Study of Efficacy and Safety of Buparlisib (BKM120) Plus Paclitaxel Versus Placebo Plus Paclitaxel in Recurrent or Metastatic Head and Neck Cancer Previously Pre-treated With a Platinum Therapy

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01852292
• Collaborator: (none)
• Enrollment: 157
• Locations: 58
• Arms: 2
• Actual Duration (Months): 41.9
• Patients Per Site: 2.7
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Phase II Study of efficacy and safety of buparlisib (BKM120) plus paclitaxel versus placebo plus paclitaxel in recurrent or metastatic Head and Neck cancer previously pre-treated with a platinum therapy.The primary endpoint was PFS and the key secondary endpoint was Overall Survival.

Condition or Disease	Intervention/Treatment	Phase
Head and Neck Squamous Cell Carcinoma	Drug: Buparlisib; Drug: Buparlisib matching Placebo; Drug: Paclitaxel	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 157 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Double Blind, Placebo Controlled Study Assessing the Efficacy of Buparlisib (BKM120) Plus Paclitaxel Versus Placebo Plus Paclitaxel in Patients With Platinum Pre-treated Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (HNSCC)
• Actual Study Start Date: Oct 1, 2013
• Actual Primary Completion Date: Mar 30, 2017
• Actual Study Completion Date: Mar 30, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Buparlisib + weekly Paclitaxel Patients who were randomized to this arm on a 1:1 randomization, took buparlisib 100 mg daily and paclitaxel 80 mg/m^2 weekly.	Drug: Buparlisib; Buparlisib comes in gelatin capsules and is taken orally at a dose of 100 mg/day.; Other Names: BKM120 ; Drug: Paclitaxel; Paclitaxel is an intravenous infusion that is given once every week in 80 mg/m^2.
Placebo Comparator: Buparlisib matching placebo + Paclitaxel Patients who were randomized to this arm on a 1:1 randomization, took buparlisib matching placebo 100 mg daily and paclitaxel 80 mg/m^2 weekly.	Drug: Buparlisib matching Placebo; Buparlisib matching placebo comes in gelatin capsules and is taken orally at a dose of 100 mg/day.; Drug: Paclitaxel; Paclitaxel is an intravenous infusion that is given once every week in 80 mg/m^2.

Outcome Measures

Primary Outcome Measures

1. Progression Free Survival (PFS) Per Investigator Assessment [4 weeks and thereafter every 6 weeks until disease progression or death up to 3.5 years]

   PFS was defined as the time from the date of randomization to the date of the event, defined as the first radiologically documented disease progression per RECIST v. 1.1 or death due to any cause. If a patient has not progressed or died at the analysis cut-off date or when the patient receives further anti-neoplastic therapy, PFS was censored on the date of the last adequate tumor assessment before the earlier of the cut-off date or start of the further anti-neoplastic therapy date.

Secondary Outcome Measures

1. Overall Survival (OS) [4 weeks and thereafter every 6 weeks until disease progression or death up to 3.5 years]

   Overall survival (OS) was defined as the time from date of randomization to date of death due to any cause. If a patient was not known to have died by the date of analysis cut-off, OS was censored at the date of last contact.

2. Overall Response Rate (ORR) as Per Local Radiological Assessment [4 weeks and thereafter every 6 weeks until disease progression or death up to 3.5 years]

   ORR: percentage of patients with best overall response of complete response (CR) or partial response (PR) according to RECIST v1.1. CR is defined as disappearance of all target lesions and any pathological lymph nodes must have a short axis of <10 mm and the disappearance of all non-target lesions). PR is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters or the persistence of 1 or more non-target lesions or lymph nodes identified as a site of disease at Baseline with a short axis of ≥10mm).

3. Time to Response (TTR) as Per Local Radiological Assessment [4 weeks and thereafter every 6 weeks until disease progression or death up to 3.5 years]

   TTR is the time from date of randomization until first documented response (CR or PR, which has to be confirmed subsequently) according to RECIST v1.1. CR is defined as disappearance of all target lesions and any pathological lymph nodes must have a short axis of <10 mm and the disappearance of all non-target lesions). PR is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters or the persistence of 1 or more non-target lesions or lymph nodes identified as a site of disease at Baseline with a short axis of ≥10mm).

4. Disease Control Rate (DCR) as Per Local Radiological Assessment [4 weeks and thereafter every 6 weeks until disease progression or death up to 3.5 years]

   DCR is the percentage of patients with a best overall response of CR, PR or stable disease (SD), according to RECIST v1.1. CR is defined as disappearance of all target lesions & any pathological lymph nodes must have a short axis of <10 mm & the disappearance of all non-target lesions). PR is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters or the persistence of 1 or more non-target lesions or lymph nodes identified as a site of disease at Baseline with a short axis of ≥10mm). SD is defined as neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD. PD is defined as at least a 20% increase in the sum of diameters of 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^2.

5. Duration of Response (DoR) as Per Local Investigator [4 weeks and thereafter every 6 weeks until disease progression or death up to 3.5 years]

   DoR is the time from the date of the first documented response (CR or PR, which had to be confirmed subsequently) to the date of the first radiologically documented disease progression or death due to disease according to RECIST v1.1 .

6. Health-related Quality of Life (HRQoL):Time to 10% Definitive Deterioration in the Global Health Status/Quality of Life Per EORTC-QLQ-C30 [Baseline, every 6 weeks starting from cycle 2 day 15 up to 3.5 years]

   A summary of EORTC-QLQ-C30 scores by time window. Time to deterioration is the number of days between the date of randomization and the date of the assessment at which definitive deterioration is seen. Definitive Deterioration in global health status and symptoms was defined as a decrease in the subscale score by at least 10% compared to baseline, with no later increase above this threshold observed during the course of the study. If a patient had not had an event prior to analysis cut-off or start of another anticancer therapy, time to deterioration was censored at the date of the last quality of life (QoL) evaluation.

