B CLL/SLL: DUR 1500 mg + IBR 420 mgPart 2, Arm B MCL: DUR 1500 mg + IBR 560 mgPart 2, Arm C FL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m²Part 2 Arm C DLBCL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m²Part 2, Arm C CLL/SLL: DUR + RIT 375 mg/m² + BEN 70 mg/m²Part 2, Arm D FL: DUR 1500 mgPart 2, Arm D DLBCL: DUR 1500 mgPart 2, Arm D CLL/SLL: DUR 1500 mgPart 2, Arm D MCL: DUR 1500 mgPart 2, Arm D hL: DUR 1500 mg
    Arm/Group DescriptionParticipants received durvalumab (DUR) 1500 mg intravenous (IV) infusion on Day 1 of Cycles 1 through 13 (ie, 12 months) and lenalidomide (LEN) 20 mg orally once daily on Days 1 to 21 of Cycles 1 through 13 for participants with indolent non-Hodgkin's lymphoma (NHL) or for all cycles of treatment period until disease progression, unacceptable toxicity, or discontinuation for any other reason in participants with aggressive NHL.Participants received durvalumab (DUR) 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and lenalidomide (LEN) 20 mg orally once daily on Days 1 to 21 of Cycles 1 through 13 for participants with indolent NHL or until disease progression, unacceptable toxicity, or discontinuation for any other reason in participants with aggressive NHL, and rituximab 375 mg/m² IV infusion on Days 2, 8, 15, 22 of Cycle 1 and on Day 1 of every 28-day cycle from Cycles 2 through 5.Participants received durvalumab (DUR) 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and lenalidomide (LEN) 10 mg orally once daily on Days 1 to 21 of Cycles 1 through 13 for participants with indolent NHL or until disease progression, unacceptable toxicity, or discontinuation for any other reason in participants with aggressive NHL, and rituximab 375 mg/m² IV infusion on Days 2, 8, 15, 22 of Cycle 1 and on Day 1 of every 28-day cycle from Cycles 2 through 5.Participants received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and ibrutinib orally 420 mg once daily until disease progression, unacceptable toxicity or discontinuation for any other reasonParticipants received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and ibrutinib orally 560 mg once daily until disease progression, unacceptable toxicity or discontinuation for any other reason.Participants received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13, and rituximab 375 mg/m² IV infusion on Day 2 of Cycles 1 through 6 (for participants with CLL the rituximab dose was 375 mg/m² Cycle 1 first dose and 500 mg/m² for each subsequent dose).Participants received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and bendamustine 70 mg/m² IV infusion on Days 1 and 2 of Cycles 1 through 6.Participants received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13, bendamustine 70 mg/m² IV infusion on Days 1 and 2 of Cycles 1 through 6, and rituximab 375 mg/m² IV infusion on Day 2 of Cycles 1 through 6 (for CLL the rituximab dose was 375 mg/m² Cycle 1 first dose and 500 mg/m² for each subsequent dose).Participants received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13, bendamustine 90 mg/m² IV infusion on Days 1 and 2 of Cycles 1 through 6, and rituximab 375 mg/m² IV infusion on Day 2 of Cycles 1 through 6 (for CLL the rituximab dose was 375 mg/m² Cycle 1 first dose and 500 mg/m² for each subsequent dose).Participants with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and ibrutinib 420 mg orally once daily until disease progression, unacceptable toxicity or discontinuation for any other reason.Participants with mantle cell lymphoma (MCL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13 and ibrutinib 560 mg orally once daily until disease progression, unacceptable toxicity or discontinuation for any other reason.Participants with follicular lymphoma (FL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13, bendamustine 70 mg/m² IV infusion on Days 1 and 2 of Cycles 1 through 6, and rituximab 375 mg/m² IV infusion on Day 2 of Cycles 1 through 6.Participants with diffuse large B-cell lymphoma (DLBCL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13, bendamustine 70 mg/m² IV infusion on Days 1 and 2 of Cycles 1 through 6, and rituximab 375 mg/m² IV infusion on Day 2 of Cycles 1 through 6.Participants with CLL or SLL received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13, bendamustine 70 mg/m² IV infusion on Days 1 and 2 of Cycles 1 through 6, and rituximab 375 mg/m² IV infusion on Day 2 of Cycles 1 through 6 (for CLL the rituximab dose was 375 mg/m² Cycle 1 first dose and 500 mg/m² for each subsequent dose).Participants with follicular lymphoma received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13.Participants with diffuse large B-cell lymphoma (DLBCL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13.Participants with CLL or SLL received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13.Participants with mantle cell lymphoma (MCL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13.Participants with Hodgkin lymphoma (HL) received durvalumab 1500 mg IV infusion on Day 1 of Cycles 1 through 13.
