Trial Outcomes & Findings for Brain Metastases In ErbB2-Positive Breast Cancer (NCT NCT00437073)

NCT ID: NCT00437073

Last Updated: 2015-10-15

Results Overview

CNS OR is defined as the number of participants with either a complete response (CR) or partial response (PR) as assessed by volumetric analysis of brain magnetic resonance imaging (MRI) and Response Evaluation Criteria In Solid Tumors (RECIST). CR: complete resolution of all evaluable and non-evaluable brain metastases; PR: =\>50% reduction in the volumetric sum of all evaluable brain metastases compared to baseline.

• Recruitment status: TERMINATED
• Study phase: PHASE2
• Target enrollment: 22 participants
• Primary outcome timeframe: From the start of treatment until disease progression, death, or discontinuation from the study, up to a maximum of Week 88
• Results posted on: 2015-10-15

Participant Flow

Participant milestones

Measure	Lapatinib Plus Capecitabine Participants received a daily dose of 5 tablets of lapatinib (1250 milligrams \[mg\]) at approximately the same time every day, either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received capecitabine 2000 mg per meters squared (mg/m\^2) per day, divided and administered orally twice daily, 12 hours apart, for 14 days, every 21 days. Capecitabine was taken with food or within 30 minutes after a breakfast meal with approximately 200 milliliters (ml) of water.	Lapatinib Plus Topotecan Participants received a daily dose of 5 tablets of lapatinib (1250 milligrams \[mg\]) at approximately the same time every day, either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received an intravenous (IV) infusion of topotecan 3.2 mg/m\^2 over the course of at least 30 minutes on Days 1, 8, and 15 (+/- 2 days) of a 28-day treatment cycle.
Overall Study STARTED	13	9
Overall Study COMPLETED	12	8
Overall Study NOT COMPLETED	1	1

Reasons for withdrawal

Measure	Lapatinib Plus Capecitabine Participants received a daily dose of 5 tablets of lapatinib (1250 milligrams \[mg\]) at approximately the same time every day, either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received capecitabine 2000 mg per meters squared (mg/m\^2) per day, divided and administered orally twice daily, 12 hours apart, for 14 days, every 21 days. Capecitabine was taken with food or within 30 minutes after a breakfast meal with approximately 200 milliliters (ml) of water.	Lapatinib Plus Topotecan Participants received a daily dose of 5 tablets of lapatinib (1250 milligrams \[mg\]) at approximately the same time every day, either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received an intravenous (IV) infusion of topotecan 3.2 mg/m\^2 over the course of at least 30 minutes on Days 1, 8, and 15 (+/- 2 days) of a 28-day treatment cycle.
Overall Study Sponsor Terminated Study	1	0
Overall Study Physician Decision	0	1

Baseline Characteristics

Brain Metastases In ErbB2-Positive Breast Cancer

Baseline characteristics by cohort

Measure	Lapatinib Plus Capecitabine n=13 Participants Participants received a daily dose of 5 tablets of lapatinib (1250 milligrams \[mg\]) at approximately the same time every day, either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received capecitabine 2000 mg per meters squared (mg/m\^2) per day, divided and administered orally twice daily, 12 hours apart, for 14 days, every 21 days. Capecitabine was taken with food or within 30 minutes after a breakfast meal with approximately 200 milliliters (ml) of water.	Lapatinib Plus Topotecan n=9 Participants Participants received a daily dose of 5 tablets of lapatinib (1250 milligrams \[mg\]) at approximately the same time every day, either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received an intravenous (IV) infusion of topotecan 3.2 mg/m\^2 over the course of at least 30 minutes on Days 1, 8, and 15 (+/- 2 days) of a 28-day treatment cycle.	Total n=22 Participants Total of all reporting groups
Age, Continuous	49.4 Years STANDARD_DEVIATION 9.29 • n=5 Participants	54.6 Years STANDARD_DEVIATION 10.54 • n=7 Participants	51.5 Years STANDARD_DEVIATION 9.92 • n=5 Participants
Sex: Female, Male Female	13 Participants n=5 Participants	9 Participants n=7 Participants	22 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized White	13 participants n=5 Participants	9 participants n=7 Participants	22 participants n=5 Participants

PRIMARY outcome

Timeframe: From the start of treatment until disease progression, death, or discontinuation from the study, up to a maximum of Week 88

Population: Modified Intent-to-Treat (mITT) Population: all participants who had at least one evaluable CNS target lesion at baseline and who had received at least two doses of lapatinib medication

CNS OR is defined as the number of participants with either a complete response (CR) or partial response (PR) as assessed by volumetric analysis of brain magnetic resonance imaging (MRI) and Response Evaluation Criteria In Solid Tumors (RECIST). CR: complete resolution of all evaluable and non-evaluable brain metastases; PR: =>50% reduction in the volumetric sum of all evaluable brain metastases compared to baseline.