7. Health-related Quality of Life (HRQoL):Time to 10% Definitive Deterioration in the Head and Neck Cancer Symptoms Scales for Pain, Speech Problems, Swallowing and Sense Problems Per EORTC-QLQ-HN35 [Baseline, every 6 weeks starting from cycle 2 day 15 up to 3.5 years]

   A summary of EORTC-QLQ-HN35 scores by time window. Time to deterioration is the number of days between the date of randomization and the date of the assessment at which definitive deterioration is seen. Definitive Deterioration in global health status and symptoms was defined as an increase in the subscale score of at least 10% compared to baseline, with no later decrease above this threshold observed during the course of the study. If a patient had not had an event prior to analysis cut-off or start of another anticancer therapy, time to deterioration was censored at the date of the last quality of life (QoL) evaluation.

8. Plasma Concentration-time Profiles of BKM120 Pharmacokinetics (PK) for AUC0-24 and AUClast [Time point(s) at which PK samples for Non-Compartmental analysis were collected were 0, 0.5,1,1.5, 2, 3, 4, 6, 9 and 24 hours at Cycle 1, Day 15]

   To Characterize PK of buparlisib given in combination with paclitaxel for AUC0-24 (area under plasma concentration-time curve from time 0 to end of dosing interval of 24 hours) & AUClast (AUC from time 0 to last measurable concentration sampling time).

9. Plasma Concentration-time Profiles of BKM120 Pharmacokinetics (PK) for Cmax [Time point(s) at which PK samples for Non-Compartmental analysis were collected were 0, 0.5,1,1.5, 2, 3, 4, 6, 9 and 24 hours at Cycle 1, Day 15]

   To characterize the pharmacokinetics of buparlisib given in combination with paclitaxel for Cmax.

10. Plasma Concentration-time Profiles of BKM120 Pharmacokinetics (PK) for Tmax [Time point(s) at which PK samples for Non-Compartmental analysis were collected were 0, 0.5,1,1.5, 2, 3, 4, 6, 9 and 24 hours at Cycle 1, Day 15]

    To characterize the pharmacokinetics of buparlisib given in combination with paclitaxel for Tmax.

11. Plasma Concentration-time Profiles of BKM120 Pharmacokinetics (PK) for CL/F [Time point(s) at which PK samples for Non-Compartmental analysis were collected were 0, 0.5,1,1.5, 2, 3, 4, 6, 9 and 24 hours at Cycle 1, Day 15]

    To characterize the pharmacokinetics of buparlisib given in combination with paclitaxel for CL/F.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patient has histologically/cytologically-confirmed HNSCC.

• Patient has archival or fresh tumor tissue for the analysis of PI3K-related biomarkers. One tumor block (preferred) or a minimum of 12 unstained slides to be provided. Enrollment in the study is contingent on confirmation of an adequate amount of tumor tissue.

• Patients with recurrent or metastatic disease resistant to platinum-based chemotherapy (defined as progression while on platinum-based chemotherapy given in the recurrent/metastatic setting). Pretreatment with cetuximab is allowed

• Measurable disease as determined by per RECIST criteria v1.1. If the only site of measurable disease is a previously irradiated lesion, documented progression of disease and a 4 week period since radiotherapy completion is required

• Adequate bone marrow function and organ function

• ECOG Performance Status ≤ 1

Exclusion Criteria:

• Patient has received previous treatment with any AKT, mTOR inhibitors or PI3K pathway inhibitors;

• Patient treated with more than one prior chemotherapy regimen for recurrent/metastatic disease

• Patient has symptomatic CNS metastases. Patients with asymptomatic CNS metastases may participate in this trial. The patient must have completed any prior local treatment for CNS metastases ≥ 28 days prior to the start of study treatment (including radiotherapy and/or surgery) and must have stable low dose of corticosteroid therapy;

• Patient has not recovered to ≤ grade 1 (except alopecia) from related side effects of any prior antineoplastic therapy

• Patient has any of the following cardiac abnormalities:symptomatic congestive heart failure, history of documented congestive heart failure (New York Heart Association functional classification III-IV), documented cardiomyopathy, Left Ventricular Ejection Fraction (LVEF) <50% as determined by Multiple Gated acquisition (MUGA) scan or echocardiogram (ECHO); myocardial infarction ≤ 6 months prior to enrolment, unstable angina pectoris, serious uncontrolled cardiac arrhythmia, symptomatic pericarditis, QTcF > 480 msec on the screening ECG (using the QTcF formula);

