Trial Outcomes & Findings for Palifermin for the Reduction of Oral Mucositis in Patients With Locally Advanced Head and Neck Cancer (NCT NCT00101582)

Last Updated: 2016-09-27

Results Overview

Participants underwent evaluations of oral mucosal (OM) surfaces (mucositis assessments) 2 times weekly throughout radio/chemotherapy, and 2 times weekly thereafter until severe OM returned to grade ≤ 2 or until Week 15. During each evaluation, the following anatomical areas were assessed: upper lip; lower lip; right cheek; left cheek; right ventral \& lateral tongue; left ventral \& lateral tongue; floor of the mouth; hard palate; soft palate. A trained evaluator documented the findings using the World Health Organization (WHO) oral toxicity scale according to the following: Grade 0 = None; Grade 1 = Soreness, erythema; Grade 2 = Erythema, ulcers, ability to eat solids; Grade 3 = Ulcers, requires liquid diet; Grade 4 = Alimentation not possible.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

188 participants

Primary outcome timeframe

Up to Week 15

Results posted on

2016-09-27

Participant Flow

This study was conducted from 03 August 2005 (first participant enrolled) to 11 September 2007 (last participant's last visit at 4 months of follow-up) at 46 study centers in the United States, Canada, and Europe At the time of this report, the long-term safety follow-up period is ongoing.

Participant milestones

Participant milestones
Measure	Placebo Participants received a single intravenous (IV) dose of placebo three days before the start of radiotherapy, and then 7 once weekly placebo doses during a 7-week radiotherapy/chemotherapy course. Chemotherapy consisted of 100 mg/m\^2 cisplatin administered by IV infusion on Days 1, 22, and 43.	Palifermin Participants received a single intravenous dose of palifermin at 180 μg/kg three days before the start of radiotherapy, and then 7 once weekly palifermin doses at the same dose level during a 7-week radiotherapy/chemotherapy course. Chemotherapy consisted of 100 mg/m\^2 cisplatin administered by IV infusion on Days 1, 22, and 43.
Overall Study STARTED	94	94
Overall Study Received Study Drug	91	94
Overall Study COMPLETED	83	79
Overall Study NOT COMPLETED	11	15

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants received a single intravenous (IV) dose of placebo three days before the start of radiotherapy, and then 7 once weekly placebo doses during a 7-week radiotherapy/chemotherapy course. Chemotherapy consisted of 100 mg/m\^2 cisplatin administered by IV infusion on Days 1, 22, and 43.	Palifermin Participants received a single intravenous dose of palifermin at 180 μg/kg three days before the start of radiotherapy, and then 7 once weekly palifermin doses at the same dose level during a 7-week radiotherapy/chemotherapy course. Chemotherapy consisted of 100 mg/m\^2 cisplatin administered by IV infusion on Days 1, 22, and 43.
Overall Study Ineligibility determined	0	1
Overall Study Adverse Event	1	4
Overall Study Withdrawal by Subject	6	4
Overall Study Physician Decision	1	0
Overall Study Death	3	5
Overall Study Other	0	1

Baseline Characteristics

Palifermin for the Reduction of Oral Mucositis in Patients With Locally Advanced Head and Neck Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=94 Participants Participants received a single IV dose of placebo three days before the start of radiotherapy, and then 7 once weekly placebo doses during a 7-week radiotherapy/chemotherapy course.	Palifermin n=94 Participants Participants received a single intravenous dose of palifermin at 180 μg/kg three days before the start of radiotherapy, and then 7 once weekly palifermin doses at the same dose level during a 7-week radiotherapy/chemotherapy course.	Total n=188 Participants Total of all reporting groups
Age, Continuous	55.4 years STANDARD_DEVIATION 8.3 • n=5 Participants	55.5 years STANDARD_DEVIATION 8.6 • n=7 Participants	55.5 years STANDARD_DEVIATION 8.5 • n=5 Participants
Sex: Female, Male Female	14 Participants n=5 Participants	15 Participants n=7 Participants	29 Participants n=5 Participants
Sex: Female, Male Male	80 Participants n=5 Participants	79 Participants n=7 Participants	159 Participants n=5 Participants
Race/Ethnicity, Customized Caucasian	90 participants n=5 Participants	83 participants n=7 Participants	173 participants n=5 Participants
Race/Ethnicity, Customized Black	2 participants n=5 Participants	7 participants n=7 Participants	9 participants n=5 Participants
Race/Ethnicity, Customized Hispanic	2 participants n=5 Participants	3 participants n=7 Participants	5 participants n=5 Participants
Race/Ethnicity, Customized American Indian/ Alaska Native	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants
Weight	71.8 kilograms STANDARD_DEVIATION 15.7 • n=5 Participants	74.5 kilograms STANDARD_DEVIATION 16.4 • n=7 Participants	73.2 kilograms STANDARD_DEVIATION 16.1 • n=5 Participants
Disease Stage Stage III	29 participants n=5 Participants	26 participants n=7 Participants	55 participants n=5 Participants
Disease Stage Stage IV A	54 participants n=5 Participants	60 participants n=7 Participants	114 participants n=5 Participants
Disease Stage Stage IV B	11 participants n=5 Participants	8 participants n=7 Participants	19 participants n=5 Participants
Tumor Site Oral Cavity	9 participants n=5 Participants	5 participants n=7 Participants	14 participants n=5 Participants
Tumor Site Oropharynx	51 participants n=5 Participants	55 participants n=7 Participants	106 participants n=5 Participants
Tumor Site Nasopharynx	3 participants n=5 Participants	4 participants n=7 Participants	7 participants n=5 Participants
Tumor Site Larynx	9 participants n=5 Participants	16 participants n=7 Participants	25 participants n=5 Participants
Tumor Site Hypopharynx	22 participants n=5 Participants	14 participants n=7 Participants	36 participants n=5 Participants