Outcome measures

Measure	Lapatinib Plus Capecitabine n=13 Participants Participants received a daily dose of 5 tablets of lapatinib (1250 milligrams \[mg\]) at approximately the same time every day, either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received capecitabine 2000 mg per meters squared (mg/m\^2) per day, divided and administered orally twice daily, 12 hours apart, for 14 days, every 21 days. Capecitabine was taken with food or within 30 minutes after a breakfast meal with approximately 200 milliliters (ml) of water.	Lapatinib Plus Topotecan n=9 Participants Participants received a daily dose of 5 tablets of lapatinib (1250 milligrams \[mg\]) at approximately the same time every day, either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received an intravenous (IV) infusion of topotecan 3.2 mg/m\^2 over the course of at least 30 minutes on Days 1, 8, and 15 (+/- 2 days) of a 28-day treatment cycle.
Number of Participants With the Indicated Central Nervous System (CNS) Objective Response (OR)	5 participants	0 participants

PRIMARY outcome

Timeframe: From the start of treatment until disease progression, death, or discontinuation from the study, up to a maximum of Week 88

Population: mITT Population

CNS responses were assessed by volumetric (V) analysis of brain MRI and RECIST. CR: complete resolution of all evaluable and non-evaluable brain metastases (BMs). PR: =>50% reduction in the V sum of all evaluable BMs compared to baseline. A response of "Other" was used for participants who discontinued the study prior to the first efficacy assessment. Stable Disease (SD): disease that does not meet CR, PR, or CNS progression criteria. Progressive disease (PD): a requirement for a new steroid or an increasing steroid dose for the treatment of worsening neurological signs/symptoms due to BMs.

Outcome measures

Measure	Lapatinib Plus Capecitabine n=13 Participants Participants received a daily dose of 5 tablets of lapatinib (1250 milligrams \[mg\]) at approximately the same time every day, either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received capecitabine 2000 mg per meters squared (mg/m\^2) per day, divided and administered orally twice daily, 12 hours apart, for 14 days, every 21 days. Capecitabine was taken with food or within 30 minutes after a breakfast meal with approximately 200 milliliters (ml) of water.	Lapatinib Plus Topotecan n=9 Participants Participants received a daily dose of 5 tablets of lapatinib (1250 milligrams \[mg\]) at approximately the same time every day, either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received an intravenous (IV) infusion of topotecan 3.2 mg/m\^2 over the course of at least 30 minutes on Days 1, 8, and 15 (+/- 2 days) of a 28-day treatment cycle.
Number of Participants With the Indicated CNS Responses Stable Disease	6 participants	3 participants
Number of Participants With the Indicated CNS Responses Progressive Disease	2 participants	1 participants
Number of Participants With the Indicated CNS Responses Other	0 participants	2 participants
Number of Participants With the Indicated CNS Responses Complete response	0 participants	0 participants
Number of Participants With the Indicated CNS Responses Partial response	5 participants	0 participants
Number of Participants With the Indicated CNS Responses Unknown	0 participants	3 participants

SECONDARY outcome

Timeframe: From the start of treatment until disease progression, death, or discontinuation from the study, up to a maximum of Week 88

Population: mITT Population

CNS OR is defined as the number of participants with either a CR or PR as assessed by volumetric analysis of brain MRI and RECIST. CR: complete resolution of all evaluable and non-evaluable brain metastases; PR: =>50% reduction in the volumetric sum of all evaluable brain metastases compared to baseline. This study was closed before full enrollment was achieved; thus, predefined secondary efficacy endpoints were not assessed because there were not enough participants enrolled in the study to provide statistically valid analyses.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From the start of treatment until disease progression, death, or discontinuation from the study, up to a maximum of Week 88

Population: mITT Population

Clinical benefit is defined as CR (complete resolution of all evaluable and non-evaluable brain metastases), PR (=>50% reduction in the volumetric sum of all evaluable brain metastases compared to baseline), or stable disease (disease that does not meet CR, PR, or CNS progression criteria) for at least 6 months. This study was closed before full enrollment was achieved; thus, predefined secondary efficacy endpoints were not assessed because there were not enough participants enrolled in the study to provide statistically valid analyses.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From the start of treatment until disease progression, death, or discontinuation from the study, up to a maximum of Week 88