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Highlands Oncology Group	Fayetteville	Arkansas	United States	72703
2	Dana Farber Cancer Institute IRB	Boston	Massachusetts	United States	02215
3	Washington U School of Medicine Center for Clinical Studies SC - BKM120H2201	Saint Louis	Missouri	United States	63110
4	The Mount Sinai Hospital Dept of Oncology	New York	New York	United States	10029
5	University of N.C. at Chapel Hill Lineberger Comp. Cancer Ctr.	Chapel Hill	North Carolina	United States	27599-7600
6	University Hospitals Case Medical Center Univ. Hospitals of Cleveland	Cleveland	Ohio	United States	44106
7	UPMC Cancer Centers BKM120H2201	Pittsburgh	Pennsylvania	United States	15232
8	Novartis Investigative Site	St Leonards	New South Wales	Australia	2065
9	Novartis Investigative Site	Hamilton	Ontario	Canada	L8V 5C2
10	Novartis Investigative Site	Montreal	Quebec	Canada	H2L 4M1
11	Novartis Investigative Site	Saint Herblain cedex		France	44805
12	Novartis Investigative Site	Berlin		Germany	12203
13	Novartis Investigative Site	Essen		Germany	45147
14	Novartis Investigative Site	Hannover		Germany	30625
15	Novartis Investigative Site	Budapest		Hungary	1082
16	Novartis Investigative Site	Budapest		Hungary	H-1115
17	Novartis Investigative Site	Budapest		Hungary	H-1122
18	Novartis Investigative Site	Nyiregyhaza		Hungary	4400
19	Novartis Investigative Site	Nashik	Maharashtra	India	422 004
20	Novartis Investigative Site	Dehli	New Delhi	India	110005
21	Novartis Investigative Site	Jaipur	Rajasthan	India	302017
22	Novartis Investigative Site	Kolkata	West Bengal	India	700160
23	Novartis Investigative Site	Kerala		India	695 011
24	Novartis Investigative Site	Mumbai		India	400 012
25	Novartis Investigative Site	Dublin 4		Ireland
26	Novartis Investigative Site	Firenze	FI	Italy	50134
27	Novartis Investigative Site	Milano	MI	Italy	20133
28	Novartis Investigative Site	Milano	MI	Italy	20141
29	Novartis Investigative Site	Milano	MI	Italy	20142
30	Novartis Investigative Site	Palermo	PA	Italy	90127
31	Novartis Investigative Site	Roma	RM	Italy	00168
32	Novartis Investigative Site	Salerno	SA	Italy	84131
33	Novartis Investigative Site	Torino	TO	Italy	10126
34	Novartis Investigative Site	Venezia	VE	Italy	30174
35	Novartis Investigative Site	Kashiwa	Chiba	Japan	277-8577
36	Novartis Investigative Site	Koto-ku	Tokyo	Japan	135 8550
37	Novartis Investigative Site	Minato-ku	Tokyo	Japan	105-8471
38	Novartis Investigative Site	Seoul	Korea	Korea, Republic of	05505
39	Novartis Investigative Site	Seoul	Seocho-gu	Korea, Republic of	06591
40	Novartis Investigative Site	Warszawa		Poland	02-781
41	Novartis Investigative Site	Leningrad Region	Russia	Russian Federation	188663
42	Novartis Investigative Site	Nizhniy Novgorod		Russian Federation
43	Novartis Investigative Site	St. Petersburg		Russian Federation	197758
44	Novartis Investigative Site	Barcelona	Catalunya	Spain	08035
45	Novartis Investigative Site	Hospitalet de LLobregat	Catalunya	Spain	08907
46	Novartis Investigative Site	Madrid		Spain	28034
47	Novartis Investigative Site	Basel		Switzerland	4031
48	Novartis Investigative Site	Genève		Switzerland	1211
49	Novartis Investigative Site	Tainan	Taiwan ROC	Taiwan	70421
50	Novartis Investigative Site	Kaohsiung City		Taiwan	83301
51	Novartis Investigative Site	Taichung City		Taiwan	407
52	Novartis Investigative Site	Songkla	Hat Yai	Thailand	90110
53	Novartis Investigative Site	Bangkok		Thailand	10330
54	Novartis Investigative Site	Bangkok		Thailand	10700
55	Novartis Investigative Site	Glasgow	Scotland	United Kingdom	G12 0YN
56	Novartis Investigative Site	London		United Kingdom	NW1 2PJ
57	Novartis Investigative Site	London		United Kingdom	SE1 9RT
58	Novartis Investigative Site	Manchester		United Kingdom	M20 9BX

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

• Statistical Analysis Plan - Apr 22, 2016
• Study Protocol - Aug 30, 2016

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01852292
• Other Study ID Numbers: CBKM120H2201; 2013-000744-26
• First Posted: May 13, 2013
• Last Update Posted: Jul 24, 2018
• Last Verified: Jun 1, 2018

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Novartis Pharmaceuticals: platinum pre-treated recurrent or metastatic; Head and neck squamous cell carcinoma; recurrent; metastatic; BKM120
• Additional relevant MeSH terms: Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Paclitaxel

Study Results

Participant Flow

Recruitment Details	Planned: 150; Analyzed: 158. Patients were randomized to receive treatment with buparlisib 100 mg daily (n=79) or placebo (n=79) in combination with paclitaxel.
Pre-assignment Detail	158 patients randomized in a 1:1 ratio to treatment with buparlisib plus paclitaxel or placebo plus paclitaxel; stratification: number of prior lines of treatment in the recurrent/metastatic setting (1 vs.2) & region of Investigator site (North America vs. Rest of the World). In this study, Not Completed = Discontinued study treatment per Protocol

Arm/Group Title	Buparlisib + Weekly Paclitaxel	Buparlisib Matching Placebo + Paclitaxel
Arm/Group Description	Patients who were randomized to this arm on a 1:1 randomization, took buparlisib 100 mg daily and weekly paclitaxel.	Patients who were randomized to this arm on a 1:1 randomization, took buparlisib matching placebo 100 mg daily and weekly paclitaxel.
Period Title: Overall Study
STARTED	79	79
COMPLETED	0	0
NOT COMPLETED	79	79

Baseline Characteristics

Arm/Group Title	Buparlisib + Paclitaxel	Buparlisib Matching Placebo + Paclitaxel	Total
Arm/Group Description	Patients who were randomized to this arm on a 1:1 randomization, took buparlisib 100 mg daily and paclitaxel 80 mg/m^2 weekly.	Patients who were randomized to this arm on a 1:1 randomization, took buparlisib matching placebo 100 mg daily and paclitaxel 80 mg/m^2 weekly.	Total of all reporting groups
Overall Participants	79	79	158
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	58.0 (9.44)	58.2 (9.44)	58.1 (9.41)
Sex: Female, Male (Count of Participants)
Female	14 17.7%	11 13.9%	25 15.8%
Male	65 82.3%	68 86.1%	133 84.2%
Race/Ethnicity, Customized (Count of Participants)
Hispanic or Latino	3 3.8%	0 0%	3 1.9%
East Asian	12 15.2%	9 11.4%	21 13.3%
Southeast Asian	4 5.1%	9 11.4%	13 8.2%
South Asian	6 7.6%	5 6.3%	11 7%
Russian	7 8.9%	4 5.1%	11 7%
Mixed ethnicity	1 1.3%	2 2.5%	3 1.9%
Not reported	13 16.5%	10 12.7%	23 14.6%
Unknown	3 3.8%	6 7.6%	9 5.7%
Other	30 38%	34 43%	64 40.5%

Outcome Measures

1. Primary Outcome

Title	Progression Free Survival (PFS) Per Investigator Assessment
Description	PFS was defined as the time from the date of randomization to the date of the event, defined as the first radiologically documented disease progression per RECIST v. 1.1 or death due to any cause. If a patient has not progressed or died at the analysis cut-off date or when the patient receives further anti-neoplastic therapy, PFS was censored on the date of the last adequate tumor assessment before the earlier of the cut-off date or start of the further anti-neoplastic therapy date.
Time Frame	4 weeks and thereafter every 6 weeks until disease progression or death up to 3.5 years

Outcome Measure Data

Analysis Population Description

The Full analysis set (FAS) includes all patients who were randomized to study treatment.

