Trial Outcomes & Findings for Efficacy and Safety Study of Reslizumab to Treat Eosinophilic Esophagitis in Subjects Aged 5 to 18 Years (NCT NCT00538434)

Last Updated: 2016-09-02

Results Overview

Participants underwent esophagogastroduodenoscopy (EGD) with biopsy (2 biopsies each at proximal and distal esophageal locations, plus any inflamed or abnormal areas) per standard clinical practice for the determination of esophageal eosinophils.

Recruitment status

COMPLETED

Study phase

PHASE2/PHASE3

Target enrollment

227 participants

Primary outcome timeframe

Baseline, End of Treatment (up to 15 weeks [+/- 4 days])

Results posted on

2016-09-02

Participant Flow

Participant milestones

Participant milestones
Measure	Reslizumab 1 mg/kg reslizumab 1 mg/kg intravenous (IV) on Day 0 of each 28-day (+/-7 days) cycle, for up to 4 cycles	Reslizumab 2 mg/kg reslizumab 2 mg/kg IV on Day 0 of each 28-day (+/-7 days) cycle, for up to 4 cycles	Reslizumab 3 mg/kg reslizumab 3 mg/kg IV on Day 0 of each 28-day (+/-7 days) cycle, for up to 4 cycles	Placebo saline placebo IV on Day 0 of each 28-day (+/-7 days) cycle, for up to 4 cycles
Overall Study STARTED	56	57	57	57
Overall Study Intent-to-treat (ITT) Population	55	57	57	57
Overall Study COMPLETED	47	46	50	51
Overall Study NOT COMPLETED	9	11	7	6

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Efficacy and Safety Study of Reslizumab to Treat Eosinophilic Esophagitis in Subjects Aged 5 to 18 Years

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Reslizumab 1 mg/kg n=55 Participants reslizumab 1 mg/kg intravenous (IV) on Day 0 of each 28-day (+/-7 days) cycle, for up to 4 cycles	Reslizumab 2 mg/kg n=57 Participants reslizumab 2 mg/kg IV on Day 0 of each 28-day (+/-7 days) cycle, for up to 4 cycles	Reslizumab 3 mg/kg n=57 Participants reslizumab 3 mg/kg IV on Day 0 of each 28-day (+/-7 days) cycle, for up to 4 cycles	Placebo n=57 Participants saline placebo IV on Day 0 of each 28-day (+/-7 days) cycle, for up to 4 cycles	Total n=226 Participants Total of all reporting groups
Age, Continuous	12.3 years STANDARD_DEVIATION 3.83 • n=5 Participants	11.8 years STANDARD_DEVIATION 3.82 • n=7 Participants	11.5 years STANDARD_DEVIATION 4.04 • n=5 Participants	11.9 years STANDARD_DEVIATION 4.17 • n=4 Participants	11.9 years STANDARD_DEVIATION 3.95 • n=21 Participants
Age, Customized 5 to < 12 years	21 participants n=5 Participants	26 participants n=7 Participants	27 participants n=5 Participants	25 participants n=4 Participants	99 participants n=21 Participants
Age, Customized 12 to < 19 years	34 participants n=5 Participants	31 participants n=7 Participants	30 participants n=5 Participants	32 participants n=4 Participants	127 participants n=21 Participants
Sex: Female, Male Female	14 Participants n=5 Participants	15 Participants n=7 Participants	12 Participants n=5 Participants	13 Participants n=4 Participants	54 Participants n=21 Participants
Sex: Female, Male Male	41 Participants n=5 Participants	42 Participants n=7 Participants	45 Participants n=5 Participants	44 Participants n=4 Participants	172 Participants n=21 Participants

PRIMARY outcome

Timeframe: Baseline, End of Treatment (up to 15 weeks [+/- 4 days])

Population: ITT population: all randomized participants who received any amount of study drug.

