A 42-day Parallel Group Safety Study of Revefenacin and Formoterol, Administered in Sequence and as a Combination, in Participants With COPD

• Sponsor: Mylan Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03573817
• Collaborator: Theravance Biopharma (Industry)
• Enrollment: 122
• Locations: 12
• Arms: 4
• Actual Duration (Months): 3.8
• Patients Per Site: 10.2
• Patients Per Site Per Month: 2.6

Study Details

Study Description

Brief Summary

The primary objective of the study was to characterize the safety and tolerability of once-daily revefenacin inhalation solution when dosed sequentially with twice-daily formoterol inhalation solution (PERFOROMIST®) compared to PERFOROMIST®, in a population of participants with moderate-to-very severe Chronic Obstructive Pulmonary Disease (COPD) over 21 days.

Condition or Disease	Intervention/Treatment	Phase
Chronic Obstructive Pulmonary Disease (COPD)	Drug: Revefenacin; Drug: Placebo; Drug: Formoterol	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 122 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: This is a randomized, double-blind, placebo-controlled, parallel-group study. Each participant will receive treatment daily for a total of 42 days. One group will receive placebo and formoterol and one group will receive revefenacin and formoterol.This is a randomized, double-blind, placebo-controlled, parallel-group study. Each participant will receive treatment daily for a total of 42 days. One group will receive placebo and formoterol and one group will receive revefenacin and formoterol.
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 3b, 42-day, Randomized, Double-Blind, Placebo Controlled, Parallel Group Study to Evaluate the Safety and Tolerability of Nebulized Revefenacin and Nebulized Formoterol Fumarate (PERFOROMIST®) Administered in Sequence and as a Combined Solution in Subjects With Chronic Obstructive Pulmonary Disease
• Actual Study Start Date: May 31, 2018
• Actual Primary Completion Date: Sep 25, 2018
• Actual Study Completion Date: Sep 25, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Period 1: Revefenacin + Formoterol (Sequential) Days 1 to 21: Revefenacin and formoterol will be sequentially administered in the morning. Formoterol will be administered again in the evening.	Drug: Revefenacin; Revefenacin is administered via a nebulizer.; Other Names: TD-4208 ; Drug: Formoterol; Administered sequentially in both revefenacin and placebo arms using a nebulizer.
Experimental: Period 2: Revefenacin + Formoterol (Combo Solution) Days 22 to 42: After a 21 day period, the participants from the Revefenacin + Formoterol (Sequential) Arm will be dosed for 21 days with a combination of revefenacin and formoterol administered as a combined solution. Formoterol will be administered again in the evening.	Drug: Revefenacin; Revefenacin is administered via a nebulizer.; Other Names: TD-4208 ; Drug: Formoterol; Administered sequentially in both revefenacin and placebo arms using a nebulizer.
Placebo Comparator: Period 1: Placebo + Formoterol (Sequential) Days 1 to 21: Placebo versions of revefenacin and formoterol will be sequentially administered in the morning. Formoterol will be administered again in the evening.	Drug: Placebo; Placebo version of Revefenacin is administered via a nebulizer.; Drug: Formoterol; Administered sequentially in both revefenacin and placebo arms using a nebulizer.
Placebo Comparator: Period 2: Placebo + Formoterol (Combo Solution) Days 22 to 42: After a 21 day period, the participants from Placebo + Formoterol (Sequential) Arm the will be dosed for 21 days with a combination of placebo revefenacin and formoterol administered as a combined solution. Formoterol will be administered again in the evening.	Drug: Placebo; Placebo version of Revefenacin is administered via a nebulizer.; Drug: Formoterol; Administered sequentially in both revefenacin and placebo arms using a nebulizer.

Outcome Measures

Primary Outcome Measures

1. Number of Participants Who Experienced at Least One Treatment-Emergent Adverse Event [Day 1 to End of Period 2, a Maximum of 42 days + 7 days follow-up (Each period was 21 days)]

   An adverse event (AE) was any untoward medical occurrence in a participant administered a pharmaceutical product that did not necessarily have to have a causal relationship with this treatment. A treatment-emergent AE is an AE that occurred after the participant has received the study drug.