Population: mITT Population

Non-CNS disease (for par. with measurable baseline non-CNS disease) OR is defined as the number of par. with either a CR or PR as assessed by computed tomography (CT) or MRI scan and RECIST. CR: disappearance of all target lesions; PR: at least a 30% decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD. This study was closed before full enrollment was achieved; thus, predefined secondary efficacy endpoints were not assessed because there were not enough par. enrolled in the study to provide statistically valid analyses.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From the start of treatment until disease progression, death, or discontinuation from the study, up to a maximum of Week 88

Population: mITT Population

CNS OR is defined as the number of participants with either a CR or PR as assessed by volumetric analysis of brain MRI and RECIST. CR: complete resolution of all evaluable and non-evaluable brain metastases; PR: =>50% reduction in the volumetric sum of all evaluable brain metastases compared to baseline. This study was closed before full enrollment was achieved; thus, predefined secondary efficacy endpoints were not assessed because there were not enough participants enrolled in the study to provide statistically valid analyses.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From the start of treatment until disease progression, death, or discontinuation from the study, up to a maximum of Week 88

Population: mITT Population

The site of initial disease will be determined by taking the earliest date of known progression and assigning the appropriate category (CNS or non-CNS) based on the source of the earliest date. This study was closed before full enrollment was achieved; thus, predefined secondary efficacy endpoints were not assessed because there were not enough participants enrolled in the study to provide statistically valid analyses.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From the start of treatment until disease progression, death, or discontinuation from the study, up to a maximum of Week 88

Population: mITT Population

Progression-free survival is defined as the time from the start of treatment until the first documented sign of disease progression at any site or death due to any cause, if sooner. This study was closed before full enrollment was achieved; thus, predefined secondary efficacy endpoints were not assessed because there were not enough participants enrolled in the study to provide statistically valid analyses.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From the start of treatment until disease progression, death, or discontinuation from the study, up to a maximum of Week 88

Population: mITT Population

Overall survival is defined as the time from the start of treatment until death due to any cause. This study was closed before full enrollment was achieved; thus, predefined secondary efficacy endpoints were not assessed because there were not enough participants enrolled in the study to provide statistically valid analyses.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From the start of treatment until disease progression, death, or discontinuation from the study, up to a maximum of Week 88

Population: mITT Population

TR NSS was to be recorded by the Investigator on the NEW, using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE V3.0). Improvement was to be defined as a decrease of 1 or more CTCAE grades from baseline of any TR NSS. This study was closed before full enrollment was achieved; thus, predefined secondary efficacy endpoints were not assessed because there were not enough participants enrolled in the study to provide statistically valid analyses.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From the start of treatment until disease progression, death, or discontinuation from the study, up to a maximum of Week 88

Population: mITT Population

The percentage participants with disease stabiliztion for 6 months or more were defined as those treated participants with a best CNS objective response of SD whose disease stabilization lasted 6 months or more from the start of treatment. This study was closed before full enrollment was achieved; thus, predefined secondary efficacy endpoints were not assessed because there were not enough participants enrolled in the study to provide statistically valid analyses.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline; from the start of treatment until disease progression, death, or discontinuation from the study, up to a maximum of Week 88

Population: mITT Population

The percentage of participants with a >=20% volumetric reduction in CNS lesions was defined as the percentage of treated participants achieving at least a 20% volumetric reduction in CNS lesions relative to baseline. This study was closed before full enrollment was achieved; thus, predefined secondary efficacy endpoints were not assessed because there were not enough participants enrolled in the study to provide statistically valid analyses.

