Trial Outcomes & Findings for Study of Safety and Efficacy of Talimogene Laherparepvec With Cisplatin and Radiotherapy for Treatment of Locally Advanced Head and Neck Cancer (NCT NCT01161498)

Last Updated: 2016-02-08

Results Overview

Event-free survival is defined as the time from randomization until the first evidence of relapse, disease progression (local, regional, metastatic, or second primary), or death from any cause. Because this study was terminated with only 5 participants enrolled, and the study was terminated in the first year, this endpoint was not analyzed.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

5 participants

Primary outcome timeframe

2 years

Results posted on

2016-02-08

Participant Flow

This study was open to patients with advanced, non-metastatic, stage III or IV squamous cell carcinoma of the head and neck (SCCHN).

Participant milestones

Participant milestones
Measure	Radiation/Cisplatin Participants received cisplatin (100 mg/m²) administered intravenously on Days 0, 21, and 42. Radiation was administered concurrently with cisplatin in 35 fractions over a 7-week period.	Talimogene Laherparepvec + Radiation/Cisplatin The first dose of talimogene laherparepvec was up to 8 mL total volume (up to 4 mL per lesion) at 10⁶ plaque-forming units (PFU)/mL, administered into all injectable affected nodes on Day 0. Subsequent doses were up to 8 mL total volume (up to 4 mL per lesion) at 10⁸ PFU/mL on Days 21, 42, and 63. Participants also received cisplatin (100 mg/m²) administered intravenously on Days 0, 21, and 42 and radiation administered concurrently in 35 fractions over a 7-week period.
Overall Study STARTED	3	2
Overall Study COMPLETED	3	1
Overall Study NOT COMPLETED	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Radiation/Cisplatin Participants received cisplatin (100 mg/m²) administered intravenously on Days 0, 21, and 42. Radiation was administered concurrently with cisplatin in 35 fractions over a 7-week period.	Talimogene Laherparepvec + Radiation/Cisplatin The first dose of talimogene laherparepvec was up to 8 mL total volume (up to 4 mL per lesion) at 10⁶ plaque-forming units (PFU)/mL, administered into all injectable affected nodes on Day 0. Subsequent doses were up to 8 mL total volume (up to 4 mL per lesion) at 10⁸ PFU/mL on Days 21, 42, and 63. Participants also received cisplatin (100 mg/m²) administered intravenously on Days 0, 21, and 42 and radiation administered concurrently in 35 fractions over a 7-week period.
Overall Study Disease Progression	0	1

Baseline Characteristics

Study of Safety and Efficacy of Talimogene Laherparepvec With Cisplatin and Radiotherapy for Treatment of Locally Advanced Head and Neck Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Radiation/Cisplatin n=3 Participants Participants received cisplatin (100 mg/m²) administered intravenously on Days 0, 21, and 42. Radiation was administered concurrently with cisplatin in 35 fractions over a 7-week period.	Talimogene Laherparepvec + Radiation/Cisplatin n=2 Participants The first dose of talimogene laherparepvec was up to 8 mL total volume (up to 4 mL per lesion) at 10⁶ PFU/mL, administered into all injectable affected nodes on Day 0. Subsequent doses were up to 8 mL total volume (up to 4 mL per lesion) at 10⁸ PFU/mL on Days 21, 42, and 63. Participants also received cisplatin (100 mg/m²) administered intravenously on Days 0, 21, and 42 and radiation administered concurrently in 35 fractions over a 7-week period.	Total n=5 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants

PRIMARY outcome

Timeframe: 2 years

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: End of trial; the maximum time on study was 20 weeks.

Population: All randomized participants

Tumor response was assessed by computed tomography (CT) scan according to a modified version of the revised Response Evaluation Criteria In Solid Tumors (RECIST) criteria (version 1.1). Objective response is defined as achieving a clinical partial response (cPR) or complete response (cCR). cCR is defined as disappearance of all baseline lesions. Any pathological lymph nodes must have a reduction in short axis to \< 10 mm. cPR is defined as at least a 30% decrease in the sum of diameters of baseline lesions. Progressive disease (PD) is defined as at least a 20% increase in the sum of diameters of baseline lesions, taking as reference the smallest sum on study, and an absolute increase of at least 5 mm, or the appearance of any new lesions. Because this study was terminated with 5 patients enrolled, data for this endpoint were summarized in by-patient listings only and the cOR rate was not calculated. Therefore a summary of response at the end of study is reported.

