Trial Outcomes & Findings for Clinical Efficacy Study of Salmeterol Xinafoate/Fluticasone Propionate in Asthma (NCT NCT02260492)

Last Updated: 2017-06-15

Results Overview

Bioequivalence comparison of lung function (FEV1) for 12 hours after the first dose on Day 1 following OT329 Solis and Advair Diskus treatment. Serial lung function measurements were made pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hours postdose.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

879 participants

Primary outcome timeframe

0-12 hours after dosing on Day 1

Results posted on

2017-06-15

Participant Flow

1526 Patients with asthma were screened at 48 clinical sites

647 Failed screening (42%) * 239 failed because they did not have 40-85% pred FEV1 * 240 failed because they were not \>15% reversible with albuterol * 168 failed for other inclusion/exclusion criteria

Participant milestones

Participant milestones
Measure	OT329 Solis OT329 Solis (twice daily inhalation throughout the study) OT329 (combination of fluticasone propionate and salmeterol xinafoate): Fluticasone propionate (100 mcg) and salmeterol xinafoate (50 mcg) administered by Solis dry powder inhaler	Advair Diskus Advair Diskus (twice daily inhalation throughout the study) Advair Diskus (combination of fluticasone propionate and salmeterol xinafoate): Fluticasone propionate (100 mcg) and salmeterol xinafoate (50 mcg) administered by Diskus dry powder inhaler	Placebo Placebo (twice daily inhalation throughout the study) Placebo: Placebo (lactose) administered via the Solis dry powder inhaler
Overall Study STARTED	418	419	42
Overall Study Completed Day 1	418	419	42
Overall Study COMPLETED	395	406	37
Overall Study NOT COMPLETED	23	13	5

Reasons for withdrawal

Reasons for withdrawal
Measure	OT329 Solis OT329 Solis (twice daily inhalation throughout the study) OT329 (combination of fluticasone propionate and salmeterol xinafoate): Fluticasone propionate (100 mcg) and salmeterol xinafoate (50 mcg) administered by Solis dry powder inhaler	Advair Diskus Advair Diskus (twice daily inhalation throughout the study) Advair Diskus (combination of fluticasone propionate and salmeterol xinafoate): Fluticasone propionate (100 mcg) and salmeterol xinafoate (50 mcg) administered by Diskus dry powder inhaler	Placebo Placebo (twice daily inhalation throughout the study) Placebo: Placebo (lactose) administered via the Solis dry powder inhaler
Overall Study Adverse Event	6	1	2
Overall Study Death	0	1	0
Overall Study Lost to Follow-up	12	9	0
Overall Study Physician Decision	2	0	1
Overall Study Withdrawal by Subject	3	2	2

