Trial Outcomes & Findings for Phase 3 Study to Evaluate Efficacy of Amifampridine Phosphate in Lambert-Eaton Myasthenic Syndrome (LEMS) (NCT NCT02970162)

Last Updated: 2018-12-24

Results Overview

The QMG is a physician-rated test including 13 assessments such as facial strength, swallowing, grip strength, and duration of time that limbs can be maintained in outstretched positions. Each assessment is graded as 0 (none), 1 (mild), 2 (moderate), or 3 (severe), for a total range of 0-39. A higher total score indicates a worse outcome.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

26 participants

Primary outcome timeframe

change from baseline in QMG score at end of day 4

Results posted on

2018-12-24

Participant Flow

Participant milestones

Participant milestones
Measure	Amifampridine Phosphate amifampridine phosphate 10 mg (amifampridine equivalent) by mouth, 30 to 80 mg total daily dose, 3 to 4 times per day for 4 days Amifampridine Phosphate	Placebo (for Amifampridine Phosphate) placebo by mouth 3 to 4 times per day for 4 days Placebo Oral Tablet
Overall Study STARTED	13	13
Overall Study COMPLETED	13	13
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Phase 3 Study to Evaluate Efficacy of Amifampridine Phosphate in Lambert-Eaton Myasthenic Syndrome (LEMS)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Amifampridine Phosphate n=13 Participants amifampridine phosphate 10 mg (amifampridine equivalent) by mouth, 30 to 80 mg total daily dose, 3 to 4 times per day for 4 days Amifampridine Phosphate	Placebo (for Amifampridine Phosphate) n=13 Participants placebo by mouth 3 to 4 times per day for 4 days Placebo Oral Tablet	Total n=26 Participants Total of all reporting groups
Age, Continuous	54.9 years STANDARD_DEVIATION 11.51 • n=5 Participants	53.4 years STANDARD_DEVIATION 13.46 • n=7 Participants	54.2 years STANDARD_DEVIATION 12.30 • n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	9 Participants n=7 Participants	16 Participants n=5 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	4 Participants n=7 Participants	10 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=5 Participants	1 Participants n=7 Participants	5 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	9 Participants n=5 Participants	12 Participants n=7 Participants	21 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Weight	77.62 kg STANDARD_DEVIATION 20.312 • n=5 Participants	93.95 kg STANDARD_DEVIATION 15.449 • n=7 Participants	85.78 kg STANDARD_DEVIATION 19.545 • n=5 Participants

PRIMARY outcome

Timeframe: change from baseline in QMG score at end of day 4

Outcome measures

Outcome measures
Measure	Amifampridine Phosphate n=13 Participants amifampridine phosphate 10 mg (amifampridine equivalent) by mouth, 30 to 80 mg total daily dose, 3 to 4 times per day for 4 days Amifampridine Phosphate	Placebo (for Amifampridine Phosphate) n=13 Participants placebo by mouth 3 to 4 times per day for 4 days Placebo Oral Tablet
Quantitative Myasthenia Gravis (QMG) Score Baseline	7.8 scores on a scale Standard Deviation 4.20	8.5 scores on a scale Standard Deviation 5.43
Quantitative Myasthenia Gravis (QMG) Score Day 4	7.9 scores on a scale Standard Deviation 4.94	15.0 scores on a scale Standard Deviation 5.90
Quantitative Myasthenia Gravis (QMG) Score Change from baseline	0.1 scores on a scale Standard Deviation 3.07	6.5 scores on a scale Standard Deviation 4.82

PRIMARY outcome

Timeframe: change from baseline in SGI score at end of day 4

The SGI is a 7-point scale on which the patient rates their global impression of the effects of a study treatment (1=terrible to 7=delighted). The SGI was assessed by the patient or the patient's parent/guardian/caregiver if the patient was unable to complete the SGI. The SGI has demonstrated concordance with the physician's assessment of improvement.

