Trial Outcomes & Findings for Effectiveness of 3,4-Diaminopyridine in Lambert-Eaton Myasthenic Syndrome (NCT NCT01511978)

NCT ID: NCT01511978

Last Updated: 2017-07-11

Results Overview

The 3TUG time obtained 2 hours after the last dose of the withdrawal period (i.e., at time of theoretical "peak drug effect") was compared to the average time-matched 3TUG tests performed during 2 days of baseline observation prior to randomization. The study endpoint was a change of more than 30% in the final post-dose 3TUG during the withdrawal period and was based on blinded readings of video recordings of 3TUG tests.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 32 participants
• Primary outcome timeframe: Baseline period (days 0, 1, 2); Randomized treatment period (starting with last dose of day 2, and days 3, 4, 5, and ending with first dose on day 6 when pre-randomization regimen was resumed, or rescue, if indicated sooner)
• Results posted on: 2017-07-11

Participant Flow

Participants were referred by active Investigational New Drug (IND) holders involved with the Jacobus Pharmaceutical Company's 3,4-diaminopyridine (3,4-DAP) free base compassionate distribution program.

52 patients were assessed for eligibility. 20 were ineligible. 32 were randomized and completed the study.

Participant milestones

Measure	Continuous 3,4-DAP Subjects were administered their usual dosage on their regular personalized schedule	Taper 3,4-DAP to Placebo Subjects were administered decreasing amounts of 3,4-DAP on their regular personalized schedule
Overall Study STARTED	14	18
Overall Study COMPLETED	14	18
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Effectiveness of 3,4-Diaminopyridine in Lambert-Eaton Myasthenic Syndrome

Baseline characteristics by cohort

Measure	Continuous 3,4-Diaminopyridine (3,4-DAP) n=14 Participants Subjects were administered their usual dosage on their regular personalized schedule	3,4-DAP Taper to Placebo n=18 Participants Subjects were administered decreasing amounts of 3,4-DAP on their regular personalized schedule	Total n=32 Participants Total of all reporting groups
Age, Continuous	50.7 years STANDARD_DEVIATION 15.97 • n=5 Participants	59.3 years STANDARD_DEVIATION 14.99 • n=7 Participants	55.5 years STANDARD_DEVIATION 15.77 • n=5 Participants
Sex: Female, Male Female	10 Participants n=5 Participants	11 Participants n=7 Participants	21 Participants n=5 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	7 Participants n=7 Participants	11 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	14 Participants n=5 Participants	17 Participants n=7 Participants	31 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
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	0 Participants n=5 Participants	0 Participants n=7 Participants	0 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	3 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) White	11 Participants n=5 Participants	18 Participants n=7 Participants	29 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
Height	168.5 cm STANDARD_DEVIATION 5.67 • n=5 Participants	169.6 cm STANDARD_DEVIATION 8.98 • n=7 Participants	169.2 cm STANDARD_DEVIATION 7.67 • n=5 Participants
Weight	78.0 kg STANDARD_DEVIATION 19.11 • n=5 Participants	80.3 kg STANDARD_DEVIATION 18.95 • n=7 Participants	79.3 kg STANDARD_DEVIATION 18.73 • n=5 Participants
Body Mass Index (BMI)	27.3 kg/m2 STANDARD_DEVIATION 5.92 • n=5 Participants	27.7 kg/m2 STANDARD_DEVIATION 5.14 • n=7 Participants	27.5 kg/m2 STANDARD_DEVIATION 5.39 • n=5 Participants
Age at diagnosis	44.1 years STANDARD_DEVIATION 13.79 • n=5 Participants	52.7 years STANDARD_DEVIATION 14.76 • n=7 Participants	48.9 years STANDARD_DEVIATION 14.76 • n=5 Participants
Time between symptom onset and diagnosis	0.9 years STANDARD_DEVIATION 0.62 • n=5 Participants	2.2 years STANDARD_DEVIATION 3.00 • n=7 Participants	1.7 years STANDARD_DEVIATION 2.35 • n=5 Participants
Duration of diagnosis prior to randomization	6.7 years STANDARD_DEVIATION 5.70 • n=5 Participants	6.7 years STANDARD_DEVIATION 6.08 • n=7 Participants	6.7 years STANDARD_DEVIATION 5.82 • n=5 Participants
Positive P/Q type voltage-gated calcium channel (VGCC) antibodies at screening	12 Participants n=5 Participants	17 Participants n=7 Participants	29 Participants n=5 Participants
Compound Muscle Action Potential (CMAP) consistent with Lambert-Eaton Myasthenia (LEM) at screening	7 Participants n=5 Participants	10 Participants n=7 Participants	17 Participants n=5 Participants
Total Daily Dose of 3,4-DAP at randomization	80.0 mg n=5 Participants	80.0 mg n=7 Participants	80 mg n=5 Participants
Number of 3,4-DAP individual daily doses at randomization	4.5 number of daily doses n=5 Participants	5.0 number of daily doses n=7 Participants	5.0 number of daily doses n=5 Participants

