Study of LGX818 and Cetuximab or LGX818, BYL719, and Cetuximab in BRAF Mutant Metastatic Colorectal Cancer
Sponsor
Pfizer (Industry)
Overall Status
Completed
CT.gov ID
NCT01719380
Collaborator
(none)
156
52
2
74.6
3
0
Study Details
Study Description
Brief Summary
This study will assess the safety and efficacy of LGX818 when combined with cetuximab or combined with cetuximab and BYL719 in patients with BRAF mutant metastatic colorectal cancer
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
156 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase Ib/II Multi-center, Open-label, Dose Escalation Study of LGX818 and Cetuximab or LGX818, BYL719, and Cetuximab in Patients With BRAF Mutant Metastatic Colorectal Cancer
Actual Study Start Date
:
Nov 23, 2012
Actual Primary Completion Date
:
Oct 31, 2015
Actual Study Completion Date
:
Feb 12, 2019
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: LGX818 + cetuximab
|
Drug: LGX818
Drug: Cetuximab
|
| Experimental: LGX818 + BYL719 + cetuximab
|
Drug: LGX818
Drug: Cetuximab
Drug: BYL719
|
Outcome Measures
Primary Outcome Measures
- Phase 1b: Number of Participants With Incidence of Dose Limiting Toxicities (DLTs): Cycle 1 [Cycle 1: Day 1 to Day 28]
DLTs were defined as an adverse event (AE) or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurred within the first 28 days of treatment and meets any of the criteria included blood and lymphatic system disorders, investigations (blood, renal, hepatic, metabolic), skin and subcutaneous tissue disorders: rash, HFSR (hand foot skin reaction) and/or photosensitivity, metabolism and nutrition disorders: hyperglycemia, gastrointestinal disorders, cardiac disorders, vascular disorders, general disorders and administration site conditions, tumor lysis syndrome, ophthalmologic and other adverse events: study drug-related fever, alkaline phosphatase elevation.
- Phase 2: Progression Free Survival (PFS) [From the date of randomization until the first documentation of disease progression or death due to any cause, censored date, whichever occurred first (maximum up to 43 months)]
PFS was defined as the time from the date of randomization to the date of the first documented disease progression or death due to any cause. Participants who did not progress per RECIST (Response Evaluation Criteria in Solid Tumors) version (v) 1.1, were not known to have died prior to the data cut-off, or received any further anticancer therapy were censored at the date of last adequate tumor assessment or the anticancer therapy date, whichever was earlier.
Secondary Outcome Measures
- Number of Participants With Treatment - Emergent Adverse Events of Grade 3 or 4 Severity Based on National Cancer Institute of Common Terminology Criteria (NCI-CTCAE), Version 4.0 [From screening up to 30 days after the last dose of study treatment (for a maximum duration of 43 months, approximately)]
An AE was any untoward medical occurrence attributed to study drug in participants who received study drug. As per NCI-CTCAE v4.0, Grade 1: asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental activities of daily life (ADL); Grade 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to study drug. Treatment-emergent AEs are between first dose of study drug and up to 30 days after last dose of study drug, that were absent before treatment or that worsened relative to pretreatment state. Number of participants with any Grade 3 or 4 treatment-emergent AE were reported in this outcome measure.
- Apparent Total Plasma Clearance (CL/F) of LGX818 (Encorafenib) [Cycle 1 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose]
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
- Apparent Total Plasma Clearance at Steady State (CL/F, ss) of LGX818 (Encorafenib) [Cycle 1 Day 8, Cycle 2 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose]
Clearance of a drug at steady state is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
- Apparent Total Plasma Clearance (CL/F) of BYL719 (Alpelisib) [Cycle 1 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose]
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
- Apparent Total Plasma Clearance at Steady State (CL/F, ss) of BYL719 (Alpelisib) [Cycle 1 Day 8, Cycle 2 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose]
Clearance of a drug at steady state is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
- Apparent Terminal Volume of Distribution (Vz/F) of LGX818 (Encorafenib) [Cycle 1 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose]
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed.
- Apparent Terminal Volume of Distribution at Steady State (Vz/F, ss) of LGX818 (Encorafenib) [Cycle 1 Day 8, Cycle 2 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose]
Volume of distribution at steady state is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F, ss) is influenced by the fraction absorbed.
- Apparent Terminal Volume of Distribution (Vz/F) of BYL719 (Alpelisib) [Cycle 1 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose]
Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed.
- Apparent Terminal Volume of Distribution at Steady State (Vz/F, ss) of BYL719 (Alpelisib) [Cycle 1 Day 8, Cycle 2 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose]
Volume of distribution at steady state was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F, ss) is influenced by the fraction absorbed.
- Time to Reach Maximum Observed Plasma Concentration (Tmax) of LGX818 (Encorafenib) [Cycle 1 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose]
Tmax was defined as the time to reach maximum observed plasma concentration of encorafenib.
- Time to Reach Maximum Plasma Concentration at Steady State (Tmax, ss) of LGX818 (Encorafenib) [Cycle 1 Day 8, Cycle 2 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose]
Tmax, ss was defined as the time to reach maximum observed plasma concentration of LGX818 (encorafenib) at steady state.
- Time to Reach Maximum Observed Plasma Concentration (Tmax) of BYL719 (Alpelisib) [Cycle 1 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose]
Tmax was defined as the time to reach maximum observed plasma concentration of alpelisib.
- Time to Reach Maximum Plasma Concentration at Steady State (Tmax, ss) of BYL719 (Alpelisib) [Cycle 1 Day 8, Cycle 2 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose]
Tmax, ss was defined as the time to reach maximum observed plasma concentration of BYL719 (alpelisib) at steady state.
- Time of Last Observed Plasma Concentration (T-last) of LGX818 (Encorafenib) [Cycle 1 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose]
T-last was defined as the time to reach last observed plasma concentration of encorafenib.
- Time of Last Observed Plasma Concentration at Steady State (T-last, ss) of LGX818 (Encorafenib) [Cycle 1 Day 8, Cycle 2 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose]
T-last, ss was defined as the time to reach last observed plasma concentration of encorafenib at steady state.
- Time of Last Observed Plasma Concentration (T-last) of BYL719 (Alpelisib) [Cycle 1 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose]
T-last was defined as the time to reach last observed plasma concentration of alpelisib.
- Time of Last Observed Plasma Concentration at Steady State (T-last, ss) of BYL719 (Alpelisib) [Cycle 1 Day 8, Cycle 2 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose]
T-last, ss was defined as the time to reach last observed plasma concentration of alpelisib at steady state.
- Plasma Trough Concentration at Steady State (Ctrough, ss) of LGX818 (Encorafenib) [Cycle 2 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose]
Ctrough, ss was defined as plasma trough concentration of encorafenib at steady state.
- Plasma Trough Concentration at Steady State (Ctrough, ss) of BYL719 (Alpelisib) [Cycle 2 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose]
Ctrough, ss was defined as plasma trough concentration of alpelisib at steady state.
- Overall Survival (OS) [From the date of randomization or date of start of treatment to the date of death due to any cause or data censoring date, whichever occurred first (up to 43 months)]
OS was defined as the time (in months) from the date of randomization or date of start of treatment to the date of death due to any cause or data censoring date, whichever occurred first. Participants last known to be alive were censored at date of last contact. Analysis was performed using Kaplan-Meier method.
- Overall Response Rate (ORR) [From date of randomization or date of start of treatment until date of first documentation of PD or death due to any cause (maximum up to 43 months)]
Overall response rate as assessed by the investigator per RECIST v1.1, was defined as percentage of participants with a best overall response of complete response (CR) or partial response (PR), were recorded from date of randomization or date of start of treatment until date of first documentation of progressive disease (PD) or death due to any cause. CR was defined as complete disappearance of all target and non-nodal target lesions, and sustained for at least 4 weeks apart before progression. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<) 10 millimeter (mm). PR defined as at least 30 percent (%) decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters. Only confirmed CR and PR are counted (those confirmed at least 4 weeks).
- Duration of Response (DOR) [From the first documentation of OR (confirmed CR or PR) to first documentation of PD/death due to any cause or censoring date, whichever occurred first (up to 43 months)]
DOR: Time between date of the first documented response (CR or PR) and the date of first documented PD or death due to underlying cancer. If PD or death due to underlying cancer not occurred, then participant was censored at the date of last tumor assessment other than unknown. DOR was calculated for responders (confirmed) only. CR: Disappearance of all target, non-target lesions sustained for >=4 weeks and any pathological lymph nodes reduced in short axis to <10mm. PR: >=30% decrease in sum of diameters of target lesions, taking as reference baseline sum of diameter. PD for target lesions: At least a 20% increase in sum of diameters of target lesions, taking as reference smallest sum on study treatment, with absolute increase of >=5 mm, or appearance of >=1 new lesions. PD for non-target lesions: Unequivocal progression of pre-existing lesions/increase in overall tumor burden leading to discontinuation of therapy or appearance of new unequivocal malignant lesion.
- Time to Response (TTR) [From the date of randomization or date of start of treatment until first documented response (CR or PR) or data censoring date, whichever occurred first (maximum up to 43 months)]
TTR as assessed by investigator according to RECIST v1.1, was defined as the time (in months) from date of randomization or date of start of treatment until first documented response (CR or PR) or data censoring date, whichever occurred first. CR was defined as complete disappearance of all target and non-target lesions sustained for at least 4 weeks apart before progression. Any pathological lymph nodes (whether target or non-target) reduced in short axis to <10 mm. PR was defined as at least 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters. Participants who did not achieve a confirmed PR or CR, were censored at last adequate tumor assessment date when they did not progress (including deaths not due to underlying disease) or at maximum follow-up (from study start to study end date) when participant had an event for progression-free survival.
- Phase 1b: Progression Free Survival (PFS) [From date of start of treatment to the date of event defined as the first documented progression or death due to any cause, censored date, whichever occurred first (maximum up to 43 months)]
PFS was defined as 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. Participants who did not progress per RECIST v1.1, were not known to have died prior to the data cut-off, or received any further anticancer therapy were censored at the date of last adequate tumor assessment or the anticancer therapy date, whichever was earlier.
- Phase 2: Number of Participants With Any Variant in Gene Status at Baseline [Baseline (Day 1)]
Gene alterations/expression relevant to the RAF/MEK/ERK (proto-oncogene serine/threonine-protein kinase/ mitogen-activated ERK kinase/ extracellular signal-regulated kinases) and EGFR/PI3K/AKT (epidermal growth factor receptor/ phosphatidylinositol 3-kinase/ protein kinase B) pathways in tumor tissue, baseline molecular status (mutation/amplification/expression) in tumor tissue of potential predictive markers of tumor response or resistance i.e. BRAF (v-raf murine sarcoma viral oncogene homolog B1), HRAS (harvey rat sarcoma protein), KRAS (V-Ki-ras2 kirsten rat sarcoma viral oncogene homolog B1), NRAS (neuroblastoma RAS viral oncogene homolog), PTEN (phosphatase and tensin homolog), PIK3CA (phosphatidylinositol 3-kinase gene), MAP2K1 (mitogen-activated protein kinase 1), MAP2K2 (mitogen-activated protein kinase 2), ARAF, c-MET, RAF1, EGFR was analyzed.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Metastatic colorectal cancer
-
Progression after at least one prior standard of care regimen or be intolerant to irinotecan-based regimens
-
Life expectancy ≥ 3 months
-
ECOG performance status ≤ 2
Exclusion Criteria:
-
Symptomatic or untreated leptomeningeal disease
-
Symptomatic brain metastasis
-
Patients with clinically manifested diabetes
-
Acute or chronic pancreatitis
-
Clinically significant cardiac disease
Other protocol-defined inclusion/exclusion criteria may apply.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Keck Hospital of USC | Los Angeles | California | United States | 90033 |
| 2 | LAC&USC Medical Center | Los Angeles | California | United States | 90033 |
| 3 | USC/Norris Comprehensive Cancer Center | Los Angeles | California | United States | 90033 |
| 4 | Ronald Reagan UCLA Medical Center | Los Angeles | California | United States | 90095 |
| 5 | UCLA University of California Los Angeles | Los Angeles | California | United States | 90095 |
| 6 | Westwood Bowyer Clinic, Peter Morton Medical Building | Los Angeles | California | United States | 90095 |
| 7 | UCLA Hematology Oncology | Santa Monica | California | United States | 90404 |
| 8 | UCLA Santa Monica Medical Center & Orthopaedic Hospital | Santa Monica | California | United States | 90404 |
| 9 | Smilow Cancer Hospital at Yale-New Haven | New Haven | Connecticut | United States | 06510 |
| 10 | Yale University | New Haven | Connecticut | United States | 06520 |
| 11 | Smilow Cancer Hospital Care Center at North Haven | North Haven | Connecticut | United States | 06473 |
| 12 | Massachusetts General Hospital | Boston | Massachusetts | United States | 02114-2620 |
| 13 | Hackensack University Medical Center | Hackensack | New Jersey | United States | 07601 |
| 14 | John Theurer Cancer Center at Hackensack University Medical Center | Hackensack | New Jersey | United States | 07601 |
| 15 | Memorial Sloan-Kettering Cancer Center | New York | New York | United States | 10017-6706 |
| 16 | Memorial Sloan Kettering Cancer Center | New York | New York | United States | 10022 |
| 17 | Tennessee Oncology, PLLC | Dickson | Tennessee | United States | 37055 |
| 18 | Tennessee Oncology, PLLC | Franklin | Tennessee | United States | 37067 |
| 19 | Tennessee Oncology, PLLC | Gallatin | Tennessee | United States | 37066 |
| 20 | Tennessee Oncology, PLLC | Hermitage | Tennessee | United States | 37076 |
| 21 | Tennessee Oncology, PLLC | Lebanon | Tennessee | United States | 37909 |
| 22 | Tennessee Oncology, PLLC | Murfreesboro | Tennessee | United States | 37129 |
| 23 | Tennessee Oncology, PLLC | Nashville | Tennessee | United States | 37203 |
| 24 | Tennessee Oncology, PLLC | Nashville | Tennessee | United States | 37205 |
| 25 | Tennessee Oncology, PLLC | Nashville | Tennessee | United States | 37207 |
| 26 | Tennessee Oncology, PLLC | Nashville | Tennessee | United States | 37211 |
| 27 | Tennessee Oncology, PLLC | Shelbyville | Tennessee | United States | 37160 |
| 28 | Tennessee Oncology, PLLC | Smyrna | Tennessee | United States | 37167 |
| 29 | University of Utah - Huntsman Cancer Institute - PPDS | Salt Lake City | Utah | United States | 84112-5550 |
| 30 | Huntsman Cancer Hospital | Salt Lake City | Utah | United States | 84112 |
| 31 | Redwood Health Center - ARUP Lab Draw Location | Salt Lake City | Utah | United States | 84119 |
| 32 | John A Moran Eye Center | Salt Lake City | Utah | United States | 84132 |
| 33 | Royal Melbourne Hospital | Parkville | Victoria | Australia | 3050 |
| 34 | UZ Gasthuisberg | Leuven | Vlaams Brabant | Belgium | 3000 |
| 35 | Princess Margaret Cancer Centre | Toronto | Ontario | Canada | M5G 2M9 |
| 36 | Sir Mortimer B. Davis Jewish General Hospital | Montreal | Quebec | Canada | H3T 1E2 |
| 37 | Centre Régional de Lutte Contre Le Cancer Val D'aurelle Paul Lamarque | Montpellier | France | 34298 | |
| 38 | EDOG - Institut Claudius Regaud - PPDS | Toulouse | France | 31052 | |
| 39 | University Hospital of Koln | Köln | Nordrhein-westfalen | Germany | 50937 |
| 40 | Universitätsklinikum Essen | Essen | Germany | 45147 | |
| 41 | Ospedaliero Universitaria di Modena Policlinico | Modena | Italy | 41100 | |
| 42 | Pharmacy of National Cancer Center Hospital East | Kashiwa | Chiba | Japan | 277-8577 |
| 43 | National Cancer Center Hospital | Chuo-ku | Tokyo | Japan | 104-0045 |
| 44 | Samsung Medical Center - PPDS | Gangnam-Gu | Seoul Teugbyeolsi | Korea, Republic of | 06351 |
| 45 | Asan Medical Center - PPDS | Songpa-Gu | Seoul Teugbyeolsi | Korea, Republic of | 05505 |
| 46 | Het Nederlands Kanker Instituut Antoni Van Leeuwenhoek Ziekenhuis | Amsterdam | Noord-holland | Netherlands | 1066 CX |
| 47 | Erasmus MC | Rotterdam | Zuid-holland | Netherlands | 3015 CE |
| 48 | Universitair Medisch Centrum Utrecht | Utrecht | Netherlands | 3584 CX | |
| 49 | Oslo Myeloma Center - PPDS | Oslo | Norway | 0379 | |
| 50 | Instituto de Investigacion Oncologica Vall d'Hebron (VHIO) - EPON | Barcelona | Spain | 08035 | |
| 51 | Hospital Universitario 12 de Octubre | Madrid | Spain | 28026 | |
| 52 | Hospital Universitario Virgen del Rocio - PPDS | Sevilla | Spain | 41013 |
Sponsors and Collaborators
- Pfizer
Investigators
- Study Director: Pfizer CT.gov Call Center, Pfizer
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT01719380
Other Study ID Numbers:
- CLGX818X2103
- C4221002
- 2012-002138-35
First Posted:
Nov 1, 2012
Last Update Posted:
Jun 23, 2021
Last Verified:
May 1, 2021
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Keywords provided by Pfizer