Outcome measures

Outcome measures
Measure	Reslizumab 1 mg/kg n=55 Participants reslizumab 1 mg/kg intravenous (IV) on Day 0 of each 28-day (+/-7 days) cycle, for up to 4 cycles	Reslizumab 2 mg/kg n=57 Participants reslizumab 2 mg/kg IV on Day 0 of each 28-day (+/-7 days) cycle, for up to 4 cycles	Reslizumab 3 mg/kg n=57 Participants reslizumab 3 mg/kg IV on Day 0 of each 28-day (+/-7 days) cycle, for up to 4 cycles	Placebo n=57 Participants saline placebo IV on Day 0 of each 28-day (+/-7 days) cycle, for up to 4 cycles
Mean Percent Change From Baseline to End of Treatment in Peak Esophageal Eosinophil (EE) Levels	-37.60 percentage change in eosinophils/hpf Standard Deviation 70.86	-58.27 percentage change in eosinophils/hpf Standard Deviation 35.45	-56.46 percentage change in eosinophils/hpf Standard Deviation 34.82	11.50 percentage change in eosinophils/hpf Standard Deviation 91.42

PRIMARY outcome

Timeframe: Baseline (Day 1, pre-treatment), End of Treatment (Week 15, 3 weeks [± 4 days] after the last dose of study drug, or at early withdrawal)

Population: ITT population: all randomized participants who received any amount of study drug with both a baseline and an End of Treatment assessment.

The investigator completed the Physician's EE Global Assessment based upon the participant's reporting of symptoms, weight, dietary status, and overall well-being. The assessment rated severity on a five-point scale (0=none to 4=very severe), taking into account physical findings, vital signs, the Subject's Predominant EE Symptom Assessment, the subject's diary data, and dietary questions. The Subject's Predominant EE Symptom was the EE symptom (vomiting/regurgitation, abdominal/chest pain, or dysphagia) that had the greatest negative impact on the subject based on patient diary data as of the baseline visit. The full range for change from baseline values is -4 (very severe at baseline, none at end of study) to 4 (none at baseline, severe at end of study). Negative change from baseline scores in the Physician's EE Global Assessment indicate improvement in EE status.

Outcome measures

Outcome measures
Measure	Reslizumab 1 mg/kg n=55 Participants reslizumab 1 mg/kg intravenous (IV) on Day 0 of each 28-day (+/-7 days) cycle, for up to 4 cycles	Reslizumab 2 mg/kg n=57 Participants reslizumab 2 mg/kg IV on Day 0 of each 28-day (+/-7 days) cycle, for up to 4 cycles	Reslizumab 3 mg/kg n=57 Participants reslizumab 3 mg/kg IV on Day 0 of each 28-day (+/-7 days) cycle, for up to 4 cycles	Placebo n=57 Participants saline placebo IV on Day 0 of each 28-day (+/-7 days) cycle, for up to 4 cycles
Mean Change From Baseline in Physician's Esophageal Eosinophil (EE) Global Assessment At The End-of-Treatment Visit (or at Early Withdrawal)	-0.85 units on a scale Standard Deviation NA Study documentation from an acquired company does not contain the measure of dispersion.	-1.02 units on a scale Standard Deviation NA Study documentation from an acquired company does not contain the measure of dispersion.	-1.12 units on a scale Standard Deviation NA Study documentation from an acquired company does not contain the measure of dispersion.	-1.14 units on a scale Standard Deviation NA Study documentation from an acquired company does not contain the measure of dispersion.

SECONDARY outcome

Timeframe: Baseline (Day 1, pre-treatment), End of Treatment (Week 15, 3 weeks [± 4 days] after the last dose of study drug, or at early withdrawal)

Population: ITT population: all randomized participants who received any amount of study drug with both a baseline and an End of Treatment assessment.

Participants rated the severity of each EE symptom (vomiting/regurgitation, abdominal/chest pain, and dysphagia) based on the previous week's daily diary as none (=0), mild, moderate, severe, or very severe (=4). The predominant symptom was selected at the baseline visit and remained the same throughout the trial. The predominant symptom was defined as the EE symptom that had the greatest negative impact on the participant. The full range for change from baseline values is -4 (very severe at baseline, none at end of study) to 4 (none at baseline, severe at end of study). Negative change from baseline scores in the Patient's EE Predominant Symptom Assessment indicate improvement in the selected symptom.

