Trial Outcomes & Findings for Lapatinib Combined With Paclitaxel For Patients With First-Line ErbB2-Amplified Metastatic Breast Cancer (NCT NCT00356811)

Last Updated: 2014-07-21

Results Overview

OR is defined as the number of participants achieving either a CR or PR, per Response Evaulation Criteria in Solid Tumors (RECIST). The best OR is defined as the best response recorded from the start of treatment until progressive disease (PD)/recurrence. CR is defined as the disappearance of all target lesions (TLs) and non-TLs. PR is defined as at least a 30% decrease in the sum of the longest diameters (LD) of TLs, taking as a reference the Baseline sum LD and no PD, or complete resolution of TLs and the persistence of one or more non-TL(s), as assessed by the IRC. PD is defined as at least a 20% increase in the sum of the LD of TLs, taking as a reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions or unequivocal progression of existing non-TLs. Responses were confirmed at subsequent assessments made \>=28 days after the original response. Participants with an unknown or missing response are treated as non-responders.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

57 participants

Primary outcome timeframe

From the first dose of study medication to the first documented evidence of a confirmed CR or PR (up to Week 86)

Results posted on

2014-07-21

Participant Flow

Participant milestones

Participant milestones
Measure	Lapatinib With Paclitaxel Participants received lapatinib 1500 milligrams (mg) orally once daily (OD) with paclitaxel, administered as a 1-hour intravenous (IV) infusion at a dose of 80 mg/meters squared (m\^2) on Days 1, 8, and 15 (±2 days) of a 28-day treatment cycle for at least 6 months. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal.
Overall Study STARTED	57
Overall Study COMPLETED	8
Overall Study NOT COMPLETED	49

Reasons for withdrawal

Reasons for withdrawal
Measure	Lapatinib With Paclitaxel Participants received lapatinib 1500 milligrams (mg) orally once daily (OD) with paclitaxel, administered as a 1-hour intravenous (IV) infusion at a dose of 80 mg/meters squared (m\^2) on Days 1, 8, and 15 (±2 days) of a 28-day treatment cycle for at least 6 months. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal.
Overall Study Death	35
Overall Study Lost to Follow-up	2
Overall Study Withdrawal by Subject	6
Overall Study Participant Could Not Make a Checkup	1
Overall Study Study Is Terminating	3
Overall Study Site Closed during Follow-up	2

Baseline Characteristics

Lapatinib Combined With Paclitaxel For Patients With First-Line ErbB2-Amplified Metastatic Breast Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Lapatinib Plus Paclitaxel n=57 Participants Participants received lapatinib 1500 mg orally OD with paclitaxel, administered as a 1-hour IV infusion at a dose of 80 mg/m\^2 on Days 1, 8, and 15 (±2 days) of a 28-day treatment cycle for at least 6 months. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal.
Age, Continuous	52.3 Years STANDARD_DEVIATION 9.30 • n=5 Participants
Sex: Female, Male Female	57 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants
Race/Ethnicity, Customized White - White/Caucasian/European Heritage	57 Participants n=5 Participants

PRIMARY outcome

Timeframe: From the first dose of study medication to the first documented evidence of a confirmed CR or PR (up to Week 86)

Population: Intent-to-Treat (ITT) Population: all participants who received study medication.

Outcome measures

Outcome measures
Measure	Lapatinib Plus Paclitaxel n=57 Participants Participants received lapatinib 1500 mg orally OD with paclitaxel, administered as a 1-hour IV infusion at a dose of 80 mg/m\^2 on Days 1, 8, and 15 (±2 days) of a 28-day treatment cycle for at least 6 months. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal.
Number of Participants With a Best Overall Response (OR) of Confirmed Complete Response (CR) or Partial Response (PR), as Assessed by the Independent Review Committee (IRC) CR	0 Participants
Number of Participants With a Best Overall Response (OR) of Confirmed Complete Response (CR) or Partial Response (PR), as Assessed by the Independent Review Committee (IRC) PR	29 Participants

