Trial Outcomes & Findings for Randomized, Placebo-controlled, Multi-dose, Study Comparing Budesonide/Formoterol to Symbicort® in Asthmatic Patients (NCT NCT03015259)

Last Updated: 2022-08-24

Results Overview

FEV1 Area calculated over 12 hours (measurements at 0, 1, 2, 3, 4, 6, 8, 12 hours post-dose) on Day 1 of treatment. Because this was a primary endpoint, Per Protocol Population used to calculate this endpoint.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1762 participants

Primary outcome timeframe

Day 1

Results posted on

2022-08-24

Participant Flow

Participants (N=1762) were provided a generic placebo pressurized metered dose inhaler (pMDI) device for use during a 2-week Run-in Period for device training. Then, qualified participants (N=1439) were randomly assigned to treatment on a 3:3:1 ratio of generic budesonide/formoterol fumarate dihydrate, Symbicort, or Placebo, respectively.

Participant milestones

Participant milestones
Measure	Treatment 1 Generic Budesonide/Formoterol Fumarate Dihydrate (80mcg/4.5mcg) Inhalation Aerosol, two inhalation twice daily, consisting of a 2-week run-in period followed by a 6-week treatment period Budesonide/Formoterol fumarate dihydrate: Experimental: Treatment 1	Treatment 2 Symbicort (Budesonide/Formoterol Fumarate Dihydrate) Inhalation Aerosol, two inhalation twice daily, consisting of a 2-week run-in period followed by a 6-week treatment period Symbicort: Active Comparator: Treatment 2	Treatment 3 Placebo Inhalation Aerosol, two inhalation twice daily, consisting of a 2-week run-in period followed by a 6-week treatment period Placebo: Placebo Comparator: Treatment 3
Overall Study STARTED	613	622	204
Overall Study COMPLETED	598	604	199
Overall Study NOT COMPLETED	15	18	5

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Randomized, Placebo-controlled, Multi-dose, Study Comparing Budesonide/Formoterol to Symbicort® in Asthmatic Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment 1 n=613 Participants Generic Budesonide/Formoterol Fumarate Dihydrate (80mcg/4.5mcg) Inhalation Aerosol, two inhalation twice daily, consisting of a 2-week run-in period followed by a 6-week treatment period Budesonide/Formoterol fumarate dihydrate: Experimental: Treatment 1	Treatment 2 n=622 Participants Symbicort (Budesonide/Formoterol Fumarate Dihydrate) Inhalation Aerosol, two inhalation twice daily, consisting of a 2-week run-in period followed by a 6-week treatment period Symbicort: Active Comparator: Treatment 2	Treatment 3 n=204 Participants Placebo Inhalation Aerosol, two inhalation twice daily, consisting of a 2-week run-in period followed by a 6-week treatment period Placebo: Placebo Comparator: Treatment 3	Total n=1439 Participants Total of all reporting groups
Age, Continuous	46.3 years STANDARD_DEVIATION 15.02 • n=99 Participants	45.5 years STANDARD_DEVIATION 14.44 • n=107 Participants	45.5 years STANDARD_DEVIATION 14.78 • n=206 Participants	45.8 years STANDARD_DEVIATION 14.73 • n=7 Participants
Sex: Female, Male Female	375 Participants n=99 Participants	392 Participants n=107 Participants	137 Participants n=206 Participants	904 Participants n=7 Participants
Sex: Female, Male Male	238 Participants n=99 Participants	230 Participants n=107 Participants	67 Participants n=206 Participants	535 Participants n=7 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	153 Participants n=99 Participants	151 Participants n=107 Participants	55 Participants n=206 Participants	359 Participants n=7 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	460 Participants n=99 Participants	471 Participants n=107 Participants	149 Participants n=206 Participants	1080 Participants n=7 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants
Race (NIH/OMB) American Indian or Alaska Native	2 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	2 Participants n=7 Participants
Race (NIH/OMB) Asian	5 Participants n=99 Participants	6 Participants n=107 Participants	4 Participants n=206 Participants	15 Participants n=7 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants
Race (NIH/OMB) Black or African American	107 Participants n=99 Participants	112 Participants n=107 Participants	43 Participants n=206 Participants	262 Participants n=7 Participants
Race (NIH/OMB) White	490 Participants n=99 Participants	495 Participants n=107 Participants	154 Participants n=206 Participants	1139 Participants n=7 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants
Race (NIH/OMB) Unknown or Not Reported	9 Participants n=99 Participants	9 Participants n=107 Participants	3 Participants n=206 Participants	21 Participants n=7 Participants
Body Mass Index	30.73 kg/m^2 STANDARD_DEVIATION 7.667 • n=99 Participants	31.27 kg/m^2 STANDARD_DEVIATION 8.108 • n=107 Participants	30.93 kg/m^2 STANDARD_DEVIATION 7.960 • n=206 Participants	30.99 kg/m^2 STANDARD_DEVIATION 7.900 • n=7 Participants