Outcome measures

Outcome measures
Measure	Reslizumab 1 mg/kg n=54 Participants reslizumab 1 mg/kg intravenous (IV) on Day 0 of each 28-day (+/-7 days) cycle, for up to 4 cycles	Reslizumab 2 mg/kg n=56 Participants reslizumab 2 mg/kg IV on Day 0 of each 28-day (+/-7 days) cycle, for up to 4 cycles	Reslizumab 3 mg/kg n=57 Participants reslizumab 3 mg/kg IV on Day 0 of each 28-day (+/-7 days) cycle, for up to 4 cycles	Placebo n=55 Participants saline placebo IV on Day 0 of each 28-day (+/-7 days) cycle, for up to 4 cycles
Mean Change From Baseline to End of Treatment in EE Predominant Symptom Assessment	-0.94 units on a scale Standard Deviation NA Study documentation from an acquired company does not contain the measure of dispersion.	-1.20 units on a scale Standard Deviation NA Study documentation from an acquired company does not contain the measure of dispersion.	-1.28 units on a scale Standard Deviation NA Study documentation from an acquired company does not contain the measure of dispersion.	-1.44 units on a scale Standard Deviation NA Study documentation from an acquired company does not contain the measure of dispersion.

SECONDARY outcome

Timeframe: Baseline, End of Treatment (up to 15 weeks +/- 4 days)

Population: ITT population: all randomized participants who received any amount of study drug with both a baseline and an End of Treatment assessment; n=number of participants with a response in the given category.

CHQ is a quality-of-life (QoL), observer-rated (the parent in this study) instrument designed to assess the general health and well-being of pediatric subjects aged 5 to 18 years. The instrument comprises 50 items that cover 14 unique physical and psychological concepts. Each item was scored separately following different scales and timeframes for response. Proprietary scoring algorithms are used. This outcome reports the two CHQ Summary Scores (Physical Summary Score and the Psychosocial Summary Scores) which are indexed to a 0 (poorest quality of life) to 100 (best quality of life) scores. The two summary scores are subsequently combined (via proprietary algorithm) to create the Global Health Summary Score (also on a 0-100 scale). Percent change from baseline values range from 100% (poorest QoL at baseline, best QoL at end of treatment) to -100% (best QoL at baseline, poorest QoL at end of treatment). Higher percent change from baseline values indicate improved QoL.

Outcome measures

Outcome measures
Measure	Reslizumab 1 mg/kg n=55 Participants reslizumab 1 mg/kg intravenous (IV) on Day 0 of each 28-day (+/-7 days) cycle, for up to 4 cycles	Reslizumab 2 mg/kg n=57 Participants reslizumab 2 mg/kg IV on Day 0 of each 28-day (+/-7 days) cycle, for up to 4 cycles	Reslizumab 3 mg/kg n=57 Participants reslizumab 3 mg/kg IV on Day 0 of each 28-day (+/-7 days) cycle, for up to 4 cycles	Placebo n=57 Participants saline placebo IV on Day 0 of each 28-day (+/-7 days) cycle, for up to 4 cycles
Mean Percent Change From Baseline to End of Treatment in the Child Health Questionnaire (CHQ) Physical Summary Score; n=49, 52, 53, 57	11.2 percentage change in score Standard Deviation NA Study documentation from an acquired company does not contain the measure of dispersion.	18.6 percentage change in score Standard Deviation NA Study documentation from an acquired company does not contain the measure of dispersion.	18.5 percentage change in score Standard Deviation NA Study documentation from an acquired company does not contain the measure of dispersion.	11.8 percentage change in score Standard Deviation NA Study documentation from an acquired company does not contain the measure of dispersion.
Mean Percent Change From Baseline to End of Treatment in the Child Health Questionnaire (CHQ) Psychosocial Summary Score; n=51, 52, 53, 55	5.0 percentage change in score Standard Deviation NA Study documentation from an acquired company does not contain the measure of dispersion.	12.2 percentage change in score Standard Deviation NA Study documentation from an acquired company does not contain the measure of dispersion.	14.1 percentage change in score Standard Deviation NA Study documentation from an acquired company does not contain the measure of dispersion.	10.1 percentage change in score Standard Deviation NA Study documentation from an acquired company does not contain the measure of dispersion.
Mean Percent Change From Baseline to End of Treatment in the Child Health Questionnaire (CHQ) Global Health Summary Score; n=50, 54, 54, 55	10.2 percentage change in score Standard Deviation NA Study documentation from an acquired company does not contain the measure of dispersion.	15.5 percentage change in score Standard Deviation NA Study documentation from an acquired company does not contain the measure of dispersion.	10.3 percentage change in score Standard Deviation NA Study documentation from an acquired company does not contain the measure of dispersion.	9.7 percentage change in score Standard Deviation NA Study documentation from an acquired company does not contain the measure of dispersion.

