Trial Outcomes & Findings for A Randomized Phase 2 Pharmacokinetic Trial of Chemotherapy With or Without Panitumumab in Patients With Metastatic and/or Recurrent Squamous Cell Carcinoma of the Head and Neck (NCT NCT00756444)

Last Updated: 2018-11-15

Results Overview

AUC refers to area under the concentration curve from time 0 to last measurable concentration. AUC of total plasma cisplatin-derived platinum levels is estimated both for subjects receiving cisplatin with panitumumab and for subjects receiving cisplatin without panitumumab.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

67 participants

Primary outcome timeframe

Levels measured at 0.5, 1, 2, 3, 4, 6 and 24 hours following start of cycle 2 cisplatin infusion

Results posted on

2018-11-15

Participant Flow

Men and women ≥ 18 years of age with metastatic and/or recurrent squamous cell carcinoma of the head and neck were enrolled from 21 October 2008 to 23 August 2011. This study was conducted at 15 centers in Argentina, Brazil, France, Japan, Romania, and Russia.

Patients were screened at 15 sites to determine eligibility. Using an IVRS, eligible subjects were randomized to panitumumab plus cisplatin and 5-FU or cisplatin and 5-FU alone. It was estimated that approximately 45 subjects would be needed to obtain 30 evaluable subjects. More than 45 subjects were needed and 67 total subjects were enrolled.

Participant milestones

Participant milestones
Measure	Panitumumab Plus Chemotherapy Treatment will be administered in cycles repeated every 21 days. On day 1 of each cycle, panitumumab will be administered intravenously, prior to chemotherapy, at a dose of 9 mg/kg over 1 hour. Cisplatin will be administered intravenously on day 1 at a dose of 100 mg/m2 over 1 hour. 5-FU will be administered at a dose of 1000 mg/m2/day by continuous intravenous infusion on day 1 to 4 (96 hours).	Chemotherapy Alone Treatment will be administered in cycles repeated every 21 days. Cisplatin will be administered intravenously on day 1 at a dose of 100 mg/m2 over 1 hour. 5-FU will be administered at a dose of 1000 mg/m2/day by continuous intravenous infusion on day 1 to 4 (96 hours).
Overall Study STARTED	33	34
Overall Study COMPLETED	18	13
Overall Study NOT COMPLETED	15	21

Reasons for withdrawal

Reasons for withdrawal
Measure	Panitumumab Plus Chemotherapy Treatment will be administered in cycles repeated every 21 days. On day 1 of each cycle, panitumumab will be administered intravenously, prior to chemotherapy, at a dose of 9 mg/kg over 1 hour. Cisplatin will be administered intravenously on day 1 at a dose of 100 mg/m2 over 1 hour. 5-FU will be administered at a dose of 1000 mg/m2/day by continuous intravenous infusion on day 1 to 4 (96 hours).	Chemotherapy Alone Treatment will be administered in cycles repeated every 21 days. Cisplatin will be administered intravenously on day 1 at a dose of 100 mg/m2 over 1 hour. 5-FU will be administered at a dose of 1000 mg/m2/day by continuous intravenous infusion on day 1 to 4 (96 hours).
Overall Study Adverse Event	1	1
Overall Study Withdrawal by Subject	6	8
Overall Study Lost to Follow-up	0	1
Overall Study Death	5	4
Overall Study Disease Progression	2	7
Overall Study Ineligibility Determined	1	0

Baseline Characteristics

A Randomized Phase 2 Pharmacokinetic Trial of Chemotherapy With or Without Panitumumab in Patients With Metastatic and/or Recurrent Squamous Cell Carcinoma of the Head and Neck

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Panitumumab Plus Chemotherapy n=33 Participants Treatment will be administered in cycles repeated every 21 days. On day 1 of each cycle, panitumumab will be administered intravenously, prior to chemotherapy, at a dose of 9 mg/kg over 1 hour. Cisplatin will be administered intravenously on day 1 at a dose of 100 mg/m2 over 1 hour. 5-FU will be administered at a dose of 1000 mg/m2/day by continuous intravenous infusion on day 1 to 4 (96 hours).	Chemotherapy Alone n=34 Participants Treatment will be administered in cycles repeated every 21 days. Cisplatin will be administered intravenously on day 1 at a dose of 100 mg/m2 over 1 hour. 5-FU will be administered at a dose of 1000 mg/m2/day by continuous intravenous infusion on day 1 to 4 (96 hours).	Total n=67 Participants Total of all reporting groups
Age, Continuous	56.2 Years STANDARD_DEVIATION 7.5 • n=5 Participants	58.3 Years STANDARD_DEVIATION 9.1 • n=7 Participants	57.3 Years STANDARD_DEVIATION 8.4 • n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Sex: Female, Male Male	31 Participants n=5 Participants	33 Participants n=7 Participants	64 Participants n=5 Participants

