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
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).
Condition or Disease | Intervention/Treatment | Phase |
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Phase 1/Phase 2 |
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:
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Arm A: durvalumab and lenalidomide ± rituximab
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Arm B: durvalumab and ibrutinib
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Arm C: durvalumab and rituximab ± bendamustine
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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
Arms and Interventions
Arm | Intervention/Treatment |
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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:
Drug: Lenalidomide
Administered orally
Other Names:
Drug: Rituximab
Administered by intravenous infusion
Other Names:
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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:
Drug: Ibrutinib
Administered orally
Other Names:
|
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:
Drug: Rituximab
Administered by intravenous infusion
Other Names:
Drug: Bendamustine
Administered as a 30-minute intravenous infusion
Other Names:
|
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:
|
Outcome Measures
Primary Outcome Measures
- 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.
- 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
- 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).
- 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).
- 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).
- 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.
- 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.
- 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.]
- 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.]
- 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.]
- 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.]
- 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.]
- 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.]
- 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.]
- 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.]
- 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.]
- 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]
- 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.]
- 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.]
- 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]
- 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
Inclusion Criteria:
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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.
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Subject who has high-risk chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL).
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Subject who was previously treated with at least one prior systemic chemotherapy, immunotherapy, or chemoimmunotherapy.
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Subject who has the Eastern Cooperative Oncology Group performance status of 0, 1, or
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Subject who is willing and able to undergo biopsy.
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Subject who has documented active relapsed or refractory disease requiring therapeutic intervention.
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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.
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Subject who fulfills the laboratory requirements as per protocol
Exclusion Criteria
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Subject who has central nervous system (CNS) or meningeal involvement by lymphoma.
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Subject who has any histopathologic finding consistent with myelodysplastic syndrome on bone marrow studies.
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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:
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Arm A only: drugs with immunomodulatory and other properties (eg, lenalidomide, thalidomide);
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Arm B only: ibrutinib or other Bruton's tyrosine kinase (BTK) inhibitor;
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Arms C only: bendamustine
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Subject who has active auto-immune disease.
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Subject who has history of organ transplant or allogeneic hematopoietic stem cell transplantation.
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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)
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Subject who has known seropositivity for or active infection for human immunodeficiency virus (HIV) or hepatitis C virus (HCV).
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Subject who has history of primary immunodeficiency or tuberculosis.
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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
Site | City | State | Country | Postal Code | |
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1 | Banner MD Anderson Cancer Center | Gilbert | Arizona | United States | 85234 |
2 | Pinnacle Oncology Hematology | Scottsdale | Arizona | United States | 85258 |
3 | University of Colorado Cancer Center | Aurora | Colorado | United States | 80045 |
4 | Shands Cancer Center University of Florida | Gainesville | Florida | United States | 32610 |
5 | Moffitt Cancer Center | Tampa | Florida | United States | 33612 |
6 | Emory University | Atlanta | Georgia | United States | 30322 |
7 | Northwestern University Feinberg School of Medicine | Chicago | Illinois | United States | 60611 |
8 | Mayo Clinic | Rochester | Minnesota | United States | 55905 |
9 | Washington University School of Medicine | Saint Louis | Missouri | United States | 63110 |
10 | John Theurer Cancer Center at Hackensack University Medical Center | Hackensack | New Jersey | United States | 07601 |
11 | Weill Cornell Medical College | New York | New York | United States | 10065 |
12 | University of Rochester | Rochester | New York | United States | 14642 |
13 | The Ohio State University | Columbus | Ohio | United States | 43210 |
14 | University of Oklahoma Peggy and Charles Stephenson Cancer Center | Oklahoma City | Oklahoma | United States | 73104 |
15 | Jefferson Medical Oncology Associates | Philadelphia | Pennsylvania | United States | 19107 |
16 | MD Anderson Cancer Center | Houston | Texas | United States | 77030-4009 |
17 | Houston Methodist Cancer Center | Houston | Texas | United States | 77030 |
18 | MD Anderson Cancer Center | Houston | Texas | United States | 77030 |
19 | Centre Hospitalier Universitaire d'Avicennes | Bobigny Cedex | France | 93009 | |
20 | Hopital Henri Mondor | Creteil | France | 94010 | |
21 | Centre Hospitalier | Dijon Cedex | France | 21079 | |
22 | Institut Paoli Calmettes | Marseille Cedex 9 | France | 13273 | |
23 | CHU Montpellier | Montpellier Cedex 5 | France | 34295 | |
24 | Centre Hospitalier Universitaire de Nantes | Nantes | France | 44093 | |
25 | Hopital Haut Leveque | Pessac Cedex | France | 33604 | |
26 | Centre Hospitalier Lyon-Sud | Pierre-Benite CEDEX | France | 69495 | |
27 | CHRU Rennes | Rennes | France | 35033 | |
28 | Centre Henri Becquerel | Rouen Cedex | France | 76038 | |
29 | Universitatsklinikum Essen | Essen | Germany | 45122 | |
30 | UKG Universitatsklinikum Gottingen | Göttingen | Germany | 37099 | |
31 | Universitatsklinikum des Saarlandes | Homburg-Saar | Germany | 66421 | |
32 | Universitatsklinik Koln | Köln | Germany | 50924 | |
33 | Medizinische Klinik III Klinikum der Universität München-Großhadern | München | Germany | 81377 | |
34 | University of Bologna | Bologna | Italy | 40138 | |
35 | Spedali Civili Di Brescia | Brescia | Italy | 25123 | |
36 | IEO- Istituto Europeo di Oncologia | Milano | Italy | 20144 | |
37 | A.O. Ospedale Ca Granda - Niguarda | Milano | Italy | 20162 | |
38 | Istituto Nazionale Per Lo Studio E La Cura Dei Tumori Fondazione Giovanni Pascale | Napoli, Campania | Italy | 80131 | |
39 | I.R.C.C.S. Policlinico San Matteo | Pavia | Italy | 27100 | |
40 | IRCCS Humanitas Clinical Institute | Rozzano (milano) | Italy | 20089 | |
41 | National Cancer Center Hospital | Chuo-ku | Japan | 104-0045 | |
42 | Tokai University Hospital | Isehara City, Kanagawa | Japan | 259-1193 | |
43 | Aichi Cancer Center | Nagoya | Japan | 464-8681 | |