2. Number of Participants Who Experienced at Least One Serious Treatment-Emergent Adverse Event [Day 1 to End of Period 2, a Maximum of 42 days + 7 days follow-up (Each period was 21 days)]

   A serious adverse event (SAE) was defined as any untoward medical occurrence occurring at any dose that resulted in any of the following outcomes: Death Life-threatening situation. "Life-threatening" refers to a situation in which the participant was at risk of death at the time of the event; it does not refer to an event which might have caused death if it were more severe Inpatient hospitalization or prolongation of existing hospitalization Congenital anomaly in the offspring of a participant who received study drug Important medical events that may not result in death, be immediately life-threatening, or require hospitalization, could have been considered an SAE when, based upon appropriate medical judgment, they may have jeopardized the participant and may have required medical or surgical intervention to prevent one of the outcomes listed in this definition A treatment-emergent SAE is an SAE that occurred after the participant has received the study drug.

3. Number of Participants With Clinically Relevant Changes in Vital Sign Measurements [Baseline to End of Period 2, a Maximum of 42 days + 7 days follow-up (Each period was 21 days)]

   Clinically significant changes identified based on change from baseline. Vital signs measured included heart rate, systolic blood pressure and diastolic blood pressure.

4. Number of Participants With Clinically Relevant Changes in Clinical Laboratory Measurements [Baseline to End of Period 2, a Maximum of 42 days + 7 days follow-up (Each period was 21 days)]

   Clinically relevant changes identified based on change from baseline. Laboratory Measures assessed included hematology and serum.

5. Number of Participants With Clinically Relevant Changes in Electrocardiogram Results [Baseline to End of Period 2, a Maximum of 42 days + 7 days follow-up (Each period was 21 days)]

   Clinically relevant changes identified based on change from baseline.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Participant is a male or female subject 40 years of age or older.

• Participant is willing and able to provide signed and dated written informed consent.

• Participant has a current or past cigarette smoking history (or equivalent for cigar or pipe smoking history) of at least 10 pack-years.

• Participant must be willing and able to attend study visits according to the visit schedule and adhere to all study assessments/procedures.

Exclusion Criteria:

• Participant has a concurrent disease or condition that, in the opinion of the investigator, would interfere with study participation or confound the evaluation of safety, tolerability, or pharmacokinetics of the study drug.

• Participant has a history of reactions or hypersensitivity to inhaled or nebulized anticholinergics, short-acting beta-agonists and long-acting beta-agonists.

• Participant with clinically significant and uncontrolled hypertension, hypercholesterolemia or Type II diabetes mellitus, as assessed by the investigator.

• Participant is unwilling or unable to stop the use of prohibited medications during the washout (if required) and treatment period and follow-up period of the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Theravance Biopharma Investigational Site	Miami	Florida	United States	33155
2	Theravance Biopharma Investigational Site	Orlando	Florida	United States	32825
3	Theravance Biopharma Investigational Site	Sarasota	Florida	United States	34239
4	Theravance Biopharma Investigational Site	Tampa	Florida	United States	33603
5	Theravance Biopharma Investigational Site	Saint Charles	Missouri	United States	63301
6	Theravance Biopharma Investigational Site	Monroe	North Carolina	United States	28112
7	Theravance Biopharma Investigational Site	Columbus	Ohio	United States	43213
8	Theravance Biopharma Investigational Site	Medford	Oregon	United States	97504
9	Theravance Biopharma Investigational Site	Erie	Pennsylvania	United States	16508
10	Theravance Biopharma Investigational Site	Gaffney	South Carolina	United States	29341
11	Theravance Biopharma Investigational Site	Greenville	South Carolina	United States	29615
12	Theravance Biopharma Investigational Site	Spartanburg	South Carolina	United States	29303

Sponsors and Collaborators

• Mylan Inc.
• Theravance Biopharma

Investigators

• Study Director: Medical Monitor, Theravance Biopharma

Study Documents (Full-Text)

• Study Protocol - Apr 16, 2018
• Statistical Analysis Plan - Oct 1, 2018

More Information

Publications

None provided.

• Responsible Party: Mylan Inc.
• ClinicalTrials.gov Identifier: NCT03573817
• Other Study ID Numbers: 0167
• First Posted: Jun 29, 2018
• Last Update Posted: Feb 24, 2022
• Last Verified: Feb 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Mylan Inc.: Chronic Obstructive Pulmonary Disease; Pulmonary Function; COPD; Performist
• Additional relevant MeSH terms: Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Formoterol Fumarate

Study Results

Participant Flow

Pre-assignment Detail	Participants were randomized 1:1 to one of two treatment groups and received treatment twice-daily for the two 21-day treatment periods. The participants in Arms 1 and 2 are the same (minus attrition), and the participants in Arms 3 and 4 are the same (minus attrition).