PRIMARY outcome

Timeframe: Baseline period (days 0, 1, 2); Randomized treatment period (starting with last dose of day 2, and days 3, 4, 5, and ending with first dose on day 6 when pre-randomization regimen was resumed, or rescue, if indicated sooner)

The 3TUG time obtained 2 hours after the last dose of the withdrawal period (i.e., at time of theoretical "peak drug effect") was compared to the average time-matched 3TUG tests performed during 2 days of baseline observation prior to randomization.

The study endpoint was a change of more than 30% in the final post-dose 3TUG during the withdrawal period and was based on blinded readings of video recordings of 3TUG tests.

Outcome measures

Measure	Continuous 3,4-Diaminopyridine (3,4-DAP) n=14 Participants Subjects were continued on their usual pre-randomization 3,4-DAP dosing regimen.	3,4-DAP Taper to Placebo n=18 Participants Subjects were tapered off of their pre-randomization 3,4-DAP dosing regimen over 3 days with up to an additional 16 hours of placebo.
Number of Participants With 30% or More Deterioration in Triple Timed Up & Go (3TUG) Test, Compared to Time-matched Baseline	0 Participants	13 Participants

SECONDARY outcome

Timeframe: Participants were followed for up to 7 days

The last post-dose self-assessment of LEMS-related weakness from the withdrawal period with categories of much much weaker (-3), much weaker (-2), somewhat weaker (-1), about the same (0), somewhat stronger (1), much stronger (2), and much much stronger (3).

Outcome measures

Measure	Continuous 3,4-Diaminopyridine (3,4-DAP) n=14 Participants Subjects were continued on their usual pre-randomization 3,4-DAP dosing regimen.	3,4-DAP Taper to Placebo n=18 Participants Subjects were tapered off of their pre-randomization 3,4-DAP dosing regimen over 3 days with up to an additional 16 hours of placebo.
Self-assessment of LEMS-related Weakness, W-SAS	-0.2 units on a scale Standard Deviation 1.24	-2.4 units on a scale Standard Deviation 0.85

Adverse Events

Continuous 3,4-Diaminopyridine (3,4-DAP)

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

3,4-DAP Taper to Placebo

Serious events: 1 serious events

Other events: 12 other events

Deaths: 0 deaths

Serious adverse events

Measure	Continuous 3,4-Diaminopyridine (3,4-DAP) n=14 participants at risk Subjects were administered their usual dosage on their regular personalized schedule	3,4-DAP Taper to Placebo n=18 participants at risk Subjects were administered decreasing amounts of 3,4-DAP on their regular personalized schedule
Infections and infestations pneumonia	0.00% 0/14 • Adverse events were collected during the inpatient stay of up to 7 days on the clinical research unit and then weekly with standard telephone follow-up and diary entries for one month following discharge from the clinical research unit. The return of Lambert-Eaton Myasthenic Syndrome (LEMS)-related signs and symptoms in a withdrawal design was anticipated and therefore adverse events were categorized as (1) treatment emergent adverse events, (2) treatment emergent adverse events excluding LEMS-related signs and symptoms, and (3) LEMS-related signs and symptoms adverse events	5.6% 1/18 • Number of events 1 • Adverse events were collected during the inpatient stay of up to 7 days on the clinical research unit and then weekly with standard telephone follow-up and diary entries for one month following discharge from the clinical research unit. The return of Lambert-Eaton Myasthenic Syndrome (LEMS)-related signs and symptoms in a withdrawal design was anticipated and therefore adverse events were categorized as (1) treatment emergent adverse events, (2) treatment emergent adverse events excluding LEMS-related signs and symptoms, and (3) LEMS-related signs and symptoms adverse events