Arm/Group Title	Buparlisib + Paclitaxel	Buparlisib Matching Placebo + Paclitaxel
Arm/Group Description	Patients who were randomized to this arm on a 1:1 randomization, took buparlisib 100 mg daily and paclitaxel 80 mg/m^2 weekly.	Patients who were randomized to this arm on a 1:1 randomization, took buparlisib matching placebo 100 mg daily and paclitaxel 80 mg/m^2 weekly.
Measure Participants	79	79
Median (95% Confidence Interval) [months]	4.63	3.45

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Buparlisib + Paclitaxel, Buparlisib Matching Placebo + Paclitaxel
	Comments
	Type of Statistical Test	Other
	Comments	Double Criteria for PFS
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	0.646
	Confidence Interval	(2-Sided) 95%; 0.44 to 0.94
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Overall Survival (OS)
Description	Overall survival (OS) was defined as the time from date of randomization to date of death due to any cause. If a patient was not known to have died by the date of analysis cut-off, OS was censored at the date of last contact.
Time Frame	4 weeks and thereafter every 6 weeks until disease progression or death up to 3.5 years

Outcome Measure Data

Analysis Population Description

The Full analysis set (FAS) includes all patients who were randomized to study treatment.

Arm/Group Title	Buparlisib + Paclitaxel	Buparlisib Matching Placebo + Paclitaxel
Arm/Group Description	Patients who were randomized to this arm on a 1:1 randomization, took buparlisib 100 mg daily and paclitaxel 80 mg/m^2 weekly.	Patients who were randomized to this arm on a 1:1 randomization, took buparlisib matching placebo 100 mg daily and paclitaxel 80 mg/m^2 weekly.
Measure Participants	79	79
Median (95% Confidence Interval) [months]	10.41	6.54

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Buparlisib + Paclitaxel, Buparlisib Matching Placebo + Paclitaxel
	Comments
	Type of Statistical Test	Other
	Comments	Double criteria for OS
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	0.72
	Confidence Interval	(2-Sided) 95%; 0.49 to 1.04
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Overall Response Rate (ORR) as Per Local Radiological Assessment
Description	ORR: percentage of patients with best overall response of complete response (CR) or partial response (PR) according to RECIST v1.1. CR is defined as disappearance of all target lesions and any pathological lymph nodes must have a short axis of <10 mm and the disappearance of all non-target lesions). PR is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters or the persistence of 1 or more non-target lesions or lymph nodes identified as a site of disease at Baseline with a short axis of ≥10mm).
Time Frame	4 weeks and thereafter every 6 weeks until disease progression or death up to 3.5 years

Outcome Measure Data

Analysis Population Description

The Full analysis set (FAS) includes all patients who were randomized to study treatment.

Arm/Group Title	Buparlisib + Paclitaxel	Buparlisib Matching Placebo + Paclitaxel
Arm/Group Description	Patients who were randomized to this arm on a 1:1 randomization, took buparlisib 100 mg daily and paclitaxel 80 mg/m^2 weekly.	Patients who were randomized to this arm on a 1:1 randomization, took buparlisib matching placebo 100 mg daily and paclitaxel 80 mg/m^2 weekly.
Measure Participants	79	79
Median (95% Confidence Interval) [Percentage of participants]	39.2 49.6%	13.9 17.6%

4. Secondary Outcome

Title	Time to Response (TTR) as Per Local Radiological Assessment
Description	TTR is the time from date of randomization until first documented response (CR or PR, which has to be confirmed subsequently) according to RECIST v1.1. CR is defined as disappearance of all target lesions and any pathological lymph nodes must have a short axis of <10 mm and the disappearance of all non-target lesions). PR is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters or the persistence of 1 or more non-target lesions or lymph nodes identified as a site of disease at Baseline with a short axis of ≥10mm).
Time Frame	4 weeks and thereafter every 6 weeks until disease progression or death up to 3.5 years

Outcome Measure Data

Analysis Population Description

The Full analysis set (FAS) includes all patients who were randomized to study treatment.

Arm/Group Title	Buparlisib + Paclitaxel	Buparlisib Matching Placebo + Paclitaxel
Arm/Group Description	Patients who were randomized to this arm on a 1:1 randomization, took buparlisib 100 mg daily and paclitaxel 80 mg/m^2 weekly.	Patients who were randomized to this arm on a 1:1 randomization, took buparlisib matching placebo 100 mg daily and paclitaxel 80 mg/m^2 weekly.
Measure Participants	79	79
Median (Full Range) [months]	1.02	0.99

5. Secondary Outcome

Title	Disease Control Rate (DCR) as Per Local Radiological Assessment
Description	DCR is the percentage of patients with a best overall response of CR, PR or stable disease (SD), according to RECIST v1.1. CR is defined as disappearance of all target lesions & any pathological lymph nodes must have a short axis of <10 mm & the disappearance of all non-target lesions). PR is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters or the persistence of 1 or more non-target lesions or lymph nodes identified as a site of disease at Baseline with a short axis of ≥10mm). SD is defined as neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD. PD is defined as at least a 20% increase in the sum of diameters of 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^2.
Time Frame	4 weeks and thereafter every 6 weeks until disease progression or death up to 3.5 years

Outcome Measure Data

Analysis Population Description

The Full analysis set (FAS) includes all patients who were randomized to study treatment.