Arm/Group Title	Revefenacin + Formoterol	Placebo + Formoterol
Arm/Group Description	Includes participants from Arm 1 (Day 1-21) and Arm 2 (Day 22-42).	Includes participants from Arm 3 (Day 1-21) and Arm 4 (Day 22-42).
Period Title: Overall Study
STARTED	63	59
Randomized and Treated With Study Drug	63	59
COMPLETED	62	55
NOT COMPLETED	1	4

Baseline Characteristics

Arm/Group Title	Revefenacin + Formoterol	Placebo + Formoterol	Total
Arm/Group Description	Includes participants from Arm 1 (Day 1-21) and Arm 2 (Day 22-42).	Includes participants from Arm 3 (Day 1-21) and Arm 4 (Day 22-42).	Total of all reporting groups
Overall Participants	63	59	122
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	63.1 (8.71)	64.4 (8.43)	63.7 (8.56)
Sex: Female, Male (Count of Participants)
Female	28 44.4%	25 42.4%	53 43.4%
Male	35 55.6%	34 57.6%	69 56.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	7 11.1%	3 5.1%	10 8.2%
Not Hispanic or Latino	56 88.9%	56 94.9%	112 91.8%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	2 3.2%	3 5.1%	5 4.1%
White	60 95.2%	56 94.9%	116 95.1%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	1 1.6%	0 0%	1 0.8%
Region of Enrollment (participants) [Number]
United States	63 100%	59 100%	122 100%
Body Mass Index (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	29.22 (6.642)	29.11 (6.349)	29.17 (6.475)

Outcome Measures

1. Primary Outcome

Title	Number of Participants Who Experienced at Least One Treatment-Emergent Adverse Event
Description	An adverse event (AE) was any untoward medical occurrence in a participant administered a pharmaceutical product that did not necessarily have to have a causal relationship with this treatment. A treatment-emergent AE is an AE that occurred after the participant has received the study drug.
Time Frame	Day 1 to End of Period 2, a Maximum of 42 days + 7 days follow-up (Each period was 21 days)

Outcome Measure Data

Analysis Population Description

The populations for Arms 1 and 2 are made up of the same participants, however 4 participants dropped out prior to beginning Period 2. Similarly, the populations for Arms 3 and 4 are made up of the same participants, but one participant dropped out prior to beginning Period 2.

Arm/Group Title	Period 1: Revefenacin + Formoterol (Sequential)	Period 2: Revefenacin + Formoterol (Combo Solution)	Period 1: Placebo + Formoterol (Sequential)	Period 2: Placebo + Formoterol (Combo Solution)
Arm/Group Description	Days 1 to 21: revefenacin and formoterol sequentially administered via nebulizer in the morning. Formoterol will be administered again in the evening. .	Days 22 to 42: After a 21 day period, the participants from the Revefenacin + Formoterol (Sequential) Arm will be dosed for 21 days with a combination of revefenacin and formoterol administered as a combined solution via a single nebulization. Formoterol will be administered again in the evening.	Days 1 to 21: Placebo versions of revefenacin and formoterol will be sequentially administered via nebulizer in the morning. Formoterol will be administered again in the evening.	Days 22 to 42: After a 21 day period, the participants from Placebo + Formoterol (Sequential) Arm the will be dosed for 21 days with a combination of placebo revefenacin and formoterol administered as a combined solution via a single nebulization. Formoterol will be administered again in the evening.
Measure Participants	59	55	63	62
Count of Participants [Participants]	7 11.1%	6 10.2%	3 2.5%	5 NaN

