Study of Safety and Efficacy in Patients With Malignant Rhabdoid Tumors (MRT) and Neuroblastoma
Sponsor
Novartis Pharmaceuticals (Industry)
Overall Status
Terminated
CT.gov ID
NCT01747876
Collaborator
(none)
32
13
1
49.1
2.5
0.1
Study Details
Study Description
Brief Summary
LEE011 is a small molecule inhibitor of CDK4/6. LEE011 has demonstrated in vitro and in vivo activity in both tumor models. The primary purpose of this study was to determine the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE) in pediatric patients and to delineate a clinical dose to be used in future studies. This study was also to have assessed the safety, tolerability, PK and preliminary evidence of antitumor activity of LEE011 in patients with MRT or neuroblastoma.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Detailed Description
Due to lack of efficacy, enrollment in the study was stopped at the end of dose escalation (sites were notified of the early enrollment halt on 7-Aug-2014) and the dose-expansion part was not conducted. Due to halted enrollment and/or lack of complete responses (CR) and partial responses (PR), efficacy analysis was only performed in terms of TTP for the patients treated during the dose-escalation part at the maximum tolerated dose (MTD) and recommended dose expansion (RDE).
Study Design
Study Type:
Interventional
Actual Enrollment
:
32 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase I, Multi-center, Open-label Study of LEE011 in Patients With Malignant Rhabdoid Tumors and Neuroblastoma
Actual Study Start Date
:
May 28, 2013
Actual Primary Completion Date
:
Jun 29, 2017
Actual Study Completion Date
:
Jun 29, 2017
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: LEE011
|
Drug: LEE011
LEE011 is a small molecule inhibitor of CDK4/6.
|
Outcome Measures
Primary Outcome Measures
- Incidence Rate of Dose Limiting Toxicities (DLTs) by Primary System Organ Class, Preferred Term and Treatment [cycle 1 = 28 days (from the time of first dose)]
A DLT was defined as an AE or clinically significant 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 with LEE011 and met any of the predefined criteria. For the purpose of dose-escalation decisions, DLTs were considered and included in the Bayesian Logistic Regression Model (BLRM). Patients who did not experience DLT during the first cycle were considered to have had sufficient safety evaluations if they were observed for ≥ 28 days following the first dose and were considered to have had enough safety data to conclude that a DLT did not occur. Patients who did not meet these minimum safety evaluation requirements were regarded as ineligible for the DDS. A patient with multiple DLTs within a primary system organ class is counted only once in the total row.
Secondary Outcome Measures
- Overall Response Rate [Every 2 cycles (cycle = 28 days) up to end of treatment, the maximum time a patient was on study was 1311 days]
This analysis was not done as there were no responders.
- Time to Disease Progression (TTP) Per RECIST 1.1 [Every 2 cycles (cycle = 28 days) up to end of treatment, the maximum time a patient was on study was 1311 days]
TTP was assessed per Investigator, for the malignant rhabdoid tumor (MRT) & neuroblastoma patients for the pooled maximum tolerated dose (MTD) & recommended dose for expansion (RDE) according to RECIST 1.1 criteria using Kaplan-Meier method. Time to progression (TTP) is the time from date of randomization/start of treatment to the date of event defined as the first documented progression or death due to underlying cancer. If a patient had not had an event, time to progression was censored at the date of last adequate tumor assessment. At least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
- Duration of Response (DOR) [Every 2 cycles (cycle = 28 days) up to end of treatment, the maximum time a patient was on study was 1311 days]
Assess the anti-tumor activity of LEE011 by RECIST 1.1. DOR was not assessed.
- Pharmacokinetics (PK) Parameter: AUC0-24 [0,1, 2, 4, 8 hours post dose Cycle 1 Day 1 (C1D1) and Cycle 1 Day 15 (C1D15)]
The AUC calculated to the end of a dosing interval (tau) following single dose or at steady-state (amount x time x volume-1). PK parameters were estimated from individual plasma concentration-time profiles using noncompartmental methods in Phoenix WinNonlin.
- Pharmacokinetics (PK) Parameter: Cmax [C1D1, C1D15]
Cmax is the maximum (peak) observed plasma, blood, serum, or other body fluid drug concentration after single dose administration or at steady-state (mass x volume-1). PK parameters were estimated from individual plasma concentration-time profiles using noncompartmental methods in Phoenix WinNonlin
- Pharmacokinetics (PK) Parameter: Tmax [C1D1, C1D15]
Tmax is the time to reach maximum (peak) plasma, blood, serum, or other body fluid drug concentration after single dose administration or at steady-state (time). PK parameters were estimated from individual plasma concentration-time profiles using noncompartmental methods in Phoenix WinNonlin.
Eligibility Criteria
Criteria
Ages Eligible for Study:
1 Year
to 21 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Confirmed diagnosis of MRT or, neuroblastoma or in dose escalation part, other tumors with documented evidence of D-cyclin-CDK4/6-INK4a-Rb pathway abnormalities (dose escalation part only),
-
Patients with CNS disease should be on stable doses of steroids for at least 7 days prior to first dose of LEE011 with no plans for escalation.
-
In expansion part, patients must have at least one measurable disease as defined by RECIST v1.1.
-
Patients must have a Lansky (≤ 16 years) or Karnofsky (> 16 years) score of at least
Exclusion Criteria:
-
Prior history of QTc prolongation or QTcF > 450 ms on screening ECG.
-
Patients with the following laboratory values during screening:
-
Serum creatinine > 1.5 x upper limit of normal (ULN) for age
-
Total bilirubin >1.5 x ULN for age
-
Alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase (SGPT) > 3 x ULN for age; aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase(SGOT) > 3 x ULN for age except in patients with tumor involvement of the liver who must have AST/SGOT and ALT/SGPT ≤ 5 x ULN for age. For the purpose of this study, the ULN for SGPT/ALT is 45 U/L.
-
Patients who are currently receiving treatment with agents that are metabolized predominantly through CYP3A4/5 and have a narrow therapeutic window and/or agents that are known strong inducers or inhibitors CYP3A4/5 are prohibited. In particular, enzyme-inducing antiepileptic drugs (EIAEDs).