PRIMARY outcome

Timeframe: Up to Week 15

Population: The Full Analysis Set included all randomized participants.

Outcome measures

Outcome measures
Measure	Placebo n=94 Participants Participants received a single IV dose of placebo three days before the start of radiotherapy, and then 7 once weekly placebo doses during a 7-week radiotherapy/chemotherapy course.	Palifermin n=94 Participants Participants received a single intravenous dose of palifermin at 180 μg/kg three days before the start of radiotherapy, and then 7 once weekly palifermin doses at the same dose level during a 7-week radiotherapy/chemotherapy course.
Number of Participants With Severe (Grade 3 or 4) Oral Mucositis Yes	62 participants	51 participants
Number of Participants With Severe (Grade 3 or 4) Oral Mucositis No	29 participants	43 participants
Number of Participants With Severe (Grade 3 or 4) Oral Mucositis Unknown	3 participants	0 participants

SECONDARY outcome

Timeframe: Up to 15 weeks

Population: Full analysis set

The duration of severe oral mucositis (OM) was calculated as the number of days from the onset of severe OM (first time a WHO grade 3 or 4 was observed) to the day when severe OM was resolved (first time WHO grade 2 or less was observed after last WHO grade 3 or 4). Durations of 0 days were assigned to those participants who did not experience any WHO grade 3 or 4 during the study.

Outcome measures

Outcome measures
Measure	Placebo n=94 Participants Participants received a single IV dose of placebo three days before the start of radiotherapy, and then 7 once weekly placebo doses during a 7-week radiotherapy/chemotherapy course.	Palifermin n=94 Participants Participants received a single intravenous dose of palifermin at 180 μg/kg three days before the start of radiotherapy, and then 7 once weekly palifermin doses at the same dose level during a 7-week radiotherapy/chemotherapy course.
Duration of Severe (WHO Grade 3 or 4) Oral Mucositis	26.0 days Interval 0.0 to 50.0	5.0 days Interval 0.0 to 40.0

SECONDARY outcome

Timeframe: Up to 15 weeks

Population: Full analysis set

Time to onset of severe (WHO Grade 3 or 4) oral mucositis (OM) was analyzed using the Kaplan-Meier procedure. Participants without an assessed event by the end of the acute OM evaluation phase were censored at the date of last assessment for severe OM.

Outcome measures

Outcome measures
Measure	Placebo n=94 Participants Participants received a single IV dose of placebo three days before the start of radiotherapy, and then 7 once weekly placebo doses during a 7-week radiotherapy/chemotherapy course.	Palifermin n=94 Participants Participants received a single intravenous dose of palifermin at 180 μg/kg three days before the start of radiotherapy, and then 7 once weekly palifermin doses at the same dose level during a 7-week radiotherapy/chemotherapy course.
Time to Onset of Severe (WHO Grade 3 or 4) Oral Mucositis	35.0 days Interval 22.0 to Could not be estimated due to the low number of events	47.0 days Interval 27.0 to Could not be estimated due to the low number of events

SECONDARY outcome

Timeframe: Month 4

Population: Full Analysis Set

The number of participants with grade 2 or higher xerostomia (dryness of the oral mucosa) at the Month 4 visit, graded according to the Common Terminology Criteria for Adverse Events (CTCAE) v3.0 Dry Mouth/Xerostomia scale.