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | This study was conducted in two phases Phase 1b and Phase 2. Phase 1b of the study was dose escalation phase to determine maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of LGX818 in combination with cetuximab (dual combination) and of LGX818 in combination with BYL719 and cetuximab (triple combination). Phase 2 of the study was to determine the clinical efficacy and safety of dual and triple combination in study participants. |
| Arm/Group Title | Phase 1b: LGX818 100 mg + Cetuximab | Phase 1b: LGX818 200 mg + Cetuximab | Phase 1b: LGX818 400 mg + Cetuximab | Phase 1b: LGX818 450 mg + Cetuximab | Phase 1b: LGX818 200 mg + BYL719 100 mg + Cetuximab | Phase 1b: LGX818 200 mg + BYL719 200 mg + Cetuximab | Phase 1b: LGX818 200 mg + BYL719 300 mg + Cetuximab | Phase 1b: LGX818 300 mg + BYL719 200 mg + Cetuximab | Phase 2: LGX818 200 mg + Cetuximab | Phase 2: LGX818 200 mg + BYL719 300 mg + Cetuximab |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received 100 mg of LGX818 (encorafenib) orally once daily along with cetuximab orally once weekly in each cycle of 28 days continuously, until disease progression (PD), unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 orally once daily along with cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 400 mg of LGX818 orally once daily along with cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 450 mg of LGX818 orally once daily along with cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 100 mg of BYL719 (alpelisib) orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 200 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 300 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 300 mg of LGX818 along with 200 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 orally once daily along with cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 300 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). |
| Period Title: Overall Study | ||||||||||
| STARTED | 2 | 7 | 9 | 8 | 3 | 8 | 10 | 7 | 50 | 52 |
| COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| NOT COMPLETED | 2 | 7 | 9 | 8 | 3 | 8 | 10 | 7 | 50 | 51 |
Baseline Characteristics
| Arm/Group Title | Phase 1b: LGX818 100 mg + Cetuximab | Phase 1b: LGX818 200 mg + Cetuximab | Phase 1b: LGX818 400 mg + Cetuximab | Phase 1b: LGX818 450 mg + Cetuximab | Phase 1b: LGX818 200 mg + BYL719 100 mg + Cetuximab | Phase 1b: LGX818 200 mg + BYL719 200 mg + Cetuximab | Phase 1b: LGX818 200 mg + BYL719 300 mg + Cetuximab | Phase 1b: LGX818 300 mg + BYL719 200 mg + Cetuximab | Phase 2: LGX818 200 mg + Cetuximab | Phase 2: LGX818 200 mg + BYL719 300 mg + Cetuximab | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received 100 mg of LGX818 (encorafenib) orally once daily along with cetuximab orally once weekly in each cycle of 28 days continuously, until disease progression (PD), unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 orally once daily along with cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 400 mg of LGX818 orally once daily along with cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 450 mg of LGX818 orally once daily along with cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 100 mg of BYL719 (alpelisib) orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 200 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 300 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 300 mg of LGX818 along with 200 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 orally once daily along with cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 300 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Total of all reporting groups |
| Overall Participants | 2 | 7 | 9 | 8 | 3 | 8 | 10 | 7 | 50 | 52 | 156 |
| Age, Customized (Count of Participants) | |||||||||||
| <65 years |
1
50%
|
4
57.1%
|
7
77.8%
|
5
62.5%
|
2
66.7%
|
4
50%
|
8
80%
|
6
85.7%
|
32
64%
|
38
73.1%
|
107
68.6%
|
| >=65 years |
1
50%
|
3
42.9%
|
2
22.2%
|
3
37.5%
|
1
33.3%
|
4
50%
|
2
20%
|
1
14.3%
|
18
36%
|
14
26.9%
|
49
31.4%
|
| Sex: Female, Male (Count of Participants) | |||||||||||
| Female |
2
100%
|
3
42.9%
|
6
66.7%
|
4
50%
|
1
33.3%
|
5
62.5%
|
7
70%
|
5
71.4%
|
36
72%
|
27
51.9%
|
96
61.5%
|
| Male |
0
0%
|
4
57.1%
|
3
33.3%
|
4
50%
|
2
66.7%
|
3
37.5%
|
3
30%
|
2
28.6%
|
14
28%
|
25
48.1%
|
60
38.5%
|
Outcome Measures
| Title | Phase 1b: Number of Participants With Incidence of Dose Limiting Toxicities (DLTs): Cycle 1 |
|---|---|
| Description | DLTs were defined as an adverse event (AE) or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurred within the first 28 days of treatment and meets any of the criteria included blood and lymphatic system disorders, investigations (blood, renal, hepatic, metabolic), skin and subcutaneous tissue disorders: rash, HFSR (hand foot skin reaction) and/or photosensitivity, metabolism and nutrition disorders: hyperglycemia, gastrointestinal disorders, cardiac disorders, vascular disorders, general disorders and administration site conditions, tumor lysis syndrome, ophthalmologic and other adverse events: study drug-related fever, alkaline phosphatase elevation. |
| Time Frame | Cycle 1: Day 1 to Day 28 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The dose-determining set consisted of all participants from the phase 1b safety set who either met the following minimum exposure criterion and had scheduled safety evaluations or discontinued earlier due to DLT. |
| Arm/Group Title | Phase 1b: LGX818 100 mg + Cetuximab | Phase 1b: LGX818 200 mg + Cetuximab | Phase 1b: LGX818 400 mg + Cetuximab | Phase 1b: LGX818 450 mg + Cetuximab | Phase 1b: LGX818 200 mg + BYL719 100 mg + Cetuximab | Phase 1b: LGX818 200 mg + BYL719 200 mg + Cetuximab | Phase 1b: LGX818 200 mg + BYL719 300 mg + Cetuximab | Phase 1b: LGX818 300 mg + BYL719 200 mg + Cetuximab |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received 100 mg of LGX818 (encorafenib) orally once daily along with cetuximab orally once weekly in each cycle of 28 days continuously, until disease progression (PD), unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 orally once daily along with cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 400 mg of LGX818 orally once daily along with cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 450 mg of LGX818 orally once daily along with cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 100 mg of BYL719 (alpelisib) orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 200 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 300 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 300 mg of LGX818 along with 200 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). |
| Measure Participants | 2 | 7 | 8 | 7 | 3 | 7 | 9 | 7 |
| Count of Participants [Participants] |
0
0%
|
1
14.3%
|
1
11.1%
|
1
12.5%
|
0
0%
|
0
0%
|
1
10%
|
1
14.3%
|
| Title | Phase 2: Progression Free Survival (PFS) |
|---|---|
| Description | PFS was defined as the time from the date of randomization to the date of the first documented disease progression or death due to any cause. Participants who did not progress per RECIST (Response Evaluation Criteria in Solid Tumors) version (v) 1.1, were not known to have died prior to the data cut-off, or received any further anticancer therapy were censored at the date of last adequate tumor assessment or the anticancer therapy date, whichever was earlier. |
| Time Frame | From the date of randomization until the first documentation of disease progression or death due to any cause, censored date, whichever occurred first (maximum up to 43 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The full analysis set 2 (FAS2) comprised of all participants to whom study treatment was assigned by randomization. |
| Arm/Group Title | Phase 2: LGX818 200 mg + Cetuximab | Phase 2: LGX818 200 mg + BYL719 300 mg + Cetuximab |
|---|---|---|
| Arm/Group Description | Participants received 200 mg of LGX818 orally once daily along with cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 300 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). |
| Measure Participants | 50 | 52 |
| Median (95% Confidence Interval) [months] |
4.2
|
4.9
|
| Title | Number of Participants With Treatment - Emergent Adverse Events of Grade 3 or 4 Severity Based on National Cancer Institute of Common Terminology Criteria (NCI-CTCAE), Version 4.0 |
|---|---|
| Description | An AE was any untoward medical occurrence attributed to study drug in participants who received study drug. As per NCI-CTCAE v4.0, Grade 1: asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental activities of daily life (ADL); Grade 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to study drug. Treatment-emergent AEs are between first dose of study drug and up to 30 days after last dose of study drug, that were absent before treatment or that worsened relative to pretreatment state. Number of participants with any Grade 3 or 4 treatment-emergent AE were reported in this outcome measure. |
| Time Frame | From screening up to 30 days after the last dose of study treatment (for a maximum duration of 43 months, approximately) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety set included all participants from the full analysis set who received at least 1 dose of LGX818 (encorafenib), BYL719 (alpelisib) or cetuximab and had at least 1 valid post baseline safety assessment. |
| Arm/Group Title | Phase 1b: LGX818 100 mg + Cetuximab | Phase 1b: LGX818 200 mg + Cetuximab | Phase 1b: LGX818 400 mg + Cetuximab | Phase 1b: LGX818 450 mg + Cetuximab | Phase 1b: LGX818 200 mg + BYL719 100 mg + Cetuximab | Phase 1b: LGX818 200 mg + BYL719 200 mg + Cetuximab | Phase 1b: LGX818 200 mg + BYL719 300 mg + Cetuximab | Phase 1b: LGX818 300 mg + BYL719 200 mg + Cetuximab | Phase 2: LGX818 200 mg + Cetuximab | Phase 2: LGX818 200 mg + BYL719 300 mg + Cetuximab |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received 100 mg of LGX818 (encorafenib) orally once daily along with cetuximab orally once weekly in each cycle of 28 days continuously, until disease progression (PD), unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 orally once daily along with cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 400 mg of LGX818 orally once daily along with cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 450 mg of LGX818 orally once daily along with cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 100 mg of BYL719 (alpelisib) orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 200 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 300 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 300 mg of LGX818 along with 200 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 orally once daily along with cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 300 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). |
| Measure Participants | 2 | 7 | 9 | 8 | 3 | 8 | 10 | 7 | 50 | 52 |
| Count of Participants [Participants] |
2
100%
|
4
57.1%
|
6
66.7%
|
7
87.5%
|
3
100%
|
5
62.5%
|
7
70%
|
6
85.7%
|
33
66%
|
43
82.7%
|
| Title | Apparent Total Plasma Clearance (CL/F) of LGX818 (Encorafenib) |
|---|---|
| Description | Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. |
| Time Frame | Cycle 1 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK analysis set consisted of all participants who had at least one blood sample providing evaluable PK data, received at least 1 dose of study drug, and experienced no major protocol deviations with relevant impact on the PK data. Here 'Overall Number of Participants Analyzed' signifies number of participants who were evaluable for this outcome measure. |
| Arm/Group Title | Phase 1b: LGX818 100 mg + Cetuximab | Phase 1b: LGX818 200 mg + Cetuximab | Phase 1b: LGX818 400 mg + Cetuximab | Phase 1b: LGX818 450 mg + Cetuximab | Phase 1b: LGX818 200 mg + BYL719 100 mg + Cetuximab | Phase 1b: LGX818 200 mg + BYL719 200 mg + Cetuximab | Phase 1b: LGX818 200 mg + BYL719 300 mg + Cetuximab | Phase 1b: LGX818 300 mg + BYL719 200 mg + Cetuximab | Phase 2: LGX818 200 mg + Cetuximab | Phase 2: LGX818 200 mg + BYL719 300 mg + Cetuximab |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received 100 mg of LGX818 (encorafenib) orally once daily along with cetuximab orally once weekly in each cycle of 28 days continuously, until disease progression (PD), unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 orally once daily along with cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 400 mg of LGX818 orally once daily along with cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 450 mg of LGX818 orally once daily along with cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 100 mg of BYL719 (alpelisib) orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 200 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 300 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 300 mg of LGX818 along with 200 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 orally once daily along with cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 300 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). |
| Measure Participants | 2 | 6 | 8 | 5 | 3 | 8 | 6 | 4 | 15 | 15 |
| Mean (Standard Deviation) [liter per hour] |
16.8
(3.60)
|
11.7
(6.10)
|
12.1
(5.95)
|
12.3
(4.96)
|
7.69
(3.13)
|
14.2
(5.75)
|
14.1
(3.65)
|
17.8
(17.4)
|
13.1
(5.07)
|
10.9
(5.70)
|
| Title | Apparent Total Plasma Clearance at Steady State (CL/F, ss) of LGX818 (Encorafenib) |
|---|---|
| Description | Clearance of a drug at steady state is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. |
| Time Frame | Cycle 1 Day 8, Cycle 2 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK analysis set consisted of all participants who had at least one blood sample providing evaluable PK data, received at least 1 dose of study drug, and experienced no major protocol deviations with relevant impact on the PK data. Here 'number analyzed' signifies number of participants evaluable for each specified category and 'Overall Number of Participants Analyzed' signifies number of participants with at least one PK sample analyzed. |
| Arm/Group Title | Phase 1b: LGX818 100 mg + Cetuximab | Phase 1b: LGX818 200 mg + Cetuximab | Phase 1b: LGX818 400 mg + Cetuximab | Phase 1b: LGX818 450 mg + Cetuximab | Phase 1b: LGX818 200 mg + BYL719 100 mg + Cetuximab | Phase 1b: LGX818 200 mg + BYL719 200 mg + Cetuximab | Phase 1b: LGX818 200 mg + BYL719 300 mg + Cetuximab | Phase 1b: LGX818 300 mg + BYL719 200 mg + Cetuximab | Phase 2: LGX818 200 mg + Cetuximab | Phase 2: LGX818 200 mg + BYL719 300 mg + Cetuximab |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received 100 mg of LGX818 (encorafenib) orally once daily along with cetuximab orally once weekly in each cycle of 28 days continuously, until disease progression (PD), unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 orally once daily along with cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 400 mg of LGX818 orally once daily along with cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 450 mg of LGX818 orally once daily along with cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 100 mg of BYL719 (alpelisib) orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 200 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 300 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 300 mg of LGX818 along with 200 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 orally once daily along with cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 300 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). |
| Measure Participants | 2 | 7 | 9 | 8 | 3 | 8 | 10 | 6 | 28 | 36 |
| Cycle 1 Day 8 |
17.0
(3.42)
|
24.4
(18.3)
|
15.4
(4.25)
|
22.4
(17.7)
|
||||||
| Cycle 2 Day 1 |
13.9
(4.72)
|
31.1
(11.9)
|
31.6
(2.19)
|
30.5
(12.3)
|
32.6
(6.88)
|
20.2
(7.91)
|
22.7
(5.68)
|
38.4
(16.4)
|
28.2
(8.97)
|
23.3
(11.6)
|
| Title | Apparent Total Plasma Clearance (CL/F) of BYL719 (Alpelisib) |
|---|---|
| Description | Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. |
| Time Frame | Cycle 1 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK analysis set consisted of all participants who had at least 1 blood sample providing evaluable PK data, received at least 1 dose of study drug, and experienced no major protocol deviations with relevant impact on the PK data. Here 'Overall Number of Participants Analyzed' signifies number of participants who were evaluable for this outcome measure. |
| Arm/Group Title | Phase 1b: LGX818 200 mg + BYL719 100 mg + Cetuximab | Phase 1b: LGX818 200 mg + BYL719 200 mg + Cetuximab | Phase 1b: LGX818 200 mg + BYL719 300 mg + Cetuximab | Phase 1b: LGX818 300 mg + BYL719 200 mg + Cetuximab | Phase 2: LGX818 200 mg + BYL719 300 mg + Cetuximab |
|---|---|---|---|---|---|
| Arm/Group Description | Participants received 200 mg of LGX818 along with 100 mg of BYL719 (alpelisib) orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 200 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 300 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 300 mg of LGX818 along with 200 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 300 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). |
| Measure Participants | 3 | 5 | 7 | 4 | 10 |
| Mean (Standard Deviation) [liter per hour] |
12.7
(2.03)
|
12.1
(3.96)
|
11.6
(1.85)
|
11.7
(5.38)
|
15.6
(9.61)
|
| Title | Apparent Total Plasma Clearance at Steady State (CL/F, ss) of BYL719 (Alpelisib) |
|---|---|
| Description | Clearance of a drug at steady state is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. |
| Time Frame | Cycle 1 Day 8, Cycle 2 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK analysis set consisted of all participants who had at least 1 blood sample providing evaluable PK data, received at least 1 dose of study drug, and experienced no major protocol deviations with relevant impact on the PK data. Here 'number analyzed' signifies number of participants evaluable for each specified category and 'Overall Number of Participants Analyzed' signifies number of participants with at least one PK sample analyzed. |
| Arm/Group Title | Phase 1b: LGX818 200 mg + BYL719 100 mg + Cetuximab | Phase 1b: LGX818 200 mg + BYL719 200 mg + Cetuximab | Phase 1b: LGX818 200 mg + BYL719 300 mg + Cetuximab | Phase 1b: LGX818 300 mg + BYL719 200 mg + Cetuximab | Phase 2: LGX818 200 mg + BYL719 300 mg + Cetuximab |
|---|---|---|---|---|---|
| Arm/Group Description | Participants received 200 mg of LGX818 along with 100 mg of BYL719 (alpelisib) orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 200 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 300 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 300 mg of LGX818 along with 200 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 300 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). |
| Measure Participants | 3 | 8 | 10 | 6 | 36 |
| Cycle 1 Day 8 |
16.5
(5.96)
|
13.2
(2.29)
|
13.7
(7.20)
|
11.6
(6.05)
|
|
| Cycle 2 Day 1 |
18.3
(0.794)
|
10.3
(1.23)