Outcome measures

Outcome measures
Measure	Amifampridine Phosphate n=13 Participants amifampridine phosphate 10 mg (amifampridine equivalent) by mouth, 30 to 80 mg total daily dose, 3 to 4 times per day for 4 days Amifampridine Phosphate	Placebo (for Amifampridine Phosphate) n=13 Participants placebo by mouth 3 to 4 times per day for 4 days Placebo Oral Tablet
Subject Global Impression (SGI) Score Baseline	6.1 scores on a scale Standard Deviation 0.86	5.8 scores on a scale Standard Deviation 0.90
Subject Global Impression (SGI) Score Day 4	5.3 scores on a scale Standard Deviation 1.65	2.4 scores on a scale Standard Deviation 1.76
Subject Global Impression (SGI) Score Change from baseline to Day 4	-0.8 scores on a scale Standard Deviation 1.74	-3.5 scores on a scale Standard Deviation 2.18

SECONDARY outcome

Timeframe: change from baseline in CGI-I score at end of day 4

The CGI-I captures the Investigator's global impression of the patient's improvement or worsening from baseline status. The 7-point scale is scored by the Investigator based on changes in symptoms, behavior, and functional abilities. Each symptom is rated as 1 (very much improved), 2 (much improved), 3 (minimally improved), 4 (no change), 5 (minimally worse), 6 (much worse), or 7 (very much worse). The total score can range from 0 to 49. A higher score indicates a worse outcome.

Outcome measures

Outcome measures
Measure	Amifampridine Phosphate n=13 Participants amifampridine phosphate 10 mg (amifampridine equivalent) by mouth, 30 to 80 mg total daily dose, 3 to 4 times per day for 4 days Amifampridine Phosphate	Placebo (for Amifampridine Phosphate) n=13 Participants placebo by mouth 3 to 4 times per day for 4 days Placebo Oral Tablet
Change in Clinician's Global Impression of Improvement (CGI-I) at Day 4 Compared to Baseline	3.8 scores on a scale Standard Deviation 0.8	5.5 scores on a scale Standard Deviation 1.27

OTHER_PRE_SPECIFIED outcome

Timeframe: change from baseline in 3TUG at end of day 4

Population: The number and proportion of patients with a ≥20% increase in 3TUG average time

The 3TUG is a functional mobility test that requires a patient to stand up from a straight-backed armchair, walk 3 meters, turn around, walk back, and sit down in the chair. A modification of this is where the individual performs the test 3 times without pause, and the measurement is the average time required to complete each of the 3 repetitions. Based upon literature reports that a significant change in gait for a similar walk-test is an increase in time of more than 20%, this has been incorporated into the endpoint.

Outcome measures

Outcome measures
Measure	Amifampridine Phosphate n=13 Participants amifampridine phosphate 10 mg (amifampridine equivalent) by mouth, 30 to 80 mg total daily dose, 3 to 4 times per day for 4 days Amifampridine Phosphate	Placebo (for Amifampridine Phosphate) n=13 Participants placebo by mouth 3 to 4 times per day for 4 days Placebo Oral Tablet
Triple Timed Up and Go Walk Test (3TUG)	1 Participants	8 Participants

Adverse Events

Amifampridine Phosphate

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Placebo (for Amifampridine Phosphate)

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Gary Ingenito

Catalyst Pharmaceuticals, Inc.