-
Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may interfere with the interpretation of study results, and in the judgment of the investigator would make the patient inappropriate for the study.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | UCSF Medical Center Dept of Pediatic Oncology | San Francisco | California | United States | 94143 |
| 2 | Childrens Healthcare of Atlanta Dept of Oncology | Atlanta | Georgia | United States | 30342 |
| 3 | Dana Farber Cancer Institute SC-7 | Boston | Massachusetts | United States | 02215 |
| 4 | Memorial Sloan Kettering Dept of Onc | New York | New York | United States | 10017 |
| 5 | Cincinnati Children's Hospital Medical Center Dept of Oncology | Cincinnati | Ohio | United States | 45229-3039 |
| 6 | St Jude s Childrens Research Hospital Dept of Oncology | Memphis | Tennessee | United States | 38105-2794 |
| 7 | Novartis Investigative Site | Perth | Western Australia | Australia | 6840 |
| 8 | Novartis Investigative Site | Lyon Cedex | France | 69373 | |
| 9 | Novartis Investigative Site | Paris | France | 75231 | |
| 10 | Novartis Investigative Site | Villejuif Cedex | France | 94805 | |
| 11 | Novartis Investigative Site | Koeln | Nordrhein-Westfalen | Germany | 50937 |
| 12 | Novartis Investigative Site | Augsburg | Germany | 86156 | |
| 13 | Novartis Investigative Site | Sutton | Surrey | United Kingdom | SM2 5PT |
Sponsors and Collaborators
- Novartis Pharmaceuticals
Investigators
- Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01747876
Other Study ID Numbers:
- CLEE011X2102
- 2012-004228-40
First Posted:
Dec 12, 2012
Last Update Posted:
Nov 22, 2019
Last Verified:
Nov 1, 2019
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Novartis Pharmaceuticals
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Approximately 64 patients were to be treated during the entire study; however, 32 patients were enrolled and treated at the time of the enrollment halt. |
|---|---|
| Pre-assignment Detail | The escalation part of the study explored the 3 doses 280, 350 & 470 mg/m2) in successive cohorts. The dose expansion phase of the study was not conducted (due to enrollment halt). |
| Arm/Group Title | LEE011 280 mg/m2 - Dose Escalation Only | LEE011 350 mg/m2 - Dose Escalation Only | LEE011 470 mg/m2 - Dose Escalation Only |
|---|---|---|---|
| Arm/Group Description | Patients who took 280 mg/m2 of LEE011 | Patients who took 350 mg/m2 of LEE011. The dose escalation part of the study | Patients who took 470 mg/m2 of LEE011 |
| Period Title: Overall Study | |||
| STARTED | 5 | 15 | 12 |
| COMPLETED | 0 | 0 | 0 |
| NOT COMPLETED | 5 | 15 | 12 |
Baseline Characteristics
| Arm/Group Title | LEE011 280 mg/m2 - Dose Escalation Only | LEE011 350 mg/m2 - Dose Escalation Only | LEE011 470 mg/m2 - Dose Escalation Only | Total |
|---|---|---|---|---|
| Arm/Group Description | Patients who took 280 mg/m2 of LEE011 | Patients who took 350 mg/m2 of LEE011. The dose escalation part of the study | Patients who took 470 mg/m2 of LEE011 | Total of all reporting groups |
| Overall Participants | 5 | 15 | 12 | 32 |
| Age, Customized (Count of Participants) | ||||
| 1 to <2 |
2
40%
|
0
0%
|
1
8.3%
|
3
9.4%
|
| 2 to <5 |
2
40%
|
7
46.7%
|
4
33.3%
|
13
40.6%
|
| 6 to <12 |
0
0%
|
3
20%
|
3
25%
|
6
18.8%
|
| 12 to <18 |
1
20%
|
4
26.7%
|
2
16.7%
|
7
21.9%
|
| >= 18 |
0
0%
|
1
6.7%
|
2
16.7%
|
3
9.4%
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
1
20%
|
6
40%
|
4
33.3%
|
11
34.4%
|
| Male |
4
80%
|
9
60%
|
8
66.7%
|
21
65.6%
|
| Race/Ethnicity, Customized (Count of Participants) | ||||
| Caucasian |
2
40%
|
10
66.7%
|
9
75%
|
21
65.6%
|
| Asian |
1
20%
|
0
0%
|
0
0%
|
1
3.1%
|
| Other |
0
0%
|
2
13.3%
|
2
16.7%
|
4
12.5%
|
| Not Available |
2
40%
|
3
20%
|
1
8.3%
|
6
18.8%
|
Outcome Measures
| Title | Incidence Rate of Dose Limiting Toxicities (DLTs) by Primary System Organ Class, Preferred Term and Treatment |
|---|---|
| Description | A DLT was defined as an AE or clinically significant 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 with LEE011 and met any of the predefined criteria. For the purpose of dose-escalation decisions, DLTs were considered and included in the Bayesian Logistic Regression Model (BLRM). Patients who did not experience DLT during the first cycle were considered to have had sufficient safety evaluations if they were observed for ≥ 28 days following the first dose and were considered to have had enough safety data to conclude that a DLT did not occur. Patients who did not meet these minimum safety evaluation requirements were regarded as ineligible for the DDS. A patient with multiple DLTs within a primary system organ class is counted only once in the total row. |