Baseline Characteristics

Clinical Efficacy Study of Salmeterol Xinafoate/Fluticasone Propionate in Asthma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	OT329 Solis n=418 Participants OT329 Solis (twice daily inhalation throughout the study) OT329 (combination of fluticasone propionate and salmeterol xinafoate): Fluticasone propionate (100 mcg) and salmeterol xinafoate (50 mcg) administered by Solis dry powder inhaler	Advair Diskus n=419 Participants Advair Diskus (twice daily inhalation throughout the study) Advair Diskus (combination of fluticasone propionate and salmeterol xinafoate): Fluticasone propionate (100 mcg) and salmeterol xinafoate (50 mcg) administered by Diskus dry powder inhaler	Placebo n=42 Participants Placebo (twice daily inhalation throughout the study) Placebo: Placebo (lactose) administered via the Solis dry powder inhaler	Total n=879 Participants Total of all reporting groups
Age, Continuous	43.9 years STANDARD_DEVIATION 14.52 • n=39 Participants	43.3 years STANDARD_DEVIATION 14.26 • n=41 Participants	43.2 years STANDARD_DEVIATION 15.25 • n=35 Participants	43.6 years STANDARD_DEVIATION 14.42 • n=31 Participants
Sex: Female, Male Female	274 Participants n=39 Participants	251 Participants n=41 Participants	30 Participants n=35 Participants	555 Participants n=31 Participants
Sex: Female, Male Male	144 Participants n=39 Participants	168 Participants n=41 Participants	12 Participants n=35 Participants	324 Participants n=31 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	122 Participants n=39 Participants	118 Participants n=41 Participants	9 Participants n=35 Participants	249 Participants n=31 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	296 Participants n=39 Participants	301 Participants n=41 Participants	33 Participants n=35 Participants	630 Participants n=31 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=39 Participants	0 Participants n=41 Participants	0 Participants n=35 Participants	0 Participants n=31 Participants
Race (NIH/OMB) American Indian or Alaska Native	2 Participants n=39 Participants	2 Participants n=41 Participants	0 Participants n=35 Participants	4 Participants n=31 Participants
Race (NIH/OMB) Asian	3 Participants n=39 Participants	4 Participants n=41 Participants	1 Participants n=35 Participants	8 Participants n=31 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=39 Participants	3 Participants n=41 Participants	0 Participants n=35 Participants	3 Participants n=31 Participants
Race (NIH/OMB) Black or African American	74 Participants n=39 Participants	89 Participants n=41 Participants	10 Participants n=35 Participants	173 Participants n=31 Participants
Race (NIH/OMB) White	332 Participants n=39 Participants	308 Participants n=41 Participants	29 Participants n=35 Participants	669 Participants n=31 Participants
Race (NIH/OMB) More than one race	7 Participants n=39 Participants	13 Participants n=41 Participants	2 Participants n=35 Participants	22 Participants n=31 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=39 Participants	0 Participants n=41 Participants	0 Participants n=35 Participants	0 Participants n=31 Participants
Region of Enrollment United States	418 participants n=39 Participants	419 participants n=41 Participants	42 participants n=35 Participants	879 participants n=31 Participants
Weight (kg)	88.5 Kg STANDARD_DEVIATION 22.9 • n=39 Participants	85.9 Kg STANDARD_DEVIATION 23.1 • n=41 Participants	81.0 Kg STANDARD_DEVIATION 17.2 • n=35 Participants	86.9 Kg STANDARD_DEVIATION 22.8 • n=31 Participants
Height (cm)	167.5 cm STANDARD_DEVIATION 9.9 • n=39 Participants	169.2 cm STANDARD_DEVIATION 10.7 • n=41 Participants	166.3 cm STANDARD_DEVIATION 8.3 • n=35 Participants	168.2 cm STANDARD_DEVIATION 10.2 • n=31 Participants
Body Mass Index	31.49 Kg/m^2 STANDARD_DEVIATION 7.61 • n=39 Participants	29.91 Kg/m^2 STANDARD_DEVIATION 7.20 • n=41 Participants	29.32 Kg/m^2 STANDARD_DEVIATION 6.30 • n=35 Participants	30.63 Kg/m^2 STANDARD_DEVIATION 7.40 • n=31 Participants
Airways Reversibility with Albuterol	30.5 % change from pre-albuterol lung functio STANDARD_DEVIATION 19.3 • n=39 Participants	29.7 % change from pre-albuterol lung functio STANDARD_DEVIATION 17.5 • n=41 Participants	25.9 % change from pre-albuterol lung functio STANDARD_DEVIATION 13.3 • n=35 Participants	29.9 % change from pre-albuterol lung functio STANDARD_DEVIATION 18.3 • n=31 Participants

PRIMARY outcome

Timeframe: 0-12 hours after dosing on Day 1

Population: Intent-to-treat (ITT)

Outcome measures

Outcome measures
Measure	OT329 Solis n=418 Participants OT329 Solis (twice daily inhalation throughout the study) OT329 (combination of fluticasone propionate and salmeterol xinafoate): Fluticasone propionate (100 mcg) and salmeterol xinafoate (50 mcg) administered by Solis dry powder inhaler	Advair Diskus n=419 Participants Advair Diskus (twice daily inhalation throughout the study) Advair Diskus (combination of fluticasone propionate and salmeterol xinafoate): Fluticasone propionate (100 mcg) and salmeterol xinafoate (50 mcg) administered by Diskus dry powder inhaler	Placebo n=42 Participants Placebo (twice daily inhalation throughout the study) Placebo: Placebo (lactose) administered via the Solis dry powder inhaler
Area Under the Serial FEV1-time Curve (AUC 0-12h)	29.610 Liters Standard Deviation 9.044	30.151 Liters Standard Deviation 9.107	27.270 Liters Standard Deviation 7.710

PRIMARY outcome

Timeframe: Post-4 weeks of treatment

Population: Intent-to-Treat

Bioequivalence comparison of trough lung function (FEV1) after 4 weeks of treatment with OT329 SOLIS or ADVAIR DISKUS.