Adverse Events

Reslizumab 1 mg/kg

Serious events: 1 serious events

Other events: 38 other events

Deaths: 0 deaths

Reslizumab 2 mg/kg

Serious events: 1 serious events

Other events: 29 other events

Deaths: 0 deaths

Reslizumab 3 mg/kg

Serious events: 1 serious events

Other events: 39 other events

Deaths: 0 deaths

Placebo

Serious events: 2 serious events

Other events: 40 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Reslizumab 1 mg/kg n=55 participants at risk reslizumab 1 mg/kg intravenous (IV) on Day 0 of each 28-day (+/-7 days) cycle, for up to 4 cycles	Reslizumab 2 mg/kg n=57 participants at risk reslizumab 2 mg/kg IV on Day 0 of each 28-day (+/-7 days) cycle, for up to 4 cycles	Reslizumab 3 mg/kg n=57 participants at risk reslizumab 3 mg/kg IV on Day 0 of each 28-day (+/-7 days) cycle, for up to 4 cycles	Placebo n=57 participants at risk saline placebo IV on Day 0 of each 28-day (+/-7 days) cycle, for up to 4 cycles
Gastrointestinal disorders ABDOMINAL PAIN	0.00% 0/55 • Baseline through Safety Follow-up (Week 16)	0.00% 0/57 • Baseline through Safety Follow-up (Week 16)	0.00% 0/57 • Baseline through Safety Follow-up (Week 16)	1.8% 1/57 • Number of events 1 • Baseline through Safety Follow-up (Week 16)
Gastrointestinal disorders GASTROINTESTINAL INFLAMMATION	1.8% 1/55 • Number of events 1 • Baseline through Safety Follow-up (Week 16)	0.00% 0/57 • Baseline through Safety Follow-up (Week 16)	0.00% 0/57 • Baseline through Safety Follow-up (Week 16)	0.00% 0/57 • Baseline through Safety Follow-up (Week 16)
Immune system disorders ANAPHYLACTIC REACTION	0.00% 0/55 • Baseline through Safety Follow-up (Week 16)	0.00% 0/57 • Baseline through Safety Follow-up (Week 16)	0.00% 0/57 • Baseline through Safety Follow-up (Week 16)	1.8% 1/57 • Number of events 1 • Baseline through Safety Follow-up (Week 16)
Infections and infestations GASTROENTERITIS VIRAL	0.00% 0/55 • Baseline through Safety Follow-up (Week 16)	1.8% 1/57 • Number of events 1 • Baseline through Safety Follow-up (Week 16)	0.00% 0/57 • Baseline through Safety Follow-up (Week 16)	0.00% 0/57 • Baseline through Safety Follow-up (Week 16)
Nervous system disorders SYNCOPE	0.00% 0/55 • Baseline through Safety Follow-up (Week 16)	0.00% 0/57 • Baseline through Safety Follow-up (Week 16)	0.00% 0/57 • Baseline through Safety Follow-up (Week 16)	1.8% 1/57 • Number of events 1 • Baseline through Safety Follow-up (Week 16)
Respiratory, thoracic and mediastinal disorders RESPIRATORY DISTRESS	0.00% 0/55 • Baseline through Safety Follow-up (Week 16)	0.00% 0/57 • Baseline through Safety Follow-up (Week 16)	1.8% 1/57 • Number of events 1 • Baseline through Safety Follow-up (Week 16)	0.00% 0/57 • Baseline through Safety Follow-up (Week 16)

Other adverse events

Additional Information

Director, Clinical Research

Teva Branded Pharmaceutical Products, R&D Inc.