Outcome measures

Outcome measures
Measure	Radiation/Cisplatin n=3 Participants Participants received cisplatin (100 mg/m²) administered intravenously on Days 0, 21, and 42. Radiation was administered concurrently with cisplatin in 35 fractions over a 7-week period.	Talimogene Laherparepvec + Radiation/Cisplatin n=2 Participants The first dose of talimogene laherparepvec was up to 8 mL total volume (up to 4 mL per lesion) at 10⁶ PFU/mL, administered into all injectable affected nodes on Day 0. Subsequent doses were up to 8 mL total volume (up to 4 mL per lesion) at 10⁸ PFU/mL on Days 21, 42, and 63. Participants also received cisplatin (100 mg/m²) administered intravenously on Days 0, 21, and 42 and radiation administered concurrently in 35 fractions over a 7-week period.
Clinical Objective Response (cOR) Clinical Complete Response (cCR)	2 participants	1 participants
Clinical Objective Response (cOR) Clinical Partial Response (cPR)	0 participants	0 participants
Clinical Objective Response (cOR) Progressive Disease	1 participants	0 participants
Clinical Objective Response (cOR) Unevaluable	0 participants	1 participants

SECONDARY outcome

Timeframe: End of study; the maximum time on study was 20 weeks.

Population: All randomized participants

Response to therapy was assessed using \[(18)F\] fluorodeoxyglucose positron emission tomography (FDG PET) imaging to detect metabolically active tumors. Metabolic complete response (mCR) is defined as complete disappearance of FDG uptake attributable to tumor compared to baseline scan. Partial metabolic response (mPR) is defined as a \> 40% decrease in specific uptake compared to the initial value in over half of the lesions. Disease progression (mPD) is defined as a specific uptake increase in any lesion, appearance of new lesions, or presence of extended areas of disease activity. Stable metabolic response (mSD) is defined as a decrease in uptake \< 40% of the initial value of over half the lesions. Because this study was terminated with 5 patients enrolled, data for this endpoint were summarized in by-patient listings only and the metabolic complete response rate was not calculated. Therefore a summary of metabolic response at end of study is reported.

Outcome measures

Outcome measures
Measure	Radiation/Cisplatin n=3 Participants Participants received cisplatin (100 mg/m²) administered intravenously on Days 0, 21, and 42. Radiation was administered concurrently with cisplatin in 35 fractions over a 7-week period.	Talimogene Laherparepvec + Radiation/Cisplatin n=2 Participants The first dose of talimogene laherparepvec was up to 8 mL total volume (up to 4 mL per lesion) at 10⁶ PFU/mL, administered into all injectable affected nodes on Day 0. Subsequent doses were up to 8 mL total volume (up to 4 mL per lesion) at 10⁸ PFU/mL on Days 21, 42, and 63. Participants also received cisplatin (100 mg/m²) administered intravenously on Days 0, 21, and 42 and radiation administered concurrently in 35 fractions over a 7-week period.
Metabolic Complete Response (mCR) Metabolic Complete Response (mCR)	1 participants	1 participants
Metabolic Complete Response (mCR) Metabolic Partial Response (mPR)	0 participants	0 participants
Metabolic Complete Response (mCR) Metabolic Progressive Disease (mPD)	1 participants	0 participants
Metabolic Complete Response (mCR) Stable Metabolic Response (mSD)	0 participants	0 participants
Metabolic Complete Response (mCR) Unevaluable	1 participants	1 participants

SECONDARY outcome

Timeframe: Up to Week 20

Population: Randomized participants who had protocol-specified surgery

Response to therapy was assessed histopathologically from biopsies taken at surgery for those participants who had surgery prior to Week 22. If no viable tumor cells were identified in surgical specimens (where the patient had surgery) the patient was classified as having a pathological complete response (pCR), and if viable tumor cells were identified, the patient was classified as having an incomplete pathologic response. Because this study was terminated with 5 patients enrolled, data for this endpoint were summarized in by-patient listings only and the pathologic complete response rate was not calculated. Therefore a summary of participants with a pathologic complete response before the end of study is reported.

