Trial Outcomes & Findings for Study to Evaluate Palifermin in the Reduction of Dysphagia in Patients With Locally Advanced Non-Small Cell Lung Cancer (NSCLC) (NCT NCT00094861)

Last Updated: 2017-03-14

Results Overview

Participants underwent acute dysphagia assessments twice weekly during Weeks 1 through 7, and twice weekly thereafter (Weeks 8 through 12) and once weekly after Week 12 until dysphagia resolved to grade ≤ 1 but not beyond Week 16. Dysphagia (difficulty swallowing) was graded using the Common Terminology Criteria for Adverse Events, Version 3.0 (CTCAE v3.0) dysphagia scale according to the following: Grade 1: Symptomatic, able to eat regular diet; Grade 2: Symptomatic and altered eating/swallowing (e.g., altered dietary habits, oral supplements), IV fluids indicated \<24 hours; Grade 3: Symptomatic and severely altered eating/swallowing (e.g., inadequate oral caloric or fluid intake), IV fluids, tube feedings, or total parenteral nutrition (TPN) indicated ≥24 hours; Grade 4: Life-threatening consequences (e.g., obstruction, perforation).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

100 participants

Primary outcome timeframe

Start of treatment through Week 16

Results posted on

2017-03-14

Participant Flow

This study was conducted from 06 January 2005 until 20 December 2007 (last participant's last visit for the acute dysphagia evaluation phase). At the time of this report, the long-term safety follow-up period is ongoing.

100 patients were initially enrolled at 25 sites, however, data from one site could not be used and is excluded from this results analysis.

Participant milestones

Participant milestones
Measure	Placebo Participants received a single intravenous (IV) dose of placebo administered 3 days before the initiation of concurrent chemo/radiotherapy, then once weekly during Weeks 1 through 6, for a total of 7 doses. Concurrent radio/chemotherapy was given as follows: * standard radiotherapy 2 Gy once daily x 30 to 33 fractions (6 to 7 weeks) for a total target dose of 60 to 66 Gy * paclitaxel 50 mg/m\^2 intravenous (IV) infusion on Days 1, 8, 15, 22, 29, 36 (and day 43 for those receiving 66 Gy) * carboplatin dosed at an area under the curve (AUC) 2.0 IV on Days 1, 8, 15, 22, 29, 36 (and day 43 for those receiving 66 Gy). Participants subsequently received two 21-day cycles of consolidation chemotherapy with paclitaxel 225 mg/m\^2 and carboplatin dosed at AUC 6.0.	Palifermin Participants received a single IV dose of palifermin at 180 μg/kg administered 3 days before the initiation of concurrent chemo/radiotherapy, then once weekly during Weeks 1 through 6, typically for a total of 7 doses. Concurrent radio/chemotherapy (administered for 6 to 7 weeks) was given as follows: * standard radiotherapy 2 Gy once daily x 30 to 33 fractions (6 to 7 weeks) for a total target dose of 60 to 66 Gy * paclitaxel 50 mg/m\^2 IV infusion on Days 1, 8, 15, 22, 29, 36 (and day 43 for those receiving 66 Gy) * carboplatin dosed at an area under the curve (AUC) 2.0 IV on Days 1, 8, 15, 22, 29, 36 (and day 43 for those receiving 66 Gy). Participants subsequently received two 21-day cycles of consolidation chemotherapy with paclitaxel 225 mg/m\^2 and carboplatin dosed at AUC 6.0.
Overall Study STARTED	46	49
Overall Study Participants Treated	46	48
Overall Study COMPLETED	28	40
Overall Study NOT COMPLETED	18	9

