Trial Outcomes & Findings for Multicenter Study to Evaluate the Efficacy and Safety of Metoclopramide Nasal Spray in Women With Diabetic Gastroparesis (NCT NCT02025725)

NCT ID: NCT02025725

Last Updated: 2020-07-07

Results Overview

Change from the Baseline Period to Week 4 of the Treatment Period in the mean daily Gastroparesis Symptom Assessment (GSA) total score for subjects receiving Metoclopramide Nasal Spray 10 mg versus subjects receiving placebo. The GSA minimum value is 0 (no symptoms) and the maximum value is 4 (very severe symptoms). A higher score is a worse outcome.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

205 participants

Primary outcome timeframe

Baseline Period to Week 4 of the Treatment Period

Results posted on

2020-07-07

Participant Flow

Recruitment Period: 27 March 2014 to 27 May 2016 Types of Location: Medical Clinics, University-Based Practices Screening Period consisted of Washout Period, Qualification Period and Baseline Period. Mean daily Gastroparesis Symptom Assessment (GSA) total score ≥ 1.4 and ≤ 3.5 was required during Qualification and Baseline periods

613 participants Screened, 205 participants completed and randomized to treatment. Negative Gastric Emptying Scintigraphy 129 Inclusion/Exclusion Failed 213 Withdrawal by participant 25 Other Reasons 41

Participant milestones

Participant milestones
Measure	10 mg Metoclopramide Nasal Spray Metoclopramide Nasal Spray 10 mg, 30 minutes before meals and at bedtime (QID) for 4 weeks Metoclopramide Nasal Spray: nasal spray formulation of metoclopramide	Placebo Nasal Spray Placebo Nasal Spray 30 minutes before meals and at bedtime (QID) for 4 weeks Placebo Nasal Spray: nasal spray formulation with vehicle only
Overall Study STARTED	102	103
Overall Study COMPLETED	91	99
Overall Study NOT COMPLETED	11	4

Reasons for withdrawal

Reasons for withdrawal
Measure	10 mg Metoclopramide Nasal Spray Metoclopramide Nasal Spray 10 mg, 30 minutes before meals and at bedtime (QID) for 4 weeks Metoclopramide Nasal Spray: nasal spray formulation of metoclopramide	Placebo Nasal Spray Placebo Nasal Spray 30 minutes before meals and at bedtime (QID) for 4 weeks Placebo Nasal Spray: nasal spray formulation with vehicle only
Overall Study Adverse Event	5	0
Overall Study Lost to Follow-up	2	0
Overall Study Protocol Violation	1	1
Overall Study Withdrawal by Subject	3	2
Overall Study Post-dose QTcB > 270 msec	0	1

