Phase I/II Study of PDR001 in Patients With Advanced Malignancies
Sponsor
Novartis Pharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT02404441
Collaborator
(none)
319
41
2
62.8
7.8
0.1
Study Details
Study Description
Brief Summary
The purpose of this "first-in-human" study of PDR001 was to characterize the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and antitumor activity of PDR001 administered i.v. as a single agent to adult patients with solid tumors.
By blocking the interaction between PD-1 and its ligands, PD-L1 and PD-L2, PDR001 inhibits the PD-1 immune checkpoint, resulting in activation of an antitumor immune response by activating effector T-cells and inhibiting regulatory T-cells.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Detailed Description
This study was designed as a phase I/II, multi-center, open-label study starting with a phase I dose escalation part followed by a phase II part.
Although the study had 2 'arms', the phase I part of the study had 5 dosing cohorts and the phase ll part had 5 treatment groups for a total of 10 reporting groups.
PDR001 was administered every 2 weeks until patient experienced unacceptable toxicity, progressive disease per immune related Response Criteria (irRC) and/or treatment was discontinued at the discretion of the investigator or the patient.
Study Design
Study Type:
Interventional
Actual Enrollment
:
319 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Intervention Model Description:
Although the study had 2 'arms', the phase I part of the study had 5 dosing cohorts and the phase ll part had 5 treatment groups for a total of 10 reporting groups.Although the study had 2 'arms', the phase I part of the study had 5 dosing cohorts and the phase ll part had 5 treatment groups for a total of 10 reporting groups.
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Open Label Multicenter Phase I/II Study of the Safety and Efficacy of PDR001 Administered to Patients With Advanced Malignancies
Actual Study Start Date
:
Apr 27, 2015
Actual Primary Completion Date
:
Jul 21, 2020
Actual Study Completion Date
:
Jul 21, 2020
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Other: patients with solid tumors Phase I Dose escalation cohorts |
Biological: PDR001
anti-PD1 antibody
|
| Other: Selected tumor types Phase II expansion: Selected tumor types: melanoma, NSCLC, triple negative breast cancer, anaplastic thyroid cancer |
Biological: PDR001
anti-PD1 antibody
|
Outcome Measures
Primary Outcome Measures
- Phase l: The Exposure (AUC(0-336h)) After First Dose of Treatment at Cycle 3 (Each Cycle = 28 Days) [Predose, 1hour (h), 24h, 48h, 72h, 168h, 240h, 336h post dose (cycle 3)]
Estimated the recommended phase 2 dose (RP2D) and/or the maximum tolerated dose (MTD) for PDR001. AUC0-336h is the AUC from time zero to 336 hour post dose of a measurable concentration sampling time.
- Phase l: Incidence of Dose Limiting Toxicities (DLTs) [8 months]
DLT is defined as an adverse event (AE) or abnormal laboratory value of common terminology criteria for adverse events (CTCAE) grade ≥ 3 assessed as unrelated to disease, disease progression, inter-current illness or concomitant medications, which occurs within the first cycle of treatment with PDR001 during the dose escalation part of the study for which relationship to study treatment cannot be ruled out, with some exceptions.
- Phase ll: Overall Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST v1.1) [61 months]
ORR is the percentage of participants with a best overall response of complete response (CR) or partial response (PR) as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 CR = at least 2 determinations of CR at least 4 weeks apart before progression where confirmation required or 1 determination of CR prior to progression where confirmation not required. PR = at least 2 determinations of PR or better at least 4 weeks apart before progression (and not qualifying for a CR) where confirmation required or 1 determination of PR prior to progression where confirmation not required. RECIST criteria is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progress") during treatment.
Secondary Outcome Measures
- Phase I: Serum Pharmacokinetic (PK) Parameter AUCs (AUC0-336h (Cycle 1 Only), AUCinf, AUClast AUCtau) [Predose, 1hour (h), 24h, 48h, 72h, 168h, 240h, 336h post dose (cycle 1 & 3)]
AUC0-336h is the AUC from time zero to 336 hour post dose of a measurable concentration sampling time. AUClast: The AUC from time zero to the last measurable concentration sampling time (tlast) (mass x time x volume-1). AUCinf: The AUC from time zero to infinity (mass x time x volume-1). AUCtau: The AUC calculated to the end of a dosing interval (tau) at steady-state (amount x time x volume-1).
- Phase I: Serum Pharmacokinetic (PK) Parameter Cmax [Predose, 1hour (h), 24h, 48h, 72h, 168h, 240h, 336h post dose (Cycle 1 & 3)]
The maximum (peak) observed plasma, blood, serum, or other body fluid drug concentration after single dose administration (mass x volume-1)
- Phase I: Serum Pharmacokinetic (PK) Parameter Tmax [Predose, 1hour (h), 24h, 48h, 72h, 168h, 240h, 336h post dose (cycle 1 & 3)]
The time to reach maximum (peak) plasma, blood, serum, or other body fluid drug concentration after single dose administration (time)
- Phase ll: Serum Pharmacokinetic (PK) Parameter AUCs (AUC336h, AUCinf, AUClast, AUCtau) [Predose, 1hour (h), 24h, 48h, 72h, 168h, 240h, 336h post dose (cycle 1 & 3)]
AUC0-336h is the AUC from time zero to 336 hour post dose of a measurable concentration sampling time. AUClast: The AUC from time zero to the last measurable concentration sampling time (tlast) (mass x time x volume-1). AUCinf: The AUC from time zero to infinity (mass x time x volume-1). AUCtau: The AUC calculated to the end of a dosing interval (tau) at steady-state (amount x time x volume-1).
- Phase ll: Serum Pharmacokinetic (PK) Parameter Cmax [Predose, 1hour (h), 24h, 48h, 72h, 168h, 240h, 336h post dose (Cycle 1 & 3)]
The maximum (peak) observed plasma, blood, serum, or other body fluid drug concentration after single dose administration (mass x volume-1)
- Phase ll: Serum Pharmacokinetic (PK) Parameter Tmax [Predose, 1hour (h), 24h, 48h, 72h, 168h, 240h, 336h post dose (Cycle 1 & 3)]
The time to reach maximum (peak) plasma, blood, serum, or other body fluid drug concentration after single dose administration (time)
- Phase I: Presence and/or Concentration of Anti-PDR001 [42 months]
Assessed PDR001 anti-drug anti-body (ADA) incidence in Phase I patients - the emergence of anti-PDR001 antibodies following one or more intravenous (i.v.) infusions of PDR001. Each cycle = 28 days; End of treatment was expected to be on average 1 year after the start of study treatment.
- Phase II: Presence and/or Concentration of Anti-PDR001 [42 months]
Assessed PDR001 anti-drug anti-body (ADA) incidence in Phase I patients - the emergence of anti-PDR001 antibodies following one or more intravenous (i.v.) infusions of PDR001. Each cycle = 28 days; End of treatment was expected to be on average 1 year after the start of study treatment. For Treatment -induced ADA-positive, Percentage was based on subjects ADA-negative at baseline. For Treatment-boosted ADA-positive, Percentage was based on subjects ADA-positive at baseline.
- Phase l: Overall Response Rate (ORR) as Per Investigator Based on RECIST v1.1 [27 months]
ORR is the percentage of participants with a best overall response of complete response CR or partial response PR as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 CR = at least two determinations of CR at least 4 weeks apart before progression where confirmation required or one determination of CR prior to progression where confirmation not required. PR = at least two determinations of PR or better at least 4 weeks apart before progression (and not qualifying for a CR) where confirmation required or one determination of PR prior to progression where confirmation not required. RECIST criteria is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progress") during treatment.
- Phase l: Disease Control Rate (DCR) as Per Investigator Based on RECIST v1.1 [27 months]
DCR is the percentage of patients with a best overall response of CR or PR or stable disease (SD). CR = at least two determinations of CR at least 4 weeks apart before progression where confirmation required or one determination of CR prior to progression where confirmation not required PR = at least two determinations of PR or better at least 4 weeks apart before progression (and not qualifying for a CR) where confirmation required or one determination of PR prior to progression where confirmation not required. SD = at least one SD assessment (or better) > 6 weeks after randomization/start of treatment (and not qualifying for CR or PR). RECIST criteria is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progress") during treatment.
- Phase l: Progression Free Survival (PFS) as Per RECIST v1.1 [27 months]
PFS is the time from date of start of treatment to the date of event defined as the first documented progression or death due to any cause. PFS is per Kaplan-Meier estimates. RECIST criteria, published in February 2000 by an international collaboration including the European Organization for Research and Treatment of Cancer (EORTC), National Cancer Institute of the United States, and the National Cancer Institute of Canada Clinical Trials Group, is a Response evaluation criteria in solid tumors is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progress") during treatment. RECIST criteria is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progress") during treatment.
- Phase I: Duration of Response (DOR) as Per RECIST v1.1 [27 months]
DOR is measured from the time measurement criteria are met for CR or PR (whichever status is recorded first) until the first date that recurrence or PD is objectively documented. CR = at least 2 determinations of CR at least 4 weeks apart before progression where confirmation required or 1 determination of CR prior to progression where confirmation not required; PR = at least 2 determinations of PR or better at least 4 weeks apart before progression (and not qualifying for a CR) where confirmation required or 1 determination of PR prior to progression where confirmation not required; PD =progression <= 12 weeks after randomization/start of treatment (and not qualifying for CR, PR or SD). SD = at least 1 SD assessment (or better) > 6 weeks after randomization/start of treatment (and not qualifying for CR or PR). RECIST criteria is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progress") during treatment
- Phase l Only: Overall Response Rate (ORR) as Per Investigator Based on Immune Related Response Criteria (irRC) [27 months]
ORR is the percentage of participants with a best overall response of complete response (CR) or partial response (PR) as per irRC. CR = at least two determinations of CR at least 4 weeks apart before progression where confirmation required or one determination of CR prior to progression where confirmation not required. PR = at least two determinations of PR or better at least 4 weeks apart before progression (and not qualifying for a CR) where confirmation required or one determination of PR prior to progression where confirmation not required. The immune-related response criteria (irRC) is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progress") during treatment, where the compound being evaluated is an immuno-oncology drug.
- Phase l Only: Disease Control Rate (DCR) as Per Investigator Based on irRC [27 months]
DCR is the percentage of patients with a best overall response of CR or PR or stable disease (SD). CR = at least two determinations of CR at least 4 weeks apart before progression where confirmation required or one determination of CR prior to progression where confirmation not required PR = at least two determinations of PR or better at least 4 weeks apart before progression (and not qualifying for a CR) where confirmation required or one determination of PR prior to progression where confirmation not required. SD = at least one SD assessment (or better) > 6 weeks after randomization/start of treatment (and not qualifying for CR or PR). The immune-related response criteria (irRC) is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progress") during treatment, where the compound being evaluated is an immuno-oncology drug.
- Phase l Only: Progression Free Survival (PFS) as Per irRC [27 months]
PFS is the time from date of start of treatment to the date of event defined as the first documented progression or death due to any cause. PFS is per Kaplan-Meier estimates. The immune-related response criteria (irRC) is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progress") during treatment, where the compound being evaluated is an immuno-oncology drug.
- Phase I: Duration of Response (DOR) as Per irRC [61 Days]
DOR: measured from time measurement criteria are met for CR or PR (whichever status is recorded first) until first date that recurrence or PD is objectively documented CR: at least 2 determinations of CR at least 4 weeks apart before progression where confirmation required or 1 determination of CR prior to progression where confirmation not required PR: at least 1 determination of PR or better at least 4 weeks apart before progression (& not qualifying for a CR) where confirmation required or 1 determination of PR prior to progression where confirmation not required PD: progression <= start of treatment (& not qualifying for CR, PR or SD) SD: at least 1 SD assessment (or better) > 6 weeks after randomization/start of treatment (& not qualifying for CR or PR) irRC is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progress") during treatment, where the compound being evaluated is an immuno-oncology drug
- Phase II: Disease Control Rate (DCR) as Per Investigator Based on RECIST v1.1 [61 months]
DCR is the percentage of patients with a best overall response of CR or PR or stable disease (SD). CR = at least two determinations of CR at least 4 weeks apart before progression where confirmation required or one determination of CR prior to progression where confirmation not required PR = at least two determinations of PR or better at least 4 weeks apart before progression (and not qualifying for a CR) where confirmation required or one determination of PR prior to progression where confirmation not required. SD = at least one SD assessment (or better) > 6 weeks after randomization/start of treatment (and not qualifying for CR or PR). RECIST criteria is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progress") during treatment.
- Phase II: Progression Free Survival as Per Investigator Based on RECIST v1.1 [61 months]
PFS is the time from date of start of treatment to the date of event defined as the first documented progression or death due to any cause. PFS is per Kaplan-Meier estimates. RECIST criteria, published in February 2000 by an international collaboration including the European Organization for Research and Treatment of Cancer (EORTC), National Cancer Institute of the United States, and the National Cancer Institute of Canada Clinical Trials Group, is a Response evaluation criteria in solid tumors is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progress") during treatment.
- Phase II: Duration of Response (DOR) as Per Investigator Based on RECIST v1.1 [61 months]
DOR is measured from the time measurement criteria are met for CR or PR (whichever status is recorded first) until the first date that recurrence or PD is objectively documented. CR = at least two determinations of CR at least 4 weeks apart before progression where confirmation required or one determination of CR prior to progression where confirmation not required PR = at least two determinations of PR or better at least 4 weeks apart before progression (and not qualifying for a CR) where confirmation required or one determination of PR prior to progression where confirmation not required. PD = progression <= start of treatment (and not qualifying for CR, PR or SD). SD = at least one SD assessment (or better) > 6 weeks after randomization/start of treatment (and not qualifying for CR or PR). RECIST criteria is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progress") during treatment.
- Phase II: Overall Response Rate (ORR) as Per Investigator Based on irRC [61 months]
ORR is the percentage of participants with a best overall response CR or PR as per irRC. CR = at least two determinations of CR at least 4 weeks apart before progression where confirmation required or one determination of CR prior to progression where confirmation not required. PR = at least two determinations of PR or better at least 4 weeks apart before progression (and not qualifying for a CR) where confirmation required or one determination of PR prior to progression where confirmation not required. The immune-related response criteria (irRC) is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progress") during treatment, where the compound being evaluated is an immuno-oncology drug.
- Phase II: Disease Control Rate (DCR) as Per Investigator Based on irRC [61 months]
DCR is the percentage of patients with a best overall response of CR or PR or stable disease (SD). CR = at least two determinations of CR at least 4 weeks apart before progression where confirmation required or one determination of CR prior to progression where confirmation not required PR = at least two determinations of PR or better at least 4 weeks apart before progression (and not qualifying for a CR) where confirmation required or one determination of PR prior to progression where confirmation not required. SD = at least one SD assessment (or better) > 6 weeks after randomization/start of treatment (and not qualifying for CR or PR). The immune-related response criteria (irRC) is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progress") during treatment, where the compound being evaluated is an immuno-oncology drug.
- Phase II: Progression Free Survival (PFS) Per irRC [61 months]
PFS is the time from date of start of treatment to the date of event defined as the first documented progression or death due to any cause. PFS is per Kaplan-Meier estimates. The immune-related response criteria (irRC) is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progress") during treatment, where the compound being evaluated is an immuno-oncology drug.
- Phase II: Duration of Response (DOR) Per irRC [61 months]
DOR: measured from time measurement criteria are met for CR or PR (whichever status is recorded first) until first date that recurrence or PD is objectively documented CR: at least 2 determinations of CR at least 4 weeks apart before progression where confirmation required or 1 determination of CR prior to progression where confirmation not required PR: at least 1 determination of PR or better at least 4 weeks apart before progression (& not qualifying for a CR) where confirmation required or 1 determination of PR prior to progression where confirmation not required PD: progression <= start of treatment (& not qualifying for CR, PR or SD) SD: at least 1 SD assessment (or better) > 6 weeks after randomization/start of treatment (& not qualifying for CR or PR) irRC is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progress") during treatment, where the compound being evaluated is an immuno-oncology drug
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Written informed consent must have been obtained prior to any screening procedures
-
Phase I part: Patients with advanced/metastatic solid tumors, with measurable or non-measurable disease as determined by RECIST version 1.1 (refer to Appendix 1), who have progressed despite standard therapy or are intolerant of standard therapy, or for whom no standard therapy exists.
-
Phase II part: Patients with advanced/metastatic solid tumors, with at least one measurable lesion as determined by RECIST version 1.1, who have progressed following their last prior therapy, and fit into one of the following groups:
-
Group 1a and 1b: NSCLC:
Patients with NSCLC must have had disease recurrence or progression during or after no more than one prior systemic chemotherapy regimen (platinum doublet-based) for advanced or metastatic disease. Prior maintenance therapy is allowed (e.g. pemetrexed, erlotinib, bevacizumab).
Only patients with EGFR mutation-negative tumor are eligible (defined as negative for exon 19 deletions and for the L858R mutation in EGFR at a minimum; however, if more extensive EGFR mutation testing has been performed, the tumor must not harbor any known activating EGFR mutations in Exons 18-21 in order to be considered EGFR mutation-negative). All patients must be tested for EGFR mutational status and, for ALK translocation status if no mutation is detected in EGFR. Patients with ALK translocation-positive NSCLC must have had disease progression following treatment with a corresponding inhibitor and no more than one systemic chemotherapy regimen (platinum doublet-based), in any sequence.
- Group 2: Melanoma:
All patients must have been tested for BRAF mutations. Patients with V600 mutation positive melanoma must have clinical or radiological evidence of disease progression during or after treatment with a BRAF inhibitor alone or in combination with other agents.
-
Group 3: Triple negatice breast cancer.
-
Group 4: Anaplastic thyroid cancer
-
Patients are not required to have received or progressed on a prior therapy.
-
Patients must not be at short term risk for life threatening complications (such as airway compromise or bleeding from locoregional or metastatic disease).
-
Chemoradiation and/or surgery should be considered prior to study entry for those patients with locally advanced disease if those therapies are considered to be in the best interest of the patient.
-
ECOG Performance Status ≤ 1.
-
Patients must have a site of disease amenable to biopsy, and be a candidate for tumor biopsy. Patient must be willing to undergo a new tumor biopsy at baseline or at molecular pre-screening if applicable, and during therapy on this study. For patients in the phase II part of the study, exceptions may be granted after documented discussion with Novartis. After a sufficient number of paired biopsies are collected, the decision may be taken to stop the collection of biopsies.
Exclusion Criteria:
-
History of severe hypersensitivity reactions to other mAbs
-
Subjects with active, known or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
-
Active infection requiring systemic antibiotic therapy.
-
HIV infection.
-
Active HBV or HCV infection.
-
Patients with ocular melanoma.
-
Systemic anti-cancer therapy within 2 weeks of the first dose of study treatment. For cytotoxic agents that have major delayed toxicity, e.g. mitomycin C and nitrosoureas, 4 weeks washout period. For patients receiving anticancer immunotherapies such as CTLA-4 antagonists, 6 weeks is indicated as the washout period.
-
Prior PD-1- or PD-L1-directed therapy.
-
Patients requiring chronic treatment with systemic steroid therapy, other than replacement-dose steroids in the setting of adrenal insufficiency. Topical, inhaled, nasal and ophthalmic steroids are not prohibited.
-
Patients receiving systemic treatment with any immunosuppressive medication (other than steroids as described above).
-
Use of any vaccines against infectious diseases (e.g. influenza, varicella, pneumococcus) within 4 weeks of initiation of study treatment.