PRIMARY outcome

Timeframe: Levels measured at 0.5, 1, 2, 3, 4, 6 and 24 hours following start of cycle 2 cisplatin infusion

Population: Subjects who receive at least 2 cycles of assigned treatment and who have sufficient plasma collection to derive AUC

Outcome measures

Outcome measures
Measure	Panitumuab Plus Chemotherapy n=23 Participants Treatment will be administered in cycles repeated every 21 days. On day 1 of each cycle, panitumumab will be administered intravenously, prior to chemotherapy, at a dose of 9 mg/kg over 1 hour. Cisplatin will be administered intravenously on day 1 at a dose of 100 mg/m2 over 1 hour. 5-FU will be administered at a dose of 1000 mg/m2/day by continuous intravenous infusion on day 1 to 4 (96 hours).	Chemotherapy Alone n=16 Participants Treatment will be administered in cycles repeated every 21 days. Cisplatin will be administered intravenously on day 1 at a dose of 100 mg/m2 over 1 hour. 5-FU will be administered at a dose of 1000 mg/m2/day by continuous intravenous infusion on day 1 to 4 (96 hours).
Area Under the Curve (AUC) of Total Plasma Cisplatin-derived Platinum Levels With and Without the Presence of Panitumumab	58000 ng*hr/mL Standard Deviation 9530	62300 ng*hr/mL Standard Deviation 10200

PRIMARY outcome

Timeframe: 24 to 96 hours following start of cycle 2 infusion with 5-FU

Population: Subjects who receive at least 2 cycles of assigned treatment and who have sufficient plasma collection to derive Css

Steady-state plasma concentrations (Css) of 5-FU were estimated as the mean of two or more evaluable concentrations at 24, 72, and 96 hours after the start of 5-FU infusion. Css is estimated both for subjects receiving 5-FU with panitumumab and for subjects receiving 5-FU without panitumumab

Outcome measures

Outcome measures
Measure	Panitumuab Plus Chemotherapy n=22 Participants Treatment will be administered in cycles repeated every 21 days. On day 1 of each cycle, panitumumab will be administered intravenously, prior to chemotherapy, at a dose of 9 mg/kg over 1 hour. Cisplatin will be administered intravenously on day 1 at a dose of 100 mg/m2 over 1 hour. 5-FU will be administered at a dose of 1000 mg/m2/day by continuous intravenous infusion on day 1 to 4 (96 hours).	Chemotherapy Alone n=13 Participants Treatment will be administered in cycles repeated every 21 days. Cisplatin will be administered intravenously on day 1 at a dose of 100 mg/m2 over 1 hour. 5-FU will be administered at a dose of 1000 mg/m2/day by continuous intravenous infusion on day 1 to 4 (96 hours).
Steady-state Plasma Concentrations (Css) for 5-FU With and Without the Presence of Panitumumab	328 ng/mL Standard Deviation 180	378 ng/mL Standard Deviation 184