Baseline Characteristics

Multicenter Study to Evaluate the Efficacy and Safety of Metoclopramide Nasal Spray in Women With Diabetic Gastroparesis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	10 mg Metoclopramide Nasal Spray n=102 Participants Metoclopramide Nasal Spray 10 mg, 30 minutes before meals and at bedtime (QID) for 4 weeks Metoclopramide Nasal Spray: nasal spray formulation of metoclopramide	Placebo Nasal Spray n=103 Participants Placebo Nasal Spray 30 minutes before meals and at bedtime (QID) for 4 weeks Placebo Nasal Spray: nasal spray formulation with vehicle only	Total n=205 Participants Total of all reporting groups
Age, Categorical Age (years) · <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Age (years) · Between 18 and 65 years	87 Participants n=5 Participants	90 Participants n=7 Participants	177 Participants n=5 Participants
Age, Categorical Age (years) · >=65 years	15 Participants n=5 Participants	13 Participants n=7 Participants	28 Participants n=5 Participants
Age, Continuous	52.9 Years STANDARD_DEVIATION 11.6 • n=5 Participants	52.5 Years STANDARD_DEVIATION 10.9 • n=7 Participants	52.7 Years STANDARD_DEVIATION 11.2 • n=5 Participants
Sex: Female, Male Female	102 Participants n=5 Participants	103 Participants n=7 Participants	205 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	11 Participants n=5 Participants	14 Participants n=7 Participants	25 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	91 Participants n=5 Participants	89 Participants n=7 Participants	180 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	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants	0 Participants n=7 Participants	2 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	20 Participants n=5 Participants	37 Participants n=7 Participants	57 Participants n=5 Participants
Race (NIH/OMB) White	78 Participants n=5 Participants	63 Participants n=7 Participants	141 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	102 Participants n=5 Participants	103 Participants n=7 Participants	205 Participants n=5 Participants
Qualification Mean Daily GSA Score	2.259 units on a scale STANDARD_DEVIATION 0.481 • n=5 Participants	2.242 units on a scale STANDARD_DEVIATION 0.487 • n=7 Participants	2.251 units on a scale STANDARD_DEVIATION 0.483 • n=5 Participants
Baseline Mean Daily GSA Score	2.28 units on a scale STANDARD_DEVIATION 0.518 • n=5 Participants	2.30 units on a scale STANDARD_DEVIATION 0.552 • n=7 Participants	2.29 units on a scale STANDARD_DEVIATION 0.53 • n=5 Participants
Diabetes Mellitus Type Type 1	13 Participants n=5 Participants	11 Participants n=7 Participants	24 Participants n=5 Participants
Diabetes Mellitus Type Type 2	89 Participants n=5 Participants	92 Participants n=7 Participants	181 Participants n=5 Participants
Diabetes Mellitus Duration	12.4 years STANDARD_DEVIATION 10.51 • n=5 Participants	13.4 years STANDARD_DEVIATION 10.9 • n=7 Participants	12.9 years STANDARD_DEVIATION 10.7 • n=5 Participants
Current Diabetes Mellitus Treatment Diet	30 Participants n=5 Participants	33 Participants n=7 Participants	63 Participants n=5 Participants
Current Diabetes Mellitus Treatment Oral Diabetic Medications	69 Participants n=5 Participants	74 Participants n=7 Participants	143 Participants n=5 Participants
Current Diabetes Mellitus Treatment Insulin	51 Participants n=5 Participants	54 Participants n=7 Participants	105 Participants n=5 Participants
Current Diabetes Mellitus Treatment Other	11 Participants n=5 Participants	17 Participants n=7 Participants	28 Participants n=5 Participants
Current Diabetes Mellitus Treatment None	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Co-Existing Complications of Diabetes No Complications	64 Participants n=5 Participants	60 Participants n=7 Participants	124 Participants n=5 Participants
Co-Existing Complications of Diabetes Any Complication	38 Participants n=5 Participants	41 Participants n=7 Participants	79 Participants n=5 Participants
Co-Existing Complications of Diabetes Diabetic Retinopathy	7 Participants n=5 Participants	2 Participants n=7 Participants	9 Participants n=5 Participants
Co-Existing Complications of Diabetes Neuropathy	35 Participants n=5 Participants	39 Participants n=7 Participants	74 Participants n=5 Participants
Co-Existing Complications of Diabetes Nephropathy	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Co-Existing Complications of Diabetes Peripheral Vascular Disease/Amputation	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline Period to Week 4 of the Treatment Period

Population: Intent-to-Treat (ITT) Population

Outcome measures

Outcome measures
Measure	10 mg Metoclopramide Nasal Spray n=102 Participants Metoclopramide Nasal Spray 10 mg, 30 minutes before meals and at bedtime for 4 weeks Metoclopramide Nasal Spray: nasal spray formulation of metoclopramide	Placebo Nasal Spray n=103 Participants Placebo Nasal Spray 30 minutes before meals and at bedtime for 4 weeks Placebo Nasal Spray: nasal spray formulation with vehicle only
Gastroparesis Symptom Assessment (GSA), a Patient Reported Outcome Measure	-0.925 score on a scale Standard Deviation 0.935	-0.896 score on a scale Standard Deviation 0.947

POST_HOC outcome

Timeframe: Baseline Period to Weeks 1, 2, 3 and 4 of the Treatment Period

Population: Subjects in the intent-to-treat population with moderate to severe disease (symptoms) at Baseline (i.e., baseline GSA scores higher than 2.7 on the 0-4 scale). Results presented are Weeks 1, 2, 3 and 4 compared to the Baseline Period.