-
Presence of ≥ CTCAE grade 2 toxicity (except alopecia, peripheral neuropathy and ototoxicity, which are excluded if ≥ CTCAE grade 3) due to prior cancer therapy
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | The Sidney Kimmel Cancer Center at Johns Hopkins Hospital Johns Hopkins | Baltimore | Maryland | United States | 21287-0013 |
| 2 | Massachusetts General Hospital | Boston | Massachusetts | United States | 02114 |
| 3 | Oregon Health and Science University SC-10 | Portland | Oregon | United States | 97239 |
| 4 | Sarah Cannon Research Institute SCRI RC | Nashville | Tennessee | United States | 37203 |
| 5 | University of Texas MD Anderson Cancer Center MD Anderson PSC | Houston | Texas | United States | 77030 |
| 6 | Huntsman Cancer Institute Univ. of Utah HCI | Salt Lake City | Utah | United States | 84112-0550 |
| 7 | Novartis Investigative Site | Toronto | Ontario | Canada | M5G 1Z6 |
| 8 | Novartis Investigative Site | Paris Cedex 10 | France | 75475 | |
| 9 | Novartis Investigative Site | Toulouse Cedex 9 | France | 31059 | |
| 10 | Novartis Investigative Site | Villejuif Cedex | France | 94800 | |
| 11 | Novartis Investigative Site | Essen | Germany | 45147 | |
| 12 | Novartis Investigative Site | Jena | Germany | 07740 | |
| 13 | Novartis Investigative Site | Ulm | Germany | 89081 | |
| 14 | Novartis Investigative Site | Budapest | Hungary | 1134 | |
| 15 | Novartis Investigative Site | Debrecen | Hungary | 4032 | |
| 16 | Novartis Investigative Site | Bologna | BO | Italy | 40138 |
| 17 | Novartis Investigative Site | Milano | MI | Italy | 20132 |
| 18 | Novartis Investigative Site | Rozzano | MI | Italy | 20089 |
| 19 | Novartis Investigative Site | Modena | MO | Italy | 41124 |
| 20 | Novartis Investigative Site | Napoli | Italy | 80131 | |
| 21 | Novartis Investigative Site | Ashrafieh | Lebanon | 166830 | |
| 22 | Novartis Investigative Site | Amsterdam | Netherlands | 1066 CX | |
| 23 | Novartis Investigative Site | Leiden | Netherlands | 2300 RC | |
| 24 | Novartis Investigative Site | Oslo | Norway | 0310 | |
| 25 | Novartis Investigative Site | Gdansk | Poland | 80 952 | |
| 26 | Novartis Investigative Site | Poznan | Poland | 60-693 | |
| 27 | Novartis Investigative Site | Rzeszow | Poland | 35-021 | |
| 28 | Novartis Investigative Site | Warszawa | Poland | 02 781 | |
| 29 | Novartis Investigative Site | Barcelona | Catalunya | Spain | 08035 |
| 30 | Novartis Investigative Site | Madrid | Spain | 28034 | |
| 31 | Novartis Investigative Site | Madrid | Spain | 28041 | |
| 32 | Novartis Investigative Site | Madrid | Spain | 28050 | |
| 33 | Novartis Investigative Site | Tainan | Taiwan ROC | Taiwan | 70403 |
| 34 | Novartis Investigative Site | Taipei | Taiwan | 10002 | |
| 35 | Novartis Investigative Site | Songkhla | Hat Yai | Thailand | 90110 |
| 36 | Novartis Investigative Site | Bangkok | Thailand | 10330 | |
| 37 | Novartis Investigative Site | Adana | Turkey | 01250 | |
| 38 | Novartis Investigative Site | Edirne | Turkey | 22030 | |
| 39 | Novartis Investigative Site | Istanbul | Turkey | 34303 | |
| 40 | Novartis Investigative Site | Istanbul | Turkey | 34890 | |
| 41 | Novartis Investigative Site | Izmir | Turkey | 35040 |
Sponsors and Collaborators
- Novartis Pharmaceuticals
Investigators
- Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT02404441
Other Study ID Numbers:
- CPDR001X2101
- 2014-003929-17
First Posted:
Mar 31, 2015
Last Update Posted:
Aug 3, 2022
Last Verified:
Aug 1, 2022
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Novartis Pharmaceuticals
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | 58 patients were analyzed in Phase l and 261 patients were analyzed in Phase II of this study. |
|---|---|
| Pre-assignment Detail | The study planned to analyze about 58 patients in Phase I and about 120 patients in Phase II. |
| Arm/Group Title | 1mg/kg q2w | 3mg/kg q2w | 10mg/kg q2w | 3mg/kg q4w | 5mg/kg q4w | NSCLC 400mg/q4w | Melanoma 400mg/q4w | TNBC 400mg/q4w | NSCLC 300mg/q3w | ATC 400 mg/q4w |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Phase I Dose escalation cohort patients who took PDR001 1 mg/kg q2w | Phase I Dose escalation cohort patients who took PRD001 3 mg/kg q2w | Phase I Dose escalation cohort patients who took PRD001 10 mg/kg q2w | Phase I Dose escalation cohort patients who took PRD001 3 mg/kg q4w | Phase I Dose escalation cohort patients who took PRD001 5 mg/kg q4w | Phase II: non-small cell cancer patients who took PDR001 400 mg/q4w | Phase II: Melanoma patients who took PDR001 400 mg/q4w | Phase II: Triple negative breast cancer (TNBC) patients who took PDR001 400 mg/q4w | Phase II: non-small cell cancer patients who took PDR001 300 mg/q3w | Patients in Phase II with anaplastic thyroid cancer (ATC) who took PDR001 400 mg/q4w |
| Period Title: Phase 1 Part | ||||||||||
| STARTED | 16 | 15 | 11 | 6 | 10 | 0 | 0 | 0 | 0 | 0 |
| COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 16 | 15 | 11 | 6 | 10 | 0 | 0 | 0 | 0 | 0 |
| Period Title: Phase 1 Part | ||||||||||
| STARTED | 0 | 0 | 0 | 0 | 0 | 59 | 61 | 40 | 59 | 42 |
| Entered Post-treatment Follow-up | 0 | 0 | 0 | 0 | 0 | 2 | 6 | 1 | 6 | 1 |
| No Longer Being Followed for Post-treatment Follow-up | 0 | 0 | 0 | 0 | 0 | 2 | 6 | 1 | 6 | 1 |
| Entered Survival Follow-up | 0 | 0 | 0 | 0 | 0 | 38 | 34 | 26 | 35 | 25 |
| COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 59 | 61 | 40 | 59 | 42 |
Baseline Characteristics
| Arm/Group Title | 1mg/kg q2w | 3mg/kg q2w | 10mg/kg q2w | 3mg/kg q4w | 5mg/kg q4w | NSCLC 400mg/q4w | Melanoma 400mg/q4w | TNBC 400mg/q4w | NSCLC 300mg/q3w | ATC 400 mg/q4w | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Phase I Dose escalation cohort patients who took PDR001 1 mg/kg q2w | Phase I Dose escalation cohort patients who took PRD001 3 mg/kg q2w | Phase I Dose escalation cohort patients who took PDR001 10 mg/kg q2w | Phase I Dose escalation cohort patients who took PRD001 3 mg/kg q4w | Phase I Dose escalation cohort patients who took PRD001 5 mg/kg q4w | Phase II: non-small cell cancer patients who took PDR001 400 mg/q4w | Phase II: Melanoma patients who took PDR001 400 mg/q4w | Phase II: Triple negative breast cancer (TNBC) patients who took PDR001 400 mg/q4w | Phase II: non-small cell cancer patients who took PDR001 300 mg/q3w | Patients in Phase II with anaplastic thyroid cancer (ATC) who took PDR001 400 mg/q4w | Total of all reporting groups |
| Overall Participants | 16 | 15 | 11 | 6 | 10 | 59 | 61 | 40 | 59 | 42 | 319 |
| Age, Customized (Number) [Number] | |||||||||||
| < 65 years |
12
75%
|
9
60%
|
8
72.7%
|
6
100%
|
8
80%
|
33
55.9%
|
37
60.7%
|
29
72.5%
|
35
59.3%
|
25
59.5%
|
202
63.3%
|
| ≥ 65years |
4
25%
|
6
40%
|
3
27.3%
|
0
0%
|
2
20%
|
26
44.1%
|
24
39.3%
|
11
27.5%
|
24
40.7%
|
17
40.5%
|
117
36.7%
|
| Sex: Female, Male (Count of Participants) | |||||||||||
| Female |
9
56.3%
|
7
46.7%
|
4
36.4%
|
2
33.3%
|
4
40%
|
23
39%
|
22
36.1%
|
40
100%
|
20
33.9%
|
19
45.2%
|
150
47%
|
| Male |
7
43.8%
|
8
53.3%
|
7
63.6%
|
4
66.7%
|
6
60%
|
36
61%
|
39
63.9%
|
0
0%
|
39
66.1%
|
23
54.8%
|
169
53%
|
| Race/Ethnicity, Customized (Number) [Number] | |||||||||||
| Caucasian |
10
62.5%
|
14
93.3%
|
8
72.7%
|
4
66.7%
|
8
80%
|
42
71.2%
|
37
60.7%
|
32
80%
|
50
84.7%
|
33
78.6%
|
238
74.6%
|
| Black |
2
12.5%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
1.6%
|
1
2.5%
|
0
0%
|
1
2.4%
|
5
1.6%
|
| Asian |
3
18.8%
|
1
6.7%
|
2
18.2%
|
2
33.3%
|
1
10%
|
12
20.3%
|
23
37.7%
|
4
10%
|
8
13.6%
|
4
9.5%
|
60
18.8%
|
| Unknown |
1
6.3%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
5
8.5%
|
0
0%
|
2
5%
|
1
1.7%
|
4
9.5%
|
13
4.1%
|
| Other |
0
0%
|
0
0%
|
1
9.1%
|
0
0%
|
1
10%
|
0
0%
|
0
0%
|
1
2.5%
|
0
0%
|
0
0%
|
3
0.9%
|
Outcome Measures
| Title | Phase l: The Exposure (AUC(0-336h)) After First Dose of Treatment at Cycle 3 (Each Cycle = 28 Days) |
|---|---|
| Description | Estimated the recommended phase 2 dose (RP2D) and/or the maximum tolerated dose (MTD) for PDR001. AUC0-336h is the AUC from time zero to 336 hour post dose of a measurable concentration sampling time. |
| Time Frame | Predose, 1hour (h), 24h, 48h, 72h, 168h, 240h, 336h post dose (cycle 3) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic analysis set (PAS): The PAS consisted of all subjects who had at least one blood sample providing evaluable PK data. |
| Arm/Group Title | 1mg/kg q2w | 3mg/kg q2w | 10mg/kg q2w | 3mg/kg q4w | 5mg/kg q4w |
|---|---|---|---|---|---|
| Arm/Group Description | Phase I Dose escalation cohort patients who took PDR001 1 mg/kg q2w | Phase I Dose escalation cohort patients who took PRD001 3 mg/kg q2w | Phase I Dose escalation cohort patients who took PDR001 10 mg/kg q2w | Phase I Dose escalation cohort patients who took PRD001 3 mg/kg q4w | Phase I Dose escalation cohort patients who took PRD001 5 mg/kg q4w |
| Measure Participants | 8 | 4 | 4 | 3 | 4 |
| Geometric Mean (Geometric Coefficient of Variation) [day*ug/mL] |
270
(52.5)
|
1150
(51.1)
|
3110
(33.1)
|
575
(21.8)
|
1490
(34.2)
|
| Title | Phase l: Incidence of Dose Limiting Toxicities (DLTs) |
|---|---|
| Description | DLT is defined as an adverse event (AE) or abnormal laboratory value of common terminology criteria for adverse events (CTCAE) grade ≥ 3 assessed as unrelated to disease, disease progression, inter-current illness or concomitant medications, which occurs within the first cycle of treatment with PDR001 during the dose escalation part of the study for which relationship to study treatment cannot be ruled out, with some exceptions. |
| Time Frame | 8 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Set: The Safety Set included all subjects from the FAS who received at least one dose of spartalizumab and had at least one valid post-baseline safety assessment. |
| Arm/Group Title | 1mg/kg q2w | 3mg/kg q2w | 10mg/kg q2w | 3mg/kg q4w | 5mg/kg q4w |
|---|---|---|---|---|---|
| Arm/Group Description | Phase I Dose escalation cohort patients who took PDR001 1 mg/kg q2w | Phase I Dose escalation cohort patients who took PRD001 3 mg/kg q2w | Phase I Dose escalation cohort patients who took PDR001 10 mg/kg q2w | Phase I Dose escalation cohort patients who took PRD001 3 mg/kg q4w | Phase I Dose escalation cohort patients who took PRD001 5 mg/kg q4w |
| Measure Participants | 16 | 15 | 11 | 6 | 10 |
| Number [Participants] |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Phase ll: Overall Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST v1.1) |
|---|---|
| Description | ORR is the percentage of participants with a best overall response of complete response (CR) or partial response (PR) as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 CR = at least 2 determinations of CR at least 4 weeks apart before progression where confirmation required or 1 determination of CR prior to progression where confirmation not required. PR = at least 2 determinations of PR or better at least 4 weeks apart before progression (and not qualifying for a CR) where confirmation required or 1 determination of PR prior to progression where confirmation not required. RECIST criteria is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progress") during treatment. |
| Time Frame | 61 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS): The FAS included all subjects who received at least one dose of spartalizumab. Subjects were analyzed according to the planned treatment (dose level and regimen). |
| Arm/Group Title | NSCLC 400 mg/q4w | Melanoma 400 mg/q4w | TNBC 400 mg/q4w | NSCLC 300 mg/q3w | ATC 400 mg/q4w | All Phase II Patients |
|---|---|---|---|---|---|---|
| Arm/Group Description | Patients in Phase II with non-small cell cancer who took PDR001 400 mg/q4w | Patients in Phase II with Melanoma who took PDR001 400 mg/q4w | Patients in Phase II with TNBC who took PDR001 400 mg/q4w | Patients in Phase II with non-small cell cancer who took PDR001 300 mg/q3w | Patients in Phase II with anaplastic thyroid cancer (ATC) who took PDR001 400 mg/q4w | All patients in Phase II regardless of how they took PDR001 |
| Measure Participants | 59 | 61 | 40 | 59 | 42 | 261 |
| Number (90% Confidence Interval) [Percentage of participants] |
15.3
95.6%
|
27.9
186%
|
0.0
0%
|
6.8
113.3%
|
19.0
190%
|
14.6
24.7%
|
| Title | Phase I: Serum Pharmacokinetic (PK) Parameter AUCs (AUC0-336h (Cycle 1 Only), AUCinf, AUClast AUCtau) |
|---|---|
| Description | AUC0-336h is the AUC from time zero to 336 hour post dose of a measurable concentration sampling time. AUClast: The AUC from time zero to the last measurable concentration sampling time (tlast) (mass x time x volume-1). AUCinf: The AUC from time zero to infinity (mass x time x volume-1). AUCtau: The AUC calculated to the end of a dosing interval (tau) at steady-state (amount x time x volume-1). |
| Time Frame | Predose, 1hour (h), 24h, 48h, 72h, 168h, 240h, 336h post dose (cycle 1 & 3) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic analysis set (PAS): The PAS consisted of all subjects who had at least one blood sample providing evaluable PK data. |
| Arm/Group Title | 1mg/kg q2w | 3mg/kg q2w | 10mg/kg q2w | 3mg/kg q4w | 5mg/kg q4w |
|---|---|---|---|---|---|
| Arm/Group Description | Phase I Dose escalation cohort patients who took PDR001 1 mg/kg q2w | Phase I Dose escalation cohort patients who took PRD001 3 mg/kg q2w | Phase I Dose escalation cohort patients who took PDR001 10 mg/kg q2w | Phase I Dose escalation cohort patients who took PRD001 3 mg/kg q4w | Phase I Dose escalation cohort patients who took PRD001 5 mg/kg q4w |
| Measure Participants | 16 | 15 | 11 | 6 | 10 |
| Cycle (C) 1: AUC0-336h (n=16, 13, 10, 6, 10) |
126
(29.5)
|
324
(24.4)
|
1270
(20.3)
|
350
(35.0)
|
638
(35.3)
|
| C1: AUCinf (n = 1, 0,0,2,3) |
123
(0)
|
384
(9.8)
|
726
(16.0)
|
||
| C1: AUClast |
125
(29.9)
|
353
(31.4)
|
1240
(21.6)
|
522
(39.1)
|
943
(37.4)
|
| C1: AUCtau (n = 16, 13, 10, 6, 10) |
126
(29.5)
|
324
(24.4)
|
1270
(20.3)
|
524
(39.6)
|
984
(41.9)
|
| C3: AUClast |
260
(44.8)
|
995
(60.5)
|
2520
(58.4)
|
933
(21.3)
|
2560
(37.2)
|
| C3: AUCtau (n = 8, 4, 4, 2, 2) |
270
(52.5)
|
1150
(51.1)
|
3110
(33.1)
|
1040
(19.1)
|
2770
(26.6)
|
| Title | Phase I: Serum Pharmacokinetic (PK) Parameter Cmax |
|---|---|
| Description | The maximum (peak) observed plasma, blood, serum, or other body fluid drug concentration after single dose administration (mass x volume-1) |
| Time Frame | Predose, 1hour (h), 24h, 48h, 72h, 168h, 240h, 336h post dose (Cycle 1 & 3) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic analysis set (PAS): The PAS consisted of all subjects who had at least one blood sample providing evaluable PK data. |
| Arm/Group Title | 1mg/kg q2w | 3mg/kg q2w | 10mg/kg q2w | 3mg/kg q4w | 5mg/kg q4w |
|---|---|---|---|---|---|
| Arm/Group Description | Phase I Dose escalation cohort patients who took PDR001 1 mg/kg q2w | Phase I Dose escalation cohort patients who took PRD001 3 mg/kg q2w | Phase I Dose escalation cohort patients who took PDR001 10 mg/kg q2w | Phase I Dose escalation cohort patients who took PRD001 3 mg/kg q4w | Phase I Dose escalation cohort patients who took PRD001 5 mg/kg q4w |
| Measure Participants | 16 | 15 | 11 | 6 | 10 |
| C1 (n = 15, 15, 10, 6, 9) |
18.2
(26.5)
|
53.8
(23.6)
|
185
(18.3)
|
53.8
(29.4)
|
106
(34.2)
|
| C3 (n = 10, 7, 3, 3, 2) |
29.7
(41.0)
|
112
(27.3)
|
312
(30.0)
|
69.7
(9.4)
|
179
(45.2)
|
| Title | Phase I: Serum Pharmacokinetic (PK) Parameter Tmax |
|---|---|
| Description | The time to reach maximum (peak) plasma, blood, serum, or other body fluid drug concentration after single dose administration (time) |
| Time Frame | Predose, 1hour (h), 24h, 48h, 72h, 168h, 240h, 336h post dose (cycle 1 & 3) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic analysis set (PAS): The PAS consisted of all subjects who had at least one blood sample providing evaluable PK data. |
| Arm/Group Title | 1mg/kg q2w | 3mg/kg q2w | 10mg/kg q2w | 3mg/kg q4w | 5mg/kg q4w |
|---|---|---|---|---|---|
| Arm/Group Description | Phase I Dose escalation cohort patients who took PDR001 1 mg/kg q2w | Phase I Dose escalation cohort patients who took PRD001 3 mg/kg q2w | Phase I Dose escalation cohort patients who took PDR001 10 mg/kg q2w | Phase I Dose escalation cohort patients who took PRD001 3 mg/kg q4w | Phase I Dose escalation cohort patients who took PRD001 5 mg/kg q4w |
| Measure Participants | 16 | 15 | 11 | 6 | 10 |
| C1 (n = 15, 15, 10, 6, 9) |
1.58
|
1.57
|
1.55
|
1.55
|
1.58
|
| C3 (n = 10, 7, 3, 3, 2) |
1.55
|
1.55
|
1.58
|
1.5
|
1.3
|
| Title | Phase ll: Serum Pharmacokinetic (PK) Parameter AUCs (AUC336h, AUCinf, AUClast, AUCtau) |
|---|---|
| Description | AUC0-336h is the AUC from time zero to 336 hour post dose of a measurable concentration sampling time. AUClast: The AUC from time zero to the last measurable concentration sampling time (tlast) (mass x time x volume-1). AUCinf: The AUC from time zero to infinity (mass x time x volume-1). AUCtau: The AUC calculated to the end of a dosing interval (tau) at steady-state (amount x time x volume-1). |
| Time Frame | Predose, 1hour (h), 24h, 48h, 72h, 168h, 240h, 336h post dose (cycle 1 & 3) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic analysis set (PAS): The PAS consisted of all subjects who had at least one blood sample providing evaluable PK data. |
| Arm/Group Title | NSCLC 400 mg/q4w | Melanoma 400 mg/q4w | TNBC 400 mg/q4w | NSCLC 300 mg/q3w | ATC 400 mg/q4w |
|---|---|---|---|---|---|
