Trial Outcomes & Findings for Phase I/II Study of Lapatinib in Combination With Oxaliplatin and Capecitabine in Subjects With Advanced Colorectal Cancer (NCT NCT00536809)

NCT ID: NCT00536809

Last Updated: 2017-12-18

Results Overview

The overall response is defined as the number of participants whose tumor response was classified as a complete response (CR; disappearance of all target lesions) or partial response (PR; 30% decrease in the sum of the longest diameter of target lesions) per Response Evaluation Criteria in Solid Tumors. Response was measured for participants in Phase II only. To determine response, radiographic images were taken at baseline, 8 weeks, and every 8 weeks thereafter until the participant withdrew from the study.

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 12 participants
• Primary outcome timeframe: Baseline to response (up to 135 days)
• Results posted on: 2017-12-18

Participant Flow

This was a Phase I/II study. Enrollment of Phase I was complete; however, Phase II of the study was terminated early due to lake of interest by sites in participating. Only 2 of the 15 planned participants were enrolled prior to termination.

Participant milestones

Measure	Lapatinib/Oxaliplatin/Capecitabine Phase I: Dose escalation to a maximum tolerated dose of lapatinib 1000 milligrams (mg)/day administered orally on Days 1-21, oxaliplatin 130 mg/square meters (m\^2) administered intravenously on Day 1, and capecitabine 1500 mg/m\^2/day on Days 1-14 of a 21-day cycle. Phase II: Lapatinib 1000 mg/day administered orally on Days 1-21, oxaliplatin 130 mg/m\^2 administered intravenously on Day 1, and capecitabine 1500 mg/m\^2/day on Days 1-14 of a 21-day cycle.
Phase I (Dose-finding Phase) STARTED	10
Phase I (Dose-finding Phase) COMPLETED	10
Phase I (Dose-finding Phase) NOT COMPLETED	0
Phase II STARTED	2
Phase II COMPLETED	0
Phase II NOT COMPLETED	2

Reasons for withdrawal

Measure	Lapatinib/Oxaliplatin/Capecitabine Phase I: Dose escalation to a maximum tolerated dose of lapatinib 1000 milligrams (mg)/day administered orally on Days 1-21, oxaliplatin 130 mg/square meters (m\^2) administered intravenously on Day 1, and capecitabine 1500 mg/m\^2/day on Days 1-14 of a 21-day cycle. Phase II: Lapatinib 1000 mg/day administered orally on Days 1-21, oxaliplatin 130 mg/m\^2 administered intravenously on Day 1, and capecitabine 1500 mg/m\^2/day on Days 1-14 of a 21-day cycle.
Phase II Adverse Event	1
Phase II Referred for surgical resection	1

Baseline Characteristics

Phase I/II Study of Lapatinib in Combination With Oxaliplatin and Capecitabine in Subjects With Advanced Colorectal Cancer

Baseline characteristics by cohort

Measure	Lap. 1000 mg/Oxaliplatin 130 mg/m^2/Capecitabine 1500 mg/m^2 n=12 Participants Lapatinib (Lap.) 1000 milligrams (mg)/day administered orally on Days 1-21, oxaliplatin 130 mg/square meters (m\^2) administered intravenously on Day 1, and capecitabine 1500 mg/m\^2/day on Days 1-14 of a 21-day cycle
Age, Continuous	59.9 years n=93 Participants
Sex: Female, Male Female	11 Participants n=93 Participants
Sex: Female, Male Male	1 Participants n=93 Participants
Race/Ethnicity, Customized White/Caucasian/European heritage	12 participants n=93 Participants

PRIMARY outcome

Timeframe: Baseline to response (up to 135 days)

Population: All-Treated Population for Phase II: all participants who received at least one dose of lapatinib

The overall response is defined as the number of participants whose tumor response was classified as a complete response (CR; disappearance of all target lesions) or partial response (PR; 30% decrease in the sum of the longest diameter of target lesions) per Response Evaluation Criteria in Solid Tumors. Response was measured for participants in Phase II only. To determine response, radiographic images were taken at baseline, 8 weeks, and every 8 weeks thereafter until the participant withdrew from the study.