44 | VU Academic Medical Center, Amsterdam | Amsterdam | Netherlands | 1081 HV | |
45 | UMC Groningen | Groningen | Netherlands | 9713 GZ | |
46 | Leids Universitair Medisch Centrum | Leiden | Netherlands | 2333 ZA | |
47 | Erasmus Medical Center | Rotterdam | Netherlands | 3015 CN | |
48 | St James University Hospital | Leeds | United Kingdom | LS9 7TF | |
49 | UCL Cancer Institute | London | United Kingdom | WC1E 6BT | |
50 | Christie Hospital NHS Trust | Manchester | United Kingdom | M20 4BX | |
51 | Nottingham University Hospitals NHS Trust | Nottingham | United Kingdom | Ng5 1PB | |
52 | Oxford University Hospitals NHS Trust- Churchill Hospital-Oxford Centre for Respiratory Medicine | Oxford | United Kingdom | 0X3 7LE | |
53 | Derriford Hospital | Plymouth | United Kingdom | PL6 8DH | |
54 | Southampton University Hospitals NHS Trust | Southampton | United Kingdom | SO16 6YD |
Sponsors and Collaborators
- Celgene
Investigators
- Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb
Study Documents (Full-Text)
More Information
Publications
None provided.- MEDI4736-NHL-001
- 2015-003516-21
Study Results
Participant Flow
Recruitment Details | The 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. |
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Pre-assignment Detail | Participants 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 Title | Part 1, Arm A: DUR 1500 mg + LEN 20 mg | Part 1, Arm A: DUR 1500 mg + LEN 20 mg + RIT 375 mg/m² | Part 1, Arm A: DUR 1500 mg + LEN 10 mg + RIT 375 mg/m² | Part 1, Arm B: DUR 1500 mg + IBR 420 mg | Part 1, Arm B: DUR 1500 mg + IBR 560 mg | 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 | Part 2, Arm B CLL/SLL: DUR 1500 mg + IBR 420 mg | Part 2, Arm B MCL: DUR 1500 mg + IBR 560 mg | Part 2, Arm C FL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Part 2 Arm C DLBCL: DUR mg + RIT 375 mg/m² + BEN 70 mg/m² | Part 2, Arm C CLL/SLL: DUR + RIT 375 mg/m² + BEN 70 mg/m² | Part 2, Arm D FL: DUR 1500 mg | Part 2, Arm D DLBCL: DUR 1500 mg | Part 2, Arm D CLL/SLL: DUR 1500 mg | Part 2, Arm D MCL: DUR 1500 mg | Part 2 Arm D HL: DUR 1500 mg |
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Arm/Group Description | Participants 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 | |||||||||||||||||||
STARTED | 3 | 3 | 8 | 3 | 4 | 3 | 1 | 4 | 5 | 10 | 10 | 10 | 10 | 5 | 5 | 10 | 2 | 5 | 5 |
COMPLETED | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 4 | 1 | 1 | 0 | 0 | 0 | 0 | 0 |
NOT COMPLETED | 3 | 2 | 7 | 3 | 4 | 3 | 1 | 3 | 5 | 10 | 10 | 6 | 9 | 4 | 5 | 10 | 2 | 5 | 5 |
Period Title: Treatment Period | |||||||||||||||||||
STARTED | 3 | 3 | 6 | 3 | 1 | 2 | 0 | 4 | 4 | 2 | 5 | 9 | 9 | 4 | 1 | 5 | 0 | 3 | 2 |
COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
NOT COMPLETED | 3 | 3 | 6 | 3 | 1 | 2 | 0 | 4 | 4 | 2 | 5 | 9 | 9 | 4 | 1 | 5 | 0 | 2 | 2 |
Baseline Characteristics
Arm/Group Title | Part 1, Arm A: DUR 1500 mg + LEN 20 mg | Part 1, Arm A: DUR 1500 mg + LEN 20 mg + RIT 375 mg/m² | Part 1, Arm A: DUR 1500 mg + LEN 10 mg + RIT 375 mg/m² | Part 1, Arm B: DUR 1500 mg + IBR 420 mg | Part 1, Arm B: DUR 1500 mg + IBR 560 mg | 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 | Part 2, Arm B CLL/SLL: DUR 1500 mg + IBR 420 mG | Part 2, Arm B MCL: DUR 1500 mg + IBR 560 mg | Part 2, Arm C FL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Part 2 Arm C DLBCL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Part 2, Arm C CLL/SLL: DUR + RIT 375 mg/m² + BEN 70 mg/m² | Part 2, Arm D FL: DUR 1500 mg | Part 2, Arm D DLBCL: DUR 1500 mg | Part 2, Arm D CLL/SLL: DUR 1500 mg | Part 2, Arm D MCL: DUR 1500 mg | Part 2 Arm D HL: DUR 1500 mg | Total |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Arm/Group Description | Participants 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 Participants | 3 | 3 | 8 | 3 | 4 | 3 | 1 | 4 | 5 | 10 | 10 | 10 | 10 | 5 | 5 | 10 | 2 | 5 | 5 | 106 |
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
Title | Part 1: Number of Participants With Dose Limiting Toxicities (DLTs) |
---|---|
Description | 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. |
Time Frame | Cycle 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 Title | Part 1, Arm A: DUR 1500 mg + LEN 20 mg | Part 1, Arm A: DUR 1500 mg + LEN 20 mg + RIT 375 mg/m² | Part 1, Arm A: DUR 1500 mg + LEN 10 mg + RIT 375 mg/m² | Part 1, Arm B: DUR 1500 mg + IBR 420 mg | Part 1, Arm B: DUR 1500 mg + IBR 560 mg | 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 |
---|---|---|---|---|---|---|---|---|---|
Arm/Group Description | Participants 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 Participants | 3 | 3 | 6 | 3 | 4 | 3 | 0 | 4 | 5 |
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 Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Other Statistical Analysis | For 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 Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Other Statistical Analysis | For Arm C the RP2D was confirmed as rituximab 375 mg/m² + bendamustine 70 mg/m². |
Title | Number of Participants With Treatment-emergent Adverse Events |
---|---|
Description | 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). |
Time Frame | 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. |
Outcome Measure Data
Analysis Population Description |
---|
The Safety population included all participants who received at least 1 dose of study drug. |
Arm/Group Title | Part 1, Arm A: DUR 1500 mg + LEN 20 mg | Part 1, Arm A: DUR 1500 mg + LEN 20 mg + RIT 375 mg/m² | Part 1, Arm A: DUR 1500 mg + LEN 10 mg + RIT 375 mg/m² | Part 1, Arm B: DUR 1500 mg + IBR 420 mg | Part 1, Arm B: DUR 1500 mg + IBR 560 mg | 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 | Part 2, Arm B CLL/SLL: DUR 1500 mg + IBR 420 mg | Part 2, Arm B MCL: DUR 1500 mg + IBR 560 mg | Part 2, Arm C FL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Part 2 Arm C DLBCL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Part 2, Arm C CLL/SLL: DUR + RIT 375 mg/m² + BEN 70 mg/m² | Part 2, Arm D FL: DUR 1500 mg | Part 2, Arm D DLBCL: DUR 1500 mg | Part 2, Arm D CLL/SLL: DUR 1500 mg | Part 2, Arm D MCL: DUR 1500 mg | Part 2 Arm D HL: DUR 1500 mg |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Arm/Group Description | Participants 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 Participants | 3 | 3 | 8 | 3 | 4 | 3 | 1 | 4 | 5 | 10 | 10 | 10 | 10 | 5 | 5 | 10 | 2 | 5 | 5 |
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%
|
Title | Overall Response Rate (ORR) During Durvalumab Treatment |
---|---|
Description | 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). |
Time Frame | Up 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 Title | Part 1, Arm A: DUR 1500 mg + LEN 20 mg | Part 1, Arm A: DUR 1500 mg + LEN 20 mg + RIT 375 mg/m² | Part 1, Arm A: DUR 1500 mg + LEN 10 mg + RIT 375 mg/m² | Part 1, Arm B: DUR 1500 mg + IBR 420 mg | Part 1, Arm B: DUR 1500 mg + IBR 560 mg | 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 | Part 2, Arm B CLL/SLL: DUR 1500 mg + IBR 420 mg | Part 2, Arm B MCL: DUR 1500 mg + IBR 560 mg | Part 2, Arm C FL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Part 2 Arm C DLBCL: DUR + RIT 375 mg/m² + BEN 70 mg/m² | Part 2, Arm C CLL/SLL: DUR + RIT 375 mg/m² + BEN 70 mg/m² | Part 2, Arm D FL: DUR 1500 mg | Part 2, Arm D DLBCL: DUR 1500 mg | Part 2, Arm D CLL/SLL: DUR 1500 mg | Part 2, Arm D MCL: DUR 1500 mg | Part 2 Arm D HL: DUR 1500 mg |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Arm/Group Description | Participants 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 Participants | 3 | 3 | 5 | 3 | 4 | 3 | 0 | 4 | 4 | 9 | 10 | 9 | 10 | 4 | 5 | 10 | 2 | 5 | 5 |
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%
|
Title | Overall Response Rate During the Entire Study |
---|---|
Description | 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). |
Time Frame | 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. |
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 Title | Part 1, Arm A: DUR 1500 mg + LEN 20 mg | Part 1, Arm A: DUR 1500 mg + LEN 20 mg + RIT 375 mg/m² | Part 1, Arm A: DUR 1500 mg + LEN 10 mg + RIT 375 mg/m² | Part 1, Arm B: DUR 1500 mg + IBR 420 mg | Part 1, Arm B: DUR 1500 mg + IBR 560 mg | 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 | Part 2, Arm B CLL/SLL: DUR 1500 mg + IBR 420 mg | Part 2, Arm B MCL: DUR 1500 mg + IBR 560 mg | Part 2, Arm C FL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Part 2 Arm C DLBCL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Part 2, Arm C CLL/SLL: DUR + RIT 375 mg/m² + BEN 70 mg/m² | Part 2, Arm D FL: DUR 1500 mg | Part 2, Arm D DLBCL: DUR 1500 mg | Part 2, Arm D CLL/SLL: DUR 1500 mg | Part 2, Arm D MCL: DUR 1500 mg | Part 2 Arm D HL: DUR 1500 mg |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Arm/Group Description | Participants 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 Participants | 3 | 3 | 5 | 3 | 4 | 3 | 0 | 4 | 4 | 9 | 10 | 9 | 10 | 4 | 5 | 10 | 2 | 5 | 5 |