| Arm/Group Description | Patients in Phase II with non-small cell cancer who took PDR001 400 mg/q4w | Patients in Phase II with Melanoma who took PDR001 400 mg/q4w | Patients in Phase II with TNBC who took PDR001 400 mg/q4w | Patients in Phase II with non-small cell cancer who took PDR001 300 mg/q3w | Patients in Phase II with anaplastic thyroid cancer (ATC) who took PDR001 400 mg/q4w |
| Measure Participants | 59 | 61 | 40 | 59 | 42 |
| C1: AUC0-336h (n =58, 58, 37, 54, 37) |
681
(39.4)
|
775
(31.7)
|
752
(29.3)
|
535
(38.3)
|
704
(28.2)
|
| C1: AUCinf (n = 13, 8, 7, 5, 2) |
1090
(29.6)
|
1080
(45.4)
|
1240
(25.2)
|
491
(22.7)
|
1160
(7.1)
|
| C1: AUClast |
980
(42.5)
|
1020
(109.9)
|
923
(76.1)
|
602
(62.2)
|
865
(69.8)
|
| C1: AUCtau (n= 54, 55, 32, 48, 36) |
1010
(39.8)
|
1190
(35.0)
|
1130
(34.9)
|
689
(40.4)
|
1070
(31.3)
|
| C3: AUC0-336h (n = 36, 49, 12, 40, 16) |
1210
(36.3)
|
1140
(43.8)
|
1360
(45.7)
|
850
(50.6)
|
1290
(30.0)
|
| C3: AUCinf (n = 1, 1, 1, 1, 0) |
1050
(NA)
|
1070
(NA)
|
2340
(NA)
|
135
(NA)
|
|
| C3: AUClast (n = 37, 51, 16, 44, 19) |
1860
(39.9)
|
1650
(59.7)
|
1630
(73.4)
|
984
(78.0)
|
1600
(88.0)
|
| C3: AUCtau (n= 31, 44, 7, 38, 14) |
1940
(35.5)
|
1790
(53.4)
|
1920
(44.4)
|
1100
(54.5)
|
2120
(32.7)
|
| Title | Phase ll: Serum Pharmacokinetic (PK) Parameter Cmax |
|---|---|
| Description | The maximum (peak) observed plasma, blood, serum, or other body fluid drug concentration after single dose administration (mass x volume-1) |
| Time Frame | Predose, 1hour (h), 24h, 48h, 72h, 168h, 240h, 336h post dose (Cycle 1 & 3) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic analysis set (PAS): The PAS consisted of all subjects who had at least one blood sample providing evaluable PK data. |
| Arm/Group Title | NSCLC 400 mg/q4w | Melanoma 400 mg/q4w | TNBC 400 mg/q4w | NSCLC 300 mg/q3w | ATC 400 mg/q4w |
|---|---|---|---|---|---|
| Arm/Group Description | Patients in Phase II with non-small cell cancer who took PDR001 400 mg/q4w | Patients in Phase II with Melanoma who took PDR001 400 mg/q4w | Patients in Phase II with TNBC who took PDR001 400 mg/q4w | Patients in Phase II with non-small cell cancer who took PDR001 300 mg/q3w | Patients in Phase II with anaplastic thyroid cancer (ATC) who took PDR001 400 mg/q4w |
| Measure Participants | 59 | 61 | 40 | 59 | 42 |
| C1 (n = 52, 58, 32, 55, 35) |
103
(37.0)
|
111
(26.6)
|
114
(23.6)
|
79.9
(31.8)
|
100
(27.3)
|
| C3 (n = 33, 45, 11, 39, 18) |
151
(32.0)
|
141
(33.4)
|
163
(34.7)
|
103
(36.6)
|
146
(22.6)
|
| Title | Phase ll: Serum Pharmacokinetic (PK) Parameter Tmax |
|---|---|
| Description | The time to reach maximum (peak) plasma, blood, serum, or other body fluid drug concentration after single dose administration (time) |
| Time Frame | Predose, 1hour (h), 24h, 48h, 72h, 168h, 240h, 336h post dose (Cycle 1 & 3) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic analysis set (PAS): The PAS consisted of all subjects who had at least one blood sample providing evaluable PK data. |
| Arm/Group Title | NSCLC 400 mg/q4w | Melanoma 400 mg/q4w | TNBC 400 mg/q4w | NSCLC 300 mg/q3w | ATC 400 mg/q4w |
|---|---|---|---|---|---|
| Arm/Group Description | Patients in Phase II with non-small cell cancer who took PDR001 400 mg/q4w | Patients in Phase II with Melanoma who took PDR001 400 mg/q4w | Patients in Phase II with TNBC who took PDR001 400 mg/q4w | Patients in Phase II with non-small cell cancer who took PDR001 300 mg/q3w | Patients in Phase II with anaplastic thyroid cancer (ATC) who took PDR001 400 mg/q4w |
| Measure Participants | 59 | 61 | 40 | 59 | 42 |
| C1 (n= 52, 58, 32, 55, 35) |
1.58
|
1.58
|
1.58
|
1.65
|
1.55
|
| C3 (n = 33, 45, 11, 39, 18) |
1.6
|
1.55
|
1.53
|
1.58
|
1.57
|
| Title | Phase I: Presence and/or Concentration of Anti-PDR001 |
|---|---|
| Description | Assessed PDR001 anti-drug anti-body (ADA) incidence in Phase I patients - the emergence of anti-PDR001 antibodies following one or more intravenous (i.v.) infusions of PDR001. Each cycle = 28 days; End of treatment was expected to be on average 1 year after the start of study treatment. |
| Time Frame | 42 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Immunogenicity incidence Set: The Immunogenicity incidence set includes all subjects in FAS with a determinant baseline immunoglobulin (IG) sample and at least one determinant post-baseline IG sample. Treatment-induced ADA-positive was performed on ADA-positive patients only. Treatment-boosted ADA-positive was performed on ADA-positive patients only. |
| Arm/Group Title | 1mg/kg q2w | 3mg/kg q2w | 10mg/kg q2w | All Phase I q2w | 3mg/kg q4w | 5mg/kg q4w | All Phase I q4w | All Phase I Patients |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Phase I Dose escalation cohort patients who took PDR001 1 mg/kg q2w | Phase I Dose escalation cohort patients who took PRD001 3 mg/kg q2w | Phase I Dose escalation cohort patients who took PDR001 10 mg/kg q2w | Phase I dose Cohorts - All patients in Phase I who took PDR001 q2w | Phase I Dose escalation cohort patients who took PRD001 3 mg/kg q4w | Phase I Dose escalation cohort patients who took PRD001 5 mg/kg q4w | Phase I dose Cohorts - All patients in Phase I who took PDR001 q4w | All patients in Phase I regardless of how they took PDR001 |
| Measure Participants | 16 | 11 | 3 | 30 | 6 | 10 | 16 | 46 |
| Patients with ADA-negative sample at baseline |
11
68.8%
|
9
60%
|
1
9.1%
|
21
350%
|
5
50%
|
9
15.3%
|
14
23%
|
35
87.5%
|
| Patients with ADA-positive sample at baseline |
5
31.3%
|
2
13.3%
|
2
18.2%
|
9
150%
|
1
10%
|
1
1.7%
|
2
3.3%
|
11
27.5%
|
| ADA-negative |
10
62.5%
|
8
53.3%
|
1
9.1%
|
19
316.7%
|
4
40%
|
8
13.6%
|
12
19.7%
|
31
77.5%
|
| ADA-positive (i.e., ADA incidence) |
4
25%
|
2
13.3%
|
2
18.2%
|
8
133.3%
|
1
10%
|
1
1.7%
|
2
3.3%
|
10
25%
|
| Treatment-induced ADA-positive |
1
6.3%
|
1
6.7%
|
0
0%
|
2
33.3%
|
1
10%
|
1
1.7%
|
2
3.3%
|
4
10%
|
| Treatment-boosted ADA-positive |
3
18.8%
|
1
6.7%
|
2
18.2%
|
6
100%
|
0
0%
|
0
0%
|
0
0%
|
6
15%
|
| Title | Phase II: Presence and/or Concentration of Anti-PDR001 |
|---|---|
| Description | Assessed PDR001 anti-drug anti-body (ADA) incidence in Phase I patients - the emergence of anti-PDR001 antibodies following one or more intravenous (i.v.) infusions of PDR001. Each cycle = 28 days; End of treatment was expected to be on average 1 year after the start of study treatment. For Treatment -induced ADA-positive, Percentage was based on subjects ADA-negative at baseline. For Treatment-boosted ADA-positive, Percentage was based on subjects ADA-positive at baseline. |
| Time Frame | 42 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Immunogenicity incidence Set: The Immunogenicity incidence set includes all subjects in FAS with a determinant baseline immunoglobulin (IG) sample and at least one determinant post-baseline IG sample. |
| Arm/Group Title | NSCLC 400 mg/q4w | Melanoma 400 mg/q4w | TNBC 400 mg/q4w | NSCLC 300 mg/q3w | ATC 400 mg/q4w | All Phase II Patients |
|---|---|---|---|---|---|---|
| Arm/Group Description | Patients in Phase II with non-small cell cancer who took PDR001 400 mg/q4w | Patients in Phase II with Melanoma who took PDR001 400 mg/q4w | Patients in Phase II with TNBC who took PDR001 400 mg/q4w | Patients in Phase II with non-small cell cancer who took PDR001 300 mg/q3w | Patients in Phase II with anaplastic thyroid cancer (ATC) who took PDR001 400 mg/q4w | All patients in Phase II regardless of how they took PDR001 |
| Measure Participants | 52 | 54 | 33 | 46 | 31 | 216 |
| Patients with ADA-negative sample at baseline |
43
268.8%
|
48
320%
|
29
263.6%
|
41
683.3%
|
29
290%
|
190
322%
|
| Patients with ADA-positive sample at baseline |
9
56.3%
|
6
40%
|
4
36.4%
|
5
83.3%
|
2
20%
|
26
44.1%
|
| ADA-negative |
34
212.5%
|
46
306.7%
|
23
209.1%
|
31
516.7%
|
24
240%
|
158
267.8%
|
| ADA-positive (i.e., ADA incidence) |
11
68.8%
|
4
26.7%
|
7
63.6%
|
12
200%
|
6
60%
|
40
67.8%
|
| Treatment-induced ADA-positive |
9
56.3%
|
2
13.3%
|
6
54.5%
|
10
166.7%
|
5
50%
|
32
54.2%
|
| Treatment-boosted ADA-positive |
2
12.5%
|
2
13.3%
|
1
9.1%
|
2
33.3%
|
1
10%
|
8
13.6%
|
| Title | Phase l: Overall Response Rate (ORR) as Per Investigator Based on RECIST v1.1 |
|---|---|
| Description | ORR is the percentage of participants with a best overall response of complete response CR or partial response PR as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 CR = at least two determinations of CR at least 4 weeks apart before progression where confirmation required or one determination of CR prior to progression where confirmation not required. PR = at least two determinations of PR or better at least 4 weeks apart before progression (and not qualifying for a CR) where confirmation required or one determination of PR prior to progression where confirmation not required. RECIST criteria is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progress") during treatment. |
| Time Frame | 27 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS): The FAS included all subjects who received at least one dose of spartalizumab. Subjects were analyzed according to the planned treatment (dose level and regimen). |
| Arm/Group Title | 1mg/kg q2w | 3mg/kg q2w | 10mg/kg q2w | All Phase I q2w | 3mg/kg q4w | 5mg/kg q4w | All Phase I q4w | All Phase I Patients |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Phase I Dose escalation cohort patients who took PDR001 1 mg/kg q2w | Phase I Dose escalation cohort patients who took PRD001 3 mg/kg q2w | Phase I Dose escalation cohort patients who took PDR001 10 mg/kg q2w | Phase I dose Cohorts - All patients in Phase I who took PDR001 q2w | Phase I Dose escalation cohort patients who took PRD001 3 mg/kg q4w | Phase I Dose escalation cohort patients who took PRD001 5 mg/kg q4w | Phase I dose Cohorts - All patients in Phase I who took PDR001 q4w | All patients in Phase I regardless of how they took PDR001 |
| Measure Participants | 16 | 15 | 11 | 42 | 6 | 10 | 16 | 58 |
| Number (90% Confidence Interval) [Percentage of participants] |
0.00
0%
|
6.7
44.7%
|
9.1
82.7%
|
4.8
80%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
3.4
8.5%
|
| Title | Phase l: Disease Control Rate (DCR) as Per Investigator Based on RECIST v1.1 |
|---|---|
| Description | DCR is the percentage of patients with a best overall response of CR or PR or stable disease (SD). CR = at least two determinations of CR at least 4 weeks apart before progression where confirmation required or one determination of CR prior to progression where confirmation not required PR = at least two determinations of PR or better at least 4 weeks apart before progression (and not qualifying for a CR) where confirmation required or one determination of PR prior to progression where confirmation not required. SD = at least one SD assessment (or better) > 6 weeks after randomization/start of treatment (and not qualifying for CR or PR). RECIST criteria is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progress") during treatment. |
| Time Frame | 27 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS): The FAS included all subjects who received at least one dose of spartalizumab. Subjects were analyzed according to the planned treatment (dose level and regimen). |
| Arm/Group Title | 1mg/kg q2w | 3mg/kg q2w | 10mg/kg q2w | All Phase I q2w | 3mg/kg q4w | 5mg/kg q4w | All Phase I q4w | All Phase I Patients |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Phase I Dose escalation cohort patients who took PDR001 1 mg/kg q2w | Phase I Dose escalation cohort patients who took PRD001 3 mg/kg q2w | Phase I Dose escalation cohort patients who took PDR001 10 mg/kg q2w | Phase I dose Cohorts - All patients in Phase I who took PDR001 q2w | Phase I Dose escalation cohort patients who took PRD001 3 mg/kg q4w | Phase I Dose escalation cohort patients who took PRD001 5 mg/kg q4w | Phase I dose Cohorts - All patients in Phase I who took PDR001 q4w | All patients in Phase I regardless of how they took PDR001 |
| Measure Participants | 16 | 15 | 11 | 42 | 6 | 10 | 16 | 58 |
| Number (90% Confidence Interval) [Percentage of participants] |
56.3
351.9%
|
46.7
311.3%
|
27.3
248.2%
|
45.2
753.3%
|
50.0
500%
|
20.0
33.9%
|
31.3
51.3%
|
41.4
103.5%
|
| Title | Phase l: Progression Free Survival (PFS) as Per RECIST v1.1 |
|---|---|
| Description | PFS is the time from date of start of treatment to the date of event defined as the first documented progression or death due to any cause. PFS is per Kaplan-Meier estimates. RECIST criteria, published in February 2000 by an international collaboration including the European Organization for Research and Treatment of Cancer (EORTC), National Cancer Institute of the United States, and the National Cancer Institute of Canada Clinical Trials Group, is a Response evaluation criteria in solid tumors is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progress") during treatment. RECIST criteria is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progress") during treatment. |
| Time Frame | 27 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS): The FAS included all subjects who received at least one dose of spartalizumab. Subjects were analyzed according to the planned treatment (dose level and regimen). |
| Arm/Group Title | 1mg/kg q2w | 3mg/kg q2w | 10mg/kg q2w | 3mg/kg q4w | 5mg/kg q4w |
|---|---|---|---|---|---|
| Arm/Group Description | Phase I Dose escalation cohort patients who took PDR001 1 mg/kg q2w | Phase I Dose escalation cohort patients who took PRD001 3 mg/kg q2w | Phase I Dose escalation cohort patients who took PDR001 10 mg/kg q2w | Phase I Dose escalation cohort patients who took PRD001 3 mg/kg q4w | Phase I Dose escalation cohort patients who took PRD001 5 mg/kg q4w |
| Measure Participants | 16 | 15 | 6 | 11 | 10 |
| Median (90% Confidence Interval) [Percentage of participants] |
3.5
21.9%
|
1.9
12.7%
|
2.2
20%
|
2.7
45%
|
1.8
18%
|
| Title | Phase I: Duration of Response (DOR) as Per RECIST v1.1 |
|---|---|
| Description | DOR is measured from the time measurement criteria are met for CR or PR (whichever status is recorded first) until the first date that recurrence or PD is objectively documented. CR = at least 2 determinations of CR at least 4 weeks apart before progression where confirmation required or 1 determination of CR prior to progression where confirmation not required; PR = at least 2 determinations of PR or better at least 4 weeks apart before progression (and not qualifying for a CR) where confirmation required or 1 determination of PR prior to progression where confirmation not required; PD =progression <= 12 weeks after randomization/start of treatment (and not qualifying for CR, PR or SD). SD = at least 1 SD assessment (or better) > 6 weeks after randomization/start of treatment (and not qualifying for CR or PR). RECIST criteria is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progress") during treatment |
| Time Frame | 27 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set - Dose escalation |
| Arm/Group Title | 3mg/kg q2w | 10mg/kg q2w | All Phase I q2w | All Phase I Patients |
|---|---|---|---|---|
| Arm/Group Description | Phase I Dose escalation cohort patients who took PRD001 3 mg/kg q2w | Phase I Dose escalation cohort patients who took PRD001 10 mg/kg q2w | Phase I dose Cohorts - All patients in Phase I who took PDR001 q2w | All patients in Phase I regardless of how they took PDR001 |
| Measure Participants | 1 | 1 | 2 | 2 |
| Mean (Full Range) [days] |
261.00
|
55.00
|
158.00
|
158.00
|
| Title | Phase l Only: Overall Response Rate (ORR) as Per Investigator Based on Immune Related Response Criteria (irRC) |
|---|---|
| Description | ORR is the percentage of participants with a best overall response of complete response (CR) or partial response (PR) as per irRC. CR = at least two determinations of CR at least 4 weeks apart before progression where confirmation required or one determination of CR prior to progression where confirmation not required. PR = at least two determinations of PR or better at least 4 weeks apart before progression (and not qualifying for a CR) where confirmation required or one determination of PR prior to progression where confirmation not required. The immune-related response criteria (irRC) is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progress") during treatment, where the compound being evaluated is an immuno-oncology drug. |
| Time Frame | 27 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS): The FAS included all subjects who received at least one dose of spartalizumab. Subjects were analyzed according to the planned treatment (dose level and regimen). |
| Arm/Group Title | 1mg/kg q2w | 3mg/kg q2w | 10mg/kg q2w | All Phase I q2w | 3mg/kg q4w | 5mg/kg q4w | All Phase I q4w | All Phase I Patients |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Phase I Dose escalation cohort patients who took PDR001 1 mg/kg q2w | Phase I Dose escalation cohort patients who took PRD001 3 mg/kg q2w | Phase I Dose escalation cohort patients who took PRD001 10 mg/kg q2w | Phase I dose Cohorts - All patients in Phase I who took PDR001 q2w | Phase I Dose escalation cohort patients who took PRD001 3 mg/kg q4w | Phase I Dose escalation cohort patients who took PRD001 5 mg/kg q4w | Phase I dose Cohorts - All patients in Phase I who took PDR001 q4w | All patients in Phase I regardless of how they took PDR001 |
| Measure Participants | 16 | 15 | 11 | 42 | 6 | 10 | 16 | 58 |
| Number (90% Confidence Interval) [Percentage of participants] |