Arm/Group Title	Buparlisib + Paclitaxel	Buparlisib Matching Placebo + Paclitaxel
Arm/Group Description	Patients who were randomized to this arm on a 1:1 randomization, took buparlisib 100 mg daily and paclitaxel 80 mg/m^2 weekly.	Patients who were randomized to this arm on a 1:1 randomization, took buparlisib matching placebo 100 mg daily and paclitaxel 80 mg/m^2 weekly.
Measure Participants	79	79
Number (95% Confidence Interval) [Percentage of participants]	72.2 91.4%	69.6 88.1%

6. Secondary Outcome

Title	Duration of Response (DoR) as Per Local Investigator
Description	DoR is the time from the date of the first documented response (CR or PR, which had to be confirmed subsequently) to the date of the first radiologically documented disease progression or death due to disease according to RECIST v1.1 .
Time Frame	4 weeks and thereafter every 6 weeks until disease progression or death up to 3.5 years

Outcome Measure Data

Analysis Population Description

The Full analysis set (FAS) includes all patients who were randomized to study treatment.

Arm/Group Title	Buparlisib + Paclitaxel	Buparlisib Matching Placebo + Paclitaxel
Arm/Group Description	Patients who were randomized to this arm on a 1:1 randomization, took buparlisib 100 mg daily and paclitaxel 80 mg/m^2 weekly.	Patients who were randomized to this arm on a 1:1 randomization, took buparlisib matching placebo 100 mg daily and paclitaxel 80 mg/m^2 weekly.
Measure Participants	79	79
Median (Full Range) [months]	3.06	4.17

7. Secondary Outcome

Title	Health-related Quality of Life (HRQoL):Time to 10% Definitive Deterioration in the Global Health Status/Quality of Life Per EORTC-QLQ-C30
Description	A summary of EORTC-QLQ-C30 scores by time window. Time to deterioration is the number of days between the date of randomization and the date of the assessment at which definitive deterioration is seen. Definitive Deterioration in global health status and symptoms was defined as a decrease in the subscale score by at least 10% compared to baseline, with no later increase above this threshold observed during the course of the study. If a patient had not had an event prior to analysis cut-off or start of another anticancer therapy, time to deterioration was censored at the date of the last quality of life (QoL) evaluation.
Time Frame	Baseline, every 6 weeks starting from cycle 2 day 15 up to 3.5 years

Outcome Measure Data

Analysis Population Description

The Full analysis set (FAS) includes all patients who were randomized to study treatment.

Arm/Group Title	Buparlisib + Paclitaxel	Buparlisib Matching Placebo + Paclitaxel
Arm/Group Description	Patients who were randomized to this arm on a 1:1 randomization, took buparlisib 100 mg daily and paclitaxel 80 mg/m^2 weekly.	Patients who were randomized to this arm on a 1:1 randomization, took buparlisib matching placebo 100 mg daily and paclitaxel 80 mg/m^2 weekly.
Measure Participants	79	79
Median (95% Confidence Interval) [months]	3.0	3.5

8. Secondary Outcome

Title	Health-related Quality of Life (HRQoL):Time to 10% Definitive Deterioration in the Head and Neck Cancer Symptoms Scales for Pain, Speech Problems, Swallowing and Sense Problems Per EORTC-QLQ-HN35
Description	A summary of EORTC-QLQ-HN35 scores by time window. Time to deterioration is the number of days between the date of randomization and the date of the assessment at which definitive deterioration is seen. Definitive Deterioration in global health status and symptoms was defined as an increase in the subscale score of at least 10% compared to baseline, with no later decrease above this threshold observed during the course of the study. If a patient had not had an event prior to analysis cut-off or start of another anticancer therapy, time to deterioration was censored at the date of the last quality of life (QoL) evaluation.
Time Frame	Baseline, every 6 weeks starting from cycle 2 day 15 up to 3.5 years

Outcome Measure Data

Analysis Population Description

The Full analysis set (FAS) includes all patients who were randomized to study treatment.

Arm/Group Title	Buparlisib + Paclitaxel	Buparlisib Matching Placebo + Paclitaxel
Arm/Group Description	Patients who were randomized to this arm on a 1:1 randomization, took buparlisib 100 mg daily and paclitaxel 80 mg/m^2 weekly.	Patients who were randomized to this arm on a 1:1 randomization, took buparlisib matching placebo 100 mg daily and paclitaxel 80 mg/m^2 weekly.
Measure Participants	79	79
Pain Subscale	5.8	5.3
Speech problems	5.6	4.2
Swallowing	5.1	4.6
Sense Problems	5.1	4.6

9. Secondary Outcome

Title	Plasma Concentration-time Profiles of BKM120 Pharmacokinetics (PK) for AUC0-24 and AUClast
Description	To Characterize PK of buparlisib given in combination with paclitaxel for AUC0-24 (area under plasma concentration-time curve from time 0 to end of dosing interval of 24 hours) & AUClast (AUC from time 0 to last measurable concentration sampling time).
Time Frame	Time point(s) at which PK samples for Non-Compartmental analysis were collected were 0, 0.5,1,1.5, 2, 3, 4, 6, 9 and 24 hours at Cycle 1, Day 15

Outcome Measure Data

Analysis Population Description

Full Sampling Pharmacokinetic Analysis Set (FPAS): All pts in PAS who received planned dose of buparlisib every day for last consecutive 7 days before full PK profile assessment on C1D15, didn't vomit within 4 hours of buparlisib dosing, had at least 1 dose of paclitaxel before collection of PK sample for PK profile & had evaluable full PK profile

Arm/Group Title	Buparlisib + Paclitaxel
Arm/Group Description	Patients who were randomized to this arm on a 1:1 randomization, took buparlisib 100 mg daily and paclitaxel 80 mg/m^2 weekly.
Measure Participants	79
AUC0-24 (n = 4)	25628.56
AUClast (n = 4)	25734.33

10. Secondary Outcome

Title	Plasma Concentration-time Profiles of BKM120 Pharmacokinetics (PK) for Cmax
Description	To characterize the pharmacokinetics of buparlisib given in combination with paclitaxel for Cmax.
Time Frame	Time point(s) at which PK samples for Non-Compartmental analysis were collected were 0, 0.5,1,1.5, 2, 3, 4, 6, 9 and 24 hours at Cycle 1, Day 15