Outcome measures

Outcome data not reported

Adverse Events

Lapatinib Plus Capecitabine

Serious events: 6 serious events

Other events: 13 other events

Deaths: 0 deaths

Lapatinib Plus Topotecan

Serious events: 5 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Measure	Lapatinib Plus Capecitabine n=13 participants at risk Participants received a daily dose of 5 tablets of lapatinib (1250 milligrams \[mg\]) at approximately the same time every day, either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received capecitabine 2000 mg per meters squared (mg/m\^2) per day, divided and administered orally twice daily, 12 hours apart, for 14 days, every 21 days. Capecitabine was taken with food or within 30 minutes after a breakfast meal with approximately 200 milliliters (ml) of water.	Lapatinib Plus Topotecan n=9 participants at risk Participants received a daily dose of 5 tablets of lapatinib (1250 milligrams \[mg\]) at approximately the same time every day, either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received an intravenous (IV) infusion of topotecan 3.2 mg/m\^2 over the course of at least 30 minutes on Days 1, 8, and 15 (+/- 2 days) of a 28-day treatment cycle.
Gastrointestinal disorders Diarrhoea	15.4% 2/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	11.1% 1/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Gastrointestinal disorders Constipation	7.7% 1/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	0.00% 0/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
General disorders General physical health deterioration	7.7% 1/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	11.1% 1/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
General disorders Multi-organ failure	7.7% 1/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	0.00% 0/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
General disorders Pyrexia	7.7% 1/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	0.00% 0/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Infections and infestations Erysipelas	7.7% 1/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	0.00% 0/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Infections and infestations Sepsis	0.00% 0/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	22.2% 2/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Infections and infestations Urinary tract infection	0.00% 0/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	11.1% 1/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Metabolism and nutrition disorders Dehydration	0.00% 0/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	11.1% 1/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Metabolism and nutrition disorders Hypokalaemia	7.7% 1/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	11.1% 1/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Metabolism and nutrition disorders Hypocalcaemia	7.7% 1/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	0.00% 0/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Nervous system disorders Loss of consciousness	7.7% 1/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	0.00% 0/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Nervous system disorders Memory impairment	7.7% 1/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	0.00% 0/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Nervous system disorders Syncope	0.00% 0/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	11.1% 1/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Investigations Hepatic enzyme increased	7.7% 1/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	0.00% 0/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Psychiatric disorders Confusional state	7.7% 1/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	0.00% 0/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	7.7% 1/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	0.00% 0/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.