Outcome measures

Measure	Lap. 1000 mg/Oxaliplatin 130 mg/m^2/Capecitabine 1500 mg/m^2 n=2 Participants Lapatinib (Lap.) 1000 milligrams (mg)/day administered orally on Days 1-21, oxaliplatin 130 mg/square meters (m\^2) administered intravenously on Day 1, and capecitabine 1500 mg/m\^2 administered orally twice a day on Days 1-14 of a 21-day cycle
Overall Response in Phase II	2 participants

SECONDARY outcome

Timeframe: Plasma TS mRNA is collected at screening. Pre-treatment tumor sample can be archived tissue if collected within 5 years from screening; if not, tumor sample should be collected at screening.

Population: All-Treated population for Phase II

Exploring if there is an association with a reduction in thymidylate synthase (TS) gene expression in both plasma and tumor prior to treatment and increased sensitivity in clinical activity. This analysis was not completed due to the study being closed early and the small number of participants enrolled in Phase II.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Blood samples were collected to determine TS levels at screening phase; Days 43 and 85; after every 2 cycles of treatment (+/- 3 days); and at discontinuation (if possible).

Population: All-Treated population for Phase II

A possible association between a reduction in thymidylate synthase (TS) gene expression and increased sensitivity in clinical activity was to be explored. This analysis was not completed due to the study being closed early and the small number of participants enrolled in Phase II.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Pre-treatment tumor sample should have been provided for the most recent biopsy (not older than 5 years) prior to dosing. The post-treatment sample is suggested, not mandatory, and should have been collected at 43 +/-3 days.

Population: All-Treated population for Phase II

Exploring tumor-derived biomarkers including TS, DPD, TP, EGFR (ErbB1), and additional downstream markers involved in the mechanism of action of each compound (e.g., ERCC1) and comparison to clinical response. This analysis was not completed due to the study being closed early and the small number of participants enrolled in Phase II.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Pre-treatment tumor sample should have been provided for the most recent biopsy (not older than 5 years) prior to dosing. The post-treatment sample is suggested, not mandatory, and should have been collected at end of Cycle 2, +/-3 days from Cycle 3.

Population: All-Treated population for Phase II

DNA sequencing was done to identify genetic aberrations in somatic (tumor) DNA that may associate with clinical outcomes in response to therapy. This analysis was not completed due to the study being closed early and the small number of participants enrolled in Phase II.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Optional pharmacogenetics sample may be collected at any time during the study after consent has been obtained; however, it is recommended that it be collected at the earliest time point possible

Population: Participants in the All-Treated Population who signed a PGx informed consent.

This outcome measure was conducted to investigate a possible genetic relationship to handling or response to lapatinib, oxaliplatin, and capecitabine. This measure was not analyzed due to the small number of participants who signed the optional pharmacogenetics consent.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Date of the first dose of study drug to the date of documented and confirmed progression by clinical, radiographic, or biochemical criteria, whichever occurred earliest, or to date of death due to any causes (up to 135 Days)

Population: All-Treated Population for Phase II

Both participants that entered Phase II of the study were censored for progression-free survival. Progression-free survival (PFS) is defined as the time from first dose until the first documented sign of disease progression or death due to any cause. For participants who do not progress or die, PFS was censored at the time of last radiological scan preceding the initiation of alternative anti-cancer therapy. Of the 2 participants in Phase II of the study, one discontinued due to adverse events, and the other was referred for a surgical resection.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline to study completion (up to 135 days)

Population: All-Treated Population for Phase II

Each on-study and follow-up laboratory parameter and vital sign was compared to the participant's baseline values to investigate what changes occurred. This analysis was not completed due to the study being closed early and the small number of participants enrolled in Phase II.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline to study completion (up to 135 days)

Population: All-Treated Population for Phase II

Each on-study and follow-up laboratory parameter and vital sign was compared to the participant's baseline values to investigate what changes occurred. This analysis was not completed due to the study being closed early and the small number of participants enrolled in Phase II.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline to study completion (up to 135 days)

Population: All-Treated Population for Phase II

Each on-study and follow-up laboratory parameter and vital sign was compared to the participant's baseline values to investigate what changes occurred. This analysis was not completed due to the study being closed early and the small number of participants enrolled in Phase II.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline to study completion (up to 135 days)