Outcome measures

Outcome measures
Measure	Placebo n=94 Participants Participants received a single IV dose of placebo three days before the start of radiotherapy, and then 7 once weekly placebo doses during a 7-week radiotherapy/chemotherapy course.	Palifermin n=94 Participants Participants received a single intravenous dose of palifermin at 180 μg/kg three days before the start of radiotherapy, and then 7 once weekly palifermin doses at the same dose level during a 7-week radiotherapy/chemotherapy course.
Number of Participants With Xerostomia at Month 4 (Grade 2 or Higher) Yes	57 participants	37 participants
Number of Participants With Xerostomia at Month 4 (Grade 2 or Higher) No	19 participants	31 participants
Number of Participants With Xerostomia at Month 4 (Grade 2 or Higher) Unknown	18 participants	26 participants

SECONDARY outcome

Timeframe: Assessed twice a week for up to 15 weeks.

Population: The Patient Reported Outcome-evaluable analysis set included all randomized patients with a valid Baseline assessment for MTS question 3 of the OMWQ-HN and either: * At least 1 completed assessment each week for MTS up to withdrawal/Week 8, whichever came first, or * 70% or greater overall compliance for MTS until withdrawal/Week 8.

The average patient-reported mouth and throat soreness (MTS) score as reported on question 3 of the Oral Mucositis Weekly Questionnaire for Head and Neck Cancer \[OMWQ-HN\]): "How much mouth and throat soreness did you experience in the past 24 hours?" Participants answered on a scale from 0 (no soreness) to 4 (extreme soreness). For each participant, an average patient-reported mouth and throat soreness score was calculated by dividing the sum of the MTS scores at each assessment by the total number of assessments.

Outcome measures

Outcome measures
Measure	Placebo n=88 Participants Participants received a single IV dose of placebo three days before the start of radiotherapy, and then 7 once weekly placebo doses during a 7-week radiotherapy/chemotherapy course.	Palifermin n=89 Participants Participants received a single intravenous dose of palifermin at 180 μg/kg three days before the start of radiotherapy, and then 7 once weekly palifermin doses at the same dose level during a 7-week radiotherapy/chemotherapy course.
Patient-Reported Mouth and Throat Soreness Score	1.86 units on a scale Standard Deviation 0.65	1.66 units on a scale Standard Deviation 0.73

SECONDARY outcome

Timeframe: Up to 15 weeks

Population: Full analysis set

The total dose of opioid analgesics (mg of intravenous \[IV\] morphine equivalents) used by all participants. Participants with at least one reported administration of opioid analgesic (parenteral, peroral or transdermal) were considered to have received opioid analgesics. The total dose of opioid analgesics is the sum of all opioid analgesic administrations that have been converted to morphine equivalents.

Outcome measures

Outcome measures
Measure	Placebo n=94 Participants Participants received a single IV dose of placebo three days before the start of radiotherapy, and then 7 once weekly placebo doses during a 7-week radiotherapy/chemotherapy course.	Palifermin n=94 Participants Participants received a single intravenous dose of palifermin at 180 μg/kg three days before the start of radiotherapy, and then 7 once weekly palifermin doses at the same dose level during a 7-week radiotherapy/chemotherapy course.
Total Dose of Opioid Analgesics Used for Mucositis Within 15 Weeks	1219.55 mg of IV morphine equivalents Standard Deviation 1769.29	1243.31 mg of IV morphine equivalents Standard Deviation 2700.28

SECONDARY outcome

Timeframe: During the 7 weeks of chemotherapy treatment

Population: Full analysis set

Cisplatin was administered on Days 1, 22, and 43. An unplanned break in cisplatin refers to a delay of ≥ 5 days from the scheduled Day 22 or Day 43 cisplatin administration or a discontinuation of cisplatin for any reason.

Outcome measures

Outcome measures
Measure	Placebo n=94 Participants Participants received a single IV dose of placebo three days before the start of radiotherapy, and then 7 once weekly placebo doses during a 7-week radiotherapy/chemotherapy course.	Palifermin n=94 Participants Participants received a single intravenous dose of palifermin at 180 μg/kg three days before the start of radiotherapy, and then 7 once weekly palifermin doses at the same dose level during a 7-week radiotherapy/chemotherapy course.
Number of Participants With Unplanned Breaks in Cisplatin Chemotherapy Treatment	42 participants	49 participants

SECONDARY outcome

Timeframe: During the 7 weeks of radiotherapy

Population: Full analysis set

Participants with a duration of 5 days or more without an administration of radiotherapy or who discontinue radiotherapy prior to completion of planned radiotherapy were considered to have an unplanned break in radiotherapy.