Other adverse events

Measure	Continuous 3,4-Diaminopyridine (3,4-DAP) n=14 participants at risk Subjects were administered their usual dosage on their regular personalized schedule	3,4-DAP Taper to Placebo n=18 participants at risk Subjects were administered decreasing amounts of 3,4-DAP on their regular personalized schedule
Gastrointestinal disorders Abdominal discomfort	0.00% 0/14 • Adverse events were collected during the inpatient stay of up to 7 days on the clinical research unit and then weekly with standard telephone follow-up and diary entries for one month following discharge from the clinical research unit. The return of Lambert-Eaton Myasthenic Syndrome (LEMS)-related signs and symptoms in a withdrawal design was anticipated and therefore adverse events were categorized as (1) treatment emergent adverse events, (2) treatment emergent adverse events excluding LEMS-related signs and symptoms, and (3) LEMS-related signs and symptoms adverse events	11.1% 2/18 • Adverse events were collected during the inpatient stay of up to 7 days on the clinical research unit and then weekly with standard telephone follow-up and diary entries for one month following discharge from the clinical research unit. The return of Lambert-Eaton Myasthenic Syndrome (LEMS)-related signs and symptoms in a withdrawal design was anticipated and therefore adverse events were categorized as (1) treatment emergent adverse events, (2) treatment emergent adverse events excluding LEMS-related signs and symptoms, and (3) LEMS-related signs and symptoms adverse events
Infections and infestations Respiratory tract infection	0.00% 0/14 • Adverse events were collected during the inpatient stay of up to 7 days on the clinical research unit and then weekly with standard telephone follow-up and diary entries for one month following discharge from the clinical research unit. The return of Lambert-Eaton Myasthenic Syndrome (LEMS)-related signs and symptoms in a withdrawal design was anticipated and therefore adverse events were categorized as (1) treatment emergent adverse events, (2) treatment emergent adverse events excluding LEMS-related signs and symptoms, and (3) LEMS-related signs and symptoms adverse events	11.1% 2/18 • Adverse events were collected during the inpatient stay of up to 7 days on the clinical research unit and then weekly with standard telephone follow-up and diary entries for one month following discharge from the clinical research unit. The return of Lambert-Eaton Myasthenic Syndrome (LEMS)-related signs and symptoms in a withdrawal design was anticipated and therefore adverse events were categorized as (1) treatment emergent adverse events, (2) treatment emergent adverse events excluding LEMS-related signs and symptoms, and (3) LEMS-related signs and symptoms adverse events
Musculoskeletal and connective tissue disorders Back pain	7.1% 1/14 • Adverse events were collected during the inpatient stay of up to 7 days on the clinical research unit and then weekly with standard telephone follow-up and diary entries for one month following discharge from the clinical research unit. The return of Lambert-Eaton Myasthenic Syndrome (LEMS)-related signs and symptoms in a withdrawal design was anticipated and therefore adverse events were categorized as (1) treatment emergent adverse events, (2) treatment emergent adverse events excluding LEMS-related signs and symptoms, and (3) LEMS-related signs and symptoms adverse events	5.6% 1/18 • Adverse events were collected during the inpatient stay of up to 7 days on the clinical research unit and then weekly with standard telephone follow-up and diary entries for one month following discharge from the clinical research unit. The return of Lambert-Eaton Myasthenic Syndrome (LEMS)-related signs and symptoms in a withdrawal design was anticipated and therefore adverse events were categorized as (1) treatment emergent adverse events, (2) treatment emergent adverse events excluding LEMS-related signs and symptoms, and (3) LEMS-related signs and symptoms adverse events
Nervous system disorders Headache	7.1% 1/14 • Adverse events were collected during the inpatient stay of up to 7 days on the clinical research unit and then weekly with standard telephone follow-up and diary entries for one month following discharge from the clinical research unit. The return of Lambert-Eaton Myasthenic Syndrome (LEMS)-related signs and symptoms in a withdrawal design was anticipated and therefore adverse events were categorized as (1) treatment emergent adverse events, (2) treatment emergent adverse events excluding LEMS-related signs and symptoms, and (3) LEMS-related signs and symptoms adverse events	5.6% 1/18 • Adverse events were collected during the inpatient stay of up to 7 days on the clinical research unit and then weekly with standard telephone follow-up and diary entries for one month following discharge from the clinical research unit. The return of Lambert-Eaton Myasthenic Syndrome (LEMS)-related signs and symptoms in a withdrawal design was anticipated and therefore adverse events were categorized as (1) treatment emergent adverse events, (2) treatment emergent adverse events excluding LEMS-related signs and symptoms, and (3) LEMS-related signs and symptoms adverse events