|
12.5
(1.60)
|
19.0
(6.51)
|
17.9
(10.5)
|
| Title | Apparent Terminal Volume of Distribution (Vz/F) of LGX818 (Encorafenib) |
|---|---|
| Description | Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed. |
| Time Frame | Cycle 1 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK analysis set consisted of all participants who had at least 1 blood sample providing evaluable PK data, received at least 1 dose of study drug, and experienced no major protocol deviations with relevant impact on the PK data. Here 'Overall Number of Participants Analyzed' signifies number of participants who were evaluable for this outcome measure. |
| Arm/Group Title | Phase 1b: LGX818 100 mg + Cetuximab | Phase 1b: LGX818 200 mg + Cetuximab | Phase 1b: LGX818 400 mg + Cetuximab | Phase 1b: LGX818 450 mg + Cetuximab | Phase 1b: LGX818 200 mg + BYL719 100 mg + Cetuximab | Phase 1b: LGX818 200 mg + BYL719 200 mg + Cetuximab | Phase 1b: LGX818 200 mg + BYL719 300 mg + Cetuximab | Phase 1b: LGX818 300 mg + BYL719 200 mg + Cetuximab | Phase 2: LGX818 200 mg + Cetuximab | Phase 2: LGX818 200 mg + BYL719 300 mg + Cetuximab |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received 100 mg of LGX818 (encorafenib) orally once daily along with cetuximab orally once weekly in each cycle of 28 days continuously, until disease progression (PD), unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 orally once daily along with cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 400 mg of LGX818 orally once daily along with cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 450 mg of LGX818 orally once daily along with cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 100 mg of BYL719 (alpelisib) orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 200 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 300 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 300 mg of LGX818 along with 200 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 orally once daily along with cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 300 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). |
| Measure Participants | 2 | 6 | 8 | 5 | 3 | 8 | 6 | 4 | 15 | 15 |
| Mean (Standard Deviation) [liter] |
104
(28.3)
|
60.3
(25.8)
|
62.8
(31.8)
|
57.2
(29.6)
|
49.2
(12.4)
|
75.7
(31.6)
|
64.6
(20.6)
|
60.7
(44.0)
|
63.5
(29.9)
|
80.9
(93.9)
|
| Title | Apparent Terminal Volume of Distribution at Steady State (Vz/F, ss) of LGX818 (Encorafenib) |
|---|---|
| Description | Volume of distribution at steady state is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F, ss) is influenced by the fraction absorbed. |
| Time Frame | Cycle 1 Day 8, Cycle 2 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK analysis set consisted of all participants who had at least 1 blood sample providing evaluable PK data, received at least 1 dose of study drug, and experienced no major protocol deviations with relevant impact on the PK data. Here 'number analyzed' signifies number of participants evaluable for each specified category and 'Overall Number of Participants Analyzed' signifies number of participants with at least one PK sample analyzed. |
| Arm/Group Title | Phase 1b: LGX818 100 mg + Cetuximab | Phase 1b: LGX818 200 mg + Cetuximab | Phase 1b: LGX818 400 mg + Cetuximab | Phase 1b: LGX818 450 mg + Cetuximab | Phase 1b: LGX818 200 mg + BYL719 100 mg + Cetuximab | Phase 1b: LGX818 200 mg + BYL719 200 mg + Cetuximab | Phase 1b: LGX818 200 mg + BYL719 300 mg + Cetuximab | Phase 1b: LGX818 300 mg + BYL719 200 mg + Cetuximab | Phase 2: LGX818 200 mg + Cetuximab | Phase 2: LGX818 200 mg + BYL719 300 mg + Cetuximab |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received 100 mg of LGX818 (encorafenib) orally once daily along with cetuximab orally once weekly in each cycle of 28 days continuously, until disease progression (PD), unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 orally once daily along with cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 400 mg of LGX818 orally once daily along with cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 450 mg of LGX818 orally once daily along with cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 100 mg of BYL719 (alpelisib) orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 200 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 300 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 300 mg of LGX818 along with 200 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 orally once daily along with cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 300 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). |
| Measure Participants | 2 | 7 | 9 | 8 | 3 | 8 | 10 | 6 | 28 | 36 |
| Cycle 1 Day 8 |
78.4
(13.0)
|
98.2
(84.5)
|
78.6
(26.2)
|
88.8
(53.6)
|
||||||
| Cycle 2 Day 1 |
66.8
(13.7)
|
131
(45.8)
|
110
(41.1)
|
142
(84.5)
|
137
(32.9)
|
91.6
(41.4)
|
102
(39.9)
|
187
(89.5)
|
117
(37.6)
|
105
(42.2)
|
| Title | Apparent Terminal Volume of Distribution (Vz/F) of BYL719 (Alpelisib) |
|---|---|
| Description | Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed. |
| Time Frame | Cycle 1 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK analysis set consisted of all participants who had at least 1 blood sample providing evaluable PK data, received at least 1 dose of study drug, and experienced no major protocol deviations with relevant impact on the PK data. Here 'Overall Number of Participants Analyzed' signifies number of participants who were evaluable for this outcome measure. |
| Arm/Group Title | Phase 1b: LGX818 200 mg + BYL719 100 mg + Cetuximab | Phase 1b: LGX818 200 mg + BYL719 200 mg + Cetuximab | Phase 1b: LGX818 200 mg + BYL719 300 mg + Cetuximab | Phase 1b: LGX818 300 mg + BYL719 200 mg + Cetuximab | Phase 2: LGX818 200 mg + BYL719 300 mg + Cetuximab |
|---|---|---|---|---|---|
| Arm/Group Description | Participants received 200 mg of LGX818 along with 100 mg of BYL719 (alpelisib) orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 200 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 300 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 300 mg of LGX818 along with 200 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 300 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). |
| Measure Participants | 3 | 5 | 7 | 4 | 10 |
| Mean (Standard Deviation) [liter] |
112
(22.0)
|
104
(31.0)
|
105
(34.3)
|
106
(78.6)
|
123
(50.7)
|
| Title | Apparent Terminal Volume of Distribution at Steady State (Vz/F, ss) of BYL719 (Alpelisib) |
|---|---|
| Description | Volume of distribution at steady state was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F, ss) is influenced by the fraction absorbed. |
| Time Frame | Cycle 1 Day 8, Cycle 2 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK analysis set consisted of all participants who had at least 1 blood sample providing evaluable PK data, received at least 1 dose of study drug, and experienced no major protocol deviations with relevant impact on the PK data. Here 'number analyzed' signifies number of participants evaluable for each specified category and 'Overall Number of Participants Analyzed' signifies number of participants with at least one PK sample analyzed. |
| Arm/Group Title | Phase 1b: LGX818 200 mg + BYL719 100 mg + Cetuximab | Phase 1b: LGX818 200 mg + BYL719 200 mg + Cetuximab | Phase 1b: LGX818 200 mg + BYL719 300 mg + Cetuximab | Phase 1b: LGX818 300 mg + BYL719 200 mg + Cetuximab | Phase 2: LGX818 200 mg + BYL719 300 mg + Cetuximab |
|---|---|---|---|---|---|
| Arm/Group Description | Participants received 200 mg of LGX818 along with 100 mg of BYL719 (alpelisib) orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 200 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 300 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 300 mg of LGX818 along with 200 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 300 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). |
| Measure Participants | 3 | 8 | 10 | 6 | 36 |
| Cycle 1 Day 8 |
110
(40.7)
|
97.0
(20.6)
|
105
(30.2)
|
82.5
(18.8)
|
|
| Cycle 2 Day 1 |
138
(20.7)
|
75.4
(11.2)
|
104
(10.7)
|
144
(44.5)
|
149
(100)
|
| Title | Time to Reach Maximum Observed Plasma Concentration (Tmax) of LGX818 (Encorafenib) |
|---|---|
| Description | Tmax was defined as the time to reach maximum observed plasma concentration of encorafenib. |
| Time Frame | Cycle 1 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK analysis set consisted of all participants who had at least 1 blood sample providing evaluable PK data, received at least 1 dose of study drug, and experienced no major protocol deviations with relevant impact on the PK data. Here 'Overall Number of Participants Analyzed' signifies number of participants who were evaluable for this outcome measure. |
| Arm/Group Title | Phase 1b: LGX818 100 mg + Cetuximab | Phase 1b: LGX818 200 mg + Cetuximab | Phase 1b: LGX818 400 mg + Cetuximab | Phase 1b: LGX818 450 mg + Cetuximab | Phase 1b: LGX818 200 mg + BYL719 100 mg + Cetuximab | Phase 1b: LGX818 200 mg + BYL719 200 mg + Cetuximab | Phase 1b: LGX818 200 mg + BYL719 300 mg + Cetuximab | Phase 1b: LGX818 300 mg + BYL719 200 mg + Cetuximab | Phase 2: LGX818 200 mg + Cetuximab | Phase 2: LGX818 200 mg + BYL719 300 mg + Cetuximab |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received 100 mg of LGX818 (encorafenib) orally once daily along with cetuximab orally once weekly in each cycle of 28 days continuously, until disease progression (PD), unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 orally once daily along with cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 400 mg of LGX818 orally once daily along with cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 450 mg of LGX818 orally once daily along with cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 100 mg of BYL719 (alpelisib) orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 200 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 300 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 300 mg of LGX818 along with 200 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 orally once daily along with cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 300 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). |
| Measure Participants | 2 | 6 | 9 | 7 | 3 | 8 | 9 | 5 | 17 | 21 |
| Median (Full Range) [hour] |
2.00
|
1.99
|
2.03
|
2.17
|
1.00
|
2.02
|
2.00
|
3.87
|
2.00
|
2.03
|
| Title | Time to Reach Maximum Plasma Concentration at Steady State (Tmax, ss) of LGX818 (Encorafenib) |
|---|---|
| Description | Tmax, ss was defined as the time to reach maximum observed plasma concentration of LGX818 (encorafenib) at steady state. |
| Time Frame | Cycle 1 Day 8, Cycle 2 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK analysis set consisted of all participants who had at least 1 blood sample providing evaluable PK data, received at least 1 dose of study drug, and experienced no major protocol deviations with relevant impact on the PK data. Here 'number analyzed' signifies number of participants evaluable for each specified category and 'Overall Number of Participants Analyzed' signifies number of participants with at least one PK sample analyzed. |
| Arm/Group Title | Phase 1b: LGX818 100 mg + Cetuximab | Phase 1b: LGX818 200 mg + Cetuximab | Phase 1b: LGX818 400 mg + Cetuximab | Phase 1b: LGX818 450 mg + Cetuximab | Phase 1b: LGX818 200 mg + BYL719 100 mg + Cetuximab | Phase 1b: LGX818 200 mg + BYL719 200 mg + Cetuximab | Phase 1b: LGX818 200 mg + BYL719 300 mg + Cetuximab | Phase 1b: LGX818 300 mg + BYL719 200 mg + Cetuximab | Phase 2: LGX818 200 mg + Cetuximab | Phase 2: LGX818 200 mg + BYL719 300 mg + Cetuximab |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received 100 mg of LGX818 (encorafenib) orally once daily along with cetuximab orally once weekly in each cycle of 28 days continuously, until disease progression (PD), unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 orally once daily along with cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 400 mg of LGX818 orally once daily along with cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 450 mg of LGX818 orally once daily along with cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 100 mg of BYL719 (alpelisib) orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 200 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 300 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 300 mg of LGX818 along with 200 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 orally once daily along with cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 300 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). |
| Measure Participants | 2 | 7 | 9 | 8 | 3 | 8 | 10 | 6 | 28 | 36 |
| Cycle 1 Day 8 |
0.98
|
1.98
|
2.00
|
3.92
|
||||||
| Cycle 2 Day 1 |
1.51
|
2.00
|
1.98
|
1.98
|
2.00
|
2.02
|
3.00
|
2.27
|
1.15
|
2.00
|
| Title | Time to Reach Maximum Observed Plasma Concentration (Tmax) of BYL719 (Alpelisib) |
|---|---|
| Description | Tmax was defined as the time to reach maximum observed plasma concentration of alpelisib. |
| Time Frame | Cycle 1 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK analysis set consisted of all participants who had at least 1 blood sample providing evaluable PK data, received at least 1 dose of study drug, and experienced no major protocol deviations with relevant impact on the PK data. Here 'Overall Number of Participants Analyzed' signifies number of participants who were evaluable for this outcome measure. |
| Arm/Group Title | Phase 1b: LGX818 200 mg + BYL719 100 mg + Cetuximab | Phase 1b: LGX818 200 mg + BYL719 200 mg + Cetuximab | Phase 1b: LGX818 200 mg + BYL719 300 mg + Cetuximab | Phase 1b: LGX818 300 mg + BYL719 200 mg + Cetuximab | Phase 2: LGX818 200 mg + BYL719 300 mg + Cetuximab |
|---|---|---|---|---|---|
| Arm/Group Description | Participants received 200 mg of LGX818 along with 100 mg of BYL719 (alpelisib) orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 200 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 300 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 300 mg of LGX818 along with 200 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 300 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). |
| Measure Participants | 3 | 8 | 8 | 5 | 15 |
| Median (Full Range) [hour] |
1.98
|
3.97
|
2.00
|
2.10
|
2.05
|
| Title | Time to Reach Maximum Plasma Concentration at Steady State (Tmax, ss) of BYL719 (Alpelisib) |
|---|---|
| Description | Tmax, ss was defined as the time to reach maximum observed plasma concentration of BYL719 (alpelisib) at steady state. |
| Time Frame | Cycle 1 Day 8, Cycle 2 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK analysis set consisted of all participants who had at least 1 blood sample providing evaluable PK data, received at least 1 dose of study drug, and experienced no major protocol deviations with relevant impact on the PK data. Here 'number analyzed' signifies number of participants evaluable for each specified category and 'Overall Number of Participants Analyzed' signifies number of participants with at least one PK sample analyzed. |
| Arm/Group Title | Phase 1b: LGX818 200 mg + BYL719 100 mg + Cetuximab | Phase 1b: LGX818 200 mg + BYL719 200 mg + Cetuximab | Phase 1b: LGX818 200 mg + BYL719 300 mg + Cetuximab | Phase 1b: LGX818 300 mg + BYL719 200 mg + Cetuximab | Phase 2: LGX818 200 mg + BYL719 300 mg + Cetuximab |
|---|---|---|---|---|---|
| Arm/Group Description | Participants received 200 mg of LGX818 along with 100 mg of BYL719 (alpelisib) orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 200 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 300 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 300 mg of LGX818 along with 200 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 300 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). |
| Measure Participants | 3 | 8 | 10 | 6 | 36 |
| Cycle 1 Day 8 |
1.97
|
3.99
|
2.15
|
4.07
|
|
| Cycle 2 Day 1 |
2.02
|
4.00
|
3.93
|
4.03
|
2.02
|
| Title | Time of Last Observed Plasma Concentration (T-last) of LGX818 (Encorafenib) |
|---|---|
| Description | T-last was defined as the time to reach last observed plasma concentration of encorafenib. |
| Time Frame | Cycle 1 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK analysis set consisted of all participants who had at least 1 blood sample providing evaluable PK data, received at least 1 dose of study drug, and experienced no major protocol deviations with relevant impact on the PK data. Here 'Overall Number of Participants Analyzed' signifies number of participants who were evaluable for this outcome measure. |
| Arm/Group Title | Phase 1b: LGX818 100 mg + Cetuximab | Phase 1b: LGX818 200 mg + Cetuximab | Phase 1b: LGX818 400 mg + Cetuximab | Phase 1b: LGX818 450 mg + Cetuximab | Phase 1b: LGX818 200 mg + BYL719 100 mg + Cetuximab | Phase 1b: LGX818 200 mg + BYL719 200 mg + Cetuximab | Phase 1b: LGX818 200 mg + BYL719 300 mg + Cetuximab | Phase 1b: LGX818 300 mg + BYL719 200 mg + Cetuximab | Phase 2: LGX818 200 mg + Cetuximab | Phase 2: LGX818 200 mg + BYL719 300 mg + Cetuximab |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received 100 mg of LGX818 (encorafenib) orally once daily along with cetuximab orally once weekly in each cycle of 28 days continuously, until disease progression (PD), unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 orally once daily along with cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 400 mg of LGX818 orally once daily along with cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 450 mg of LGX818 orally once daily along with cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 100 mg of BYL719 (alpelisib) orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 200 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 300 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 300 mg of LGX818 along with 200 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 orally once daily along with cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 300 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). |
| Measure Participants | 2 | 6 | 9 | 7 | 3 | 8 | 9 | 5 | 17 | 21 |
| Median (Full Range) [hour] |
23.98
|
23.69
|
24.03
|
23.58
|
23.00
|
23.06
|
22.02
|
23.87
|
23.85
|
23.50
|
| Title | Time of Last Observed Plasma Concentration at Steady State (T-last, ss) of LGX818 (Encorafenib) |
|---|---|
| Description | T-last, ss was defined as the time to reach last observed plasma concentration of encorafenib at steady state. |
| Time Frame | Cycle 1 Day 8, Cycle 2 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK analysis set consisted of all participants who had at least 1 blood sample providing evaluable PK data, received at least 1 dose of study drug, and experienced no major protocol deviations with relevant impact on the PK data. Here 'number analyzed' signifies number of participants evaluable for each specified category and 'Overall Number of Participants Analyzed' signifies number of participants with at least one PK sample analyzed. |