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%
|
Title | Time to First Response |
---|---|
Description | 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). |
Time Frame | 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. |
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 Title | Part 1, Arm A: DUR 1500 mg + LEN 20 mg | Part 1, Arm A: DUR 1500 mg + LEN 20 mg + RIT 375 mg/m² | Part 1, Arm A: DUR 1500 mg + LEN 10 mg + RIT 375 mg/m² | Part 1, Arm B: DUR 1500 mg + IBR 420 mg | Part 1, Arm B: DUR 1500 mg + IBR 560 mg | 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 | Part 2, Arm B CLL/SLL: DUR 1500 mg + IBR 420 mg | Part 2, Arm B MCL: DUR 1500 mg + IBR 560 mg | Part 2, Arm C FL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Part 2 Arm C DLBCL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Part 2, Arm C CLL/SLL: DUR + RIT 375 mg/m² + BEN 70 mg/m² | Part 2, Arm D FL: DUR 1500 mg | Part 2, Arm D DLBCL: DUR 1500 mg | Part 2, Arm D CLL/SLL: DUR 1500 mg | Part 2, Arm D MCL: DUR 1500 mg | Part 2 Arm D HL: DUR 1500 mg |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Arm/Group Description | Participants 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 Participants | 2 | 2 | 4 | 2 | 3 | 1 | 0 | 2 | 0 | 9 | 7 | 8 | 3 | 2 | 0 | 0 | 0 | 0 | 1 |
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
|
Title | Kaplan-Meier Estimate of Duration of Response |
---|---|
Description | 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. |
Time Frame | 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. |
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 Title | Part 1, Arm A: DUR 1500 mg + LEN 20 mg | Part 1, Arm A: DUR 1500 mg + LEN 20 mg + RIT 375 mg/m² | Part 1, Arm A: DUR 1500 mg + LEN 10 mg + RIT 375 mg/m² | Part 1, Arm B: DUR 1500 mg + IBR 420 mg | Part 1, Arm B: DUR 1500 mg + IBR 560 mg | 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 | Part 2, Arm B CLL/SLL: DUR 1500 mg + IBR 420 mg | Part 2, Arm B MCL: DUR 1500 mg + IBR 560 mg | Part 2, Arm C FL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Part 2 Arm C DLBCL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Part 2, Arm C CLL/SLL: DUR + RIT 375 mg/m² + BEN 70 mg/m² | Part 2, Arm D FL: DUR 1500 mg | Part 2, Arm D DLBCL: DUR 1500 mg | Part 2, Arm D CLL/SLL: DUR 1500 mg | Part 2, Arm D MCL: DUR 1500 mg | Part 2 Arm D HL: DUR 1500 mg |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Arm/Group Description | Participants 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 Participants | 2 | 2 | 4 | 2 | 3 | 1 | 0 | 2 | 0 | 9 | 7 | 8 | 3 | 2 | 0 | 0 | 0 | 0 | 1 |
Median (95% Confidence Interval) [weeks] |
10.14
|
NA
|
NA
|
NA
|
NA
|
29.29
|
NA
|
NA
|
NA
|
NA
|
24.14
|
NA
|
11.14
|
Title | Kaplan-Meier Estimate of Progression-free Survival (PFS) |
---|---|
Description | 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. |
Time Frame | 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. |
Outcome Measure Data
Analysis Population Description |
---|
Safety population |
Arm/Group Title | Part 1, Arm A: DUR 1500 mg + LEN 20 mg | Part 1, Arm A: DUR 1500 mg + LEN 20 mg + RIT 375 mg/m² | Part 1, Arm A: DUR 1500 mg + LEN 10 mg + RIT 375 mg/m² | Part 1, Arm B: DUR 1500 mg + IBR 420 mg | Part 1, Arm B: DUR 1500 mg + IBR 560 mg | 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 | Part 2, Arm B CLL/SLL: DUR 1500 mg + IBR 420 mg | Part 2, Arm B MCL: DUR 1500 mg + IBR 560 mg | Part 2, Arm C FL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Part 2 Arm C DLBCL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Part 2, Arm C CLL/SLL: DUR + RIT 375 mg/m² + BEN 70 mg/m² | Part 2, Arm D FL: DUR 1500 mg | Part 2, Arm D DLBCL: DUR 1500 mg | Part 2, Arm D CLL/SLL: DUR 1500 mg | Part 2, Arm D MCL: DUR 1500 mg | Part 2 Arm D HL: DUR 1500 mg |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Arm/Group Description | Participants 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 Participants | 3 | 3 | 8 | 3 | 4 | 3 | 1 | 4 | 5 | 10 | 10 | 10 | 10 | 5 | 5 | 10 | 2 | 5 | 5 |
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
|
Title | Maximum Observed Plasma Concentration (Cmax) of Durvalumab |
---|---|
Description | |
Time Frame | 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. |
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 Title | Arm A: Durvalumab + Lenalidomide ± Rituximab | Arm B: Durvalumab + Ibrutinib | Arm C: Durvalumab + Bendamustine ± Rituximab | Arm D: Durvalumab Monotherapy |
---|---|---|---|---|
Arm/Group Description | Participants 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 Participants | 14 | 27 | 38 | 26 |
Geometric Mean (Geometric Coefficient of Variation) [μg/L] |
420264.066
(22.7)
|
361906.229
(30.1)
|
331572.478
(33.4)
|
392663.668
(41.1)
|
Title | Time to Maximum Plasma Concentration (Tmax) of Durvalumab |
---|---|
Description | |
Time Frame | 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. |
Outcome Measure Data
Analysis Population Description |
---|
PK population |
Arm/Group Title | Arm A: Durvalumab + Lenalidomide ± Rituximab | Arm B: Durvalumab + Ibrutinib | Arm C: Durvalumab + Bendamustine ± Rituximab | Arm D: Durvalumab Monotherapy |
---|---|---|---|---|
Arm/Group Description | Participants 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 Participants | 14 | 27 | 38 | 26 |
Median (Full Range) [days] |
0.0510
|
0.0479
|
0.0510
|
0.0420
|
Title | Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUClast) of Durvalumab |
---|---|
Description | |
Time Frame | 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. |
Outcome Measure Data
Analysis Population Description |
---|
The PK population |
Arm/Group Title | Arm A: Durvalumab + Lenalidomide ± Rituximab | Arm B: Durvalumab + Ibrutinib | Arm C: Durvalumab + Bendamustine ± Rituximab | Arm D: Durvalumab Monotherapy |
---|---|---|---|---|
Arm/Group Description | Participants 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 Participants | 14 | 27 | 38 | 26 |
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)
|
Title | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUCinf) of Durvalumab |
---|---|
Description | |
Time Frame | 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. |
Outcome Measure Data
Analysis Population Description |
---|
The PK population |
Arm/Group Title | Arm A: Durvalumab + Lenalidomide ± Rituximab | Arm B: Durvalumab + Ibrutinib | Arm C: Durvalumab + Bendamustine ± Rituximab | Arm D: Durvalumab Monotherapy |
---|---|---|---|---|
Arm/Group Description | Participants 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 Participants | 14 | 27 | 38 | 25 |
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)
|
Title | Terminal Elimination Phase Half-Life (t½) of Durvalumab |
---|---|
Description | |
Time Frame | 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. |
Outcome Measure Data
Analysis Population Description |
---|
The PK population |
Arm/Group Title | Arm A: Durvalumab + Lenalidomide ± Rituximab | Arm B: Durvalumab + Ibrutinib | Arm C: Durvalumab + Bendamustine ± Rituximab | Arm D: Durvalumab Monotherapy |
---|---|---|---|---|
Arm/Group Description | Participants 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 Participants | 14 | 27 | 38 | 25 |
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)
|
Title | Clearance (CL) of Durvalumab |
---|---|
Description | |
Time Frame | 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. |
Outcome Measure Data
Analysis Population Description |
---|
The PK population |
Arm/Group Title | Arm A: Durvalumab + Lenalidomide ± Rituximab | Arm B: Durvalumab + Ibrutinib | Arm C: Durvalumab + Bendamustine ± Rituximab | Arm D: Durvalumab Monotherapy |
---|---|---|---|---|
Arm/Group Description | Participants 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 Participants | 14 | 27 | 38 | 25 |
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)
|
Title | Volume of Distribution (Vz) of Durvalumab |
---|---|
Description | |
Time Frame | 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. |
Outcome Measure Data
Analysis Population Description |
---|
The PK population |
Arm/Group Title | Arm A: Durvalumab + Lenalidomide ± Rituximab | Arm B: Durvalumab + Ibrutinib | Arm C: Durvalumab + Bendamustine ± Rituximab | Arm D: Durvalumab Monotherapy |
---|---|---|---|---|
Arm/Group Description | Participants 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 Participants | 14 | 27 | 38 | 25 |