Infections and infestations Nasopharyngitis	7.1% 1/14 • Adverse events were collected during the inpatient stay of up to 7 days on the clinical research unit and then weekly with standard telephone follow-up and diary entries for one month following discharge from the clinical research unit. The return of Lambert-Eaton Myasthenic Syndrome (LEMS)-related signs and symptoms in a withdrawal design was anticipated and therefore adverse events were categorized as (1) treatment emergent adverse events, (2) treatment emergent adverse events excluding LEMS-related signs and symptoms, and (3) LEMS-related signs and symptoms adverse events	5.6% 1/18 • Adverse events were collected during the inpatient stay of up to 7 days on the clinical research unit and then weekly with standard telephone follow-up and diary entries for one month following discharge from the clinical research unit. The return of Lambert-Eaton Myasthenic Syndrome (LEMS)-related signs and symptoms in a withdrawal design was anticipated and therefore adverse events were categorized as (1) treatment emergent adverse events, (2) treatment emergent adverse events excluding LEMS-related signs and symptoms, and (3) LEMS-related signs and symptoms adverse events
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	7.1% 1/14 • Adverse events were collected during the inpatient stay of up to 7 days on the clinical research unit and then weekly with standard telephone follow-up and diary entries for one month following discharge from the clinical research unit. The return of Lambert-Eaton Myasthenic Syndrome (LEMS)-related signs and symptoms in a withdrawal design was anticipated and therefore adverse events were categorized as (1) treatment emergent adverse events, (2) treatment emergent adverse events excluding LEMS-related signs and symptoms, and (3) LEMS-related signs and symptoms adverse events	5.6% 1/18 • Adverse events were collected during the inpatient stay of up to 7 days on the clinical research unit and then weekly with standard telephone follow-up and diary entries for one month following discharge from the clinical research unit. The return of Lambert-Eaton Myasthenic Syndrome (LEMS)-related signs and symptoms in a withdrawal design was anticipated and therefore adverse events were categorized as (1) treatment emergent adverse events, (2) treatment emergent adverse events excluding LEMS-related signs and symptoms, and (3) LEMS-related signs and symptoms adverse events
Gastrointestinal disorders Abdominal pain lower	0.00% 0/14 • Adverse events were collected during the inpatient stay of up to 7 days on the clinical research unit and then weekly with standard telephone follow-up and diary entries for one month following discharge from the clinical research unit. The return of Lambert-Eaton Myasthenic Syndrome (LEMS)-related signs and symptoms in a withdrawal design was anticipated and therefore adverse events were categorized as (1) treatment emergent adverse events, (2) treatment emergent adverse events excluding LEMS-related signs and symptoms, and (3) LEMS-related signs and symptoms adverse events	5.6% 1/18 • Adverse events were collected during the inpatient stay of up to 7 days on the clinical research unit and then weekly with standard telephone follow-up and diary entries for one month following discharge from the clinical research unit. The return of Lambert-Eaton Myasthenic Syndrome (LEMS)-related signs and symptoms in a withdrawal design was anticipated and therefore adverse events were categorized as (1) treatment emergent adverse events, (2) treatment emergent adverse events excluding LEMS-related signs and symptoms, and (3) LEMS-related signs and symptoms adverse events
Investigations Blood glucose increased	0.00% 0/14 • Adverse events were collected during the inpatient stay of up to 7 days on the clinical research unit and then weekly with standard telephone follow-up and diary entries for one month following discharge from the clinical research unit. The return of Lambert-Eaton Myasthenic Syndrome (LEMS)-related signs and symptoms in a withdrawal design was anticipated and therefore adverse events were categorized as (1) treatment emergent adverse events, (2) treatment emergent adverse events excluding LEMS-related signs and symptoms, and (3) LEMS-related signs and symptoms adverse events	5.6% 1/18 • Adverse events were collected during the inpatient stay of up to 7 days on the clinical research unit and then weekly with standard telephone follow-up and diary entries for one month following discharge from the clinical research unit. The return of Lambert-Eaton Myasthenic Syndrome (LEMS)-related signs and symptoms in a withdrawal design was anticipated and therefore adverse events were categorized as (1) treatment emergent adverse events, (2) treatment emergent adverse events excluding LEMS-related signs and symptoms, and (3) LEMS-related signs and symptoms adverse events