    All Cause Mortality
    Part 1, Arm A: DUR 1500 mg + LEN 20 mgPart 1, Arm A: DUR 1500 mg + LEN 20 mg + RIT 375 mg/m²Part 1, Arm A: DUR 1500 mg + LEN 10 mg + RIT 375 mg/m²Part 1, Arm B: DUR 1500 mg + IBR 420 mgPart 1, Arm B: DUR 1500 mg + IBR 560 mgPart 1, Arm C: DUR 1500 mg + RIT 375 mg/m²Part 1, Arm C: DUR 1500 mg + BEN 70 mg/m²Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m²Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 90 mg/m²Part 2, Arm B CLL/SLL: DUR 1500 mg + IBR 420 mgPart 2, Arm B MCL: DUR 1500 mg + IBR 560 mgPart 2, Arm C FL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m²Part 2 Arm C DLBCL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m²Part 2, Arm C CLL/SLL: DUR + RIT 375 mg/m² + BEN 70 mg/m²Part 2, Arm D FL: DUR 1500 mgPart 2, Arm D DLBCL: DUR 1500 mgPart 2, Arm D CLL/SLL: DUR 1500 mgPart 2, Arm D MCL: DUR 1500 mgPart 2, Arm D hL: DUR 1500 mg
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total1/3 (33.3%) 1/3 (33.3%) 2/8 (25%) 0/3 (0%) 1/4 (25%) 2/3 (66.7%) 1/1 (100%) 3/4 (75%) 4/5 (80%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 9/10 (90%) 2/5 (40%) 4/5 (80%) 9/10 (90%) 0/2 (0%) 3/5 (60%) 3/5 (60%)
    Serious Adverse Events
    Part 1, Arm A: DUR 1500 mg + LEN 20 mgPart 1, Arm A: DUR 1500 mg + LEN 20 mg + RIT 375 mg/m²Part 1, Arm A: DUR 1500 mg + LEN 10 mg + RIT 375 mg/m²Part 1, Arm B: DUR 1500 mg + IBR 420 mgPart 1, Arm B: DUR 1500 mg + IBR 560 mgPart 1, Arm C: DUR 1500 mg + RIT 375 mg/m²Part 1, Arm C: DUR 1500 mg + BEN 70 mg/m²Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m²Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 90 mg/m²Part 2, Arm B CLL/SLL: DUR 1500 mg + IBR 420 mgPart 2, Arm B MCL: DUR 1500 mg + IBR 560 mgPart 2, Arm C FL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m²Part 2 Arm C DLBCL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m²Part 2, Arm C CLL/SLL: DUR + RIT 375 mg/m² + BEN 70 mg/m²Part 2, Arm D FL: DUR 1500 mgPart 2, Arm D DLBCL: DUR 1500 mgPart 2, Arm D CLL/SLL: DUR 1500 mgPart 2, Arm D MCL: DUR 1500 mgPart 2, Arm D hL: DUR 1500 mg
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total1/3 (33.3%) 2/3 (66.7%) 4/8 (50%) 2/3 (66.7%) 2/4 (50%) 2/3 (66.7%) 1/1 (100%) 1/4 (25%) 3/5 (60%) 6/10 (60%) 7/10 (70%) 5/10 (50%) 5/10 (50%) 2/5 (40%) 4/5 (80%) 8/10 (80%) 0/2 (0%) 4/5 (80%) 2/5 (40%)
    Blood and lymphatic system disorders
    Anaemia0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 1/4 (25%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 1/5 (20%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Cytopenia0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 1/5 (20%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Febrile neutropenia1/3 (33.3%) 0/3 (0%) 1/8 (12.5%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 1/10 (10%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Neutropenia0/3 (0%) 1/3 (33.3%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Pancytopenia0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 1/5 (20%) 0/5 (0%)
    Thrombocytopenia0/3 (0%) 1/3 (33.3%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 1/5 (20%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Cardiac disorders
    Acute coronary syndrome0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Atrial fibrillation0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 1/10 (10%) 1/10 (10%) 1/10 (10%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Cardiac failure0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 1/10 (10%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Myocardial infarction0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 1/5 (20%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Endocrine disorders
    Adrenal insufficiency0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 1/5 (20%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Gastrointestinal disorders
    Abdominal pain0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Abdominal wall haematoma0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 1/4 (25%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Aptyalism0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 1/5 (20%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Colon dysplasia0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 1/10 (10%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Diarrhoea0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 1/3 (33.3%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 1/5 (20%) 0/5 (0%)
    Gastric haemorrhage0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 1/5 (20%) 0/5 (0%)
    Gastrointestinal perforation0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 1/5 (20%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Haematemesis0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 1/5 (20%) 0/5 (0%)
    Rectal haemorrhage0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 1/3 (33.3%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Small intestinal haemorrhage0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 1/10 (10%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Small intestinal obstruction0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 1/5 (20%) 0/5 (0%)
    Vomiting0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 1/5 (20%) 0/5 (0%)
    General disorders
    Asthenia0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 1/5 (20%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    General physical health deterioration0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 1/5 (20%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 2/10 (20%) 0/2 (0%) 2/5 (40%) 1/5 (20%)
    Generalised oedema0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 1/3 (33.3%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 1/5 (20%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Malaise0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Multiple organ dysfunction syndrome0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 1/10 (10%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Pain0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Pyrexia0/3 (0%) 1/3 (33.3%) 1/8 (12.5%) 0/3 (0%) 0/4 (0%) 1/3 (33.3%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 1/10 (10%) 0/5 (0%) 1/5 (20%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 2/5 (40%)
    Hepatobiliary disorders
    Hepatitis0/3 (0%) 1/3 (33.3%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Hyperbilirubinaemia0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 1/10 (10%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Immune system disorders
    Cytokine release syndrome0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Infections and infestations
    Bronchiolitis0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 1/3 (33.3%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Bronchitis0/3 (0%) 0/3 (0%) 1/8 (12.5%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Bronchitis viral0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Cellulitis0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 1/5 (20%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Device related infection0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 1/5 (20%) 0/5 (0%)
    Influenza0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Lower respiratory tract infection0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 1/4 (25%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Lower respiratory tract infection viral0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 1/5 (20%) 0/5 (0%)
    Lung infection0/3 (0%) 1/3 (33.3%) 0/8 (0%) 1/3 (33.3%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Neutropenic sepsis0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 1/5 (20%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Parainfluenzae virus infection0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Pleural infection bacterial0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 1/5 (20%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Pneumonia0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 1/4 (25%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) 0/5 (0%) 0/5 (0%) 1/10 (10%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Sepsis0/3 (0%) 1/3 (33.3%) 1/8 (12.5%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 1/1 (100%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 1/5 (20%) 1/5 (20%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 1/5 (20%)