Adverse Events

Panitumumab Plus Chemotherapy

Serious events: 11 serious events

Other events: 33 other events

Deaths: 0 deaths

Chemotherapy Alone

Serious events: 8 serious events

Other events: 33 other events

Deaths: 0 deaths

Total

Serious events: 19 serious events

Other events: 66 other events

Deaths: 0 deaths

Serious adverse events

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

Serious adverse events
Measure	Panitumumab Plus Chemotherapy n=33 participants at risk Treatment will be administered in cycles repeated every 21 days. On day 1 of each cycle, panitumumab will be administered intravenously, prior to chemotherapy, at a dose of 9 mg/kg over 1 hour. Cisplatin will be administered intravenously on day 1 at a dose of 100 mg/m2 over 1 hour. 5-FU will be administered at a dose of 1000 mg/m2/day by continuous intravenous infusion on day 1 to 4 (96 hours).	Chemotherapy Alone n=34 participants at risk Treatment will be administered in cycles repeated every 21 days. Cisplatin will be administered intravenously on day 1 at a dose of 100 mg/m2 over 1 hour. 5-FU will be administered at a dose of 1000 mg/m2/day by continuous intravenous infusion on day 1 to 4 (96 hours).	Total n=67 participants at risk
Blood and lymphatic system disorders Neutropenia	3.0% 1/33 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.00% 0/34 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	1.5% 1/67 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Blood and lymphatic system disorders Thrombocytopenia	3.0% 1/33 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	2.9% 1/34 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	3.0% 2/67 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Gastrointestinal disorders Duodenal ulcer haemorrhage	0.00% 0/33 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	2.9% 1/34 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	1.5% 1/67 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Gastrointestinal disorders Dysphagia	3.0% 1/33 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.00% 0/34 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	1.5% 1/67 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Gastrointestinal disorders Vomiting	3.0% 1/33 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.00% 0/34 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	1.5% 1/67 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
General disorders Performance status decreased	3.0% 1/33 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.00% 0/34 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	1.5% 1/67 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
General disorders Pyrexia	3.0% 1/33 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.00% 0/34 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	1.5% 1/67 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Infections and infestations Pneumonia	3.0% 1/33 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.00% 0/34 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	1.5% 1/67 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Infections and infestations Sepsis	0.00% 0/33 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	2.9% 1/34 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	1.5% 1/67 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Infections and infestations Staphylococcal infection	3.0% 1/33 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.00% 0/34 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	1.5% 1/67 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Metabolism and nutrition disorders Diabetes mellitus	0.00% 0/33 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	2.9% 1/34 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	1.5% 1/67 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Metabolism and nutrition disorders Hypercalcaemia	3.0% 1/33 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.00% 0/34 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	1.5% 1/67 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Metabolism and nutrition disorders Hypernatraemia	3.0% 1/33 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.00% 0/34 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	1.5% 1/67 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Metabolism and nutrition disorders Hypokalaemia	3.0% 1/33 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.00% 0/34 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	1.5% 1/67 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Infected neoplasm	0.00% 0/33 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	2.9% 1/34 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	1.5% 1/67 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasm malignant	0.00% 0/33 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	2.9% 1/34 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	1.5% 1/67 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pharyngeal cancer metastatic	0.00% 0/33 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	2.9% 1/34 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	1.5% 1/67 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour haemorrhage	0.00% 0/33 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	5.9% 2/34 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	3.0% 2/67 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Nervous system disorders Carotid artery thrombosis	3.0% 1/33 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.00% 0/34 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	1.5% 1/67 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Nervous system disorders Cerebrovascular accident	6.1% 2/33 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.00% 0/34 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	3.0% 2/67 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Nervous system disorders Ischaemic stroke	3.0% 1/33 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.00% 0/34 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	1.5% 1/67 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Psychiatric disorders Agitation	3.0% 1/33 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.00% 0/34 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	1.5% 1/67 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Renal and urinary disorders Renal failure	3.0% 1/33 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.00% 0/34 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	1.5% 1/67 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Renal and urinary disorders Renal failure acute	3.0% 1/33 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.00% 0/34 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	1.5% 1/67 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/33 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	2.9% 1/34 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	1.5% 1/67 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/33 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	2.9% 1/34 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	1.5% 1/67 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Respiratory, thoracic and mediastinal disorders Respiratory distress	3.0% 1/33 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.00% 0/34 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	1.5% 1/67 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Surgical and medical procedures Chest tube insertion	0.00% 0/33 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	2.9% 1/34 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	1.5% 1/67 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Vascular disorders Hypotension	3.0% 1/33 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.00% 0/34 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	1.5% 1/67 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.