| Time Frame | cycle 1 = 28 days (from the time of first dose) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Dose-determining analysis set consisted of all pts from safety set who either met the following minimum exposure criterion & had scheduled safety evaluations, or experienced a DLT. A patient was considered to have met the minimum exposure criterion if he/she had received at least 16 of 21 planned daily doses of LEE011 in first 28 days of dosing. |
| Arm/Group Title | LEE011 280 mg/m2 - Dose Escalation Only | LEE011 350 mg/m2 - Dose Escalation Only | LEE011 470 mg/m2 - Dose Escalation Only |
|---|---|---|---|
| Arm/Group Description | Patients who took 280 mg/m2 of LEE011 | Patients who took 350 mg/m2 of LEE011. The dose escalation part of the study | Patients who took 470 mg/m2 of LEE011 |
| Measure Participants | 5 | 15 | 10 |
| Any primary system organ class total |
1
20%
|
0
0%
|
2
16.7%
|
| Blood & lymphatic sys. disorders(Thrombocytopenia) |
0
0%
|
0
0%
|
1
8.3%
|
| Gen. disorders & admin. site conditions (fatigue) |
1
20%
|
0
0%
|
0
0%
|
| Investigations (Platelet count decreased) |
0
0%
|
0
0%
|
1
8.3%
|
| Title | Overall Response Rate |
|---|---|
| Description | This analysis was not done as there were no responders. |
| Time Frame | Every 2 cycles (cycle = 28 days) up to end of treatment, the maximum time a patient was on study was 1311 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set (FAS) included all patients who received at least one dose of LEE011. This analysis was not done as there were no responders. |
| Arm/Group Title | LEE011 280 mg/m2 - Dose Escalation Only | LEE011 350 mg/m2 - Dose Escalation Only | LEE011 470 mg/m2 - Dose Escalation Only |
|---|---|---|---|
| Arm/Group Description | Patients who took 280 mg/m2 of LEE011 | Patients who took 350 mg/m2 of LEE011. The dose escalation part of the study | Patients who took 470 mg/m2 of LEE011 |
| Measure Participants | 5 | 15 | 12 |
| Median (95% Confidence Interval) [months] |
NA
|
NA
|
NA
|
| Title | Time to Disease Progression (TTP) Per RECIST 1.1 |
|---|---|
| Description | TTP was assessed per Investigator, for the malignant rhabdoid tumor (MRT) & neuroblastoma patients for the pooled maximum tolerated dose (MTD) & recommended dose for expansion (RDE) according to RECIST 1.1 criteria using Kaplan-Meier method. Time to progression (TTP) is the time from date of randomization/start of treatment to the date of event defined as the first documented progression or death due to underlying cancer. If a patient had not had an event, time to progression was censored at the date of last adequate tumor assessment. At least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. |
| Time Frame | Every 2 cycles (cycle = 28 days) up to end of treatment, the maximum time a patient was on study was 1311 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set (FAS) included all patients who received at least one dose of LEE011. |
| Arm/Group Title | MRT Group | Neuroblastoma (NB) |
|---|---|---|
| Arm/Group Description | Patients had a confirmed diagnosis of malignant rhabdoid tumors | Patients had a confirmed diagnosis of neuroblastoma. |
| Measure Participants | 11 | 14 |
| Median (95% Confidence Interval) [months] |
1.8
|
1.8
|
| Title | Duration of Response (DOR) |
|---|---|
| Description | Assess the anti-tumor activity of LEE011 by RECIST 1.1. DOR was not assessed. |
| Time Frame | Every 2 cycles (cycle = 28 days) up to end of treatment, the maximum time a patient was on study was 1311 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set included all patients who received at least 1 dose of LEE011. Due to halted enrollment and/or lack of complete responses (CR) & partial responses (PR), efficacy analysis was only performed in terms of DOR for the patients treated during the dose-escalation part at the MTD and RDE. Therefore, Duration of response was not assessed. |
| Arm/Group Title | LEE011 280 mg/m2 - Dose Escalation Only | LEE011 350 mg/m2 - Dose Escalation Only | LEE011 470 mg/m2 - Dose Escalation Only |
|---|---|---|---|
| Arm/Group Description | Patients who took 280 mg/m2 of LEE011 | Patients who took 350 mg/m2 of LEE011. The dose escalation part of the study | Patients who took 470 mg/m2 of LEE011 |