SECONDARY outcome

Timeframe: From the first dose of study medication to the first documented evidence of a confirmed CR or PR (up to Week 86)

Population: ITT Population

OR is defined as the number of participants achieving either a CR or PR, per RECIST. The best OR is defined as the best response recorded from the start of treatment until progressive disease (PD)/recurrence. CR is defined as the disappearance of all target lesions (TLs) and non-TLs. PR is defined as at least a 30% decrease in the sum of the longest diameters (LD) of TLs, taking as a reference the Baseline sum LD and no PD, or complete resolution of TLs and the persistence of one or more non-TL(s), as assessed by the Investigator. PD is defined as at least a 20% increase in the sum of the LD of TLs, taking as a reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions or unequivocal progression of existing non-TLs. Responses were confirmed at subsequent assessments made \>=28 days after the original response. Participants with an unknown or missing response are treated as non-responders.

Outcome measures

Outcome measures
Measure	Lapatinib Plus Paclitaxel n=57 Participants Participants received lapatinib 1500 mg orally OD with paclitaxel, administered as a 1-hour IV infusion at a dose of 80 mg/m\^2 on Days 1, 8, and 15 (±2 days) of a 28-day treatment cycle for at least 6 months. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal.
Number of Participants With a Best Overall Response (OR) of Confirmed Complete Response (CR) or Partial Response (PR), as Assessed by the Investigator CR	3 Participants
Number of Participants With a Best Overall Response (OR) of Confirmed Complete Response (CR) or Partial Response (PR), as Assessed by the Investigator PR	41 Participants

SECONDARY outcome

Timeframe: From the first documented evidence of a PR or CR until the earlier of the date of disease progression or the date of death due to breast cancer (up to Week 86)

Population: ITT Population. Only those participants with CR or PR were analyzed.

DoR is defined for the subset of participants who had a confirmed CR (disappearance of all TLs and non-TLs) or PR (\>=30% decrease in the sum of the LD of TLs, taking as a reference the Baseline sum LD and no PD, or complete resolution of TLs and the persistence of one or more non-TL\[s\]) as the time from the first documented evidence of a CR or PR until the first documentation of radiological PD or death due to breast cancer, if sooner. PD is defined as a \>=20% increase in the sum of the LD of TLs, taking as a reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions or unequivocal progression of existing non-TLs. For participants who did not progress or die, DoR was censored on the date of the last radiological scan. If a participant had only a Baseline visit or did not have a date of a radiological scan that was later than the date of initiation of anti-cancer therapy, DoR was censored at the start date of treatment.

Outcome measures

Outcome measures
Measure	Lapatinib Plus Paclitaxel n=29 Participants Participants received lapatinib 1500 mg orally OD with paclitaxel, administered as a 1-hour IV infusion at a dose of 80 mg/m\^2 on Days 1, 8, and 15 (±2 days) of a 28-day treatment cycle for at least 6 months. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal.
Duration of Response (DoR), as Assessed by the IRC	39.7 weeks Interval 26.9 to 50.0

SECONDARY outcome

Timeframe: From the first documented evidence of a PR or CR until the earlier of the date of disease progression or the date of death due to breast cancer (up to Week 86)

Population: ITT Population. Only those participants with CR or PR were analyzed.

Outcome measures

Outcome measures
Measure	Lapatinib Plus Paclitaxel n=44 Participants Participants received lapatinib 1500 mg orally OD with paclitaxel, administered as a 1-hour IV infusion at a dose of 80 mg/m\^2 on Days 1, 8, and 15 (±2 days) of a 28-day treatment cycle for at least 6 months. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal.
Duration of Response (DoR), as Assessed by the Investigator	42.3 Weeks Interval 37.7 to 64.1

SECONDARY outcome

Timeframe: From randomization until the first documented evidence of a PR or CR (up to Week 86)

Population: ITT Population. Only those participants with CR or PR were analyzed.