    Septic shock0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Sinusitis0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Skin infection0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 1/10 (10%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Streptococcal infection0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 1/5 (20%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Investigations
    Alanine aminotransferase increased0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 2/10 (20%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Electrocardiogram QT prolonged0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 1/5 (20%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    General physical condition abnormal0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 1/5 (20%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Metabolism and nutrition disorders
    Dehydration0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 1/5 (20%) 0/5 (0%)
    Hyponatraemia0/3 (0%) 0/3 (0%) 1/8 (12.5%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Musculoskeletal and connective tissue disorders
    Flank pain0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Basal cell carcinoma0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 2/10 (20%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Prostate cancer0/3 (0%) 0/3 (0%) 0/8 (0%) 1/3 (33.3%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Squamous cell carcinoma of lung0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Nervous system disorders
    Cerebral ischaemia0/3 (0%) 0/3 (0%) 1/8 (12.5%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Syncope0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Renal and urinary disorders
    Acute kidney injury0/3 (0%) 1/3 (33.3%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 1/1 (100%) 0/4 (0%) 0/5 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 1/4 (25%) 1/5 (20%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 1/10 (10%) 0/2 (0%) 1/5 (20%) 0/5 (0%)
    Organising pneumonia0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 1/10 (10%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Pleural effusion0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 1/5 (20%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Pneumonitis0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Pulmonary embolism0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Skin and subcutaneous tissue disorders
    Drug reaction with eosinophilia and systemic symptoms0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 1/5 (20%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Vascular disorders
    Hypotension0/3 (0%) 1/3 (33.3%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 1/5 (20%)
    Jugular vein thrombosis0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Superior vena cava syndrome0/3 (0%) 0/3 (0%) 1/8 (12.5%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Other (Not Including Serious) Adverse Events
    Part 1, Arm A: DUR 1500 mg + LEN 20 mgPart 1, Arm A: DUR 1500 mg + LEN 20 mg + RIT 375 mg/m²Part 1, Arm A: DUR 1500 mg + LEN 10 mg + RIT 375 mg/m²Part 1, Arm B: DUR 1500 mg + IBR 420 mgPart 1, Arm B: DUR 1500 mg + IBR 560 mgPart 1, Arm C: DUR 1500 mg + RIT 375 mg/m²Part 1, Arm C: DUR 1500 mg + BEN 70 mg/m²Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m²Part 1, Arm C: DUR 1500 mg + RIT 375 mg/m² + BEN 90 mg/m²Part 2, Arm B CLL/SLL: DUR 1500 mg + IBR 420 mgPart 2, Arm B MCL: DUR 1500 mg + IBR 560 mgPart 2, Arm C FL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m²Part 2 Arm C DLBCL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m²Part 2, Arm C CLL/SLL: DUR + RIT 375 mg/m² + BEN 70 mg/m²Part 2, Arm D FL: DUR 1500 mgPart 2, Arm D DLBCL: DUR 1500 mgPart 2, Arm D CLL/SLL: DUR 1500 mgPart 2, Arm D MCL: DUR 1500 mgPart 2, Arm D hL: DUR 1500 mg
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total3/3 (100%) 3/3 (100%) 8/8 (100%) 3/3 (100%) 4/4 (100%) 3/3 (100%) 1/1 (100%) 4/4 (100%) 5/5 (100%) 10/10 (100%) 10/10 (100%) 10/10 (100%) 9/10 (90%) 5/5 (100%) 5/5 (100%) 10/10 (100%) 2/2 (100%) 5/5 (100%) 5/5 (100%)
    Blood and lymphatic system disorders
    Anaemia2/3 (66.7%) 0/3 (0%) 3/8 (37.5%) 0/3 (0%) 2/4 (50%) 0/3 (0%) 0/1 (0%) 1/4 (25%) 3/5 (60%) 0/10 (0%) 3/10 (30%) 1/10 (10%) 5/10 (50%) 1/5 (20%) 1/5 (20%) 2/10 (20%) 2/2 (100%) 1/5 (20%) 2/5 (40%)
    Bone marrow failure0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Eosinophilia0/3 (0%) 0/3 (0%) 1/8 (12.5%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 1/10 (10%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Febrile neutropenia0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 1/4 (25%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Haemolytic anaemia0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 1/5 (20%) 0/5 (0%) 0/10 (0%) 1/2 (50%) 0/5 (0%) 0/5 (0%)
    Immune thrombocytopenic purpura0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Increased tendency to bruise0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Leukopenia0/3 (0%) 0/3 (0%) 3/8 (37.5%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 2/5 (40%) 1/10 (10%) 2/10 (20%) 1/10 (10%) 2/10 (20%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Lymphopenia0/3 (0%) 1/3 (33.3%) 2/8 (25%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 1/4 (25%) 2/5 (40%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Neutropenia1/3 (33.3%) 1/3 (33.3%) 4/8 (50%) 1/3 (33.3%) 1/4 (25%) 1/3 (33.3%) 0/1 (0%) 2/4 (50%) 1/5 (20%) 4/10 (40%) 3/10 (30%) 6/10 (60%) 3/10 (30%) 1/5 (20%) 0/5 (0%) 3/10 (30%) 2/2 (100%) 3/5 (60%) 1/5 (20%)
    Pancytopenia0/3 (0%) 0/3 (0%) 1/8 (12.5%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Thrombocytopenia0/3 (0%) 1/3 (33.3%) 2/8 (25%) 0/3 (0%) 2/4 (50%) 0/3 (0%) 0/1 (0%) 1/4 (25%) 2/5 (40%) 3/10 (30%) 3/10 (30%) 2/10 (20%) 6/10 (60%) 1/5 (20%) 1/5 (20%) 4/10 (40%) 2/2 (100%) 3/5 (60%) 1/5 (20%)
    Cardiac disorders
    Atrial fibrillation0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 1/4 (25%) 0/5 (0%) 1/10 (10%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Palpitations0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 2/4 (50%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 1/5 (20%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Pericardial disease1/3 (33.3%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Sinus bradycardia0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 1/4 (25%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Sinus tachycardia0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) 1/10 (10%) 0/5 (0%) 1/5 (20%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Supraventricular tachycardia0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 1/5 (20%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Tachycardia0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 1/5 (20%) 1/10 (10%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Congenital, familial and genetic disorders
    Epidermolysis0/3 (0%) 0/3 (0%) 1/8 (12.5%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Ear and labyrinth disorders
    Ear discomfort0/3 (0%) 1/3 (33.3%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Ear pain0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 1/5 (20%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Hypoacusis0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 1/5 (20%)
    Tinnitus0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 1/5 (20%)
    Vertigo0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 1/4 (25%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 1/10 (10%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 1/10 (10%) 0/2 (0%) 1/5 (20%) 0/5 (0%)
    Endocrine disorders
    Hyperthyroidism0/3 (0%) 0/3 (0%) 1/8 (12.5%) 0/3 (0%) 1/4 (25%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 1/5 (20%) 0/5 (0%)
    Hypothyroidism0/3 (0%) 0/3 (0%) 2/8 (25%) 0/3 (0%) 1/4 (25%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Thyroiditis0/3 (0%) 1/3 (33.3%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Eye disorders
    Angle closure glaucoma0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 1/4 (25%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Blepharitis0/3 (0%) 1/3 (33.3%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Cataract0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 1/4 (25%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 1/10 (10%) 0/5 (0%) 0/5 (0%) 1/10 (10%) 1/2 (50%) 0/5 (0%) 0/5 (0%)
    Conjunctival haemorrhage0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 1/5 (20%) 0/5 (0%) 0/10 (0%) 1/2 (50%) 1/5 (20%) 0/5 (0%)