2. Primary Outcome

Title	Number of Participants Who Experienced at Least One Serious Treatment-Emergent Adverse Event
Description	A serious adverse event (SAE) was defined as any untoward medical occurrence occurring at any dose that resulted in any of the following outcomes: Death Life-threatening situation. "Life-threatening" refers to a situation in which the participant was at risk of death at the time of the event; it does not refer to an event which might have caused death if it were more severe Inpatient hospitalization or prolongation of existing hospitalization Congenital anomaly in the offspring of a participant who received study drug Important medical events that may not result in death, be immediately life-threatening, or require hospitalization, could have been considered an SAE when, based upon appropriate medical judgment, they may have jeopardized the participant and may have required medical or surgical intervention to prevent one of the outcomes listed in this definition A treatment-emergent SAE is an SAE that occurred after the participant has received the study drug.
Time Frame	Day 1 to End of Period 2, a Maximum of 42 days + 7 days follow-up (Each period was 21 days)

Outcome Measure Data

Analysis Population Description

The populations for Arms 1 and 2 are made up of the same participants, however 4 participants dropped out prior to beginning Period 2. Similarly, the populations for Arms 3 and 4 are made up of the same participants, but one participant dropped out prior to beginning Period 2.

Arm/Group Title	Period 1: Revefenacin + Formoterol (Sequential)	Period 2: Revefenacin + Formoterol (Combo Solution)	Period 1: Placebo + Formoterol (Sequential)	Period 2: Placebo + Formoterol (Combo Solution)
Arm/Group Description	Days 1 to 21: Revefenacin and formoterol will be sequentially administered via nebulizer in the morning. Formoterol will be administered again in the evening.	Days 22 to 42: After a 21 day period, the participants from the Revefenacin + Formoterol (Sequential) Arm will be dosed for 21 days with a combination of revefenacin and formoterol administered as a combined solution via a single nebulization. Formoterol will be administered again in the evening.	Days 1 to 21: Placebo versions of revefenacin and formoterol will be sequentially administered via nebulizer in the morning. Formoterol will be administered again in the evening.	Days 22 to 42: After a 21 day period, the participants from Placebo + Formoterol (Sequential) Arm the will be dosed for 21 days with a combination of placebo revefenacin and formoterol administered as a combined solution via a single nebulization. Formoterol will be administered again in the evening.
Measure Participants	59	55	63	62
Count of Participants [Participants]	0 0%	0 0%	0 0%	0 NaN

3. Primary Outcome

Title	Number of Participants With Clinically Relevant Changes in Vital Sign Measurements
Description	Clinically significant changes identified based on change from baseline. Vital signs measured included heart rate, systolic blood pressure and diastolic blood pressure.
Time Frame	Baseline to End of Period 2, a Maximum of 42 days + 7 days follow-up (Each period was 21 days)

Outcome Measure Data

Analysis Population Description

The populations for Arms 1 and 2 are made up of the same participants, however 4 participants dropped out prior to beginning Period 2. Similarly, the populations for Arms 3 and 4 are made up of the same participants, but one participant dropped out prior to beginning Period 2.

Arm/Group Title	Period 1: Revefenacin + Formoterol (Sequential)	Period 2: Revefenacin + Formoterol (Combo Solution)	Period 1: Placebo + Formoterol (Sequential)	Period 2: Placebo + Formoterol (Combo Solution)
Arm/Group Description	Days 1 to 21: Revefenacin and formoterol will be sequentially administered via nebulizer in the morning. Formoterol will be administered again in the evening.	Days 22 to 42: After a 21 day period, the participants from the Revefenacin + Formoterol (Sequential) Arm will be dosed for 21 days with a combination of revefenacin and formoterol administered as a combined solution via a single nebulization. Formoterol will be administered again in the evening.	Days 1 to 21: Placebo versions of revefenacin and formoterol will be sequentially administered via nebulizer in the morning. Formoterol will be administered again in the evening.	Days 22 to 42: After a 21 day period, the participants from Placebo + Formoterol (Sequential) Arm the will be dosed for 21 days with a combination of placebo revefenacin and formoterol administered as a combined solution via a single nebulization. Formoterol will be administered again in the evening.
Measure Participants	59	55	63	62
Count of Participants [Participants]	0 0%	0 0%	0 0%	0 NaN

4. Primary Outcome

Title	Number of Participants With Clinically Relevant Changes in Clinical Laboratory Measurements
Description	Clinically relevant changes identified based on change from baseline. Laboratory Measures assessed included hematology and serum.
Time Frame	Baseline to End of Period 2, a Maximum of 42 days + 7 days follow-up (Each period was 21 days)

Outcome Measure Data

Analysis Population Description

The populations for Arms 1 and 2 are made up of the same participants, however 4 participants dropped out prior to beginning Period 2. Similarly, the populations for Arms 3 and 4 are made up of the same participants, but one participant dropped out prior to beginning Period 2.