Change from the Baseline Period to Weeks 1, 2, 3 and 4 of the Treatment Period in the mean daily Gastroparesis Symptom Assessment (GSA) total score in subjects with moderate to severe symptoms at Baseline (GSA score greater than 2.7) receiving Metoclopramide Nasal Spray 10 mg versus subjects receiving placebo. The GSA minimum value is 0 (no symptoms) and the maximum value is 4 (very severe symptoms). A higher score is a worse outcome.

Outcome measures

Outcome measures
Measure	10 mg Metoclopramide Nasal Spray n=52 Participants Metoclopramide Nasal Spray 10 mg, 30 minutes before meals and at bedtime for 4 weeks Metoclopramide Nasal Spray: nasal spray formulation of metoclopramide	Placebo Nasal Spray n=53 Participants Placebo Nasal Spray 30 minutes before meals and at bedtime for 4 weeks Placebo Nasal Spray: nasal spray formulation with vehicle only
Gastroparesis Symptom Assessment (GSA) Week 1 of Treatment compared to Baseline Period	-0.587 score on a scale Standard Deviation 0.520	-0.388 score on a scale Standard Deviation 0.444
Gastroparesis Symptom Assessment (GSA) Week 2 of Treatment compared to Baseline Period	-0.949 score on a scale Standard Deviation 0.864	-0.616 score on a scale Standard Deviation 0.635
Gastroparesis Symptom Assessment (GSA) Week 3 of Treatment compared to Baseline Period	-1.095 score on a scale Standard Deviation 0.912	-0.750 score on a scale Standard Deviation 0.785
Gastroparesis Symptom Assessment (GSA) Week 4 of Treatment compared to Baseline Period	-1.218 score on a scale Standard Deviation 0.991	-0.857 score on a scale Standard Deviation 0.938