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)
|
Title | Maximum Observed Plasma Concentration (Cmax) of Lenalidomide |
---|---|
Description | |
Time Frame | 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. |
Outcome Measure Data
Analysis Population Description |
---|
PK population with available data at each time point |
Arm/Group Title | Arm A: Lenalidomide 10 mg | Arm A: Lenalidomide 20 mg |
---|---|---|
Arm/Group Description | Participants 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 Participants | 5 | 4 |
Cycle 1 Day 1 |
141.881
(22.0)
|
309.917
(6.9)
|
Cycle 1 Day 15 |
107.635
(40.9)
|
174.090
|
Title | Time to Maximum Observed Plasma Concentration (Tmax) of Lenalidomide |
---|---|
Description | |
Time Frame | 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. |
Outcome Measure Data
Analysis Population Description |
---|
PK population with available data at each time point |
Arm/Group Title | Arm A: Lenalidomide 10 mg | Arm A: Lenalidomide 20 mg |
---|---|---|
Arm/Group Description | Participants 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 Participants | 5 | 4 |
Cycle 1 Day 1 |
1.9500
|
1.1667
|
Cycle 1 Day 15 |
3.0333
|
1.000
|
Title | Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUClast) of Lenalidomide |
---|---|
Description | |
Time Frame | Cycle 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 Title | Arm A: Lenalidomide 10 mg | Arm A: Lenalidomide 20 mg |
---|---|---|
Arm/Group Description | Participants 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 Participants | 5 | 4 |
Geometric Least Squares Mean (Geometric Coefficient of Variation) [h*ng/mL] |
789.297
(84.3)
|
805.299
(56.0)
|
Title | Maximum Observed Plasma Concentration (Cmax) of Ibrutinib |
---|---|
Description | |
Time Frame | 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. |
Outcome Measure Data
Analysis Population Description |
---|
PK population with available data at each time point |
Arm/Group Title | Arm B: Ibrutinib 420 mg | Arm B: Ibrutinib 560 mg |
---|---|---|
Arm/Group Description | Participants 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 Participants | 13 | 13 |
Cycle 1 Day 1 |
129.704
(98.0)
|
67.728
(197.9)
|
Cycle 1 Day 15 |
86.840
(136.9)
|
72.436
(166.3)
|
Title | Time to Maximum Observed Plasma Concentration (Tmax) of Ibrutinib |
---|---|
Description | |
Time Frame | 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. |
Outcome Measure Data
Analysis Population Description |
---|
PK population with available data at each time point |
Arm/Group Title | Arm B: Ibrutinib 420 mg | Arm B: Ibrutinib 560 mg |
---|---|---|
Arm/Group Description | Participants 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 Participants | 13 | 13 |
Cycle 1 Day 1 |
2.000
|
1.9333
|
Cycle 1 Day 15 |
1.8833
|
2.000
|
Title | Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUClast) of Ibrutinib |
---|---|
Description | |
Time Frame | Cycle 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 Title | Arm B: Ibrutinib 420 mg | Arm B: Ibrutinib 560 mg |
---|---|---|
Arm/Group Description | Participants 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 Participants | 13 | 13 |
Geometric Least Squares Mean (Geometric Coefficient of Variation) [h*ng/mL] |
586.396
(117.2)
|
436.855
(246.5)
|
Title | Change From Baseline in Soluble Programmed Cell Death Ligand-1 (sPD-L1) Concentration |
---|---|
Description | 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). |
Time Frame | Baseline (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 Title | Part 1, Arm A: DUR 1500 mg + LEN 20 mg | Part 1, Arm A: DUR 1500 mg + LEN 20 mg + RIT 375 mg/m² | Part 1, Arm A: DUR 1500 mg + LEN 10 mg + RIT 375 mg/m² | Part 1, Arm B: DUR 1500 mg + IBR 420 mg | Part 1, Arm B: DUR 1500 mg + IBR 560 mg | 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 | Part 2, Arm B CLL/SLL: DUR 1500 mg + IBR 420 mg | Part 2, Arm B MCL: DUR 1500 mg + IBR 560 mg | Part 2, Arm C FL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Part 2 Arm C DLBCL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Part 2, Arm C CLL/SLL: DUR + RIT 375 mg/m² + BEN 70 mg/m² | Part 2, Arm D FL: DUR 1500 mg | Part 2, Arm D DLBCL: DUR 1500 mg | Part 2, Arm D CLL/SLL: DUR 1500 mg | Part 2, Arm D MCL: DUR 1500 mg | Part 2 Arm D HL: DUR 1500 mg |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Arm/Group Description | Participants 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 Participants | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Adverse Events
Time Frame | 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. 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. | |||||||||||||||||||||||||||||||||||||
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Adverse Event Reporting Description | ||||||||||||||||||||||||||||||||||||||
Arm/Group Title | Part 1, Arm A: DUR 1500 mg + LEN 20 mg | Part 1, Arm A: DUR 1500 mg + LEN 20 mg + RIT 375 mg/m² | Part 1, Arm A: DUR 1500 mg + LEN 10 mg + RIT 375 mg/m² | Part 1, Arm B: DUR 1500 mg + IBR 420 mg | Part 1, Arm B: DUR 1500 mg + IBR 560 mg | 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 | Part 2, Arm B CLL/SLL: DUR 1500 mg + IBR 420 mg | Part 2, Arm B MCL: DUR 1500 mg + IBR 560 mg | Part 2, Arm C FL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Part 2 Arm C DLBCL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Part 2, Arm C CLL/SLL: DUR + RIT 375 mg/m² + BEN 70 mg/m² | Part 2, Arm D FL: DUR 1500 mg | Part 2, Arm D DLBCL: DUR 1500 mg | Part 2, Arm D CLL/SLL: DUR 1500 mg | Part 2, Arm D MCL: DUR 1500 mg | Part 2, Arm D hL: DUR 1500 mg | |||||||||||||||||||
Arm/Group Description | Participants 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 reason | Participants 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 |
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Part 1, Arm A: DUR 1500 mg + LEN 20 mg | Part 1, Arm A: DUR 1500 mg + LEN 20 mg + RIT 375 mg/m² | Part 1, Arm A: DUR 1500 mg + LEN 10 mg + RIT 375 mg/m² | Part 1, Arm B: DUR 1500 mg + IBR 420 mg | Part 1, Arm B: DUR 1500 mg + IBR 560 mg | 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 | Part 2, Arm B CLL/SLL: DUR 1500 mg + IBR 420 mg | Part 2, Arm B MCL: DUR 1500 mg + IBR 560 mg | Part 2, Arm C FL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Part 2 Arm C DLBCL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Part 2, Arm C CLL/SLL: DUR + RIT 375 mg/m² + BEN 70 mg/m² | Part 2, Arm D FL: DUR 1500 mg | Part 2, Arm D DLBCL: DUR 1500 mg | Part 2, Arm D CLL/SLL: DUR 1500 mg | Part 2, Arm D MCL: DUR 1500 mg | Part 2, Arm D hL: DUR 1500 mg | ||||||||||||||||||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 1/3 (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 |
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Part 1, Arm A: DUR 1500 mg + LEN 20 mg | Part 1, Arm A: DUR 1500 mg + LEN 20 mg + RIT 375 mg/m² | Part 1, Arm A: DUR 1500 mg + LEN 10 mg + RIT 375 mg/m² | Part 1, Arm B: DUR 1500 mg + IBR 420 mg | Part 1, Arm B: DUR 1500 mg + IBR 560 mg | 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 | Part 2, Arm B CLL/SLL: DUR 1500 mg + IBR 420 mg | Part 2, Arm B MCL: DUR 1500 mg + IBR 560 mg | Part 2, Arm C FL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Part 2 Arm C DLBCL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Part 2, Arm C CLL/SLL: DUR + RIT 375 mg/m² + BEN 70 mg/m² | Part 2, Arm D FL: DUR 1500 mg | Part 2, Arm D DLBCL: DUR 1500 mg | Part 2, Arm D CLL/SLL: DUR 1500 mg | Part 2, Arm D MCL: DUR 1500 mg | Part 2, Arm D hL: DUR 1500 mg | ||||||||||||||||||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 1/3 (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 | ||||||||||||||||||||||||||||||||||||||
Anaemia | 0/3 (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%) | |||||||||||||||||||
Cytopenia | 0/3 (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 neutropenia | 1/3 (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%) | |||||||||||||||||||
Neutropenia | 0/3 (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%) | |||||||||||||||||||
Pancytopenia | 0/3 (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%) | |||||||||||||||||||
Thrombocytopenia | 0/3 (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 syndrome | 0/3 (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 fibrillation | 0/3 (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 failure | 0/3 (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 infarction | 0/3 (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 insufficiency | 0/3 (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 pain | 0/3 (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 haematoma | 0/3 (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%) | |||||||||||||||||||