Phone: 305-420-3200

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Other adverse events
Measure	Amifampridine Phosphate n=13 participants at risk amifampridine phosphate 10 mg (amifampridine equivalent) by mouth, 30 to 80 mg total daily dose, 3 to 4 times per day for 4 days Amifampridine Phosphate	Placebo (for Amifampridine Phosphate) n=13 participants at risk placebo by mouth 3 to 4 times per day for 4 days Placebo Oral Tablet
Cardiac disorders atrial fibrillation	0.00% 0/13 • All AEs were observed for each patient from enrollment until study completion (up to 12 days per patient). Treatment-emergent AEs (TEAEs) were summarized using system organ class and PT by treatment and overall for all patients in the safety population.	7.7% 1/13 • All AEs were observed for each patient from enrollment until study completion (up to 12 days per patient). Treatment-emergent AEs (TEAEs) were summarized using system organ class and PT by treatment and overall for all patients in the safety population.
Cardiac disorders myocardial ischemia	0.00% 0/13 • All AEs were observed for each patient from enrollment until study completion (up to 12 days per patient). Treatment-emergent AEs (TEAEs) were summarized using system organ class and PT by treatment and overall for all patients in the safety population.	30.8% 4/13 • All AEs were observed for each patient from enrollment until study completion (up to 12 days per patient). Treatment-emergent AEs (TEAEs) were summarized using system organ class and PT by treatment and overall for all patients in the safety population.
Ear and labyrinth disorders motion sickness	0.00% 0/13 • All AEs were observed for each patient from enrollment until study completion (up to 12 days per patient). Treatment-emergent AEs (TEAEs) were summarized using system organ class and PT by treatment and overall for all patients in the safety population.	7.7% 1/13 • All AEs were observed for each patient from enrollment until study completion (up to 12 days per patient). Treatment-emergent AEs (TEAEs) were summarized using system organ class and PT by treatment and overall for all patients in the safety population.
Eye disorders diplopia	0.00% 0/13 • All AEs were observed for each patient from enrollment until study completion (up to 12 days per patient). Treatment-emergent AEs (TEAEs) were summarized using system organ class and PT by treatment and overall for all patients in the safety population.	7.7% 1/13 • All AEs were observed for each patient from enrollment until study completion (up to 12 days per patient). Treatment-emergent AEs (TEAEs) were summarized using system organ class and PT by treatment and overall for all patients in the safety population.
Eye disorders eyelid ptosis	0.00% 0/13 • All AEs were observed for each patient from enrollment until study completion (up to 12 days per patient). Treatment-emergent AEs (TEAEs) were summarized using system organ class and PT by treatment and overall for all patients in the safety population.	7.7% 1/13 • All AEs were observed for each patient from enrollment until study completion (up to 12 days per patient). Treatment-emergent AEs (TEAEs) were summarized using system organ class and PT by treatment and overall for all patients in the safety population.
Gastrointestinal disorders dry mouth	0.00% 0/13 • All AEs were observed for each patient from enrollment until study completion (up to 12 days per patient). Treatment-emergent AEs (TEAEs) were summarized using system organ class and PT by treatment and overall for all patients in the safety population.	15.4% 2/13 • All AEs were observed for each patient from enrollment until study completion (up to 12 days per patient). Treatment-emergent AEs (TEAEs) were summarized using system organ class and PT by treatment and overall for all patients in the safety population.
Gastrointestinal disorders diarrhoea	0.00% 0/13 • All AEs were observed for each patient from enrollment until study completion (up to 12 days per patient). Treatment-emergent AEs (TEAEs) were summarized using system organ class and PT by treatment and overall for all patients in the safety population.	7.7% 1/13 • All AEs were observed for each patient from enrollment until study completion (up to 12 days per patient). Treatment-emergent AEs (TEAEs) were summarized using system organ class and PT by treatment and overall for all patients in the safety population.
Gastrointestinal disorders dysphagia	0.00% 0/13 • All AEs were observed for each patient from enrollment until study completion (up to 12 days per patient). Treatment-emergent AEs (TEAEs) were summarized using system organ class and PT by treatment and overall for all patients in the safety population.	7.7% 1/13 • All AEs were observed for each patient from enrollment until study completion (up to 12 days per patient). Treatment-emergent AEs (TEAEs) were summarized using system organ class and PT by treatment and overall for all patients in the safety population.
Gastrointestinal disorders hypoaesthesia, oral	0.00% 0/13 • All AEs were observed for each patient from enrollment until study completion (up to 12 days per patient). Treatment-emergent AEs (TEAEs) were summarized using system organ class and PT by treatment and overall for all patients in the safety population.	7.7% 1/13 • All AEs were observed for each patient from enrollment until study completion (up to 12 days per patient). Treatment-emergent AEs (TEAEs) were summarized using system organ class and PT by treatment and overall for all patients in the safety population.