| Arm/Group Title | Phase 1b: LGX818 100 mg + Cetuximab | Phase 1b: LGX818 200 mg + Cetuximab | Phase 1b: LGX818 400 mg + Cetuximab | Phase 1b: LGX818 450 mg + Cetuximab | Phase 1b: LGX818 200 mg + BYL719 100 mg + Cetuximab | Phase 1b: LGX818 200 mg + BYL719 200 mg + Cetuximab | Phase 1b: LGX818 200 mg + BYL719 300 mg + Cetuximab | Phase 1b: LGX818 300 mg + BYL719 200 mg + Cetuximab | Phase 2: LGX818 200 mg + Cetuximab | Phase 2: LGX818 200 mg + BYL719 300 mg + Cetuximab |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received 100 mg of LGX818 (encorafenib) orally once daily along with cetuximab orally once weekly in each cycle of 28 days continuously, until disease progression (PD), unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 orally once daily along with cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 400 mg of LGX818 orally once daily along with cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 450 mg of LGX818 orally once daily along with cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 100 mg of BYL719 (alpelisib) orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 200 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 300 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 300 mg of LGX818 along with 200 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 orally once daily along with cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 300 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). |
| Measure Participants | 2 | 7 | 9 | 8 | 3 | 8 | 10 | 6 | 28 | 36 |
| Cycle 1 Day 8 |
23.78
|
23.36
|
23.92
|
23.87
|
||||||
| Cycle 2 Day 1 |
23.89
|
22.13
|
14.05
|
23.45
|
23.97
|
23.08
|
23.94
|
23.42
|
23.80
|
23.42
|
| Title | Time of Last Observed Plasma Concentration (T-last) of BYL719 (Alpelisib) |
|---|---|
| Description | T-last was defined as the time to reach last observed plasma concentration of alpelisib. |
| Time Frame | Cycle 1 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK analysis set consisted of all participants who had at least 1 blood sample providing evaluable PK data, received at least 1 dose of study drug, and experienced no major protocol deviations with relevant impact on the PK data. Here 'Overall Number of Participants Analyzed' signifies number of participants who were evaluable for this outcome measure. |
| Arm/Group Title | Phase 1b: LGX818 200 mg + BYL719 100 mg + Cetuximab | Phase 1b: LGX818 200 mg + BYL719 200 mg + Cetuximab | Phase 1b: LGX818 200 mg + BYL719 300 mg + Cetuximab | Phase 1b: LGX818 300 mg + BYL719 200 mg + Cetuximab | Phase 2: LGX818 200 mg + BYL719 300 mg + Cetuximab |
|---|---|---|---|---|---|
| Arm/Group Description | Participants received 200 mg of LGX818 along with 100 mg of BYL719 (alpelisib) orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 200 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 300 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 300 mg of LGX818 along with 200 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 300 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). |
| Measure Participants | 3 | 8 | 8 | 5 | 15 |
| Median (Full Range) [hour] |
23.00
|
23.06
|
22.76
|
23.87
|
23.17
|
| Title | Time of Last Observed Plasma Concentration at Steady State (T-last, ss) of BYL719 (Alpelisib) |
|---|---|
| Description | T-last, ss was defined as the time to reach last observed plasma concentration of alpelisib at steady state. |
| Time Frame | Cycle 1 Day 8, Cycle 2 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK analysis set consisted of all participants who had at least 1 blood sample providing evaluable PK data, received at least 1 dose of study drug, and experienced no major protocol deviations with relevant impact on the PK data. Here 'number analyzed' signifies number of participants evaluable for each specified category and 'Overall Number of Participants Analyzed' signifies number of participants with at least one PK sample analyzed. |
| Arm/Group Title | Phase 1b: LGX818 200 mg + BYL719 100 mg + Cetuximab | Phase 1b: LGX818 200 mg + BYL719 200 mg + Cetuximab | Phase 1b: LGX818 200 mg + BYL719 300 mg + Cetuximab | Phase 1b: LGX818 300 mg + BYL719 200 mg + Cetuximab | Phase 2: LGX818 200 mg + BYL719 300 mg + Cetuximab |
|---|---|---|---|---|---|
| Arm/Group Description | Participants received 200 mg of LGX818 along with 100 mg of BYL719 (alpelisib) orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 200 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 300 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 300 mg of LGX818 along with 200 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 300 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). |
| Measure Participants | 3 | 8 | 10 | 6 | 36 |
| Cycle 1 Day 8 |
23.78
|
23.36
|
23.87
|
23.87
|
|
| Cycle 2 Day 1 |
23.97
|
23.08
|
23.94
|
23.47
|
23.77
|
| Title | Plasma Trough Concentration at Steady State (Ctrough, ss) of LGX818 (Encorafenib) |
|---|---|
| Description | Ctrough, ss was defined as plasma trough concentration of encorafenib at steady state. |
| Time Frame | Cycle 2 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK analysis set consisted of all participants who had at least 1 blood sample providing evaluable PK data, received at least 1 dose of study drug, and experienced no major protocol deviations with relevant impact on the PK data. Here 'Overall Number of Participants Analyzed' signifies number of participants who were evaluable for this outcome measure. |
| Arm/Group Title | Phase 1b: LGX818 100 mg + Cetuximab | Phase 1b: LGX818 200 mg + Cetuximab | Phase 1b: LGX818 400 mg + Cetuximab | Phase 1b: LGX818 450 mg + Cetuximab | Phase 1b: LGX818 200 mg + BYL719 100 mg + Cetuximab | Phase 1b: LGX818 200 mg + BYL719 200 mg + Cetuximab | Phase 1b: LGX818 200 mg + BYL719 300 mg + Cetuximab | Phase 1b: LGX818 300 mg + BYL719 200 mg + Cetuximab | Phase 2: LGX818 200 mg + Cetuximab | Phase 2: LGX818 200 mg + BYL719 300 mg + Cetuximab |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received 100 mg of LGX818 (encorafenib) orally once daily along with cetuximab orally once weekly in each cycle of 28 days continuously, until disease progression (PD), unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 orally once daily along with cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 400 mg of LGX818 orally once daily along with cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 450 mg of LGX818 orally once daily along with cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 100 mg of BYL719 (alpelisib) orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 200 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 300 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 300 mg of LGX818 along with 200 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 orally once daily along with cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 300 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). |
| Measure Participants | 2 | 5 | 6 | 6 | 3 | 7 | 8 | 1 | 11 | 15 |
| Mean (Standard Deviation) [nanogram per milliliter] |
9.87
(6.69)
|
20.5
(28.0)
|
15.7
(22.0)
|
20.6
(18.4)
|
7.69
(1.76)
|
10.4
(5.05)
|
26.5
(31.4)
|
29.2
(NA)
|
9.24
(5.19)
|
15.0
(17.8)
|
| Title | Plasma Trough Concentration at Steady State (Ctrough, ss) of BYL719 (Alpelisib) |
|---|---|
| Description | Ctrough, ss was defined as plasma trough concentration of alpelisib at steady state. |
| Time Frame | Cycle 2 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK analysis set consisted of all participants who had at least 1 blood sample providing evaluable PK data, received at least 1 dose of study drug, and experienced no major protocol deviations with relevant impact on the PK data. Here 'Overall Number of Participants Analyzed' signifies number of participants who were evaluable for this outcome measure. |
| Arm/Group Title | Phase 1b: LGX818 200 mg + BYL719 100 mg + Cetuximab | Phase 1b: LGX818 200 mg + BYL719 200 mg + Cetuximab | Phase 1b: LGX818 200 mg + BYL719 300 mg + Cetuximab | Phase 1b: LGX818 300 mg + BYL719 200 mg + Cetuximab | Phase 2: LGX818 200 mg + BYL719 300 mg + Cetuximab |
|---|---|---|---|---|---|
| Arm/Group Description | Participants received 200 mg of LGX818 along with 100 mg of BYL719 (alpelisib) orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 200 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 300 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 300 mg of LGX818 along with 200 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 300 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). |
| Measure Participants | 3 | 7 | 8 | 1 | 8 |
| Mean (Standard Deviation) [nanogram per milliliter] |
36.7
(21.0)
|
108
(41.1)
|
283
(156)
|
66.0
(NA)
|
141
(76.5)
|
| Title | Overall Survival (OS) |
|---|---|
| Description | OS was defined as the time (in months) from the date of randomization or date of start of treatment to the date of death due to any cause or data censoring date, whichever occurred first. Participants last known to be alive were censored at date of last contact. Analysis was performed using Kaplan-Meier method. |
| Time Frame | From the date of randomization or date of start of treatment to the date of death due to any cause or data censoring date, whichever occurred first (up to 43 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The FAS1 comprised all participants who received at least 1 full or partial dose of their assigned combination of study drugs during Phase 1b. The FAS2 comprised all randomized participants in Phase 2. |
| Arm/Group Title | Phase 1b: LGX818 100 mg + Cetuximab | Phase 1b: LGX818 200 mg + Cetuximab | Phase 1b: LGX818 400 mg + Cetuximab | Phase 1b: LGX818 450 mg + Cetuximab | Phase 1b: LGX818 200 mg + BYL719 100 mg + Cetuximab | Phase 1b: LGX818 200 mg + BYL719 200 mg + Cetuximab | Phase 1b: LGX818 200 mg + BYL719 300 mg + Cetuximab | Phase 1b: LGX818 300 mg + BYL719 200 mg + Cetuximab | Phase 2: LGX818 200 mg + Cetuximab | Phase 2: LGX818 200 mg + BYL719 300 mg + Cetuximab |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received 100 mg of LGX818 (encorafenib) orally once daily along with cetuximab orally once weekly in each cycle of 28 days continuously, until disease progression (PD), unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 orally once daily along with cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 400 mg of LGX818 orally once daily along with cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 450 mg of LGX818 orally once daily along with cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 100 mg of BYL719 (alpelisib) orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 200 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 300 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 300 mg of LGX818 along with 200 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 orally once daily along with cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 300 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). |
| Measure Participants | 2 | 7 | 9 | 8 | 3 | 8 | 10 | 7 | 50 | 52 |
| Median (95% Confidence Interval) [months] |
15.0
|
5.4
|
NA
|
16.6
|
6.6
|
8.7
|
9.8
|
NA
|
9.3
|
8.5
|
| Title | Overall Response Rate (ORR) |
|---|---|
| Description | Overall response rate as assessed by the investigator per RECIST v1.1, was defined as percentage of participants with a best overall response of complete response (CR) or partial response (PR), were recorded from date of randomization or date of start of treatment until date of first documentation of progressive disease (PD) or death due to any cause. CR was defined as complete disappearance of all target and non-nodal target lesions, and sustained for at least 4 weeks apart before progression. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<) 10 millimeter (mm). PR defined as at least 30 percent (%) decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters. Only confirmed CR and PR are counted (those confirmed at least 4 weeks). |
| Time Frame | From date of randomization or date of start of treatment until date of first documentation of PD or death due to any cause (maximum up to 43 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The FAS 1 comprised all participants who received at least 1 full or partial dose of their assigned combination of study drugs during Phase 1b. The FAS2 comprised all randomized participants in Phase 2. |
| Arm/Group Title | Phase 1b: LGX818 100 mg + Cetuximab | Phase 1b: LGX818 200 mg + Cetuximab | Phase 1b: LGX818 400 mg + Cetuximab | Phase 1b: LGX818 450 mg + Cetuximab | Phase 1b: LGX818 200 mg + BYL719 100 mg + Cetuximab | Phase 1b: LGX818 200 mg + BYL719 200 mg + Cetuximab | Phase 1b: LGX818 200 mg + BYL719 300 mg + Cetuximab | Phase 1b: LGX818 300 mg + BYL719 200 mg + Cetuximab | Phase 2: LGX818 200 mg + Cetuximab | Phase 2: LGX818 200 mg + BYL719 300 mg + Cetuximab |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received 100 mg of LGX818 (encorafenib) orally once daily along with cetuximab orally once weekly in each cycle of 28 days continuously, until disease progression (PD), unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 orally once daily along with cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 400 mg of LGX818 orally once daily along with cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 450 mg of LGX818 orally once daily along with cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 100 mg of BYL719 (alpelisib) orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 200 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 300 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 300 mg of LGX818 along with 200 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 orally once daily along with cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 300 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). |
| Measure Participants | 2 | 7 | 9 | 8 | 3 | 8 | 10 | 7 | 50 | 52 |
| Number (95% Confidence Interval) [percentage of participants] |
50.0
2500%
|
14.3
204.3%
|
11.1
123.3%
|
25.0
312.5%
|
33.3
1110%
|
25.0
312.5%
|
20.0
200%
|
0
0%
|
24.0
48%
|
26.9
51.7%
|
| Title | Duration of Response (DOR) |
|---|---|
| Description | DOR: Time between date of the first documented response (CR or PR) and the date of first documented PD or death due to underlying cancer. If PD or death due to underlying cancer not occurred, then participant was censored at the date of last tumor assessment other than unknown. DOR was calculated for responders (confirmed) only. CR: Disappearance of all target, non-target lesions sustained for >=4 weeks and any pathological lymph nodes reduced in short axis to <10mm. PR: >=30% decrease in sum of diameters of target lesions, taking as reference baseline sum of diameter. PD for target lesions: At least a 20% increase in sum of diameters of target lesions, taking as reference smallest sum on study treatment, with absolute increase of >=5 mm, or appearance of >=1 new lesions. PD for non-target lesions: Unequivocal progression of pre-existing lesions/increase in overall tumor burden leading to discontinuation of therapy or appearance of new unequivocal malignant lesion. |
| Time Frame | From the first documentation of OR (confirmed CR or PR) to first documentation of PD/death due to any cause or censoring date, whichever occurred first (up to 43 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The FAS 1 comprised all participants who received at least 1 full or partial dose of their assigned combination of study drugs during Phase 1b. The FAS2 comprised all randomized participants in Phase 2. Here 'Overall Number of Participants Analyzed' signifies number of participants who were evaluable for this outcome measure. |
| Arm/Group Title | Phase 1b: LGX818 100 mg + Cetuximab | Phase 1b: LGX818 200 mg + Cetuximab | Phase 1b: LGX818 400 mg + Cetuximab | Phase 1b: LGX818 450 mg + Cetuximab | Phase 1b: LGX818 200 mg + BYL719 100 mg + Cetuximab | Phase 1b: LGX818 200 mg + BYL719 200 mg + Cetuximab | Phase 1b: LGX818 200 mg + BYL719 300 mg + Cetuximab | Phase 1b: LGX818 300 mg + BYL719 200 mg + Cetuximab | Phase 2: LGX818 200 mg + Cetuximab | Phase 2: LGX818 200 mg + BYL719 300 mg + Cetuximab |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received 100 mg of LGX818 (encorafenib) orally once daily along with cetuximab orally once weekly in each cycle of 28 days continuously, until disease progression (PD), unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 orally once daily along with cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 400 mg of LGX818 orally once daily along with cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 450 mg of LGX818 orally once daily along with cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 100 mg of BYL719 (alpelisib) orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 200 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 300 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 300 mg of LGX818 along with 200 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 orally once daily along with cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 300 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). |
| Measure Participants | 1 | 1 | 1 | 2 | 1 | 2 | 2 | 0 | 11 | 14 |
| Median (95% Confidence Interval) [months] |
10.6
|
2.3
|
21.7
|
8.1
|
3.9
|
3.6
|
3.3
|
5.6
|
5.3
|
| Title | Time to Response (TTR) |
|---|---|
| Description | TTR as assessed by investigator according to RECIST v1.1, was defined as the time (in months) from date of randomization or date of start of treatment until first documented response (CR or PR) or data censoring date, whichever occurred first. CR was defined as complete disappearance of all target and non-target lesions sustained for at least 4 weeks apart before progression. Any pathological lymph nodes (whether target or non-target) reduced in short axis to <10 mm. PR was defined as at least 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters. Participants who did not achieve a confirmed PR or CR, were censored at last adequate tumor assessment date when they did not progress (including deaths not due to underlying disease) or at maximum follow-up (from study start to study end date) when participant had an event for progression-free survival. |
| Time Frame | From the date of randomization or date of start of treatment until first documented response (CR or PR) or data censoring date, whichever occurred first (maximum up to 43 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The FAS 1 comprised all participants who received at least 1 full or partial dose of their assigned combination of study drugs during Phase 1b. The FAS2 comprised all randomized participants in Phase 2. Here 'Overall Number of Participants Analyzed' signifies number of participants who were evaluable for this outcome measure. |