Gastrointestinal disorders Cheilitis	0.00% 0/14 • Adverse events were collected during the inpatient stay of up to 7 days on the clinical research unit and then weekly with standard telephone follow-up and diary entries for one month following discharge from the clinical research unit. The return of Lambert-Eaton Myasthenic Syndrome (LEMS)-related signs and symptoms in a withdrawal design was anticipated and therefore adverse events were categorized as (1) treatment emergent adverse events, (2) treatment emergent adverse events excluding LEMS-related signs and symptoms, and (3) LEMS-related signs and symptoms adverse events	5.6% 1/18 • Adverse events were collected during the inpatient stay of up to 7 days on the clinical research unit and then weekly with standard telephone follow-up and diary entries for one month following discharge from the clinical research unit. The return of Lambert-Eaton Myasthenic Syndrome (LEMS)-related signs and symptoms in a withdrawal design was anticipated and therefore adverse events were categorized as (1) treatment emergent adverse events, (2) treatment emergent adverse events excluding LEMS-related signs and symptoms, and (3) LEMS-related signs and symptoms adverse events
Nervous system disorders Dizziness	0.00% 0/14 • Adverse events were collected during the inpatient stay of up to 7 days on the clinical research unit and then weekly with standard telephone follow-up and diary entries for one month following discharge from the clinical research unit. The return of Lambert-Eaton Myasthenic Syndrome (LEMS)-related signs and symptoms in a withdrawal design was anticipated and therefore adverse events were categorized as (1) treatment emergent adverse events, (2) treatment emergent adverse events excluding LEMS-related signs and symptoms, and (3) LEMS-related signs and symptoms adverse events	5.6% 1/18 • Adverse events were collected during the inpatient stay of up to 7 days on the clinical research unit and then weekly with standard telephone follow-up and diary entries for one month following discharge from the clinical research unit. The return of Lambert-Eaton Myasthenic Syndrome (LEMS)-related signs and symptoms in a withdrawal design was anticipated and therefore adverse events were categorized as (1) treatment emergent adverse events, (2) treatment emergent adverse events excluding LEMS-related signs and symptoms, and (3) LEMS-related signs and symptoms adverse events
Investigations Electrocardiogram QT prolonged	0.00% 0/14 • Adverse events were collected during the inpatient stay of up to 7 days on the clinical research unit and then weekly with standard telephone follow-up and diary entries for one month following discharge from the clinical research unit. The return of Lambert-Eaton Myasthenic Syndrome (LEMS)-related signs and symptoms in a withdrawal design was anticipated and therefore adverse events were categorized as (1) treatment emergent adverse events, (2) treatment emergent adverse events excluding LEMS-related signs and symptoms, and (3) LEMS-related signs and symptoms adverse events	5.6% 1/18 • Adverse events were collected during the inpatient stay of up to 7 days on the clinical research unit and then weekly with standard telephone follow-up and diary entries for one month following discharge from the clinical research unit. The return of Lambert-Eaton Myasthenic Syndrome (LEMS)-related signs and symptoms in a withdrawal design was anticipated and therefore adverse events were categorized as (1) treatment emergent adverse events, (2) treatment emergent adverse events excluding LEMS-related signs and symptoms, and (3) LEMS-related signs and symptoms adverse events
Metabolism and nutrition disorders Gout	0.00% 0/14 • Adverse events were collected during the inpatient stay of up to 7 days on the clinical research unit and then weekly with standard telephone follow-up and diary entries for one month following discharge from the clinical research unit. The return of Lambert-Eaton Myasthenic Syndrome (LEMS)-related signs and symptoms in a withdrawal design was anticipated and therefore adverse events were categorized as (1) treatment emergent adverse events, (2) treatment emergent adverse events excluding LEMS-related signs and symptoms, and (3) LEMS-related signs and symptoms adverse events	5.6% 1/18 • Adverse events were collected during the inpatient stay of up to 7 days on the clinical research unit and then weekly with standard telephone follow-up and diary entries for one month following discharge from the clinical research unit. The return of Lambert-Eaton Myasthenic Syndrome (LEMS)-related signs and symptoms in a withdrawal design was anticipated and therefore adverse events were categorized as (1) treatment emergent adverse events, (2) treatment emergent adverse events excluding LEMS-related signs and symptoms, and (3) LEMS-related signs and symptoms adverse events
Gastrointestinal disorders Nausea	0.00% 0/14 • Adverse events were collected during the inpatient stay of up to 7 days on the clinical research unit and then weekly with standard telephone follow-up and diary entries for one month following discharge from the clinical research unit. The return of Lambert-Eaton Myasthenic Syndrome (LEMS)-related signs and symptoms in a withdrawal design was anticipated and therefore adverse events were categorized as (1) treatment emergent adverse events, (2) treatment emergent adverse events excluding LEMS-related signs and symptoms, and (3) LEMS-related signs and symptoms adverse events	5.6% 1/18 • Adverse events were collected during the inpatient stay of up to 7 days on the clinical research unit and then weekly with standard telephone follow-up and diary entries for one month following discharge from the clinical research unit. The return of Lambert-Eaton Myasthenic Syndrome (LEMS)-related signs and symptoms in a withdrawal design was anticipated and therefore adverse events were categorized as (1) treatment emergent adverse events, (2) treatment emergent adverse events excluding LEMS-related signs and symptoms, and (3) LEMS-related signs and symptoms adverse events