Aptyalism | 0/3 (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 dysplasia | 0/3 (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%) | |||||||||||||||||||
Diarrhoea | 0/3 (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 haemorrhage | 0/3 (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 perforation | 0/3 (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%) | |||||||||||||||||||
Haematemesis | 0/3 (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 haemorrhage | 0/3 (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 haemorrhage | 0/3 (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 obstruction | 0/3 (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%) | |||||||||||||||||||
Vomiting | 0/3 (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 | ||||||||||||||||||||||||||||||||||||||
Asthenia | 0/3 (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 deterioration | 0/3 (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 oedema | 0/3 (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%) | |||||||||||||||||||
Malaise | 0/3 (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 syndrome | 0/3 (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%) | |||||||||||||||||||
Pain | 0/3 (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%) | |||||||||||||||||||
Pyrexia | 0/3 (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 | ||||||||||||||||||||||||||||||||||||||
Hepatitis | 0/3 (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%) | |||||||||||||||||||
Hyperbilirubinaemia | 0/3 (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 syndrome | 0/3 (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 | ||||||||||||||||||||||||||||||||||||||
Bronchiolitis | 0/3 (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%) | |||||||||||||||||||
Bronchitis | 0/3 (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 viral | 0/3 (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%) | |||||||||||||||||||
Cellulitis | 0/3 (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 infection | 0/3 (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%) | |||||||||||||||||||
Influenza | 0/3 (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 infection | 0/3 (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 viral | 0/3 (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 infection | 0/3 (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 sepsis | 0/3 (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 infection | 0/3 (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 bacterial | 0/3 (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%) | |||||||||||||||||||
Pneumonia | 0/3 (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%) | |||||||||||||||||||
Sepsis | 0/3 (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 shock | 0/3 (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%) | |||||||||||||||||||
Sinusitis | 0/3 (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 infection | 0/3 (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 infection | 0/3 (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 increased | 0/3 (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 prolonged | 0/3 (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 abnormal | 0/3 (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 | ||||||||||||||||||||||||||||||||||||||
Dehydration | 0/3 (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%) | |||||||||||||||||||
Hyponatraemia | 0/3 (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 pain | 0/3 (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 carcinoma | 0/3 (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 cancer | 0/3 (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 lung | 0/3 (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 ischaemia | 0/3 (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%) | |||||||||||||||||||
Syncope | 0/3 (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 injury | 0/3 (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 | ||||||||||||||||||||||||||||||||||||||
Dyspnoea | 0/3 (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 pneumonia | 0/3 (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 effusion | 0/3 (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%) | |||||||||||||||||||
Pneumonitis | 0/3 (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 embolism | 0/3 (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 symptoms | 0/3 (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 | ||||||||||||||||||||||||||||||||||||||
Hypotension | 0/3 (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 thrombosis | 0/3 (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 syndrome | 0/3 (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 mg | Part 1, Arm A: DUR 1500 mg + LEN 20 mg + RIT 375 mg/m² | Part 1, Arm A: DUR 1500 mg + LEN 10 mg + RIT 375 mg/m² | Part 1, Arm B: DUR 1500 mg + IBR 420 mg | Part 1, Arm B: DUR 1500 mg + IBR 560 mg | 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 | Part 2, Arm B CLL/SLL: DUR 1500 mg + IBR 420 mg | Part 2, Arm B MCL: DUR 1500 mg + IBR 560 mg | Part 2, Arm C FL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Part 2 Arm C DLBCL: DUR 1500 mg + RIT 375 mg/m² + BEN 70 mg/m² | Part 2, Arm C CLL/SLL: DUR + RIT 375 mg/m² + BEN 70 mg/m² | Part 2, Arm D FL: DUR 1500 mg | Part 2, Arm D DLBCL: DUR 1500 mg | Part 2, Arm D CLL/SLL: DUR 1500 mg | Part 2, Arm D MCL: DUR 1500 mg | Part 2, Arm D hL: DUR 1500 mg | ||||||||||||||||||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 3/3 (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 | ||||||||||||||||||||||||||||||||||||||
Anaemia | 2/3 (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 failure | 0/3 (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%) | |||||||||||||||||||
Eosinophilia | 0/3 (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 neutropenia | 0/3 (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 anaemia | 0/3 (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 purpura | 0/3 (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 bruise | 0/3 (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%) | |||||||||||||||||||
Leukopenia | 0/3 (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%) | |||||||||||||||||||
Lymphopenia | 0/3 (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%) | |||||||||||||||||||
Neutropenia | 1/3 (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%) | |||||||||||||||||||
Pancytopenia | 0/3 (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%) | |||||||||||||||||||
Thrombocytopenia | 0/3 (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 fibrillation | 0/3 (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%) | |||||||||||||||||||
Palpitations | 0/3 (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 disease | 1/3 (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 bradycardia | 0/3 (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 tachycardia | 0/3 (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 tachycardia | 0/3 (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%) | |||||||||||||||||||
Tachycardia | 0/3 (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 | ||||||||||||||||||||||||||||||||||||||
Epidermolysis | 0/3 (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 discomfort | 0/3 (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 pain | 0/3 (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%) | |||||||||||||||||||
Hypoacusis | 0/3 (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%) | |||||||||||||||||||
Tinnitus | 0/3 (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%) | |||||||||||||||||||
Vertigo | 0/3 (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 | ||||||||||||||||||||||||||||||||||||||
Hyperthyroidism | 0/3 (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%) | |||||||||||||||||||
Hypothyroidism | 0/3 (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%) | |||||||||||||||||||
Thyroiditis | 0/3 (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 glaucoma | 0/3 (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%) | |||||||||||||||||||
Blepharitis | 0/3 (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%) | |||||||||||||||||||
Cataract | 0/3 (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 haemorrhage | 0/3 (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 oedema | 0/3 (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 allergic | 0/3 (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 eye | 0/3 (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 disorder | 0/3 (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 ptosis | 0/3 (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%) | |||||||||||||||||||