| Arm/Group Title | Phase 1b: LGX818 100 mg + Cetuximab | Phase 1b: LGX818 200 mg + Cetuximab | Phase 1b: LGX818 400 mg + Cetuximab | Phase 1b: LGX818 450 mg + Cetuximab | Phase 1b: LGX818 200 mg + BYL719 100 mg + Cetuximab | Phase 1b: LGX818 200 mg + BYL719 200 mg + Cetuximab | Phase 1b: LGX818 200 mg + BYL719 300 mg + Cetuximab | Phase 1b: LGX818 300 mg + BYL719 200 mg + Cetuximab | Phase 2: LGX818 200 mg + Cetuximab | Phase 2: LGX818 200 mg + BYL719 300 mg + Cetuximab |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received 100 mg of LGX818 (encorafenib) orally once daily along with cetuximab orally once weekly in each cycle of 28 days continuously, until disease progression (PD), unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 orally once daily along with cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 400 mg of LGX818 orally once daily along with cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 450 mg of LGX818 orally once daily along with cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 100 mg of BYL719 (alpelisib) orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 200 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 300 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 300 mg of LGX818 along with 200 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 orally once daily along with cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 300 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). |
| Measure Participants | 1 | 1 | 1 | 2 | 1 | 2 | 2 | 0 | 12 | 15 |
| Median (95% Confidence Interval) [months] |
2.8
|
1.4
|
3.9
|
4.0
|
1.5
|
3.5
|
2.0
|
1.7
|
1.5
|
| Title | Phase 1b: Progression Free Survival (PFS) |
|---|---|
| Description | PFS was defined as 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. Participants who did not progress per RECIST v1.1, were not known to have died prior to the data cut-off, or received any further anticancer therapy were censored at the date of last adequate tumor assessment or the anticancer therapy date, whichever was earlier. |
| Time Frame | From date of start of treatment to the date of event defined as the first documented progression or death due to any cause, censored date, whichever occurred first (maximum up to 43 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The FAS 1 comprised all participants who received at least 1 full or partial dose of their assigned combination of study drugs during Phase 1b. |
| Arm/Group Title | Phase 1b: LGX818 100 mg + Cetuximab | Phase 1b: LGX818 200 mg + Cetuximab | Phase 1b: LGX818 400 mg + Cetuximab | Phase 1b: LGX818 450 mg + Cetuximab | Phase 1b: LGX818 200 mg + BYL719 100 mg + Cetuximab | Phase 1b: LGX818 200 mg + BYL719 200 mg + Cetuximab | Phase 1b: LGX818 200 mg + BYL719 300 mg + Cetuximab | Phase 1b: LGX818 300 mg + BYL719 200 mg + Cetuximab |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received 100 mg of LGX818 (encorafenib) orally once daily along with cetuximab orally once weekly in each cycle of 28 days continuously, until disease progression (PD), unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 orally once daily along with cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 400 mg of LGX818 orally once daily along with cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 450 mg of LGX818 orally once daily along with cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 100 mg of BYL719 (alpelisib) orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 200 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 300 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 300 mg of LGX818 along with 200 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). |
| Measure Participants | 2 | 7 | 9 | 8 | 3 | 8 | 10 | 7 |
| Median (95% Confidence Interval) [months] |
12.0
|
3.7
|
2.8
|
12.0
|
5.4
|
4.3
|
4.1
|
4.2
|
| Title | Phase 2: Number of Participants With Any Variant in Gene Status at Baseline |
|---|---|
| Description | Gene alterations/expression relevant to the RAF/MEK/ERK (proto-oncogene serine/threonine-protein kinase/ mitogen-activated ERK kinase/ extracellular signal-regulated kinases) and EGFR/PI3K/AKT (epidermal growth factor receptor/ phosphatidylinositol 3-kinase/ protein kinase B) pathways in tumor tissue, baseline molecular status (mutation/amplification/expression) in tumor tissue of potential predictive markers of tumor response or resistance i.e. BRAF (v-raf murine sarcoma viral oncogene homolog B1), HRAS (harvey rat sarcoma protein), KRAS (V-Ki-ras2 kirsten rat sarcoma viral oncogene homolog B1), NRAS (neuroblastoma RAS viral oncogene homolog), PTEN (phosphatase and tensin homolog), PIK3CA (phosphatidylinositol 3-kinase gene), MAP2K1 (mitogen-activated protein kinase 1), MAP2K2 (mitogen-activated protein kinase 2), ARAF, c-MET, RAF1, EGFR was analyzed. |
| Time Frame | Baseline (Day 1) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The FAS2 comprised all randomized participants in Phase 2. |
| Arm/Group Title | Phase 2: LGX818 200 mg + Cetuximab | Phase 2: LGX818 200 mg + BYL719 300 mg + Cetuximab |
|---|---|---|
| Arm/Group Description | Participants received 200 mg of LGX818 orally once daily along with cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 300 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). |
| Measure Participants | 50 | 52 |
| Count of Participants [Participants] |
30
1500%
|
34
485.7%
|
Adverse Events
| Time Frame | From screening up to 30 days after the last dose of study treatment (maximum up to 43 months) | |||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may experience both SAE and non-SAE. The safety set included all participants from the FAS who received at least one dose of LGX818 (encorafenib), BYL719 (alpelisib) or cetuximab and had at least one valid post baseline safety assessment. | |||||||||||||||||||
| Arm/Group Title | Phase 1b: LGX818 100 mg + Cetuximab | Phase 1b: LGX818 200 mg + Cetuximab | Phase 1b: LGX818 400 mg + Cetuximab | Phase 1b: LGX818 450 mg + Cetuximab | Phase 1b: LGX818 200 mg + BYL719 100 mg + Cetuximab | Phase 1b: LGX818 200 mg + BYL719 200 mg + Cetuximab | Phase 1b: LGX818 200 mg + BYL719 300 mg + Cetuximab | Phase 1b: LGX818 300 mg + BYL719 200 mg + Cetuximab | Phase 2: LGX818 200 mg + Cetuximab | Phase 2: LGX818 200 mg + BYL719 300 mg + Cetuximab | ||||||||||
| Arm/Group Description | Participants received 100 mg of LGX818 (encorafenib) orally once daily along with cetuximab orally once weekly in each cycle of 28 days continuously, until disease progression (PD), unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 orally once daily along with cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 400 mg of LGX818 orally once daily along with cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 450 mg of LGX818 orally once daily along with cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 100 mg of BYL719 (alpelisib) orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 200 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 300 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 300 mg of LGX818 along with 200 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 orally once daily along with cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | Participants received 200 mg of LGX818 along with 300 mg of BYL719 orally once daily and cetuximab orally once weekly in each cycle of 28 days continuously, until PD, unacceptable toxicity, withdrawal of informed consent or death, whichever occurred first. Participants were followed up to 30 days after last dose of study treatment (up to a maximum duration of 43 months). | ||||||||||
All Cause Mortality |
||||||||||||||||||||
| Phase 1b: LGX818 100 mg + Cetuximab | Phase 1b: LGX818 200 mg + Cetuximab | Phase 1b: LGX818 400 mg + Cetuximab | Phase 1b: LGX818 450 mg + Cetuximab | Phase 1b: LGX818 200 mg + BYL719 100 mg + Cetuximab | Phase 1b: LGX818 200 mg + BYL719 200 mg + Cetuximab | Phase 1b: LGX818 200 mg + BYL719 300 mg + Cetuximab | Phase 1b: LGX818 300 mg + BYL719 200 mg + Cetuximab | Phase 2: LGX818 200 mg + Cetuximab | Phase 2: LGX818 200 mg + BYL719 300 mg + Cetuximab | |||||||||||
| 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 | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||||||||
Serious Adverse Events |
||||||||||||||||||||
| Phase 1b: LGX818 100 mg + Cetuximab | Phase 1b: LGX818 200 mg + Cetuximab | Phase 1b: LGX818 400 mg + Cetuximab | Phase 1b: LGX818 450 mg + Cetuximab | Phase 1b: LGX818 200 mg + BYL719 100 mg + Cetuximab | Phase 1b: LGX818 200 mg + BYL719 200 mg + Cetuximab | Phase 1b: LGX818 200 mg + BYL719 300 mg + Cetuximab | Phase 1b: LGX818 300 mg + BYL719 200 mg + Cetuximab | Phase 2: LGX818 200 mg + Cetuximab | Phase 2: LGX818 200 mg + BYL719 300 mg + Cetuximab | |||||||||||
| 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 | 2/2 (100%) | 5/7 (71.4%) | 6/9 (66.7%) | 6/8 (75%) | 2/3 (66.7%) | 5/8 (62.5%) | 6/10 (60%) | 4/7 (57.1%) | 25/50 (50%) | 33/52 (63.5%) | ||||||||||
| Blood and lymphatic system disorders | ||||||||||||||||||||
| Neutropenia | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Anaemia | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Cardiac disorders | ||||||||||||||||||||
| Cardiac arrest | 0/2 (0%) | 1/7 (14.3%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Cardiac failure congestive | 0/2 (0%) | 1/7 (14.3%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Myocardial infarction | 0/2 (0%) | 1/7 (14.3%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 1/10 (10%) | 0/7 (0%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Ventricular fibrillation | 0/2 (0%) | 1/7 (14.3%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Atrial fibrillation | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 1/7 (14.3%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Atrial flutter | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 1/7 (14.3%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Sinus tachycardia | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 1/7 (14.3%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Tachycardia | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Eye disorders | ||||||||||||||||||||
| Chorioretinopathy | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Gastrointestinal disorders | ||||||||||||||||||||
| Abdominal pain | 0/2 (0%) | 1/7 (14.3%) | 1/9 (11.1%) | 3/8 (37.5%) | 0/3 (0%) | 1/8 (12.5%) | 2/10 (20%) | 0/7 (0%) | 5/50 (10%) | 5/52 (9.6%) | ||||||||||
| Haematochezia | 0/2 (0%) | 1/7 (14.3%) | 0/9 (0%) | 1/8 (12.5%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Ileus | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 2/8 (25%) | 0/3 (0%) | 0/8 (0%) | 2/10 (20%) | 0/7 (0%) | 2/50 (4%) | 1/52 (1.9%) | ||||||||||
| Constipation | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 1/8 (12.5%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 2/50 (4%) | 1/52 (1.9%) | ||||||||||
| Proctalgia | 0/2 (0%) | 0/7 (0%) | 1/9 (11.1%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Vomiting | 0/2 (0%) | 0/7 (0%) | 1/9 (11.1%) | 0/8 (0%) | 0/3 (0%) | 2/8 (25%) | 0/10 (0%) | 0/7 (0%) | 2/50 (4%) | 3/52 (5.8%) | ||||||||||
| Nausea | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 2/8 (25%) | 0/10 (0%) | 0/7 (0%) | 2/50 (4%) | 2/52 (3.8%) | ||||||||||
| Diarrhoea | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 1/7 (14.3%) | 1/50 (2%) | 1/52 (1.9%) | ||||||||||
| Large intestine perforation | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 1/8 (12.5%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Small intestinal obstruction | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 1/8 (12.5%) | 0/10 (0%) | 0/7 (0%) | 2/50 (4%) | 1/52 (1.9%) | ||||||||||
| Abdominal pain upper | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Anal haemorrhage | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Gastrointestinal fistula | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Intestinal perforation | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Pancreatitis | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Subileus | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 2/52 (3.8%) | ||||||||||
| Ascites | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 2/52 (3.8%) | ||||||||||
| Duodenal obstruction | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Dyspepsia | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Gastrointestinal obstruction | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Gingival bleeding | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Intestinal obstruction | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Large intestinal haemorrhage | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Large intestinal obstruction | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| General disorders | ||||||||||||||||||||
| Pain | 0/2 (0%) | 1/7 (14.3%) | 1/9 (11.1%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Asthenia | 0/2 (0%) | 1/7 (14.3%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Non-cardiac chest pain | 0/2 (0%) | 0/7 (0%) | 1/9 (11.1%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Pyrexia | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 1/8 (12.5%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 3/50 (6%) | 3/52 (5.8%) | ||||||||||
| Malaise | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 2/50 (4%) | 0/52 (0%) | ||||||||||
| Fatigue | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 1/52 (1.9%) | ||||||||||
| General physical health deterioration | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Chills | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Influenza like illness | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Infusion site extravasation | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Oedema | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Hepatobiliary disorders | ||||||||||||||||||||
| Bile duct stenosis | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 1/8 (12.5%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Hyperbilirubinaemia | 0/2 (0%) | 0/7 (0%) | 1/9 (11.1%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Jaundice cholestatic | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 1/10 (10%) | 0/7 (0%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Cholangitis | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 2/52 (3.8%) | ||||||||||
| Cholecystitis | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 2/52 (3.8%) | ||||||||||
| Hepatic function abnormal | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Immune system disorders | ||||||||||||||||||||
| Hypersensitivity | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 1/8 (12.5%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Drug hypersensitivity | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Infections and infestations | ||||||||||||||||||||
| Pneumonia | 1/2 (50%) | 1/7 (14.3%) | 1/9 (11.1%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 1/7 (14.3%) | 2/50 (4%) | 1/52 (1.9%) | ||||||||||
| Device related infection | 0/2 (0%) | 0/7 (0%) | 1/9 (11.1%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Escherichia bacteraemia | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 1/8 (12.5%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Abdominal abscess | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 1/8 (12.5%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Gastrointestinal infection | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Meningitis aseptic | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Skin infection | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Urinary tract infection | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 1/52 (1.9%) | ||||||||||
| Cellulitis | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Clostridial infection | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Clostridium difficile colitis | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Device related sepsis | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Gastroenteritis | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Incision site abscess | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Peritonitis | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Sepsis | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Injury, poisoning and procedural complications | ||||||||||||||||||||
| Infusion related reaction | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 5/50 (10%) | 0/52 (0%) | ||||||||||
| Hip fracture | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Procedural pain | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Refractoriness to platelet transfusion | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Investigations | ||||||||||||||||||||
| Blood bilirubin increased | 0/2 (0%) | 0/7 (0%) | 1/9 (11.1%) | 1/8 (12.5%) | 1/3 (33.3%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Brain natriuretic peptide increased | 0/2 (0%) | 0/7 (0%) | 1/9 (11.1%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Electrocardiogram QT prolonged | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 1/8 (12.5%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Lipase increased | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 1/8 (12.5%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Blood creatinine increased | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 1/8 (12.5%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 1/52 (1.9%) | ||||||||||
| Metabolism and nutrition disorders | ||||||||||||||||||||
| Decreased appetite | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 2/50 (4%) | 1/52 (1.9%) | ||||||||||
| Dehydration | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 1/52 (1.9%) | ||||||||||
| Hyperglycaemia | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 2/52 (3.8%) | ||||||||||
| Musculoskeletal and connective tissue disorders | ||||||||||||||||||||
| Back pain | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 1/7 (14.3%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Arthralgia | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Flank pain | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||||||||||
| Tumour pain | 1/2 (50%) | 0/7 (0%) | 1/9 (11.1%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Malignant melanoma | 0/2 (0%) | 0/7 (0%) | 1/9 (11.1%) | 0/8 (0%) | 0/3 (0%) | 1/8 (12.5%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 3/52 (5.8%) | ||||||||||
| Eye naevus | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Nervous system disorders | ||||||||||||||||||||
| Cerebrovascular accident | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 1/8 (12.5%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Syncope | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Product Issues | ||||||||||||||||||||