Nervous system disorders Paresthesia	0.00% 0/14 • Adverse events were collected during the inpatient stay of up to 7 days on the clinical research unit and then weekly with standard telephone follow-up and diary entries for one month following discharge from the clinical research unit. The return of Lambert-Eaton Myasthenic Syndrome (LEMS)-related signs and symptoms in a withdrawal design was anticipated and therefore adverse events were categorized as (1) treatment emergent adverse events, (2) treatment emergent adverse events excluding LEMS-related signs and symptoms, and (3) LEMS-related signs and symptoms adverse events	5.6% 1/18 • Adverse events were collected during the inpatient stay of up to 7 days on the clinical research unit and then weekly with standard telephone follow-up and diary entries for one month following discharge from the clinical research unit. The return of Lambert-Eaton Myasthenic Syndrome (LEMS)-related signs and symptoms in a withdrawal design was anticipated and therefore adverse events were categorized as (1) treatment emergent adverse events, (2) treatment emergent adverse events excluding LEMS-related signs and symptoms, and (3) LEMS-related signs and symptoms adverse events
General disorders Pyrexia	0.00% 0/14 • Adverse events were collected during the inpatient stay of up to 7 days on the clinical research unit and then weekly with standard telephone follow-up and diary entries for one month following discharge from the clinical research unit. The return of Lambert-Eaton Myasthenic Syndrome (LEMS)-related signs and symptoms in a withdrawal design was anticipated and therefore adverse events were categorized as (1) treatment emergent adverse events, (2) treatment emergent adverse events excluding LEMS-related signs and symptoms, and (3) LEMS-related signs and symptoms adverse events	5.6% 1/18 • Adverse events were collected during the inpatient stay of up to 7 days on the clinical research unit and then weekly with standard telephone follow-up and diary entries for one month following discharge from the clinical research unit. The return of Lambert-Eaton Myasthenic Syndrome (LEMS)-related signs and symptoms in a withdrawal design was anticipated and therefore adverse events were categorized as (1) treatment emergent adverse events, (2) treatment emergent adverse events excluding LEMS-related signs and symptoms, and (3) LEMS-related signs and symptoms adverse events
Skin and subcutaneous tissue disorders Rash	0.00% 0/14 • Adverse events were collected during the inpatient stay of up to 7 days on the clinical research unit and then weekly with standard telephone follow-up and diary entries for one month following discharge from the clinical research unit. The return of Lambert-Eaton Myasthenic Syndrome (LEMS)-related signs and symptoms in a withdrawal design was anticipated and therefore adverse events were categorized as (1) treatment emergent adverse events, (2) treatment emergent adverse events excluding LEMS-related signs and symptoms, and (3) LEMS-related signs and symptoms adverse events	5.6% 1/18 • Adverse events were collected during the inpatient stay of up to 7 days on the clinical research unit and then weekly with standard telephone follow-up and diary entries for one month following discharge from the clinical research unit. The return of Lambert-Eaton Myasthenic Syndrome (LEMS)-related signs and symptoms in a withdrawal design was anticipated and therefore adverse events were categorized as (1) treatment emergent adverse events, (2) treatment emergent adverse events excluding LEMS-related signs and symptoms, and (3) LEMS-related signs and symptoms adverse events
Immune system disorders Seasonal allergy	0.00% 0/14 • Adverse events were collected during the inpatient stay of up to 7 days on the clinical research unit and then weekly with standard telephone follow-up and diary entries for one month following discharge from the clinical research unit. The return of Lambert-Eaton Myasthenic Syndrome (LEMS)-related signs and symptoms in a withdrawal design was anticipated and therefore adverse events were categorized as (1) treatment emergent adverse events, (2) treatment emergent adverse events excluding LEMS-related signs and symptoms, and (3) LEMS-related signs and symptoms adverse events	5.6% 1/18 • Adverse events were collected during the inpatient stay of up to 7 days on the clinical research unit and then weekly with standard telephone follow-up and diary entries for one month following discharge from the clinical research unit. The return of Lambert-Eaton Myasthenic Syndrome (LEMS)-related signs and symptoms in a withdrawal design was anticipated and therefore adverse events were categorized as (1) treatment emergent adverse events, (2) treatment emergent adverse events excluding LEMS-related signs and symptoms, and (3) LEMS-related signs and symptoms adverse events