    Conjunctival oedema0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 1/3 (33.3%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Conjunctivitis allergic0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 1/3 (33.3%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Dry eye0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 1/4 (25%) 0/3 (0%) 0/1 (0%) 1/4 (25%) 0/5 (0%) 1/10 (10%) 1/10 (10%) 0/10 (0%) 1/10 (10%) 1/5 (20%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Eyelid disorder0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Eyelid ptosis0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 1/4 (25%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Iritis0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Periorbital oedema0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 1/10 (10%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Retinopathy hypertensive0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 1/2 (50%) 0/5 (0%) 0/5 (0%)
    Vision blurred0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 1/5 (20%) 0/5 (0%) 1/10 (10%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Visual impairment0/3 (0%) 0/3 (0%) 0/8 (0%) 1/3 (33.3%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Vitreous detachment0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Vitreous floaters0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 1/10 (10%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Vitreous haemorrhage0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Gastrointestinal disorders
    Abdominal discomfort0/3 (0%) 0/3 (0%) 0/8 (0%) 1/3 (33.3%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Abdominal distension0/3 (0%) 0/3 (0%) 1/8 (12.5%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Abdominal pain0/3 (0%) 1/3 (33.3%) 1/8 (12.5%) 0/3 (0%) 2/4 (50%) 1/3 (33.3%) 0/1 (0%) 1/4 (25%) 2/5 (40%) 1/10 (10%) 1/10 (10%) 0/10 (0%) 1/10 (10%) 2/5 (40%) 1/5 (20%) 1/10 (10%) 0/2 (0%) 1/5 (20%) 1/5 (20%)
    Abdominal pain upper0/3 (0%) 1/3 (33.3%) 1/8 (12.5%) 0/3 (0%) 2/4 (50%) 0/3 (0%) 0/1 (0%) 1/4 (25%) 0/5 (0%) 2/10 (20%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 1/5 (20%) 1/10 (10%) 0/2 (0%) 1/5 (20%) 0/5 (0%)
    Abdominal wall haematoma0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 1/4 (25%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Anal fissure0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 1/2 (50%) 0/5 (0%) 0/5 (0%)
    Ascites0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 1/5 (20%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Constipation3/3 (100%) 1/3 (33.3%) 4/8 (50%) 0/3 (0%) 3/4 (75%) 1/3 (33.3%) 0/1 (0%) 1/4 (25%) 0/5 (0%) 0/10 (0%) 1/10 (10%) 3/10 (30%) 1/10 (10%) 1/5 (20%) 2/5 (40%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Dental caries0/3 (0%) 0/3 (0%) 0/8 (0%) 1/3 (33.3%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Diarrhoea1/3 (33.3%) 1/3 (33.3%) 2/8 (25%) 3/3 (100%) 2/4 (50%) 1/3 (33.3%) 0/1 (0%) 1/4 (25%) 1/5 (20%) 5/10 (50%) 5/10 (50%) 2/10 (20%) 1/10 (10%) 1/5 (20%) 1/5 (20%) 0/10 (0%) 0/2 (0%) 2/5 (40%) 3/5 (60%)
    Dry mouth1/3 (33.3%) 0/3 (0%) 0/8 (0%) 1/3 (33.3%) 1/4 (25%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 1/10 (10%) 1/10 (10%) 0/10 (0%) 1/10 (10%) 0/5 (0%) 1/5 (20%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 1/5 (20%)
    Dyspepsia0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 1/5 (20%) 1/5 (20%) 0/10 (0%) 1/2 (50%) 0/5 (0%) 0/5 (0%)
    Dysphagia0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 1/10 (10%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Eructation0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Flatulence0/3 (0%) 0/3 (0%) 0/8 (0%) 1/3 (33.3%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 1/5 (20%) 1/5 (20%)
    Gastritis0/3 (0%) 0/3 (0%) 0/8 (0%) 1/3 (33.3%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Gastrointestinal haemorrhage0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 1/10 (10%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Gastrooesophageal reflux disease1/3 (33.3%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 1/3 (33.3%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 1/10 (10%) 2/10 (20%) 1/10 (10%) 0/10 (0%) 0/5 (0%) 1/5 (20%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Gingival pain0/3 (0%) 1/3 (33.3%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Haematemesis0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 1/10 (10%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Haemorrhoids0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 1/10 (10%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Lip dry0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Lip haematoma0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 1/5 (20%) 0/5 (0%)
    Mouth ulceration0/3 (0%) 0/3 (0%) 0/8 (0%) 1/3 (33.3%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Nausea1/3 (33.3%) 1/3 (33.3%) 0/8 (0%) 0/3 (0%) 2/4 (50%) 1/3 (33.3%) 0/1 (0%) 1/4 (25%) 2/5 (40%) 1/10 (10%) 2/10 (20%) 3/10 (30%) 3/10 (30%) 2/5 (40%) 1/5 (20%) 1/10 (10%) 0/2 (0%) 3/5 (60%) 1/5 (20%)
    Oesophageal pain0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 1/4 (25%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Oral pain0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 1/4 (25%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 2/10 (20%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Proctalgia0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 1/5 (20%) 0/5 (0%)
    Rectal haemorrhage1/3 (33.3%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 1/4 (25%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Stomatitis0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 2/10 (20%) 0/10 (0%) 1/10 (10%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 1/5 (20%)
    Toothache0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 1/10 (10%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Upper gastrointestinal haemorrhage0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 1/1 (100%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Vomiting0/3 (0%) 0/3 (0%) 1/8 (12.5%) 1/3 (33.3%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 1/5 (20%) 1/10 (10%) 1/10 (10%) 1/10 (10%) 2/10 (20%) 0/5 (0%) 1/5 (20%) 1/10 (10%) 0/2 (0%) 1/5 (20%) 0/5 (0%)
    General disorders
    Asthenia1/3 (33.3%) 0/3 (0%) 0/8 (0%) 1/3 (33.3%) 1/4 (25%) 1/3 (33.3%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 2/10 (20%) 1/10 (10%) 3/10 (30%) 0/5 (0%) 1/5 (20%) 2/10 (20%) 2/2 (100%) 3/5 (60%) 2/5 (40%)
    Chills0/3 (0%) 0/3 (0%) 0/8 (0%) 1/3 (33.3%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 1/4 (25%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 1/5 (20%) 1/5 (20%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Discomfort0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 1/3 (33.3%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Early satiety1/3 (33.3%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Face oedema0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Fatigue2/3 (66.7%) 2/3 (66.7%) 2/8 (25%) 1/3 (33.3%) 1/4 (25%) 1/3 (33.3%) 0/1 (0%) 1/4 (25%) 2/5 (40%) 2/10 (20%) 2/10 (20%) 3/10 (30%) 3/10 (30%) 2/5 (40%) 0/5 (0%) 1/10 (10%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Gait disturbance0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    General physical health deterioration0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 1/4 (25%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 1/5 (20%) 0/5 (0%)
    Gravitational oedema0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Inflammation0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 1/4 (25%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Influenza like illness0/3 (0%) 0/3 (0%) 0/8 (0%) 1/3 (33.3%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 1/5 (20%) 0/5 (0%) 1/10 (10%) 0/2 (0%) 0/5 (0%) 1/5 (20%)
    Injection site bruising0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 1/4 (25%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Localised oedema0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Malaise0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 1/5 (20%) 0/10 (0%) 1/10 (10%) 1/10 (10%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Mucosal inflammation0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 2/10 (20%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Nodule0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Non-cardiac chest pain0/3 (0%) 1/3 (33.3%) 1/8 (12.5%) 0/3 (0%) 1/4 (25%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 1/10 (10%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Oedema peripheral0/3 (0%) 0/3 (0%) 2/8 (25%) 0/3 (0%) 1/4 (25%) 0/3 (0%) 0/1 (0%) 1/4 (25%) 1/5 (20%) 0/10 (0%) 1/10 (10%) 1/10 (10%) 0/10 (0%) 0/5 (0%) 2/5 (40%) 1/10 (10%) 0/2 (0%) 0/5 (0%) 2/5 (40%)