| Thrombosis in device | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 1/8 (12.5%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Renal and urinary disorders | ||||||||||||||||||||
| Acute kidney injury | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 1/10 (10%) | 1/7 (14.3%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Hydronephrosis | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Renal failure | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 1/52 (1.9%) | ||||||||||
| Chronic kidney disease | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Urinary retention | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Reproductive system and breast disorders | ||||||||||||||||||||
| Female genital tract fistula | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 1/8 (12.5%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||||||||
| Dyspnoea | 0/2 (0%) | 1/7 (14.3%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 1/8 (12.5%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Pleural effusion | 0/2 (0%) | 1/7 (14.3%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 2/52 (3.8%) | ||||||||||
| Respiratory arrest | 0/2 (0%) | 0/7 (0%) | 1/9 (11.1%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Respiratory failure | 0/2 (0%) | 1/7 (14.3%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Dyspnoea at rest | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 1/7 (14.3%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Interstitial lung disease | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 1/10 (10%) | 0/7 (0%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Pulmonary embolism | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Epistaxis | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Respiratory distress | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Vascular disorders | ||||||||||||||||||||
| Deep vein thrombosis | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 1/3 (33.3%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Hypertension | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 1/8 (12.5%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Pelvic venous thrombosis | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Venous thrombosis limb | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
Other (Not Including Serious) Adverse Events |
||||||||||||||||||||
| Phase 1b: LGX818 100 mg + Cetuximab | Phase 1b: LGX818 200 mg + Cetuximab | Phase 1b: LGX818 400 mg + Cetuximab | Phase 1b: LGX818 450 mg + Cetuximab | Phase 1b: LGX818 200 mg + BYL719 100 mg + Cetuximab | Phase 1b: LGX818 200 mg + BYL719 200 mg + Cetuximab | Phase 1b: LGX818 200 mg + BYL719 300 mg + Cetuximab | Phase 1b: LGX818 300 mg + BYL719 200 mg + Cetuximab | Phase 2: LGX818 200 mg + Cetuximab | Phase 2: LGX818 200 mg + BYL719 300 mg + Cetuximab | |||||||||||
| 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 | 2/2 (100%) | 7/7 (100%) | 9/9 (100%) | 8/8 (100%) | 3/3 (100%) | 8/8 (100%) | 10/10 (100%) | 7/7 (100%) | 50/50 (100%) | 52/52 (100%) | ||||||||||
| Blood and lymphatic system disorders | ||||||||||||||||||||
| Anaemia | 0/2 (0%) | 1/7 (14.3%) | 2/9 (22.2%) | 2/8 (25%) | 0/3 (0%) | 1/8 (12.5%) | 0/10 (0%) | 0/7 (0%) | 8/50 (16%) | 12/52 (23.1%) | ||||||||||
| Lymphopenia | 0/2 (0%) | 0/7 (0%) | 1/9 (11.1%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 2/50 (4%) | 1/52 (1.9%) | ||||||||||
| Thrombocytopenia | 0/2 (0%) | 1/7 (14.3%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 1/10 (10%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Leukocytosis | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 1/8 (12.5%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Lymphadenopathy | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 1/7 (14.3%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Neutropenia | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 1/52 (1.9%) | ||||||||||
| Cardiac disorders | ||||||||||||||||||||
| Pericardial effusion | 1/2 (50%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 1/8 (12.5%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Sinus tachycardia | 0/2 (0%) | 0/7 (0%) | 1/9 (11.1%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Tachycardia | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 1/8 (12.5%) | 0/10 (0%) | 2/7 (28.6%) | 1/50 (2%) | 1/52 (1.9%) | ||||||||||
| Atrial fibrillation | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 2/7 (28.6%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Palpitations | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 2/7 (28.6%) | 1/50 (2%) | 2/52 (3.8%) | ||||||||||
| Angina pectoris | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 1/7 (14.3%) | 0/50 (0%) | 2/52 (3.8%) | ||||||||||
| Aortic valve incompetence | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 1/7 (14.3%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Arrhythmia | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 1/10 (10%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Atrial flutter | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 1/7 (14.3%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Bradycardia | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 1/7 (14.3%) | 2/50 (4%) | 0/52 (0%) | ||||||||||
| Diastolic dysfunction | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 1/7 (14.3%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Mitral valve incompetence | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 1/7 (14.3%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Tachyarrhythmia | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Atrial tachycardia | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Ventricular arrhythmia | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Congenital, familial and genetic disorders | ||||||||||||||||||||
| Distichiasis | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 1/8 (12.5%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 2/52 (3.8%) | ||||||||||
| Ear and labyrinth disorders | ||||||||||||||||||||
| Deafness unilateral | 0/2 (0%) | 1/7 (14.3%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Ear discomfort | 0/2 (0%) | 1/7 (14.3%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Ear congestion | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Ear pain | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Hypoacusis | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Middle ear inflammation | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Tinnitus | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Vertigo | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Endocrine disorders | ||||||||||||||||||||
| Hypothyroidism | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Eye disorders | ||||||||||||||||||||
| Dry eye | 0/2 (0%) | 0/7 (0%) | 1/9 (11.1%) | 1/8 (12.5%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 3/50 (6%) | 4/52 (7.7%) | ||||||||||
| Eye irritation | 0/2 (0%) | 1/7 (14.3%) | 1/9 (11.1%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Blepharitis | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 1/8 (12.5%) | 0/3 (0%) | 0/8 (0%) | 1/10 (10%) | 0/7 (0%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Cataract | 1/2 (50%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 1/8 (12.5%) | 0/10 (0%) | 0/7 (0%) | 2/50 (4%) | 3/52 (5.8%) | ||||||||||
| Lacrimation increased | 0/2 (0%) | 1/7 (14.3%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Photopsia | 1/2 (50%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Uveitis | 0/2 (0%) | 0/7 (0%) | 1/9 (11.1%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Vision blurred | 0/2 (0%) | 0/7 (0%) | 1/9 (11.1%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 1/10 (10%) | 1/7 (14.3%) | 1/50 (2%) | 3/52 (5.8%) | ||||||||||
| Visual acuity reduced | 0/2 (0%) | 0/7 (0%) | 1/9 (11.1%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 2/52 (3.8%) | ||||||||||
| Abnormal sensation in eye | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 1/3 (33.3%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Chalazion | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 1/10 (10%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Conjunctival haemorrhage | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 1/7 (14.3%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Eye pain | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 1/8 (12.5%) | 0/10 (0%) | 0/7 (0%) | 2/50 (4%) | 0/52 (0%) | ||||||||||
| Glaucoma | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 1/8 (12.5%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Myopia | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 1/7 (14.3%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Ocular hyperaemia | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 1/3 (33.3%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Trichomegaly | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 1/10 (10%) | 0/7 (0%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Accommodation disorder | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 1/7 (14.3%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Retinopathy | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 2/50 (4%) | 0/52 (0%) | ||||||||||
| Eye pruritus | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 2/52 (3.8%) | ||||||||||
| Blindness unilateral | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Diplopia | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Eczema eyelids | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Erythema of eyelid | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Eyelid irritation | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Periorbital oedema | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Retinal degeneration | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Vitreous floaters | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Gastrointestinal disorders | ||||||||||||||||||||
| Vomiting | 1/2 (50%) | 2/7 (28.6%) | 5/9 (55.6%) | 4/8 (50%) | 0/3 (0%) | 4/8 (50%) | 7/10 (70%) | 3/7 (42.9%) | 17/50 (34%) | 25/52 (48.1%) | ||||||||||
| Nausea | 2/2 (100%) | 1/7 (14.3%) | 1/9 (11.1%) | 4/8 (50%) | 0/3 (0%) | 4/8 (50%) | 8/10 (80%) | 5/7 (71.4%) | 23/50 (46%) | 30/52 (57.7%) | ||||||||||
| Abdominal pain | 1/2 (50%) | 2/7 (28.6%) | 0/9 (0%) | 4/8 (50%) | 1/3 (33.3%) | 3/8 (37.5%) | 1/10 (10%) | 2/7 (28.6%) | 17/50 (34%) | 21/52 (40.4%) | ||||||||||
| Constipation | 0/2 (0%) | 1/7 (14.3%) | 2/9 (22.2%) | 4/8 (50%) | 0/3 (0%) | 0/8 (0%) | 2/10 (20%) | 2/7 (28.6%) | 14/50 (28%) | 6/52 (11.5%) | ||||||||||
| Diarrhoea | 0/2 (0%) | 0/7 (0%) | 3/9 (33.3%) | 4/8 (50%) | 0/3 (0%) | 7/8 (87.5%) | 5/10 (50%) | 5/7 (71.4%) | 14/50 (28%) | 29/52 (55.8%) | ||||||||||
| Stomatitis | 0/2 (0%) | 2/7 (28.6%) | 2/9 (22.2%) | 2/8 (25%) | 0/3 (0%) | 1/8 (12.5%) | 3/10 (30%) | 1/7 (14.3%) | 5/50 (10%) | 18/52 (34.6%) | ||||||||||
| Dry mouth | 1/2 (50%) | 0/7 (0%) | 1/9 (11.1%) | 0/8 (0%) | 0/3 (0%) | 1/8 (12.5%) | 1/10 (10%) | 0/7 (0%) | 2/50 (4%) | 3/52 (5.8%) | ||||||||||
| Haemorrhoids | 1/2 (50%) | 0/7 (0%) | 1/9 (11.1%) | 0/8 (0%) | 0/3 (0%) | 2/8 (25%) | 1/10 (10%) | 0/7 (0%) | 0/50 (0%) | 2/52 (3.8%) | ||||||||||
| Ileus | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 1/8 (12.5%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Abdominal discomfort | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 1/8 (12.5%) | 0/3 (0%) | 0/8 (0%) | 1/10 (10%) | 0/7 (0%) | 1/50 (2%) | 1/52 (1.9%) | ||||||||||
| Abdominal distension | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 1/8 (12.5%) | 0/3 (0%) | 1/8 (12.5%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 1/52 (1.9%) | ||||||||||
| Abdominal pain lower | 0/2 (0%) | 0/7 (0%) | 1/9 (11.1%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 2/50 (4%) | 0/52 (0%) | ||||||||||
| Haematemesis | 1/2 (50%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Dyspepsia | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 2/8 (25%) | 2/10 (20%) | 1/7 (14.3%) | 4/50 (8%) | 8/52 (15.4%) | ||||||||||
| Abdominal pain upper | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 2/8 (25%) | 1/10 (10%) | 1/7 (14.3%) | 5/50 (10%) | 4/52 (7.7%) | ||||||||||
| Flatulence | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 2/7 (28.6%) | 2/50 (4%) | 3/52 (5.8%) | ||||||||||
| Dysphagia | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 1/7 (14.3%) | 1/50 (2%) | 1/52 (1.9%) | ||||||||||
| Eructation | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 1/7 (14.3%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Gingival pain | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 1/8 (12.5%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Haemorrhoidal haemorrhage | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 1/8 (12.5%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Impaired gastric emptying | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 1/7 (14.3%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Oral dysaesthesia | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 1/7 (14.3%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Oral pain | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 1/3 (33.3%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Painful defaecation | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 1/3 (33.3%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Rectal haemorrhage | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 1/3 (33.3%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 2/50 (4%) | 1/52 (1.9%) | ||||||||||
| Ascites | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 3/50 (6%) | 3/52 (5.8%) | ||||||||||
| Proctalgia | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 2/50 (4%) | 1/52 (1.9%) | ||||||||||
| Abdominal adhesions | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Anal incontinence | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Frequent bowel movements | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Gastritis | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 1/52 (1.9%) | ||||||||||
| Haematochezia | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Lip oedema | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Lip pain | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Lower gastrointestinal haemorrhage | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 1/52 (1.9%) | ||||||||||
| Oesophageal haemorrhage | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Oral disorder | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Peritoneal adhesions | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Rectal tenesmus | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Upper gastrointestinal haemorrhage | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Abdominal rigidity | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Anal fistula | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Anorectal discomfort | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Cheilitis | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Enterovesical fistula | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Faeces discoloured | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Gastrooesophageal reflux disease | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Gingival bleeding | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Large intestinal ulcer | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Lip blister | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Mouth haemorrhage | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Oral mucosal blistering | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Small intestinal obstruction | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| General disorders | ||||||||||||||||||||
| Fatigue | 2/2 (100%) | 2/7 (28.6%) | 5/9 (55.6%) | 5/8 (62.5%) | 1/3 (33.3%) | 2/8 (25%) | 6/10 (60%) | 3/7 (42.9%) | 25/50 (50%) | 27/52 (51.9%) | ||||||||||
| Chills | 1/2 (50%) | 0/7 (0%) | 1/9 (11.1%) | 2/8 (25%) | 0/3 (0%) | 1/8 (12.5%) | 0/10 (0%) | 0/7 (0%) | 2/50 (4%) | 2/52 (3.8%) | ||||||||||
| Malaise | 0/2 (0%) | 1/7 (14.3%) | 1/9 (11.1%) | 1/8 (12.5%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 3/50 (6%) | 3/52 (5.8%) | ||||||||||
| Pyrexia | 1/2 (50%) | 1/7 (14.3%) | 0/9 (0%) | 1/8 (12.5%) | 1/3 (33.3%) | 2/8 (25%) | 2/10 (20%) | 3/7 (42.9%) | 12/50 (24%) | 11/52 (21.2%) | ||||||||||
| Asthenia | 0/2 (0%) | 0/7 (0%) | 1/9 (11.1%) | 1/8 (12.5%) | 0/3 (0%) | 1/8 (12.5%) | 1/10 (10%) | 0/7 (0%) | 0/50 (0%) | 8/52 (15.4%) | ||||||||||
| Non-cardiac chest pain | 0/2 (0%) | 0/7 (0%) | 1/9 (11.1%) | 1/8 (12.5%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 1/7 (14.3%) | 1/50 (2%) | 2/52 (3.8%) | ||||||||||
| Oedema peripheral | 0/2 (0%) | 1/7 (14.3%) | 0/9 (0%) | 1/8 (12.5%) | 0/3 (0%) | 3/8 (37.5%) | 2/10 (20%) | 2/7 (28.6%) | 5/50 (10%) | 5/52 (9.6%) | ||||||||||
| Feeling cold | 0/2 (0%) | 0/7 (0%) | 1/9 (11.1%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Influenza like illness | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 1/8 (12.5%) | 0/3 (0%) | 1/8 (12.5%) | 1/10 (10%) | 0/7 (0%) | 1/50 (2%) | 3/52 (5.8%) | ||||||||||
| Injection site reaction | 0/2 (0%) | 0/7 (0%) | 1/9 (11.1%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Pain | 0/2 (0%) | 1/7 (14.3%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 1/7 (14.3%) | 4/50 (8%) | 0/52 (0%) | ||||||||||
| Tenderness | 0/2 (0%) | 0/7 (0%) | 1/9 (11.1%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Xerosis | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 1/8 (12.5%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 2/7 (28.6%) | 1/50 (2%) | 1/52 (1.9%) | ||||||||||
| Adverse event | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 1/8 (12.5%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Chest discomfort | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 1/7 (14.3%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Facial pain | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 1/8 (12.5%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Gait disturbance | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 1/7 (14.3%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Mucosal dryness | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 1/10 (10%) | 0/7 (0%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| General physical health deterioration | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 2/50 (4%) | 1/52 (1.9%) | ||||||||||
| Face oedema | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Peripheral swelling | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Complication associated with device | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Early satiety | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Oedema | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Hepatobiliary disorders | ||||||||||||||||||||