| Measure Participants | 0 | 0 | 0 |
| Title | Pharmacokinetics (PK) Parameter: AUC0-24 |
|---|---|
| Description | The AUC calculated to the end of a dosing interval (tau) following single dose or at steady-state (amount x time x volume-1). PK parameters were estimated from individual plasma concentration-time profiles using noncompartmental methods in Phoenix WinNonlin. |
| Time Frame | 0,1, 2, 4, 8 hours post dose Cycle 1 Day 1 (C1D1) and Cycle 1 Day 15 (C1D15) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The pharmacokinetic analysis set (PAS) consisted of all patients who had at least one blood sample providing evaluable drug concentration data. |
| Arm/Group Title | LEE011 280 mg/m2 - Dose Escalation Only | LEE011 350 mg/m2 - Dose Escalation Only | LEE011 470 mg/m2 - Dose Escalation Only |
|---|---|---|---|
| Arm/Group Description | Patients who took 280 mg/m2 of LEE011 | Patients who took 350 mg/m2 of LEE011. The dose escalation part of the study | Patients who took 470 mg/m2 of LEE011 |
| Measure Participants | 5 | 12 | 7 |
| C1D1 |
9250
|
10000
|
17600
|
| C1D15 |
13800
|
24500
|
29100
|
| Title | Pharmacokinetics (PK) Parameter: Cmax |
|---|---|
| Description | Cmax is the maximum (peak) observed plasma, blood, serum, or other body fluid drug concentration after single dose administration or at steady-state (mass x volume-1). PK parameters were estimated from individual plasma concentration-time profiles using noncompartmental methods in Phoenix WinNonlin |
| Time Frame | C1D1, C1D15 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The pharmacokinetic analysis set (PAS) consisted of all patients who had at least one blood sample providing evaluable drug concentration data. |
| Arm/Group Title | LEE011 280 mg/m2 - Dose Escalation Only | LEE011 350 mg/m2 - Dose Escalation Only | LEE011 470 mg/m2 - Dose Escalation Only |
|---|---|---|---|
| Arm/Group Description | Patients who took 280 mg/m2 of LEE011 | Patients who took 350 mg/m2 of LEE011. The dose escalation part of the study | Patients who took 470 mg/m2 of LEE011 |
| Measure Participants | 5 | 12 | 10 |
| C1D1 |
937
|
1130
|
1960
|
| C1D15 |
1110
|
2010
|
2500
|
| Title | Pharmacokinetics (PK) Parameter: Tmax |
|---|---|
| Description | Tmax is the time to reach maximum (peak) plasma, blood, serum, or other body fluid drug concentration after single dose administration or at steady-state (time). PK parameters were estimated from individual plasma concentration-time profiles using noncompartmental methods in Phoenix WinNonlin. |
| Time Frame | C1D1, C1D15 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The pharmacokinetic analysis set (PAS) consisted of all patients who had at least one blood sample providing evaluable drug concentration data. |
| Arm/Group Title | LEE011 280 mg/m2 - Dose Escalation Only | LEE011 350 mg/m2 - Dose Escalation Only | LEE011 470 mg/m2 - Dose Escalation Only |
|---|---|---|---|
| Arm/Group Description | Patients who took 280 mg/m2 of LEE011 | Patients who took 350 mg/m2 of LEE011. The dose escalation part of the study | Patients who took 470 mg/m2 of LEE011 |
| Measure Participants | 5 | 12 | 10 |
| C1D1 |
2.03
|
2.02
|
4
|
| C1D15 |
2.08
|
2.13
|
3.92
|
Adverse Events
| Time Frame | From date of first administration of study treatment to 30 days after date of last actual administration of study | |||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||
| Arm/Group Title | LEE011 280 mg/m2 - Dose Escalation Only | LEE011 350 mg/m2 - Dose Escalation Only | LEE011 470 mg/m2 - Dose Escalation Only | All Patients | ||||
| Arm/Group Description | Patients who took 280 mg/m2 of LEE011 | Patients who took 350 mg/m2 of LEE011. The dose escalation part of the study | Patients who took 470 mg/m2 of LEE011 | All patients who took either 280 mg/m2 or 350 mg/m2 or 470 mg/m2 of LEE011 | ||||
All Cause Mortality |
||||||||
| LEE011 280 mg/m2 - Dose Escalation Only | LEE011 350 mg/m2 - Dose Escalation Only | LEE011 470 mg/m2 - Dose Escalation Only | All Patients | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 2/5 (40%) | 2/15 (13.3%) | 1/12 (8.3%) | 5/32 (15.6%) | ||||
Serious Adverse Events |
||||||||
| LEE011 280 mg/m2 - Dose Escalation Only | LEE011 350 mg/m2 - Dose Escalation Only | LEE011 470 mg/m2 - Dose Escalation Only | All Patients | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 3/5 (60%) | 7/15 (46.7%) | 4/12 (33.3%) | 14/32 (43.8%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Febrile neutropenia | 0/5 (0%) | 1/15 (6.7%) | 0/12 (0%) | 1/32 (3.1%) | ||||