Population: All-Treated Population for Phase II

Each on-study and follow-up laboratory parameter and vital sign was compared to the participant's baseline values to investigate what changes occurred. This analysis was not completed due to the study being closed early and the small number of participants enrolled in Phase II.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline to study completion (up to 135 days)

Population: All-Treated Population for Phase II

Each on-study and follow-up laboratory parameter and vital sign was compared to the participant's baseline values to investigate what changes occurred. This analysis was not completed due to the study being closed early and the small number of participants enrolled in Phase II.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline to study completion (up to 135 days)

Population: All-Treated Population for Phase II

Each on-study and follow-up laboratory parameter and vital sign was compared to the participant's baseline values to investigate what changes occurred. This analysis was not completed due to the study being closed early and the small number of participants enrolled in Phase II.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline to study completion (up to 135 days)

Population: All-Treated Population for Phase II

Each on-study and follow-up laboratory parameter and vital sign was compared to the participant's baseline values to investigate what changes occurred. This analysis was not completed due to the study being closed early and the small number of participants enrolled in Phase II.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline to study completion (up to 135 days)

Population: All-Treated Population for Phase II

Each on-study and follow-up laboratory parameter and vital sign was compared to the participant's baseline values to investigate what changes occurred. This analysis was not completed due to the study being closed early and the small number of participants enrolled in Phase II.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline to study completion (up to 135 days)

Population: All-Treated Population for Phase II

Each on-study and follow-up laboratory parameter and vital sign was compared to the participant's baseline values to investigate what changes occurred. This analysis was not completed due to the study being closed early and the small number of participants enrolled in Phase II.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline to study completion (up to 135 days)

Population: All-Treated Population for Phase II

Each on-study and follow-up laboratory parameter and vital sign was compared to the participant's baseline values to investigate what changes occurred. This analysis was not completed due to the study being closed early and the small number of participants enrolled in Phase II.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline to study completion (up to 135 days)

Population: All-Treated Population for Phase II

Each on-study and follow-up laboratory parameter and vital sign was compared to the participant's baseline values to investigate what changes occurred. This analysis was not completed due to the study being closed early and the small number of participants enrolled in Phase II.

Outcome measures

Outcome data not reported

Adverse Events

Lap. 1000 mg/Oxaliplatin 130 mg/m^2/Capecitabine 1500 mg/m^2

Serious events: 5 serious events

Other events: 12 other events

Deaths: 0 deaths

Serious adverse events

Measure	Lap. 1000 mg/Oxaliplatin 130 mg/m^2/Capecitabine 1500 mg/m^2 n=12 participants at risk Lapatinib (Lap.) 1000 milligrams (mg)/day administered orally on Days 1-21, oxaliplatin 130 mg/square meters (m\^2) administered intravenously on Day 1, and capecitabine 1500 mg/m\^2 administered orally twice a day on Days 1-14 of a 21-day cycle
Metabolism and nutrition disorders Hypokalemia	33.3% 4/12 • Phases I and II GSK typically summarizes all AEs and all SAEs. The SAE summary will include participants with only an SAE. The data summarized below under the heading Other AEs (non-serious) are actually a summary of all AEs, which does include some SAEs.
Metabolism and nutrition disorders Dehydration	16.7% 2/12 • Phases I and II GSK typically summarizes all AEs and all SAEs. The SAE summary will include participants with only an SAE. The data summarized below under the heading Other AEs (non-serious) are actually a summary of all AEs, which does include some SAEs.
Metabolism and nutrition disorders Hyponatremia	8.3% 1/12 • Phases I and II GSK typically summarizes all AEs and all SAEs. The SAE summary will include participants with only an SAE. The data summarized below under the heading Other AEs (non-serious) are actually a summary of all AEs, which does include some SAEs.
Respiratory, thoracic and mediastinal disorders Laryngeal disorder	8.3% 1/12 • Phases I and II GSK typically summarizes all AEs and all SAEs. The SAE summary will include participants with only an SAE. The data summarized below under the heading Other AEs (non-serious) are actually a summary of all AEs, which does include some SAEs.
Gastrointestinal disorders Diarrhoea	8.3% 1/12 • Phases I and II GSK typically summarizes all AEs and all SAEs. The SAE summary will include participants with only an SAE. The data summarized below under the heading Other AEs (non-serious) are actually a summary of all AEs, which does include some SAEs.
Gastrointestinal disorders Nausea	8.3% 1/12 • Phases I and II GSK typically summarizes all AEs and all SAEs. The SAE summary will include participants with only an SAE. The data summarized below under the heading Other AEs (non-serious) are actually a summary of all AEs, which does include some SAEs.
Gastrointestinal disorders Vomiting	8.3% 1/12 • Phases I and II GSK typically summarizes all AEs and all SAEs. The SAE summary will include participants with only an SAE. The data summarized below under the heading Other AEs (non-serious) are actually a summary of all AEs, which does include some SAEs.
Hepatobiliary disorders Hyperbilirubinemia	8.3% 1/12 • Phases I and II GSK typically summarizes all AEs and all SAEs. The SAE summary will include participants with only an SAE. The data summarized below under the heading Other AEs (non-serious) are actually a summary of all AEs, which does include some SAEs.
Nervous system disorders Dizziness	8.3% 1/12 • Phases I and II GSK typically summarizes all AEs and all SAEs. The SAE summary will include participants with only an SAE. The data summarized below under the heading Other AEs (non-serious) are actually a summary of all AEs, which does include some SAEs.