0.00
0%
|
6.7
44.7%
|
9.1
82.7%
|
4.8
80%
|
0.0
0%
|
0.0
0%
|
0.0
0%
|
3.4
8.5%
|
| Title | Phase l Only: Disease Control Rate (DCR) as Per Investigator Based on irRC |
|---|---|
| Description | DCR is the percentage of patients with a best overall response of CR or PR or stable disease (SD). CR = at least two determinations of CR at least 4 weeks apart before progression where confirmation required or one determination of CR prior to progression where confirmation not required PR = at least two determinations of PR or better at least 4 weeks apart before progression (and not qualifying for a CR) where confirmation required or one determination of PR prior to progression where confirmation not required. SD = at least one SD assessment (or better) > 6 weeks after randomization/start of treatment (and not qualifying for CR or PR). The immune-related response criteria (irRC) is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progress") during treatment, where the compound being evaluated is an immuno-oncology drug. |
| Time Frame | 27 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS): The FAS included all subjects who received at least one dose of spartalizumab. Subjects were analyzed according to the planned treatment (dose level and regimen). |
| Arm/Group Title | 1mg/kg q2w | 3mg/kg q2w | 10mg/kg q2w | All Phase I q2w | 3mg/kg q4w | 5mg/kg q4w | All Phase I q4w | All Phase I Patients |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Phase I Dose escalation cohort patients who took PDR001 1 mg/kg q2w | Phase I Dose escalation cohort patients who took PRD001 3 mg/kg q2w | Phase I Dose escalation cohort patients who took PRD001 10 mg/kg q2w | Phase I dose Cohorts - All patients in Phase I who took PDR001 q2w | Phase I Dose escalation cohort patients who took PRD001 3 mg/kg q4w | Phase I Dose escalation cohort patients who took PRD001 5 mg/kg q4w | Phase I dose Cohorts - All patients in Phase I who took PDR001 q4w | All patients in Phase I regardless of how they took PDR001 |
| Measure Participants | 16 | 15 | 11 | 42 | 6 | 10 | 16 | 58 |
| Number (90% Confidence Interval) [Percentage of participants] |
62.5
390.6%
|
53.3
355.3%
|
27.3
248.2%
|
50.0
833.3%
|
50.0
500%
|
30.0
50.8%
|
37.5
61.5%
|
46.6
116.5%
|
| Title | Phase l Only: Progression Free Survival (PFS) as Per irRC |
|---|---|
| Description | PFS is the time from date of start of treatment to the date of event defined as the first documented progression or death due to any cause. PFS is per Kaplan-Meier estimates. The immune-related response criteria (irRC) is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progress") during treatment, where the compound being evaluated is an immuno-oncology drug. |
| Time Frame | 27 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS): The FAS included all subjects who received at least one dose of spartalizumab. Subjects were analyzed according to the planned treatment (dose level and regimen). |
| Arm/Group Title | 1mg/kg q2w | 3mg/kg q2w | 10mg/kg q2w | 3mg/kg q4w | 5mg/kg q4w |
|---|---|---|---|---|---|
| Arm/Group Description | Phase I Dose escalation cohort patients who took PDR001 1 mg/kg q2w | Phase I Dose escalation cohort patients who took PRD001 3 mg/kg q2w | Phase I Dose escalation cohort patients who took PDR001 10 mg/kg q2w | Phase I Dose escalation cohort patients who took PRD001 3 mg/kg q4w | Phase I Dose escalation cohort patients who took PRD001 5 mg/kg q4w |
| Measure Participants | 16 | 15 | 11 | 11 | 10 |
| Median (90% Confidence Interval) [Percentage of participants] |
3.6
22.5%
|
2.7
18%
|
2.2
20%
|
2.7
45%
|
1.8
18%
|
| Title | Phase I: Duration of Response (DOR) as Per irRC |
|---|---|
| Description | DOR: measured from time measurement criteria are met for CR or PR (whichever status is recorded first) until first date that recurrence or PD is objectively documented CR: at least 2 determinations of CR at least 4 weeks apart before progression where confirmation required or 1 determination of CR prior to progression where confirmation not required PR: at least 1 determination of PR or better at least 4 weeks apart before progression (& not qualifying for a CR) where confirmation required or 1 determination of PR prior to progression where confirmation not required PD: progression <= start of treatment (& not qualifying for CR, PR or SD) SD: at least 1 SD assessment (or better) > 6 weeks after randomization/start of treatment (& not qualifying for CR or PR) irRC is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progress") during treatment, where the compound being evaluated is an immuno-oncology drug |
| Time Frame | 61 Days |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set - Dose escalation |
| Arm/Group Title | 3mg/kg q2w | 10mg/kg q2w | All Phase I q2w | All Phase I Patients |
|---|---|---|---|---|
| Arm/Group Description | Phase I Dose escalation cohort patients who took PRD001 3 mg/kg q2w | Phase I Dose escalation cohort patients who took PRD001 10 mg/kg q2w | Phase I dose Cohorts - All patients in Phase I who took PDR001 q2w | All patients in Phase I regardless of how they took PDR001 |
| Measure Participants | 1 | 1 | 2 | 2 |
| Mean (Full Range) [days] |
261.00
|
55.00
|
158.00
|
158.00
|
| Title | Phase II: Disease Control Rate (DCR) as Per Investigator Based on RECIST v1.1 |
|---|---|
| Description | DCR is the percentage of patients with a best overall response of CR or PR or stable disease (SD). CR = at least two determinations of CR at least 4 weeks apart before progression where confirmation required or one determination of CR prior to progression where confirmation not required PR = at least two determinations of PR or better at least 4 weeks apart before progression (and not qualifying for a CR) where confirmation required or one determination of PR prior to progression where confirmation not required. SD = at least one SD assessment (or better) > 6 weeks after randomization/start of treatment (and not qualifying for CR or PR). RECIST criteria is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progress") during treatment. |
| Time Frame | 61 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS): The FAS included all subjects who received at least one dose of spartalizumab. Subjects were analyzed according to the planned treatment (dose level and regimen). |
| Arm/Group Title | NSCLC 400 mg/q4w | Melanoma 400 mg/q4w | TNBC 400 mg/q4w | NSCLC 300 mg/q3w | ATC 400 mg/q4w | All Phase II Patients |
|---|---|---|---|---|---|---|
| Arm/Group Description | Patients in Phase II with non-small cell cancer who took PDR001 400 mg/q4w | Patients in Phase II with Melanoma who took PDR001 400 mg/q4w | Patients in Phase II with TNBC who took PDR001 400 mg/q4w | Patients in Phase II with non-small cell cancer who took PDR001 300 mg/q3w | Patients in Phase II with anaplastic thyroid cancer (ATC) who took PDR001 400 mg/q4w | All patients in Phase II regardless of how they took PDR001 |
| Measure Participants | 59 | 61 | 40 | 59 | 42 | 261 |
| Number (90% Confidence Interval) [Percentage of participants] |
49.2
307.5%
|
62.3
415.3%
|
20.0
181.8%
|
35.6
593.3%
|
31.0
310%
|
41.8
70.8%
|
| Title | Phase II: Progression Free Survival as Per Investigator Based on RECIST v1.1 |
|---|---|
| Description | PFS is the time from date of start of treatment to the date of event defined as the first documented progression or death due to any cause. PFS is per Kaplan-Meier estimates. RECIST criteria, published in February 2000 by an international collaboration including the European Organization for Research and Treatment of Cancer (EORTC), National Cancer Institute of the United States, and the National Cancer Institute of Canada Clinical Trials Group, is a Response evaluation criteria in solid tumors is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progress") during treatment. |
| Time Frame | 61 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS): The FAS included all subjects who received at least one dose of spartalizumab. Subjects were analyzed according to the planned treatment (dose level and regimen). |
| Arm/Group Title | NSCLC 400 mg/q4w | Melanoma 400 mg/q4w | TNBC 400 mg/q4w | NSCLC 300 mg/q3w | ATC 400 mg/q4w |
|---|---|---|---|---|---|
| Arm/Group Description | Patients in Phase II with non-small cell cancer who took PDR001 400 mg/q4w | Patients in Phase II with Melanoma who took PDR001 400 mg/q4w | Patients in Phase II with TNBC who took PDR001 400 mg/q4w | Patients in Phase II with non-small cell cancer who took PDR001 300 mg/q3w | Patients in Phase II with anaplastic thyroid cancer (ATC) who took PDR001 400 mg/q4w |
| Measure Participants | 59 | 61 | 40 | 59 | 42 |
| Median (90% Confidence Interval) [Percentage of participants] |
2.7
16.9%
|
4.7
31.3%
|
1.7
15.5%
|
1.9
31.7%
|
1.7
17%
|
| Title | Phase II: Duration of Response (DOR) as Per Investigator Based on RECIST v1.1 |
|---|---|
| Description | DOR is measured from the time measurement criteria are met for CR or PR (whichever status is recorded first) until the first date that recurrence or PD is objectively documented. CR = at least two determinations of CR at least 4 weeks apart before progression where confirmation required or one determination of CR prior to progression where confirmation not required PR = at least two determinations of PR or better at least 4 weeks apart before progression (and not qualifying for a CR) where confirmation required or one determination of PR prior to progression where confirmation not required. PD = progression <= start of treatment (and not qualifying for CR, PR or SD). SD = at least one SD assessment (or better) > 6 weeks after randomization/start of treatment (and not qualifying for CR or PR). RECIST criteria is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progress") during treatment. |
| Time Frame | 61 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS): The FAS included all subjects who received at least one dose of spartalizumab. Subjects were analyzed according to the planned treatment (dose level and regimen). |
| Arm/Group Title | NSCLC 400 mg/q4w | Melanoma 400 mg/q4w | NSCLC 300 mg/q3w | ATC 400 mg/q4w |
|---|---|---|---|---|
| Arm/Group Description | Patients in Phase II with non-small cell cancer who took PDR001 400 mg/q4w | Patients in Phase II with Melanoma who took PDR001 400 mg/q4w | Patients in Phase II with non-small cell cancer who took PDR001 300 mg/q3w | Patients in Phase II with anaplastic thyroid cancer (ATC) who took PDR001 400 mg/q4w |
| Measure Participants | 9 | 17 | 4 | 8 |
| Mean (Full Range) [months] |
5.6
|
32.0
|
10.9
|
22.8
|
| Title | Phase II: Overall Response Rate (ORR) as Per Investigator Based on irRC |
|---|---|
| Description | ORR is the percentage of participants with a best overall response CR or PR as per irRC. CR = at least two determinations of CR at least 4 weeks apart before progression where confirmation required or one determination of CR prior to progression where confirmation not required. PR = at least two determinations of PR or better at least 4 weeks apart before progression (and not qualifying for a CR) where confirmation required or one determination of PR prior to progression where confirmation not required. The immune-related response criteria (irRC) is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progress") during treatment, where the compound being evaluated is an immuno-oncology drug. |
| Time Frame | 61 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS): The FAS included all subjects who received at least one dose of spartalizumab. Subjects were analyzed according to the planned treatment (dose level and regimen). |
| Arm/Group Title | NSCLC 400 mg/q4w | Melanoma 400 mg/q4w | TNBC 400 mg/q4w | NSCLC 300 mg/q3w | ATC 400 mg/q4w | All Phase II Patients |
|---|---|---|---|---|---|---|
| Arm/Group Description | Patients in Phase II with non-small cell cancer who took PDR001 400 mg/q4w | Patients in Phase II with Melanoma who took PDR001 400 mg/q4w | Patients in Phase II with TNBC who took PDR001 400 mg/q4w | Patients in Phase II with non-small cell cancer who took PDR001 300 mg/q3w | Patients in Phase II with anaplastic thyroid cancer (ATC) who took PDR001 400 mg/q4w | All patients in Phase II regardless of how they took PDR001 |
| Measure Participants | 59 | 61 | 40 | 59 | 42 | 261 |
| Number (90% Confidence Interval) [Percentage of participants] |
18.6
116.3%
|
31.1
207.3%
|
0.0
0%
|
8.5
141.7%
|
23.8
238%
|
17.2
29.2%
|
| Title | Phase II: Disease Control Rate (DCR) as Per Investigator Based on irRC |
|---|---|
| Description | DCR is the percentage of patients with a best overall response of CR or PR or stable disease (SD). CR = at least two determinations of CR at least 4 weeks apart before progression where confirmation required or one determination of CR prior to progression where confirmation not required PR = at least two determinations of PR or better at least 4 weeks apart before progression (and not qualifying for a CR) where confirmation required or one determination of PR prior to progression where confirmation not required. SD = at least one SD assessment (or better) > 6 weeks after randomization/start of treatment (and not qualifying for CR or PR). The immune-related response criteria (irRC) is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progress") during treatment, where the compound being evaluated is an immuno-oncology drug. |
| Time Frame | 61 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS): The FAS included all subjects who received at least one dose of spartalizumab. Subjects were analyzed according to the planned treatment (dose level and regimen). |
| Arm/Group Title | NSCLC 400 mg/q4w | Melanoma 400 mg/q4w | TNBC 400 mg/q4w | NSCLC 300 mg/q3w | ATC 400 mg/q4w | All Phase II Patients |
|---|---|---|---|---|---|---|
| Arm/Group Description | Patients in Phase II with non-small cell cancer who took PDR001 400 mg/q4w | Patients in Phase II with Melanoma who took PDR001 400 mg/q4w | Patients in Phase II with TNBC who took PDR001 400 mg/q4w | Patients in Phase II with non-small cell cancer who took PDR001 300 mg/q3w | Patients in Phase II with anaplastic thyroid cancer (ATC) who took PDR001 400 mg/q4w | All patients in Phase II regardless of how they took PDR001 |
| Measure Participants | 59 | 61 | 40 | 59 | 42 | 261 |
| Number (90% Confidence Interval) [Percentage of participants] |
55.9
349.4%
|
67.2
448%
|
22.5
204.5%
|
39.0
650%
|
35.7
357%
|
46.4
78.6%
|
| Title | Phase II: Progression Free Survival (PFS) Per irRC |
|---|---|
| Description | PFS is the time from date of start of treatment to the date of event defined as the first documented progression or death due to any cause. PFS is per Kaplan-Meier estimates. The immune-related response criteria (irRC) is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progress") during treatment, where the compound being evaluated is an immuno-oncology drug. |
| Time Frame | 61 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS): The FAS included all subjects who received at least one dose of spartalizumab. Subjects were analyzed according to the planned treatment (dose level and regimen). |
| Arm/Group Title | NSCLC 400 mg/q4w | Melanoma 400 mg/q4w | TNBC 400 mg/q4w | NSCLC 300 mg/q3w | ATC 400 mg/q4w |
|---|---|---|---|---|---|
| Arm/Group Description | Patients in Phase II with non-small cell cancer who took PDR001 400 mg/q4w | Patients in Phase II with Melanoma who took PDR001 400 mg/q4w | Patients in Phase II with TNBC who took PDR001 400 mg/q4w | Patients in Phase II with non-small cell cancer who took PDR001 300 mg/q3w | Patients in Phase II with anaplastic thyroid cancer (ATC) who took PDR001 400 mg/q4w |
| Measure Participants | 59 | 61 | 40 | 59 | 42 |
| Median (90% Confidence Interval) [Percentage of participants] |
3.7
23.1%
|
5.4
36%
|
1.8
16.4%
|
2.0
33.3%
|
1.7
17%
|
| Title | Phase II: Duration of Response (DOR) Per irRC |
|---|---|
| Description | DOR: measured from time measurement criteria are met for CR or PR (whichever status is recorded first) until first date that recurrence or PD is objectively documented CR: at least 2 determinations of CR at least 4 weeks apart before progression where confirmation required or 1 determination of CR prior to progression where confirmation not required PR: at least 1 determination of PR or better at least 4 weeks apart before progression (& not qualifying for a CR) where confirmation required or 1 determination of PR prior to progression where confirmation not required PD: progression <= start of treatment (& not qualifying for CR, PR or SD) SD: at least 1 SD assessment (or better) > 6 weeks after randomization/start of treatment (& not qualifying for CR or PR) irRC is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progress") during treatment, where the compound being evaluated is an immuno-oncology drug |
| Time Frame | 61 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS): The FAS included all subjects who received at least one dose of spartalizumab. Subjects were analyzed according to the planned treatment (dose level and regimen). |
| Arm/Group Title | NSCLC 400 mg/q4w | Melanoma 400 mg/q4w | NSCLC 300 mg/q3w | ATC 400 mg/q4w |
|---|---|---|---|---|
| Arm/Group Description | Patients in Phase II with non-small cell cancer who took PDR001 400 mg/q4w | Patients in Phase II with Melanoma who took PDR001 400 mg/q4w | Patients in Phase II with non-small cell cancer who took PDR001 300 mg/q3w | Patients in Phase II with anaplastic thyroid cancer (ATC) who took PDR001 400 mg/q4w |