    Pain1/3 (33.3%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 2/10 (20%) 0/10 (0%) 0/10 (0%) 1/10 (10%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 2/5 (40%)
    Peripheral swelling0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Pneumatosis0/3 (0%) 0/3 (0%) 0/8 (0%) 1/3 (33.3%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Pyrexia1/3 (33.3%) 1/3 (33.3%) 2/8 (25%) 0/3 (0%) 1/4 (25%) 1/3 (33.3%) 0/1 (0%) 1/4 (25%) 3/5 (60%) 3/10 (30%) 2/10 (20%) 3/10 (30%) 4/10 (40%) 1/5 (20%) 2/5 (40%) 6/10 (60%) 1/2 (50%) 4/5 (80%) 2/5 (40%)
    Temperature intolerance0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 1/4 (25%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Hepatobiliary disorders
    Cholestasis0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Hepatitis0/3 (0%) 1/3 (33.3%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Hepatocellular injury0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 2/10 (20%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Hypertransaminasaemia0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 1/10 (10%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Jaundice cholestatic0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 1/5 (20%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Ocular icterus0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 1/5 (20%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Immune system disorders
    Drug hypersensitivity0/3 (0%) 1/3 (33.3%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Hypogammaglobulinaemia0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Immunodeficiency0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 1/5 (20%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Seasonal allergy0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Infections and infestations
    Bacterial sepsis0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Bronchiolitis0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 1/3 (33.3%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Bronchitis0/3 (0%) 1/3 (33.3%) 0/8 (0%) 1/3 (33.3%) 1/4 (25%) 2/3 (66.7%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 3/10 (30%) 1/10 (10%) 2/10 (20%) 1/10 (10%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Chronic sinusitis0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 1/3 (33.3%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Conjunctivitis0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 1/5 (20%) 0/5 (0%)
    Cystitis0/3 (0%) 0/3 (0%) 1/8 (12.5%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Cytomegalovirus infection0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 1/5 (20%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Ear infection0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Enterocolitis infectious0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Eye infection0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 1/5 (20%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Folliculitis0/3 (0%) 0/3 (0%) 1/8 (12.5%) 0/3 (0%) 1/4 (25%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Gastroenteritis0/3 (0%) 0/3 (0%) 0/8 (0%) 1/3 (33.3%) 0/4 (0%) 1/3 (33.3%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 1/10 (10%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Gastroenteritis viral1/3 (33.3%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 1/4 (25%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Herpes ophthalmic0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 1/4 (25%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Herpes simplex0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 1/5 (20%) 0/5 (0%)
    Herpes virus infection0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 1/4 (25%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Herpes zoster0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 1/4 (25%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 2/10 (20%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Hordeolum0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 1/4 (25%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Human herpesvirus 6 infection0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Influenza0/3 (0%) 0/3 (0%) 1/8 (12.5%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Laryngitis0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 1/5 (20%)
    Lip infection0/3 (0%) 0/3 (0%) 1/8 (12.5%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Lower respiratory tract infection0/3 (0%) 1/3 (33.3%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 1/5 (20%) 0/5 (0%)
    Lung infection0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 3/10 (30%) 0/10 (0%) 0/10 (0%) 1/10 (10%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Metapneumovirus infection0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 1/5 (20%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Nasopharyngitis0/3 (0%) 0/3 (0%) 1/8 (12.5%) 0/3 (0%) 0/4 (0%) 1/3 (33.3%) 0/1 (0%) 1/4 (25%) 0/5 (0%) 1/10 (10%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 0/5 (0%) 1/5 (20%) 0/10 (0%) 0/2 (0%) 1/5 (20%) 1/5 (20%)
    Oral candidiasis0/3 (0%) 0/3 (0%) 1/8 (12.5%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 1/5 (20%) 0/5 (0%)
    Oral fungal infection1/3 (33.3%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 1/4 (25%) 0/5 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Otitis media0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 1/4 (25%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Otitis media acute0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 1/5 (20%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Paronychia0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Pharyngitis0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Pneumonia0/3 (0%) 0/3 (0%) 0/8 (0%) 1/3 (33.3%) 1/4 (25%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 1/5 (20%) 0/5 (0%)
    Pneumonia pseudomonal0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 1/5 (20%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Pseudomonas infection0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 1/10 (10%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Respiratory tract infection0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 1/5 (20%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Rhinitis0/3 (0%) 0/3 (0%) 0/8 (0%) 1/3 (33.3%) 1/4 (25%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Rhinovirus infection0/3 (0%) 0/3 (0%) 1/8 (12.5%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 1/5 (20%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 1/10 (10%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Sepsis0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 1/5 (20%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 1/10 (10%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Sinusitis0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 2/4 (50%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 1/5 (20%) 0/5 (0%) 0/10 (0%) 1/2 (50%) 0/5 (0%) 0/5 (0%)
    Skin infection0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 1/1 (100%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 1/5 (20%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Stenotrophomonas sepsis0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Tonsillitis0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 1/5 (20%)
    Tooth infection0/3 (0%) 1/3 (33.3%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Upper respiratory tract infection1/3 (33.3%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 2/4 (50%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 1/10 (10%) 2/10 (20%) 0/10 (0%) 0/5 (0%) 1/5 (20%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 1/5 (20%)
    Urinary tract infection0/3 (0%) 0/3 (0%) 1/8 (12.5%) 1/3 (33.3%) 1/4 (25%) 1/3 (33.3%) 0/1 (0%) 1/4 (25%) 0/5 (0%) 3/10 (30%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 1/5 (20%) 0/5 (0%)
    Urinary tract infection viral0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Viral infection0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 1/5 (20%)
    Injury, poisoning and procedural complications
    Allergic transfusion reaction0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 1/10 (10%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Arthropod bite0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Contusion0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 1/4 (25%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 2/10 (20%) 2/10 (20%) 0/10 (0%) 0/10 (0%) 1/5 (20%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Eye contusion0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 1/4 (25%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Fall0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 1/4 (25%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 1/10 (10%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 2/5 (40%) 0/5 (0%)