Outcome measures

Outcome measures
Measure	OT329 Solis n=395 Participants OT329 Solis (twice daily inhalation throughout the study) OT329 (combination of fluticasone propionate and salmeterol xinafoate): Fluticasone propionate (100 mcg) and salmeterol xinafoate (50 mcg) administered by Solis dry powder inhaler	Advair Diskus n=406 Participants Advair Diskus (twice daily inhalation throughout the study) Advair Diskus (combination of fluticasone propionate and salmeterol xinafoate): Fluticasone propionate (100 mcg) and salmeterol xinafoate (50 mcg) administered by Diskus dry powder inhaler	Placebo n=37 Participants Placebo (twice daily inhalation throughout the study) Placebo: Placebo (lactose) administered via the Solis dry powder inhaler
FEV1 Trough	2.516 Liters Standard Deviation 0.792	2.579 Liters Standard Deviation 0.774	2.323 Liters Standard Deviation 0.736

SECONDARY outcome

Timeframe: From Screen (Day -28) until 1 week post last treatment

Population: One subject who was assigned OT329 SOLIS received placebo treatment kit in error. The mistake was discovered on Day 1 and the patient was removed from the study. The patient was included in the OT329 SOLIS group for the intent-to-treat analysis but was put in the Placebo group for the Safety analysis as defined by the Statisical Analysis Plan.

Outcome measures

Outcome measures
Measure	OT329 Solis n=417 Participants OT329 Solis (twice daily inhalation throughout the study) OT329 (combination of fluticasone propionate and salmeterol xinafoate): Fluticasone propionate (100 mcg) and salmeterol xinafoate (50 mcg) administered by Solis dry powder inhaler	Advair Diskus n=418 Participants Advair Diskus (twice daily inhalation throughout the study) Advair Diskus (combination of fluticasone propionate and salmeterol xinafoate): Fluticasone propionate (100 mcg) and salmeterol xinafoate (50 mcg) administered by Diskus dry powder inhaler	Placebo n=43 Participants Placebo (twice daily inhalation throughout the study) Placebo: Placebo (lactose) administered via the Solis dry powder inhaler
Number of Participants With Adverse Events	67 Participants	66 Participants	7 Participants

Adverse Events

OT329 Solis

Serious events: 0 serious events

Other events: 52 other events

Deaths: 0 deaths

Advair Diskus

Serious events: 2 serious events

Other events: 47 other events

Deaths: 1 deaths

Placebo

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	OT329 Solis n=417 participants at risk OT329 Solis (twice daily inhalation throughout the study) OT329 (combination of fluticasone propionate and salmeterol xinafoate): Fluticasone propionate (100 mcg) and salmeterol xinafoate (50 mcg) administered by Solis dry powder inhaler	Advair Diskus n=419 participants at risk Advair Diskus (twice daily inhalation throughout the study) Advair Diskus (combination of fluticasone propionate and salmeterol xinafoate): Fluticasone propionate (100 mcg) and salmeterol xinafoate (50 mcg) administered by Diskus dry powder inhaler	Placebo n=43 participants at risk Placebo (twice daily inhalation throughout the study) Placebo: Placebo (lactose) administered via the Solis dry powder inhaler
Cardiac disorders Myocardial Infarction	0.00% 0/417 • Adverse events were collected from time of consent until 1 week post last treatment, up to 5 weeks. Adverse events from screen failed subjects are omitted. Treatment emergent adverse events are reported from Day 1 of treatment.	0.24% 1/419 • Number of events 1 • Adverse events were collected from time of consent until 1 week post last treatment, up to 5 weeks. Adverse events from screen failed subjects are omitted. Treatment emergent adverse events are reported from Day 1 of treatment.	0.00% 0/43 • Adverse events were collected from time of consent until 1 week post last treatment, up to 5 weeks. Adverse events from screen failed subjects are omitted. Treatment emergent adverse events are reported from Day 1 of treatment.
Infections and infestations H. pylori infection	0.00% 0/417 • Adverse events were collected from time of consent until 1 week post last treatment, up to 5 weeks. Adverse events from screen failed subjects are omitted. Treatment emergent adverse events are reported from Day 1 of treatment.	0.24% 1/419 • Number of events 1 • Adverse events were collected from time of consent until 1 week post last treatment, up to 5 weeks. Adverse events from screen failed subjects are omitted. Treatment emergent adverse events are reported from Day 1 of treatment.	0.00% 0/43 • Adverse events were collected from time of consent until 1 week post last treatment, up to 5 weeks. Adverse events from screen failed subjects are omitted. Treatment emergent adverse events are reported from Day 1 of treatment.