Outcome Measure Data

Analysis Population Description

Full Sampling Pharmacokinetic Analysis Set (FPAS): All pts in PAS who received planned dose of buparlisib every day for last consecutive 7 days before full PK profile assessment on C1D15, didn't vomit within 4 hours of buparlisib dosing, had at least 1 dose of paclitaxel before collection of PK sample for PK profile & had evaluable full PK profile

Arm/Group Title	Buparlisib + Paclitaxel
Arm/Group Description	Patients who were randomized to this arm on a 1:1 randomization, took buparlisib 100 mg daily and paclitaxel 80 mg/m^2 weekly.
Measure Participants	79
Median (Full Range) [ng/mL]	1775.00

11. Secondary Outcome

Title	Plasma Concentration-time Profiles of BKM120 Pharmacokinetics (PK) for Tmax
Description	To characterize the pharmacokinetics of buparlisib given in combination with paclitaxel for Tmax.
Time Frame	Time point(s) at which PK samples for Non-Compartmental analysis were collected were 0, 0.5,1,1.5, 2, 3, 4, 6, 9 and 24 hours at Cycle 1, Day 15

Outcome Measure Data

Analysis Population Description

Full Sampling Pharmacokinetic Analysis Set (FPAS): All pts in PAS who received planned dose of buparlisib every day for last consecutive 7 days before full PK profile assessment on C1D15, didn't vomit within 4 hours of buparlisib dosing, had at least 1 dose of paclitaxel before collection of PK sample for PK profile & had evaluable full PK profile

Arm/Group Title	Buparlisib + Paclitaxel
Arm/Group Description	Patients who were randomized to this arm on a 1:1 randomization, took buparlisib 100 mg daily and paclitaxel 80 mg/m^2 weekly.
Measure Participants	79
Median (Full Range) [hour (hr)]	2.42

12. Secondary Outcome

Title	Plasma Concentration-time Profiles of BKM120 Pharmacokinetics (PK) for CL/F
Description	To characterize the pharmacokinetics of buparlisib given in combination with paclitaxel for CL/F.
Time Frame	Time point(s) at which PK samples for Non-Compartmental analysis were collected were 0, 0.5,1,1.5, 2, 3, 4, 6, 9 and 24 hours at Cycle 1, Day 15

Outcome Measure Data

Analysis Population Description

Full Sampling Pharmacokinetic Analysis Set (FPAS): All pts in PAS who received planned dose of buparlisib every day for last consecutive 7 days before full PK profile assessment on C1D15, didn't vomit within 4 hours of buparlisib dosing, had at least 1 dose of paclitaxel before collection of PK sample for PK profile & had evaluable full PK profile

Arm/Group Title	Buparlisib + Paclitaxel
Arm/Group Description	Patients who were randomized to this arm on a 1:1 randomization, took buparlisib 100 mg daily and paclitaxel 80 mg/m^2 weekly.
Measure Participants	79
Median (Full Range) [L/hr]	4.14