Time to response is defined as the time from randomization until the first documented evidence of a PR or CR (whichever status is recorded first). Analysis was based on responses confirmed at a repeat assessment made at least 4 weeks after the initial response, with the time to response taken as the first time the response was observed, not the confirmation assessment. Participants who withdraw with no tumor response were censored at the date of withdrawal from the study. CR is defined as the disappearance of all TLs and non-TLs. PR is defined as at least a 30% decrease in the sum of the LD of TLs, taking as a reference the Baseline sum LD and no PD, or complete resolution of TLs and the persistence of one or more non-TL(s). PD is defined as at least a 20% increase in the sum of the LD of TLs, taking as a reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions or unequivocal progression of existing non-TLs.

Outcome measures

Outcome measures
Measure	Lapatinib Plus Paclitaxel n=29 Participants Participants received lapatinib 1500 mg orally OD with paclitaxel, administered as a 1-hour IV infusion at a dose of 80 mg/m\^2 on Days 1, 8, and 15 (±2 days) of a 28-day treatment cycle for at least 6 months. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal.
Time to Response, as Assessed by the IRC	8.4 weeks Interval 7.9 to 11.1

SECONDARY outcome

Timeframe: From randomization until the first documented evidence of a PR or CR (up to Week 86)

Population: ITT Population. Only those participants with CR or PR were analyzed.

Outcome measures

Outcome measures
Measure	Lapatinib Plus Paclitaxel n=44 Participants Participants received lapatinib 1500 mg orally OD with paclitaxel, administered as a 1-hour IV infusion at a dose of 80 mg/m\^2 on Days 1, 8, and 15 (±2 days) of a 28-day treatment cycle for at least 6 months. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal.
Time to Response, as Assessed by the Investigator	8.0 Weeks Interval 7.9 to 8.1

SECONDARY outcome

Timeframe: From the start date of treatment until the date of radiological disease progression or the date of death due to breast cancer (up to Week 86)

Population: ITT Population

Time to progression is defined as the interval between the start date of treatment and the date of radiological disease progression or death due to breast cancer, whichever occurs first. Participents who did not progress or die were censored on the date of their last radiological assessment preceding the start of any additional anti-cancer therapy. PD is defined as at least a 20% increase in the sum of the LD of TLs, taking as a reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions or unequivocal progression of existing non-TLs. Responses were confirmed at a subsequent assessment made no less than 28 days after the original response.

Outcome measures

Outcome measures
Measure	Lapatinib Plus Paclitaxel n=57 Participants Participants received lapatinib 1500 mg orally OD with paclitaxel, administered as a 1-hour IV infusion at a dose of 80 mg/m\^2 on Days 1, 8, and 15 (±2 days) of a 28-day treatment cycle for at least 6 months. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal.
Time to Progression, as Assessed by the IRC and the Investigator IRC	47.9 weeks Interval 40.0 to The upper limit of the 95% confidence interval could not be determined (not reached) because there were not enough events to be able to calculate it.
Time to Progression, as Assessed by the IRC and the Investigator Investigator	50.9 weeks Interval 47.0 to 64.3

SECONDARY outcome

Timeframe: From the start date of treatment until the date of radiological disease progression or death due to any cause, whichever occurs first (up to Week 86)

Population: ITT Population

Progression-free survival is defined as the interval between the start date of treatment and the date of radiological disease progression or death due to any cause, whichever occurs first. Participants who did not progress in their disease were censored on the date of their last radiological assessment preceding the start of any additional anti-cancer therapy. PD is defined as at least a 20% increase in the sum of the LD of TLs, taking as a reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions or unequivocal progression of existing non-TLs. Responses were confirmed at a subsequent assessment made no less than 28 days after the original response.