Other adverse events

Additional Information

Malinda Longphre PhD, Director Clinical Reserach

Oriel Therapeutics, a Novartis Company

Phone: 9193131290

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	OT329 Solis n=417 participants at risk OT329 Solis (twice daily inhalation throughout the study) OT329 (combination of fluticasone propionate and salmeterol xinafoate): Fluticasone propionate (100 mcg) and salmeterol xinafoate (50 mcg) administered by Solis dry powder inhaler	Advair Diskus n=419 participants at risk Advair Diskus (twice daily inhalation throughout the study) Advair Diskus (combination of fluticasone propionate and salmeterol xinafoate): Fluticasone propionate (100 mcg) and salmeterol xinafoate (50 mcg) administered by Diskus dry powder inhaler	Placebo n=43 participants at risk Placebo (twice daily inhalation throughout the study) Placebo: Placebo (lactose) administered via the Solis dry powder inhaler
Ear and labyrinth disorders Vertigo	0.00% 0/417 • Adverse events were collected from time of consent until 1 week post last treatment, up to 5 weeks. Adverse events from screen failed subjects are omitted. Treatment emergent adverse events are reported from Day 1 of treatment.	0.00% 0/419 • Adverse events were collected from time of consent until 1 week post last treatment, up to 5 weeks. Adverse events from screen failed subjects are omitted. Treatment emergent adverse events are reported from Day 1 of treatment.	2.3% 1/43 • Number of events 1 • Adverse events were collected from time of consent until 1 week post last treatment, up to 5 weeks. Adverse events from screen failed subjects are omitted. Treatment emergent adverse events are reported from Day 1 of treatment.
Gastrointestinal disorders Nausea	0.72% 3/417 • Number of events 3 • Adverse events were collected from time of consent until 1 week post last treatment, up to 5 weeks. Adverse events from screen failed subjects are omitted. Treatment emergent adverse events are reported from Day 1 of treatment.	0.00% 0/419 • Adverse events were collected from time of consent until 1 week post last treatment, up to 5 weeks. Adverse events from screen failed subjects are omitted. Treatment emergent adverse events are reported from Day 1 of treatment.	2.3% 1/43 • Number of events 1 • Adverse events were collected from time of consent until 1 week post last treatment, up to 5 weeks. Adverse events from screen failed subjects are omitted. Treatment emergent adverse events are reported from Day 1 of treatment.
Gastrointestinal disorders Vomiting	0.00% 0/417 • Adverse events were collected from time of consent until 1 week post last treatment, up to 5 weeks. Adverse events from screen failed subjects are omitted. Treatment emergent adverse events are reported from Day 1 of treatment.	0.48% 2/419 • Number of events 2 • Adverse events were collected from time of consent until 1 week post last treatment, up to 5 weeks. Adverse events from screen failed subjects are omitted. Treatment emergent adverse events are reported from Day 1 of treatment.	2.3% 1/43 • Number of events 1 • Adverse events were collected from time of consent until 1 week post last treatment, up to 5 weeks. Adverse events from screen failed subjects are omitted. Treatment emergent adverse events are reported from Day 1 of treatment.
Gastrointestinal disorders Toothache	0.00% 0/417 • Adverse events were collected from time of consent until 1 week post last treatment, up to 5 weeks. Adverse events from screen failed subjects are omitted. Treatment emergent adverse events are reported from Day 1 of treatment.	0.00% 0/419 • Adverse events were collected from time of consent until 1 week post last treatment, up to 5 weeks. Adverse events from screen failed subjects are omitted. Treatment emergent adverse events are reported from Day 1 of treatment.	2.3% 1/43 • Number of events 1 • Adverse events were collected from time of consent until 1 week post last treatment, up to 5 weeks. Adverse events from screen failed subjects are omitted. Treatment emergent adverse events are reported from Day 1 of treatment.