| Measure Participants | 11 | 19 | 5 | 10 |
| Mean (Full Range) [months] |
5.6
|
32.0
|
10.9
|
22.1
|
| Title | All Collected Deaths |
|---|---|
| Description | On treatment deaths were collected from the start of study treatment up to 30 days after last study treatment exposure, for a maximum duration of 114.3 weeks for Phase I part (treatment duration ranged from 2 to 110.3 weeks) and a maximum duration of 194.9 weeks for Phase II part (treatment duration ranged from 0.6 tp 190.9 weeks). Total deaths were collected from the start of treatment up to end of follow-up phase (approx. 70 months). |
| Time Frame | On treatment deaths: approx. 114.3 weeks (Phase I) & 194.9 weeks (phase II), all deaths: approx. 70 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Clinical database population: All treated patients |
| Arm/Group Title | 1mg/kg q2w | 3mg/kg q2w | 10mg/kg q2w | 3mg/kg q4w | 5mg/kg q4w | NSCLC 400 mg/q4w | Melanoma 400 mg/q4w | TNBC 400 mg/q4w | NSCLC 300 mg/q3w | ATC 400 mg/q4w |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Phase I Dose escalation cohort patients who took PDR001 1 mg/kg q2w | Phase I Dose escalation cohort patients who took PRD001 3 mg/kg q2w | Phase I Dose escalation cohort patients who took PDR001 10 mg/kg q2w | Phase I Dose escalation cohort patients who took PRD001 3 mg/kg q4w | Phase I Dose escalation cohort patients who took PRD001 5 mg/kg q4w | Patients in Phase II with non-small cell cancer who took PDR001 400 mg/q4w | Patients in Phase II with Melanoma who took PDR001 400 mg/q4w | Patients in Phase II with TNBC who took PDR001 400 mg/q4w | Patients in Phase II with non-small cell cancer who took PDR001 300 mg/q3w | Patients in Phase II with anaplastic thyroid cancer (ATC) who took PDR001 400 mg/q4w |
| Measure Participants | 16 | 15 | 11 | 6 | 10 | 59 | 61 | 40 | 59 | 42 |
| On-treatment deaths |
2
12.5%
|
2
13.3%
|
1
9.1%
|
1
16.7%
|
2
20%
|
4
6.8%
|
4
6.6%
|
4
10%
|
12
20.3%
|
11
26.2%
|
| Total deaths |
10
62.5%
|
10
66.7%
|
6
54.5%
|
4
66.7%
|
7
70%
|
39
66.1%
|
32
52.5%
|
28
70%
|
47
79.7%
|
31
73.8%
|
Adverse Events
| Time Frame | On treatment deaths were collected from the start of study treatment up to 30 days after last study treatment exposure, for a maximum duration of 114.3 weeks for the Part I phase (treatment duration ranged from 2 to 110.3 weeks) and for a maximum duration of 194.9 weeks for the Phase II part (treatment duration ranged from 0.6 to 190.9 weeks). | |||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | AE: Any sign or symptom that occurs during treatment plus 30 days post treatment. | |||||||||||||||||||||||||||
| Arm/Group Title | 1mg/kg q2w | 3mg/kg q2w | 10mg/kg q2w | All Phase I q2w | 3mg/kg q4w | 5mg/kg q4w | All Phase I q4w | All Phase I Patients | NSCLC 400mg/q4w | Melanoma 400mg/q4w | TNBC 400mg/q4w | NSCLC 300mg/q3w | ATC 400 mg/q4w | All Phase II Patients | ||||||||||||||
| Arm/Group Description | Phase I Dose escalation cohort patients who took PDR001 1 mg/kg q2w | Phase I Dose escalation cohort patients who took PRD001 3 mg/kg q2w | Phase I Dose escalation cohort patients who took PRD001 10 mg/kg q2w | Phase I dose Cohorts - All patients in Phase I who took PDR001 q2w | Phase I Dose escalation cohort patients who took PRD001 3 mg/kg q4w | Phase I Dose escalation cohort patients who took PRD001 5 mg/kg q4w | Phase I dose Cohorts - All patients in Phase I who took PDR001 q4w | All patients in Phase I regardless of how they took PDR001 | Phase II: non-small cell cancer patients who took PDR001 400 mg/q4w | Phase II: Melanoma patients who took PDR001 400 mg/q4w | Phase II: Triple negative breast cancer (TNBC) patients who took PDR001 400 mg/q4w | Phase II: non-small cell cancer patients who took PDR001 300 mg/q3w | Patients in Phase II with anaplastic thyroid cancer (ATC) who took PDR001 400 mg/q4w | All patients in Phase II regardless of how they took PDR001 | ||||||||||||||
All Cause Mortality |
||||||||||||||||||||||||||||
| 1mg/kg q2w | 3mg/kg q2w | 10mg/kg q2w | All Phase I q2w | 3mg/kg q4w | 5mg/kg q4w | All Phase I q4w | All Phase I Patients | NSCLC 400mg/q4w | Melanoma 400mg/q4w | TNBC 400mg/q4w | NSCLC 300mg/q3w | ATC 400 mg/q4w | All Phase II Patients | |||||||||||||||
| 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 | 2/16 (12.5%) | 2/15 (13.3%) | 1/11 (9.1%) | 5/42 (11.9%) | 1/6 (16.7%) | 2/10 (20%) | 3/16 (18.8%) | 8/58 (13.8%) | 4/59 (6.8%) | 4/61 (6.6%) | 4/40 (10%) | 12/59 (20.3%) | 11/42 (26.2%) | 35/261 (13.4%) | ||||||||||||||
Serious Adverse Events |
||||||||||||||||||||||||||||
| 1mg/kg q2w | 3mg/kg q2w | 10mg/kg q2w | All Phase I q2w | 3mg/kg q4w | 5mg/kg q4w | All Phase I q4w | All Phase I Patients | NSCLC 400mg/q4w | Melanoma 400mg/q4w | TNBC 400mg/q4w | NSCLC 300mg/q3w | ATC 400 mg/q4w | All Phase II Patients | |||||||||||||||
| 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 | 9/16 (56.3%) | 7/15 (46.7%) | 4/11 (36.4%) | 20/42 (47.6%) | 2/6 (33.3%) | 2/10 (20%) | 4/16 (25%) | 24/58 (41.4%) | 27/59 (45.8%) | 22/61 (36.1%) | 18/40 (45%) | 37/59 (62.7%) | 22/42 (52.4%) | 126/261 (48.3%) | ||||||||||||||
| Blood and lymphatic system disorders | ||||||||||||||||||||||||||||
| Anaemia | 2/16 (12.5%) | 0/15 (0%) | 0/11 (0%) | 2/42 (4.8%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 2/58 (3.4%) | 1/59 (1.7%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 1/42 (2.4%) | 2/261 (0.8%) | ||||||||||||||
| Lymphadenopathy | 0/16 (0%) | 0/15 (0%) | 1/11 (9.1%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 0/261 (0%) | ||||||||||||||
| Thrombocytopenia | 0/16 (0%) | 1/15 (6.7%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 0/261 (0%) | ||||||||||||||
| Cardiac disorders | ||||||||||||||||||||||||||||
| Acute coronary syndrome | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 1/59 (1.7%) | 0/42 (0%) | 1/261 (0.4%) | ||||||||||||||
| Acute myocardial infarction | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 1/59 (1.7%) | 0/42 (0%) | 1/261 (0.4%) | ||||||||||||||
| Arrhythmia | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 0/59 (0%) | 1/61 (1.6%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 1/261 (0.4%) | ||||||||||||||
| Atrial fibrillation | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 3/59 (5.1%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 1/42 (2.4%) | 4/261 (1.5%) | ||||||||||||||
| Atrial flutter | 0/16 (0%) | 0/15 (0%) | 1/11 (9.1%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 0/261 (0%) | ||||||||||||||
| Cardiac arrest | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 2/59 (3.4%) | 1/42 (2.4%) | 3/261 (1.1%) | ||||||||||||||
| Cardiac tamponade | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 1/59 (1.7%) | 0/42 (0%) | 1/261 (0.4%) | ||||||||||||||
| Coronary artery stenosis | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 0/59 (0%) | 1/61 (1.6%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 1/261 (0.4%) | ||||||||||||||
| Myocardial infarction | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 1/59 (1.7%) | 0/42 (0%) | 1/261 (0.4%) | ||||||||||||||
| Pericardial effusion | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 1/59 (1.7%) | 0/61 (0%) | 0/40 (0%) | 2/59 (3.4%) | 0/42 (0%) | 3/261 (1.1%) | ||||||||||||||
| Tachycardia | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 0/59 (0%) | 0/61 (0%) | 1/40 (2.5%) | 1/59 (1.7%) | 0/42 (0%) | 2/261 (0.8%) | ||||||||||||||
| Endocrine disorders | ||||||||||||||||||||||||||||
| Adrenal insufficiency | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 0/59 (0%) | 1/61 (1.6%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 1/261 (0.4%) | ||||||||||||||
| Eye disorders | ||||||||||||||||||||||||||||
| Diplopia | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 1/59 (1.7%) | 0/42 (0%) | 1/261 (0.4%) | ||||||||||||||
| Gastrointestinal disorders | ||||||||||||||||||||||||||||
| Abdominal distension | 1/16 (6.3%) | 0/15 (0%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 0/261 (0%) | ||||||||||||||
| Abdominal pain | 1/16 (6.3%) | 2/15 (13.3%) | 0/11 (0%) | 3/42 (7.1%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 3/58 (5.2%) | 0/59 (0%) | 1/61 (1.6%) | 2/40 (5%) | 0/59 (0%) | 0/42 (0%) | 3/261 (1.1%) | ||||||||||||||
| Autoimmune colitis | 0/16 (0%) | 0/15 (0%) | 1/11 (9.1%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 0/261 (0%) | ||||||||||||||
| Constipation | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 1/59 (1.7%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 1/261 (0.4%) | ||||||||||||||
| Diarrhoea | 0/16 (0%) | 1/15 (6.7%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 2/59 (3.4%) | 0/42 (0%) | 2/261 (0.8%) | ||||||||||||||
| Dysphagia | 0/16 (0%) | 0/15 (0%) | 1/11 (9.1%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 1/59 (1.7%) | 2/42 (4.8%) | 3/261 (1.1%) | ||||||||||||||
| Gastric ulcer | 0/16 (0%) | 1/15 (6.7%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 0/261 (0%) | ||||||||||||||
| Gastrointestinal haemorrhage | 1/16 (6.3%) | 1/15 (6.7%) | 0/11 (0%) | 2/42 (4.8%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 2/58 (3.4%) | 0/59 (0%) | 1/61 (1.6%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 1/261 (0.4%) | ||||||||||||||
| Ileus | 0/16 (0%) | 1/15 (6.7%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 1/59 (1.7%) | 0/42 (0%) | 1/261 (0.4%) | ||||||||||||||
| Intestinal obstruction | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 1/6 (16.7%) | 0/10 (0%) | 1/16 (6.3%) | 1/58 (1.7%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 0/261 (0%) | ||||||||||||||
| Melaena | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 1/42 (2.4%) | 1/261 (0.4%) | ||||||||||||||
| Nausea | 0/16 (0%) | 1/15 (6.7%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 1/10 (10%) | 1/16 (6.3%) | 2/58 (3.4%) | 0/59 (0%) | 0/61 (0%) | 1/40 (2.5%) | 0/59 (0%) | 0/42 (0%) | 1/261 (0.4%) | ||||||||||||||
| Rectal haemorrhage | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 1/59 (1.7%) | 0/42 (0%) | 1/261 (0.4%) | ||||||||||||||
| Upper gastrointestinal haemorrhage | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 0/59 (0%) | 1/61 (1.6%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 1/261 (0.4%) | ||||||||||||||
| Vomiting | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 1/10 (10%) | 1/16 (6.3%) | 1/58 (1.7%) | 1/59 (1.7%) | 0/61 (0%) | 1/40 (2.5%) | 0/59 (0%) | 0/42 (0%) | 2/261 (0.8%) | ||||||||||||||
| General disorders | ||||||||||||||||||||||||||||
| Asthenia | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 1/42 (2.4%) | 1/261 (0.4%) | ||||||||||||||
| Complication of device insertion | 1/16 (6.3%) | 0/15 (0%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 0/261 (0%) | ||||||||||||||
| Fatigue | 0/16 (0%) | 1/15 (6.7%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 1/59 (1.7%) | 0/42 (0%) | 1/261 (0.4%) | ||||||||||||||
| Non-cardiac chest pain | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 1/59 (1.7%) | 0/42 (0%) | 1/261 (0.4%) | ||||||||||||||
| Oedema peripheral | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 0/59 (0%) | 1/61 (1.6%) | 0/40 (0%) | 1/59 (1.7%) | 0/42 (0%) | 2/261 (0.8%) | ||||||||||||||
| Pain | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 0/59 (0%) | 0/61 (0%) | 1/40 (2.5%) | 0/59 (0%) | 0/42 (0%) | 1/261 (0.4%) | ||||||||||||||
| Peripheral swelling | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 0/59 (0%) | 1/61 (1.6%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 1/261 (0.4%) | ||||||||||||||
| Pyrexia | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 0/59 (0%) | 1/61 (1.6%) | 1/40 (2.5%) | 2/59 (3.4%) | 0/42 (0%) | 4/261 (1.5%) | ||||||||||||||
| Hepatobiliary disorders | ||||||||||||||||||||||||||||
| Autoimmune hepatitis | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 0/59 (0%) | 0/61 (0%) | 1/40 (2.5%) | 0/59 (0%) | 0/42 (0%) | 1/261 (0.4%) | ||||||||||||||
| Bile duct obstruction | 0/16 (0%) | 1/15 (6.7%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 1/42 (2.4%) | 1/261 (0.4%) | ||||||||||||||
| Hepatic failure | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 0/59 (0%) | 0/61 (0%) | 1/40 (2.5%) | 0/59 (0%) | 0/42 (0%) | 1/261 (0.4%) | ||||||||||||||
| Hyperbilirubinaemia | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 1/59 (1.7%) | 0/42 (0%) | 1/261 (0.4%) | ||||||||||||||
| Jaundice | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 1/59 (1.7%) | 0/42 (0%) | 1/261 (0.4%) | ||||||||||||||
| Immune system disorders | ||||||||||||||||||||||||||||
| Anaphylactic reaction | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 1/59 (1.7%) | 0/42 (0%) | 1/261 (0.4%) | ||||||||||||||
| Sarcoidosis | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 0/59 (0%) | 1/61 (1.6%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 1/261 (0.4%) | ||||||||||||||
| Infections and infestations | ||||||||||||||||||||||||||||
| Bacteraemia | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 1/42 (2.4%) | 1/261 (0.4%) | ||||||||||||||
| Bronchitis | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 1/59 (1.7%) | 0/42 (0%) | 1/261 (0.4%) | ||||||||||||||
| Cellulitis | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 0/59 (0%) | 2/61 (3.3%) | 0/40 (0%) | 0/59 (0%) | 2/42 (4.8%) | 4/261 (1.5%) | ||||||||||||||
| Clostridium difficile infection | 1/16 (6.3%) | 0/15 (0%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 0/261 (0%) | ||||||||||||||
| Empyema | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 0/59 (0%) | 1/61 (1.6%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 1/261 (0.4%) | ||||||||||||||
| Gastroenteritis viral | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 1/59 (1.7%) | 0/42 (0%) | 1/261 (0.4%) | ||||||||||||||
| Localised infection | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 1/42 (2.4%) | 1/261 (0.4%) | ||||||||||||||
| Pneumonia | 1/16 (6.3%) | 1/15 (6.7%) | 0/11 (0%) | 2/42 (4.8%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 2/58 (3.4%) | 3/59 (5.1%) | 0/61 (0%) | 0/40 (0%) | 5/59 (8.5%) | 3/42 (7.1%) | 11/261 (4.2%) | ||||||||||||||
| Postoperative wound infection | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 1/59 (1.7%) | 0/42 (0%) | 1/261 (0.4%) | ||||||||||||||
| Respiratory tract infection | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 1/59 (1.7%) | 0/61 (0%) | 1/40 (2.5%) | 0/59 (0%) | 0/42 (0%) | 2/261 (0.8%) | ||||||||||||||
| Sepsis | 1/16 (6.3%) | 1/15 (6.7%) | 0/11 (0%) | 2/42 (4.8%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 2/58 (3.4%) | 1/59 (1.7%) | 0/61 (0%) | 1/40 (2.5%) | 1/59 (1.7%) | 0/42 (0%) | 3/261 (1.1%) | ||||||||||||||
| Septic shock | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 1/59 (1.7%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 1/42 (2.4%) | 2/261 (0.8%) | ||||||||||||||
| Urinary tract infection | 1/16 (6.3%) | 0/15 (0%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 0/59 (0%) | 0/61 (0%) | 2/40 (5%) | 0/59 (0%) | 0/42 (0%) | 2/261 (0.8%) | ||||||||||||||
| Injury, poisoning and procedural complications | ||||||||||||||||||||||||||||
| Hip fracture | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 1/59 (1.7%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 1/42 (2.4%) | 2/261 (0.8%) | ||||||||||||||
| Overdose | 1/16 (6.3%) | 0/15 (0%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 0/261 (0%) | ||||||||||||||
| Thoracic vertebral fracture | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 1/42 (2.4%) | 1/261 (0.4%) | ||||||||||||||
| Tracheal obstruction | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 0/59 (0%) | 1/61 (1.6%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 1/261 (0.4%) | ||||||||||||||
| Wound dehiscence | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 0/59 (0%) | 1/61 (1.6%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 1/261 (0.4%) | ||||||||||||||
| Investigations | ||||||||||||||||||||||||||||
| Blood bilirubin increased | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 1/42 (2.4%) | 1/261 (0.4%) | ||||||||||||||
| Metabolism and nutrition disorders | ||||||||||||||||||||||||||||
| Dehydration | 0/16 (0%) | 1/15 (6.7%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 1/10 (10%) | 1/16 (6.3%) | 2/58 (3.4%) | 1/59 (1.7%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 2/42 (4.8%) | 3/261 (1.1%) | ||||||||||||||
| Diabetic ketoacidosis | 1/16 (6.3%) | 0/15 (0%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 0/261 (0%) | ||||||||||||||
| Failure to thrive | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 1/10 (10%) | 1/16 (6.3%) | 1/58 (1.7%) | 0/59 (0%) | 1/61 (1.6%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 1/261 (0.4%) | ||||||||||||||
| Hypercalcaemia | 1/16 (6.3%) | 1/15 (6.7%) | 0/11 (0%) | 2/42 (4.8%) | 1/6 (16.7%) | 0/10 (0%) | 1/16 (6.3%) | 3/58 (5.2%) | 1/59 (1.7%) | 0/61 (0%) | 0/40 (0%) | 1/59 (1.7%) | 1/42 (2.4%) | 3/261 (1.1%) | ||||||||||||||
| Hyperkalaemia | 0/16 (0%) | 0/15 (0%) | 1/11 (9.1%) | 1/42 (2.4%) | 0/6 (0%) | 1/10 (10%) | 1/16 (6.3%) | 2/58 (3.4%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 0/261 (0%) | ||||||||||||||
| Hypoglycaemia | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 0/59 (0%) | 1/61 (1.6%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 1/261 (0.4%) | ||||||||||||||
| Hypokalaemia | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 1/59 (1.7%) | 0/61 (0%) | 1/40 (2.5%) | 0/59 (0%) | 0/42 (0%) | 2/261 (0.8%) | ||||||||||||||