Adverse Events

Time Frame	Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to approximately 3.5 years.
Adverse Event Reporting Description	AEs, SAEs based on Safety Set: all pts who received at least 1 dose of study trtmnt & had at least 1 post-baseline safety assessment. Pts analyzed according to study trtmnt actually received, defined as trtmnt pt received on 1st day of study trtmnt
Arm/Group Title	Buparlisib + Paclitaxel		Buparlisib Matching Placebo + Paclitaxel
Arm/Group Description	Patients who were randomized to this arm on a 1:1 randomization, took buparlisib 100 mg daily and paclitaxel 80 mg/m^2 weekly.		Patients who were randomized to this arm on a 1:1 randomization, took buparlisib matching placebo 100 mg daily and paclitaxel 80 mg/m^2 weekly.
All Cause Mortality
	Buparlisib + Paclitaxel		Buparlisib Matching Placebo + Paclitaxel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	16/76 (21.1%)		17/78 (21.8%)
Serious Adverse Events
	Buparlisib + Paclitaxel		Buparlisib Matching Placebo + Paclitaxel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	43/76 (56.6%)		37/78 (47.4%)
Blood and lymphatic system disorders
Anaemia	3/76 (3.9%)		3/78 (3.8%)
Febrile neutropenia	1/76 (1.3%)		1/78 (1.3%)
Leukopenia	1/76 (1.3%)		0/78 (0%)
Neutropenia	2/76 (2.6%)		0/78 (0%)
Thrombocytopenia	1/76 (1.3%)		0/78 (0%)
Cardiac disorders
Cardiac arrest	1/76 (1.3%)		1/78 (1.3%)
Sinus bradycardia	0/76 (0%)		1/78 (1.3%)
Endocrine disorders
Hypercalcaemia of malignancy	0/76 (0%)		1/78 (1.3%)
Eye disorders
Blindness	0/76 (0%)		1/78 (1.3%)
Gastrointestinal disorders
Abdominal pain	2/76 (2.6%)		1/78 (1.3%)
Aorto-oesophageal fistula	1/76 (1.3%)		0/78 (0%)
Diarrhoea	4/76 (5.3%)		0/78 (0%)
Dysphagia	2/76 (2.6%)		3/78 (3.8%)
Gastrointestinal haemorrhage	1/76 (1.3%)		0/78 (0%)
Mouth haemorrhage	0/76 (0%)		2/78 (2.6%)
Nausea	1/76 (1.3%)		0/78 (0%)
Oesophageal obstruction	0/76 (0%)		1/78 (1.3%)
Oesophagitis	1/76 (1.3%)		0/78 (0%)
Oral cavity fistula	1/76 (1.3%)		0/78 (0%)
Stomatitis	1/76 (1.3%)		0/78 (0%)
Upper gastrointestinal haemorrhage	1/76 (1.3%)		0/78 (0%)
Vomiting	2/76 (2.6%)		0/78 (0%)
General disorders
Asthenia	2/76 (2.6%)		2/78 (2.6%)
Face oedema	0/76 (0%)		2/78 (2.6%)
Fatigue	1/76 (1.3%)		4/78 (5.1%)
General physical health deterioration	3/76 (3.9%)		0/78 (0%)
Non-cardiac chest pain	1/76 (1.3%)		2/78 (2.6%)
Pain	0/76 (0%)		1/78 (1.3%)
Pyrexia	0/76 (0%)		2/78 (2.6%)
Systemic inflammatory response syndrome	0/76 (0%)		1/78 (1.3%)
Hepatobiliary disorders
Hepatic failure	1/76 (1.3%)		0/78 (0%)
Jaundice	1/76 (1.3%)		0/78 (0%)
Infections and infestations
Anal abscess	2/76 (2.6%)		0/78 (0%)
Bronchitis	1/76 (1.3%)		2/78 (2.6%)
Candida sepsis	1/76 (1.3%)		0/78 (0%)
Chest wall abscess	0/76 (0%)		1/78 (1.3%)
Clostridium difficile colitis	1/76 (1.3%)		0/78 (0%)
Erysipelas	0/76 (0%)		1/78 (1.3%)
Herpes zoster	1/76 (1.3%)		0/78 (0%)
Lower respiratory tract infection	0/76 (0%)		1/78 (1.3%)
Lung abscess	1/76 (1.3%)		1/78 (1.3%)
Lung infection	2/76 (2.6%)		0/78 (0%)
Pneumonia	6/76 (7.9%)		6/78 (7.7%)
Post procedural infection	1/76 (1.3%)		0/78 (0%)
Pulmonary tuberculosis	1/76 (1.3%)		0/78 (0%)
Respiratory tract infection	1/76 (1.3%)		0/78 (0%)
Sepsis	0/76 (0%)		1/78 (1.3%)
Septic shock	3/76 (3.9%)		1/78 (1.3%)
Urinary tract infection	1/76 (1.3%)		0/78 (0%)
Wound infection	2/76 (2.6%)		0/78 (0%)
Injury, poisoning and procedural complications
Femur fracture	0/76 (0%)		1/78 (1.3%)
Post procedural discharge	1/76 (1.3%)		0/78 (0%)
Post procedural fistula	0/76 (0%)		1/78 (1.3%)
Post procedural haemorrhage	0/76 (0%)		1/78 (1.3%)
Spinal compression fracture	0/76 (0%)		1/78 (1.3%)
Investigations
Blood creatinine increased	1/76 (1.3%)		0/78 (0%)
Neutrophil count decreased	1/76 (1.3%)		0/78 (0%)
Metabolism and nutrition disorders
Cachexia	1/76 (1.3%)		3/78 (3.8%)
Decreased appetite	3/76 (3.9%)		2/78 (2.6%)
Dehydration	2/76 (2.6%)		1/78 (1.3%)
Hypercalcaemia	1/76 (1.3%)		1/78 (1.3%)
Hyperglycaemia	3/76 (3.9%)		0/78 (0%)
Hypocalcaemia	1/76 (1.3%)		0/78 (0%)
Hypoglycaemia	1/76 (1.3%)		0/78 (0%)
Hypokalaemia	1/76 (1.3%)		2/78 (2.6%)
Hypomagnesaemia	1/76 (1.3%)		0/78 (0%)
Musculoskeletal and connective tissue disorders
Spinal pain	1/76 (1.3%)		0/78 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain	0/76 (0%)		1/78 (1.3%)
Malignant neoplasm progression	0/76 (0%)		1/78 (1.3%)
Tumour haemorrhage	3/76 (3.9%)		5/78 (6.4%)
Tumour invasion	0/76 (0%)		1/78 (1.3%)
Nervous system disorders
Dizziness	0/76 (0%)		1/78 (1.3%)
Hypoaesthesia	1/76 (1.3%)		0/78 (0%)
Intracranial pressure increased	0/76 (0%)		1/78 (1.3%)
Ischaemic cerebral infarction	1/76 (1.3%)		0/78 (0%)
Neuralgia	1/76 (1.3%)		0/78 (0%)
Paraplegia	1/76 (1.3%)		0/78 (0%)
Somnolence	1/76 (1.3%)		0/78 (0%)
Spinal cord compression	1/76 (1.3%)		0/78 (0%)
Syncope	1/76 (1.3%)		2/78 (2.6%)
Product Issues
Device connection issue	1/76 (1.3%)		0/78 (0%)
Psychiatric disorders