Other adverse events

Measure	Lap. 1000 mg/Oxaliplatin 130 mg/m^2/Capecitabine 1500 mg/m^2 n=12 participants at risk Lapatinib (Lap.) 1000 milligrams (mg)/day administered orally on Days 1-21, oxaliplatin 130 mg/square meters (m\^2) administered intravenously on Day 1, and capecitabine 1500 mg/m\^2 administered orally twice a day on Days 1-14 of a 21-day cycle
Gastrointestinal disorders Diarrhoea	100.0% 12/12 • Phases I and II GSK typically summarizes all AEs and all SAEs. The SAE summary will include participants with only an SAE. The data summarized below under the heading Other AEs (non-serious) are actually a summary of all AEs, which does include some SAEs.
Metabolism and nutrition disorders Anorexia	83.3% 10/12 • Phases I and II GSK typically summarizes all AEs and all SAEs. The SAE summary will include participants with only an SAE. The data summarized below under the heading Other AEs (non-serious) are actually a summary of all AEs, which does include some SAEs.
Gastrointestinal disorders Nausea	83.3% 10/12 • Phases I and II GSK typically summarizes all AEs and all SAEs. The SAE summary will include participants with only an SAE. The data summarized below under the heading Other AEs (non-serious) are actually a summary of all AEs, which does include some SAEs.
Nervous system disorders Peripheral sensory neuropathy	75.0% 9/12 • Phases I and II GSK typically summarizes all AEs and all SAEs. The SAE summary will include participants with only an SAE. The data summarized below under the heading Other AEs (non-serious) are actually a summary of all AEs, which does include some SAEs.
Gastrointestinal disorders Vomiting	75.0% 9/12 • Phases I and II GSK typically summarizes all AEs and all SAEs. The SAE summary will include participants with only an SAE. The data summarized below under the heading Other AEs (non-serious) are actually a summary of all AEs, which does include some SAEs.
General disorders Fatigue	66.7% 8/12 • Phases I and II GSK typically summarizes all AEs and all SAEs. The SAE summary will include participants with only an SAE. The data summarized below under the heading Other AEs (non-serious) are actually a summary of all AEs, which does include some SAEs.
Nervous system disorders Dizziness	50.0% 6/12 • Phases I and II GSK typically summarizes all AEs and all SAEs. The SAE summary will include participants with only an SAE. The data summarized below under the heading Other AEs (non-serious) are actually a summary of all AEs, which does include some SAEs.
Gastrointestinal disorders Constipation	41.7% 5/12 • Phases I and II GSK typically summarizes all AEs and all SAEs. The SAE summary will include participants with only an SAE. The data summarized below under the heading Other AEs (non-serious) are actually a summary of all AEs, which does include some SAEs.
Metabolism and nutrition disorders Hypokalemia	41.7% 5/12 • Phases I and II GSK typically summarizes all AEs and all SAEs. The SAE summary will include participants with only an SAE. The data summarized below under the heading Other AEs (non-serious) are actually a summary of all AEs, which does include some SAEs.
Nervous system disorders Neuropathy peripheral	33.3% 4/12 • Phases I and II GSK typically summarizes all AEs and all SAEs. The SAE summary will include participants with only an SAE. The data summarized below under the heading Other AEs (non-serious) are actually a summary of all AEs, which does include some SAEs.
Investigations Weight decreased	33.3% 4/12 • Phases I and II GSK typically summarizes all AEs and all SAEs. The SAE summary will include participants with only an SAE. The data summarized below under the heading Other AEs (non-serious) are actually a summary of all AEs, which does include some SAEs.
Gastrointestinal disorders Abdominal distension	25.0% 3/12 • Phases I and II GSK typically summarizes all AEs and all SAEs. The SAE summary will include participants with only an SAE. The data summarized below under the heading Other AEs (non-serious) are actually a summary of all AEs, which does include some SAEs.
Gastrointestinal disorders Abdominal pain	25.0% 3/12 • Phases I and II GSK typically summarizes all AEs and all SAEs. The SAE summary will include participants with only an SAE. The data summarized below under the heading Other AEs (non-serious) are actually a summary of all AEs, which does include some SAEs.