| Eye disorders | ||||||||
| Orbital oedema | 0/5 (0%) | 0/15 (0%) | 1/12 (8.3%) | 1/32 (3.1%) | ||||
| Gastrointestinal disorders | ||||||||
| Abdominal pain | 1/5 (20%) | 0/15 (0%) | 0/12 (0%) | 1/32 (3.1%) | ||||
| General disorders | ||||||||
| Face oedema | 0/5 (0%) | 0/15 (0%) | 1/12 (8.3%) | 1/32 (3.1%) | ||||
| Pain | 0/5 (0%) | 1/15 (6.7%) | 0/12 (0%) | 1/32 (3.1%) | ||||
| Pyrexia | 0/5 (0%) | 2/15 (13.3%) | 0/12 (0%) | 2/32 (6.3%) | ||||
| Infections and infestations | ||||||||
| Device related infection | 0/5 (0%) | 1/15 (6.7%) | 0/12 (0%) | 1/32 (3.1%) | ||||
| Influenza | 0/5 (0%) | 0/15 (0%) | 1/12 (8.3%) | 1/32 (3.1%) | ||||
| Pneumococcal bacteraemia | 0/5 (0%) | 1/15 (6.7%) | 0/12 (0%) | 1/32 (3.1%) | ||||
| Pneumococcal infection | 0/5 (0%) | 0/15 (0%) | 1/12 (8.3%) | 1/32 (3.1%) | ||||
| Pneumonia | 0/5 (0%) | 1/15 (6.7%) | 0/12 (0%) | 1/32 (3.1%) | ||||
| Investigations | ||||||||
| Lymphocyte count decreased | 0/5 (0%) | 1/15 (6.7%) | 0/12 (0%) | 1/32 (3.1%) | ||||
| Metabolism and nutrition disorders | ||||||||
| Decreased appetite | 0/5 (0%) | 0/15 (0%) | 1/12 (8.3%) | 1/32 (3.1%) | ||||
| Dehydration | 0/5 (0%) | 1/15 (6.7%) | 0/12 (0%) | 1/32 (3.1%) | ||||
| Hypercalcaemia | 1/5 (20%) | 0/15 (0%) | 0/12 (0%) | 1/32 (3.1%) | ||||
| Hypokalaemia | 0/5 (0%) | 1/15 (6.7%) | 0/12 (0%) | 1/32 (3.1%) | ||||
| Polydipsia | 1/5 (20%) | 0/15 (0%) | 0/12 (0%) | 1/32 (3.1%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| Pain in extremity | 0/5 (0%) | 1/15 (6.7%) | 0/12 (0%) | 1/32 (3.1%) | ||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
| Central nervous system neuroblastoma | 0/5 (0%) | 1/15 (6.7%) | 0/12 (0%) | 1/32 (3.1%) | ||||
| Nervous system disorders | ||||||||
| Brain oedema | 0/5 (0%) | 0/15 (0%) | 1/12 (8.3%) | 1/32 (3.1%) | ||||
| Depressed level of consciousness | 0/5 (0%) | 0/15 (0%) | 1/12 (8.3%) | 1/32 (3.1%) | ||||
| Extrapyramidal disorder | 1/5 (20%) | 0/15 (0%) | 0/12 (0%) | 1/32 (3.1%) | ||||
| Febrile convulsion | 0/5 (0%) | 1/15 (6.7%) | 0/12 (0%) | 1/32 (3.1%) | ||||
| Headache | 0/5 (0%) | 0/15 (0%) | 2/12 (16.7%) | 2/32 (6.3%) | ||||
| Hydrocephalus | 0/5 (0%) | 0/15 (0%) | 1/12 (8.3%) | 1/32 (3.1%) | ||||
| Intracranial pressure increased | 1/5 (20%) | 0/15 (0%) | 0/12 (0%) | 1/32 (3.1%) | ||||
| Seizure | 0/5 (0%) | 1/15 (6.7%) | 0/12 (0%) | 1/32 (3.1%) | ||||
| Psychiatric disorders | ||||||||
| Irritability | 0/5 (0%) | 0/15 (0%) | 1/12 (8.3%) | 1/32 (3.1%) | ||||
| Renal and urinary disorders | ||||||||
| Polyuria | 1/5 (20%) | 0/15 (0%) | 0/12 (0%) | 1/32 (3.1%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Apnoea | 0/5 (0%) | 0/15 (0%) | 1/12 (8.3%) | 1/32 (3.1%) | ||||
| Dyspnoea | 0/5 (0%) | 1/15 (6.7%) | 0/12 (0%) | 1/32 (3.1%) | ||||
Other (Not Including Serious) Adverse Events |
||||||||
| LEE011 280 mg/m2 - Dose Escalation Only | LEE011 350 mg/m2 - Dose Escalation Only | LEE011 470 mg/m2 - Dose Escalation Only | All Patients | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 5/5 (100%) | 15/15 (100%) | 12/12 (100%) | 32/32 (100%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Anaemia | 1/5 (20%) | 8/15 (53.3%) | 6/12 (50%) | 15/32 (46.9%) | ||||
| Haemolysis | 0/5 (0%) | 0/15 (0%) | 1/12 (8.3%) | 1/32 (3.1%) | ||||
| Leukopenia | 0/5 (0%) | 1/15 (6.7%) | 0/12 (0%) | 1/32 (3.1%) | ||||
| Lymphopenia | 0/5 (0%) | 1/15 (6.7%) | 1/12 (8.3%) | 2/32 (6.3%) | ||||
| Neutropenia | 2/5 (40%) | 3/15 (20%) | 3/12 (25%) | 8/32 (25%) | ||||
| Thrombocytopenia | 0/5 (0%) | 1/15 (6.7%) | 3/12 (25%) | 4/32 (12.5%) | ||||
| Cardiac disorders | ||||||||
| Sinus bradycardia | 0/5 (0%) | 0/15 (0%) | 1/12 (8.3%) | 1/32 (3.1%) | ||||
| Sinus tachycardia | 1/5 (20%) | 1/15 (6.7%) | 1/12 (8.3%) | 3/32 (9.4%) | ||||
| Ear and labyrinth disorders | ||||||||
| Deafness | 0/5 (0%) | 0/15 (0%) | 1/12 (8.3%) | 1/32 (3.1%) | ||||
| Ear pain | 0/5 (0%) | 1/15 (6.7%) | 0/12 (0%) | 1/32 (3.1%) | ||||
| External ear inflammation | 0/5 (0%) | 1/15 (6.7%) | 1/12 (8.3%) | 2/32 (6.3%) | ||||
| External ear pain | 0/5 (0%) | 0/15 (0%) | 1/12 (8.3%) | 1/32 (3.1%) | ||||
| Hypoacusis | 0/5 (0%) | 2/15 (13.3%) | 0/12 (0%) | 2/32 (6.3%) | ||||
| Middle ear inflammation | 0/5 (0%) | 1/15 (6.7%) | 1/12 (8.3%) | 2/32 (6.3%) | ||||
| Endocrine disorders | ||||||||
| Hypothyroidism | 0/5 (0%) | 1/15 (6.7%) | 1/12 (8.3%) | 2/32 (6.3%) | ||||
| Eye disorders | ||||||||
| Dry eye | 0/5 (0%) | 1/15 (6.7%) | 0/12 (0%) | 1/32 (3.1%) | ||||