    Humerus fracture0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 1/5 (20%) 0/5 (0%)
    Infusion related reaction0/3 (0%) 0/3 (0%) 2/8 (25%) 0/3 (0%) 0/4 (0%) 1/3 (33.3%) 0/1 (0%) 1/4 (25%) 1/5 (20%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Joint dislocation0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Joint injury0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Laceration0/3 (0%) 1/3 (33.3%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Ligament sprain0/3 (0%) 0/3 (0%) 1/8 (12.5%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Overdose0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 1/5 (20%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Procedural pain0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 1/4 (25%) 0/3 (0%) 0/1 (0%) 1/4 (25%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Subdural haematoma0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Thermal burn0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Tooth fracture0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Transfusion reaction0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Wound0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 1/5 (20%) 0/5 (0%)
    Investigations
    Alanine aminotransferase increased0/3 (0%) 0/3 (0%) 1/8 (12.5%) 1/3 (33.3%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 1/5 (20%)
    Amylase increased0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Aspartate aminotransferase increased0/3 (0%) 1/3 (33.3%) 1/8 (12.5%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 1/5 (20%) 0/10 (0%) 1/10 (10%) 1/10 (10%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 1/10 (10%) 0/2 (0%) 0/5 (0%) 1/5 (20%)
    Blood alkaline phosphatase increased0/3 (0%) 0/3 (0%) 1/8 (12.5%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 1/10 (10%) 1/10 (10%) 0/10 (0%) 0/5 (0%) 1/5 (20%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 1/5 (20%)
    Blood bilirubin increased0/3 (0%) 0/3 (0%) 0/8 (0%) 1/3 (33.3%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 1/5 (20%) 0/10 (0%) 1/10 (10%) 1/10 (10%) 0/10 (0%) 0/5 (0%) 2/5 (40%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Blood creatine phosphokinase increased0/3 (0%) 0/3 (0%) 1/8 (12.5%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Blood creatinine increased0/3 (0%) 1/3 (33.3%) 0/8 (0%) 0/3 (0%) 1/4 (25%) 0/3 (0%) 0/1 (0%) 1/4 (25%) 0/5 (0%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 1/10 (10%) 1/5 (20%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 1/5 (20%)
    Blood glucose increased0/3 (0%) 0/3 (0%) 1/8 (12.5%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Blood lactate dehydrogenase increased0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 1/5 (20%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 1/5 (20%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Blood urine present0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Gamma-glutamyltransferase increased0/3 (0%) 0/3 (0%) 1/8 (12.5%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Heart rate irregular0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 1/4 (25%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Immunoglobulins decreased0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 2/5 (40%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    International normalised ratio increased0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 1/5 (20%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Lipase increased0/3 (0%) 0/3 (0%) 1/8 (12.5%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Lymphocyte count decreased1/3 (33.3%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Lymphocyte count increased0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Monocyte count increased0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Neutrophil count decreased0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 1/4 (25%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Platelet count decreased1/3 (33.3%) 0/3 (0%) 0/8 (0%) 1/3 (33.3%) 1/4 (25%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Streptococcus test positive0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Urine output decreased0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 1/5 (20%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Weight decreased1/3 (33.3%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 1/5 (20%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 1/10 (10%) 0/5 (0%) 1/5 (20%) 1/10 (10%) 0/2 (0%) 3/5 (60%) 0/5 (0%)
    Weight increased0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 1/4 (25%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    White blood cell count decreased1/3 (33.3%) 0/3 (0%) 1/8 (12.5%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Metabolism and nutrition disorders
    Decreased appetite2/3 (66.7%) 1/3 (33.3%) 2/8 (25%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 1/5 (20%) 0/10 (0%) 1/10 (10%) 2/10 (20%) 3/10 (30%) 1/5 (20%) 2/5 (40%) 2/10 (20%) 0/2 (0%) 1/5 (20%) 2/5 (40%)
    Dehydration0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 2/5 (40%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Gout0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Hypercalcaemia0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 1/4 (25%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 1/10 (10%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Hyperglycaemia0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 1/4 (25%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) 1/10 (10%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Hyperkalaemia1/3 (33.3%) 0/3 (0%) 0/8 (0%) 1/3 (33.3%) 1/4 (25%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Hyperlactacidaemia0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 1/5 (20%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Hypertriglyceridaemia0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 1/5 (20%) 0/5 (0%)
    Hyperuricaemia0/3 (0%) 0/3 (0%) 0/8 (0%) 1/3 (33.3%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 1/4 (25%) 0/5 (0%) 1/10 (10%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 2/10 (20%) 0/2 (0%) 1/5 (20%) 1/5 (20%)
    Hypoalbuminaemia0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 1/5 (20%) 1/5 (20%)
    Hypocalcaemia1/3 (33.3%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 1/4 (25%) 0/5 (0%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 1/5 (20%) 1/10 (10%) 1/2 (50%) 2/5 (40%) 1/5 (20%)
    Hypoglycaemia0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Hypokalaemia1/3 (33.3%) 0/3 (0%) 1/8 (12.5%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 1/10 (10%) 0/5 (0%) 1/5 (20%) 2/10 (20%) 0/2 (0%) 3/5 (60%) 1/5 (20%)
    Hypomagnesaemia0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 1/5 (20%) 1/10 (10%) 0/2 (0%) 2/5 (40%) 1/5 (20%)
    Hyponatraemia0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 1/4 (25%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 1/5 (20%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Hypophosphataemia0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 1/5 (20%)
    Polydipsia0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 1/5 (20%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Tumour lysis syndrome0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Musculoskeletal and connective tissue disorders
    Arthralgia0/3 (0%) 0/3 (0%) 1/8 (12.5%) 0/3 (0%) 2/4 (50%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 3/10 (30%) 2/10 (20%) 0/10 (0%) 0/10 (0%) 1/5 (20%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Arthritis0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Back pain1/3 (33.3%) 1/3 (33.3%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 1/4 (25%) 1/5 (20%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 1/5 (20%) 0/5 (0%) 1/10 (10%) 0/2 (0%) 1/5 (20%) 2/5 (40%)
    Bone pain0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 1/5 (20%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 1/5 (20%) 1/5 (20%)
    Flank pain0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 1/10 (10%) 1/10 (10%) 0/10 (0%) 1/5 (20%) 1/5 (20%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Groin pain0/3 (0%) 1/3 (33.3%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Intervertebral disc degeneration1/3 (33.3%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Intervertebral disc disorder0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Joint noise0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 1/5 (20%)