Outcome measures

Outcome measures
Measure	Lapatinib Plus Paclitaxel n=57 Participants Participants received lapatinib 1500 mg orally OD with paclitaxel, administered as a 1-hour IV infusion at a dose of 80 mg/m\^2 on Days 1, 8, and 15 (±2 days) of a 28-day treatment cycle for at least 6 months. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal.
Progression-free Survival, as Assessed by the IRC and the Investigator IRC	47.9 weeks Interval 40.0 to The upper limit of the 95% confidence interval could not be determined (not reached) because there were not enough events to be able to calculate it.
Progression-free Survival, as Assessed by the IRC and the Investigator Investigator	50.9 weeks Interval 47.0 to 64.3

SECONDARY outcome

Timeframe: From the date of the first dose until the date of death due to any cause (up to Week 86)

Population: ITT Population

Overall survival is defined as the interval between the date of treatment start and the date of death due to any cause. For participants who did not die, follow-up was censored as the date of last contact. For participants who did not die, follow-up was censored at the date of last contact.

Outcome measures

Outcome measures
Measure	Lapatinib Plus Paclitaxel n=57 Participants Participants received lapatinib 1500 mg orally OD with paclitaxel, administered as a 1-hour IV infusion at a dose of 80 mg/m\^2 on Days 1, 8, and 15 (±2 days) of a 28-day treatment cycle for at least 6 months. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal.
Overall Survival	NA weeks At the time of this analysis, the median and the 95% confidence interval could not be determined because there were not enough deaths to calculate these estimates.

SECONDARY outcome

Timeframe: From the start of study medication until 28 days after the last dose (up to Study Week 381)

Population: ITT Population

An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect. Medical or scientific judgment was exercised in deciding whether reporting was appropriate in other situations.

Outcome measures

Outcome measures
Measure	Lapatinib Plus Paclitaxel n=57 Participants Participants received lapatinib 1500 mg orally OD with paclitaxel, administered as a 1-hour IV infusion at a dose of 80 mg/m\^2 on Days 1, 8, and 15 (±2 days) of a 28-day treatment cycle for at least 6 months. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal.
Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) Any AE	57 Participants
Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) Any SAE	11 Participants

Adverse Events

Lapatinib Plus Paclitaxel

Serious events: 11 serious events

Other events: 56 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Lapatinib Plus Paclitaxel n=57 participants at risk Participants received lapatinib 1500 mg orally OD with paclitaxel, administered as a 1-hour IV infusion at a dose of 80 mg/m\^2 on Days 1, 8, and 15 (±2 days) of a 28-day treatment cycle for at least 6 months. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal.
Blood and lymphatic system disorders Neutropenia	7.0% 4/57 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until 28 days after the last dose (up to Study Week 381). SAEs and non-serious AEs are reported for members of the ITT Population, comprised of all participants who received study medication.
Infections and infestations Abscess limb	1.8% 1/57 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until 28 days after the last dose (up to Study Week 381). SAEs and non-serious AEs are reported for members of the ITT Population, comprised of all participants who received study medication.
Infections and infestations Abscess soft tissue	1.8% 1/57 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until 28 days after the last dose (up to Study Week 381). SAEs and non-serious AEs are reported for members of the ITT Population, comprised of all participants who received study medication.
Infections and infestations Upper respiratory tract infection	1.8% 1/57 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until 28 days after the last dose (up to Study Week 381). SAEs and non-serious AEs are reported for members of the ITT Population, comprised of all participants who received study medication.
Gastrointestinal disorders Diarrhoea	3.5% 2/57 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until 28 days after the last dose (up to Study Week 381). SAEs and non-serious AEs are reported for members of the ITT Population, comprised of all participants who received study medication.
Cardiac disorders Cardiopulmonary failure	1.8% 1/57 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until 28 days after the last dose (up to Study Week 381). SAEs and non-serious AEs are reported for members of the ITT Population, comprised of all participants who received study medication.
Metabolism and nutrition disorders Dehydration	1.8% 1/57 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until 28 days after the last dose (up to Study Week 381). SAEs and non-serious AEs are reported for members of the ITT Population, comprised of all participants who received study medication.
Respiratory, thoracic and mediastinal disorders Bronchospasm	1.8% 1/57 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until 28 days after the last dose (up to Study Week 381). SAEs and non-serious AEs are reported for members of the ITT Population, comprised of all participants who received study medication.