Blood and lymphatic system disorders Anaemia	25.0% 3/12 • Phases I and II GSK typically summarizes all AEs and all SAEs. The SAE summary will include participants with only an SAE. The data summarized below under the heading Other AEs (non-serious) are actually a summary of all AEs, which does include some SAEs.
Nervous system disorders Dysgeusia	25.0% 3/12 • Phases I and II GSK typically summarizes all AEs and all SAEs. The SAE summary will include participants with only an SAE. The data summarized below under the heading Other AEs (non-serious) are actually a summary of all AEs, which does include some SAEs.
Blood and lymphatic system disorders Neutropenia	25.0% 3/12 • Phases I and II GSK typically summarizes all AEs and all SAEs. The SAE summary will include participants with only an SAE. The data summarized below under the heading Other AEs (non-serious) are actually a summary of all AEs, which does include some SAEs.
Gastrointestinal disorders Abdominal pain upper	16.7% 2/12 • Phases I and II GSK typically summarizes all AEs and all SAEs. The SAE summary will include participants with only an SAE. The data summarized below under the heading Other AEs (non-serious) are actually a summary of all AEs, which does include some SAEs.
Psychiatric disorders Anxiety	16.7% 2/12 • Phases I and II GSK typically summarizes all AEs and all SAEs. The SAE summary will include participants with only an SAE. The data summarized below under the heading Other AEs (non-serious) are actually a summary of all AEs, which does include some SAEs.
Investigations Blood albumin decreased	16.7% 2/12 • Phases I and II GSK typically summarizes all AEs and all SAEs. The SAE summary will include participants with only an SAE. The data summarized below under the heading Other AEs (non-serious) are actually a summary of all AEs, which does include some SAEs.
Investigations Blood alkaline phosphatase increased	16.7% 2/12 • Phases I and II GSK typically summarizes all AEs and all SAEs. The SAE summary will include participants with only an SAE. The data summarized below under the heading Other AEs (non-serious) are actually a summary of all AEs, which does include some SAEs.
Metabolism and nutrition disorders Dehydration	16.7% 2/12 • Phases I and II GSK typically summarizes all AEs and all SAEs. The SAE summary will include participants with only an SAE. The data summarized below under the heading Other AEs (non-serious) are actually a summary of all AEs, which does include some SAEs.
Gastrointestinal disorders Dyspepsia	16.7% 2/12 • Phases I and II GSK typically summarizes all AEs and all SAEs. The SAE summary will include participants with only an SAE. The data summarized below under the heading Other AEs (non-serious) are actually a summary of all AEs, which does include some SAEs.
Gastrointestinal disorders Flatulence	16.7% 2/12 • Phases I and II GSK typically summarizes all AEs and all SAEs. The SAE summary will include participants with only an SAE. The data summarized below under the heading Other AEs (non-serious) are actually a summary of all AEs, which does include some SAEs.
Hepatobiliary disorders Hyperbilirubunaemia	16.7% 2/12 • Phases I and II GSK typically summarizes all AEs and all SAEs. The SAE summary will include participants with only an SAE. The data summarized below under the heading Other AEs (non-serious) are actually a summary of all AEs, which does include some SAEs.
Blood and lymphatic system disorders Leukopenia	16.7% 2/12 • Phases I and II GSK typically summarizes all AEs and all SAEs. The SAE summary will include participants with only an SAE. The data summarized below under the heading Other AEs (non-serious) are actually a summary of all AEs, which does include some SAEs.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	16.7% 2/12 • Phases I and II GSK typically summarizes all AEs and all SAEs. The SAE summary will include participants with only an SAE. The data summarized below under the heading Other AEs (non-serious) are actually a summary of all AEs, which does include some SAEs.