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants received a single intravenous (IV) dose of placebo administered 3 days before the initiation of concurrent chemo/radiotherapy, then once weekly during Weeks 1 through 6, for a total of 7 doses. Concurrent radio/chemotherapy was given as follows: * standard radiotherapy 2 Gy once daily x 30 to 33 fractions (6 to 7 weeks) for a total target dose of 60 to 66 Gy * paclitaxel 50 mg/m\^2 intravenous (IV) infusion on Days 1, 8, 15, 22, 29, 36 (and day 43 for those receiving 66 Gy) * carboplatin dosed at an area under the curve (AUC) 2.0 IV on Days 1, 8, 15, 22, 29, 36 (and day 43 for those receiving 66 Gy). Participants subsequently received two 21-day cycles of consolidation chemotherapy with paclitaxel 225 mg/m\^2 and carboplatin dosed at AUC 6.0.	Palifermin Participants received a single IV dose of palifermin at 180 μg/kg administered 3 days before the initiation of concurrent chemo/radiotherapy, then once weekly during Weeks 1 through 6, typically for a total of 7 doses. Concurrent radio/chemotherapy (administered for 6 to 7 weeks) was given as follows: * standard radiotherapy 2 Gy once daily x 30 to 33 fractions (6 to 7 weeks) for a total target dose of 60 to 66 Gy * paclitaxel 50 mg/m\^2 IV infusion on Days 1, 8, 15, 22, 29, 36 (and day 43 for those receiving 66 Gy) * carboplatin dosed at an area under the curve (AUC) 2.0 IV on Days 1, 8, 15, 22, 29, 36 (and day 43 for those receiving 66 Gy). Participants subsequently received two 21-day cycles of consolidation chemotherapy with paclitaxel 225 mg/m\^2 and carboplatin dosed at AUC 6.0.
Overall Study Adverse Event	5	2
Overall Study Withdrawal by Subject	5	3
Overall Study Physician Decision	1	1
Overall Study Lost to Follow-up	0	1
Overall Study Death	4	2
Overall Study Other	3	0

Baseline Characteristics

Study to Evaluate Palifermin in the Reduction of Dysphagia in Patients With Locally Advanced Non-Small Cell Lung Cancer (NSCLC)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=46 Participants Participants received a single intravenous (IV) dose of placebo administered 3 days before the initiation of concurrent chemo/radiotherapy, then once weekly during Weeks 1 through 6, typically for a total of 7 doses.	Palifermin n=49 Participants Participants received a single IV dose of palifermin at 180 μg/kg administered 3 days before the initiation of concurrent chemo/radiotherapy, then once weekly during Weeks 1 through 6, typically for a total of 7 doses.	Total n=95 Participants Total of all reporting groups
Age, Continuous	64.2 years STANDARD_DEVIATION 7.7 • n=99 Participants	61.6 years STANDARD_DEVIATION 9.8 • n=107 Participants	62.9 years STANDARD_DEVIATION 8.9 • n=206 Participants
Sex: Female, Male Female	14 Participants n=99 Participants	15 Participants n=107 Participants	29 Participants n=206 Participants
Sex: Female, Male Male	32 Participants n=99 Participants	34 Participants n=107 Participants	66 Participants n=206 Participants
Race/Ethnicity, Customized White or Causcasian	43 Participants n=99 Participants	43 Participants n=107 Participants	86 Participants n=206 Participants
Race/Ethnicity, Customized Black or African-American	2 Participants n=99 Participants	2 Participants n=107 Participants	4 Participants n=206 Participants
Race/Ethnicity, Customized Hispanic or Latino	1 Participants n=99 Participants	1 Participants n=107 Participants	2 Participants n=206 Participants
Race/Ethnicity, Customized Asian	0 Participants n=99 Participants	1 Participants n=107 Participants	1 Participants n=206 Participants
Race/Ethnicity, Customized Japanese	0 Participants n=99 Participants	1 Participants n=107 Participants	1 Participants n=206 Participants
Race/Ethnicity, Customized Other	0 Participants n=99 Participants	1 Participants n=107 Participants	1 Participants n=206 Participants
Disease Stage Stage 3A	14 participants n=99 Participants	19 participants n=107 Participants	33 participants n=206 Participants
Disease Stage Stage 3B	32 participants n=99 Participants	30 participants n=107 Participants	62 participants n=206 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status Grade 0	21 participants n=99 Participants	21 participants n=107 Participants	42 participants n=206 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status Grade 1	23 participants n=99 Participants	26 participants n=107 Participants	49 participants n=206 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status Grade 2	2 participants n=99 Participants	2 participants n=107 Participants	4 participants n=206 Participants
Weight Loss Over Last 3 Months < 5%	35 participants n=99 Participants	37 participants n=107 Participants	72 participants n=206 Participants
Weight Loss Over Last 3 Months 5 - 10%	11 participants n=99 Participants	12 participants n=107 Participants	23 participants n=206 Participants
Randomization Strata 3A, 0-1, <5%	10 participants n=99 Participants	11 participants n=107 Participants	21 participants n=206 Participants
Randomization Strata 3A, 0-1, 5-10%	4 participants n=99 Participants	6 participants n=107 Participants	10 participants n=206 Participants
Randomization Strata 3A, 2, <5%	1 participants n=99 Participants	2 participants n=107 Participants	3 participants n=206 Participants
Randomization Strata 3A, 2, 5-10%	1 participants n=99 Participants	0 participants n=107 Participants	1 participants n=206 Participants
Randomization Strata 3B, 0-1, <5%	24 participants n=99 Participants	25 participants n=107 Participants	49 participants n=206 Participants
Randomization Strata 3B, 0-1, 5-10%	6 participants n=99 Participants	5 participants n=107 Participants	11 participants n=206 Participants
Randomization Strata 3B, 2, <5%	0 participants n=99 Participants	0 participants n=107 Participants	0 participants n=206 Participants
Randomization Strata 3B, 2, 5-10%	0 participants n=99 Participants	0 participants n=107 Participants	0 participants n=206 Participants