| Hyponatraemia | 1/16 (6.3%) | 0/15 (0%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 1/10 (10%) | 1/16 (6.3%) | 2/58 (3.4%) | 0/59 (0%) | 0/61 (0%) | 1/40 (2.5%) | 0/59 (0%) | 0/42 (0%) | 1/261 (0.4%) | ||||||||||||||
| Musculoskeletal and connective tissue disorders | ||||||||||||||||||||||||||||
| Back pain | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 1/59 (1.7%) | 0/61 (0%) | 1/40 (2.5%) | 4/59 (6.8%) | 0/42 (0%) | 6/261 (2.3%) | ||||||||||||||
| Bone pain | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 1/59 (1.7%) | 0/42 (0%) | 1/261 (0.4%) | ||||||||||||||
| Fistula | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 1/42 (2.4%) | 1/261 (0.4%) | ||||||||||||||
| Groin pain | 0/16 (0%) | 1/15 (6.7%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 0/261 (0%) | ||||||||||||||
| Musculoskeletal chest pain | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 0/59 (0%) | 1/61 (1.6%) | 0/40 (0%) | 1/59 (1.7%) | 0/42 (0%) | 2/261 (0.8%) | ||||||||||||||
| Pain in extremity | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 0/59 (0%) | 0/61 (0%) | 1/40 (2.5%) | 0/59 (0%) | 0/42 (0%) | 1/261 (0.4%) | ||||||||||||||
| Sjogren's syndrome | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 0/59 (0%) | 1/61 (1.6%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 1/261 (0.4%) | ||||||||||||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||||||||||||||||||
| Bladder cancer | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 1/59 (1.7%) | 0/42 (0%) | 1/261 (0.4%) | ||||||||||||||
| Cancer pain | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 1/59 (1.7%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 1/261 (0.4%) | ||||||||||||||
| Intracranial tumour haemorrhage | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 0/59 (0%) | 1/61 (1.6%) | 0/40 (0%) | 0/59 (0%) | 1/42 (2.4%) | 2/261 (0.8%) | ||||||||||||||
| Metastases to central nervous system | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 1/59 (1.7%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 1/42 (2.4%) | 2/261 (0.8%) | ||||||||||||||
| Second primary malignancy | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 0/59 (0%) | 1/61 (1.6%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 1/261 (0.4%) | ||||||||||||||
| Tumour haemorrhage | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 0/59 (0%) | 2/61 (3.3%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 2/261 (0.8%) | ||||||||||||||
| Tumour inflammation | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 1/42 (2.4%) | 1/261 (0.4%) | ||||||||||||||
| Tumour pain | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 1/59 (1.7%) | 0/61 (0%) | 2/40 (5%) | 0/59 (0%) | 0/42 (0%) | 3/261 (1.1%) | ||||||||||||||
| Nervous system disorders | ||||||||||||||||||||||||||||
| Ataxia | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 0/59 (0%) | 0/61 (0%) | 1/40 (2.5%) | 0/59 (0%) | 0/42 (0%) | 1/261 (0.4%) | ||||||||||||||
| Carotid artery occlusion | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 0/59 (0%) | 1/61 (1.6%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 1/261 (0.4%) | ||||||||||||||
| Central nervous system lesion | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 1/59 (1.7%) | 0/42 (0%) | 1/261 (0.4%) | ||||||||||||||
| Cognitive disorder | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 1/59 (1.7%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 1/261 (0.4%) | ||||||||||||||
| Encephalopathy | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 0/59 (0%) | 0/61 (0%) | 1/40 (2.5%) | 0/59 (0%) | 0/42 (0%) | 1/261 (0.4%) | ||||||||||||||
| Facial paralysis | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 0/59 (0%) | 0/61 (0%) | 1/40 (2.5%) | 0/59 (0%) | 0/42 (0%) | 1/261 (0.4%) | ||||||||||||||
| Haemorrhage intracranial | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 0/59 (0%) | 1/61 (1.6%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 1/261 (0.4%) | ||||||||||||||
| Hydrocephalus | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 1/59 (1.7%) | 0/42 (0%) | 1/261 (0.4%) | ||||||||||||||
| Intracranial pressure increased | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 0/59 (0%) | 1/61 (1.6%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 1/261 (0.4%) | ||||||||||||||
| Ischaemic stroke | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 1/59 (1.7%) | 0/42 (0%) | 1/261 (0.4%) | ||||||||||||||
| Seizure | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 0/59 (0%) | 1/61 (1.6%) | 0/40 (0%) | 1/59 (1.7%) | 0/42 (0%) | 2/261 (0.8%) | ||||||||||||||
| Spinal cord compression | 0/16 (0%) | 1/15 (6.7%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 3/59 (5.1%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 3/261 (1.1%) | ||||||||||||||
| Psychiatric disorders | ||||||||||||||||||||||||||||
| Confusional state | 0/16 (0%) | 1/15 (6.7%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 0/59 (0%) | 1/61 (1.6%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 1/261 (0.4%) | ||||||||||||||
| Depression | 1/16 (6.3%) | 0/15 (0%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 0/261 (0%) | ||||||||||||||
| Mental status changes | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 1/6 (16.7%) | 0/10 (0%) | 1/16 (6.3%) | 1/58 (1.7%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 0/261 (0%) | ||||||||||||||
| Renal and urinary disorders | ||||||||||||||||||||||||||||
| Renal failure | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 1/59 (1.7%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 1/261 (0.4%) | ||||||||||||||
| Reproductive system and breast disorders | ||||||||||||||||||||||||||||
| Pelvic pain | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 1/59 (1.7%) | 0/42 (0%) | 1/261 (0.4%) | ||||||||||||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||||||||||||||||
| Acute respiratory distress syndrome | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 1/59 (1.7%) | 0/42 (0%) | 1/261 (0.4%) | ||||||||||||||
| Bronchial obstruction | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 1/59 (1.7%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 1/261 (0.4%) | ||||||||||||||
| Chronic obstructive pulmonary disease | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 1/59 (1.7%) | 0/42 (0%) | 1/261 (0.4%) | ||||||||||||||
| Cough | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 1/59 (1.7%) | 0/42 (0%) | 1/261 (0.4%) | ||||||||||||||
| Dyspnoea | 1/16 (6.3%) | 0/15 (0%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 1/10 (10%) | 1/16 (6.3%) | 2/58 (3.4%) | 3/59 (5.1%) | 1/61 (1.6%) | 3/40 (7.5%) | 7/59 (11.9%) | 2/42 (4.8%) | 16/261 (6.1%) | ||||||||||||||
| Haemoptysis | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 2/59 (3.4%) | 0/42 (0%) | 2/261 (0.8%) | ||||||||||||||
| Hypoxia | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 1/10 (10%) | 1/16 (6.3%) | 1/58 (1.7%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 1/42 (2.4%) | 1/261 (0.4%) | ||||||||||||||
| Obstructive airways disorder | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 1/42 (2.4%) | 1/261 (0.4%) | ||||||||||||||
| Pharyngeal haemorrhage | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 1/42 (2.4%) | 1/261 (0.4%) | ||||||||||||||
| Pleural effusion | 0/16 (0%) | 0/15 (0%) | 1/11 (9.1%) | 1/42 (2.4%) | 0/6 (0%) | 1/10 (10%) | 1/16 (6.3%) | 2/58 (3.4%) | 1/59 (1.7%) | 1/61 (1.6%) | 5/40 (12.5%) | 2/59 (3.4%) | 2/42 (4.8%) | 11/261 (4.2%) | ||||||||||||||
| Pneumonia aspiration | 1/16 (6.3%) | 1/15 (6.7%) | 0/11 (0%) | 2/42 (4.8%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 2/58 (3.4%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 0/261 (0%) | ||||||||||||||
| Pneumonitis | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 2/59 (3.4%) | 1/61 (1.6%) | 0/40 (0%) | 1/59 (1.7%) | 0/42 (0%) | 4/261 (1.5%) | ||||||||||||||
| Pneumothorax | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 1/59 (1.7%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 1/261 (0.4%) | ||||||||||||||
| Pulmonary embolism | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 1/59 (1.7%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 1/261 (0.4%) | ||||||||||||||
| Respiratory distress | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 1/59 (1.7%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 1/261 (0.4%) | ||||||||||||||
| Respiratory failure | 0/16 (0%) | 1/15 (6.7%) | 1/11 (9.1%) | 2/42 (4.8%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 2/58 (3.4%) | 2/59 (3.4%) | 0/61 (0%) | 0/40 (0%) | 1/59 (1.7%) | 0/42 (0%) | 3/261 (1.1%) | ||||||||||||||
| Tracheal stenosis | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 1/42 (2.4%) | 1/261 (0.4%) | ||||||||||||||
| Skin and subcutaneous tissue disorders | ||||||||||||||||||||||||||||
| Dermatitis atopic | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 1/59 (1.7%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 1/261 (0.4%) | ||||||||||||||
| Vascular disorders | ||||||||||||||||||||||||||||
| Embolism | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 1/59 (1.7%) | 1/61 (1.6%) | 0/40 (0%) | 0/59 (0%) | 1/42 (2.4%) | 3/261 (1.1%) | ||||||||||||||
| Hypotension | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 1/42 (2.4%) | 1/261 (0.4%) | ||||||||||||||
| Lymphoedema | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 0/59 (0%) | 0/61 (0%) | 1/40 (2.5%) | 0/59 (0%) | 0/42 (0%) | 1/261 (0.4%) | ||||||||||||||
| Lymphorrhoea | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 0/59 (0%) | 0/61 (0%) | 1/40 (2.5%) | 0/59 (0%) | 0/42 (0%) | 1/261 (0.4%) | ||||||||||||||
| Superior vena cava syndrome | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 1/59 (1.7%) | 0/42 (0%) | 1/261 (0.4%) | ||||||||||||||
Other (Not Including Serious) Adverse Events |
||||||||||||||||||||||||||||
| 1mg/kg q2w | 3mg/kg q2w | 10mg/kg q2w | All Phase I q2w | 3mg/kg q4w | 5mg/kg q4w | All Phase I q4w | All Phase I Patients | NSCLC 400mg/q4w | Melanoma 400mg/q4w | TNBC 400mg/q4w | NSCLC 300mg/q3w | ATC 400 mg/q4w | All Phase II Patients | |||||||||||||||
| 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 | 16/16 (100%) | 15/15 (100%) | 11/11 (100%) | 42/42 (100%) | 6/6 (100%) | 10/10 (100%) | 16/16 (100%) | 58/58 (100%) | 54/59 (91.5%) | 55/61 (90.2%) | 37/40 (92.5%) | 56/59 (94.9%) | 39/42 (92.9%) | 241/261 (92.3%) | ||||||||||||||
| Blood and lymphatic system disorders | ||||||||||||||||||||||||||||
| Anaemia | 5/16 (31.3%) | 7/15 (46.7%) | 2/11 (18.2%) | 14/42 (33.3%) | 1/6 (16.7%) | 3/10 (30%) | 4/16 (25%) | 18/58 (31%) | 16/59 (27.1%) | 13/61 (21.3%) | 6/40 (15%) | 8/59 (13.6%) | 11/42 (26.2%) | 54/261 (20.7%) | ||||||||||||||
| Disseminated intravascular coagulation | 0/16 (0%) | 1/15 (6.7%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 0/261 (0%) | ||||||||||||||
| Eosinophilia | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 1/6 (16.7%) | 0/10 (0%) | 1/16 (6.3%) | 1/58 (1.7%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 0/261 (0%) | ||||||||||||||
| Iron deficiency anaemia | 0/16 (0%) | 1/15 (6.7%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 0/261 (0%) | ||||||||||||||
| Leukocytosis | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 1/10 (10%) | 1/16 (6.3%) | 1/58 (1.7%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 1/42 (2.4%) | 1/261 (0.4%) | ||||||||||||||
| Leukopenia | 1/16 (6.3%) | 0/15 (0%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 0/59 (0%) | 2/61 (3.3%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 2/261 (0.8%) | ||||||||||||||
| Lymph node pain | 1/16 (6.3%) | 0/15 (0%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 0/261 (0%) | ||||||||||||||
| Lymphopenia | 0/16 (0%) | 1/15 (6.7%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 1/59 (1.7%) | 3/61 (4.9%) | 1/40 (2.5%) | 1/59 (1.7%) | 1/42 (2.4%) | 7/261 (2.7%) | ||||||||||||||
| Neutropenia | 1/16 (6.3%) | 0/15 (0%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 1/59 (1.7%) | 1/42 (2.4%) | 2/261 (0.8%) | ||||||||||||||
| Thrombocytopenia | 0/16 (0%) | 2/15 (13.3%) | 0/11 (0%) | 2/42 (4.8%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 2/58 (3.4%) | 0/59 (0%) | 2/61 (3.3%) | 1/40 (2.5%) | 2/59 (3.4%) | 1/42 (2.4%) | 6/261 (2.3%) | ||||||||||||||
| Cardiac disorders | ||||||||||||||||||||||||||||
| Palpitations | 0/16 (0%) | 0/15 (0%) | 1/11 (9.1%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 0/261 (0%) | ||||||||||||||
| Sinus tachycardia | 1/16 (6.3%) | 0/15 (0%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 1/59 (1.7%) | 1/61 (1.6%) | 1/40 (2.5%) | 2/59 (3.4%) | 1/42 (2.4%) | 6/261 (2.3%) | ||||||||||||||
| Tachycardia | 0/16 (0%) | 1/15 (6.7%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 1/10 (10%) | 1/16 (6.3%) | 2/58 (3.4%) | 1/59 (1.7%) | 2/61 (3.3%) | 0/40 (0%) | 1/59 (1.7%) | 1/42 (2.4%) | 5/261 (1.9%) | ||||||||||||||
| Ear and labyrinth disorders | ||||||||||||||||||||||||||||
| Hypoacusis | 0/16 (0%) | 0/15 (0%) | 1/11 (9.1%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 0/59 (0%) | 0/61 (0%) | 1/40 (2.5%) | 0/59 (0%) | 0/42 (0%) | 1/261 (0.4%) | ||||||||||||||
| Otorrhoea | 1/16 (6.3%) | 0/15 (0%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 0/261 (0%) | ||||||||||||||
| Vertigo | 0/16 (0%) | 1/15 (6.7%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 0/59 (0%) | 1/61 (1.6%) | 0/40 (0%) | 1/59 (1.7%) | 1/42 (2.4%) | 3/261 (1.1%) | ||||||||||||||
| Endocrine disorders | ||||||||||||||||||||||||||||
| Hyperthyroidism | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 5/59 (8.5%) | 4/61 (6.6%) | 1/40 (2.5%) | 2/59 (3.4%) | 1/42 (2.4%) | 13/261 (5%) | ||||||||||||||
| Hypothyroidism | 3/16 (18.8%) | 3/15 (20%) | 1/11 (9.1%) | 7/42 (16.7%) | 0/6 (0%) | 2/10 (20%) | 2/16 (12.5%) | 9/58 (15.5%) | 4/59 (6.8%) | 5/61 (8.2%) | 3/40 (7.5%) | 3/59 (5.1%) | 2/42 (4.8%) | 17/261 (6.5%) | ||||||||||||||
| Eye disorders | ||||||||||||||||||||||||||||
| Periorbital oedema | 0/16 (0%) | 1/15 (6.7%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 0/261 (0%) | ||||||||||||||
| Photopsia | 0/16 (0%) | 0/15 (0%) | 1/11 (9.1%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 0/261 (0%) | ||||||||||||||
| Vision blurred | 1/16 (6.3%) | 1/15 (6.7%) | 0/11 (0%) | 2/42 (4.8%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 2/58 (3.4%) | 0/59 (0%) | 0/61 (0%) | 1/40 (2.5%) | 0/59 (0%) | 0/42 (0%) | 1/261 (0.4%) | ||||||||||||||
| Gastrointestinal disorders | ||||||||||||||||||||||||||||
| Abdominal discomfort | 1/16 (6.3%) | 0/15 (0%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 0/261 (0%) | ||||||||||||||
| Abdominal distension | 1/16 (6.3%) | 1/15 (6.7%) | 1/11 (9.1%) | 3/42 (7.1%) | 0/6 (0%) | 1/10 (10%) | 1/16 (6.3%) | 4/58 (6.9%) | 1/59 (1.7%) | 1/61 (1.6%) | 1/40 (2.5%) | 0/59 (0%) | 1/42 (2.4%) | 4/261 (1.5%) | ||||||||||||||
| Abdominal pain | 3/16 (18.8%) | 2/15 (13.3%) | 2/11 (18.2%) | 7/42 (16.7%) | 2/6 (33.3%) | 3/10 (30%) | 5/16 (31.3%) | 12/58 (20.7%) | 3/59 (5.1%) | 2/61 (3.3%) | 5/40 (12.5%) | 5/59 (8.5%) | 3/42 (7.1%) | 18/261 (6.9%) | ||||||||||||||
| Abdominal pain lower | 0/16 (0%) | 0/15 (0%) | 1/11 (9.1%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 0/59 (0%) | 1/61 (1.6%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 1/261 (0.4%) | ||||||||||||||
| Abdominal pain upper | 1/16 (6.3%) | 1/15 (6.7%) | 1/11 (9.1%) | 3/42 (7.1%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 3/58 (5.2%) | 1/59 (1.7%) | 1/61 (1.6%) | 0/40 (0%) | 2/59 (3.4%) | 0/42 (0%) | 4/261 (1.5%) | ||||||||||||||
| Ascites | 1/16 (6.3%) | 0/15 (0%) | 0/11 (0%) | 1/42 (2.4%) | 2/6 (33.3%) | 2/10 (20%) | 4/16 (25%) | 5/58 (8.6%) | 0/59 (0%) | 0/61 (0%) | 2/40 (5%) | 0/59 (0%) | 0/42 (0%) | 2/261 (0.8%) | ||||||||||||||
| Autoimmune colitis | 0/16 (0%) | 0/15 (0%) | 1/11 (9.1%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 0/261 (0%) | ||||||||||||||
| Constipation | 5/16 (31.3%) | 5/15 (33.3%) | 0/11 (0%) | 10/42 (23.8%) | 2/6 (33.3%) | 0/10 (0%) | 2/16 (12.5%) | 12/58 (20.7%) | 8/59 (13.6%) | 7/61 (11.5%) | 9/40 (22.5%) | 9/59 (15.3%) | 5/42 (11.9%) | 38/261 (14.6%) | ||||||||||||||
| Diarrhoea | 7/16 (43.8%) | 6/15 (40%) | 1/11 (9.1%) | 14/42 (33.3%) | 0/6 (0%) | 3/10 (30%) | 3/16 (18.8%) | 17/58 (29.3%) | 8/59 (13.6%) | 8/61 (13.1%) | 1/40 (2.5%) | 12/59 (20.3%) | 8/42 (19%) | 37/261 (14.2%) | ||||||||||||||
| Dry mouth | 3/16 (18.8%) | 1/15 (6.7%) | 1/11 (9.1%) | 5/42 (11.9%) | 0/6 (0%) | 1/10 (10%) | 1/16 (6.3%) | 6/58 (10.3%) | 3/59 (5.1%) | 3/61 (4.9%) | 1/40 (2.5%) | 0/59 (0%) | 3/42 (7.1%) | 10/261 (3.8%) | ||||||||||||||
| Dyspepsia | 0/16 (0%) | 0/15 (0%) | 1/11 (9.1%) | 1/42 (2.4%) | 0/6 (0%) | 1/10 (10%) | 1/16 (6.3%) | 2/58 (3.4%) | 2/59 (3.4%) | 3/61 (4.9%) | 0/40 (0%) | 1/59 (1.7%) | 1/42 (2.4%) | 7/261 (2.7%) | ||||||||||||||
| Dysphagia | 1/16 (6.3%) | 2/15 (13.3%) | 0/11 (0%) | 3/42 (7.1%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 3/58 (5.2%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 3/59 (5.1%) | 5/42 (11.9%) | 8/261 (3.1%) | ||||||||||||||
| Flatulence | 0/16 (0%) | 1/15 (6.7%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 0/261 (0%) | ||||||||||||||
| Gastrooesophageal reflux disease | 2/16 (12.5%) | 1/15 (6.7%) | 0/11 (0%) | 3/42 (7.1%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 3/58 (5.2%) | 1/59 (1.7%) | 1/61 (1.6%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 2/261 (0.8%) | ||||||||||||||