Iritis | 0/3 (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 oedema | 0/3 (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 hypertensive | 0/3 (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 blurred | 0/3 (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 impairment | 0/3 (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 detachment | 0/3 (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 floaters | 0/3 (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 haemorrhage | 0/3 (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 discomfort | 0/3 (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 distension | 0/3 (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 pain | 0/3 (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 upper | 0/3 (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 haematoma | 0/3 (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 fissure | 0/3 (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%) | |||||||||||||||||||
Ascites | 0/3 (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%) | |||||||||||||||||||
Constipation | 3/3 (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 caries | 0/3 (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%) | |||||||||||||||||||
Diarrhoea | 1/3 (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 mouth | 1/3 (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%) | |||||||||||||||||||
Dyspepsia | 0/3 (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%) | |||||||||||||||||||
Dysphagia | 0/3 (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%) | |||||||||||||||||||
Eructation | 0/3 (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%) | |||||||||||||||||||
Flatulence | 0/3 (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%) | |||||||||||||||||||
Gastritis | 0/3 (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 haemorrhage | 0/3 (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 disease | 1/3 (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 pain | 0/3 (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%) | |||||||||||||||||||
Haematemesis | 0/3 (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%) | |||||||||||||||||||
Haemorrhoids | 0/3 (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 dry | 0/3 (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 haematoma | 0/3 (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 ulceration | 0/3 (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%) | |||||||||||||||||||
Nausea | 1/3 (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 pain | 0/3 (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 pain | 0/3 (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%) | |||||||||||||||||||
Proctalgia | 0/3 (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 haemorrhage | 1/3 (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%) | |||||||||||||||||||
Stomatitis | 0/3 (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%) | |||||||||||||||||||
Toothache | 0/3 (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 haemorrhage | 0/3 (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%) | |||||||||||||||||||
Vomiting | 0/3 (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 | ||||||||||||||||||||||||||||||||||||||
Asthenia | 1/3 (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%) | |||||||||||||||||||
Chills | 0/3 (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%) | |||||||||||||||||||
Discomfort | 0/3 (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 satiety | 1/3 (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 oedema | 0/3 (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%) | |||||||||||||||||||
Fatigue | 2/3 (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 disturbance | 0/3 (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 deterioration | 0/3 (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 oedema | 0/3 (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%) | |||||||||||||||||||
Inflammation | 0/3 (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 illness | 0/3 (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 bruising | 0/3 (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 oedema | 0/3 (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%) | |||||||||||||||||||
Malaise | 0/3 (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 inflammation | 0/3 (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%) | |||||||||||||||||||
Nodule | 0/3 (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 pain | 0/3 (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 peripheral | 0/3 (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%) | |||||||||||||||||||
Pain | 1/3 (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 swelling | 0/3 (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%) | |||||||||||||||||||
Pneumatosis | 0/3 (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%) | |||||||||||||||||||
Pyrexia | 1/3 (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 intolerance | 0/3 (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 | ||||||||||||||||||||||||||||||||||||||
Cholestasis | 0/3 (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%) | |||||||||||||||||||
Hepatitis | 0/3 (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 injury | 0/3 (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%) | |||||||||||||||||||
Hypertransaminasaemia | 0/3 (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 cholestatic | 0/3 (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 icterus | 0/3 (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 hypersensitivity | 0/3 (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%) | |||||||||||||||||||
Hypogammaglobulinaemia | 0/3 (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%) | |||||||||||||||||||
Immunodeficiency | 0/3 (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 allergy | 0/3 (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 sepsis | 0/3 (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%) | |||||||||||||||||||
Bronchiolitis | 0/3 (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%) | |||||||||||||||||||
Bronchitis | 0/3 (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 sinusitis | 0/3 (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 | 0/3 (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%) | |||||||||||||||||||
Cystitis | 0/3 (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 infection | 0/3 (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 infection | 0/3 (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 infectious | 0/3 (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 infection | 0/3 (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%) | |||||||||||||||||||
Folliculitis | 0/3 (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%) | |||||||||||||||||||
Gastroenteritis | 0/3 (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 viral | 1/3 (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 ophthalmic | 0/3 (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 simplex | 0/3 (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 infection | 0/3 (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 zoster | 0/3 (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%) | |||||||||||||||||||
Hordeolum | 0/3 (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 infection | 0/3 (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%) | |||||||||||||||||||
Influenza | 0/3 (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%) | |||||||||||||||||||
Laryngitis | 0/3 (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 infection | 0/3 (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 infection | 0/3 (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 infection | 0/3 (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 infection | 0/3 (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%) | |||||||||||||||||||
Nasopharyngitis | 0/3 (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 candidiasis | 0/3 (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 infection | 1/3 (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 media | 0/3 (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 acute | 0/3 (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%) | |||||||||||||||||||
Paronychia | 0/3 (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%) | |||||||||||||||||||