Phone: 215-591-3000

Results disclosure agreements

Principal investigator is a sponsor employee Sponsor has the right 60 days before submission for publication to review/provide comments. If the Sponsor's review shows that potentially patentable subject matter would be disclosed, publication or public disclosure shall be delayed for up to 90 additional days in order for the Sponsor, or Sponsor's designees, to file the necessary patent applications. In multicenter trials, each PI will postpone single center publications until after disclosure or publication of multicenter data.
Publication restrictions are in place

Restriction type: OTHER

Measure	Reslizumab 1 mg/kg n=55 participants at risk reslizumab 1 mg/kg intravenous (IV) on Day 0 of each 28-day (+/-7 days) cycle, for up to 4 cycles	Reslizumab 2 mg/kg n=57 participants at risk reslizumab 2 mg/kg IV on Day 0 of each 28-day (+/-7 days) cycle, for up to 4 cycles	Reslizumab 3 mg/kg n=57 participants at risk reslizumab 3 mg/kg IV on Day 0 of each 28-day (+/-7 days) cycle, for up to 4 cycles	Placebo n=57 participants at risk saline placebo IV on Day 0 of each 28-day (+/-7 days) cycle, for up to 4 cycles
Gastrointestinal disorders ABDOMINAL PAIN	10.9% 6/55 • Number of events 7 • Baseline through Safety Follow-up (Week 16)	0.00% 0/57 • Baseline through Safety Follow-up (Week 16)	5.3% 3/57 • Number of events 3 • Baseline through Safety Follow-up (Week 16)	3.5% 2/57 • Number of events 2 • Baseline through Safety Follow-up (Week 16)
Gastrointestinal disorders ABDOMINAL PAIN UPPER	7.3% 4/55 • Number of events 4 • Baseline through Safety Follow-up (Week 16)	3.5% 2/57 • Number of events 2 • Baseline through Safety Follow-up (Week 16)	7.0% 4/57 • Number of events 5 • Baseline through Safety Follow-up (Week 16)	8.8% 5/57 • Number of events 8 • Baseline through Safety Follow-up (Week 16)
Gastrointestinal disorders DIARRHOEA	7.3% 4/55 • Number of events 4 • Baseline through Safety Follow-up (Week 16)	5.3% 3/57 • Number of events 3 • Baseline through Safety Follow-up (Week 16)	0.00% 0/57 • Baseline through Safety Follow-up (Week 16)	8.8% 5/57 • Number of events 8 • Baseline through Safety Follow-up (Week 16)
Gastrointestinal disorders NAUSEA	10.9% 6/55 • Number of events 6 • Baseline through Safety Follow-up (Week 16)	3.5% 2/57 • Number of events 2 • Baseline through Safety Follow-up (Week 16)	7.0% 4/57 • Number of events 4 • Baseline through Safety Follow-up (Week 16)	5.3% 3/57 • Number of events 3 • Baseline through Safety Follow-up (Week 16)
Gastrointestinal disorders VOMITING	3.6% 2/55 • Number of events 2 • Baseline through Safety Follow-up (Week 16)	3.5% 2/57 • Number of events 3 • Baseline through Safety Follow-up (Week 16)	3.5% 2/57 • Number of events 4 • Baseline through Safety Follow-up (Week 16)	8.8% 5/57 • Number of events 5 • Baseline through Safety Follow-up (Week 16)
General disorders CHEST PAIN	1.8% 1/55 • Number of events 1 • Baseline through Safety Follow-up (Week 16)	1.8% 1/57 • Number of events 1 • Baseline through Safety Follow-up (Week 16)	1.8% 1/57 • Number of events 1 • Baseline through Safety Follow-up (Week 16)	5.3% 3/57 • Number of events 3 • Baseline through Safety Follow-up (Week 16)
General disorders FATIGUE	9.1% 5/55 • Number of events 7 • Baseline through Safety Follow-up (Week 16)	3.5% 2/57 • Number of events 6 • Baseline through Safety Follow-up (Week 16)	5.3% 3/57 • Number of events 6 • Baseline through Safety Follow-up (Week 16)	1.8% 1/57 • Number of events 1 • Baseline through Safety Follow-up (Week 16)