Nervous system disorders Sinus headache	0.00% 0/14 • Adverse events were collected during the inpatient stay of up to 7 days on the clinical research unit and then weekly with standard telephone follow-up and diary entries for one month following discharge from the clinical research unit. The return of Lambert-Eaton Myasthenic Syndrome (LEMS)-related signs and symptoms in a withdrawal design was anticipated and therefore adverse events were categorized as (1) treatment emergent adverse events, (2) treatment emergent adverse events excluding LEMS-related signs and symptoms, and (3) LEMS-related signs and symptoms adverse events	5.6% 1/18 • Adverse events were collected during the inpatient stay of up to 7 days on the clinical research unit and then weekly with standard telephone follow-up and diary entries for one month following discharge from the clinical research unit. The return of Lambert-Eaton Myasthenic Syndrome (LEMS)-related signs and symptoms in a withdrawal design was anticipated and therefore adverse events were categorized as (1) treatment emergent adverse events, (2) treatment emergent adverse events excluding LEMS-related signs and symptoms, and (3) LEMS-related signs and symptoms adverse events
Infections and infestations Sinusitis	0.00% 0/14 • Adverse events were collected during the inpatient stay of up to 7 days on the clinical research unit and then weekly with standard telephone follow-up and diary entries for one month following discharge from the clinical research unit. The return of Lambert-Eaton Myasthenic Syndrome (LEMS)-related signs and symptoms in a withdrawal design was anticipated and therefore adverse events were categorized as (1) treatment emergent adverse events, (2) treatment emergent adverse events excluding LEMS-related signs and symptoms, and (3) LEMS-related signs and symptoms adverse events	5.6% 1/18 • Adverse events were collected during the inpatient stay of up to 7 days on the clinical research unit and then weekly with standard telephone follow-up and diary entries for one month following discharge from the clinical research unit. The return of Lambert-Eaton Myasthenic Syndrome (LEMS)-related signs and symptoms in a withdrawal design was anticipated and therefore adverse events were categorized as (1) treatment emergent adverse events, (2) treatment emergent adverse events excluding LEMS-related signs and symptoms, and (3) LEMS-related signs and symptoms adverse events
Musculoskeletal and connective tissue disorders Sjogren	0.00% 0/14 • Adverse events were collected during the inpatient stay of up to 7 days on the clinical research unit and then weekly with standard telephone follow-up and diary entries for one month following discharge from the clinical research unit. The return of Lambert-Eaton Myasthenic Syndrome (LEMS)-related signs and symptoms in a withdrawal design was anticipated and therefore adverse events were categorized as (1) treatment emergent adverse events, (2) treatment emergent adverse events excluding LEMS-related signs and symptoms, and (3) LEMS-related signs and symptoms adverse events	5.6% 1/18 • Adverse events were collected during the inpatient stay of up to 7 days on the clinical research unit and then weekly with standard telephone follow-up and diary entries for one month following discharge from the clinical research unit. The return of Lambert-Eaton Myasthenic Syndrome (LEMS)-related signs and symptoms in a withdrawal design was anticipated and therefore adverse events were categorized as (1) treatment emergent adverse events, (2) treatment emergent adverse events excluding LEMS-related signs and symptoms, and (3) LEMS-related signs and symptoms adverse events
Gastrointestinal disorders Gastritis	7.1% 1/14 • Adverse events were collected during the inpatient stay of up to 7 days on the clinical research unit and then weekly with standard telephone follow-up and diary entries for one month following discharge from the clinical research unit. The return of Lambert-Eaton Myasthenic Syndrome (LEMS)-related signs and symptoms in a withdrawal design was anticipated and therefore adverse events were categorized as (1) treatment emergent adverse events, (2) treatment emergent adverse events excluding LEMS-related signs and symptoms, and (3) LEMS-related signs and symptoms adverse events	0.00% 0/18 • Adverse events were collected during the inpatient stay of up to 7 days on the clinical research unit and then weekly with standard telephone follow-up and diary entries for one month following discharge from the clinical research unit. The return of Lambert-Eaton Myasthenic Syndrome (LEMS)-related signs and symptoms in a withdrawal design was anticipated and therefore adverse events were categorized as (1) treatment emergent adverse events, (2) treatment emergent adverse events excluding LEMS-related signs and symptoms, and (3) LEMS-related signs and symptoms adverse events