Adverse Events

10 mg Metoclopramide Nasal Spray

Serious events: 3 serious events

Other events: 21 other events

Deaths: 0 deaths

Placebo Nasal Spray

Serious events: 2 serious events

Other events: 36 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	10 mg Metoclopramide Nasal Spray n=102 participants at risk Metoclopramide Nasal Spray 10 mg, 30 minutes before meals and at bedtime for 4 weeks Metoclopramide Nasal Spray: nasal spray formulation of metoclopramide	Placebo Nasal Spray n=103 participants at risk Placebo Nasal Spray 30 minutes before meals and at bedtime for 4 weeks Placebo Nasal Spray: nasal spray formulation with vehicle only
Vascular disorders orthostatic hypotension	0.98% 1/102 • Number of events 1 • Adverse Event (AE) data were collected through the last study visit (Day 28). Serious AEs (SAEs) were collected for up to 30 days after the final dose of study drug. Adverse event (AE) collection began after subjects signed the Informed Consent Form and continued until the subject was discharged from the study due to completion or Early Termination. All AEs observed by the Investigator, reported by the subject, from laboratory findings, or other means, were collected. AEs after the first dose of study drug were classified as treatment-emergent AEs.	0.00% 0/103 • Adverse Event (AE) data were collected through the last study visit (Day 28). Serious AEs (SAEs) were collected for up to 30 days after the final dose of study drug. Adverse event (AE) collection began after subjects signed the Informed Consent Form and continued until the subject was discharged from the study due to completion or Early Termination. All AEs observed by the Investigator, reported by the subject, from laboratory findings, or other means, were collected. AEs after the first dose of study drug were classified as treatment-emergent AEs.
Infections and infestations cellulitis	0.98% 1/102 • Number of events 1 • Adverse Event (AE) data were collected through the last study visit (Day 28). Serious AEs (SAEs) were collected for up to 30 days after the final dose of study drug. Adverse event (AE) collection began after subjects signed the Informed Consent Form and continued until the subject was discharged from the study due to completion or Early Termination. All AEs observed by the Investigator, reported by the subject, from laboratory findings, or other means, were collected. AEs after the first dose of study drug were classified as treatment-emergent AEs.	0.00% 0/103 • Adverse Event (AE) data were collected through the last study visit (Day 28). Serious AEs (SAEs) were collected for up to 30 days after the final dose of study drug. Adverse event (AE) collection began after subjects signed the Informed Consent Form and continued until the subject was discharged from the study due to completion or Early Termination. All AEs observed by the Investigator, reported by the subject, from laboratory findings, or other means, were collected. AEs after the first dose of study drug were classified as treatment-emergent AEs.
Eye disorders chalazion	0.98% 1/102 • Number of events 1 • Adverse Event (AE) data were collected through the last study visit (Day 28). Serious AEs (SAEs) were collected for up to 30 days after the final dose of study drug. Adverse event (AE) collection began after subjects signed the Informed Consent Form and continued until the subject was discharged from the study due to completion or Early Termination. All AEs observed by the Investigator, reported by the subject, from laboratory findings, or other means, were collected. AEs after the first dose of study drug were classified as treatment-emergent AEs.	0.00% 0/103 • Adverse Event (AE) data were collected through the last study visit (Day 28). Serious AEs (SAEs) were collected for up to 30 days after the final dose of study drug. Adverse event (AE) collection began after subjects signed the Informed Consent Form and continued until the subject was discharged from the study due to completion or Early Termination. All AEs observed by the Investigator, reported by the subject, from laboratory findings, or other means, were collected. AEs after the first dose of study drug were classified as treatment-emergent AEs.
Psychiatric disorders anxiety disorder	0.00% 0/102 • Adverse Event (AE) data were collected through the last study visit (Day 28). Serious AEs (SAEs) were collected for up to 30 days after the final dose of study drug. Adverse event (AE) collection began after subjects signed the Informed Consent Form and continued until the subject was discharged from the study due to completion or Early Termination. All AEs observed by the Investigator, reported by the subject, from laboratory findings, or other means, were collected. AEs after the first dose of study drug were classified as treatment-emergent AEs.	0.97% 1/103 • Number of events 1 • Adverse Event (AE) data were collected through the last study visit (Day 28). Serious AEs (SAEs) were collected for up to 30 days after the final dose of study drug. Adverse event (AE) collection began after subjects signed the Informed Consent Form and continued until the subject was discharged from the study due to completion or Early Termination. All AEs observed by the Investigator, reported by the subject, from laboratory findings, or other means, were collected. AEs after the first dose of study drug were classified as treatment-emergent AEs.
General disorders non-cardiac chest pain	0.00% 0/102 • Adverse Event (AE) data were collected through the last study visit (Day 28). Serious AEs (SAEs) were collected for up to 30 days after the final dose of study drug. Adverse event (AE) collection began after subjects signed the Informed Consent Form and continued until the subject was discharged from the study due to completion or Early Termination. All AEs observed by the Investigator, reported by the subject, from laboratory findings, or other means, were collected. AEs after the first dose of study drug were classified as treatment-emergent AEs.	0.97% 1/103 • Number of events 1 • Adverse Event (AE) data were collected through the last study visit (Day 28). Serious AEs (SAEs) were collected for up to 30 days after the final dose of study drug. Adverse event (AE) collection began after subjects signed the Informed Consent Form and continued until the subject was discharged from the study due to completion or Early Termination. All AEs observed by the Investigator, reported by the subject, from laboratory findings, or other means, were collected. AEs after the first dose of study drug were classified as treatment-emergent AEs.