Pharyngitis | 0/3 (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%) | |||||||||||||||||||
Pneumonia | 0/3 (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 pseudomonal | 0/3 (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 infection | 0/3 (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 infection | 0/3 (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%) | |||||||||||||||||||
Rhinitis | 0/3 (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 infection | 0/3 (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%) | |||||||||||||||||||
Sepsis | 0/3 (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%) | |||||||||||||||||||
Sinusitis | 0/3 (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 infection | 0/3 (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 sepsis | 0/3 (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%) | |||||||||||||||||||
Tonsillitis | 0/3 (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 infection | 0/3 (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 infection | 1/3 (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 infection | 0/3 (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 viral | 0/3 (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 infection | 0/3 (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 reaction | 0/3 (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 bite | 0/3 (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%) | |||||||||||||||||||
Contusion | 0/3 (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 contusion | 0/3 (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%) | |||||||||||||||||||
Fall | 0/3 (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 fracture | 0/3 (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 reaction | 0/3 (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 dislocation | 0/3 (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 injury | 0/3 (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%) | |||||||||||||||||||
Laceration | 0/3 (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 sprain | 0/3 (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%) | |||||||||||||||||||
Overdose | 0/3 (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 pain | 0/3 (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 haematoma | 0/3 (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 burn | 0/3 (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 fracture | 0/3 (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 reaction | 0/3 (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%) | |||||||||||||||||||
Wound | 0/3 (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 increased | 0/3 (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 increased | 0/3 (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 increased | 0/3 (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 increased | 0/3 (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 increased | 0/3 (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 increased | 0/3 (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 increased | 0/3 (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 increased | 0/3 (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 increased | 0/3 (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 present | 0/3 (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 increased | 0/3 (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 irregular | 0/3 (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 decreased | 0/3 (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 increased | 0/3 (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 increased | 0/3 (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 decreased | 1/3 (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 increased | 0/3 (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 increased | 0/3 (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 decreased | 0/3 (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 decreased | 1/3 (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 positive | 0/3 (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 decreased | 0/3 (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 decreased | 1/3 (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 increased | 0/3 (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 decreased | 1/3 (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 appetite | 2/3 (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%) | |||||||||||||||||||
Dehydration | 0/3 (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%) | |||||||||||||||||||
Gout | 0/3 (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%) | |||||||||||||||||||
Hypercalcaemia | 0/3 (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%) | |||||||||||||||||||
Hyperglycaemia | 0/3 (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%) | |||||||||||||||||||
Hyperkalaemia | 1/3 (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%) | |||||||||||||||||||
Hyperlactacidaemia | 0/3 (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%) | |||||||||||||||||||
Hypertriglyceridaemia | 0/3 (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%) | |||||||||||||||||||
Hyperuricaemia | 0/3 (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%) | |||||||||||||||||||
Hypoalbuminaemia | 0/3 (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%) | |||||||||||||||||||
Hypocalcaemia | 1/3 (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%) | |||||||||||||||||||
Hypoglycaemia | 0/3 (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%) | |||||||||||||||||||
Hypokalaemia | 1/3 (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%) | |||||||||||||||||||
Hypomagnesaemia | 0/3 (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%) | |||||||||||||||||||
Hyponatraemia | 0/3 (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%) | |||||||||||||||||||
Hypophosphataemia | 0/3 (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%) | |||||||||||||||||||
Polydipsia | 0/3 (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 syndrome | 0/3 (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 | ||||||||||||||||||||||||||||||||||||||
Arthralgia | 0/3 (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%) | |||||||||||||||||||
Arthritis | 0/3 (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 pain | 1/3 (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 pain | 0/3 (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 pain | 0/3 (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 pain | 0/3 (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 degeneration | 1/3 (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 disorder | 0/3 (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 noise | 0/3 (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 swelling | 0/3 (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 mass | 0/3 (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 spasms | 1/3 (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 weakness | 0/3 (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 pain | 0/3 (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 discomfort | 0/3 (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 pain | 0/3 (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 stiffness | 0/3 (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%) | |||||||||||||||||||
Myalgia | 2/3 (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 pain | 1/3 (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 extremity | 1/3 (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 jaw | 0/3 (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%) | |||||||||||||||||||
Periarthritis | 1/3 (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 syndrome | 0/3 (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 cyst | 0/3 (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 pain | 0/3 (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 flare | 0/3 (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 | ||||||||||||||||||||||||||||||||||||||
Amnesia | 0/3 (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%) | |||||||||||||||||||
Aphasia | 0/3 (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 consciousness | 0/3 (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%) | |||||||||||||||||||
Dizziness | 1/3 (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%) | |||||||||||||||||||
Dysaesthesia | 0/3 (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%) | |||||||||||||||||||
Dysgeusia | 0/3 (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%) | |||||||||||||||||||