General disorders Injection site bruising	7.1% 1/14 • Adverse events were collected during the inpatient stay of up to 7 days on the clinical research unit and then weekly with standard telephone follow-up and diary entries for one month following discharge from the clinical research unit. The return of Lambert-Eaton Myasthenic Syndrome (LEMS)-related signs and symptoms in a withdrawal design was anticipated and therefore adverse events were categorized as (1) treatment emergent adverse events, (2) treatment emergent adverse events excluding LEMS-related signs and symptoms, and (3) LEMS-related signs and symptoms adverse events	0.00% 0/18 • Adverse events were collected during the inpatient stay of up to 7 days on the clinical research unit and then weekly with standard telephone follow-up and diary entries for one month following discharge from the clinical research unit. The return of Lambert-Eaton Myasthenic Syndrome (LEMS)-related signs and symptoms in a withdrawal design was anticipated and therefore adverse events were categorized as (1) treatment emergent adverse events, (2) treatment emergent adverse events excluding LEMS-related signs and symptoms, and (3) LEMS-related signs and symptoms adverse events
General disorders Instillation site irritation	7.1% 1/14 • Adverse events were collected during the inpatient stay of up to 7 days on the clinical research unit and then weekly with standard telephone follow-up and diary entries for one month following discharge from the clinical research unit. The return of Lambert-Eaton Myasthenic Syndrome (LEMS)-related signs and symptoms in a withdrawal design was anticipated and therefore adverse events were categorized as (1) treatment emergent adverse events, (2) treatment emergent adverse events excluding LEMS-related signs and symptoms, and (3) LEMS-related signs and symptoms adverse events	0.00% 0/18 • Adverse events were collected during the inpatient stay of up to 7 days on the clinical research unit and then weekly with standard telephone follow-up and diary entries for one month following discharge from the clinical research unit. The return of Lambert-Eaton Myasthenic Syndrome (LEMS)-related signs and symptoms in a withdrawal design was anticipated and therefore adverse events were categorized as (1) treatment emergent adverse events, (2) treatment emergent adverse events excluding LEMS-related signs and symptoms, and (3) LEMS-related signs and symptoms adverse events
Musculoskeletal and connective tissue disorders Musculoskeletal stiffness	7.1% 1/14 • Adverse events were collected during the inpatient stay of up to 7 days on the clinical research unit and then weekly with standard telephone follow-up and diary entries for one month following discharge from the clinical research unit. The return of Lambert-Eaton Myasthenic Syndrome (LEMS)-related signs and symptoms in a withdrawal design was anticipated and therefore adverse events were categorized as (1) treatment emergent adverse events, (2) treatment emergent adverse events excluding LEMS-related signs and symptoms, and (3) LEMS-related signs and symptoms adverse events	0.00% 0/18 • Adverse events were collected during the inpatient stay of up to 7 days on the clinical research unit and then weekly with standard telephone follow-up and diary entries for one month following discharge from the clinical research unit. The return of Lambert-Eaton Myasthenic Syndrome (LEMS)-related signs and symptoms in a withdrawal design was anticipated and therefore adverse events were categorized as (1) treatment emergent adverse events, (2) treatment emergent adverse events excluding LEMS-related signs and symptoms, and (3) LEMS-related signs and symptoms adverse events
Infections and infestations Oral herpes	7.1% 1/14 • Adverse events were collected during the inpatient stay of up to 7 days on the clinical research unit and then weekly with standard telephone follow-up and diary entries for one month following discharge from the clinical research unit. The return of Lambert-Eaton Myasthenic Syndrome (LEMS)-related signs and symptoms in a withdrawal design was anticipated and therefore adverse events were categorized as (1) treatment emergent adverse events, (2) treatment emergent adverse events excluding LEMS-related signs and symptoms, and (3) LEMS-related signs and symptoms adverse events	0.00% 0/18 • Adverse events were collected during the inpatient stay of up to 7 days on the clinical research unit and then weekly with standard telephone follow-up and diary entries for one month following discharge from the clinical research unit. The return of Lambert-Eaton Myasthenic Syndrome (LEMS)-related signs and symptoms in a withdrawal design was anticipated and therefore adverse events were categorized as (1) treatment emergent adverse events, (2) treatment emergent adverse events excluding LEMS-related signs and symptoms, and (3) LEMS-related signs and symptoms adverse events

Additional Information

Dr. Kathy Aleš, Medical Director

Jacobus Pharmaceutical Company, Inc.

Phone: 6099217447

Email: kathy.ales@jacobus-pharmaceutical.com

Results disclosure agreements

• Principal investigator is a sponsor employee The first publication shall be a multicenter publication submitted after conclusion of the Study at all sites. If a multicenter publication is not submitted within 12 months, PIs may use results. The only other disclosure restriction on the PI is that the Sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period of 30 days for confidential review. This period may be extended by 60 days at Sponsor's request.
• Publication restrictions are in place

Restriction type: OTHER