Outcome measures

Outcome measures
Measure	Radiation/Cisplatin n=1 Participants Participants received cisplatin (100 mg/m²) administered intravenously on Days 0, 21, and 42. Radiation was administered concurrently with cisplatin in 35 fractions over a 7-week period.	Talimogene Laherparepvec + Radiation/Cisplatin The first dose of talimogene laherparepvec was up to 8 mL total volume (up to 4 mL per lesion) at 10⁶ PFU/mL, administered into all injectable affected nodes on Day 0. Subsequent doses were up to 8 mL total volume (up to 4 mL per lesion) at 10⁸ PFU/mL on Days 21, 42, and 63. Participants also received cisplatin (100 mg/m²) administered intravenously on Days 0, 21, and 42 and radiation administered concurrently in 35 fractions over a 7-week period.
Pathologic Complete Response (mCR)	0 participants	—

SECONDARY outcome

Timeframe: Up to 27 months

Locoregional failure is defined as disease progression in the head and neck area at any time following completion of chemoradiotherapy. Because this study was terminated with 5 subjects enrolled, time to locoregional failure was not analyzed.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 27 months

Distant failure is defined as disease progression at any site other than the head and neck area at any time following completion of chemoradiotherapy. Because this study was terminated with 5 participants enrolled, time to distant failure was not analyzed.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 27 months

Any failure is defined as disease progression at any site at any time following completion of chemoradiotherapy. Because this study was terminated with 5 participants enrolled, time to any failure was not analyzed.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 5 years after chemoradiotherapy

Overall survival is defined as the time from randomization to death from any cause. Because this study was terminated with 5 participants enrolled, overall survival was not analyzed.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 5 years after chemoradiotherapy

Disease-specific survival is defined as the time from randomization to death of the patient due to the cancer under study. Because this study was terminated with 5 participants enrolled, disease-specific survival was not analyzed.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Weeks 19 - 21

Participants with Baseline Nl or N2 disease (lymph node metastasis not more than 6 cm in greatest dimension) with persistent disease as determined at the post chemoradiotherapy assessment of response were to proceed to neck dissection as permitted by the institution no later than Week 22. Since this study terminated prematurely neck dissection data were not collected or analyzed.

Outcome measures

Outcome data not reported

Adverse Events

Radiation/Cisplatin

Serious events: 2 serious events

Other events: 3 other events

Deaths: 0 deaths

Talimogene Laherparepvec + Radiation/Cisplatin

Serious events: 2 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Radiation/Cisplatin n=3 participants at risk Participants received cisplatin (100 mg/m²) administered intravenously on Days 0, 21, and 42. Radiation was administered concurrently with cisplatin in 35 fractions over a 7-week period.	Talimogene Laherparepvec + Radiation/Cisplatin n=2 participants at risk The first dose of talimogene laherparepvec was up to 8 mL total volume (up to 4 mL per lesion) at 10⁶ PFU/mL, administered into all injectable affected nodes on Day 0. Subsequent doses were up to 8 mL total volume (up to 4 mL per lesion) at 10⁸ PFU/mL on Days 21, 42, and 63. Participants also received cisplatin (100 mg/m²) administered intravenously on Days 0, 21, and 42 and radiation administered concurrently in 35 fractions over a 7-week period.
Gastrointestinal disorders Mouth haemorrhage	33.3% 1/3 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/2 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Lung infection	0.00% 0/3 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	50.0% 1/2 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Urinary tract infection	0.00% 0/3 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	50.0% 1/2 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Metabolism and nutrition disorders Dehydration	33.3% 1/3 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/2 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/3 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	50.0% 1/2 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant neoplasm progression	0.00% 0/3 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	50.0% 1/2 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Renal and urinary disorders Renal failure acute	0.00% 0/3 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	50.0% 1/2 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/3 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	50.0% 1/2 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.

Other adverse events

Additional Information

Study Director

Amgen, Inc.

Phone: 866-572-6436

Results disclosure agreements

Principal investigator is a sponsor employee The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.
Publication restrictions are in place