| Eye discharge | 0/5 (0%) | 2/15 (13.3%) | 0/12 (0%) | 2/32 (6.3%) | ||||
| Eyelid haematoma | 0/5 (0%) | 0/15 (0%) | 1/12 (8.3%) | 1/32 (3.1%) | ||||
| Heterophoria | 0/5 (0%) | 1/15 (6.7%) | 0/12 (0%) | 1/32 (3.1%) | ||||
| Optic atrophy | 0/5 (0%) | 1/15 (6.7%) | 0/12 (0%) | 1/32 (3.1%) | ||||
| Photophobia | 0/5 (0%) | 0/15 (0%) | 1/12 (8.3%) | 1/32 (3.1%) | ||||
| Photopsia | 0/5 (0%) | 1/15 (6.7%) | 0/12 (0%) | 1/32 (3.1%) | ||||
| Retinal haemorrhage | 0/5 (0%) | 1/15 (6.7%) | 0/12 (0%) | 1/32 (3.1%) | ||||
| Strabismus | 0/5 (0%) | 1/15 (6.7%) | 0/12 (0%) | 1/32 (3.1%) | ||||
| Gastrointestinal disorders | ||||||||
| Abdominal discomfort | 0/5 (0%) | 1/15 (6.7%) | 0/12 (0%) | 1/32 (3.1%) | ||||
| Abdominal pain | 1/5 (20%) | 5/15 (33.3%) | 2/12 (16.7%) | 8/32 (25%) | ||||
| Abdominal pain upper | 0/5 (0%) | 1/15 (6.7%) | 1/12 (8.3%) | 2/32 (6.3%) | ||||
| Anorectal disorder | 0/5 (0%) | 1/15 (6.7%) | 0/12 (0%) | 1/32 (3.1%) | ||||
| Constipation | 0/5 (0%) | 6/15 (40%) | 1/12 (8.3%) | 7/32 (21.9%) | ||||
| Diarrhoea | 3/5 (60%) | 8/15 (53.3%) | 2/12 (16.7%) | 13/32 (40.6%) | ||||
| Dyschezia | 1/5 (20%) | 0/15 (0%) | 0/12 (0%) | 1/32 (3.1%) | ||||
| Eructation | 0/5 (0%) | 0/15 (0%) | 2/12 (16.7%) | 2/32 (6.3%) | ||||
| Flatulence | 0/5 (0%) | 0/15 (0%) | 1/12 (8.3%) | 1/32 (3.1%) | ||||
| Nausea | 1/5 (20%) | 6/15 (40%) | 5/12 (41.7%) | 12/32 (37.5%) | ||||
| Oral disorder | 0/5 (0%) | 2/15 (13.3%) | 0/12 (0%) | 2/32 (6.3%) | ||||
| Stomatitis | 0/5 (0%) | 2/15 (13.3%) | 2/12 (16.7%) | 4/32 (12.5%) | ||||
| Vomiting | 2/5 (40%) | 12/15 (80%) | 9/12 (75%) | 23/32 (71.9%) | ||||
| General disorders | ||||||||
| Asthenia | 0/5 (0%) | 5/15 (33.3%) | 1/12 (8.3%) | 6/32 (18.8%) | ||||
| Catheter site pain | 0/5 (0%) | 0/15 (0%) | 1/12 (8.3%) | 1/32 (3.1%) | ||||
| Chills | 0/5 (0%) | 1/15 (6.7%) | 0/12 (0%) | 1/32 (3.1%) | ||||
| Complication associated with device | 0/5 (0%) | 0/15 (0%) | 1/12 (8.3%) | 1/32 (3.1%) | ||||
| Drug intolerance | 0/5 (0%) | 0/15 (0%) | 1/12 (8.3%) | 1/32 (3.1%) | ||||
| Face oedema | 0/5 (0%) | 1/15 (6.7%) | 0/12 (0%) | 1/32 (3.1%) | ||||
| Fatigue | 1/5 (20%) | 5/15 (33.3%) | 6/12 (50%) | 12/32 (37.5%) | ||||
| Gait disturbance | 1/5 (20%) | 1/15 (6.7%) | 1/12 (8.3%) | 3/32 (9.4%) | ||||
| Malaise | 0/5 (0%) | 1/15 (6.7%) | 1/12 (8.3%) | 2/32 (6.3%) | ||||
| Pain | 1/5 (20%) | 1/15 (6.7%) | 2/12 (16.7%) | 4/32 (12.5%) | ||||
| Pyrexia | 1/5 (20%) | 5/15 (33.3%) | 2/12 (16.7%) | 8/32 (25%) | ||||
| Immune system disorders | ||||||||
| Hypersensitivity | 0/5 (0%) | 1/15 (6.7%) | 0/12 (0%) | 1/32 (3.1%) | ||||
| Infections and infestations | ||||||||
| Bacteraemia | 0/5 (0%) | 1/15 (6.7%) | 0/12 (0%) | 1/32 (3.1%) | ||||
| Conjunctivitis | 1/5 (20%) | 2/15 (13.3%) | 2/12 (16.7%) | 5/32 (15.6%) | ||||
| Device related infection | 0/5 (0%) | 1/15 (6.7%) | 0/12 (0%) | 1/32 (3.1%) | ||||
| Foot and mouth disease | 0/5 (0%) | 1/15 (6.7%) | 0/12 (0%) | 1/32 (3.1%) | ||||
| Myringitis | 0/5 (0%) | 0/15 (0%) | 1/12 (8.3%) | 1/32 (3.1%) | ||||
| Oral herpes | 0/5 (0%) | 1/15 (6.7%) | 0/12 (0%) | 1/32 (3.1%) | ||||
| Otitis media | 0/5 (0%) | 1/15 (6.7%) | 0/12 (0%) | 1/32 (3.1%) | ||||
| Pharyngitis | 0/5 (0%) | 1/15 (6.7%) | 0/12 (0%) | 1/32 (3.1%) | ||||
| Pharyngitis streptococcal | 0/5 (0%) | 0/15 (0%) | 1/12 (8.3%) | 1/32 (3.1%) | ||||
| Rash pustular | 0/5 (0%) | 1/15 (6.7%) | 0/12 (0%) | 1/32 (3.1%) | ||||
| Rhinitis | 0/5 (0%) | 0/15 (0%) | 2/12 (16.7%) | 2/32 (6.3%) | ||||
| Skin infection | 0/5 (0%) | 1/15 (6.7%) | 0/12 (0%) | 1/32 (3.1%) | ||||
| Upper respiratory tract infection | 0/5 (0%) | 2/15 (13.3%) | 2/12 (16.7%) | 4/32 (12.5%) | ||||
| Urinary tract infection | 0/5 (0%) | 1/15 (6.7%) | 0/12 (0%) | 1/32 (3.1%) | ||||
| Injury, poisoning and procedural complications | ||||||||
| Arthropod bite | 1/5 (20%) | 0/15 (0%) | 0/12 (0%) | 1/32 (3.1%) | ||||
| Contusion | 0/5 (0%) | 2/15 (13.3%) | 4/12 (33.3%) | 6/32 (18.8%) | ||||
| Fall | 0/5 (0%) | 2/15 (13.3%) | 0/12 (0%) | 2/32 (6.3%) | ||||
| Laceration | 0/5 (0%) | 2/15 (13.3%) | 0/12 (0%) | 2/32 (6.3%) | ||||
| Ligament sprain | 0/5 (0%) | 0/15 (0%) | 1/12 (8.3%) | 1/32 (3.1%) | ||||
| Procedural pain | 0/5 (0%) | 1/15 (6.7%) | 1/12 (8.3%) | 2/32 (6.3%) | ||||
| Radiation skin injury | 0/5 (0%) | 0/15 (0%) | 1/12 (8.3%) | 1/32 (3.1%) | ||||
| Scratch | 1/5 (20%) | 2/15 (13.3%) | 0/12 (0%) | 3/32 (9.4%) | ||||
| Investigations | ||||||||
| Alanine aminotransferase increased | 0/5 (0%) | 3/15 (20%) | 2/12 (16.7%) | 5/32 (15.6%) | ||||