Outcome measures

Outcome measures
Measure	Placebo n=94 Participants Participants received a single IV dose of placebo three days before the start of radiotherapy, and then 7 once weekly placebo doses during a 7-week radiotherapy/chemotherapy course.	Palifermin n=94 Participants Participants received a single intravenous dose of palifermin at 180 μg/kg three days before the start of radiotherapy, and then 7 once weekly palifermin doses at the same dose level during a 7-week radiotherapy/chemotherapy course.
Number of Participants With Unplanned Breaks in Radiotherapy	11 participants	13 participants

Adverse Events

Placebo

Serious events: 25 serious events

Other events: 81 other events

Deaths: 0 deaths

Palifermin

Serious events: 35 serious events

Other events: 89 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=91 participants at risk Participants received a single intravenous (IV) dose of placebo three days before the start of radiotherapy, and then 7 once weekly placebo doses during a 7-week radiotherapy/chemotherapy course.	Palifermin n=94 participants at risk Participants received a single intravenous dose of palifermin at 180 μg/kg three days before the start of radiotherapy, and then 7 once weekly palifermin doses at the same dose level during a 7-week radiotherapy/chemotherapy course.
Blood and lymphatic system disorders Anaemia	35.2% 32/91 • Approximately 8 weeks The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.	22.3% 21/94 • Approximately 8 weeks The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.
Blood and lymphatic system disorders Leukopenia	12.1% 11/91 • Approximately 8 weeks The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.	22.3% 21/94 • Approximately 8 weeks The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.
Blood and lymphatic system disorders Neutropenia	6.6% 6/91 • Approximately 8 weeks The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.	10.6% 10/94 • Approximately 8 weeks The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.
Blood and lymphatic system disorders Thrombocytopenia	6.6% 6/91 • Approximately 8 weeks The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.	2.1% 2/94 • Approximately 8 weeks The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.
Ear and labyrinth disorders Tinnitus	7.7% 7/91 • Approximately 8 weeks The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.	11.7% 11/94 • Approximately 8 weeks The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.
Gastrointestinal disorders Constipation	26.4% 24/91 • Approximately 8 weeks The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.	33.0% 31/94 • Approximately 8 weeks The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.
Gastrointestinal disorders Diarrhoea	15.4% 14/91 • Approximately 8 weeks The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.	7.4% 7/94 • Approximately 8 weeks The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.
Gastrointestinal disorders Dry mouth	5.5% 5/91 • Approximately 8 weeks The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.	9.6% 9/94 • Approximately 8 weeks The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.
Gastrointestinal disorders Dyspepsia	4.4% 4/91 • Approximately 8 weeks The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.	5.3% 5/94 • Approximately 8 weeks The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.
Gastrointestinal disorders Dysphagia	20.9% 19/91 • Approximately 8 weeks The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.	28.7% 27/94 • Approximately 8 weeks The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.
Gastrointestinal disorders Nausea	46.2% 42/91 • Approximately 8 weeks The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.	48.9% 46/94 • Approximately 8 weeks The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.
Gastrointestinal disorders Odynophagia	5.5% 5/91 • Approximately 8 weeks The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.	9.6% 9/94 • Approximately 8 weeks The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.
Gastrointestinal disorders Oesophagitis	0.00% 0/91 • Approximately 8 weeks The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.	5.3% 5/94 • Approximately 8 weeks The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.
Gastrointestinal disorders Oral pain	3.3% 3/91 • Approximately 8 weeks The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.	9.6% 9/94 • Approximately 8 weeks The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.
Gastrointestinal disorders Vomiting	26.4% 24/91 • Approximately 8 weeks The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.	25.5% 24/94 • Approximately 8 weeks The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.
General disorders Asthenia	5.5% 5/91 • Approximately 8 weeks The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.	4.3% 4/94 • Approximately 8 weeks The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.
General disorders Fatigue	22.0% 20/91 • Approximately 8 weeks The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.	22.3% 21/94 • Approximately 8 weeks The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.
General disorders Malaise	1.1% 1/91 • Approximately 8 weeks The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.	5.3% 5/94 • Approximately 8 weeks The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.
General disorders Oedema peripheral	4.4% 4/91 • Approximately 8 weeks The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.	6.4% 6/94 • Approximately 8 weeks The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.
General disorders Pyrexia	20.9% 19/91 • Approximately 8 weeks The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.	17.0% 16/94 • Approximately 8 weeks The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.
Infections and infestations Candidiasis	15.4% 14/91 • Approximately 8 weeks The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.	11.7% 11/94 • Approximately 8 weeks The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.