    Joint swelling0/3 (0%) 0/3 (0%) 1/8 (12.5%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Muscle mass0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 1/5 (20%) 0/5 (0%)
    Muscle spasms1/3 (33.3%) 1/3 (33.3%) 1/8 (12.5%) 1/3 (33.3%) 2/4 (50%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 3/10 (30%) 3/10 (30%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Muscular weakness0/3 (0%) 0/3 (0%) 1/8 (12.5%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Musculoskeletal chest pain0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 2/4 (50%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Musculoskeletal discomfort0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 1/5 (20%)
    Musculoskeletal pain0/3 (0%) 0/3 (0%) 0/8 (0%) 1/3 (33.3%) 1/4 (25%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 1/10 (10%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Musculoskeletal stiffness0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 1/4 (25%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Myalgia2/3 (66.7%) 3/3 (100%) 0/8 (0%) 0/3 (0%) 1/4 (25%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 2/10 (20%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Neck pain1/3 (33.3%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Pain in extremity1/3 (33.3%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 1/5 (20%)
    Pain in jaw0/3 (0%) 1/3 (33.3%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Periarthritis1/3 (33.3%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Rotator cuff syndrome0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 1/4 (25%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Synovial cyst0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Cancer pain0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 1/4 (25%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Tumour flare0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 1/5 (20%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Nervous system disorders
    Amnesia0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Aphasia0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 1/5 (20%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Depressed level of consciousness0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Dizziness1/3 (33.3%) 0/3 (0%) 0/8 (0%) 1/3 (33.3%) 1/4 (25%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 1/5 (20%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 1/5 (20%) 0/5 (0%) 1/10 (10%) 0/2 (0%) 1/5 (20%) 0/5 (0%)
    Dysaesthesia0/3 (0%) 0/3 (0%) 1/8 (12.5%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Dysgeusia0/3 (0%) 1/3 (33.3%) 1/8 (12.5%) 1/3 (33.3%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 1/4 (25%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) 0/5 (0%) 1/5 (20%) 0/10 (0%) 0/2 (0%) 2/5 (40%) 0/5 (0%)
    Headache1/3 (33.3%) 2/3 (66.7%) 0/8 (0%) 1/3 (33.3%) 2/4 (50%) 0/3 (0%) 0/1 (0%) 1/4 (25%) 0/5 (0%) 0/10 (0%) 1/10 (10%) 1/10 (10%) 1/10 (10%) 1/5 (20%) 0/5 (0%) 1/10 (10%) 0/2 (0%) 1/5 (20%) 2/5 (40%)
    Hypoaesthesia0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 1/10 (10%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 1/5 (20%)
    Lethargy0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 1/5 (20%)
    Memory impairment0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 1/5 (20%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Migraine0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 1/5 (20%)
    Paraesthesia0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 2/10 (20%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 1/5 (20%)
    Peripheral sensory neuropathy1/3 (33.3%) 0/3 (0%) 1/8 (12.5%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 1/10 (10%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 1/5 (20%) 0/5 (0%) 1/10 (10%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Sciatica0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Somnolence0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 1/5 (20%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Syncope0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 1/5 (20%) 0/5 (0%)
    Tremor0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 1/5 (20%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 1/5 (20%) 0/5 (0%)
    Psychiatric disorders
    Anxiety0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 1/10 (10%) 1/5 (20%) 1/5 (20%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Apathy0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 1/5 (20%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Cardiovascular somatic symptom disorder0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 1/4 (25%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Confusional state0/3 (0%) 0/3 (0%) 0/8 (0%) 2/3 (66.7%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 1/5 (20%) 0/5 (0%)
    Depression0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 1/10 (10%) 2/10 (20%) 0/10 (0%) 1/10 (10%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 1/5 (20%) 0/5 (0%)
    Disorientation0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 1/5 (20%) 0/5 (0%)
    Insomnia0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 1/10 (10%) 1/10 (10%) 0/10 (0%) 1/10 (10%) 2/5 (40%) 0/5 (0%) 1/10 (10%) 0/2 (0%) 0/5 (0%) 2/5 (40%)
    Irritability0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 1/5 (20%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Panic attack0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 1/5 (20%)
    Renal and urinary disorders
    Acute kidney injury0/3 (0%) 1/3 (33.3%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Cystitis haemorrhagic0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Dysuria0/3 (0%) 1/3 (33.3%) 0/8 (0%) 1/3 (33.3%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 2/10 (20%) 1/10 (10%) 1/10 (10%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 1/5 (20%) 0/5 (0%)
    Haematuria0/3 (0%) 1/3 (33.3%) 0/8 (0%) 0/3 (0%) 1/4 (25%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 2/10 (20%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Micturition urgency0/3 (0%) 1/3 (33.3%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Pollakiuria0/3 (0%) 0/3 (0%) 0/8 (0%) 1/3 (33.3%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 1/5 (20%)
    Renal failure2/3 (66.7%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 1/4 (25%) 0/5 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Renal impairment0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 1/5 (20%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Ureterolithiasis0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 1/5 (20%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Urinary incontinence0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Urinary tract pain0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Reproductive system and breast disorders
    Benign prostatic hyperplasia0/3 (0%) 1/3 (33.3%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Pelvic pain0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 1/4 (25%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Penile oedema0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 1/5 (20%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Vaginal haemorrhage0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 1/5 (20%) 0/5 (0%)
    Respiratory, thoracic and mediastinal disorders
    Allergic cough0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 1/3 (33.3%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Asthma0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 1/10 (10%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Chronic obstructive pulmonary disease0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Cough1/3 (33.3%) 0/3 (0%) 1/8 (12.5%) 1/3 (33.3%) 1/4 (25%) 1/3 (33.3%) 0/1 (0%) 0/4 (0%) 2/5 (40%) 3/10 (30%) 0/10 (0%) 4/10 (40%) 2/10 (20%) 1/5 (20%) 2/5 (40%) 1/10 (10%) 0/2 (0%) 2/5 (40%) 1/5 (20%)
    Dysphonia0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 1/10 (10%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Dyspnoea1/3 (33.3%) 0/3 (0%) 3/8 (37.5%) 0/3 (0%) 2/4 (50%) 1/3 (33.3%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 2/10 (20%) 2/5 (40%) 3/5 (60%) 2/10 (20%) 0/2 (0%) 0/5 (0%) 1/5 (20%)
    Dyspnoea exertional0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 1/5 (20%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Epistaxis0/3 (0%) 0/3 (0%) 0/8 (0%) 1/3 (33.3%) 1/4 (25%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 2/10 (20%) 0/10 (0%) 0/10 (0%) 1/10 (10%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Hiccups0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 1/4 (25%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Hypoxia0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) 0/5 (0%) 1/5 (20%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 1/5 (20%)