Infections and infestations Bronchitis	0.00% 0/417 • Adverse events were collected from time of consent until 1 week post last treatment, up to 5 weeks. Adverse events from screen failed subjects are omitted. Treatment emergent adverse events are reported from Day 1 of treatment.	0.24% 1/419 • Number of events 1 • Adverse events were collected from time of consent until 1 week post last treatment, up to 5 weeks. Adverse events from screen failed subjects are omitted. Treatment emergent adverse events are reported from Day 1 of treatment.	2.3% 1/43 • Number of events 1 • Adverse events were collected from time of consent until 1 week post last treatment, up to 5 weeks. Adverse events from screen failed subjects are omitted. Treatment emergent adverse events are reported from Day 1 of treatment.
Infections and infestations Nasopharyngitis	1.9% 8/417 • Number of events 8 • Adverse events were collected from time of consent until 1 week post last treatment, up to 5 weeks. Adverse events from screen failed subjects are omitted. Treatment emergent adverse events are reported from Day 1 of treatment.	1.4% 6/419 • Number of events 6 • Adverse events were collected from time of consent until 1 week post last treatment, up to 5 weeks. Adverse events from screen failed subjects are omitted. Treatment emergent adverse events are reported from Day 1 of treatment.	2.3% 1/43 • Number of events 1 • Adverse events were collected from time of consent until 1 week post last treatment, up to 5 weeks. Adverse events from screen failed subjects are omitted. Treatment emergent adverse events are reported from Day 1 of treatment.
Infections and infestations Sinusitis	0.96% 4/417 • Number of events 4 • Adverse events were collected from time of consent until 1 week post last treatment, up to 5 weeks. Adverse events from screen failed subjects are omitted. Treatment emergent adverse events are reported from Day 1 of treatment.	0.95% 4/419 • Number of events 4 • Adverse events were collected from time of consent until 1 week post last treatment, up to 5 weeks. Adverse events from screen failed subjects are omitted. Treatment emergent adverse events are reported from Day 1 of treatment.	0.00% 0/43 • Adverse events were collected from time of consent until 1 week post last treatment, up to 5 weeks. Adverse events from screen failed subjects are omitted. Treatment emergent adverse events are reported from Day 1 of treatment.
Infections and infestations Upper respiratory tract infection	1.7% 7/417 • Number of events 7 • Adverse events were collected from time of consent until 1 week post last treatment, up to 5 weeks. Adverse events from screen failed subjects are omitted. Treatment emergent adverse events are reported from Day 1 of treatment.	1.2% 5/419 • Number of events 5 • Adverse events were collected from time of consent until 1 week post last treatment, up to 5 weeks. Adverse events from screen failed subjects are omitted. Treatment emergent adverse events are reported from Day 1 of treatment.	0.00% 0/43 • Adverse events were collected from time of consent until 1 week post last treatment, up to 5 weeks. Adverse events from screen failed subjects are omitted. Treatment emergent adverse events are reported from Day 1 of treatment.
Infections and infestations Urinary tract infection	0.48% 2/417 • Number of events 2 • Adverse events were collected from time of consent until 1 week post last treatment, up to 5 weeks. Adverse events from screen failed subjects are omitted. Treatment emergent adverse events are reported from Day 1 of treatment.	0.24% 1/419 • Number of events 1 • Adverse events were collected from time of consent until 1 week post last treatment, up to 5 weeks. Adverse events from screen failed subjects are omitted. Treatment emergent adverse events are reported from Day 1 of treatment.	2.3% 1/43 • Number of events 1 • Adverse events were collected from time of consent until 1 week post last treatment, up to 5 weeks. Adverse events from screen failed subjects are omitted. Treatment emergent adverse events are reported from Day 1 of treatment.
Nervous system disorders Dizziness	0.96% 4/417 • Number of events 4 • Adverse events were collected from time of consent until 1 week post last treatment, up to 5 weeks. Adverse events from screen failed subjects are omitted. Treatment emergent adverse events are reported from Day 1 of treatment.	0.48% 2/419 • Number of events 2 • Adverse events were collected from time of consent until 1 week post last treatment, up to 5 weeks. Adverse events from screen failed subjects are omitted. Treatment emergent adverse events are reported from Day 1 of treatment.	0.00% 0/43 • Adverse events were collected from time of consent until 1 week post last treatment, up to 5 weeks. Adverse events from screen failed subjects are omitted. Treatment emergent adverse events are reported from Day 1 of treatment.