| Bile duct stenosis | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 1/8 (12.5%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Hepatobiliary disease | 0/2 (0%) | 0/7 (0%) | 1/9 (11.1%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Hepatomegaly | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 1/8 (12.5%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Hyperbilirubinaemia | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 1/8 (12.5%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Jaundice | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 1/8 (12.5%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Hepatic pain | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 1/7 (14.3%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Cholangitis | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Hepatic function abnormal | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Immune system disorders | ||||||||||||||||||||
| Hypersensitivity | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 1/8 (12.5%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Anaphylactic reaction | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Drug hypersensitivity | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 2/52 (3.8%) | ||||||||||
| Infections and infestations | ||||||||||||||||||||
| Urinary tract infection | 0/2 (0%) | 1/7 (14.3%) | 2/9 (22.2%) | 0/8 (0%) | 0/3 (0%) | 1/8 (12.5%) | 1/10 (10%) | 0/7 (0%) | 3/50 (6%) | 6/52 (11.5%) | ||||||||||
| Conjunctivitis | 0/2 (0%) | 0/7 (0%) | 2/9 (22.2%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 1/10 (10%) | 0/7 (0%) | 2/50 (4%) | 2/52 (3.8%) | ||||||||||
| Oral candidiasis | 1/2 (50%) | 0/7 (0%) | 1/9 (11.1%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 1/52 (1.9%) | ||||||||||
| Folliculitis | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 1/8 (12.5%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 1/7 (14.3%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Haemophilus bacteraemia | 0/2 (0%) | 1/7 (14.3%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Infection | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 1/8 (12.5%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Nasopharyngitis | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 1/8 (12.5%) | 0/3 (0%) | 2/8 (25%) | 0/10 (0%) | 1/7 (14.3%) | 1/50 (2%) | 2/52 (3.8%) | ||||||||||
| Oral herpes | 0/2 (0%) | 1/7 (14.3%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Pneumonia | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 1/8 (12.5%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Respiratory tract infection | 0/2 (0%) | 1/7 (14.3%) | 0/9 (0%) | 0/8 (0%) | 1/3 (33.3%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Skin infection | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 1/8 (12.5%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 1/52 (1.9%) | ||||||||||
| Tooth infection | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 1/8 (12.5%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 3/52 (5.8%) | ||||||||||
| Upper respiratory tract infection | 0/2 (0%) | 1/7 (14.3%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 1/8 (12.5%) | 1/10 (10%) | 0/7 (0%) | 2/50 (4%) | 2/52 (3.8%) | ||||||||||
| Paronychia | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 2/8 (25%) | 1/10 (10%) | 1/7 (14.3%) | 1/50 (2%) | 7/52 (13.5%) | ||||||||||
| Abscess | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 1/8 (12.5%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Biliary tract infection | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 1/10 (10%) | 0/7 (0%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Laryngitis | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 1/10 (10%) | 0/7 (0%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Lung infection | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 1/8 (12.5%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 2/52 (3.8%) | ||||||||||
| Oral infection | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 1/10 (10%) | 0/7 (0%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Pharyngitis | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 1/7 (14.3%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Postoperative wound infection | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 1/8 (12.5%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Rash pustular | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 1/3 (33.3%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 3/52 (5.8%) | ||||||||||
| Urosepsis | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 1/8 (12.5%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Viral infection | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 1/8 (12.5%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Angular cheilitis | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 1/52 (1.9%) | ||||||||||
| Body tinea | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Bronchitis | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 2/52 (3.8%) | ||||||||||
| Cellulitis | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Gastroenteritis | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 3/52 (5.8%) | ||||||||||
| Gastrointestinal infection | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Herpes zoster | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Influenza | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 1/52 (1.9%) | ||||||||||
| Skin candida | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Tinea pedis | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Anal abscess | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Bacteraemia | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Clostridium difficile colitis | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Cystitis | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 4/52 (7.7%) | ||||||||||
| Device related infection | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Escherichia infection | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Gastric infection | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Genital herpes | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Hordeolum | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Incision site abscess | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Lip infection | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Localised infection | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Nail infection | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 3/52 (5.8%) | ||||||||||
| Onychomycosis | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Vaginal infection | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Viral upper respiratory tract infection | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Wound infection | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Injury, poisoning and procedural complications | ||||||||||||||||||||
| Infusion related reaction | 1/2 (50%) | 1/7 (14.3%) | 4/9 (44.4%) | 2/8 (25%) | 0/3 (0%) | 0/8 (0%) | 1/10 (10%) | 0/7 (0%) | 5/50 (10%) | 2/52 (3.8%) | ||||||||||
| Spinal compression fracture | 1/2 (50%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Contusion | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 1/10 (10%) | 0/7 (0%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Ligament sprain | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 1/8 (12.5%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Fall | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Procedural pain | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 1/52 (1.9%) | ||||||||||
| Tendon injury | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Tooth fracture | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Inflammation of wound | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Post-traumatic pain | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Spinal fracture | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 2/52 (3.8%) | ||||||||||
| Stoma site haemorrhage | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Thoracic vertebral fracture | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Upper limb fracture | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Vascular access complication | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Wrist fracture | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Investigations | ||||||||||||||||||||
| Weight decreased | 1/2 (50%) | 2/7 (28.6%) | 1/9 (11.1%) | 3/8 (37.5%) | 1/3 (33.3%) | 5/8 (62.5%) | 3/10 (30%) | 2/7 (28.6%) | 9/50 (18%) | 19/52 (36.5%) | ||||||||||
| Electrocardiogram QT prolonged | 0/2 (0%) | 1/7 (14.3%) | 0/9 (0%) | 2/8 (25%) | 1/3 (33.3%) | 0/8 (0%) | 1/10 (10%) | 0/7 (0%) | 0/50 (0%) | 4/52 (7.7%) | ||||||||||
| Alanine aminotransferase increased | 0/2 (0%) | 1/7 (14.3%) | 0/9 (0%) | 1/8 (12.5%) | 0/3 (0%) | 1/8 (12.5%) | 2/10 (20%) | 1/7 (14.3%) | 5/50 (10%) | 5/52 (9.6%) | ||||||||||
| Aspartate aminotransferase increased | 0/2 (0%) | 1/7 (14.3%) | 0/9 (0%) | 1/8 (12.5%) | 0/3 (0%) | 1/8 (12.5%) | 1/10 (10%) | 1/7 (14.3%) | 5/50 (10%) | 4/52 (7.7%) | ||||||||||
| Blood bilirubin increased | 0/2 (0%) | 0/7 (0%) | 1/9 (11.1%) | 1/8 (12.5%) | 1/3 (33.3%) | 1/8 (12.5%) | 1/10 (10%) | 0/7 (0%) | 0/50 (0%) | 5/52 (9.6%) | ||||||||||
| Blood iron decreased | 0/2 (0%) | 0/7 (0%) | 1/9 (11.1%) | 1/8 (12.5%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Lipase increased | 0/2 (0%) | 1/7 (14.3%) | 1/9 (11.1%) | 0/8 (0%) | 0/3 (0%) | 1/8 (12.5%) | 1/10 (10%) | 4/7 (57.1%) | 16/50 (32%) | 7/52 (13.5%) | ||||||||||
| Amylase increased | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 1/8 (12.5%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 2/7 (28.6%) | 6/50 (12%) | 3/52 (5.8%) | ||||||||||
| Blood albumin decreased | 0/2 (0%) | 1/7 (14.3%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Blood creatine phosphokinase increased | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 1/8 (12.5%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 2/52 (3.8%) | ||||||||||
| Blood creatinine increased | 0/2 (0%) | 0/7 (0%) | 1/9 (11.1%) | 0/8 (0%) | 0/3 (0%) | 2/8 (25%) | 2/10 (20%) | 1/7 (14.3%) | 2/50 (4%) | 3/52 (5.8%) | ||||||||||
| Blood sodium decreased | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 1/8 (12.5%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Ejection fraction decreased | 0/2 (0%) | 0/7 (0%) | 1/9 (11.1%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Gamma-glutamyltransferase increased | 0/2 (0%) | 1/7 (14.3%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Troponin T increased | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 1/8 (12.5%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Vitamin D decreased | 0/2 (0%) | 1/7 (14.3%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Breath sounds abnormal | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 1/7 (14.3%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Cardiac murmur | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 1/8 (12.5%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Glycosylated haemoglobin increased | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 1/7 (14.3%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Neutrophil count decreased | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 1/7 (14.3%) | 4/50 (8%) | 0/52 (0%) | ||||||||||
| White blood cell count decreased | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 2/50 (4%) | 0/52 (0%) | ||||||||||
| Blood alkaline phosphatase increased | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 1/52 (1.9%) | ||||||||||
| Platelet count decreased | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 1/52 (1.9%) | ||||||||||
| Urine output decreased | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Blood creatine increased | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Blood iron decreased | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Blood magnesium decreased | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Blood phosphorus decreased | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 2/52 (3.8%) | ||||||||||
| Blood uric acid increased | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Eastern Cooperative Oncology Group performance status improved | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Electrocardiogram T wave inversion | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Macular reflex abnormal | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Metabolism and nutrition disorders | ||||||||||||||||||||
| Decreased appetite | 1/2 (50%) | 2/7 (28.6%) | 2/9 (22.2%) | 2/8 (25%) | 1/3 (33.3%) | 2/8 (25%) | 1/10 (10%) | 4/7 (57.1%) | 16/50 (32%) | 19/52 (36.5%) | ||||||||||
| Hypophosphataemia | 1/2 (50%) | 2/7 (28.6%) | 3/9 (33.3%) | 1/8 (12.5%) | 1/3 (33.3%) | 0/8 (0%) | 1/10 (10%) | 2/7 (28.6%) | 3/50 (6%) | 7/52 (13.5%) | ||||||||||
| Hypomagnesaemia | 0/2 (0%) | 2/7 (28.6%) | 0/9 (0%) | 2/8 (25%) | 0/3 (0%) | 3/8 (37.5%) | 2/10 (20%) | 3/7 (42.9%) | 4/50 (8%) | 11/52 (21.2%) | ||||||||||
| Hypokalaemia | 0/2 (0%) | 1/7 (14.3%) | 0/9 (0%) | 2/8 (25%) | 0/3 (0%) | 2/8 (25%) | 0/10 (0%) | 0/7 (0%) | 6/50 (12%) | 10/52 (19.2%) | ||||||||||
| Hyperglycaemia | 0/2 (0%) | 1/7 (14.3%) | 0/9 (0%) | 1/8 (12.5%) | 1/3 (33.3%) | 2/8 (25%) | 4/10 (40%) | 4/7 (57.1%) | 5/50 (10%) | 18/52 (34.6%) | ||||||||||
| Dehydration | 0/2 (0%) | 1/7 (14.3%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 2/8 (25%) | 0/10 (0%) | 1/7 (14.3%) | 2/50 (4%) | 4/52 (7.7%) | ||||||||||
| Hypoalbuminaemia | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 1/8 (12.5%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 2/50 (4%) | 2/52 (3.8%) | ||||||||||
| Hypocalcaemia | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 1/8 (12.5%) | 1/3 (33.3%) | 1/8 (12.5%) | 0/10 (0%) | 1/7 (14.3%) | 2/50 (4%) | 3/52 (5.8%) | ||||||||||
| Hyponatraemia | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 1/8 (12.5%) | 0/3 (0%) | 0/8 (0%) | 1/10 (10%) | 0/7 (0%) | 3/50 (6%) | 1/52 (1.9%) | ||||||||||
| Food craving | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 1/7 (14.3%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Hyperkalaemia | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 1/7 (14.3%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Hyperlipasaemia | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 1/7 (14.3%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Hyperphosphataemia | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 1/7 (14.3%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Hyperuricaemia | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 1/7 (14.3%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Hypophagia | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 1/7 (14.3%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Metabolic acidosis | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 1/7 (14.3%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Hypoglycaemia | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Musculoskeletal and connective tissue disorders | ||||||||||||||||||||
| Back pain | 1/2 (50%) | 3/7 (42.9%) | 1/9 (11.1%) | 3/8 (37.5%) | 1/3 (33.3%) | 1/8 (12.5%) | 0/10 (0%) | 1/7 (14.3%) | 12/50 (24%) | 10/52 (19.2%) | ||||||||||
| Myalgia | 0/2 (0%) | 1/7 (14.3%) | 3/9 (33.3%) | 3/8 (37.5%) | 0/3 (0%) | 2/8 (25%) | 1/10 (10%) | 1/7 (14.3%) | 8/50 (16%) | 12/52 (23.1%) | ||||||||||
| Pain in extremity | 1/2 (50%) | 0/7 (0%) | 2/9 (22.2%) | 3/8 (37.5%) | 0/3 (0%) | 2/8 (25%) | 0/10 (0%) | 0/7 (0%) | 8/50 (16%) | 9/52 (17.3%) | ||||||||||
| Arthralgia | 0/2 (0%) | 2/7 (28.6%) | 1/9 (11.1%) | 1/8 (12.5%) | 1/3 (33.3%) | 0/8 (0%) | 2/10 (20%) | 1/7 (14.3%) | 19/50 (38%) | 15/52 (28.8%) | ||||||||||
| Musculoskeletal pain | 1/2 (50%) | 2/7 (28.6%) | 0/9 (0%) | 1/8 (12.5%) | 0/3 (0%) | 2/8 (25%) | 1/10 (10%) | 1/7 (14.3%) | 4/50 (8%) | 9/52 (17.3%) | ||||||||||
| Flank pain | 1/2 (50%) | 1/7 (14.3%) | 0/9 (0%) | 1/8 (12.5%) | 0/3 (0%) | 1/8 (12.5%) | 0/10 (0%) | 0/7 (0%) | 2/50 (4%) | 2/52 (3.8%) | ||||||||||
| Bone pain | 0/2 (0%) | 1/7 (14.3%) | 1/9 (11.1%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 1/7 (14.3%) | 0/50 (0%) | 6/52 (11.5%) | ||||||||||
| Arthritis | 1/2 (50%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 1/7 (14.3%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Intervertebral disc degeneration | 0/2 (0%) | 0/7 (0%) | 1/9 (11.1%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Muscular weakness | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 1/8 (12.5%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 1/52 (1.9%) | ||||||||||
| Musculoskeletal chest pain | 0/2 (0%) | 1/7 (14.3%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 1/8 (12.5%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 3/52 (5.8%) | ||||||||||
| Neck pain | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 1/8 (12.5%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 1/52 (1.9%) | ||||||||||
| Osteoporosis | 1/2 (50%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 1/8 (12.5%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Spinal osteoarthritis | 0/2 (0%) | 0/7 (0%) | 1/9 (11.1%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Sjogren's syndrome | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 2/7 (28.6%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Bursitis | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 1/10 (10%) | 0/7 (0%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Groin pain | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 1/7 (14.3%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Muscle spasms | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 1/10 (10%) | 0/7 (0%) | 2/50 (4%) | 5/52 (9.6%) | ||||||||||
| Osteoarthritis | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 1/7 (14.3%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Periarthritis | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 1/8 (12.5%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 1/52 (1.9%) | ||||||||||
| Musculoskeletal discomfort | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Pain in jaw | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Rotator cuff syndrome | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Systemic lupus erythematosus | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Tendonitis | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||||||||||
| Basal cell carcinoma | 1/2 (50%) | 0/7 (0%) | 0/9 (0%) | 1/8 (12.5%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 1/7 (14.3%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Skin papilloma | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 2/8 (25%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 1/7 (14.3%) | 5/50 (10%) | 0/52 (0%) | ||||||||||