General disorders PYREXIA	7.3% 4/55 • Number of events 5 • Baseline through Safety Follow-up (Week 16)	3.5% 2/57 • Number of events 2 • Baseline through Safety Follow-up (Week 16)	5.3% 3/57 • Number of events 4 • Baseline through Safety Follow-up (Week 16)	10.5% 6/57 • Number of events 8 • Baseline through Safety Follow-up (Week 16)
Infections and infestations GASTROENTERITIS VIRAL	1.8% 1/55 • Number of events 1 • Baseline through Safety Follow-up (Week 16)	5.3% 3/57 • Number of events 3 • Baseline through Safety Follow-up (Week 16)	1.8% 1/57 • Number of events 1 • Baseline through Safety Follow-up (Week 16)	0.00% 0/57 • Baseline through Safety Follow-up (Week 16)
Infections and infestations INFLUENZA	3.6% 2/55 • Number of events 2 • Baseline through Safety Follow-up (Week 16)	0.00% 0/57 • Baseline through Safety Follow-up (Week 16)	7.0% 4/57 • Number of events 4 • Baseline through Safety Follow-up (Week 16)	1.8% 1/57 • Number of events 1 • Baseline through Safety Follow-up (Week 16)
Infections and infestations NASOPHARYNGITIS	5.5% 3/55 • Number of events 3 • Baseline through Safety Follow-up (Week 16)	3.5% 2/57 • Number of events 2 • Baseline through Safety Follow-up (Week 16)	1.8% 1/57 • Number of events 1 • Baseline through Safety Follow-up (Week 16)	12.3% 7/57 • Number of events 8 • Baseline through Safety Follow-up (Week 16)
Infections and infestations OTITIS MEDIA	0.00% 0/55 • Baseline through Safety Follow-up (Week 16)	5.3% 3/57 • Number of events 3 • Baseline through Safety Follow-up (Week 16)	1.8% 1/57 • Number of events 1 • Baseline through Safety Follow-up (Week 16)	0.00% 0/57 • Baseline through Safety Follow-up (Week 16)
Infections and infestations PHARYNGITIS STREPTOCOCCAL	5.5% 3/55 • Number of events 3 • Baseline through Safety Follow-up (Week 16)	1.8% 1/57 • Number of events 1 • Baseline through Safety Follow-up (Week 16)	0.00% 0/57 • Baseline through Safety Follow-up (Week 16)	5.3% 3/57 • Number of events 3 • Baseline through Safety Follow-up (Week 16)
Infections and infestations SINUSITIS	9.1% 5/55 • Number of events 5 • Baseline through Safety Follow-up (Week 16)	1.8% 1/57 • Number of events 1 • Baseline through Safety Follow-up (Week 16)	8.8% 5/57 • Number of events 6 • Baseline through Safety Follow-up (Week 16)	7.0% 4/57 • Number of events 4 • Baseline through Safety Follow-up (Week 16)
Infections and infestations UPPER RESPIRATORY TRACT INFECTION	9.1% 5/55 • Number of events 5 • Baseline through Safety Follow-up (Week 16)	7.0% 4/57 • Number of events 4 • Baseline through Safety Follow-up (Week 16)	10.5% 6/57 • Number of events 6 • Baseline through Safety Follow-up (Week 16)	8.8% 5/57 • Number of events 6 • Baseline through Safety Follow-up (Week 16)
Infections and infestations VIRAL INFECTION	5.5% 3/55 • Number of events 3 • Baseline through Safety Follow-up (Week 16)	5.3% 3/57 • Number of events 3 • Baseline through Safety Follow-up (Week 16)	1.8% 1/57 • Number of events 1 • Baseline through Safety Follow-up (Week 16)	0.00% 0/57 • Baseline through Safety Follow-up (Week 16)
Investigations PROTEIN URINE	0.00% 0/55 • Baseline through Safety Follow-up (Week 16)	0.00% 0/57 • Baseline through Safety Follow-up (Week 16)	0.00% 0/57 • Baseline through Safety Follow-up (Week 16)	5.3% 3/57 • Number of events 3 • Baseline through Safety Follow-up (Week 16)
Investigations RED BLOOD CELLS URINE POSITIVE	5.5% 3/55 • Number of events 3 • Baseline through Safety Follow-up (Week 16)	0.00% 0/57 • Baseline through Safety Follow-up (Week 16)	0.00% 0/57 • Baseline through Safety Follow-up (Week 16)	3.5% 2/57 • Number of events 2 • Baseline through Safety Follow-up (Week 16)