PRIMARY outcome

Timeframe: Day 1

Population: Per Protocol Population

Outcome measures

Outcome measures
Measure	Treatment 1 n=598 Participants Generic Budesonide/Formoterol Fumarate Dihydrate (80mcg/4.5mcg) Inhalation Aerosol, two inhalation twice daily, consisting of a 2-week run-in period followed by a 6-week treatment period Budesonide/Formoterol fumarate dihydrate: Experimental: Treatment 1	Treatment 2 n=604 Participants Symbicort (Budesonide/Formoterol Fumarate Dihydrate) Inhalation Aerosol, two inhalation twice daily, consisting of a 2-week run-in period followed by a 6-week treatment period Symbicort: Active Comparator: Treatment 2	Treatment 3 n=199 Participants Placebo Inhalation Aerosol, two inhalation twice daily, consisting of a 2-week run-in period followed by a 6-week treatment period Placebo: Placebo Comparator: Treatment 3
Area Under the Serial Forced Expiratory Volume in 1 Second (FEV1)	4.4453 l * hr Standard Error 0.1552	4.2790 l * hr Standard Error 0.1547	1.6876 l * hr Standard Error 0.2782

PRIMARY outcome

Timeframe: Day 1 - Day 49

Population: Per Protocol Population

Average predose FEV1 at End of Treatment defined as the average of all predose assessments on Day 42 (+/- 7 days). Baseline was defined as the average of 2 predose FEV1 values obtained on Day 1. The endpoint of baseline-adjusted predose FEV1 at end of treatment was calculated as follows: \[FEV1 at end of treatment\] - \[Baseline FEV1\].

Outcome measures

Outcome measures
Measure	Treatment 1 n=598 Participants Generic Budesonide/Formoterol Fumarate Dihydrate (80mcg/4.5mcg) Inhalation Aerosol, two inhalation twice daily, consisting of a 2-week run-in period followed by a 6-week treatment period Budesonide/Formoterol fumarate dihydrate: Experimental: Treatment 1	Treatment 2 n=604 Participants Symbicort (Budesonide/Formoterol Fumarate Dihydrate) Inhalation Aerosol, two inhalation twice daily, consisting of a 2-week run-in period followed by a 6-week treatment period Symbicort: Active Comparator: Treatment 2	Treatment 3 n=199 Participants Placebo Inhalation Aerosol, two inhalation twice daily, consisting of a 2-week run-in period followed by a 6-week treatment period Placebo: Placebo Comparator: Treatment 3
Change From Baseline in FEV1 Measured in the Morning at the End of Treatment Visit	0.3096 liter Standard Error 0.0162	0.3077 liter Standard Error 0.0162	0.1236 liter Standard Error 0.0285

SECONDARY outcome

Timeframe: 6 Weeks

Population: Safety Population: All enrolled participants who received one dose of a treatment drug. This population was larger than the Per Protocol Population that included only those participants who provided analyzable primary endpoints.

Number of participants reporting at least one adverse event (safety population)

Outcome measures

Outcome measures
Measure	Treatment 1 n=613 Participants Generic Budesonide/Formoterol Fumarate Dihydrate (80mcg/4.5mcg) Inhalation Aerosol, two inhalation twice daily, consisting of a 2-week run-in period followed by a 6-week treatment period Budesonide/Formoterol fumarate dihydrate: Experimental: Treatment 1	Treatment 2 n=622 Participants Symbicort (Budesonide/Formoterol Fumarate Dihydrate) Inhalation Aerosol, two inhalation twice daily, consisting of a 2-week run-in period followed by a 6-week treatment period Symbicort: Active Comparator: Treatment 2	Treatment 3 n=204 Participants Placebo Inhalation Aerosol, two inhalation twice daily, consisting of a 2-week run-in period followed by a 6-week treatment period Placebo: Placebo Comparator: Treatment 3
Number of Participants With Adverse Events Upper respiratory tract infection	12 Participants	15 Participants	7 Participants
Number of Participants With Adverse Events Nasopharyngitis	7 Participants	11 Participants	4 Participants
Number of Participants With Adverse Events Viral upper respiratory tract infection	6 Participants	4 Participants	1 Participants
Number of Participants With Adverse Events Bronchitis	3 Participants	4 Participants	2 Participants
Number of Participants With Adverse Events Asthma	17 Participants	24 Participants	39 Participants
Number of Participants With Adverse Events Cough	4 Participants	4 Participants	3 Participants
Number of Participants With Adverse Events Headache	4 Participants	8 Participants	2 Participants
Number of Participants With Adverse Events Chest discomfort	1 Participants	0 Participants	2 Participants