Other adverse events

Additional Information

Chief Medical Officer

Evoke

Phone: 858-345-1494

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Measure	10 mg Metoclopramide Nasal Spray n=102 participants at risk Metoclopramide Nasal Spray 10 mg, 30 minutes before meals and at bedtime for 4 weeks Metoclopramide Nasal Spray: nasal spray formulation of metoclopramide	Placebo Nasal Spray n=103 participants at risk Placebo Nasal Spray 30 minutes before meals and at bedtime for 4 weeks Placebo Nasal Spray: nasal spray formulation with vehicle only
Nervous system disorders Headache	4.9% 5/102 • Number of events 6 • Adverse Event (AE) data were collected through the last study visit (Day 28). Serious AEs (SAEs) were collected for up to 30 days after the final dose of study drug. Adverse event (AE) collection began after subjects signed the Informed Consent Form and continued until the subject was discharged from the study due to completion or Early Termination. All AEs observed by the Investigator, reported by the subject, from laboratory findings, or other means, were collected. AEs after the first dose of study drug were classified as treatment-emergent AEs.	6.8% 7/103 • Number of events 9 • Adverse Event (AE) data were collected through the last study visit (Day 28). Serious AEs (SAEs) were collected for up to 30 days after the final dose of study drug. Adverse event (AE) collection began after subjects signed the Informed Consent Form and continued until the subject was discharged from the study due to completion or Early Termination. All AEs observed by the Investigator, reported by the subject, from laboratory findings, or other means, were collected. AEs after the first dose of study drug were classified as treatment-emergent AEs.
Gastrointestinal disorders Abdominal pain	0.98% 1/102 • Number of events 1 • Adverse Event (AE) data were collected through the last study visit (Day 28). Serious AEs (SAEs) were collected for up to 30 days after the final dose of study drug. Adverse event (AE) collection began after subjects signed the Informed Consent Form and continued until the subject was discharged from the study due to completion or Early Termination. All AEs observed by the Investigator, reported by the subject, from laboratory findings, or other means, were collected. AEs after the first dose of study drug were classified as treatment-emergent AEs.	4.9% 5/103 • Number of events 5 • Adverse Event (AE) data were collected through the last study visit (Day 28). Serious AEs (SAEs) were collected for up to 30 days after the final dose of study drug. Adverse event (AE) collection began after subjects signed the Informed Consent Form and continued until the subject was discharged from the study due to completion or Early Termination. All AEs observed by the Investigator, reported by the subject, from laboratory findings, or other means, were collected. AEs after the first dose of study drug were classified as treatment-emergent AEs.
Gastrointestinal disorders Abdominal tenderness	0.98% 1/102 • Number of events 1 • Adverse Event (AE) data were collected through the last study visit (Day 28). Serious AEs (SAEs) were collected for up to 30 days after the final dose of study drug. Adverse event (AE) collection began after subjects signed the Informed Consent Form and continued until the subject was discharged from the study due to completion or Early Termination. All AEs observed by the Investigator, reported by the subject, from laboratory findings, or other means, were collected. AEs after the first dose of study drug were classified as treatment-emergent AEs.	1.9% 2/103 • Number of events 2 • Adverse Event (AE) data were collected through the last study visit (Day 28). Serious AEs (SAEs) were collected for up to 30 days after the final dose of study drug. Adverse event (AE) collection began after subjects signed the Informed Consent Form and continued until the subject was discharged from the study due to completion or Early Termination. All AEs observed by the Investigator, reported by the subject, from laboratory findings, or other means, were collected. AEs after the first dose of study drug were classified as treatment-emergent AEs.
Gastrointestinal disorders Constipation	0.98% 1/102 • Number of events 1 • Adverse Event (AE) data were collected through the last study visit (Day 28). Serious AEs (SAEs) were collected for up to 30 days after the final dose of study drug. Adverse event (AE) collection began after subjects signed the Informed Consent Form and continued until the subject was discharged from the study due to completion or Early Termination. All AEs observed by the Investigator, reported by the subject, from laboratory findings, or other means, were collected. AEs after the first dose of study drug were classified as treatment-emergent AEs.	1.9% 2/103 • Number of events 2 • Adverse Event (AE) data were collected through the last study visit (Day 28). Serious AEs (SAEs) were collected for up to 30 days after the final dose of study drug. Adverse event (AE) collection began after subjects signed the Informed Consent Form and continued until the subject was discharged from the study due to completion or Early Termination. All AEs observed by the Investigator, reported by the subject, from laboratory findings, or other means, were collected. AEs after the first dose of study drug were classified as treatment-emergent AEs.