Headache | 1/3 (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%) | |||||||||||||||||||
Hypoaesthesia | 0/3 (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%) | |||||||||||||||||||
Lethargy | 0/3 (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 impairment | 0/3 (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%) | |||||||||||||||||||
Migraine | 0/3 (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%) | |||||||||||||||||||
Paraesthesia | 0/3 (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 neuropathy | 1/3 (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%) | |||||||||||||||||||
Sciatica | 0/3 (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%) | |||||||||||||||||||
Somnolence | 0/3 (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%) | |||||||||||||||||||
Syncope | 0/3 (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%) | |||||||||||||||||||
Tremor | 0/3 (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 | ||||||||||||||||||||||||||||||||||||||
Anxiety | 0/3 (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%) | |||||||||||||||||||
Apathy | 0/3 (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 disorder | 0/3 (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 state | 0/3 (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%) | |||||||||||||||||||
Depression | 0/3 (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%) | |||||||||||||||||||
Disorientation | 0/3 (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%) | |||||||||||||||||||
Insomnia | 0/3 (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%) | |||||||||||||||||||
Irritability | 0/3 (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 attack | 0/3 (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 injury | 0/3 (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 haemorrhagic | 0/3 (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%) | |||||||||||||||||||
Dysuria | 0/3 (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%) | |||||||||||||||||||
Haematuria | 0/3 (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 urgency | 0/3 (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%) | |||||||||||||||||||
Pollakiuria | 0/3 (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 failure | 2/3 (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 impairment | 0/3 (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%) | |||||||||||||||||||
Ureterolithiasis | 0/3 (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 incontinence | 0/3 (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 pain | 0/3 (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 hyperplasia | 0/3 (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 pain | 0/3 (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 oedema | 0/3 (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 haemorrhage | 0/3 (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 cough | 0/3 (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%) | |||||||||||||||||||
Asthma | 0/3 (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 disease | 0/3 (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%) | |||||||||||||||||||
Cough | 1/3 (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%) | |||||||||||||||||||
Dysphonia | 0/3 (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%) | |||||||||||||||||||
Dyspnoea | 1/3 (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 exertional | 0/3 (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%) | |||||||||||||||||||
Epistaxis | 0/3 (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%) | |||||||||||||||||||
Hiccups | 0/3 (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%) | |||||||||||||||||||
Hypoxia | 0/3 (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 inflammation | 0/3 (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 congestion | 0/3 (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 dryness | 0/3 (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 obstruction | 0/3 (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 pain | 1/3 (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 erythema | 0/3 (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 effusion | 0/3 (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 pain | 0/3 (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 aspiration | 0/3 (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 cough | 0/3 (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 oedema | 0/3 (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%) | |||||||||||||||||||
Rales | 0/3 (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 congestion | 1/3 (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 disorder | 0/3 (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 pain | 0/3 (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%) | |||||||||||||||||||
Tachypnoea | 0/3 (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 inflammation | 0/3 (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 syndrome | 0/3 (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%) | |||||||||||||||||||
Wheezing | 0/3 (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 | ||||||||||||||||||||||||||||||||||||||
Alopecia | 0/3 (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 ulcer | 0/3 (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 acneiform | 0/3 (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 contact | 0/3 (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 generalised | 0/3 (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 skin | 0/3 (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%) | |||||||||||||||||||
Ecchymosis | 0/3 (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 asteatotic | 0/3 (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 nummular | 0/3 (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%) | |||||||||||||||||||
Erythema | 0/3 (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%) | |||||||||||||||||||
Hyperhidrosis | 0/3 (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%) | |||||||||||||||||||
Hyperkeratosis | 0/3 (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%) | |||||||||||||||||||
Neurodermatitis | 0/3 (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 sweats | 0/3 (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%) | |||||||||||||||||||
Onychoclasis | 0/3 (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%) | |||||||||||||||||||
Petechiae | 0/3 (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%) | |||||||||||||||||||
Pruritus | 1/3 (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 generalised | 0/3 (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%) | |||||||||||||||||||
Psoriasis | 0/3 (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%) | |||||||||||||||||||
Purpura | 0/3 (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%) | |||||||||||||||||||
Rash | 0/3 (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 generalised | 0/3 (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 macular | 0/3 (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-papular | 0/3 (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 pruritic | 0/3 (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 fissures | 0/3 (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 lesion | 0/3 (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%) | |||||||||||||||||||
Urticaria | 0/3 (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 stenosis | 0/3 (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 thrombosis | 0/3 (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 thrombosis | 0/3 (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%) | |||||||||||||||||||
Embolism | 0/3 (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 venous | 0/3 (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%) | |||||||||||||||||||
Haematoma | 0/3 (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%) | |||||||||||||||||||
Hypertension | 0/3 (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%) | |||||||||||||||||||
Hypotension | 0/3 (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%) | |||||||||||||||||||
Shock | 0/3 (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 thrombosis | 0/3 (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 thrombosis | 0/3 (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 limb | 1/3 (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
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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/Title | Anne McClain |
---|---|
Organization | Celgene Corporation |
Phone | 1-888-260-1599 |
clinicaltrialdisclosure@celgene.com |
- MEDI4736-NHL-001
- 2015-003516-21