Arm/Group Title	Period 1: Revefenacin + Formoterol (Sequential)	Period 2: Revefenacin + Formoterol (Combo Solution)	Period 1: Placebo + Formoterol (Sequential)	Period 2: Placebo + Formoterol (Combo Solution)
Arm/Group Description	Days 1 to 21: Revefenacin and formoterol will be sequentially administered via nebulizer in the morning. Formoterol will be administered again in the evening.	Days 22 to 42: After a 21 day period, the participants from the Revefenacin + Formoterol (Sequential) Arm will be dosed for 21 days with a combination of revefenacin and formoterol administered as a combined solution via a single nebulization. Formoterol will be administered again in the evening.	Days 1 to 21: Placebo versions of revefenacin and formoterol will be sequentially administered via nebulizer in the morning. Formoterol will be administered again in the evening.	Days 22 to 42: After a 21 day period, the participants from Placebo + Formoterol (Sequential) Arm the will be dosed for 21 days with a combination of placebo revefenacin and formoterol administered as a combined solution via a single nebulization. Formoterol will be administered again in the evening.
Measure Participants	59	55	63	62
Count of Participants [Participants]	0 0%	0 0%	0 0%	0 NaN

5. Primary Outcome

Title	Number of Participants With Clinically Relevant Changes in Electrocardiogram Results
Description	Clinically relevant changes identified based on change from baseline.
Time Frame	Baseline to End of Period 2, a Maximum of 42 days + 7 days follow-up (Each period was 21 days)

Outcome Measure Data

Analysis Population Description

The populations for Arms 1 and 2 are made up of the same participants, however 4 participants dropped out prior to beginning Period 2. Similarly, the populations for Arms 3 and 4 are made up of the same participants, but one participant dropped out prior to beginning Period 2.

Arm/Group Title	Period 1: Revefenacin + Formoterol (Sequential)	Period 2: Revefenacin + Formoterol (Combo Solution)	Period 1: Placebo + Formoterol (Sequential)	Period 2: Placebo + Formoterol (Combo Solution)
Arm/Group Description	Days 1 to 21: Revefenacin and formoterol will be sequentially administered via nebulizer in the morning. Formoterol will be administered again in the evening.	Days 22 to 42: After a 21 day period, the participants from the Revefenacin + Formoterol (Sequential) Arm will be dosed for 21 days with a combination of revefenacin and formoterol administered as a combined solution via a single nebulization. Formoterol will be administered again in the evening.	Days 1 to 21: Placebo versions of revefenacin and formoterol will be sequentially administered via nebulizer in the morning. Formoterol will be administered again in the evening.	Days 22 to 42: After a 21 day period, the participants from Placebo + Formoterol (Sequential) Arm the will be dosed for 21 days with a combination of placebo revefenacin and formoterol administered as a combined solution via a single nebulization. Formoterol will be administered again in the evening.
Measure Participants	59	55	63	62
Count of Participants [Participants]	0 0%	0 0%	0 0%	0 NaN