Adverse Events

Treatment 1

Serious events: 4 serious events

Other events: 121 other events

Deaths: 0 deaths

Treatment 2

Serious events: 3 serious events

Other events: 138 other events

Deaths: 0 deaths

Treatment 3

Serious events: 2 serious events

Other events: 71 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Treatment 1 n=613 participants at risk Generic Budesonide/Formoterol Fumarate Dihydrate (80mcg/4.5mcg) Inhalation Aerosol, two inhalation twice daily, consisting of a 2-week run-in period followed by a 6-week treatment period Budesonide/Formoterol fumarate dihydrate: Experimental: Treatment 1	Treatment 2 n=622 participants at risk Symbicort (Budesonide/Formoterol Fumarate Dihydrate) Inhalation Aerosol, two inhalation twice daily, consisting of a 2-week run-in period followed by a 6-week treatment period Symbicort: Active Comparator: Treatment 2	Treatment 3 n=204 participants at risk Placebo Inhalation Aerosol, two inhalation twice daily, consisting of a 2-week run-in period followed by a 6-week treatment period Placebo: Placebo Comparator: Treatment 3
Nervous system disorders cerebrospinal fluid leakage	0.16% 1/613 • Number of events 1 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).	0.00% 0/622 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).	0.00% 0/204 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).
Infections and infestations staphylococcal skin infection	0.16% 1/613 • Number of events 1 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).	0.00% 0/622 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).	0.00% 0/204 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).
Gastrointestinal disorders Alcoholic pancreatitis	0.16% 1/613 • Number of events 1 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).	0.00% 0/622 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).	0.00% 0/204 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).
Pregnancy, puerperium and perinatal conditions Abortion spontaneous	0.00% 0/613 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).	0.16% 1/622 • Number of events 1 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).	0.00% 0/204 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).
Musculoskeletal and connective tissue disorders Myositis	0.00% 0/613 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).	0.16% 1/622 • Number of events 1 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).	0.00% 0/204 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).
Injury, poisoning and procedural complications Head injurt	0.00% 0/613 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).	0.16% 1/622 • Number of events 1 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).	0.00% 0/204 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).
Gastrointestinal disorders Abdominal pain	0.00% 0/613 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).	0.00% 0/622 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).	0.49% 1/204 • Number of events 1 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).
Respiratory, thoracic and mediastinal disorders Asthma	0.00% 0/613 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).	0.00% 0/622 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).	0.49% 1/204 • Number of events 1 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.16% 1/613 • Number of events 1 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).	0.00% 0/622 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).	0.00% 0/204 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).