Gastrointestinal disorders Stomatitis	16.7% 2/12 • Phases I and II GSK typically summarizes all AEs and all SAEs. The SAE summary will include participants with only an SAE. The data summarized below under the heading Other AEs (non-serious) are actually a summary of all AEs, which does include some SAEs.
Investigations Alanine aminotransferase increased	8.3% 1/12 • Phases I and II GSK typically summarizes all AEs and all SAEs. The SAE summary will include participants with only an SAE. The data summarized below under the heading Other AEs (non-serious) are actually a summary of all AEs, which does include some SAEs.
Investigations Aspartate aminotransferase increased	8.3% 1/12 • Phases I and II GSK typically summarizes all AEs and all SAEs. The SAE summary will include participants with only an SAE. The data summarized below under the heading Other AEs (non-serious) are actually a summary of all AEs, which does include some SAEs.
General disorders Asthenia	8.3% 1/12 • Phases I and II GSK typically summarizes all AEs and all SAEs. The SAE summary will include participants with only an SAE. The data summarized below under the heading Other AEs (non-serious) are actually a summary of all AEs, which does include some SAEs.
Eye disorders Blindness transient	8.3% 1/12 • Phases I and II GSK typically summarizes all AEs and all SAEs. The SAE summary will include participants with only an SAE. The data summarized below under the heading Other AEs (non-serious) are actually a summary of all AEs, which does include some SAEs.
General disorders Chest discomfort	8.3% 1/12 • Phases I and II GSK typically summarizes all AEs and all SAEs. The SAE summary will include participants with only an SAE. The data summarized below under the heading Other AEs (non-serious) are actually a summary of all AEs, which does include some SAEs.
General disorders Chest pain	8.3% 1/12 • Phases I and II GSK typically summarizes all AEs and all SAEs. The SAE summary will include participants with only an SAE. The data summarized below under the heading Other AEs (non-serious) are actually a summary of all AEs, which does include some SAEs.
Respiratory, thoracic and mediastinal disorders Cough	8.3% 1/12 • Phases I and II GSK typically summarizes all AEs and all SAEs. The SAE summary will include participants with only an SAE. The data summarized below under the heading Other AEs (non-serious) are actually a summary of all AEs, which does include some SAEs.
Psychiatric disorders Depression	8.3% 1/12 • Phases I and II GSK typically summarizes all AEs and all SAEs. The SAE summary will include participants with only an SAE. The data summarized below under the heading Other AEs (non-serious) are actually a summary of all AEs, which does include some SAEs.
Gastrointestinal disorders Dry mouth	8.3% 1/12 • Phases I and II GSK typically summarizes all AEs and all SAEs. The SAE summary will include participants with only an SAE. The data summarized below under the heading Other AEs (non-serious) are actually a summary of all AEs, which does include some SAEs.
Gastrointestinal disorders Duodenal ulcer	8.3% 1/12 • Phases I and II GSK typically summarizes all AEs and all SAEs. The SAE summary will include participants with only an SAE. The data summarized below under the heading Other AEs (non-serious) are actually a summary of all AEs, which does include some SAEs.
Nervous system disorders Dyskinesia	8.3% 1/12 • Phases I and II GSK typically summarizes all AEs and all SAEs. The SAE summary will include participants with only an SAE. The data summarized below under the heading Other AEs (non-serious) are actually a summary of all AEs, which does include some SAEs.
Respiratory, thoracic and mediastinal disorders Dysphonia	8.3% 1/12 • Phases I and II GSK typically summarizes all AEs and all SAEs. The SAE summary will include participants with only an SAE. The data summarized below under the heading Other AEs (non-serious) are actually a summary of all AEs, which does include some SAEs.
Respiratory, thoracic and mediastinal disorders Dyspnoea	8.3% 1/12 • Phases I and II GSK typically summarizes all AEs and all SAEs. The SAE summary will include participants with only an SAE. The data summarized below under the heading Other AEs (non-serious) are actually a summary of all AEs, which does include some SAEs.
