Trial Outcomes & Findings for Efficacy and Safety of Dexlansoprazole in Healing and Maintaining Healing of Erosive Esophagitis (NCT NCT02873702)

Last Updated: 2019-02-22

Results Overview

Percentage of participants with complete healing of EE was assessed by endoscopy. EE was graded according to the Los Angeles (LA) classification of esophagitis grading system, based on the extent of visible mucosal breaks seen in the esophagus according to the following: Grade O (no mucosal breaks); Grade A (\>=1 mucosal break no longer than 5 millimeter \[mm\] that does not extend between the tops of 2 mucosal folds); Grade B (\>=1 mucosal break greater than \[\>\] 5 mm that does not extend between the tops of 2 mucosal folds); Grade C (\>=1 mucosal break that is continuous between the tops of 2 or more mucosal folds, but involves \<75 percent (%) of the circumference); Grade D (\>=1 mucosal break which involves \>=75% of the circumference). Healing is defined as LA Grade O.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

37 participants

Primary outcome timeframe

Week 8

Results posted on

2019-02-22

Participant Flow

Participants took part in the study at 8 investigative sites in China from 21 December 2016 to 06 November 2017.

Participants with erosive esophagitis (EE) were enrolled to receive: lansoprazole 30 milligram (mg) or dexlansoprazole 60 mg in Healing Period and dexlansoprazole 30 mg or Placebo in Maintenance Period. Study was terminated since compound was not expected to provide sufficient additional benefit to participants over currently available therapies.

Participant milestones

Participant milestones
Measure	Healing Period: Lansoprazole 30 mg Lansoprazole 30 mg, capsules, orally, once daily for up to 8 weeks in the Healing Period.	Healing Period: Dexlansoprazole 60 mg Dexlansoprazole 60 mg, capsules, orally, once daily for up to 8 weeks in the Healing Period.	Maintenance Period: Placebo Dexlansoprazole placebo-matching capsules, orally, once daily for up to 6 months in the Maintenance period. Participants who were healed at Week 8 entered the Maintenance Period.	Maintenance Period: Dexlansoprazole 30 mg Dexlansoprazole 30 mg, delayed-release capsules, orally, once daily for up to 6 months in the Maintenance period. Participants who were healed at Week 8 entered the Maintenance Period.
Healing Period (up to Week 8) STARTED	20	17	0	0
Healing Period (up to Week 8) COMPLETED	19	16	0	0
Healing Period (up to Week 8) NOT COMPLETED	1	1	0	0
Maintenance Period (up to Month 6) STARTED	0	0	8	8
Maintenance Period (up to Month 6) COMPLETED	0	0	1	6
Maintenance Period (up to Month 6) NOT COMPLETED	0	0	7	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Healing Period: Lansoprazole 30 mg Lansoprazole 30 mg, capsules, orally, once daily for up to 8 weeks in the Healing Period.	Healing Period: Dexlansoprazole 60 mg Dexlansoprazole 60 mg, capsules, orally, once daily for up to 8 weeks in the Healing Period.	Maintenance Period: Placebo Dexlansoprazole placebo-matching capsules, orally, once daily for up to 6 months in the Maintenance period. Participants who were healed at Week 8 entered the Maintenance Period.	Maintenance Period: Dexlansoprazole 30 mg Dexlansoprazole 30 mg, delayed-release capsules, orally, once daily for up to 6 months in the Maintenance period. Participants who were healed at Week 8 entered the Maintenance Period.
Maintenance Period (up to Month 6) Adverse Event	0	0	1	0
Healing Period (up to Week 8) Adverse Event	1	0	0	0
Healing Period (up to Week 8) Withdrawal by Subject	0	1	0	0
Maintenance Period (up to Month 6) Relapse of EE	0	0	4	1
Maintenance Period (up to Month 6) Withdrawal by Subject	0	0	2	1