Other adverse events

Additional Information

Lester Harrison, PhD

KINDEVA DRUG DELIVERY

Phone: 6122714814

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Treatment 1 n=613 participants at risk Generic Budesonide/Formoterol Fumarate Dihydrate (80mcg/4.5mcg) Inhalation Aerosol, two inhalation twice daily, consisting of a 2-week run-in period followed by a 6-week treatment period Budesonide/Formoterol fumarate dihydrate: Experimental: Treatment 1	Treatment 2 n=622 participants at risk Symbicort (Budesonide/Formoterol Fumarate Dihydrate) Inhalation Aerosol, two inhalation twice daily, consisting of a 2-week run-in period followed by a 6-week treatment period Symbicort: Active Comparator: Treatment 2	Treatment 3 n=204 participants at risk Placebo Inhalation Aerosol, two inhalation twice daily, consisting of a 2-week run-in period followed by a 6-week treatment period Placebo: Placebo Comparator: Treatment 3
Infections and infestations upper respiratory tract infection	2.0% 12/613 • Number of events 12 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).	2.4% 15/622 • Number of events 15 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).	3.4% 7/204 • Number of events 7 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).
Infections and infestations nasopharyngitis	1.1% 7/613 • Number of events 7 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).	1.8% 11/622 • Number of events 11 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).	2.0% 4/204 • Number of events 4 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).
Infections and infestations viral upper respiratory tract infection	0.98% 6/613 • Number of events 7 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).	0.64% 4/622 • Number of events 4 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).	0.49% 1/204 • Number of events 1 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).
Infections and infestations bronchitis	0.49% 3/613 • Number of events 3 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).	0.64% 4/622 • Number of events 4 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).	0.98% 2/204 • Number of events 2 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).
Respiratory, thoracic and mediastinal disorders asthma	2.8% 17/613 • Number of events 18 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).	3.9% 24/622 • Number of events 28 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).	19.1% 39/204 • Number of events 48 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).
Respiratory, thoracic and mediastinal disorders cough	0.65% 4/613 • Number of events 4 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).	0.64% 4/622 • Number of events 4 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).	1.5% 3/204 • Number of events 3 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).
Gastrointestinal disorders gastrointestinal disorders	1.8% 11/613 • Number of events 13 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).	1.9% 12/622 • Number of events 12 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).	0.98% 2/204 • Number of events 4 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).
Injury, poisoning and procedural complications injury, poisoning and procedural complications	1.3% 8/613 • Number of events 8 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).	1.8% 11/622 • Number of events 17 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).	0.98% 2/204 • Number of events 2 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).
Nervous system disorders nervous system disorders	1.5% 9/613 • Number of events 12 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).	1.6% 10/622 • Number of events 10 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).	0.98% 2/204 • Number of events 3 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).
Nervous system disorders headache	0.65% 4/613 • Number of events 7 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).	1.3% 8/622 • Number of events 8 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).	0.98% 2/204 • Number of events 3 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).
Infections and infestations infections and infestations	8.8% 54/613 • Number of events 58 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).	9.3% 58/622 • Number of events 61 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).	9.8% 20/204 • Number of events 21 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).
Respiratory, thoracic and mediastinal disorders respiratory, thoracic and mediastinal disorders	5.7% 35/613 • Number of events 40 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).	7.7% 48/622 • Number of events 56 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).	23.5% 48/204 • Number of events 64 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).
Musculoskeletal and connective tissue disorders musculoskeletal and connective tissue disorders	1.3% 8/613 • Number of events 11 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).	1.6% 10/622 • Number of events 15 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).	0.98% 2/204 • Number of events 2 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).
Investigations investigations	0.33% 2/613 • Number of events 2 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).	1.1% 7/622 • Number of events 7 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).	1.5% 3/204 • Number of events 3 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).
General disorders general disorders and administration site conditions	0.82% 5/613 • Number of events 5 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).	0.64% 4/622 • Number of events 4 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).	0.98% 2/204 • Number of events 3 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).
General disorders chest discomfort	0.16% 1/613 • Number of events 1 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).	0.00% 0/622 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).	0.98% 2/204 • Number of events 3 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).
Investigations metabolism and nutrition disorders	0.65% 4/613 • Number of events 4 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).	0.96% 6/622 • Number of events 6 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).	0.49% 1/204 • Number of events 1 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).
Skin and subcutaneous tissue disorders skin and subcutaneous tissue disorders	0.82% 5/613 • Number of events 5 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).	0.48% 3/622 • Number of events 3 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).	0.98% 2/204 • Number of events 2 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).
Cardiac disorders cardia disorders	0.16% 1/613 • Number of events 1 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).	0.16% 1/622 • Number of events 1 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).	0.49% 1/204 • Number of events 1 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).
Immune system disorders immune system disorders	0.33% 2/613 • Number of events 2 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).	0.00% 0/622 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).	0.49% 1/204 • Number of events 1 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).
Psychiatric disorders psychiatric disorders	0.16% 1/613 • Number of events 1 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).	0.16% 1/622 • Number of events 1 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).	0.49% 1/204 • Number of events 1 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).
Vascular disorders vascular disorders	0.16% 1/613 • Number of events 1 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).	0.16% 1/622 • Number of events 1 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).	0.49% 1/204 • Number of events 1 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).
Ear and labyrinth disorders ear and labyrinth disorders	0.33% 2/613 • Number of events 2 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).	0.00% 0/622 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).	0.00% 0/204 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).
Eye disorders eye disorders	0.16% 1/613 • Number of events 1 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).	0.16% 1/622 • Number of events 1 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).	0.00% 0/204 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).
Pregnancy, puerperium and perinatal conditions pregnancy, puerperium, and perinatal conditions	0.00% 0/613 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).	0.16% 1/622 • Number of events 1 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).	0.00% 0/204 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).
Renal and urinary disorders renal and urinary disorders	0.00% 0/613 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).	0.16% 1/622 • Number of events 1 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).	0.00% 0/204 • Day 1 - Day 70 Subjects who received at least 1 dose during the Treatment Period (Safety Population).