Other adverse events

Other adverse events
Measure	Lapatinib Plus Paclitaxel n=57 participants at risk Participants received lapatinib 1500 mg orally OD with paclitaxel, administered as a 1-hour IV infusion at a dose of 80 mg/m\^2 on Days 1, 8, and 15 (±2 days) of a 28-day treatment cycle for at least 6 months. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal.
Gastrointestinal disorders Diarrhoea	56.1% 32/57 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until 28 days after the last dose (up to Study Week 381). SAEs and non-serious AEs are reported for members of the ITT Population, comprised of all participants who received study medication.
Blood and lymphatic system disorders Neutropenia	43.9% 25/57 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until 28 days after the last dose (up to Study Week 381). SAEs and non-serious AEs are reported for members of the ITT Population, comprised of all participants who received study medication.
Skin and subcutaneous tissue disorders Rash	40.4% 23/57 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until 28 days after the last dose (up to Study Week 381). SAEs and non-serious AEs are reported for members of the ITT Population, comprised of all participants who received study medication.
General disorders Fatigue	26.3% 15/57 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until 28 days after the last dose (up to Study Week 381). SAEs and non-serious AEs are reported for members of the ITT Population, comprised of all participants who received study medication.
Nervous system disorders Peripheral sensory neuropathy	24.6% 14/57 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until 28 days after the last dose (up to Study Week 381). SAEs and non-serious AEs are reported for members of the ITT Population, comprised of all participants who received study medication.
Blood and lymphatic system disorders Leukopenia	17.5% 10/57 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until 28 days after the last dose (up to Study Week 381). SAEs and non-serious AEs are reported for members of the ITT Population, comprised of all participants who received study medication.
Investigations Alanine aminotransferase increased	17.5% 10/57 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until 28 days after the last dose (up to Study Week 381). SAEs and non-serious AEs are reported for members of the ITT Population, comprised of all participants who received study medication.
Blood and lymphatic system disorders Anaemia	15.8% 9/57 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until 28 days after the last dose (up to Study Week 381). SAEs and non-serious AEs are reported for members of the ITT Population, comprised of all participants who received study medication.
Gastrointestinal disorders Abdominal pain upper	15.8% 9/57 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until 28 days after the last dose (up to Study Week 381). SAEs and non-serious AEs are reported for members of the ITT Population, comprised of all participants who received study medication.
Gastrointestinal disorders Nausea	15.8% 9/57 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until 28 days after the last dose (up to Study Week 381). SAEs and non-serious AEs are reported for members of the ITT Population, comprised of all participants who received study medication.
Skin and subcutaneous tissue disorders Alopecia	15.8% 9/57 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until 28 days after the last dose (up to Study Week 381). SAEs and non-serious AEs are reported for members of the ITT Population, comprised of all participants who received study medication.
Nervous system disorders Neuropathy peripheral	14.0% 8/57 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until 28 days after the last dose (up to Study Week 381). SAEs and non-serious AEs are reported for members of the ITT Population, comprised of all participants who received study medication.
Gastrointestinal disorders Vomiting	10.5% 6/57 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until 28 days after the last dose (up to Study Week 381). SAEs and non-serious AEs are reported for members of the ITT Population, comprised of all participants who received study medication.
General disorders Oedema peripheral	10.5% 6/57 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until 28 days after the last dose (up to Study Week 381). SAEs and non-serious AEs are reported for members of the ITT Population, comprised of all participants who received study medication.
Infections and infestations Upper respiratory tract infection	10.5% 6/57 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until 28 days after the last dose (up to Study Week 381). SAEs and non-serious AEs are reported for members of the ITT Population, comprised of all participants who received study medication.
Musculoskeletal and connective tissue disorders Arthralgia	10.5% 6/57 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until 28 days after the last dose (up to Study Week 381). SAEs and non-serious AEs are reported for members of the ITT Population, comprised of all participants who received study medication.