PRIMARY outcome

Timeframe: Start of treatment through Week 16

Population: Full analysis set

Outcome measures

Outcome measures
Measure	Placebo n=46 Participants Participants received a single intravenous (IV) dose of placebo administered 3 days before the initiation of concurrent chemo/radiotherapy, then once weekly during Weeks 1 through 6, typically for a total of 7 doses.	Palifermin n=49 Participants Participants received a single IV dose of palifermin at 180 μg/kg administered 3 days before the initiation of concurrent chemo/radiotherapy, then once weekly during Weeks 1 through 6, typically for a total of 7 doses.
Number of Participants With Grade 2 or Higher Dysphagia Yes	32 participants	30 participants
Number of Participants With Grade 2 or Higher Dysphagia No	13 participants	18 participants
Number of Participants With Grade 2 or Higher Dysphagia No assessment	1 participants	1 participants

SECONDARY outcome

Timeframe: Start of treatment through Week 16

Population: Full analysis set

Duration of grade 2 or higher dysphagia was calculated in days from the onset (first occurrence of grade ≥ 2) to the resolution (grade ≤ 1 after the last grade ≥ 2) of dysphagia. Participants with no assessments were assumed as having grade ≥ 2 dysphagia and with a duration of the mean duration of all participants.

Outcome measures

Outcome measures
Measure	Placebo n=46 Participants Participants received a single intravenous (IV) dose of placebo administered 3 days before the initiation of concurrent chemo/radiotherapy, then once weekly during Weeks 1 through 6, typically for a total of 7 doses.	Palifermin n=49 Participants Participants received a single IV dose of palifermin at 180 μg/kg administered 3 days before the initiation of concurrent chemo/radiotherapy, then once weekly during Weeks 1 through 6, typically for a total of 7 doses.
Duration of Grade 2 or Higher Dysphagia	32.4 days Standard Deviation 30.1	25.3 days Standard Deviation 28.0

SECONDARY outcome

Timeframe: Start of treatment through Week 16

Population: Full analysis set participants with dysphagia assessments.

The mean maximal grade of dysphagia for each participant during the study. Dysphagia (difficulty swallowing) was graded using the Common Terminology Criteria for Adverse Events, Version 3.0 (CTCAE v3.0) dysphagia scale according to the following: Grade 1: Symptomatic, able to eat regular diet; Grade 2: Symptomatic and altered eating/swallowing (e.g., altered dietary habits, oral supplements), IV fluids indicated \<24 hours; Grade 3: Symptomatic and severely altered eating/swallowing (e.g., inadequate oral caloric or fluid intake), IV fluids, tube feedings, or total parenteral nutrition (TPN) indicated ≥24 hours; Grade 4: Life-threatening consequences (e.g., obstruction, perforation).