Infections and infestations Oral candidiasis	12.1% 11/91 • Approximately 8 weeks The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.	18.1% 17/94 • Approximately 8 weeks The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.
Infections and infestations Oral fungal infection	6.6% 6/91 • Approximately 8 weeks The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.	5.3% 5/94 • Approximately 8 weeks The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.
Injury, poisoning and procedural complications Radiation skin injury	14.3% 13/91 • Approximately 8 weeks The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.	26.6% 25/94 • Approximately 8 weeks The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.
Investigations Blood creatinine increased	4.4% 4/91 • Approximately 8 weeks The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.	7.4% 7/94 • Approximately 8 weeks The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.
Investigations Weight decreased	28.6% 26/91 • Approximately 8 weeks The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.	26.6% 25/94 • Approximately 8 weeks The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.
Metabolism and nutrition disorders Anorexia	11.0% 10/91 • Approximately 8 weeks The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.	12.8% 12/94 • Approximately 8 weeks The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.
Metabolism and nutrition disorders Dehydration	13.2% 12/91 • Approximately 8 weeks The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.	10.6% 10/94 • Approximately 8 weeks The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.
Metabolism and nutrition disorders Hypokalaemia	8.8% 8/91 • Approximately 8 weeks The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.	20.2% 19/94 • Approximately 8 weeks The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.
Metabolism and nutrition disorders Hypomagnesaemia	3.3% 3/91 • Approximately 8 weeks The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.	5.3% 5/94 • Approximately 8 weeks The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.
Nervous system disorders Dizziness	5.5% 5/91 • Approximately 8 weeks The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.	3.2% 3/94 • Approximately 8 weeks The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.
Nervous system disorders Dysgeusia	7.7% 7/91 • Approximately 8 weeks The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.	19.1% 18/94 • Approximately 8 weeks The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.
Nervous system disorders Headache	5.5% 5/91 • Approximately 8 weeks The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.	10.6% 10/94 • Approximately 8 weeks The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.
Psychiatric disorders Anxiety	8.8% 8/91 • Approximately 8 weeks The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.	9.6% 9/94 • Approximately 8 weeks The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.
Psychiatric disorders Depression	3.3% 3/91 • Approximately 8 weeks The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.	5.3% 5/94 • Approximately 8 weeks The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.
Psychiatric disorders Insomnia	11.0% 10/91 • Approximately 8 weeks The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.	11.7% 11/94 • Approximately 8 weeks The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.
Respiratory, thoracic and mediastinal disorders Cough	14.3% 13/91 • Approximately 8 weeks The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.	17.0% 16/94 • Approximately 8 weeks The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.
Respiratory, thoracic and mediastinal disorders Dysphonia	8.8% 8/91 • Approximately 8 weeks The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.	11.7% 11/94 • Approximately 8 weeks The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.
Respiratory, thoracic and mediastinal disorders Dyspnoea	5.5% 5/91 • Approximately 8 weeks The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.	6.4% 6/94 • Approximately 8 weeks The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.
Respiratory, thoracic and mediastinal disorders Pharyngolaryngeal pain	24.2% 22/91 • Approximately 8 weeks The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.	21.3% 20/94 • Approximately 8 weeks The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.
Skin and subcutaneous tissue disorders Alopecia	1.1% 1/91 • Approximately 8 weeks The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.	6.4% 6/94 • Approximately 8 weeks The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.
Skin and subcutaneous tissue disorders Dermatitis	11.0% 10/91 • Approximately 8 weeks The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.	4.3% 4/94 • Approximately 8 weeks The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.
Skin and subcutaneous tissue disorders Rash	4.4% 4/91 • Approximately 8 weeks The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.	9.6% 9/94 • Approximately 8 weeks The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.
Skin and subcutaneous tissue disorders Skin hyperpigmentation	1.1% 1/91 • Approximately 8 weeks The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.	5.3% 5/94 • Approximately 8 weeks The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.
Vascular disorders Flushing	0.00% 0/91 • Approximately 8 weeks The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.	6.4% 6/94 • Approximately 8 weeks The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.
Vascular disorders Hypertension	4.4% 4/91 • Approximately 8 weeks The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.	5.3% 5/94 • Approximately 8 weeks The table of Other Adverse Events summarizes non-serious occurrences of adverse events that exceeded a 5% frequency in either treatment arm.