| Mouth haemorrhage | 0/16 (0%) | 0/15 (0%) | 1/11 (9.1%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 1/42 (2.4%) | 1/261 (0.4%) | ||||||||||||||
| Mouth ulceration | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 1/10 (10%) | 1/16 (6.3%) | 1/58 (1.7%) | 1/59 (1.7%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 1/261 (0.4%) | ||||||||||||||
| Nausea | 7/16 (43.8%) | 4/15 (26.7%) | 3/11 (27.3%) | 14/42 (33.3%) | 3/6 (50%) | 4/10 (40%) | 7/16 (43.8%) | 21/58 (36.2%) | 9/59 (15.3%) | 6/61 (9.8%) | 13/40 (32.5%) | 15/59 (25.4%) | 2/42 (4.8%) | 45/261 (17.2%) | ||||||||||||||
| Pancreatic duct dilatation | 1/16 (6.3%) | 0/15 (0%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 0/261 (0%) | ||||||||||||||
| Rectal haemorrhage | 1/16 (6.3%) | 0/15 (0%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 0/261 (0%) | ||||||||||||||
| Stomatitis | 0/16 (0%) | 1/15 (6.7%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 1/59 (1.7%) | 1/61 (1.6%) | 2/40 (5%) | 1/59 (1.7%) | 1/42 (2.4%) | 6/261 (2.3%) | ||||||||||||||
| Toothache | 1/16 (6.3%) | 0/15 (0%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 1/59 (1.7%) | 0/42 (0%) | 1/261 (0.4%) | ||||||||||||||
| Vomiting | 6/16 (37.5%) | 1/15 (6.7%) | 3/11 (27.3%) | 10/42 (23.8%) | 2/6 (33.3%) | 2/10 (20%) | 4/16 (25%) | 14/58 (24.1%) | 8/59 (13.6%) | 8/61 (13.1%) | 5/40 (12.5%) | 8/59 (13.6%) | 3/42 (7.1%) | 32/261 (12.3%) | ||||||||||||||
| General disorders | ||||||||||||||||||||||||||||
| Asthenia | 1/16 (6.3%) | 1/15 (6.7%) | 0/11 (0%) | 2/42 (4.8%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 2/58 (3.4%) | 12/59 (20.3%) | 8/61 (13.1%) | 4/40 (10%) | 12/59 (20.3%) | 8/42 (19%) | 44/261 (16.9%) | ||||||||||||||
| Chills | 2/16 (12.5%) | 1/15 (6.7%) | 1/11 (9.1%) | 4/42 (9.5%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 4/58 (6.9%) | 0/59 (0%) | 1/61 (1.6%) | 2/40 (5%) | 2/59 (3.4%) | 1/42 (2.4%) | 6/261 (2.3%) | ||||||||||||||
| Face oedema | 0/16 (0%) | 0/15 (0%) | 1/11 (9.1%) | 1/42 (2.4%) | 0/6 (0%) | 1/10 (10%) | 1/16 (6.3%) | 2/58 (3.4%) | 1/59 (1.7%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 1/42 (2.4%) | 2/261 (0.8%) | ||||||||||||||
| Fatigue | 10/16 (62.5%) | 3/15 (20%) | 2/11 (18.2%) | 15/42 (35.7%) | 2/6 (33.3%) | 5/10 (50%) | 7/16 (43.8%) | 22/58 (37.9%) | 11/59 (18.6%) | 12/61 (19.7%) | 13/40 (32.5%) | 12/59 (20.3%) | 6/42 (14.3%) | 54/261 (20.7%) | ||||||||||||||
| Inflammation | 1/16 (6.3%) | 0/15 (0%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 1/42 (2.4%) | 1/261 (0.4%) | ||||||||||||||
| Influenza like illness | 0/16 (0%) | 1/15 (6.7%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 0/59 (0%) | 1/61 (1.6%) | 0/40 (0%) | 0/59 (0%) | 1/42 (2.4%) | 2/261 (0.8%) | ||||||||||||||
| Malaise | 1/16 (6.3%) | 1/15 (6.7%) | 0/11 (0%) | 2/42 (4.8%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 2/58 (3.4%) | 4/59 (6.8%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 4/261 (1.5%) | ||||||||||||||
| Non-cardiac chest pain | 1/16 (6.3%) | 2/15 (13.3%) | 1/11 (9.1%) | 4/42 (9.5%) | 0/6 (0%) | 1/10 (10%) | 1/16 (6.3%) | 5/58 (8.6%) | 2/59 (3.4%) | 3/61 (4.9%) | 2/40 (5%) | 8/59 (13.6%) | 0/42 (0%) | 15/261 (5.7%) | ||||||||||||||
| Oedema | 0/16 (0%) | 1/15 (6.7%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 0/261 (0%) | ||||||||||||||
| Oedema peripheral | 1/16 (6.3%) | 2/15 (13.3%) | 2/11 (18.2%) | 5/42 (11.9%) | 0/6 (0%) | 1/10 (10%) | 1/16 (6.3%) | 6/58 (10.3%) | 5/59 (8.5%) | 3/61 (4.9%) | 5/40 (12.5%) | 4/59 (6.8%) | 7/42 (16.7%) | 24/261 (9.2%) | ||||||||||||||
| Pain | 0/16 (0%) | 1/15 (6.7%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 1/59 (1.7%) | 1/61 (1.6%) | 0/40 (0%) | 2/59 (3.4%) | 1/42 (2.4%) | 5/261 (1.9%) | ||||||||||||||
| Peripheral swelling | 0/16 (0%) | 1/15 (6.7%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 0/59 (0%) | 3/61 (4.9%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 3/261 (1.1%) | ||||||||||||||
| Pyrexia | 2/16 (12.5%) | 2/15 (13.3%) | 1/11 (9.1%) | 5/42 (11.9%) | 0/6 (0%) | 1/10 (10%) | 1/16 (6.3%) | 6/58 (10.3%) | 9/59 (15.3%) | 9/61 (14.8%) | 3/40 (7.5%) | 11/59 (18.6%) | 9/42 (21.4%) | 41/261 (15.7%) | ||||||||||||||
| Swelling face | 1/16 (6.3%) | 0/15 (0%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 0/59 (0%) | 1/61 (1.6%) | 0/40 (0%) | 1/59 (1.7%) | 0/42 (0%) | 2/261 (0.8%) | ||||||||||||||
| Hepatobiliary disorders | ||||||||||||||||||||||||||||
| Cholecystitis | 0/16 (0%) | 1/15 (6.7%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 0/261 (0%) | ||||||||||||||
| Hyperbilirubinaemia | 0/16 (0%) | 0/15 (0%) | 1/11 (9.1%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 1/59 (1.7%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 1/261 (0.4%) | ||||||||||||||
| Immune system disorders | ||||||||||||||||||||||||||||
| Food allergy | 1/16 (6.3%) | 0/15 (0%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 0/261 (0%) | ||||||||||||||
| Seasonal allergy | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 1/10 (10%) | 1/16 (6.3%) | 1/58 (1.7%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 0/261 (0%) | ||||||||||||||
| Infections and infestations | ||||||||||||||||||||||||||||
| Abdominal infection | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 1/10 (10%) | 1/16 (6.3%) | 1/58 (1.7%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 1/42 (2.4%) | 1/261 (0.4%) | ||||||||||||||
| Acute sinusitis | 1/16 (6.3%) | 0/15 (0%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 0/59 (0%) | 1/61 (1.6%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 1/261 (0.4%) | ||||||||||||||
| Bacteraemia | 1/16 (6.3%) | 1/15 (6.7%) | 0/11 (0%) | 2/42 (4.8%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 2/58 (3.4%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 0/261 (0%) | ||||||||||||||
| Fungal skin infection | 0/16 (0%) | 1/15 (6.7%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 0/59 (0%) | 1/61 (1.6%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 1/261 (0.4%) | ||||||||||||||
| Influenza | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 4/59 (6.8%) | 0/61 (0%) | 0/40 (0%) | 1/59 (1.7%) | 1/42 (2.4%) | 6/261 (2.3%) | ||||||||||||||
| Laryngitis bacterial | 0/16 (0%) | 1/15 (6.7%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 0/261 (0%) | ||||||||||||||
| Nasopharyngitis | 1/16 (6.3%) | 0/15 (0%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 2/59 (3.4%) | 0/61 (0%) | 0/40 (0%) | 2/59 (3.4%) | 2/42 (4.8%) | 6/261 (2.3%) | ||||||||||||||
| Oral candidiasis | 1/16 (6.3%) | 1/15 (6.7%) | 0/11 (0%) | 2/42 (4.8%) | 1/6 (16.7%) | 0/10 (0%) | 1/16 (6.3%) | 3/58 (5.2%) | 0/59 (0%) | 1/61 (1.6%) | 0/40 (0%) | 1/59 (1.7%) | 1/42 (2.4%) | 3/261 (1.1%) | ||||||||||||||
| Otitis media | 1/16 (6.3%) | 0/15 (0%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 0/261 (0%) | ||||||||||||||
| Peritonitis | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 1/10 (10%) | 1/16 (6.3%) | 1/58 (1.7%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 0/261 (0%) | ||||||||||||||
| Pneumonia | 1/16 (6.3%) | 2/15 (13.3%) | 0/11 (0%) | 3/42 (7.1%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 3/58 (5.2%) | 3/59 (5.1%) | 1/61 (1.6%) | 0/40 (0%) | 3/59 (5.1%) | 3/42 (7.1%) | 10/261 (3.8%) | ||||||||||||||
| Postoperative wound infection | 1/16 (6.3%) | 0/15 (0%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 0/59 (0%) | 1/61 (1.6%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 1/261 (0.4%) | ||||||||||||||
| Rhinitis | 1/16 (6.3%) | 0/15 (0%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 1/42 (2.4%) | 1/261 (0.4%) | ||||||||||||||
| Sinusitis | 1/16 (6.3%) | 0/15 (0%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 1/10 (10%) | 1/16 (6.3%) | 2/58 (3.4%) | 0/59 (0%) | 0/61 (0%) | 1/40 (2.5%) | 0/59 (0%) | 0/42 (0%) | 1/261 (0.4%) | ||||||||||||||
| Upper respiratory tract infection | 0/16 (0%) | 1/15 (6.7%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 3/59 (5.1%) | 8/61 (13.1%) | 0/40 (0%) | 2/59 (3.4%) | 0/42 (0%) | 13/261 (5%) | ||||||||||||||
| Urinary tract infection | 1/16 (6.3%) | 3/15 (20%) | 0/11 (0%) | 4/42 (9.5%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 4/58 (6.9%) | 2/59 (3.4%) | 2/61 (3.3%) | 1/40 (2.5%) | 2/59 (3.4%) | 0/42 (0%) | 7/261 (2.7%) | ||||||||||||||
| Injury, poisoning and procedural complications | ||||||||||||||||||||||||||||
| Contusion | 0/16 (0%) | 1/15 (6.7%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 0/59 (0%) | 1/61 (1.6%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 1/261 (0.4%) | ||||||||||||||
| Fall | 1/16 (6.3%) | 1/15 (6.7%) | 0/11 (0%) | 2/42 (4.8%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 2/58 (3.4%) | 0/59 (0%) | 1/61 (1.6%) | 1/40 (2.5%) | 0/59 (0%) | 0/42 (0%) | 2/261 (0.8%) | ||||||||||||||
| Joint dislocation | 1/16 (6.3%) | 0/15 (0%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 0/261 (0%) | ||||||||||||||
| Ligament rupture | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 1/10 (10%) | 1/16 (6.3%) | 1/58 (1.7%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 0/261 (0%) | ||||||||||||||
| Post-traumatic pain | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 1/6 (16.7%) | 0/10 (0%) | 1/16 (6.3%) | 1/58 (1.7%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 0/261 (0%) | ||||||||||||||
| Procedural pain | 2/16 (12.5%) | 1/15 (6.7%) | 0/11 (0%) | 3/42 (7.1%) | 1/6 (16.7%) | 0/10 (0%) | 1/16 (6.3%) | 4/58 (6.9%) | 1/59 (1.7%) | 1/61 (1.6%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 2/261 (0.8%) | ||||||||||||||
| Wound complication | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 1/10 (10%) | 1/16 (6.3%) | 1/58 (1.7%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 1/42 (2.4%) | 1/261 (0.4%) | ||||||||||||||
| Investigations | ||||||||||||||||||||||||||||
| Alanine aminotransferase increased | 1/16 (6.3%) | 0/15 (0%) | 1/11 (9.1%) | 2/42 (4.8%) | 0/6 (0%) | 1/10 (10%) | 1/16 (6.3%) | 3/58 (5.2%) | 2/59 (3.4%) | 7/61 (11.5%) | 5/40 (12.5%) | 5/59 (8.5%) | 3/42 (7.1%) | 22/261 (8.4%) | ||||||||||||||
| Aspartate aminotransferase increased | 2/16 (12.5%) | 1/15 (6.7%) | 2/11 (18.2%) | 5/42 (11.9%) | 0/6 (0%) | 1/10 (10%) | 1/16 (6.3%) | 6/58 (10.3%) | 3/59 (5.1%) | 7/61 (11.5%) | 8/40 (20%) | 5/59 (8.5%) | 2/42 (4.8%) | 25/261 (9.6%) | ||||||||||||||
| Bacterial test positive | 0/16 (0%) | 1/15 (6.7%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 0/261 (0%) | ||||||||||||||
| Blood alkaline phosphatase increased | 3/16 (18.8%) | 2/15 (13.3%) | 0/11 (0%) | 5/42 (11.9%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 5/58 (8.6%) | 2/59 (3.4%) | 2/61 (3.3%) | 6/40 (15%) | 3/59 (5.1%) | 1/42 (2.4%) | 14/261 (5.4%) | ||||||||||||||
| Blood bilirubin increased | 1/16 (6.3%) | 1/15 (6.7%) | 0/11 (0%) | 2/42 (4.8%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 2/58 (3.4%) | 0/59 (0%) | 1/61 (1.6%) | 0/40 (0%) | 3/59 (5.1%) | 1/42 (2.4%) | 5/261 (1.9%) | ||||||||||||||
| Blood creatinine decreased | 1/16 (6.3%) | 0/15 (0%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 0/261 (0%) | ||||||||||||||
| Blood creatinine increased | 1/16 (6.3%) | 1/15 (6.7%) | 0/11 (0%) | 2/42 (4.8%) | 0/6 (0%) | 1/10 (10%) | 1/16 (6.3%) | 3/58 (5.2%) | 1/59 (1.7%) | 4/61 (6.6%) | 1/40 (2.5%) | 4/59 (6.8%) | 0/42 (0%) | 10/261 (3.8%) | ||||||||||||||
| Blood thyroid stimulating hormone increased | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 1/10 (10%) | 1/16 (6.3%) | 1/58 (1.7%) | 0/59 (0%) | 0/61 (0%) | 1/40 (2.5%) | 0/59 (0%) | 1/42 (2.4%) | 2/261 (0.8%) | ||||||||||||||
| Gamma-glutamyltransferase increased | 0/16 (0%) | 1/15 (6.7%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 1/59 (1.7%) | 1/61 (1.6%) | 2/40 (5%) | 3/59 (5.1%) | 1/42 (2.4%) | 8/261 (3.1%) | ||||||||||||||
| Lymphocyte count decreased | 0/16 (0%) | 0/15 (0%) | 1/11 (9.1%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 0/59 (0%) | 3/61 (4.9%) | 2/40 (5%) | 0/59 (0%) | 0/42 (0%) | 5/261 (1.9%) | ||||||||||||||
| Transaminases increased | 1/16 (6.3%) | 1/15 (6.7%) | 0/11 (0%) | 2/42 (4.8%) | 0/6 (0%) | 1/10 (10%) | 1/16 (6.3%) | 3/58 (5.2%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 0/261 (0%) | ||||||||||||||
| Weight decreased | 4/16 (25%) | 2/15 (13.3%) | 1/11 (9.1%) | 7/42 (16.7%) | 1/6 (16.7%) | 3/10 (30%) | 4/16 (25%) | 11/58 (19%) | 6/59 (10.2%) | 5/61 (8.2%) | 2/40 (5%) | 9/59 (15.3%) | 2/42 (4.8%) | 24/261 (9.2%) | ||||||||||||||
| Weight increased | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 1/6 (16.7%) | 0/10 (0%) | 1/16 (6.3%) | 1/58 (1.7%) | 0/59 (0%) | 0/61 (0%) | 1/40 (2.5%) | 0/59 (0%) | 0/42 (0%) | 1/261 (0.4%) | ||||||||||||||
| White blood cell count decreased | 0/16 (0%) | 0/15 (0%) | 1/11 (9.1%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 0/59 (0%) | 3/61 (4.9%) | 0/40 (0%) | 1/59 (1.7%) | 0/42 (0%) | 4/261 (1.5%) | ||||||||||||||
| Metabolism and nutrition disorders | ||||||||||||||||||||||||||||
| Cachexia | 1/16 (6.3%) | 0/15 (0%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 0/59 (0%) | 1/61 (1.6%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 1/261 (0.4%) | ||||||||||||||
| Decreased appetite | 5/16 (31.3%) | 1/15 (6.7%) | 3/11 (27.3%) | 9/42 (21.4%) | 2/6 (33.3%) | 2/10 (20%) | 4/16 (25%) | 13/58 (22.4%) | 18/59 (30.5%) | 13/61 (21.3%) | 7/40 (17.5%) | 17/59 (28.8%) | 5/42 (11.9%) | 60/261 (23%) | ||||||||||||||
| Dehydration | 0/16 (0%) | 2/15 (13.3%) | 1/11 (9.1%) | 3/42 (7.1%) | 2/6 (33.3%) | 0/10 (0%) | 2/16 (12.5%) | 5/58 (8.6%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 1/59 (1.7%) | 1/42 (2.4%) | 2/261 (0.8%) | ||||||||||||||
| Diabetes mellitus | 1/16 (6.3%) | 0/15 (0%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 1/59 (1.7%) | 1/61 (1.6%) | 0/40 (0%) | 1/59 (1.7%) | 0/42 (0%) | 3/261 (1.1%) | ||||||||||||||
| Hypercalcaemia | 0/16 (0%) | 1/15 (6.7%) | 2/11 (18.2%) | 3/42 (7.1%) | 1/6 (16.7%) | 0/10 (0%) | 1/16 (6.3%) | 4/58 (6.9%) | 4/59 (6.8%) | 0/61 (0%) | 0/40 (0%) | 2/59 (3.4%) | 3/42 (7.1%) | 9/261 (3.4%) | ||||||||||||||
| Hyperglycaemia | 3/16 (18.8%) | 0/15 (0%) | 1/11 (9.1%) | 4/42 (9.5%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 4/58 (6.9%) | 1/59 (1.7%) | 4/61 (6.6%) | 1/40 (2.5%) | 3/59 (5.1%) | 2/42 (4.8%) | 11/261 (4.2%) | ||||||||||||||
| Hyperkalaemia | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 1/6 (16.7%) | 0/10 (0%) | 1/16 (6.3%) | 1/58 (1.7%) | 1/59 (1.7%) | 0/61 (0%) | 1/40 (2.5%) | 1/59 (1.7%) | 1/42 (2.4%) | 4/261 (1.5%) | ||||||||||||||
| Hypernatraemia | 1/16 (6.3%) | 0/15 (0%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 0/261 (0%) | ||||||||||||||
| Hyperphosphataemia | 0/16 (0%) | 1/15 (6.7%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 0/59 (0%) | 0/61 (0%) | 1/40 (2.5%) | 0/59 (0%) | 0/42 (0%) | 1/261 (0.4%) | ||||||||||||||
| Hyperuricaemia | 1/16 (6.3%) | 0/15 (0%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 0/261 (0%) | ||||||||||||||
| Hypoalbuminaemia | 1/16 (6.3%) | 1/15 (6.7%) | 0/11 (0%) | 2/42 (4.8%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 2/58 (3.4%) | 3/59 (5.1%) | 2/61 (3.3%) | 3/40 (7.5%) | 4/59 (6.8%) | 2/42 (4.8%) | 14/261 (5.4%) | ||||||||||||||
| Hypocalcaemia | 1/16 (6.3%) | 0/15 (0%) | 1/11 (9.1%) | 2/42 (4.8%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 2/58 (3.4%) | 0/59 (0%) | 0/61 (0%) | 1/40 (2.5%) | 2/59 (3.4%) | 5/42 (11.9%) | 8/261 (3.1%) | ||||||||||||||
| Hypoglycaemia | 1/16 (6.3%) | 1/15 (6.7%) | 0/11 (0%) | 2/42 (4.8%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 2/58 (3.4%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 0/261 (0%) | ||||||||||||||
| Hypokalaemia | 1/16 (6.3%) | 2/15 (13.3%) | 1/11 (9.1%) | 4/42 (9.5%) | 1/6 (16.7%) | 0/10 (0%) | 1/16 (6.3%) | 5/58 (8.6%) | 2/59 (3.4%) | 3/61 (4.9%) | 2/40 (5%) | 6/59 (10.2%) | 4/42 (9.5%) | 17/261 (6.5%) | ||||||||||||||
| Hypomagnesaemia | 1/16 (6.3%) | 0/15 (0%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 0/59 (0%) | 2/61 (3.3%) | 2/40 (5%) | 3/59 (5.1%) | 3/42 (7.1%) | 10/261 (3.8%) | ||||||||||||||
| Hyponatraemia | 2/16 (12.5%) | 3/15 (20%) | 1/11 (9.1%) | 6/42 (14.3%) | 0/6 (0%) | 1/10 (10%) | 1/16 (6.3%) | 7/58 (12.1%) | 2/59 (3.4%) | 3/61 (4.9%) | 4/40 (10%) | 2/59 (3.4%) | 3/42 (7.1%) | 14/261 (5.4%) | ||||||||||||||
| Hypophosphataemia | 0/16 (0%) | 2/15 (13.3%) | 1/11 (9.1%) | 3/42 (7.1%) | 0/6 (0%) | 1/10 (10%) | 1/16 (6.3%) | 4/58 (6.9%) | 3/59 (5.1%) | 4/61 (6.6%) | 1/40 (2.5%) | 1/59 (1.7%) | 2/42 (4.8%) | 11/261 (4.2%) | ||||||||||||||
| Musculoskeletal and connective tissue disorders | ||||||||||||||||||||||||||||
| Arthralgia | 0/16 (0%) | 3/15 (20%) | 1/11 (9.1%) | 4/42 (9.5%) | 1/6 (16.7%) | 2/10 (20%) | 3/16 (18.8%) | 7/58 (12.1%) | 8/59 (13.6%) | 7/61 (11.5%) | 0/40 (0%) | 6/59 (10.2%) | 6/42 (14.3%) | 27/261 (10.3%) | ||||||||||||||
| Back pain | 2/16 (12.5%) | 2/15 (13.3%) | 0/11 (0%) | 4/42 (9.5%) | 1/6 (16.7%) | 0/10 (0%) | 1/16 (6.3%) | 5/58 (8.6%) | 8/59 (13.6%) | 1/61 (1.6%) | 3/40 (7.5%) | 10/59 (16.9%) | 5/42 (11.9%) | 27/261 (10.3%) | ||||||||||||||
| Bone pain | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 3/59 (5.1%) | 2/61 (3.3%) | 0/40 (0%) | 3/59 (5.1%) | 0/42 (0%) | 8/261 (3.1%) | ||||||||||||||
| Coccydynia | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 1/6 (16.7%) | 0/10 (0%) | 1/16 (6.3%) | 1/58 (1.7%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 0/261 (0%) | ||||||||||||||
| Flank pain | 1/16 (6.3%) | 1/15 (6.7%) | 0/11 (0%) | 2/42 (4.8%) | 0/6 (0%) | 1/10 (10%) | 1/16 (6.3%) | 3/58 (5.2%) | 1/59 (1.7%) | 2/61 (3.3%) | 1/40 (2.5%) | 0/59 (0%) | 0/42 (0%) | 4/261 (1.5%) | ||||||||||||||