| Tumour pain | 0/2 (0%) | 0/7 (0%) | 1/9 (11.1%) | 1/8 (12.5%) | 1/3 (33.3%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Dysplastic naevus | 0/2 (0%) | 0/7 (0%) | 1/9 (11.1%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 1/52 (1.9%) | ||||||||||
| Endometrial neoplasm | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 1/8 (12.5%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Melanocytic naevus | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 1/8 (12.5%) | 1/3 (33.3%) | 0/8 (0%) | 2/10 (20%) | 4/7 (57.1%) | 1/50 (2%) | 6/52 (11.5%) | ||||||||||
| Pyogenic granuloma | 0/2 (0%) | 1/7 (14.3%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Tumour associated fever | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 1/8 (12.5%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Fibroma | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 1/7 (14.3%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Acrochordon | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 2/50 (4%) | 0/52 (0%) | ||||||||||
| Keratoacanthoma | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 2/50 (4%) | 0/52 (0%) | ||||||||||
| Adenocarcinoma of colon | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Cancer pain | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Malignant ascites | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Neoplasm skin | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Oral fibroma | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Seborrhoeic keratosis | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 2/52 (3.8%) | ||||||||||
| Squamous cell carcinoma of skin | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Squamous cell carcinoma | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Eye naevus | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Nervous system disorders | ||||||||||||||||||||
| Headache | 1/2 (50%) | 3/7 (42.9%) | 3/9 (33.3%) | 1/8 (12.5%) | 0/3 (0%) | 1/8 (12.5%) | 1/10 (10%) | 2/7 (28.6%) | 17/50 (34%) | 13/52 (25%) | ||||||||||
| Dizziness | 0/2 (0%) | 2/7 (28.6%) | 0/9 (0%) | 1/8 (12.5%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 2/7 (28.6%) | 6/50 (12%) | 4/52 (7.7%) | ||||||||||
| Neuropathy peripheral | 0/2 (0%) | 1/7 (14.3%) | 1/9 (11.1%) | 0/8 (0%) | 0/3 (0%) | 1/8 (12.5%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Dysgeusia | 0/2 (0%) | 1/7 (14.3%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 4/8 (50%) | 2/10 (20%) | 0/7 (0%) | 4/50 (8%) | 7/52 (13.5%) | ||||||||||
| Lethargy | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 1/8 (12.5%) | 0/3 (0%) | 1/8 (12.5%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Memory impairment | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 1/8 (12.5%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 2/50 (4%) | 0/52 (0%) | ||||||||||
| Peripheral sensory neuropathy | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 1/8 (12.5%) | 0/3 (0%) | 0/8 (0%) | 2/10 (20%) | 2/7 (28.6%) | 0/50 (0%) | 2/52 (3.8%) | ||||||||||
| Restless legs syndrome | 1/2 (50%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Somnolence | 0/2 (0%) | 0/7 (0%) | 1/9 (11.1%) | 0/8 (0%) | 0/3 (0%) | 1/8 (12.5%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Ageusia | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 1/7 (14.3%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Paraesthesia | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 1/10 (10%) | 0/7 (0%) | 3/50 (6%) | 0/52 (0%) | ||||||||||
| Polyneuropathy | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 1/7 (14.3%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Syncope | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 1/7 (14.3%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Head discomfort | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Horner's syndrome | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Hyperaesthesia | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Tremor | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Akathisia | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 2/52 (3.8%) | ||||||||||
| Burning sensation | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Dysaesthesia | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Epilepsy | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Fine motor skill dysfunction | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Presyncope | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Product Issues | ||||||||||||||||||||
| Thrombosis in device | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 1/8 (12.5%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Psychiatric disorders | ||||||||||||||||||||
| Hallucination | 2/2 (100%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Insomnia | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 2/8 (25%) | 0/3 (0%) | 1/8 (12.5%) | 1/10 (10%) | 2/7 (28.6%) | 7/50 (14%) | 8/52 (15.4%) | ||||||||||
| Confusional state | 0/2 (0%) | 0/7 (0%) | 1/9 (11.1%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 1/7 (14.3%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Restlessness | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 1/8 (12.5%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 1/7 (14.3%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Anxiety | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 1/10 (10%) | 2/7 (28.6%) | 5/50 (10%) | 2/52 (3.8%) | ||||||||||
| Depression | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 2/7 (28.6%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Delirium | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 1/8 (12.5%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Fear | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 1/7 (14.3%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Panic attack | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Irritability | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Renal and urinary disorders | ||||||||||||||||||||
| Dysuria | 0/2 (0%) | 0/7 (0%) | 1/9 (11.1%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 1/7 (14.3%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Nocturia | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 1/8 (12.5%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Pollakiuria | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 1/8 (12.5%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 1/52 (1.9%) | ||||||||||
| Renal failure | 0/2 (0%) | 1/7 (14.3%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Haematuria | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 2/52 (3.8%) | ||||||||||
| Micturition urgency | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 1/52 (1.9%) | ||||||||||
| Proteinuria | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 3/52 (5.8%) | ||||||||||
| Acute kidney injury | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Cystitis noninfective | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Polyuria | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Renal pain | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Strangury | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Urethral pain | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Urinary incontinence | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 2/52 (3.8%) | ||||||||||
| Urinary retention | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Urinary tract obstruction | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Urinary tract pain | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Reproductive system and breast disorders | ||||||||||||||||||||
| Vaginal haemorrhage | 1/2 (50%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Haematospermia | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Nipple pain | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Ovarian cyst | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Pelvic pain | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Vaginal discharge | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Vaginal inflammation | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Dyspareunia | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Erectile dysfunction | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Prostatism | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||||||||
| Dyspnoea | 0/2 (0%) | 3/7 (42.9%) | 2/9 (22.2%) | 3/8 (37.5%) | 0/3 (0%) | 1/8 (12.5%) | 2/10 (20%) | 2/7 (28.6%) | 8/50 (16%) | 3/52 (5.8%) | ||||||||||
| Cough | 0/2 (0%) | 3/7 (42.9%) | 1/9 (11.1%) | 2/8 (25%) | 0/3 (0%) | 0/8 (0%) | 2/10 (20%) | 1/7 (14.3%) | 8/50 (16%) | 7/52 (13.5%) | ||||||||||
| Productive cough | 0/2 (0%) | 2/7 (28.6%) | 1/9 (11.1%) | 0/8 (0%) | 0/3 (0%) | 1/8 (12.5%) | 1/10 (10%) | 1/7 (14.3%) | 2/50 (4%) | 2/52 (3.8%) | ||||||||||
| Dysphonia | 0/2 (0%) | 1/7 (14.3%) | 1/9 (11.1%) | 0/8 (0%) | 1/3 (33.3%) | 1/8 (12.5%) | 2/10 (20%) | 3/7 (42.9%) | 2/50 (4%) | 7/52 (13.5%) | ||||||||||
| Pleural effusion | 0/2 (0%) | 1/7 (14.3%) | 1/9 (11.1%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 2/52 (3.8%) | ||||||||||
| Pneumonitis | 0/2 (0%) | 1/7 (14.3%) | 1/9 (11.1%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Bronchospasm | 0/2 (0%) | 0/7 (0%) | 1/9 (11.1%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 1/7 (14.3%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Dyspnoea exertional | 0/2 (0%) | 0/7 (0%) | 1/9 (11.1%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 2/50 (4%) | 1/52 (1.9%) | ||||||||||
| Nasal congestion | 1/2 (50%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 1/10 (10%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Oropharyngeal pain | 0/2 (0%) | 1/7 (14.3%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 1/10 (10%) | 1/7 (14.3%) | 4/50 (8%) | 0/52 (0%) | ||||||||||
| Upper-airway cough syndrome | 0/2 (0%) | 1/7 (14.3%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Dyspnoea at rest | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 1/7 (14.3%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Epistaxis | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 1/7 (14.3%) | 3/50 (6%) | 2/52 (3.8%) | ||||||||||
| Nasal crusting | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 1/3 (33.3%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Orthopnoea | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 1/10 (10%) | 0/7 (0%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Pleuritic pain | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 2/50 (4%) | 0/52 (0%) | ||||||||||
| Choking sensation | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Haemoptysis | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Hiccups | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Rhinorrhoea | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Sputum discoloured | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Tachypnoea | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Throat irritation | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Nasal discomfort | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Rhinitis allergic | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Increased viscosity of bronchial secretion | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 2/52 (3.8%) | ||||||||||
| Skin and subcutaneous tissue disorders | ||||||||||||||||||||
| Rash | 0/2 (0%) | 3/7 (42.9%) | 2/9 (22.2%) | 3/8 (37.5%) | 1/3 (33.3%) | 2/8 (25%) | 4/10 (40%) | 2/7 (28.6%) | 9/50 (18%) | 18/52 (34.6%) | ||||||||||
| Dry skin | 1/2 (50%) | 1/7 (14.3%) | 0/9 (0%) | 3/8 (37.5%) | 0/3 (0%) | 4/8 (50%) | 1/10 (10%) | 4/7 (57.1%) | 9/50 (18%) | 15/52 (28.8%) | ||||||||||
| Dermatitis acneiform | 0/2 (0%) | 1/7 (14.3%) | 0/9 (0%) | 2/8 (25%) | 1/3 (33.3%) | 4/8 (50%) | 2/10 (20%) | 1/7 (14.3%) | 9/50 (18%) | 12/52 (23.1%) | ||||||||||
| Erythema | 0/2 (0%) | 0/7 (0%) | 1/9 (11.1%) | 2/8 (25%) | 0/3 (0%) | 1/8 (12.5%) | 0/10 (0%) | 1/7 (14.3%) | 3/50 (6%) | 1/52 (1.9%) | ||||||||||
| Palmar-plantar erythrodysaesthesia syndrome | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 3/8 (37.5%) | 0/3 (0%) | 1/8 (12.5%) | 0/10 (0%) | 1/7 (14.3%) | 1/50 (2%) | 2/52 (3.8%) | ||||||||||
| Rash maculo-papular | 0/2 (0%) | 1/7 (14.3%) | 2/9 (22.2%) | 0/8 (0%) | 1/3 (33.3%) | 1/8 (12.5%) | 1/10 (10%) | 2/7 (28.6%) | 2/50 (4%) | 11/52 (21.2%) | ||||||||||
| Pain of skin | 1/2 (50%) | 0/7 (0%) | 0/9 (0%) | 1/8 (12.5%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 1/52 (1.9%) | ||||||||||
| Pruritus | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 2/8 (25%) | 0/3 (0%) | 0/8 (0%) | 2/10 (20%) | 0/7 (0%) | 7/50 (14%) | 9/52 (17.3%) | ||||||||||
| Pruritus generalised | 0/2 (0%) | 1/7 (14.3%) | 1/9 (11.1%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 1/7 (14.3%) | 2/50 (4%) | 3/52 (5.8%) | ||||||||||
| Skin hyperpigmentation | 0/2 (0%) | 0/7 (0%) | 1/9 (11.1%) | 1/8 (12.5%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 1/7 (14.3%) | 3/50 (6%) | 4/52 (7.7%) | ||||||||||
| Alopecia | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 1/8 (12.5%) | 0/3 (0%) | 1/8 (12.5%) | 1/10 (10%) | 1/7 (14.3%) | 2/50 (4%) | 4/52 (7.7%) | ||||||||||
| Eczema | 1/2 (50%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 1/7 (14.3%) | 1/50 (2%) | 1/52 (1.9%) | ||||||||||
| Hyperkeratosis | 0/2 (0%) | 1/7 (14.3%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 1/8 (12.5%) | 0/10 (0%) | 1/7 (14.3%) | 2/50 (4%) | 3/52 (5.8%) | ||||||||||
| Onychomadesis | 0/2 (0%) | 0/7 (0%) | 1/9 (11.1%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Skin fissures | 1/2 (50%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 1/8 (12.5%) | 1/10 (10%) | 0/7 (0%) | 5/50 (10%) | 5/52 (9.6%) | ||||||||||
| Actinic keratosis | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 1/7 (14.3%) | 1/50 (2%) | 3/52 (5.8%) | ||||||||||
| Hyperhidrosis | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 1/7 (14.3%) | 1/50 (2%) | 1/52 (1.9%) | ||||||||||
| Nail disorder | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 1/8 (12.5%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Nail ridging | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 1/8 (12.5%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Rash generalised | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 1/8 (12.5%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Rash macular | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 1/8 (12.5%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Rash morbilliform | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 1/10 (10%) | 0/7 (0%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Skin lesion | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 1/8 (12.5%) | 0/10 (0%) | 0/7 (0%) | 2/50 (4%) | 2/52 (3.8%) | ||||||||||
| Toxic skin eruption | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 1/8 (12.5%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Acne | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 6/50 (12%) | 4/52 (7.7%) | ||||||||||
| Pruritus generalised | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 2/50 (4%) | 3/52 (5.8%) | ||||||||||
| Skin lesion | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 2/50 (4%) | 2/52 (3.8%) | ||||||||||
| Blister | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Cutaneous symptom | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Dermal cyst | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Hair disorder | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Hirsutism | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Hypertrichosis | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 1/52 (1.9%) | ||||||||||
| Lipohypertrophy | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Miliaria | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Precancerous skin lesion | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Skin discolouration | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Solar dermatitis | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Urticaria | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 1/52 (1.9%) | ||||||||||
| Decubitus ulcer | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Dermatitis | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 2/52 (3.8%) | ||||||||||
| Erythema multiforme | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 3/52 (5.8%) | ||||||||||
| Melanosis | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Onychoclasis | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Onycholysis | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Papule | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Rash erythematous | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 2/52 (3.8%) | ||||||||||
| Rash papular | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Rash pruritic | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Skin depigmentation | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Skin hypopigmentation | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Splinter haemorrhages | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Vascular disorders | ||||||||||||||||||||
| Deep vein thrombosis | 0/2 (0%) | 0/7 (0%) | 1/9 (11.1%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Hypertension | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 1/8 (12.5%) | 0/3 (0%) | 2/8 (25%) | 0/10 (0%) | 2/7 (28.6%) | 4/50 (8%) | 2/52 (3.8%) | ||||||||||
| Bloody discharge | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 1/8 (12.5%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Hypotension | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 1/10 (10%) | 0/7 (0%) | 1/50 (2%) | 1/52 (1.9%) | ||||||||||
| Varicose vein | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 1/7 (14.3%) | 0/50 (0%) | 0/52 (0%) | ||||||||||
| Flushing | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 2/50 (4%) | 2/52 (3.8%) | ||||||||||
| Hot flush | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 2/50 (4%) | 0/52 (0%) | ||||||||||
| Haematoma | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Pallor | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Vasculitis | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 1/50 (2%) | 0/52 (0%) | ||||||||||
| Embolism | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
| Thrombosis | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 2/52 (3.8%) | ||||||||||
| Venous thrombosis limb | 0/2 (0%) | 0/7 (0%) | 0/9 (0%) | 0/8 (0%) | 0/3 (0%) | 0/8 (0%) | 0/10 (0%) | 0/7 (0%) | 0/50 (0%) | 1/52 (1.9%) | ||||||||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Results Point of Contact
| Name/Title | Pfizer ClinicalTrials.gov Call Center |
|---|---|
| Organization | Pfizer Inc. |
| Phone | 1-800-718-1021 |
| ClinicalTrials.gov_Inquiries@pfizer.com |
Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT01719380
Other Study ID Numbers:
- CLGX818X2103
- C4221002
- 2012-002138-35
First Posted:
Nov 1, 2012
Last Update Posted:
Jun 23, 2021
Last Verified:
May 1, 2021