Nervous system disorders Headache	1.9% 8/417 • Number of events 8 • Adverse events were collected from time of consent until 1 week post last treatment, up to 5 weeks. Adverse events from screen failed subjects are omitted. Treatment emergent adverse events are reported from Day 1 of treatment.	3.1% 13/419 • Number of events 13 • Adverse events were collected from time of consent until 1 week post last treatment, up to 5 weeks. Adverse events from screen failed subjects are omitted. Treatment emergent adverse events are reported from Day 1 of treatment.	0.00% 0/43 • Adverse events were collected from time of consent until 1 week post last treatment, up to 5 weeks. Adverse events from screen failed subjects are omitted. Treatment emergent adverse events are reported from Day 1 of treatment.
Respiratory, thoracic and mediastinal disorders Cough	0.96% 4/417 • Number of events 4 • Adverse events were collected from time of consent until 1 week post last treatment, up to 5 weeks. Adverse events from screen failed subjects are omitted. Treatment emergent adverse events are reported from Day 1 of treatment.	0.72% 3/419 • Number of events 3 • Adverse events were collected from time of consent until 1 week post last treatment, up to 5 weeks. Adverse events from screen failed subjects are omitted. Treatment emergent adverse events are reported from Day 1 of treatment.	0.00% 0/43 • Adverse events were collected from time of consent until 1 week post last treatment, up to 5 weeks. Adverse events from screen failed subjects are omitted. Treatment emergent adverse events are reported from Day 1 of treatment.
Respiratory, thoracic and mediastinal disorders Dysphonia	0.96% 4/417 • Number of events 4 • Adverse events were collected from time of consent until 1 week post last treatment, up to 5 weeks. Adverse events from screen failed subjects are omitted. Treatment emergent adverse events are reported from Day 1 of treatment.	0.95% 4/419 • Number of events 4 • Adverse events were collected from time of consent until 1 week post last treatment, up to 5 weeks. Adverse events from screen failed subjects are omitted. Treatment emergent adverse events are reported from Day 1 of treatment.	0.00% 0/43 • Adverse events were collected from time of consent until 1 week post last treatment, up to 5 weeks. Adverse events from screen failed subjects are omitted. Treatment emergent adverse events are reported from Day 1 of treatment.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	1.7% 7/417 • Number of events 7 • Adverse events were collected from time of consent until 1 week post last treatment, up to 5 weeks. Adverse events from screen failed subjects are omitted. Treatment emergent adverse events are reported from Day 1 of treatment.	1.4% 6/419 • Number of events 6 • Adverse events were collected from time of consent until 1 week post last treatment, up to 5 weeks. Adverse events from screen failed subjects are omitted. Treatment emergent adverse events are reported from Day 1 of treatment.	0.00% 0/43 • Adverse events were collected from time of consent until 1 week post last treatment, up to 5 weeks. Adverse events from screen failed subjects are omitted. Treatment emergent adverse events are reported from Day 1 of treatment.
Respiratory, thoracic and mediastinal disorders Wheezing	0.24% 1/417 • Number of events 1 • Adverse events were collected from time of consent until 1 week post last treatment, up to 5 weeks. Adverse events from screen failed subjects are omitted. Treatment emergent adverse events are reported from Day 1 of treatment.	0.00% 0/419 • Adverse events were collected from time of consent until 1 week post last treatment, up to 5 weeks. Adverse events from screen failed subjects are omitted. Treatment emergent adverse events are reported from Day 1 of treatment.	2.3% 1/43 • Number of events 1 • Adverse events were collected from time of consent until 1 week post last treatment, up to 5 weeks. Adverse events from screen failed subjects are omitted. Treatment emergent adverse events are reported from Day 1 of treatment.