Nervous system disorders Dizziness	10.5% 6/57 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until 28 days after the last dose (up to Study Week 381). SAEs and non-serious AEs are reported for members of the ITT Population, comprised of all participants who received study medication.
Skin and subcutaneous tissue disorders Nail disorder	10.5% 6/57 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until 28 days after the last dose (up to Study Week 381). SAEs and non-serious AEs are reported for members of the ITT Population, comprised of all participants who received study medication.
General disorders Asthenia	8.8% 5/57 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until 28 days after the last dose (up to Study Week 381). SAEs and non-serious AEs are reported for members of the ITT Population, comprised of all participants who received study medication.
Infections and infestations Erysipelas	8.8% 5/57 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until 28 days after the last dose (up to Study Week 381). SAEs and non-serious AEs are reported for members of the ITT Population, comprised of all participants who received study medication.
Investigations Aspartate aminotransferase increased	8.8% 5/57 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until 28 days after the last dose (up to Study Week 381). SAEs and non-serious AEs are reported for members of the ITT Population, comprised of all participants who received study medication.
Metabolism and nutrition disorders Hypokalaemia	8.8% 5/57 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until 28 days after the last dose (up to Study Week 381). SAEs and non-serious AEs are reported for members of the ITT Population, comprised of all participants who received study medication.
Respiratory, thoracic and mediastinal disorders Cough	8.8% 5/57 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until 28 days after the last dose (up to Study Week 381). SAEs and non-serious AEs are reported for members of the ITT Population, comprised of all participants who received study medication.
Immune system disorders Hypersensitivity	7.0% 4/57 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until 28 days after the last dose (up to Study Week 381). SAEs and non-serious AEs are reported for members of the ITT Population, comprised of all participants who received study medication.
Investigations Weight decreased	7.0% 4/57 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until 28 days after the last dose (up to Study Week 381). SAEs and non-serious AEs are reported for members of the ITT Population, comprised of all participants who received study medication.
Musculoskeletal and connective tissue disorders Bone pain	7.0% 4/57 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until 28 days after the last dose (up to Study Week 381). SAEs and non-serious AEs are reported for members of the ITT Population, comprised of all participants who received study medication.
Respiratory, thoracic and mediastinal disorders Epistaxis	7.0% 4/57 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until 28 days after the last dose (up to Study Week 381). SAEs and non-serious AEs are reported for members of the ITT Population, comprised of all participants who received study medication.
Hepatobiliary disorders Hyperbilirubinaemia	5.3% 3/57 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until 28 days after the last dose (up to Study Week 381). SAEs and non-serious AEs are reported for members of the ITT Population, comprised of all participants who received study medication.
Infections and infestations Paronychia	5.3% 3/57 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until 28 days after the last dose (up to Study Week 381). SAEs and non-serious AEs are reported for members of the ITT Population, comprised of all participants who received study medication.
Infections and infestations Respiratory tract infection	5.3% 3/57 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until 28 days after the last dose (up to Study Week 381). SAEs and non-serious AEs are reported for members of the ITT Population, comprised of all participants who received study medication.
Nervous system disorders Headache	5.3% 3/57 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until 28 days after the last dose (up to Study Week 381). SAEs and non-serious AEs are reported for members of the ITT Population, comprised of all participants who received study medication.
Skin and subcutaneous tissue disorders Nail dystrophy	5.3% 3/57 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until 28 days after the last dose (up to Study Week 381). SAEs and non-serious AEs are reported for members of the ITT Population, comprised of all participants who received study medication.

Additional Information

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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