Gastrointestinal disorders Diarrhoea	2.9% 3/102 • Number of events 3 • Adverse Event (AE) data were collected through the last study visit (Day 28). Serious AEs (SAEs) were collected for up to 30 days after the final dose of study drug. Adverse event (AE) collection began after subjects signed the Informed Consent Form and continued until the subject was discharged from the study due to completion or Early Termination. All AEs observed by the Investigator, reported by the subject, from laboratory findings, or other means, were collected. AEs after the first dose of study drug were classified as treatment-emergent AEs.	0.00% 0/103 • Adverse Event (AE) data were collected through the last study visit (Day 28). Serious AEs (SAEs) were collected for up to 30 days after the final dose of study drug. Adverse event (AE) collection began after subjects signed the Informed Consent Form and continued until the subject was discharged from the study due to completion or Early Termination. All AEs observed by the Investigator, reported by the subject, from laboratory findings, or other means, were collected. AEs after the first dose of study drug were classified as treatment-emergent AEs.
Respiratory, thoracic and mediastinal disorders Cough	0.98% 1/102 • Number of events 1 • Adverse Event (AE) data were collected through the last study visit (Day 28). Serious AEs (SAEs) were collected for up to 30 days after the final dose of study drug. Adverse event (AE) collection began after subjects signed the Informed Consent Form and continued until the subject was discharged from the study due to completion or Early Termination. All AEs observed by the Investigator, reported by the subject, from laboratory findings, or other means, were collected. AEs after the first dose of study drug were classified as treatment-emergent AEs.	3.9% 4/103 • Number of events 4 • Adverse Event (AE) data were collected through the last study visit (Day 28). Serious AEs (SAEs) were collected for up to 30 days after the final dose of study drug. Adverse event (AE) collection began after subjects signed the Informed Consent Form and continued until the subject was discharged from the study due to completion or Early Termination. All AEs observed by the Investigator, reported by the subject, from laboratory findings, or other means, were collected. AEs after the first dose of study drug were classified as treatment-emergent AEs.
Respiratory, thoracic and mediastinal disorders Nasal discomfort	0.98% 1/102 • Number of events 1 • Adverse Event (AE) data were collected through the last study visit (Day 28). Serious AEs (SAEs) were collected for up to 30 days after the final dose of study drug. Adverse event (AE) collection began after subjects signed the Informed Consent Form and continued until the subject was discharged from the study due to completion or Early Termination. All AEs observed by the Investigator, reported by the subject, from laboratory findings, or other means, were collected. AEs after the first dose of study drug were classified as treatment-emergent AEs.	3.9% 4/103 • Number of events 4 • Adverse Event (AE) data were collected through the last study visit (Day 28). Serious AEs (SAEs) were collected for up to 30 days after the final dose of study drug. Adverse event (AE) collection began after subjects signed the Informed Consent Form and continued until the subject was discharged from the study due to completion or Early Termination. All AEs observed by the Investigator, reported by the subject, from laboratory findings, or other means, were collected. AEs after the first dose of study drug were classified as treatment-emergent AEs.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.98% 1/102 • Number of events 1 • Adverse Event (AE) data were collected through the last study visit (Day 28). Serious AEs (SAEs) were collected for up to 30 days after the final dose of study drug. Adverse event (AE) collection began after subjects signed the Informed Consent Form and continued until the subject was discharged from the study due to completion or Early Termination. All AEs observed by the Investigator, reported by the subject, from laboratory findings, or other means, were collected. AEs after the first dose of study drug were classified as treatment-emergent AEs.	1.9% 2/103 • Number of events 2 • Adverse Event (AE) data were collected through the last study visit (Day 28). Serious AEs (SAEs) were collected for up to 30 days after the final dose of study drug. Adverse event (AE) collection began after subjects signed the Informed Consent Form and continued until the subject was discharged from the study due to completion or Early Termination. All AEs observed by the Investigator, reported by the subject, from laboratory findings, or other means, were collected. AEs after the first dose of study drug were classified as treatment-emergent AEs.