Baseline Characteristics

Efficacy and Safety of Dexlansoprazole in Healing and Maintaining Healing of Erosive Esophagitis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Healing Period: Lansoprazole 30 mg n=20 Participants Lansoprazole 30 mg, capsules, orally, once daily for up to 8 weeks in the Healing Period.	Healing Period: Dexlansoprazole 60 mg n=17 Participants Dexlansoprazole 60 mg, capsules, orally, once daily for up to 8 weeks in the Healing Period.	Total n=37 Participants Total of all reporting groups
Age, Continuous	49.4 years STANDARD_DEVIATION 14.35 • n=5 Participants	47.4 years STANDARD_DEVIATION 11.03 • n=7 Participants	48.4 years STANDARD_DEVIATION 12.80 • n=5 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	3 Participants n=7 Participants	9 Participants n=5 Participants
Sex: Female, Male Male	14 Participants n=5 Participants	14 Participants n=7 Participants	28 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	20 Participants n=5 Participants	17 Participants n=7 Participants	37 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment China	20 Participants n=5 Participants	17 Participants n=7 Participants	37 Participants n=5 Participants
Height	166.28 centimeter (cm) STANDARD_DEVIATION 8.091 • n=5 Participants	167.82 centimeter (cm) STANDARD_DEVIATION 8.346 • n=7 Participants	166.99 centimeter (cm) STANDARD_DEVIATION 8.131 • n=5 Participants
Weight	64.73 kilogram (kg) STANDARD_DEVIATION 10.002 • n=5 Participants	69.44 kilogram (kg) STANDARD_DEVIATION 11.190 • n=7 Participants	66.89 kilogram (kg) STANDARD_DEVIATION 10.683 • n=5 Participants
Baseline Body Mass Index (BMI)	23.310 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 2.2623 • n=5 Participants	24.606 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 3.5321 • n=7 Participants	23.905 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 2.9452 • n=5 Participants
BMI Categories Less than (<) 25 kg/m^2	15 Participants n=5 Participants	9 Participants n=7 Participants	24 Participants n=5 Participants
BMI Categories 25 to <30 kg/m^2	5 Participants n=5 Participants	7 Participants n=7 Participants	12 Participants n=5 Participants
BMI Categories Greater than or equal to (>=) 30 kg/m^2	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: Week 8

Population: The FAS-H included all randomized participants who had documented EE at screening and had received at least 1 dose of study drug during the first 8 weeks of treatment.

Outcome measures

Outcome measures
Measure	Healing Period: Lansoprazole 30 mg n=20 Participants Lansoprazole 30 mg, capsules, orally, once daily for up to 8 weeks in the Healing Period.	Healing Period: Dexlansoprazole 60 mg n=17 Participants Dexlansoprazole 60 mg, capsules, orally, once daily for up to 8 weeks in the Healing Period.
Healing Period: Percentage of Participants With Complete Healing of EE at Week 8	85.0 percentage of participants	82.4 percentage of participants

SECONDARY outcome

Timeframe: Month 6

Population: The full analysis set for the maintenance period (FAS-M) included all participants with healed EE by week 8 who were randomized and received at least 1 dose of study drug during 6 months of maintenance treatment.

Percentage of participants with complete healing of EE was assessed by endoscopy. EE was graded according to the LA classification of esophagitis grading system, based on the extent of visible mucosal breaks seen in the esophagus according to the following: Grade O (no mucosal breaks); Grade A (\>=1 mucosal break no longer than 5 mm that does not extend between the tops of 2 mucosal folds); Grade B (\>=1 mucosal break \>5 mm that does not extend between the tops of 2 mucosal folds); Grade C (\>=1 mucosal break that is continuous between the tops of 2 or more mucosal folds, but involves \<75% of the circumference); Grade D (\>=1 mucosal break which involves \>=75% of the circumference). Healing is defined as LA Grade O.