Gastrointestinal disorders impaired gastric emptying	0.00% 0/13 • All AEs were observed for each patient from enrollment until study completion (up to 12 days per patient). Treatment-emergent AEs (TEAEs) were summarized using system organ class and PT by treatment and overall for all patients in the safety population.	7.7% 1/13 • All AEs were observed for each patient from enrollment until study completion (up to 12 days per patient). Treatment-emergent AEs (TEAEs) were summarized using system organ class and PT by treatment and overall for all patients in the safety population.
Gastrointestinal disorders nausea	0.00% 0/13 • All AEs were observed for each patient from enrollment until study completion (up to 12 days per patient). Treatment-emergent AEs (TEAEs) were summarized using system organ class and PT by treatment and overall for all patients in the safety population.	7.7% 1/13 • All AEs were observed for each patient from enrollment until study completion (up to 12 days per patient). Treatment-emergent AEs (TEAEs) were summarized using system organ class and PT by treatment and overall for all patients in the safety population.
Gastrointestinal disorders oral disorder	0.00% 0/13 • All AEs were observed for each patient from enrollment until study completion (up to 12 days per patient). Treatment-emergent AEs (TEAEs) were summarized using system organ class and PT by treatment and overall for all patients in the safety population.	7.7% 1/13 • All AEs were observed for each patient from enrollment until study completion (up to 12 days per patient). Treatment-emergent AEs (TEAEs) were summarized using system organ class and PT by treatment and overall for all patients in the safety population.
Gastrointestinal disorders vomiting	0.00% 0/13 • All AEs were observed for each patient from enrollment until study completion (up to 12 days per patient). Treatment-emergent AEs (TEAEs) were summarized using system organ class and PT by treatment and overall for all patients in the safety population.	7.7% 1/13 • All AEs were observed for each patient from enrollment until study completion (up to 12 days per patient). Treatment-emergent AEs (TEAEs) were summarized using system organ class and PT by treatment and overall for all patients in the safety population.
General disorders fatigue	0.00% 0/13 • All AEs were observed for each patient from enrollment until study completion (up to 12 days per patient). Treatment-emergent AEs (TEAEs) were summarized using system organ class and PT by treatment and overall for all patients in the safety population.	30.8% 4/13 • All AEs were observed for each patient from enrollment until study completion (up to 12 days per patient). Treatment-emergent AEs (TEAEs) were summarized using system organ class and PT by treatment and overall for all patients in the safety population.
Gastrointestinal disorders asthenia	0.00% 0/13 • All AEs were observed for each patient from enrollment until study completion (up to 12 days per patient). Treatment-emergent AEs (TEAEs) were summarized using system organ class and PT by treatment and overall for all patients in the safety population.	15.4% 2/13 • All AEs were observed for each patient from enrollment until study completion (up to 12 days per patient). Treatment-emergent AEs (TEAEs) were summarized using system organ class and PT by treatment and overall for all patients in the safety population.
General disorders feeling hot	0.00% 0/13 • All AEs were observed for each patient from enrollment until study completion (up to 12 days per patient). Treatment-emergent AEs (TEAEs) were summarized using system organ class and PT by treatment and overall for all patients in the safety population.	15.4% 2/13 • All AEs were observed for each patient from enrollment until study completion (up to 12 days per patient). Treatment-emergent AEs (TEAEs) were summarized using system organ class and PT by treatment and overall for all patients in the safety population.
General disorders gait disturbance	0.00% 0/13 • All AEs were observed for each patient from enrollment until study completion (up to 12 days per patient). Treatment-emergent AEs (TEAEs) were summarized using system organ class and PT by treatment and overall for all patients in the safety population.	7.7% 1/13 • All AEs were observed for each patient from enrollment until study completion (up to 12 days per patient). Treatment-emergent AEs (TEAEs) were summarized using system organ class and PT by treatment and overall for all patients in the safety population.
General disorders pain	0.00% 0/13 • All AEs were observed for each patient from enrollment until study completion (up to 12 days per patient). Treatment-emergent AEs (TEAEs) were summarized using system organ class and PT by treatment and overall for all patients in the safety population.	7.7% 1/13 • All AEs were observed for each patient from enrollment until study completion (up to 12 days per patient). Treatment-emergent AEs (TEAEs) were summarized using system organ class and PT by treatment and overall for all patients in the safety population.
Infections and infestations bronchitis	0.00% 0/13 • All AEs were observed for each patient from enrollment until study completion (up to 12 days per patient). Treatment-emergent AEs (TEAEs) were summarized using system organ class and PT by treatment and overall for all patients in the safety population.	7.7% 1/13 • All AEs were observed for each patient from enrollment until study completion (up to 12 days per patient). Treatment-emergent AEs (TEAEs) were summarized using system organ class and PT by treatment and overall for all patients in the safety population.