Outcome measures

Outcome measures
Measure	Placebo n=45 Participants Participants received a single intravenous (IV) dose of placebo administered 3 days before the initiation of concurrent chemo/radiotherapy, then once weekly during Weeks 1 through 6, typically for a total of 7 doses.	Palifermin n=48 Participants Participants received a single IV dose of palifermin at 180 μg/kg administered 3 days before the initiation of concurrent chemo/radiotherapy, then once weekly during Weeks 1 through 6, typically for a total of 7 doses.
Maximal Dysphagia Grade	1.9 grade Standard Deviation 1.0	1.8 grade Standard Deviation 0.9

SECONDARY outcome

Timeframe: Start of treatment through Week 16

Population: Full analysis set

Outcome measures

Outcome measures
Measure	Placebo n=46 Participants Participants received a single intravenous (IV) dose of placebo administered 3 days before the initiation of concurrent chemo/radiotherapy, then once weekly during Weeks 1 through 6, typically for a total of 7 doses.	Palifermin n=49 Participants Participants received a single IV dose of palifermin at 180 μg/kg administered 3 days before the initiation of concurrent chemo/radiotherapy, then once weekly during Weeks 1 through 6, typically for a total of 7 doses.
Number of Participants With Severe (Grade 3 or Higher) Dysphagia Yes	13 participants	11 participants
Number of Participants With Severe (Grade 3 or Higher) Dysphagia No	32 participants	37 participants
Number of Participants With Severe (Grade 3 or Higher) Dysphagia No assessment	1 participants	1 participants

SECONDARY outcome

Timeframe: Week 1 to Week 6

Population: Full analysis set

The number of participants with unplanned breaks in radiotherapy of ≥ 5 days or who discontinued radiotherapy during Week 1 to Week 6.

Outcome measures

Outcome measures
Measure	Placebo n=46 Participants Participants received a single intravenous (IV) dose of placebo administered 3 days before the initiation of concurrent chemo/radiotherapy, then once weekly during Weeks 1 through 6, typically for a total of 7 doses.	Palifermin n=49 Participants Participants received a single IV dose of palifermin at 180 μg/kg administered 3 days before the initiation of concurrent chemo/radiotherapy, then once weekly during Weeks 1 through 6, typically for a total of 7 doses.
Number of Participants With Unplanned Breaks in Radiotherapy Yes	15 participants	9 participants
Number of Participants With Unplanned Breaks in Radiotherapy No	29 participants	38 participants
Number of Participants With Unplanned Breaks in Radiotherapy Did not receive radiotherapy	2 participants	2 participants

SECONDARY outcome

Timeframe: Baseline through Week 12

Population: Full analysis set participants with available ECOG data

Maximal increase from Baseline in Eastern Cooperative Oncology Group (ECOG) performance status. ECOG is a scale to assess how a patient's disease is progressing, how the disease affects the daily living abilities of the patient, and determine appropriate treatment and prognosis. Grade 0: Fully active, able to carry on all pre-disease performance without restriction; Grade 1: Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature; Grade 2: Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and about more than 50% of waking hours; Grade 3: Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours; Grade 4: Completely disabled. Cannot carry on any selfcare. Totally confined to bed or chair; Grade 5: Dead.

Outcome measures

Outcome measures
Measure	Placebo n=44 Participants Participants received a single intravenous (IV) dose of placebo administered 3 days before the initiation of concurrent chemo/radiotherapy, then once weekly during Weeks 1 through 6, typically for a total of 7 doses.	Palifermin n=46 Participants Participants received a single IV dose of palifermin at 180 μg/kg administered 3 days before the initiation of concurrent chemo/radiotherapy, then once weekly during Weeks 1 through 6, typically for a total of 7 doses.
Maximal Eastern Cooperative Oncology Group (ECOG) Performance Status Increase	1.5 units on a scale Standard Deviation 1.3	0.9 units on a scale Standard Deviation 1.1