Other adverse events

Measure	Lapatinib Plus Capecitabine n=13 participants at risk Participants received a daily dose of 5 tablets of lapatinib (1250 milligrams \[mg\]) at approximately the same time every day, either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received capecitabine 2000 mg per meters squared (mg/m\^2) per day, divided and administered orally twice daily, 12 hours apart, for 14 days, every 21 days. Capecitabine was taken with food or within 30 minutes after a breakfast meal with approximately 200 milliliters (ml) of water.	Lapatinib Plus Topotecan n=9 participants at risk Participants received a daily dose of 5 tablets of lapatinib (1250 milligrams \[mg\]) at approximately the same time every day, either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received an intravenous (IV) infusion of topotecan 3.2 mg/m\^2 over the course of at least 30 minutes on Days 1, 8, and 15 (+/- 2 days) of a 28-day treatment cycle.
Gastrointestinal disorders Diarrhoea	84.6% 11/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	88.9% 8/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Gastrointestinal disorders Nausea	23.1% 3/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	55.6% 5/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Gastrointestinal disorders Vomiting	30.8% 4/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	22.2% 2/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Gastrointestinal disorders Constipation	15.4% 2/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	22.2% 2/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Gastrointestinal disorders Stomatitis	23.1% 3/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	0.00% 0/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Gastrointestinal disorders Abdominal pain	7.7% 1/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	11.1% 1/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Gastrointestinal disorders Dyspepsia	15.4% 2/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	0.00% 0/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Gastrointestinal disorders Abdominal pain upper	7.7% 1/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	0.00% 0/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Gastrointestinal disorders Abdominal discomfort	0.00% 0/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	11.1% 1/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Gastrointestinal disorders Cheilitis	7.7% 1/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	0.00% 0/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Gastrointestinal disorders Gastrooesophageal reflux disease	7.7% 1/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	0.00% 0/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Gastrointestinal disorders Oesophagitis	7.7% 1/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	0.00% 0/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
General disorders Fatigue	61.5% 8/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	55.6% 5/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
General disorders Oedema peripheral	38.5% 5/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	0.00% 0/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
General disorders Mucosal inflammation	30.8% 4/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	0.00% 0/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
General disorders Asthenia	7.7% 1/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	11.1% 1/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
General disorders Oedema	7.7% 1/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	11.1% 1/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
General disorders Pyrexia	7.7% 1/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	11.1% 1/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
General disorders Chills	0.00% 0/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	11.1% 1/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
General disorders Facial pain	7.7% 1/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	0.00% 0/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
General disorders Influenza like illness	7.7% 1/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	0.00% 0/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Nervous system disorders Headache	46.2% 6/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	33.3% 3/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Nervous system disorders Dizziness	23.1% 3/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	22.2% 2/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Nervous system disorders Dysgeusia	15.4% 2/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	0.00% 0/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Nervous system disorders Peripheral sensory neuropathy	7.7% 1/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	11.1% 1/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Nervous system disorders Balance disorder	7.7% 1/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	0.00% 0/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Nervous system disorders Hemiparesis	7.7% 1/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	0.00% 0/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Nervous system disorders Memory impairment	0.00% 0/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	11.1% 1/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Nervous system disorders Muscle contraction involuntary	0.00% 0/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	11.1% 1/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Nervous system disorders Neuropathy peripheral	7.7% 1/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	0.00% 0/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Nervous system disorders Paraesthesia	7.7% 1/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	0.00% 0/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Nervous system disorders Somnolence	7.7% 1/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	0.00% 0/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Skin and subcutaneous tissue disorders Palmar-Plantar erythrodysaesthesia syndrome	61.5% 8/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	11.1% 1/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Skin and subcutaneous tissue disorders Dry skin	30.8% 4/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	22.2% 2/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Skin and subcutaneous tissue disorders Rash	38.5% 5/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	11.1% 1/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Skin and subcutaneous tissue disorders Alopecia	0.00% 0/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	22.2% 2/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Skin and subcutaneous tissue disorders Dermatitis acneiform	15.4% 2/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	0.00% 0/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Skin and subcutaneous tissue disorders Pruritus	15.4% 2/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	0.00% 0/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Skin and subcutaneous tissue disorders Acne	0.00% 0/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	11.1% 1/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Skin and subcutaneous tissue disorders Erythema	0.00% 0/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	11.1% 1/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Skin and subcutaneous tissue disorders Ingrowing nail	7.7% 1/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	0.00% 0/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Skin and subcutaneous tissue disorders Nail disorder	7.7% 1/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	0.00% 0/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Skin and subcutaneous tissue disorders Rash generalised	0.00% 0/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	11.1% 1/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Skin and subcutaneous tissue disorders Skin chapped	7.7% 1/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	0.00% 0/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Skin and subcutaneous tissue disorders Skin fissures	0.00% 0/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	11.1% 1/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Skin and subcutaneous tissue disorders Skin infection	0.00% 0/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	11.1% 1/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Blood and lymphatic system disorders Thrombocytopenia	7.7% 1/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	55.6% 5/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Blood and lymphatic system disorders Anaemia	7.7% 1/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	33.3% 3/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Blood and lymphatic system disorders Neutropenia	7.7% 1/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	33.3% 3/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Blood and lymphatic system disorders Leukocytosis	7.7% 1/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	0.00% 0/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Blood and lymphatic system disorders Leukopenia	0.00% 0/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	11.1% 1/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Blood and lymphatic system disorders Lymphopenia	0.00% 0/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	11.1% 1/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Metabolism and nutrition disorders Decreased appetite	23.1% 3/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	22.2% 2/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Metabolism and nutrition disorders Hypokalaemia	15.4% 2/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	33.3% 3/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Metabolism and nutrition disorders Hyponatraemia	7.7% 1/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	11.1% 1/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Metabolism and nutrition disorders Dehydration	7.7% 1/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	0.00% 0/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Metabolism and nutrition disorders Hyperkalaemia	0.00% 0/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	11.1% 1/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Metabolism and nutrition disorders Hypoalbuminaemia	7.7% 1/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	0.00% 0/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Metabolism and nutrition disorders Hypocalcaemia	0.00% 0/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	