Adverse Events

Time Frame	Period 1: Day 1 to Day 21; Period 2: Day 22 to 42 (+7 days follow-up)
Adverse Event Reporting Description	An adverse event was any untoward medical occurrence in a participant administered a pharmaceutical product that did not necessarily have to have a causal relationship with this treatment.
Arm/Group Title	Period 1: Revefenacin + Formoterol (Sequential)		Period 2: Revefenacin + Formoterol (Combo Solution)		Period 1: Placebo + Formoterol (Sequential)		Period 2: Placebo + Formoterol (Combo Solution)
Arm/Group Description	Days 1 to 21: Revefenacin and formoterol will be sequentially administered via nebulizer in the morning. Formoterol will be administered again in the evening.		Days 22 to 42: After a 21 day period, the participants from the Revefenacin + Formoterol (Sequential) Arm will be dosed for 21 days with a combination of revefenacin and formoterol administered as a combined solution via a single nebulization. Formoterol will be administered again in the evening.		Days 1 to 21: Placebo versions of revefenacin and formoterol will be sequentially administered via nebulizer in the morning. Formoterol will be administered again in the evening.		Days 22 to 42: After a 21 day period, the participants from Placebo + Formoterol (Sequential) Arm the will be dosed for 21 days with a combination of placebo revefenacin and formoterol administered as a combined solution via a single nebulization. Formoterol will be administered again in the evening.
All Cause Mortality
	Period 1: Revefenacin + Formoterol (Sequential)		Period 2: Revefenacin + Formoterol (Combo Solution)		Period 1: Placebo + Formoterol (Sequential)		Period 2: Placebo + Formoterol (Combo Solution)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/59 (0%)		0/55 (0%)		0/63 (0%)		0/62 (0%)
Serious Adverse Events
	Period 1: Revefenacin + Formoterol (Sequential)		Period 2: Revefenacin + Formoterol (Combo Solution)		Period 1: Placebo + Formoterol (Sequential)		Period 2: Placebo + Formoterol (Combo Solution)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/59 (0%)		0/55 (0%)		0/63 (0%)		0/62 (0%)
Other (Not Including Serious) Adverse Events
	Period 1: Revefenacin + Formoterol (Sequential)		Period 2: Revefenacin + Formoterol (Combo Solution)		Period 1: Placebo + Formoterol (Sequential)		Period 2: Placebo + Formoterol (Combo Solution)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/63 (4.8%)		5/62 (8.1%)		7/59 (11.9%)		6/55 (10.9%)
Eye disorders
Lacrimation increased	0/63 (0%)		0/62 (0%)		1/59 (1.7%)		0/55 (0%)
Gastrointestinal disorders
Abdominal discomfort	0/63 (0%)		0/62 (0%)		0/59 (0%)		1/55 (1.8%)
Oral discomfort	1/63 (1.6%)		0/62 (0%)		0/59 (0%)		0/55 (0%)
General disorders
Peripheral swelling	0/63 (0%)		0/62 (0%)		0/59 (0%)		1/55 (1.8%)
Infections and infestations
Sputum purulent	0/63 (0%)		1/62 (1.6%)		0/59 (0%)		0/55 (0%)
Tooth infection	1/63 (1.6%)		0/62 (0%)		0/59 (0%)		0/55 (0%)
Viral infection	0/63 (0%)		1/62 (1.6%)		0/59 (0%)		0/55 (0%)
Viral upper respiratory tract infection	0/63 (0%)		0/62 (0%)		1/59 (1.7%)		0/55 (0%)
Acute sinusitis	0/63 (0%)		1/62 (1.6%)		0/59 (0%)		0/55 (0%)
Cystitis	0/63 (0%)		0/62 (0%)		0/59 (0%)		1/55 (1.8%)
Injury, poisoning and procedural complications
Muscle contusion	0/63 (0%)		1/62 (1.6%)		0/59 (0%)		0/55 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/63 (0%)		0/62 (0%)		0/59 (0%)		1/55 (1.8%)
Pain in extremity	0/63 (0%)		1/62 (1.6%)		0/59 (0%)		0/55 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lipoma	0/63 (0%)		0/62 (0%)		1/59 (1.7%)		0/55 (0%)
Nervous system disorders
Dizziness	0/63 (0%)		0/62 (0%)		2/59 (3.4%)		0/55 (0%)
Headache	0/63 (0%)		0/62 (0%)		1/59 (1.7%)		0/55 (0%)
Psychiatric disorders
Insomnia	1/63 (1.6%)		0/62 (0%)		0/59 (0%)		0/55 (0%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	0/63 (0%)		1/62 (1.6%)		2/59 (3.4%)		0/55 (0%)
Cough	0/63 (0%)		0/62 (0%)		0/59 (0%)		2/55 (3.6%)
Oropharyngeal pain	1/63 (1.6%)		0/62 (0%)		0/59 (0%)		1/55 (1.8%)
Skin and subcutaneous tissue disorders
Skin lesion	0/63 (0%)		1/62 (1.6%)		0/59 (0%)		0/55 (0%)
Vascular disorders
Hypertension	0/63 (0%)		0/62 (0%)		1/59 (1.7%)		0/55 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The PI may communicate the trial results generated by the PI, but only after the first publication or presentation of the combined study results generated by all participating sites. The Sponsor can then review trial results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The Sponsor cannot require changes to the communication and cannot extend the embargo.