SECONDARY outcome

Timeframe: Baseline to Week 16

Population: Full analysis set

Outcome measures

Outcome measures
Measure	Placebo n=46 Participants Participants received a single intravenous (IV) dose of placebo administered 3 days before the initiation of concurrent chemo/radiotherapy, then once weekly during Weeks 1 through 6, typically for a total of 7 doses.	Palifermin n=49 Participants Participants received a single IV dose of palifermin at 180 μg/kg administered 3 days before the initiation of concurrent chemo/radiotherapy, then once weekly during Weeks 1 through 6, typically for a total of 7 doses.
Number of Participants Hospitalized Not hospitalized	15 participants	15 participants
Number of Participants Hospitalized Hospitalized	31 participants	34 participants

SECONDARY outcome

Timeframe: Baseline through Week 12

Population: Full analysis set with available data

Maximal weight loss observed from Baseline through to Week 12.

Outcome measures

Outcome measures
Measure	Placebo n=42 Participants Participants received a single intravenous (IV) dose of placebo administered 3 days before the initiation of concurrent chemo/radiotherapy, then once weekly during Weeks 1 through 6, typically for a total of 7 doses.	Palifermin n=45 Participants Participants received a single IV dose of palifermin at 180 μg/kg administered 3 days before the initiation of concurrent chemo/radiotherapy, then once weekly during Weeks 1 through 6, typically for a total of 7 doses.
Maximal Body Weight Loss	4.63 kilograms Standard Deviation 4.13	5.44 kilograms Standard Deviation 4.33

Adverse Events

Placebo

Serious events: 30 serious events

Other events: 45 other events

Deaths: 0 deaths

Palifermin

Serious events: 21 serious events

Other events: 48 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Hans Olivecrona, MD PhD

Biovitrum

Phone: +46 8 697 20 00

Email: [email protected]

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 sponsor a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Sponsor may remove confidential information, but authors have final control and approval of publication content. For multi-center studies, investigator agrees not to publish any results before the first multi-center publication.
Publication restrictions are in place