11.1% 1/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Metabolism and nutrition disorders Hypoproteinaemia	0.00% 0/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	11.1% 1/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Investigations Haemoglobin decreased	15.4% 2/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	22.2% 2/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Investigations Weight decreased	7.7% 1/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	11.1% 1/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Investigations Activated partial thromboplastin time shortened	0.00% 0/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	11.1% 1/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Investigations Alanine aminotransferase	0.00% 0/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	11.1% 1/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Investigations Blood alkaline phosphatase increased	7.7% 1/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	0.00% 0/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Investigations Blood bilirubin	0.00% 0/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	11.1% 1/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Investigations Blood glucose abnormal	7.7% 1/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	0.00% 0/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Investigations Blood glucose increased	0.00% 0/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	11.1% 1/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Investigations Blood phosphorus decreased	7.7% 1/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	0.00% 0/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Investigations Protein total abnormal	7.7% 1/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	0.00% 0/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Investigations Prothrombin time abnormal	7.7% 1/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	0.00% 0/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Investigations Weight increased	7.7% 1/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	0.00% 0/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Respiratory, thoracic and mediastinal disorders Dyspnoea	15.4% 2/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	11.1% 1/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Respiratory, thoracic and mediastinal disorders Cough	7.7% 1/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	11.1% 1/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Psychiatric disorders Depressed mood	15.4% 2/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	0.00% 0/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Vascular disorders Hot flush	7.7% 1/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	11.1% 1/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Infections and infestations Infection	7.7% 1/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	11.1% 1/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Psychiatric disorders Insomnia	15.4% 2/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	0.00% 0/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Musculoskeletal and connective tissue disorders Arthralgia	7.7% 1/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	11.1% 1/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Musculoskeletal and connective tissue disorders Back pain	7.7% 1/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	11.1% 1/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Musculoskeletal and connective tissue disorders Muscular weakness	0.00% 0/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	22.2% 2/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Musculoskeletal and connective tissue disorders Myalgia	15.4% 2/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	0.00% 0/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Musculoskeletal and connective tissue disorders Neck pain	7.7% 1/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	11.1% 1/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	22.2% 2/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Respiratory, thoracic and mediastinal disorders Sinus congestion	15.4% 2/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	0.00% 0/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Infections and infestations Abscess	7.7% 1/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	0.00% 0/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Psychiatric disorders Anxiety	7.7% 1/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	0.00% 0/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Musculoskeletal and connective tissue disorders Bone pain	7.7% 1/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	0.00% 0/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Infections and infestations Cellulitis	7.7% 1/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	0.00% 0/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Injury, poisoning and procedural complications Contusion	7.7% 1/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	0.00% 0/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Ear and labyrinth disorders Deafness	0.00% 0/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	11.1% 1/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Infections and infestations Fungal infection	0.00% 0/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	11.1% 1/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Hepatobiliary disorders Hyperbilirubinaemia	7.7% 1/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	0.00% 0/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Musculoskeletal and connective tissue disorders Joint swelling	7.7% 1/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	0.00% 0/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Eye disorders Lacrimation increased	7.7% 1/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	0.00% 0/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Cardiac disorders Left ventricular dysfunction	0.00% 0/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	11.1% 1/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Injury, poisoning and procedural complications Lumbar vertebral fracture	7.7% 1/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	0.00% 0/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Vascular disorders Lymphoedema	0.00% 0/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	11.1% 1/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Psychiatric disorders Major depression	7.7% 1/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	0.00% 0/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Musculoskeletal and connective tissue disorders Muscle spasms	7.7% 1/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	0.00% 0/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Respiratory, thoracic and mediastinal disorders Nasal ulcer	7.7% 1/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	0.00% 0/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Infections and infestations Nasopharyngitis	7.7% 1/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	0.00% 0/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Infections and infestations Oral fungal infection	7.7% 1/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	0.00% 0/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Infections and infestations Oral infection	7.7% 1/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	0.00% 0/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Musculoskeletal and connective tissue disorders Osteoporosis	7.7% 1/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	0.00% 0/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Infections and infestations Otitis media	7.7% 1/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	0.00% 0/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Cardiac disorders Palpitations	7.7% 1/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	0.00% 0/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Infections and infestations Paronychia	7.7% 1/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	0.00% 0/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Cardiac disorders Pericardial effusion	7.7% 1/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	0.00% 0/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	11.1% 1/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	11.1% 1/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Psychiatric disorders Restlessness	0.00% 0/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	11.1% 1/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Respiratory, thoracic and mediastinal disorders Sinus disorder	7.7% 1/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	0.00% 0/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Vascular disorders Thrombophlebitis superficial	7.7% 1/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	0.00% 0/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Infections and infestations Upper respiratory tract infection	7.7% 1/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	0.00% 0/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Infections and infestations Urinary tract infection	7.7% 1/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	0.00% 0/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Eye disorders Vision blurred	7.7% 1/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	0.00% 0/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Eye disorders Visual impairment	0.00% 0/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	11.1% 1/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Blood and lymphatic system disorders White blood cell count decreased	0.00% 0/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	11.1% 1/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Nervous system disorders Disorientation	7.7% 1/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	0.00% 0/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.
Eye disorders Dry eyes	7.7% 1/13 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.	0.00% 0/9 • All serious and non-serious on-therapy adverse events, defined as occurring from the first dose of investigational product until five days after the last dose (up to Week 37) were recorded, regardless of whether or not they were considered drug related. Serious and non-serious adverse events were collected in members of the ITT Population, comprised of all participants who received at least one dose of study medication.

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

• Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
• Publication restrictions are in place

Restriction type: OTHER