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	8.3% 1/12 • Phases I and II GSK typically summarizes all AEs and all SAEs. The SAE summary will include participants with only an SAE. The data summarized below under the heading Other AEs (non-serious) are actually a summary of all AEs, which does include some SAEs.
Eye disorders Eye pain	8.3% 1/12 • Phases I and II GSK typically summarizes all AEs and all SAEs. The SAE summary will include participants with only an SAE. The data summarized below under the heading Other AEs (non-serious) are actually a summary of all AEs, which does include some SAEs.
Nervous system disorders Headache	8.3% 1/12 • Phases I and II GSK typically summarizes all AEs and all SAEs. The SAE summary will include participants with only an SAE. The data summarized below under the heading Other AEs (non-serious) are actually a summary of all AEs, which does include some SAEs.
Respiratory, thoracic and mediastinal disorders Hiccups	8.3% 1/12 • Phases I and II GSK typically summarizes all AEs and all SAEs. The SAE summary will include participants with only an SAE. The data summarized below under the heading Other AEs (non-serious) are actually a summary of all AEs, which does include some SAEs.
Metabolism and nutrition disorders Hypercalcaemia	8.3% 1/12 • Phases I and II GSK typically summarizes all AEs and all SAEs. The SAE summary will include participants with only an SAE. The data summarized below under the heading Other AEs (non-serious) are actually a summary of all AEs, which does include some SAEs.
Metabolism and nutrition disorders Hyperglycaemia	8.3% 1/12 • Phases I and II GSK typically summarizes all AEs and all SAEs. The SAE summary will include participants with only an SAE. The data summarized below under the heading Other AEs (non-serious) are actually a summary of all AEs, which does include some SAEs.
Metabolism and nutrition disorders Hyponatraemia	8.3% 1/12 • Phases I and II GSK typically summarizes all AEs and all SAEs. The SAE summary will include participants with only an SAE. The data summarized below under the heading Other AEs (non-serious) are actually a summary of all AEs, which does include some SAEs.
Vascular disorders Hypotension	8.3% 1/12 • Phases I and II GSK typically summarizes all AEs and all SAEs. The SAE summary will include participants with only an SAE. The data summarized below under the heading Other AEs (non-serious) are actually a summary of all AEs, which does include some SAEs.
General disorders Injection site reaction	8.3% 1/12 • Phases I and II GSK typically summarizes all AEs and all SAEs. The SAE summary will include participants with only an SAE. The data summarized below under the heading Other AEs (non-serious) are actually a summary of all AEs, which does include some SAEs.
Psychiatric disorders Insomnia	8.3% 1/12 • Phases I and II GSK typically summarizes all AEs and all SAEs. The SAE summary will include participants with only an SAE. The data summarized below under the heading Other AEs (non-serious) are actually a summary of all AEs, which does include some SAEs.
Respiratory, thoracic and mediastinal disorders Laryngeal disorder	8.3% 1/12 • Phases I and II GSK typically summarizes all AEs and all SAEs. The SAE summary will include participants with only an SAE. The data summarized below under the heading Other AEs (non-serious) are actually a summary of all AEs, which does include some SAEs.
Cardiac disorders Left ventricular dysfunctionation	8.3% 1/12 • Phases I and II GSK typically summarizes all AEs and all SAEs. The SAE summary will include participants with only an SAE. The data summarized below under the heading Other AEs (non-serious) are actually a summary of all AEs, which does include some SAEs.
General disorders Mucosal inflammation	8.3% 1/12 • Phases I and II GSK typically summarizes all AEs and all SAEs. The SAE summary will include participants with only an SAE. The data summarized below under the heading Other AEs (non-serious) are actually a summary of all AEs, which does include some SAEs.