| Groin pain | 0/16 (0%) | 2/15 (13.3%) | 0/11 (0%) | 2/42 (4.8%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 2/58 (3.4%) | 0/59 (0%) | 2/61 (3.3%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 2/261 (0.8%) | ||||||||||||||
| Limb discomfort | 0/16 (0%) | 0/15 (0%) | 1/11 (9.1%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 0/261 (0%) | ||||||||||||||
| Muscle spasms | 2/16 (12.5%) | 0/15 (0%) | 0/11 (0%) | 2/42 (4.8%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 2/58 (3.4%) | 2/59 (3.4%) | 1/61 (1.6%) | 0/40 (0%) | 1/59 (1.7%) | 0/42 (0%) | 4/261 (1.5%) | ||||||||||||||
| Muscular weakness | 1/16 (6.3%) | 1/15 (6.7%) | 1/11 (9.1%) | 3/42 (7.1%) | 1/6 (16.7%) | 0/10 (0%) | 1/16 (6.3%) | 4/58 (6.9%) | 1/59 (1.7%) | 4/61 (6.6%) | 3/40 (7.5%) | 1/59 (1.7%) | 1/42 (2.4%) | 10/261 (3.8%) | ||||||||||||||
| Musculoskeletal chest pain | 2/16 (12.5%) | 0/15 (0%) | 0/11 (0%) | 2/42 (4.8%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 2/58 (3.4%) | 0/59 (0%) | 2/61 (3.3%) | 2/40 (5%) | 2/59 (3.4%) | 2/42 (4.8%) | 8/261 (3.1%) | ||||||||||||||
| Musculoskeletal pain | 0/16 (0%) | 1/15 (6.7%) | 2/11 (18.2%) | 3/42 (7.1%) | 0/6 (0%) | 1/10 (10%) | 1/16 (6.3%) | 4/58 (6.9%) | 5/59 (8.5%) | 1/61 (1.6%) | 1/40 (2.5%) | 9/59 (15.3%) | 3/42 (7.1%) | 19/261 (7.3%) | ||||||||||||||
| Myalgia | 1/16 (6.3%) | 2/15 (13.3%) | 0/11 (0%) | 3/42 (7.1%) | 2/6 (33.3%) | 0/10 (0%) | 2/16 (12.5%) | 5/58 (8.6%) | 4/59 (6.8%) | 4/61 (6.6%) | 1/40 (2.5%) | 1/59 (1.7%) | 3/42 (7.1%) | 13/261 (5%) | ||||||||||||||
| Neck pain | 0/16 (0%) | 1/15 (6.7%) | 1/11 (9.1%) | 2/42 (4.8%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 2/58 (3.4%) | 0/59 (0%) | 2/61 (3.3%) | 1/40 (2.5%) | 3/59 (5.1%) | 4/42 (9.5%) | 10/261 (3.8%) | ||||||||||||||
| Osteoarthritis | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 1/10 (10%) | 1/16 (6.3%) | 1/58 (1.7%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 0/261 (0%) | ||||||||||||||
| Pain in extremity | 0/16 (0%) | 2/15 (13.3%) | 2/11 (18.2%) | 4/42 (9.5%) | 1/6 (16.7%) | 1/10 (10%) | 2/16 (12.5%) | 6/58 (10.3%) | 1/59 (1.7%) | 4/61 (6.6%) | 3/40 (7.5%) | 4/59 (6.8%) | 0/42 (0%) | 12/261 (4.6%) | ||||||||||||||
| Pathological fracture | 0/16 (0%) | 0/15 (0%) | 1/11 (9.1%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 0/261 (0%) | ||||||||||||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||||||||||||||||||
| Cancer pain | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 1/59 (1.7%) | 2/61 (3.3%) | 0/40 (0%) | 5/59 (8.5%) | 0/42 (0%) | 8/261 (3.1%) | ||||||||||||||
| Tumour haemorrhage | 2/16 (12.5%) | 0/15 (0%) | 0/11 (0%) | 2/42 (4.8%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 2/58 (3.4%) | 0/59 (0%) | 1/61 (1.6%) | 0/40 (0%) | 0/59 (0%) | 1/42 (2.4%) | 2/261 (0.8%) | ||||||||||||||
| Tumour pain | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 0/59 (0%) | 1/61 (1.6%) | 6/40 (15%) | 0/59 (0%) | 3/42 (7.1%) | 10/261 (3.8%) | ||||||||||||||
| Nervous system disorders | ||||||||||||||||||||||||||||
| Amnesia | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 3/59 (5.1%) | 0/42 (0%) | 3/261 (1.1%) | ||||||||||||||
| Aphasia | 1/16 (6.3%) | 0/15 (0%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 0/261 (0%) | ||||||||||||||
| Dizziness | 4/16 (25%) | 6/15 (40%) | 0/11 (0%) | 10/42 (23.8%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 10/58 (17.2%) | 1/59 (1.7%) | 5/61 (8.2%) | 4/40 (10%) | 10/59 (16.9%) | 3/42 (7.1%) | 23/261 (8.8%) | ||||||||||||||
| Dysarthria | 0/16 (0%) | 1/15 (6.7%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 0/59 (0%) | 1/61 (1.6%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 1/261 (0.4%) | ||||||||||||||
| Dysgeusia | 0/16 (0%) | 2/15 (13.3%) | 0/11 (0%) | 2/42 (4.8%) | 0/6 (0%) | 1/10 (10%) | 1/16 (6.3%) | 3/58 (5.2%) | 1/59 (1.7%) | 0/61 (0%) | 0/40 (0%) | 1/59 (1.7%) | 0/42 (0%) | 2/261 (0.8%) | ||||||||||||||
| Headache | 1/16 (6.3%) | 4/15 (26.7%) | 1/11 (9.1%) | 6/42 (14.3%) | 1/6 (16.7%) | 3/10 (30%) | 4/16 (25%) | 10/58 (17.2%) | 4/59 (6.8%) | 4/61 (6.6%) | 2/40 (5%) | 7/59 (11.9%) | 5/42 (11.9%) | 22/261 (8.4%) | ||||||||||||||
| Hypoaesthesia | 1/16 (6.3%) | 1/15 (6.7%) | 0/11 (0%) | 2/42 (4.8%) | 1/6 (16.7%) | 0/10 (0%) | 1/16 (6.3%) | 3/58 (5.2%) | 1/59 (1.7%) | 1/61 (1.6%) | 1/40 (2.5%) | 0/59 (0%) | 0/42 (0%) | 3/261 (1.1%) | ||||||||||||||
| Lethargy | 0/16 (0%) | 0/15 (0%) | 1/11 (9.1%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 0/261 (0%) | ||||||||||||||
| Loss of consciousness | 1/16 (6.3%) | 0/15 (0%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 0/261 (0%) | ||||||||||||||
| Neuralgia | 0/16 (0%) | 1/15 (6.7%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 0/59 (0%) | 0/61 (0%) | 1/40 (2.5%) | 0/59 (0%) | 0/42 (0%) | 1/261 (0.4%) | ||||||||||||||
| Neuropathy peripheral | 1/16 (6.3%) | 0/15 (0%) | 0/11 (0%) | 1/42 (2.4%) | 1/6 (16.7%) | 0/10 (0%) | 1/16 (6.3%) | 2/58 (3.4%) | 0/59 (0%) | 0/61 (0%) | 1/40 (2.5%) | 0/59 (0%) | 0/42 (0%) | 1/261 (0.4%) | ||||||||||||||
| Paraesthesia | 0/16 (0%) | 0/15 (0%) | 1/11 (9.1%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 1/59 (1.7%) | 0/61 (0%) | 0/40 (0%) | 4/59 (6.8%) | 1/42 (2.4%) | 6/261 (2.3%) | ||||||||||||||
| Paralysis | 0/16 (0%) | 0/15 (0%) | 1/11 (9.1%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 1/59 (1.7%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 1/261 (0.4%) | ||||||||||||||
| Peripheral sensory neuropathy | 1/16 (6.3%) | 0/15 (0%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 1/59 (1.7%) | 1/61 (1.6%) | 0/40 (0%) | 0/59 (0%) | 1/42 (2.4%) | 3/261 (1.1%) | ||||||||||||||
| Presyncope | 0/16 (0%) | 1/15 (6.7%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 1/59 (1.7%) | 0/42 (0%) | 1/261 (0.4%) | ||||||||||||||
| Somnolence | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 1/6 (16.7%) | 0/10 (0%) | 1/16 (6.3%) | 1/58 (1.7%) | 1/59 (1.7%) | 0/61 (0%) | 0/40 (0%) | 1/59 (1.7%) | 0/42 (0%) | 2/261 (0.8%) | ||||||||||||||
| Taste disorder | 1/16 (6.3%) | 0/15 (0%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 0/59 (0%) | 0/61 (0%) | 1/40 (2.5%) | 0/59 (0%) | 0/42 (0%) | 1/261 (0.4%) | ||||||||||||||
| Tremor | 1/16 (6.3%) | 0/15 (0%) | 1/11 (9.1%) | 2/42 (4.8%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 2/58 (3.4%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 0/261 (0%) | ||||||||||||||
| Psychiatric disorders | ||||||||||||||||||||||||||||
| Affective disorder | 0/16 (0%) | 1/15 (6.7%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 0/261 (0%) | ||||||||||||||
| Agitation | 0/16 (0%) | 1/15 (6.7%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 0/59 (0%) | 0/61 (0%) | 1/40 (2.5%) | 1/59 (1.7%) | 2/42 (4.8%) | 4/261 (1.5%) | ||||||||||||||
| Anxiety | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 1/59 (1.7%) | 0/61 (0%) | 2/40 (5%) | 3/59 (5.1%) | 2/42 (4.8%) | 8/261 (3.1%) | ||||||||||||||
| Confusional state | 0/16 (0%) | 1/15 (6.7%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 1/59 (1.7%) | 0/61 (0%) | 1/40 (2.5%) | 0/59 (0%) | 0/42 (0%) | 2/261 (0.8%) | ||||||||||||||
| Depression | 1/16 (6.3%) | 0/15 (0%) | 0/11 (0%) | 1/42 (2.4%) | 1/6 (16.7%) | 0/10 (0%) | 1/16 (6.3%) | 2/58 (3.4%) | 2/59 (3.4%) | 0/61 (0%) | 1/40 (2.5%) | 2/59 (3.4%) | 2/42 (4.8%) | 7/261 (2.7%) | ||||||||||||||
| Hallucination | 0/16 (0%) | 0/15 (0%) | 1/11 (9.1%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 1/59 (1.7%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 1/261 (0.4%) | ||||||||||||||
| Insomnia | 0/16 (0%) | 1/15 (6.7%) | 0/11 (0%) | 1/42 (2.4%) | 1/6 (16.7%) | 3/10 (30%) | 4/16 (25%) | 5/58 (8.6%) | 2/59 (3.4%) | 6/61 (9.8%) | 4/40 (10%) | 5/59 (8.5%) | 2/42 (4.8%) | 19/261 (7.3%) | ||||||||||||||
| Renal and urinary disorders | ||||||||||||||||||||||||||||
| Acute kidney injury | 0/16 (0%) | 1/15 (6.7%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 0/59 (0%) | 1/61 (1.6%) | 0/40 (0%) | 1/59 (1.7%) | 1/42 (2.4%) | 3/261 (1.1%) | ||||||||||||||
| Azotaemia | 1/16 (6.3%) | 0/15 (0%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 0/261 (0%) | ||||||||||||||
| Dysuria | 0/16 (0%) | 1/15 (6.7%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 0/59 (0%) | 1/61 (1.6%) | 1/40 (2.5%) | 2/59 (3.4%) | 1/42 (2.4%) | 5/261 (1.9%) | ||||||||||||||
| Haematuria | 0/16 (0%) | 0/15 (0%) | 1/11 (9.1%) | 1/42 (2.4%) | 1/6 (16.7%) | 0/10 (0%) | 1/16 (6.3%) | 2/58 (3.4%) | 0/59 (0%) | 1/61 (1.6%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 1/261 (0.4%) | ||||||||||||||
| Hydronephrosis | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 1/6 (16.7%) | 0/10 (0%) | 1/16 (6.3%) | 1/58 (1.7%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 0/261 (0%) | ||||||||||||||
| Micturition urgency | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 1/10 (10%) | 1/16 (6.3%) | 1/58 (1.7%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 0/261 (0%) | ||||||||||||||
| Pollakiuria | 0/16 (0%) | 1/15 (6.7%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 1/10 (10%) | 1/16 (6.3%) | 2/58 (3.4%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 1/59 (1.7%) | 0/42 (0%) | 1/261 (0.4%) | ||||||||||||||
| Urinary incontinence | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 1/10 (10%) | 1/16 (6.3%) | 1/58 (1.7%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 1/59 (1.7%) | 0/42 (0%) | 1/261 (0.4%) | ||||||||||||||
| Reproductive system and breast disorders | ||||||||||||||||||||||||||||
| Pelvic pain | 1/16 (6.3%) | 0/15 (0%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 0/59 (0%) | 1/61 (1.6%) | 0/40 (0%) | 1/59 (1.7%) | 0/42 (0%) | 2/261 (0.8%) | ||||||||||||||
| Vulvovaginal pain | 0/16 (0%) | 1/15 (6.7%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 0/261 (0%) | ||||||||||||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||||||||||||||||
| Cough | 3/16 (18.8%) | 4/15 (26.7%) | 0/11 (0%) | 7/42 (16.7%) | 0/6 (0%) | 3/10 (30%) | 3/16 (18.8%) | 10/58 (17.2%) | 13/59 (22%) | 8/61 (13.1%) | 10/40 (25%) | 20/59 (33.9%) | 6/42 (14.3%) | 57/261 (21.8%) | ||||||||||||||
| Dyspnoea | 5/16 (31.3%) | 7/15 (46.7%) | 2/11 (18.2%) | 14/42 (33.3%) | 0/6 (0%) | 4/10 (40%) | 4/16 (25%) | 18/58 (31%) | 17/59 (28.8%) | 1/61 (1.6%) | 10/40 (25%) | 18/59 (30.5%) | 9/42 (21.4%) | 55/261 (21.1%) | ||||||||||||||
| Dyspnoea exertional | 1/16 (6.3%) | 0/15 (0%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 0/59 (0%) | 0/61 (0%) | 2/40 (5%) | 0/59 (0%) | 0/42 (0%) | 2/261 (0.8%) | ||||||||||||||
| Haemoptysis | 0/16 (0%) | 1/15 (6.7%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 2/59 (3.4%) | 1/61 (1.6%) | 0/40 (0%) | 2/59 (3.4%) | 4/42 (9.5%) | 9/261 (3.4%) | ||||||||||||||
| Hiccups | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 1/6 (16.7%) | 0/10 (0%) | 1/16 (6.3%) | 1/58 (1.7%) | 0/59 (0%) | 1/61 (1.6%) | 0/40 (0%) | 0/59 (0%) | 1/42 (2.4%) | 2/261 (0.8%) | ||||||||||||||
| Hypoxia | 0/16 (0%) | 0/15 (0%) | 1/11 (9.1%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 1/59 (1.7%) | 0/61 (0%) | 1/40 (2.5%) | 1/59 (1.7%) | 1/42 (2.4%) | 4/261 (1.5%) | ||||||||||||||
| Oropharyngeal pain | 0/16 (0%) | 1/15 (6.7%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 3/59 (5.1%) | 0/61 (0%) | 1/40 (2.5%) | 1/59 (1.7%) | 4/42 (9.5%) | 9/261 (3.4%) | ||||||||||||||
| Pleural effusion | 3/16 (18.8%) | 1/15 (6.7%) | 1/11 (9.1%) | 5/42 (11.9%) | 0/6 (0%) | 2/10 (20%) | 2/16 (12.5%) | 7/58 (12.1%) | 3/59 (5.1%) | 1/61 (1.6%) | 4/40 (10%) | 3/59 (5.1%) | 1/42 (2.4%) | 12/261 (4.6%) | ||||||||||||||
| Pneumonitis | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 3/59 (5.1%) | 3/61 (4.9%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 6/261 (2.3%) | ||||||||||||||
| Productive cough | 0/16 (0%) | 1/15 (6.7%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 1/10 (10%) | 1/16 (6.3%) | 2/58 (3.4%) | 6/59 (10.2%) | 1/61 (1.6%) | 3/40 (7.5%) | 2/59 (3.4%) | 3/42 (7.1%) | 15/261 (5.7%) | ||||||||||||||
| Respiratory tract congestion | 1/16 (6.3%) | 0/15 (0%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 0/261 (0%) | ||||||||||||||
| Sinus congestion | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 1/10 (10%) | 1/16 (6.3%) | 1/58 (1.7%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 0/261 (0%) | ||||||||||||||
| Tachypnoea | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 1/10 (10%) | 1/16 (6.3%) | 1/58 (1.7%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 0/261 (0%) | ||||||||||||||
| Upper respiratory tract congestion | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 1/10 (10%) | 1/16 (6.3%) | 1/58 (1.7%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 0/261 (0%) | ||||||||||||||
| Skin and subcutaneous tissue disorders | ||||||||||||||||||||||||||||
| Alopecia | 0/16 (0%) | 0/15 (0%) | 1/11 (9.1%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 0/261 (0%) | ||||||||||||||
| Cold sweat | 0/16 (0%) | 1/15 (6.7%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 0/261 (0%) | ||||||||||||||
| Dermatitis acneiform | 1/16 (6.3%) | 0/15 (0%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 0/261 (0%) | ||||||||||||||
| Dermatitis contact | 0/16 (0%) | 1/15 (6.7%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 0/261 (0%) | ||||||||||||||
| Erythema | 0/16 (0%) | 0/15 (0%) | 1/11 (9.1%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 0/59 (0%) | 2/61 (3.3%) | 1/40 (2.5%) | 1/59 (1.7%) | 0/42 (0%) | 4/261 (1.5%) | ||||||||||||||
| Hyperhidrosis | 1/16 (6.3%) | 1/15 (6.7%) | 0/11 (0%) | 2/42 (4.8%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 2/58 (3.4%) | 1/59 (1.7%) | 1/61 (1.6%) | 1/40 (2.5%) | 1/59 (1.7%) | 0/42 (0%) | 4/261 (1.5%) | ||||||||||||||
| Lichen planus | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 1/10 (10%) | 1/16 (6.3%) | 1/58 (1.7%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 0/261 (0%) | ||||||||||||||
| Night sweats | 0/16 (0%) | 1/15 (6.7%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 1/59 (1.7%) | 0/61 (0%) | 1/40 (2.5%) | 1/59 (1.7%) | 1/42 (2.4%) | 4/261 (1.5%) | ||||||||||||||
| Pain of skin | 0/16 (0%) | 1/15 (6.7%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 0/261 (0%) | ||||||||||||||
| Palmar-plantar erythrodysaesthesia syndrome | 0/16 (0%) | 1/15 (6.7%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 0/261 (0%) | ||||||||||||||
| Papule | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 1/10 (10%) | 1/16 (6.3%) | 1/58 (1.7%) | 0/59 (0%) | 0/61 (0%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 0/261 (0%) | ||||||||||||||
| Pruritus | 3/16 (18.8%) | 5/15 (33.3%) | 1/11 (9.1%) | 9/42 (21.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 9/58 (15.5%) | 7/59 (11.9%) | 8/61 (13.1%) | 4/40 (10%) | 3/59 (5.1%) | 5/42 (11.9%) | 27/261 (10.3%) | ||||||||||||||
| Rash | 1/16 (6.3%) | 1/15 (6.7%) | 0/11 (0%) | 2/42 (4.8%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 2/58 (3.4%) | 5/59 (8.5%) | 6/61 (9.8%) | 3/40 (7.5%) | 3/59 (5.1%) | 3/42 (7.1%) | 20/261 (7.7%) | ||||||||||||||
| Rash erythematous | 1/16 (6.3%) | 0/15 (0%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 0/59 (0%) | 1/61 (1.6%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 1/261 (0.4%) | ||||||||||||||
| Rash maculo-papular | 1/16 (6.3%) | 2/15 (13.3%) | 0/11 (0%) | 3/42 (7.1%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 3/58 (5.2%) | 2/59 (3.4%) | 3/61 (4.9%) | 0/40 (0%) | 1/59 (1.7%) | 1/42 (2.4%) | 7/261 (2.7%) | ||||||||||||||
| Skin ulcer | 0/16 (0%) | 0/15 (0%) | 1/11 (9.1%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 0/59 (0%) | 1/61 (1.6%) | 0/40 (0%) | 0/59 (0%) | 0/42 (0%) | 1/261 (0.4%) | ||||||||||||||
| Vitiligo | 0/16 (0%) | 0/15 (0%) | 0/11 (0%) | 0/42 (0%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 0/58 (0%) | 0/59 (0%) | 10/61 (16.4%) | 0/40 (0%) | 0/59 (0%) | 1/42 (2.4%) | 11/261 (4.2%) | ||||||||||||||
| Vascular disorders | ||||||||||||||||||||||||||||
| Deep vein thrombosis | 0/16 (0%) | 1/15 (6.7%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 0/59 (0%) | 0/61 (0%) | 2/40 (5%) | 0/59 (0%) | 0/42 (0%) | 2/261 (0.8%) | ||||||||||||||
| Hot flush | 0/16 (0%) | 1/15 (6.7%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 0/59 (0%) | 0/61 (0%) | 1/40 (2.5%) | 2/59 (3.4%) | 0/42 (0%) | 3/261 (1.1%) | ||||||||||||||
| Hypotension | 1/16 (6.3%) | 0/15 (0%) | 0/11 (0%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 1/59 (1.7%) | 0/61 (0%) | 0/40 (0%) | 1/59 (1.7%) | 1/42 (2.4%) | 3/261 (1.1%) | ||||||||||||||
| Lymphoedema | 0/16 (0%) | 0/15 (0%) | 1/11 (9.1%) | 1/42 (2.4%) | 0/6 (0%) | 0/10 (0%) | 0/16 (0%) | 1/58 (1.7%) | 0/59 (0%) | 1/61 (1.6%) | 1/40 (2.5%) | 0/59 (0%) | 1/42 (2.4%) | 3/261 (1.1%) | ||||||||||||||
Limitations/Caveats
Although the study had 2 'arms', the phase I part of the study had 5 dosing cohorts and the phase ll part had 5 treatment groups for a total of 10 reporting groups.
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of pooled data (i.e.,data from all sites) in clinical trial or disclosure of trial results in their entirety.
Results Point of Contact
| Name/Title | Study Director |
|---|---|
| Organization | Novartis Pharmaceuticals |
| Phone | 862-778-8300 |
| novartis.email@novartis.com |
Responsible Party:
Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT02404441
Other Study ID Numbers:
- CPDR001X2101
- 2014-003929-17
First Posted:
Mar 31, 2015
Last Update Posted:
Aug 3, 2022
Last Verified:
Aug 1, 2022