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	2.0% 2/102 • Number of events 2 • Adverse Event (AE) data were collected through the last study visit (Day 28). Serious AEs (SAEs) were collected for up to 30 days after the final dose of study drug. Adverse event (AE) collection began after subjects signed the Informed Consent Form and continued until the subject was discharged from the study due to completion or Early Termination. All AEs observed by the Investigator, reported by the subject, from laboratory findings, or other means, were collected. AEs after the first dose of study drug were classified as treatment-emergent AEs.	0.00% 0/103 • Adverse Event (AE) data were collected through the last study visit (Day 28). Serious AEs (SAEs) were collected for up to 30 days after the final dose of study drug. Adverse event (AE) collection began after subjects signed the Informed Consent Form and continued until the subject was discharged from the study due to completion or Early Termination. All AEs observed by the Investigator, reported by the subject, from laboratory findings, or other means, were collected. AEs after the first dose of study drug were classified as treatment-emergent AEs.
Infections and infestations Pharyngitis	0.00% 0/102 • Adverse Event (AE) data were collected through the last study visit (Day 28). Serious AEs (SAEs) were collected for up to 30 days after the final dose of study drug. Adverse event (AE) collection began after subjects signed the Informed Consent Form and continued until the subject was discharged from the study due to completion or Early Termination. All AEs observed by the Investigator, reported by the subject, from laboratory findings, or other means, were collected. AEs after the first dose of study drug were classified as treatment-emergent AEs.	1.9% 2/103 • Number of events 2 • Adverse Event (AE) data were collected through the last study visit (Day 28). Serious AEs (SAEs) were collected for up to 30 days after the final dose of study drug. Adverse event (AE) collection began after subjects signed the Informed Consent Form and continued until the subject was discharged from the study due to completion or Early Termination. All AEs observed by the Investigator, reported by the subject, from laboratory findings, or other means, were collected. AEs after the first dose of study drug were classified as treatment-emergent AEs.
Infections and infestations Upper respiratory tract infection	0.00% 0/102 • Adverse Event (AE) data were collected through the last study visit (Day 28). Serious AEs (SAEs) were collected for up to 30 days after the final dose of study drug. Adverse event (AE) collection began after subjects signed the Informed Consent Form and continued until the subject was discharged from the study due to completion or Early Termination. All AEs observed by the Investigator, reported by the subject, from laboratory findings, or other means, were collected. AEs after the first dose of study drug were classified as treatment-emergent AEs.	1.9% 2/103 • Number of events 2 • Adverse Event (AE) data were collected through the last study visit (Day 28). Serious AEs (SAEs) were collected for up to 30 days after the final dose of study drug. Adverse event (AE) collection began after subjects signed the Informed Consent Form and continued until the subject was discharged from the study due to completion or Early Termination. All AEs observed by the Investigator, reported by the subject, from laboratory findings, or other means, were collected. AEs after the first dose of study drug were classified as treatment-emergent AEs.
Musculoskeletal and connective tissue disorders Muscle twitching	2.0% 2/102 • Number of events 3 • Adverse Event (AE) data were collected through the last study visit (Day 28). Serious AEs (SAEs) were collected for up to 30 days after the final dose of study drug. Adverse event (AE) collection began after subjects signed the Informed Consent Form and continued until the subject was discharged from the study due to completion or Early Termination. All AEs observed by the Investigator, reported by the subject, from laboratory findings, or other means, were collected. AEs after the first dose of study drug were classified as treatment-emergent AEs.	0.97% 1/103 • Number of events 1 • Adverse Event (AE) data were collected through the last study visit (Day 28). Serious AEs (SAEs) were collected for up to 30 days after the final dose of study drug. Adverse event (AE) collection began after subjects signed the Informed Consent Form and continued until the subject was discharged from the study due to completion or Early Termination. All AEs observed by the Investigator, reported by the subject, from laboratory findings, or other means, were collected. AEs after the first dose of study drug were classified as treatment-emergent AEs.