Outcome measures

Outcome measures
Measure	Healing Period: Lansoprazole 30 mg n=8 Participants Lansoprazole 30 mg, capsules, orally, once daily for up to 8 weeks in the Healing Period.	Healing Period: Dexlansoprazole 60 mg n=8 Participants Dexlansoprazole 60 mg, capsules, orally, once daily for up to 8 weeks in the Healing Period.
Maintenance Period: Percentage of Participants Who Maintained Complete Healing of EE at Month 6	0 percentage of participants	25 percentage of participants

Adverse Events

Healing Period: Lansoprazole 30 mg

Serious events: 0 serious events

Other events: 15 other events

Deaths: 0 deaths

Healing Period: Dexlansoprazole 60 mg

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Maintenance Period: Placebo

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Maintenance Period: Dexlansoprazole 30 mg

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Medical Director

Takeda

Phone: +1-877-825-3327

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.
Publication restrictions are in place

Restriction type: OTHER

Other adverse events
Measure	Healing Period: Lansoprazole 30 mg n=20 participants at risk Lansoprazole 30 mg, capsules, orally, once daily for up to 8 weeks in the Healing Period.	Healing Period: Dexlansoprazole 60 mg n=17 participants at risk Dexlansoprazole 60 mg, capsules, orally, once daily for up to 8 weeks in the Healing Period.	Maintenance Period: Placebo n=8 participants at risk Dexlansoprazole placebo-matching capsules, orally, once daily for up to 6 months in the Maintenance period. Participants who were healed at Week 8 entered the Maintenance Period.	Maintenance Period: Dexlansoprazole 30 mg n=8 participants at risk Dexlansoprazole 30 mg, delayed-release capsules, orally, once daily for up to 6 months in the Maintenance period. Participants who were healed at Week 8 entered the Maintenance Period.
Infections and infestations Upper respiratory tract infection	15.0% 3/20 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	11.8% 2/17 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/8 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	12.5% 1/8 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Viral upper respiratory tract infection	10.0% 2/20 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/17 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/8 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	12.5% 1/8 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Urinary tract infection	5.0% 1/20 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/17 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/8 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/8 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Diarrhoea	5.0% 1/20 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	11.8% 2/17 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/8 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/8 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Gastric polyps	5.0% 1/20 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/17 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/8 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/8 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Nausea	5.0% 1/20 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/17 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/8 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/8 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders Dizziness	15.0% 3/20 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/17 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/8 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/8 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders Headache	0.00% 0/20 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	5.9% 1/17 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/8 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/8 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Respiratory, thoracic and mediastinal disorders Laryngeal discomfort	5.0% 1/20 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/17 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/8 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/8 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	5.0% 1/20 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/17 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/8 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	12.5% 1/8 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/20 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	5.9% 1/17 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/8 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/8 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Investigations Alanine aminotransferase increased	5.0% 1/20 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/17 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/8 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/8 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Investigations Blood urea increased	5.0% 1/20 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/17 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/8 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/8 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Renal and urinary disorders Nephrolithiasis	5.0% 1/20 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/17 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/8 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/8 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Renal and urinary disorders Haematuria	5.0% 1/20 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/17 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/8 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/8 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Cardiac disorders Ventricular extrasystoles	5.0% 1/20 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/17 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/8 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/8 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Eye disorders Dry eye	5.0% 1/20 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/17 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/8 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/8 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
General disorders Pyrexia	0.00% 0/20 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	5.9% 1/17 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/8 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/8 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Injury, poisoning and procedural complications Skin injury	0.00% 0/20 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	5.9% 1/17 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/8 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/8 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Metabolism and nutrition disorders Hyperuricaemia	5.0% 1/20 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/17 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/8 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/8 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Musculoskeletal and connective tissue disorders Back pain	5.0% 1/20 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/17 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/8 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/8 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Investigations Protein urine present	0.00% 0/20 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/17 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/8 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	25.0% 2/8 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Gastritis erosive	0.00% 0/20 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/17 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	12.5% 1/8 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/8 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Injury, poisoning and procedural complications Limb injury	0.00% 0/20 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/17 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/8 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	12.5% 1/8 • Treatment-emergent adverse events are adverse events that started after the first dose of double-blind study drug and no more than 5 to 10 days (Day 190) after the last dose of double-blind study drug. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.