Acute psychosis	0/76 (0%)		1/78 (1.3%)
Aggression	1/76 (1.3%)		0/78 (0%)
Completed suicide	1/76 (1.3%)		0/78 (0%)
Mental status changes	1/76 (1.3%)		0/78 (0%)
Renal and urinary disorders
Renal failure	1/76 (1.3%)		0/78 (0%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	0/76 (0%)		2/78 (2.6%)
Dyspnoea	2/76 (2.6%)		2/78 (2.6%)
Haemoptysis	1/76 (1.3%)		1/78 (1.3%)
Pneumonia aspiration	1/76 (1.3%)		0/78 (0%)
Pneumonitis	1/76 (1.3%)		0/78 (0%)
Pneumothorax	1/76 (1.3%)		2/78 (2.6%)
Pulmonary embolism	1/76 (1.3%)		0/78 (0%)
Respiratory arrest	1/76 (1.3%)		1/78 (1.3%)
Respiratory failure	1/76 (1.3%)		2/78 (2.6%)
Upper airway obstruction	1/76 (1.3%)		0/78 (0%)
Skin and subcutaneous tissue disorders
Erythema	1/76 (1.3%)		0/78 (0%)
Vascular disorders
Arterial rupture	1/76 (1.3%)		0/78 (0%)
Hypotension	1/76 (1.3%)		1/78 (1.3%)
Phlebitis	1/76 (1.3%)		0/78 (0%)
Other (Not Including Serious) Adverse Events
	Buparlisib + Paclitaxel		Buparlisib Matching Placebo + Paclitaxel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	76/76 (100%)		75/78 (96.2%)
Blood and lymphatic system disorders
Anaemia	29/76 (38.2%)		32/78 (41%)
Leukopenia	7/76 (9.2%)		13/78 (16.7%)
Neutropenia	23/76 (30.3%)		10/78 (12.8%)
Gastrointestinal disorders
Abdominal pain	7/76 (9.2%)		2/78 (2.6%)
Constipation	14/76 (18.4%)		8/78 (10.3%)
Diarrhoea	26/76 (34.2%)		13/78 (16.7%)
Dyspepsia	4/76 (5.3%)		2/78 (2.6%)
Dysphagia	9/76 (11.8%)		5/78 (6.4%)
Nausea	19/76 (25%)		13/78 (16.7%)
Odynophagia	4/76 (5.3%)		1/78 (1.3%)
Oral pain	4/76 (5.3%)		1/78 (1.3%)
Stomatitis	23/76 (30.3%)		10/78 (12.8%)
Vomiting	19/76 (25%)		11/78 (14.1%)
General disorders
Asthenia	20/76 (26.3%)		15/78 (19.2%)
Face oedema	2/76 (2.6%)		4/78 (5.1%)
Fatigue	31/76 (40.8%)		16/78 (20.5%)
Non-cardiac chest pain	2/76 (2.6%)		4/78 (5.1%)
Oedema peripheral	5/76 (6.6%)		10/78 (12.8%)
Pyrexia	12/76 (15.8%)		16/78 (20.5%)
Infections and infestations
Nasopharyngitis	4/76 (5.3%)		4/78 (5.1%)
Pneumonia	2/76 (2.6%)		6/78 (7.7%)
Respiratory tract infection	5/76 (6.6%)		2/78 (2.6%)
Upper respiratory tract infection	1/76 (1.3%)		4/78 (5.1%)
Investigations
Alanine aminotransferase increased	6/76 (7.9%)		4/78 (5.1%)
Aspartate aminotransferase increased	6/76 (7.9%)		7/78 (9%)
Blood alkaline phosphatase increased	6/76 (7.9%)		1/78 (1.3%)
Blood creatinine increased	4/76 (5.3%)		1/78 (1.3%)
Blood glucose increased	3/76 (3.9%)		4/78 (5.1%)
Blood lactate dehydrogenase increased	5/76 (6.6%)		5/78 (6.4%)
Gamma-glutamyltransferase increased	8/76 (10.5%)		7/78 (9%)
Neutrophil count decreased	5/76 (6.6%)		4/78 (5.1%)
Weight decreased	19/76 (25%)		9/78 (11.5%)
White blood cell count decreased	7/76 (9.2%)		3/78 (3.8%)
Metabolism and nutrition disorders
Decreased appetite	23/76 (30.3%)		14/78 (17.9%)
Hyperglycaemia	47/76 (61.8%)		27/78 (34.6%)
Hyperkalaemia	2/76 (2.6%)		8/78 (10.3%)
Hypoalbuminaemia	4/76 (5.3%)		3/78 (3.8%)
Hypocalcaemia	5/76 (6.6%)		4/78 (5.1%)
Hypokalaemia	7/76 (9.2%)		3/78 (3.8%)
Hypomagnesaemia	4/76 (5.3%)		6/78 (7.7%)
Hyponatraemia	5/76 (6.6%)		6/78 (7.7%)
Hypophosphataemia	3/76 (3.9%)		5/78 (6.4%)
Musculoskeletal and connective tissue disorders
Back pain	0/76 (0%)		6/78 (7.7%)
Muscle spasms	4/76 (5.3%)		3/78 (3.8%)
Muscular weakness	0/76 (0%)		5/78 (6.4%)
Musculoskeletal pain	5/76 (6.6%)		2/78 (2.6%)
Myalgia	4/76 (5.3%)		1/78 (1.3%)
Neck pain	6/76 (7.9%)		7/78 (9%)
Pain in extremity	1/76 (1.3%)		5/78 (6.4%)
Pain in jaw	5/76 (6.6%)		1/78 (1.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain	5/76 (6.6%)		2/78 (2.6%)
Nervous system disorders
Dizziness	6/76 (7.9%)		6/78 (7.7%)
Dysgeusia	4/76 (5.3%)		1/78 (1.3%)
Headache	14/76 (18.4%)		6/78 (7.7%)
Neuropathy peripheral	6/76 (7.9%)		18/78 (23.1%)
Paraesthesia	8/76 (10.5%)		9/78 (11.5%)
Peripheral sensory neuropathy	6/76 (7.9%)		3/78 (3.8%)
Psychiatric disorders
Anxiety	13/76 (17.1%)		9/78 (11.5%)
Depression	13/76 (17.1%)		7/78 (9%)
Insomnia	10/76 (13.2%)		6/78 (7.7%)
Mood altered	4/76 (5.3%)		5/78 (6.4%)
Respiratory, thoracic and mediastinal disorders
Catarrh	1/76 (1.3%)		4/78 (5.1%)
Cough	17/76 (22.4%)		18/78 (23.1%)
Dysphonia	3/76 (3.9%)		4/78 (5.1%)
Dyspnoea	8/76 (10.5%)		13/78 (16.7%)
Epistaxis	7/76 (9.2%)		4/78 (5.1%)
Haemoptysis	1/76 (1.3%)		7/78 (9%)
Hiccups	5/76 (6.6%)		3/78 (3.8%)
Oropharyngeal pain	5/76 (6.6%)		6/78 (7.7%)
Pneumonitis	4/76 (5.3%)		3/78 (3.8%)
Productive cough	4/76 (5.3%)		3/78 (3.8%)
Skin and subcutaneous tissue disorders
Alopecia	24/76 (31.6%)		15/78 (19.2%)
Dermatitis acneiform	5/76 (6.6%)		1/78 (1.3%)
Dry skin	8/76 (10.5%)		2/78 (2.6%)
Erythema	8/76 (10.5%)		2/78 (2.6%)
Onycholysis	0/76 (0%)		4/78 (5.1%)
Palmar-plantar erythrodysaesthesia syndrome	4/76 (5.3%)		0/78 (0%)
Pruritus	8/76 (10.5%)		3/78 (3.8%)
Rash	14/76 (18.4%)		11/78 (14.1%)
Rash maculo-papular	5/76 (6.6%)		3/78 (3.8%)
Vascular disorders
Hypertension	11/76 (14.5%)		6/78 (7.7%)

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.