Investigations URINARY CASTS	3.6% 2/55 • Number of events 2 • Baseline through Safety Follow-up (Week 16)	0.00% 0/57 • Baseline through Safety Follow-up (Week 16)	0.00% 0/57 • Baseline through Safety Follow-up (Week 16)	7.0% 4/57 • Number of events 4 • Baseline through Safety Follow-up (Week 16)
Investigations URINE OXALATE INCREASED	5.5% 3/55 • Number of events 4 • Baseline through Safety Follow-up (Week 16)	0.00% 0/57 • Baseline through Safety Follow-up (Week 16)	0.00% 0/57 • Baseline through Safety Follow-up (Week 16)	1.8% 1/57 • Number of events 1 • Baseline through Safety Follow-up (Week 16)
Investigations WHITE BLOOD CELLS URINE POSITIVE	7.3% 4/55 • Number of events 7 • Baseline through Safety Follow-up (Week 16)	0.00% 0/57 • Baseline through Safety Follow-up (Week 16)	0.00% 0/57 • Baseline through Safety Follow-up (Week 16)	1.8% 1/57 • Number of events 1 • Baseline through Safety Follow-up (Week 16)
Musculoskeletal and connective tissue disorders ARTHRALGIA	9.1% 5/55 • Number of events 6 • Baseline through Safety Follow-up (Week 16)	1.8% 1/57 • Number of events 1 • Baseline through Safety Follow-up (Week 16)	0.00% 0/57 • Baseline through Safety Follow-up (Week 16)	0.00% 0/57 • Baseline through Safety Follow-up (Week 16)
Nervous system disorders DIZZINESS	3.6% 2/55 • Number of events 3 • Baseline through Safety Follow-up (Week 16)	1.8% 1/57 • Number of events 1 • Baseline through Safety Follow-up (Week 16)	10.5% 6/57 • Number of events 7 • Baseline through Safety Follow-up (Week 16)	1.8% 1/57 • Number of events 2 • Baseline through Safety Follow-up (Week 16)
Nervous system disorders HEADACHE	14.5% 8/55 • Number of events 9 • Baseline through Safety Follow-up (Week 16)	10.5% 6/57 • Number of events 7 • Baseline through Safety Follow-up (Week 16)	21.1% 12/57 • Number of events 15 • Baseline through Safety Follow-up (Week 16)	12.3% 7/57 • Number of events 7 • Baseline through Safety Follow-up (Week 16)
Respiratory, thoracic and mediastinal disorders COUGH	9.1% 5/55 • Number of events 5 • Baseline through Safety Follow-up (Week 16)	10.5% 6/57 • Number of events 7 • Baseline through Safety Follow-up (Week 16)	10.5% 6/57 • Number of events 7 • Baseline through Safety Follow-up (Week 16)	10.5% 6/57 • Number of events 6 • Baseline through Safety Follow-up (Week 16)
Respiratory, thoracic and mediastinal disorders NASAL CONGESTION	12.7% 7/55 • Number of events 9 • Baseline through Safety Follow-up (Week 16)	5.3% 3/57 • Number of events 3 • Baseline through Safety Follow-up (Week 16)	7.0% 4/57 • Number of events 4 • Baseline through Safety Follow-up (Week 16)	14.0% 8/57 • Number of events 9 • Baseline through Safety Follow-up (Week 16)
Respiratory, thoracic and mediastinal disorders PHARYNGOLARYNGEAL PAIN	10.9% 6/55 • Number of events 6 • Baseline through Safety Follow-up (Week 16)	5.3% 3/57 • Number of events 3 • Baseline through Safety Follow-up (Week 16)	7.0% 4/57 • Number of events 5 • Baseline through Safety Follow-up (Week 16)	15.8% 9/57 • Number of events 12 • Baseline through Safety Follow-up (Week 16)
Skin and subcutaneous tissue disorders ECZEMA	0.00% 0/55 • Baseline through Safety Follow-up (Week 16)	7.0% 4/57 • Number of events 4 • Baseline through Safety Follow-up (Week 16)	0.00% 0/57 • Baseline through Safety Follow-up (Week 16)	1.8% 1/57 • Number of events 1 • Baseline through Safety Follow-up (Week 16)
Skin and subcutaneous tissue disorders RASH	7.3% 4/55 • Number of events 5 • Baseline through Safety Follow-up (Week 16)	1.8% 1/57 • Number of events 1 • Baseline through Safety Follow-up (Week 16)	0.00% 0/57 • Baseline through Safety Follow-up (Week 16)	7.0% 4/57 • Number of events 5 • Baseline through Safety Follow-up (Week 16)