Restriction type: OTHER

Measure	Radiation/Cisplatin n=3 participants at risk Participants received cisplatin (100 mg/m²) administered intravenously on Days 0, 21, and 42. Radiation was administered concurrently with cisplatin in 35 fractions over a 7-week period.	Talimogene Laherparepvec + Radiation/Cisplatin n=2 participants at risk The first dose of talimogene laherparepvec was up to 8 mL total volume (up to 4 mL per lesion) at 10⁶ PFU/mL, administered into all injectable affected nodes on Day 0. Subsequent doses were up to 8 mL total volume (up to 4 mL per lesion) at 10⁸ PFU/mL on Days 21, 42, and 63. Participants also received cisplatin (100 mg/m²) administered intravenously on Days 0, 21, and 42 and radiation administered concurrently in 35 fractions over a 7-week period.
Blood and lymphatic system disorders Anaemia	66.7% 2/3 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/2 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Blood and lymphatic system disorders Neutropenia	33.3% 1/3 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/2 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Abdominal pain	0.00% 0/3 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	100.0% 2/2 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Constipation	33.3% 1/3 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	50.0% 1/2 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Diarrhoea	33.3% 1/3 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	100.0% 2/2 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Dry mouth	0.00% 0/3 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	50.0% 1/2 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Lung infection	0.00% 0/3 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	50.0% 1/2 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Dyspepsia	33.3% 1/3 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/2 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Dysphagia	0.00% 0/3 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	50.0% 1/2 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/3 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	50.0% 1/2 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Impaired gastric emptying	0.00% 0/3 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	50.0% 1/2 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Nausea	33.3% 1/3 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	100.0% 2/2 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Oral candidiasis	0.00% 0/3 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	50.0% 1/2 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Odynophagia	0.00% 0/3 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	50.0% 1/2 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Postoperative wound infection	0.00% 0/3 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	50.0% 1/2 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Upper respiratory tract infection	33.3% 1/3 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/2 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Infections and infestations Urinary tract infection	0.00% 0/3 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	50.0% 1/2 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Oral dysaesthesia	0.00% 0/3 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	50.0% 1/2 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Saliva altered	33.3% 1/3 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/2 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Salivary duct inflammation	33.3% 1/3 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	100.0% 2/2 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Stomatitis	100.0% 3/3 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	50.0% 1/2 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Gastrointestinal disorders Vomiting	66.7% 2/3 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	50.0% 1/2 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Investigations Blood creatinine increased	0.00% 0/3 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	50.0% 1/2 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
General disorders Catheter site erythema	33.3% 1/3 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/2 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
General disorders Fatigue	33.3% 1/3 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	50.0% 1/2 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
General disorders Pain	33.3% 1/3 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/2 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Investigations Body temperature increased	33.3% 1/3 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/2 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Investigations Electrocardiogram QT prolonged	0.00% 0/3 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	50.0% 1/2 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Investigations Weight decreased	33.3% 1/3 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	50.0% 1/2 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Metabolism and nutrition disorders Dehydration	33.3% 1/3 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	50.0% 1/2 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Metabolism and nutrition disorders Hypercalcaemia	33.3% 1/3 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/2 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Metabolism and nutrition disorders Hypomagnesaemia	33.3% 1/3 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/2 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Metabolism and nutrition disorders Hyponatraemia	33.3% 1/3 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/2 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Metabolism and nutrition disorders Hypophagia	0.00% 0/3 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	50.0% 1/2 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Musculoskeletal and connective tissue disorders Muscular weakness	0.00% 0/3 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	50.0% 1/2 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.00% 0/3 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	50.0% 1/2 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Dizziness	0.00% 0/3 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	50.0% 1/2 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Nervous system disorders Dysgeusia	0.00% 0/3 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	50.0% 1/2 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Psychiatric disorders Delirium	0.00% 0/3 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	50.0% 1/2 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Psychiatric disorders Depression	0.00% 0/3 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	50.0% 1/2 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Psychiatric disorders Insomnia	0.00% 0/3 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	50.0% 1/2 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Renal and urinary disorders Dysuria	0.00% 0/3 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	50.0% 1/2 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Respiratory, thoracic and mediastinal disorders Dyspnoea	33.3% 1/3 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	50.0% 1/2 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/3 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	50.0% 1/2 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Respiratory, thoracic and mediastinal disorders Laryngeal oedema	0.00% 0/3 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	50.0% 1/2 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Respiratory, thoracic and mediastinal disorders Nasal congestion	33.3% 1/3 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/2 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/3 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	50.0% 1/2 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/3 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	50.0% 1/2 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/3 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	50.0% 1/2 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Respiratory, thoracic and mediastinal disorders Productive cough	33.3% 1/3 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	50.0% 1/2 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Skin and subcutaneous tissue disorders Decubitus ulcer	0.00% 0/3 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	50.0% 1/2 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Skin and subcutaneous tissue disorders Erythema	33.3% 1/3 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	0.00% 0/2 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
Skin and subcutaneous tissue disorders Skin ulcer	0.00% 0/3 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	50.0% 1/2 • 20 weeks Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.