General disorders Fatigue	2.0% 2/102 • Number of events 2 • Adverse Event (AE) data were collected through the last study visit (Day 28). Serious AEs (SAEs) were collected for up to 30 days after the final dose of study drug. Adverse event (AE) collection began after subjects signed the Informed Consent Form and continued until the subject was discharged from the study due to completion or Early Termination. All AEs observed by the Investigator, reported by the subject, from laboratory findings, or other means, were collected. AEs after the first dose of study drug were classified as treatment-emergent AEs.	0.97% 1/103 • Number of events 1 • Adverse Event (AE) data were collected through the last study visit (Day 28). Serious AEs (SAEs) were collected for up to 30 days after the final dose of study drug. Adverse event (AE) collection began after subjects signed the Informed Consent Form and continued until the subject was discharged from the study due to completion or Early Termination. All AEs observed by the Investigator, reported by the subject, from laboratory findings, or other means, were collected. AEs after the first dose of study drug were classified as treatment-emergent AEs.
General disorders Non-cardiac chest pain	0.00% 0/102 • Adverse Event (AE) data were collected through the last study visit (Day 28). Serious AEs (SAEs) were collected for up to 30 days after the final dose of study drug. Adverse event (AE) collection began after subjects signed the Informed Consent Form and continued until the subject was discharged from the study due to completion or Early Termination. All AEs observed by the Investigator, reported by the subject, from laboratory findings, or other means, were collected. AEs after the first dose of study drug were classified as treatment-emergent AEs.	1.9% 2/103 • Number of events 2 • Adverse Event (AE) data were collected through the last study visit (Day 28). Serious AEs (SAEs) were collected for up to 30 days after the final dose of study drug. Adverse event (AE) collection began after subjects signed the Informed Consent Form and continued until the subject was discharged from the study due to completion or Early Termination. All AEs observed by the Investigator, reported by the subject, from laboratory findings, or other means, were collected. AEs after the first dose of study drug were classified as treatment-emergent AEs.
Skin and subcutaneous tissue disorders Skin exfoliation	0.00% 0/102 • Adverse Event (AE) data were collected through the last study visit (Day 28). Serious AEs (SAEs) were collected for up to 30 days after the final dose of study drug. Adverse event (AE) collection began after subjects signed the Informed Consent Form and continued until the subject was discharged from the study due to completion or Early Termination. All AEs observed by the Investigator, reported by the subject, from laboratory findings, or other means, were collected. AEs after the first dose of study drug were classified as treatment-emergent AEs.	1.9% 2/103 • Number of events 2 • Adverse Event (AE) data were collected through the last study visit (Day 28). Serious AEs (SAEs) were collected for up to 30 days after the final dose of study drug. Adverse event (AE) collection began after subjects signed the Informed Consent Form and continued until the subject was discharged from the study due to completion or Early Termination. All AEs observed by the Investigator, reported by the subject, from laboratory findings, or other means, were collected. AEs after the first dose of study drug were classified as treatment-emergent AEs.
Ear and labyrinth disorders Ear pain	2.0% 2/102 • Number of events 2 • Adverse Event (AE) data were collected through the last study visit (Day 28). Serious AEs (SAEs) were collected for up to 30 days after the final dose of study drug. Adverse event (AE) collection began after subjects signed the Informed Consent Form and continued until the subject was discharged from the study due to completion or Early Termination. All AEs observed by the Investigator, reported by the subject, from laboratory findings, or other means, were collected. AEs after the first dose of study drug were classified as treatment-emergent AEs.	0.00% 0/103 • Adverse Event (AE) data were collected through the last study visit (Day 28). Serious AEs (SAEs) were collected for up to 30 days after the final dose of study drug. Adverse event (AE) collection began after subjects signed the Informed Consent Form and continued until the subject was discharged from the study due to completion or Early Termination. All AEs observed by the Investigator, reported by the subject, from laboratory findings, or other means, were collected. AEs after the first dose of study drug were classified as treatment-emergent AEs.