| Aspartate aminotransferase increased | 0/5 (0%) | 5/15 (33.3%) | 4/12 (33.3%) | 9/32 (28.1%) | ||||
| Bilirubin conjugated increased | 0/5 (0%) | 1/15 (6.7%) | 0/12 (0%) | 1/32 (3.1%) | ||||
| Blood alkaline phosphatase increased | 0/5 (0%) | 1/15 (6.7%) | 1/12 (8.3%) | 2/32 (6.3%) | ||||
| Blood bilirubin increased | 0/5 (0%) | 1/15 (6.7%) | 1/12 (8.3%) | 2/32 (6.3%) | ||||
| Blood creatinine decreased | 0/5 (0%) | 1/15 (6.7%) | 0/12 (0%) | 1/32 (3.1%) | ||||
| Blood creatinine increased | 0/5 (0%) | 5/15 (33.3%) | 2/12 (16.7%) | 7/32 (21.9%) | ||||
| Blood lactate dehydrogenase decreased | 0/5 (0%) | 1/15 (6.7%) | 0/12 (0%) | 1/32 (3.1%) | ||||
| Blood lactate dehydrogenase increased | 0/5 (0%) | 1/15 (6.7%) | 0/12 (0%) | 1/32 (3.1%) | ||||
| Blood potassium decreased | 0/5 (0%) | 1/15 (6.7%) | 0/12 (0%) | 1/32 (3.1%) | ||||
| Blood sodium decreased | 0/5 (0%) | 1/15 (6.7%) | 0/12 (0%) | 1/32 (3.1%) | ||||
| Blood urea increased | 0/5 (0%) | 1/15 (6.7%) | 0/12 (0%) | 1/32 (3.1%) | ||||
| Electrocardiogram QT prolonged | 0/5 (0%) | 4/15 (26.7%) | 3/12 (25%) | 7/32 (21.9%) | ||||
| Gamma-glutamyltransferase increased | 0/5 (0%) | 2/15 (13.3%) | 0/12 (0%) | 2/32 (6.3%) | ||||
| Heart rate increased | 0/5 (0%) | 1/15 (6.7%) | 0/12 (0%) | 1/32 (3.1%) | ||||
| Lymphocyte count decreased | 0/5 (0%) | 5/15 (33.3%) | 5/12 (41.7%) | 10/32 (31.3%) | ||||
| Neutrophil count decreased | 0/5 (0%) | 10/15 (66.7%) | 5/12 (41.7%) | 15/32 (46.9%) | ||||
| Platelet count decreased | 0/5 (0%) | 7/15 (46.7%) | 5/12 (41.7%) | 12/32 (37.5%) | ||||
| Weight decreased | 1/5 (20%) | 4/15 (26.7%) | 1/12 (8.3%) | 6/32 (18.8%) | ||||
| Weight increased | 0/5 (0%) | 1/15 (6.7%) | 1/12 (8.3%) | 2/32 (6.3%) | ||||
| White blood cell count decreased | 1/5 (20%) | 11/15 (73.3%) | 9/12 (75%) | 21/32 (65.6%) | ||||
| Metabolism and nutrition disorders | ||||||||
| Decreased appetite | 1/5 (20%) | 5/15 (33.3%) | 2/12 (16.7%) | 8/32 (25%) | ||||
| Hyperglycaemia | 0/5 (0%) | 1/15 (6.7%) | 1/12 (8.3%) | 2/32 (6.3%) | ||||
| Hyperkalaemia | 1/5 (20%) | 1/15 (6.7%) | 1/12 (8.3%) | 3/32 (9.4%) | ||||
| Hypermagnesaemia | 0/5 (0%) | 0/15 (0%) | 1/12 (8.3%) | 1/32 (3.1%) | ||||
| Hyperphosphataemia | 0/5 (0%) | 1/15 (6.7%) | 0/12 (0%) | 1/32 (3.1%) | ||||
| Hypoalbuminaemia | 0/5 (0%) | 2/15 (13.3%) | 1/12 (8.3%) | 3/32 (9.4%) | ||||
| Hypocalcaemia | 0/5 (0%) | 1/15 (6.7%) | 1/12 (8.3%) | 2/32 (6.3%) | ||||
| Hypokalaemia | 1/5 (20%) | 3/15 (20%) | 0/12 (0%) | 4/32 (12.5%) | ||||
| Hypomagnesaemia | 0/5 (0%) | 1/15 (6.7%) | 1/12 (8.3%) | 2/32 (6.3%) | ||||
| Hyponatraemia | 1/5 (20%) | 6/15 (40%) | 1/12 (8.3%) | 8/32 (25%) | ||||
| Hypophosphataemia | 2/5 (40%) | 4/15 (26.7%) | 0/12 (0%) | 6/32 (18.8%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| Arthralgia | 0/5 (0%) | 1/15 (6.7%) | 0/12 (0%) | 1/32 (3.1%) | ||||
| Back pain | 1/5 (20%) | 5/15 (33.3%) | 1/12 (8.3%) | 7/32 (21.9%) | ||||
| Bone pain | 0/5 (0%) | 1/15 (6.7%) | 0/12 (0%) | 1/32 (3.1%) | ||||
| Bone swelling | 0/5 (0%) | 1/15 (6.7%) | 0/12 (0%) | 1/32 (3.1%) | ||||
| Flank pain | 0/5 (0%) | 1/15 (6.7%) | 0/12 (0%) | 1/32 (3.1%) | ||||
| Muscle fatigue | 2/5 (40%) | 0/15 (0%) | 0/12 (0%) | 2/32 (6.3%) | ||||
| Muscle spasms | 0/5 (0%) | 1/15 (6.7%) | 0/12 (0%) | 1/32 (3.1%) | ||||
| Muscular weakness | 0/5 (0%) | 2/15 (13.3%) | 0/12 (0%) | 2/32 (6.3%) | ||||
| Musculoskeletal chest pain | 0/5 (0%) | 2/15 (13.3%) | 2/12 (16.7%) | 4/32 (12.5%) | ||||
| Musculoskeletal pain | 0/5 (0%) | 1/15 (6.7%) | 0/12 (0%) | 1/32 (3.1%) | ||||
| Myalgia | 1/5 (20%) | 1/15 (6.7%) | 0/12 (0%) | 2/32 (6.3%) | ||||
| Neck pain | 0/5 (0%) | 1/15 (6.7%) | 0/12 (0%) | 1/32 (3.1%) | ||||
| Pain in extremity | 0/5 (0%) | 5/15 (33.3%) | 2/12 (16.7%) | 7/32 (21.9%) | ||||
| Pain in jaw | 0/5 (0%) | 0/15 (0%) | 1/12 (8.3%) | 1/32 (3.1%) | ||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
| Metastases to meninges | 1/5 (20%) | 0/15 (0%) | 0/12 (0%) | 1/32 (3.1%) | ||||
| Tumour pain | 0/5 (0%) | 1/15 (6.7%) | 0/12 (0%) | 1/32 (3.1%) | ||||
| Nervous system disorders | ||||||||
| Aphasia | 0/5 (0%) | 1/15 (6.7%) | 0/12 (0%) | 1/32 (3.1%) | ||||
| Brain oedema | 1/5 (20%) | 0/15 (0%) | 0/12 (0%) | 1/32 (3.1%) | ||||
| Dizziness | 1/5 (20%) | 2/15 (13.3%) | 0/12 (0%) | 3/32 (9.4%) | ||||
| Dysgeusia | 1/5 (20%) | 0/15 (0%) | 0/12 (0%) | 1/32 (3.1%) | ||||
| Extrapyramidal disorder | 0/5 (0%) | 0/15 (0%) | 1/12 (8.3%) | 1/32 (3.1%) | ||||