Metabolism and nutrition disorders decreased appetite	0.00% 0/13 • All AEs were observed for each patient from enrollment until study completion (up to 12 days per patient). Treatment-emergent AEs (TEAEs) were summarized using system organ class and PT by treatment and overall for all patients in the safety population.	7.7% 1/13 • All AEs were observed for each patient from enrollment until study completion (up to 12 days per patient). Treatment-emergent AEs (TEAEs) were summarized using system organ class and PT by treatment and overall for all patients in the safety population.
Musculoskeletal and connective tissue disorders muscular weakness	0.00% 0/13 • All AEs were observed for each patient from enrollment until study completion (up to 12 days per patient). Treatment-emergent AEs (TEAEs) were summarized using system organ class and PT by treatment and overall for all patients in the safety population.	38.5% 5/13 • All AEs were observed for each patient from enrollment until study completion (up to 12 days per patient). Treatment-emergent AEs (TEAEs) were summarized using system organ class and PT by treatment and overall for all patients in the safety population.
Musculoskeletal and connective tissue disorders limb discomfort	0.00% 0/13 • All AEs were observed for each patient from enrollment until study completion (up to 12 days per patient). Treatment-emergent AEs (TEAEs) were summarized using system organ class and PT by treatment and overall for all patients in the safety population.	15.4% 2/13 • All AEs were observed for each patient from enrollment until study completion (up to 12 days per patient). Treatment-emergent AEs (TEAEs) were summarized using system organ class and PT by treatment and overall for all patients in the safety population.
Musculoskeletal and connective tissue disorders muscle spasm	0.00% 0/13 • All AEs were observed for each patient from enrollment until study completion (up to 12 days per patient). Treatment-emergent AEs (TEAEs) were summarized using system organ class and PT by treatment and overall for all patients in the safety population.	15.4% 2/13 • All AEs were observed for each patient from enrollment until study completion (up to 12 days per patient). Treatment-emergent AEs (TEAEs) were summarized using system organ class and PT by treatment and overall for all patients in the safety population.
Musculoskeletal and connective tissue disorders arthralgia	0.00% 0/13 • All AEs were observed for each patient from enrollment until study completion (up to 12 days per patient). Treatment-emergent AEs (TEAEs) were summarized using system organ class and PT by treatment and overall for all patients in the safety population.	7.7% 1/13 • All AEs were observed for each patient from enrollment until study completion (up to 12 days per patient). Treatment-emergent AEs (TEAEs) were summarized using system organ class and PT by treatment and overall for all patients in the safety population.
Musculoskeletal and connective tissue disorders back pain	7.7% 1/13 • All AEs were observed for each patient from enrollment until study completion (up to 12 days per patient). Treatment-emergent AEs (TEAEs) were summarized using system organ class and PT by treatment and overall for all patients in the safety population.	0.00% 0/13 • All AEs were observed for each patient from enrollment until study completion (up to 12 days per patient). Treatment-emergent AEs (TEAEs) were summarized using system organ class and PT by treatment and overall for all patients in the safety population.
Musculoskeletal and connective tissue disorders musculoskeletal stiffness	0.00% 0/13 • All AEs were observed for each patient from enrollment until study completion (up to 12 days per patient). Treatment-emergent AEs (TEAEs) were summarized using system organ class and PT by treatment and overall for all patients in the safety population.	7.7% 1/13 • All AEs were observed for each patient from enrollment until study completion (up to 12 days per patient). Treatment-emergent AEs (TEAEs) were summarized using system organ class and PT by treatment and overall for all patients in the safety population.
Musculoskeletal and connective tissue disorders pain in extremity	7.7% 1/13 • All AEs were observed for each patient from enrollment until study completion (up to 12 days per patient). Treatment-emergent AEs (TEAEs) were summarized using system organ class and PT by treatment and overall for all patients in the safety population.	0.00% 0/13 • All AEs were observed for each patient from enrollment until study completion (up to 12 days per patient). Treatment-emergent AEs (TEAEs) were summarized using system organ class and PT by treatment and overall for all patients in the safety population.
Nervous system disorders balance disorder	0.00% 0/13 • All AEs were observed for each patient from enrollment until study completion (up to 12 days per patient). Treatment-emergent AEs (TEAEs) were summarized using system organ class and PT by treatment and overall for all patients in the safety population.	15.4% 2/13 • All AEs were observed for each patient from enrollment until study completion (up to 12 days per patient). Treatment-emergent AEs (TEAEs) were summarized using system organ class and PT by treatment and overall for all patients in the safety population.