Other adverse events
Measure	Panitumumab Plus Chemotherapy n=33 participants at risk Treatment will be administered in cycles repeated every 21 days. On day 1 of each cycle, panitumumab will be administered intravenously, prior to chemotherapy, at a dose of 9 mg/kg over 1 hour. Cisplatin will be administered intravenously on day 1 at a dose of 100 mg/m2 over 1 hour. 5-FU will be administered at a dose of 1000 mg/m2/day by continuous intravenous infusion on day 1 to 4 (96 hours).	Chemotherapy Alone n=34 participants at risk Treatment will be administered in cycles repeated every 21 days. Cisplatin will be administered intravenously on day 1 at a dose of 100 mg/m2 over 1 hour. 5-FU will be administered at a dose of 1000 mg/m2/day by continuous intravenous infusion on day 1 to 4 (96 hours).	Total n=67 participants at risk
Blood and lymphatic system disorders Anaemia	51.5% 17/33 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	47.1% 16/34 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	49.3% 33/67 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Blood and lymphatic system disorders Granulocytopenia	6.1% 2/33 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	11.8% 4/34 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	9.0% 6/67 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Blood and lymphatic system disorders Leukopenia	21.2% 7/33 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	35.3% 12/34 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	28.4% 19/67 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Blood and lymphatic system disorders Lymphopenia	3.0% 1/33 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	14.7% 5/34 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	9.0% 6/67 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Blood and lymphatic system disorders Neutropenia	48.5% 16/33 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	44.1% 15/34 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	46.3% 31/67 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Blood and lymphatic system disorders Thrombocytopenia	24.2% 8/33 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	29.4% 10/34 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	26.9% 18/67 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Ear and labyrinth disorders Deafness	6.1% 2/33 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.00% 0/34 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	3.0% 2/67 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Gastrointestinal disorders Abdominal pain upper	6.1% 2/33 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	2.9% 1/34 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	4.5% 3/67 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Gastrointestinal disorders Constipation	12.1% 4/33 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	5.9% 2/34 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	9.0% 6/67 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Gastrointestinal disorders Diarrhoea	21.2% 7/33 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	8.8% 3/34 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	14.9% 10/67 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Gastrointestinal disorders Nausea	51.5% 17/33 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	55.9% 19/34 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	53.7% 36/67 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Gastrointestinal disorders Oral pain	6.1% 2/33 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.00% 0/34 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	3.0% 2/67 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Gastrointestinal disorders Stomatitis	24.2% 8/33 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	2.9% 1/34 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	13.4% 9/67 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Gastrointestinal disorders Vomiting	33.3% 11/33 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	26.5% 9/34 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	29.9% 20/67 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
General disorders Asthenia	33.3% 11/33 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	17.6% 6/34 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	25.4% 17/67 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
General disorders Fatigue	9.1% 3/33 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.00% 0/34 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	4.5% 3/67 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
General disorders Injection site reaction	6.1% 2/33 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.00% 0/34 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	3.0% 2/67 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
General disorders Mucosal inflammation	6.1% 2/33 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	5.9% 2/34 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	6.0% 4/67 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
General disorders Pyrexia	12.1% 4/33 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	5.9% 2/34 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	9.0% 6/67 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
General disorders Xerosis	6.1% 2/33 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.00% 0/34 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	3.0% 2/67 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Hepatobiliary disorders Hyperbilirubinaemia	0.00% 0/33 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	5.9% 2/34 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	3.0% 2/67 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Infections and infestations Paronychia	15.2% 5/33 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.00% 0/34 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	7.5% 5/67 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Infections and infestations Pneumonia	0.00% 0/33 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	5.9% 2/34 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	3.0% 2/67 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Infections and infestations Respiratory tract infection	0.00% 0/33 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	5.9% 2/34 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	3.0% 2/67 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Investigations Blood creatinine increased	12.1% 4/33 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	14.7% 5/34 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	13.4% 9/67 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Investigations Blood urea increased	3.0% 1/33 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	8.8% 3/34 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	6.0% 4/67 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Investigations Creatinine renal clearance decreased	0.00% 0/33 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	11.8% 4/34 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	6.0% 4/67 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Investigations Weight decreased	30.3% 10/33 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	29.4% 10/34 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	29.9% 20/67 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Metabolism and nutrition disorders Decreased appetite	27.3% 9/33 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	23.5% 8/34 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	25.4% 17/67 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Metabolism and nutrition disorders Hypercalcaemia	3.0% 1/33 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	5.9% 2/34 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	4.5% 3/67 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Metabolism and nutrition disorders Hypermagnesaemia	6.1% 2/33 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.00% 0/34 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	3.0% 2/67 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Metabolism and nutrition disorders Hypocalcaemia	33.3% 11/33 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.00% 0/34 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	16.4% 11/67 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Metabolism and nutrition disorders Hypokalaemia	6.1% 2/33 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.00% 0/34 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	3.0% 2/67 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Metabolism and nutrition disorders Hypomagnesaemia	51.5% 17/33 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	29.4% 10/34 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	40.3% 27/67 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Metabolism and nutrition disorders Hyponatraemia	6.1% 2/33 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	2.9% 1/34 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	4.5% 3/67 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Musculoskeletal and connective tissue disorders Neck pain	9.1% 3/33 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.00% 0/34 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	4.5% 3/67 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cancer pain	0.00% 0/33 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	8.8% 3/34 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	4.5% 3/67 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Nervous system disorders Neuropathy peripheral	6.1% 2/33 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.00% 0/34 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	3.0% 2/67 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Psychiatric disorders Insomnia	9.1% 3/33 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.00% 0/34 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	4.5% 3/67 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.
Respiratory, thoracic and mediastinal disorders Epistaxis	6.1% 2/33 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	0.00% 0/34 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.	3.0% 2/67 • 54 Weeks The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events. Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.