Restriction type: OTHER

Measure	Placebo n=46 participants at risk Participants received a single intravenous (IV) dose of placebo administered 3 days before the initiation of concurrent chemo/radiotherapy, then once weekly during Weeks 1 through 6, typically for a total of 7 doses.	Palifermin n=48 participants at risk Participants received a single IV dose of palifermin at 180 μg/kg administered 3 days before the initiation of concurrent chemo/radiotherapy, then once weekly during Weeks 1 through 6, typically for a total of 7 doses.
Blood and lymphatic system disorders Anaemia	45.7% 21/46 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	56.2% 27/48 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Blood and lymphatic system disorders Leukopenia	17.4% 8/46 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	37.5% 18/48 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Blood and lymphatic system disorders Neutropenia	23.9% 11/46 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	27.1% 13/48 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Blood and lymphatic system disorders Thrombocytopenia	10.9% 5/46 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	20.8% 10/48 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Gastrointestinal disorders Abdominal pain	8.7% 4/46 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	6.2% 3/48 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Gastrointestinal disorders Constipation	28.3% 13/46 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	29.2% 14/48 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Gastrointestinal disorders Diarrhoea	19.6% 9/46 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	18.8% 9/48 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Gastrointestinal disorders Dry mouth	2.2% 1/46 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	8.3% 4/48 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Gastrointestinal disorders Dyspepsia	15.2% 7/46 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	16.7% 8/48 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Gastrointestinal disorders Nausea	50.0% 23/46 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	52.1% 25/48 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Gastrointestinal disorders Oesophagitis	2.2% 1/46 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	8.3% 4/48 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Gastrointestinal disorders Vomiting	23.9% 11/46 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	20.8% 10/48 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
General disorders Asthenia	10.9% 5/46 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	18.8% 9/48 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
General disorders Chest pain	8.7% 4/46 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	14.6% 7/48 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
General disorders Fatigue	30.4% 14/46 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	39.6% 19/48 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
General disorders Non-cardiac chest pain	0.00% 0/46 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	6.2% 3/48 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
General disorders Oedema peripheral	8.7% 4/46 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	4.2% 2/48 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
General disorders Pain	6.5% 3/46 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	4.2% 2/48 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
General disorders Pyrexia	19.6% 9/46 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	16.7% 8/48 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Infections and infestations Pneumonia	2.2% 1/46 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	10.4% 5/48 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Injury, poisoning and procedural complications Radiation skin injury	13.0% 6/46 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	20.8% 10/48 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Investigations Weight decreased	15.2% 7/46 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	12.5% 6/48 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Metabolism and nutrition disorders Anorexia	17.4% 8/46 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	27.1% 13/48 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Metabolism and nutrition disorders Dehydration	13.0% 6/46 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	20.8% 10/48 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Metabolism and nutrition disorders Hypocalcaemia	6.5% 3/46 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	6.2% 3/48 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Metabolism and nutrition disorders Hypokalaemia	17.4% 8/46 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	16.7% 8/48 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Metabolism and nutrition disorders Hypomagnesaemia	2.2% 1/46 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	6.2% 3/48 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Metabolism and nutrition disorders Hyponatraemia	6.5% 3/46 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/48 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Musculoskeletal and connective tissue disorders Arthralgia	6.5% 3/46 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	6.2% 3/48 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Musculoskeletal and connective tissue disorders Back pain	10.9% 5/46 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	10.4% 5/48 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	6.5% 3/46 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	2.1% 1/48 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	2.2% 1/46 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	6.2% 3/48 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Musculoskeletal and connective tissue disorders Myalgia	10.9% 5/46 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	12.5% 6/48 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Musculoskeletal and connective tissue disorders Neck pain	6.5% 3/46 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	2.1% 1/48 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Nervous system disorders Dizziness	10.9% 5/46 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	12.5% 6/48 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Nervous system disorders Dysgeusia	6.5% 3/46 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	16.7% 8/48 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Nervous system disorders Headache	6.5% 3/46 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	8.3% 4/48 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Nervous system disorders Hypoaesthesia	6.5% 3/46 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.00% 0/48 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Nervous system disorders Neuropathy peripheral	0.00% 0/46 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	8.3% 4/48 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Nervous system disorders Paraesthesia	4.3% 2/46 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	6.2% 3/48 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Nervous system disorders Peripheral sensory neuropathy	6.5% 3/46 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	8.3% 4/48 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Psychiatric disorders Anxiety	13.0% 6/46 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	6.2% 3/48 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Psychiatric disorders Depression	8.7% 4/46 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	4.2% 2/48 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Psychiatric disorders Insomnia	19.6% 9/46 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	16.7% 8/48 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Respiratory, thoracic and mediastinal disorders Cough	26.1% 12/46 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	39.6% 19/48 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Respiratory, thoracic and mediastinal disorders Dysphonia	6.5% 3/46 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	18.8% 9/48 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Respiratory, thoracic and mediastinal disorders Dyspnoea	17.4% 8/46 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	25.0% 12/48 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Respiratory, thoracic and mediastinal disorders Epistaxis	8.7% 4/46 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	12.5% 6/48 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.00% 0/46 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	6.2% 3/48 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Respiratory, thoracic and mediastinal disorders Hiccups	4.3% 2/46 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	6.2% 3/48 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Respiratory, thoracic and mediastinal disorders Pharyngolaryngeal pain	23.9% 11/46 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	10.4% 5/48 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Skin and subcutaneous tissue disorders Alopecia	13.0% 6/46 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	20.8% 10/48 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Skin and subcutaneous tissue disorders Erythema	4.3% 2/46 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	16.7% 8/48 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Skin and subcutaneous tissue disorders Hyperhidrosis	6.5% 3/46 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	4.2% 2/48 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Skin and subcutaneous tissue disorders Pruritus	2.2% 1/46 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	8.3% 4/48 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Skin and subcutaneous tissue disorders Rash	10.9% 5/46 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	8.3% 4/48 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Vascular disorders Flushing	0.00% 0/46 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	10.4% 5/48 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Vascular disorders Thrombophlebitis	0.00% 0/46 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	8.3% 4/48 • From baseline up to Week 12 The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.