    Laryngeal inflammation0/3 (0%) 1/3 (33.3%) 0/8 (0%) 0/3 (0%) 1/4 (25%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Nasal congestion0/3 (0%) 0/3 (0%) 1/8 (12.5%) 0/3 (0%) 1/4 (25%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 1/5 (20%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Nasal dryness0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Nasal obstruction0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Oropharyngeal pain1/3 (33.3%) 0/3 (0%) 1/8 (12.5%) 0/3 (0%) 1/4 (25%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 1/10 (10%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Pharyngeal erythema0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 1/3 (33.3%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Pleural effusion0/3 (0%) 0/3 (0%) 1/8 (12.5%) 0/3 (0%) 2/4 (50%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 2/5 (40%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 1/5 (20%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Pleuritic pain0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 1/4 (25%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Pneumonia aspiration0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Productive cough0/3 (0%) 0/3 (0%) 1/8 (12.5%) 0/3 (0%) 1/4 (25%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) 1/10 (10%) 0/5 (0%) 0/5 (0%) 1/10 (10%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Pulmonary oedema0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Rales0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 1/5 (20%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Sinus congestion1/3 (33.3%) 0/3 (0%) 0/8 (0%) 1/3 (33.3%) 1/4 (25%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Sinus disorder0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 1/5 (20%)
    Sinus pain0/3 (0%) 0/3 (0%) 0/8 (0%) 1/3 (33.3%) 1/4 (25%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Tachypnoea0/3 (0%) 1/3 (33.3%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Upper respiratory tract inflammation0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 1/4 (25%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Upper-airway cough syndrome0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 1/4 (25%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Wheezing0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Skin and subcutaneous tissue disorders
    Alopecia0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Decubitus ulcer0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 1/5 (20%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Dermatitis acneiform0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 2/10 (20%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Dermatitis contact0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Dermatitis exfoliative generalised0/3 (0%) 1/3 (33.3%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Dry skin0/3 (0%) 1/3 (33.3%) 1/8 (12.5%) 1/3 (33.3%) 1/4 (25%) 0/3 (0%) 0/1 (0%) 1/4 (25%) 0/5 (0%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Ecchymosis0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 1/4 (25%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 1/5 (20%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Eczema asteatotic0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Eczema nummular0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Erythema0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 1/4 (25%) 1/3 (33.3%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 3/10 (30%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Hyperhidrosis0/3 (0%) 0/3 (0%) 0/8 (0%) 1/3 (33.3%) 1/4 (25%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Hyperkeratosis0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Neurodermatitis0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Night sweats0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 1/5 (20%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Onychoclasis0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 1/4 (25%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Petechiae0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Pruritus1/3 (33.3%) 1/3 (33.3%) 1/8 (12.5%) 0/3 (0%) 2/4 (50%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 1/5 (20%) 1/10 (10%) 0/10 (0%) 1/10 (10%) 2/10 (20%) 1/5 (20%) 0/5 (0%) 1/10 (10%) 0/2 (0%) 1/5 (20%) 1/5 (20%)
    Pruritus generalised0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 1/5 (20%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 1/5 (20%)
    Psoriasis0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Purpura0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 1/5 (20%) 0/5 (0%)
    Rash0/3 (0%) 0/3 (0%) 0/8 (0%) 1/3 (33.3%) 2/4 (50%) 1/3 (33.3%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 3/10 (30%) 4/10 (40%) 0/10 (0%) 2/10 (20%) 1/5 (20%) 2/5 (40%) 1/10 (10%) 0/2 (0%) 0/5 (0%) 2/5 (40%)
    Rash generalised0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 1/10 (10%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Rash macular0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 1/5 (20%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 1/5 (20%)
    Rash maculo-papular0/3 (0%) 1/3 (33.3%) 2/8 (25%) 1/3 (33.3%) 1/4 (25%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Rash pruritic0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 1/5 (20%) 0/5 (0%)
    Skin fissures0/3 (0%) 1/3 (33.3%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Skin lesion0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 2/4 (50%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 1/5 (20%)
    Urticaria0/3 (0%) 0/3 (0%) 0/8 (0%) 1/3 (33.3%) 1/4 (25%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Vascular disorders
    Aortic stenosis0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Axillary vein thrombosis0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Deep vein thrombosis0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 1/5 (20%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Embolism0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Embolism venous0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 1/4 (25%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Haematoma0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 1/10 (10%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Hypertension0/3 (0%) 0/3 (0%) 0/8 (0%) 1/3 (33.3%) 1/4 (25%) 1/3 (33.3%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 1/10 (10%) 1/10 (10%) 1/10 (10%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Hypotension0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 1/3 (33.3%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) 0/5 (0%) 2/5 (40%) 0/10 (0%) 0/2 (0%) 1/5 (20%) 1/5 (20%)
    Shock0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 1/5 (20%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Subclavian vein thrombosis0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 1/10 (10%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Venous thrombosis0/3 (0%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 1/3 (33.3%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)
    Venous thrombosis limb1/3 (33.3%) 0/3 (0%) 0/8 (0%) 0/3 (0%) 0/4 (0%) 0/3 (0%) 0/1 (0%) 0/4 (0%) 0/5 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/10 (0%) 0/5 (0%) 0/5 (0%) 0/10 (0%) 0/2 (0%) 0/5 (0%) 0/5 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

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

    Results from a center cannot be submitted for publication before results of multicenter study are published unless it is > 1 year since study completion. Then, Investigator can publish if manuscript is submitted to Celgene 60 days prior to submission. If Celgene decides publication would hinder drug development, Investigator must delay submission for up to 90 additional days. Investigator must delete confidential information before submission and defer publication to permit patent applications.

    Results Point of Contact

    Name/TitleAnne McClain
    OrganizationCelgene Corporation
    Phone1-888-260-1599
    Emailclinicaltrialdisclosure@celgene.com
    Responsible Party:
    Celgene
    ClinicalTrials.gov Identifier:
    NCT02733042
    Other Study ID Numbers:
    • MEDI4736-NHL-001
    • 2015-003516-21
    First Posted:
    Apr 11, 2016
    Last Update Posted:
    Feb 1, 2022
    Last Verified:
    Jan 1, 2022