Musculoskeletal and connective tissue disorders Muscular weakness	8.3% 1/12 • Phases I and II GSK typically summarizes all AEs and all SAEs. The SAE summary will include participants with only an SAE. The data summarized below under the heading Other AEs (non-serious) are actually a summary of all AEs, which does include some SAEs.
General disorders Oedema	8.3% 1/12 • Phases I and II GSK typically summarizes all AEs and all SAEs. The SAE summary will include participants with only an SAE. The data summarized below under the heading Other AEs (non-serious) are actually a summary of all AEs, which does include some SAEs.
Gastrointestinal disorders Oesophageal pain	8.3% 1/12 • Phases I and II GSK typically summarizes all AEs and all SAEs. The SAE summary will include participants with only an SAE. The data summarized below under the heading Other AEs (non-serious) are actually a summary of all AEs, which does include some SAEs.
Infections and infestations Oral candidiasis	8.3% 1/12 • Phases I and II GSK typically summarizes all AEs and all SAEs. The SAE summary will include participants with only an SAE. The data summarized below under the heading Other AEs (non-serious) are actually a summary of all AEs, which does include some SAEs.
Musculoskeletal and connective tissue disorders Pain in extremity	8.3% 1/12 • Phases I and II GSK typically summarizes all AEs and all SAEs. The SAE summary will include participants with only an SAE. The data summarized below under the heading Other AEs (non-serious) are actually a summary of all AEs, which does include some SAEs.
Skin and subcutaneous tissue disorders Pruritus	8.3% 1/12 • Phases I and II GSK typically summarizes all AEs and all SAEs. The SAE summary will include participants with only an SAE. The data summarized below under the heading Other AEs (non-serious) are actually a summary of all AEs, which does include some SAEs.
General disorders Pyrexia	8.3% 1/12 • Phases I and II GSK typically summarizes all AEs and all SAEs. The SAE summary will include participants with only an SAE. The data summarized below under the heading Other AEs (non-serious) are actually a summary of all AEs, which does include some SAEs.
Nervous system disorders Somnolence	8.3% 1/12 • Phases I and II GSK typically summarizes all AEs and all SAEs. The SAE summary will include participants with only an SAE. The data summarized below under the heading Other AEs (non-serious) are actually a summary of all AEs, which does include some SAEs.
Vascular disorders Thrombosis	8.3% 1/12 • Phases I and II GSK typically summarizes all AEs and all SAEs. The SAE summary will include participants with only an SAE. The data summarized below under the heading Other AEs (non-serious) are actually a summary of all AEs, which does include some SAEs.
Vascular disorders Ventricular tachycardia	8.3% 1/12 • Phases I and II GSK typically summarizes all AEs and all SAEs. The SAE summary will include participants with only an SAE. The data summarized below under the heading Other AEs (non-serious) are actually a summary of all AEs, which does include some SAEs.
Eye disorders Vision blurred	8.3% 1/12 • Phases I and II GSK typically summarizes all AEs and all SAEs. The SAE summary will include participants with only an SAE. The data summarized below under the heading Other AEs (non-serious) are actually a summary of all AEs, which does include some SAEs.
Investigations Weight increased	8.3% 1/12 • Phases I and II GSK typically summarizes all AEs and all SAEs. The SAE summary will include participants with only an SAE. The data summarized below under the heading Other AEs (non-serious) are actually a summary of all AEs, which does include some SAEs.
Nervous system disorders Hyperaesthia	8.3% 1/12 • Phases I and II GSK typically summarizes all AEs and all SAEs. The SAE summary will include participants with only an SAE. The data summarized below under the heading Other AEs (non-serious) are actually a summary of all AEs, which does include some SAEs.
Metabolism and nutrition disorders Hyporcalceamia	8.3% 1/12 • Phases I and II GSK typically summarizes all AEs and all SAEs. The SAE summary will include participants with only an SAE. The data summarized below under the heading Other AEs (non-serious) are actually a summary of all AEs, which does include some SAEs.

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