Nervous system disorders eyelid ptosis	0.00% 0/13 • All AEs were observed for each patient from enrollment until study completion (up to 12 days per patient). Treatment-emergent AEs (TEAEs) were summarized using system organ class and PT by treatment and overall for all patients in the safety population.	7.7% 1/13 • All AEs were observed for each patient from enrollment until study completion (up to 12 days per patient). Treatment-emergent AEs (TEAEs) were summarized using system organ class and PT by treatment and overall for all patients in the safety population.
Nervous system disorders facial nerve disorder	0.00% 0/13 • All AEs were observed for each patient from enrollment until study completion (up to 12 days per patient). Treatment-emergent AEs (TEAEs) were summarized using system organ class and PT by treatment and overall for all patients in the safety population.	7.7% 1/13 • All AEs were observed for each patient from enrollment until study completion (up to 12 days per patient). Treatment-emergent AEs (TEAEs) were summarized using system organ class and PT by treatment and overall for all patients in the safety population.
Nervous system disorders headache	7.7% 1/13 • All AEs were observed for each patient from enrollment until study completion (up to 12 days per patient). Treatment-emergent AEs (TEAEs) were summarized using system organ class and PT by treatment and overall for all patients in the safety population.	0.00% 0/13 • All AEs were observed for each patient from enrollment until study completion (up to 12 days per patient). Treatment-emergent AEs (TEAEs) were summarized using system organ class and PT by treatment and overall for all patients in the safety population.
Nervous system disorders movement disorder	0.00% 0/13 • All AEs were observed for each patient from enrollment until study completion (up to 12 days per patient). Treatment-emergent AEs (TEAEs) were summarized using system organ class and PT by treatment and overall for all patients in the safety population.	7.7% 1/13 • All AEs were observed for each patient from enrollment until study completion (up to 12 days per patient). Treatment-emergent AEs (TEAEs) were summarized using system organ class and PT by treatment and overall for all patients in the safety population.
Nervous system disorders somnolence	0.00% 0/13 • All AEs were observed for each patient from enrollment until study completion (up to 12 days per patient). Treatment-emergent AEs (TEAEs) were summarized using system organ class and PT by treatment and overall for all patients in the safety population.	7.7% 1/13 • All AEs were observed for each patient from enrollment until study completion (up to 12 days per patient). Treatment-emergent AEs (TEAEs) were summarized using system organ class and PT by treatment and overall for all patients in the safety population.
Nervous system disorders speech disorder	0.00% 0/13 • All AEs were observed for each patient from enrollment until study completion (up to 12 days per patient). Treatment-emergent AEs (TEAEs) were summarized using system organ class and PT by treatment and overall for all patients in the safety population.	7.7% 1/13 • All AEs were observed for each patient from enrollment until study completion (up to 12 days per patient). Treatment-emergent AEs (TEAEs) were summarized using system organ class and PT by treatment and overall for all patients in the safety population.
Psychiatric disorders insomnia	0.00% 0/13 • All AEs were observed for each patient from enrollment until study completion (up to 12 days per patient). Treatment-emergent AEs (TEAEs) were summarized using system organ class and PT by treatment and overall for all patients in the safety population.	7.7% 1/13 • All AEs were observed for each patient from enrollment until study completion (up to 12 days per patient). Treatment-emergent AEs (TEAEs) were summarized using system organ class and PT by treatment and overall for all patients in the safety population.
Respiratory, thoracic and mediastinal disorders dysphonia	0.00% 0/13 • All AEs were observed for each patient from enrollment until study completion (up to 12 days per patient). Treatment-emergent AEs (TEAEs) were summarized using system organ class and PT by treatment and overall for all patients in the safety population.	7.7% 1/13 • All AEs were observed for each patient from enrollment until study completion (up to 12 days per patient). Treatment-emergent AEs (TEAEs) were summarized using system organ class and PT by treatment and overall for all patients in the safety population.
Respiratory, thoracic and mediastinal disorders dyspnoea	0.00% 0/13 • All AEs were observed for each patient from enrollment until study completion (up to 12 days per patient). Treatment-emergent AEs (TEAEs) were summarized using system organ class and PT by treatment and overall for all patients in the safety population.	7.7% 1/13 • All AEs were observed for each patient from enrollment until study completion (up to 12 days per patient). Treatment-emergent AEs (TEAEs) were summarized using system organ class and PT by treatment and overall for all patients in the safety population.
Skin and subcutaneous tissue disorders dermatitis contact	0.00% 0/13 • All AEs were observed for each patient from enrollment until study completion (up to 12 days per patient). Treatment-emergent AEs (TEAEs) were summarized using system organ class and PT by treatment and overall for all patients in the safety population.	7.7% 1/13 • All AEs were observed for each patient from enrollment until study completion (up to 12 days per patient). Treatment-emergent AEs (TEAEs) were summarized using system organ class and PT by treatment and overall for all patients in the safety population.