| Haemorrhage intracranial | 0/5 (0%) | 1/15 (6.7%) | 0/12 (0%) | 1/32 (3.1%) | ||||
| Headache | 3/5 (60%) | 7/15 (46.7%) | 5/12 (41.7%) | 15/32 (46.9%) | ||||
| Hydrocephalus | 0/5 (0%) | 1/15 (6.7%) | 0/12 (0%) | 1/32 (3.1%) | ||||
| IIIrd nerve disorder | 0/5 (0%) | 1/15 (6.7%) | 0/12 (0%) | 1/32 (3.1%) | ||||
| Lethargy | 0/5 (0%) | 0/15 (0%) | 1/12 (8.3%) | 1/32 (3.1%) | ||||
| Monoplegia | 1/5 (20%) | 0/15 (0%) | 0/12 (0%) | 1/32 (3.1%) | ||||
| Paraesthesia | 1/5 (20%) | 0/15 (0%) | 0/12 (0%) | 1/32 (3.1%) | ||||
| Somnolence | 1/5 (20%) | 1/15 (6.7%) | 0/12 (0%) | 2/32 (6.3%) | ||||
| Syncope | 0/5 (0%) | 1/15 (6.7%) | 0/12 (0%) | 1/32 (3.1%) | ||||
| Tremor | 0/5 (0%) | 2/15 (13.3%) | 0/12 (0%) | 2/32 (6.3%) | ||||
| Psychiatric disorders | ||||||||
| Aggression | 0/5 (0%) | 1/15 (6.7%) | 0/12 (0%) | 1/32 (3.1%) | ||||
| Agitation | 1/5 (20%) | 2/15 (13.3%) | 2/12 (16.7%) | 5/32 (15.6%) | ||||
| Anxiety | 0/5 (0%) | 2/15 (13.3%) | 0/12 (0%) | 2/32 (6.3%) | ||||
| Depressed mood | 0/5 (0%) | 1/15 (6.7%) | 0/12 (0%) | 1/32 (3.1%) | ||||
| Insomnia | 1/5 (20%) | 1/15 (6.7%) | 2/12 (16.7%) | 4/32 (12.5%) | ||||
| Irritability | 0/5 (0%) | 1/15 (6.7%) | 0/12 (0%) | 1/32 (3.1%) | ||||
| Mood altered | 2/5 (40%) | 0/15 (0%) | 0/12 (0%) | 2/32 (6.3%) | ||||
| Renal and urinary disorders | ||||||||
| Haematuria | 0/5 (0%) | 1/15 (6.7%) | 0/12 (0%) | 1/32 (3.1%) | ||||
| Urinary incontinence | 0/5 (0%) | 1/15 (6.7%) | 0/12 (0%) | 1/32 (3.1%) | ||||
| Urinary retention | 0/5 (0%) | 1/15 (6.7%) | 0/12 (0%) | 1/32 (3.1%) | ||||
| Reproductive system and breast disorders | ||||||||
| Menstruation irregular | 0/5 (0%) | 1/15 (6.7%) | 0/12 (0%) | 1/32 (3.1%) | ||||
| Oedema genital | 0/5 (0%) | 1/15 (6.7%) | 0/12 (0%) | 1/32 (3.1%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Apnoea | 0/5 (0%) | 1/15 (6.7%) | 0/12 (0%) | 1/32 (3.1%) | ||||
| Bradypnoea | 0/5 (0%) | 1/15 (6.7%) | 1/12 (8.3%) | 2/32 (6.3%) | ||||
| Cough | 0/5 (0%) | 6/15 (40%) | 3/12 (25%) | 9/32 (28.1%) | ||||
| Dysphonia | 0/5 (0%) | 1/15 (6.7%) | 0/12 (0%) | 1/32 (3.1%) | ||||
| Dyspnoea | 0/5 (0%) | 2/15 (13.3%) | 0/12 (0%) | 2/32 (6.3%) | ||||
| Epistaxis | 0/5 (0%) | 0/15 (0%) | 3/12 (25%) | 3/32 (9.4%) | ||||
| Hypoxia | 1/5 (20%) | 1/15 (6.7%) | 0/12 (0%) | 2/32 (6.3%) | ||||
| Nasal congestion | 0/5 (0%) | 1/15 (6.7%) | 0/12 (0%) | 1/32 (3.1%) | ||||
| Oropharyngeal pain | 0/5 (0%) | 2/15 (13.3%) | 1/12 (8.3%) | 3/32 (9.4%) | ||||
| Respiratory distress | 0/5 (0%) | 0/15 (0%) | 1/12 (8.3%) | 1/32 (3.1%) | ||||
| Rhinitis allergic | 0/5 (0%) | 1/15 (6.7%) | 0/12 (0%) | 1/32 (3.1%) | ||||
| Rhinorrhoea | 0/5 (0%) | 3/15 (20%) | 3/12 (25%) | 6/32 (18.8%) | ||||
| Sneezing | 0/5 (0%) | 2/15 (13.3%) | 0/12 (0%) | 2/32 (6.3%) | ||||
| Tachypnoea | 0/5 (0%) | 1/15 (6.7%) | 0/12 (0%) | 1/32 (3.1%) | ||||
| Upper-airway cough syndrome | 0/5 (0%) | 0/15 (0%) | 1/12 (8.3%) | 1/32 (3.1%) | ||||
| Skin and subcutaneous tissue disorders | ||||||||
| Alopecia | 0/5 (0%) | 1/15 (6.7%) | 0/12 (0%) | 1/32 (3.1%) | ||||
| Dermatitis atopic | 0/5 (0%) | 1/15 (6.7%) | 0/12 (0%) | 1/32 (3.1%) | ||||
| Dermatitis contact | 0/5 (0%) | 1/15 (6.7%) | 0/12 (0%) | 1/32 (3.1%) | ||||
| Dry skin | 0/5 (0%) | 1/15 (6.7%) | 0/12 (0%) | 1/32 (3.1%) | ||||
| Erythema | 0/5 (0%) | 1/15 (6.7%) | 0/12 (0%) | 1/32 (3.1%) | ||||
| Nail discolouration | 0/5 (0%) | 1/15 (6.7%) | 0/12 (0%) | 1/32 (3.1%) | ||||
| Rash | 1/5 (20%) | 1/15 (6.7%) | 2/12 (16.7%) | 4/32 (12.5%) | ||||
| Rash macular | 0/5 (0%) | 0/15 (0%) | 1/12 (8.3%) | 1/32 (3.1%) | ||||
| Rash maculo-papular | 0/5 (0%) | 2/15 (13.3%) | 0/12 (0%) | 2/32 (6.3%) | ||||
| Rash morbilliform | 0/5 (0%) | 0/15 (0%) | 1/12 (8.3%) | 1/32 (3.1%) | ||||
| Vascular disorders | ||||||||
| Hypertension | 0/5 (0%) | 1/15 (6.7%) | 1/12 (8.3%) | 2/32 (6.3%) | ||||
| Hypotension | 0/5 (0%) | 2/15 (13.3%) | 1/12 (8.3%) | 3/32 (9.4%) | ||||
| Raynaud's phenomenon | 1/5 (20%) | 0/15 (0%) | 0/12 (0%) | 1/32 (3.1%) | ||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of pooled data (i.e.,data from all sites) in clinical trial or disclosure of trial results in their entirety.
Results Point of Contact
| Name/Title | Study Director |
|---|---|
| Organization | Novartis Pharmaceuticals |
| Phone | 862-778-8300 |
| novartis.email@novartis.com |
Responsible Party:
Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01747876
Other Study ID Numbers:
- CLEE011X2102
- 2012-004228-40
First Posted:
Dec 12, 2012
Last Update Posted:
Nov 22, 2019
Last Verified:
Nov 1, 2019