A Study to Evaluate the Safety and Clinical Study of Azelaic Acid Gel 15% in Patients With Moderate Facial Rosacea

• Sponsor: Actavis Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02120924
• Collaborator: (none)
• Enrollment: 1,009
• Locations: 30
• Arms: 3
• Duration (Months): 14
• Patients Per Site: 33.6
• Patients Per Site Per Month: 2.4

Study Details

Study Description

Brief Summary

The purpose of the study is to compare the safety and efficacy profiles of a generic Azelaic Acid Gel, 15% to the reference listed Finacea® (azelaic acid) Gel, 15% in the treatment of moderate facial rosacea.

Condition or Disease	Intervention/Treatment	Phase
Rosacea	Drug: Azelaic acid; Drug: Vehicle; Drug: Finacea	Phase 3

Detailed Description

FINACEA® (azelaic acid) GEL, 15% contains azelaic acid, a naturally occurring saturated dicarboxylic acid that has proven anti-inflammatory effects, as well as anti-keratinizing and antimicrobial action, although its mechanism of action in rosacea is not well understood. This study will be conducted in compliance with the protocol, Good Clinical Practices (GCP) and the applicable regulatory requirement(s). Marketed by Intendis, Finacea® (azelaic acid) Gel, 15% is a safe and effective topical therapy used for the treatment of moderate facial rosacea. Watson Laboratories, Inc. has developed a generic formulation of azelaic acid 15% gel and the current study is designed to evaluate the safety and efficacy of this formulation.

Study Design

• Study Type: Interventional
• Actual Enrollment: 1009 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Double-blind, Randomized, Parallel-group, Vehicle-Controlled Study to Evaluate the Safety and Clinical Equivalence of a Generic Azelaic Acid Gel, 15% and the Reference Listed Finacea® (Azelaic Acid) Gel, 15% in Patients With Moderate Facial Rosacea.
• Study Start Date: Jul 1, 2013
• Actual Primary Completion Date: Sep 1, 2014
• Actual Study Completion Date: Sep 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Finacea Finacea® (azelaic acid) Gel, 15% (Intendis)	Drug: Finacea; Dosage form: Topical gel Dosage: Apply gel to the affected areas of the face twice daily for 12 weeks. The amount needed depends upon the size of the lesion site. Assure that enough is applied to adequately cover each lesion. Normally 0.5 g of gel is used on each 5 cm x 5 cm lesion site.; Other Names: Finacea® (azelaic acid) Gel, 15% (Intendis)
Experimental: Azelaic Acid Azelaic Acid, 15% topical gel (Watson Laboratories, Inc.)	Drug: Azelaic acid; Dosage form: Topical gel Dosage: Apply gel to the affected areas of the face twice daily for 12 weeks. The amount needed depends upon the size of the lesion site. Assure that enough is applied to adequately cover each lesion. Normally 0.5 g of gel is used on each 5 cm x 5 cm lesion site.; Other Names: Generic
Placebo Comparator: Vehicle Gel Gel Vehicle of the test product (Watson Laboratories, Inc.)	Drug: Vehicle; Dosage form: Topical gel Dosage: Apply gel to the affected areas of the face twice daily for 12 weeks. The amount needed depends upon the size of the lesion site. Assure that enough is applied to adequately cover each lesion. Normally 0.5 g of gel is used on each 5 cm x 5 cm lesion site.; Other Names: Placebo

Outcome Measures

Primary Outcome Measures

1. Percent Change From Baseline to Week 12 in the Inflammatory (Papules and Pustules) Lesion Counts. [Baseline to Week 12]

   Percent change from baseline to Week 12 in the inflammatory (papules and pustules) lesion counts in PP population.

Secondary Outcome Measures

1. The Percentage of Subjects With a Clinical Response of "Success" at Week 12 Using Investigator Global Evaluation (IGE) [Baseline to 12 weeks]

   The secondary endpoint is the clinical response of "success" or "failure" at Week 12 on the IGE. Success is defined as an IGE score of 0 (clear) or 1 (almost clear). Any subject who is not considered to be a success will be considered to be a failure. Score-Grade-Definition 0 - Clear - No inflammatory lesions present; at most, mild erythema. - Almost Clear - Very mild erythema present. Very few small papules/pustules. - Mild - Mild erythema. Several small papules/pustules. - Moderate - Moderate erythema. Several small or large papules/pustules, and up to two nodules. - Severe - Severe erythema. Numerous small and/or large papules/pustules, up to several nodules.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Healthy male or non-pregnant female ≥18 years-of-age with a clinical diagnosis of moderate facial rosacea.

• Patient must have at least eight and not more than fifty inflammatory facial lesions (i.e., papules/pustules) and ≤2 nodules on the face. For the purposes of study treatment and evaluation, these lesions should be limited to the facial treatment area including those present on the nose. Lesions involving the eyes, and scalp should be excluded from the count.

• Patients must have persistent erythema on the face with moderate (Definite redness, easily recognized) to Severe (Marked erythema; fiery red).

• Patients must have a mild to moderate score for telangiectasia on the face - Patients must have a definite clinical diagnosis of moderate facial rosacea as per the IGE

• Patient must be willing to minimize external factors that might trigger rosacea flare-ups (e.g., spicy foods, thermally hot foods and drinks, hot environments, prolonged sun exposure, strong winds and alcoholic beverages).

• Patient must be in general good health and free from any clinically significant disease other than rosacea, that might interfere with the study evaluations.

• Patient must be willing and able to understand and comply with the requirements of the study, apply the medication as instructed, return for the required treatment period visits, comply with therapy prohibitions, and be able to complete the study.

• Female Subjects of childbearing potential (excluding women who are surgicallysterilized or postmenopausal for at least 1 year), in addition to having a negative urine pregnancy test, must be willing to use an acceptable form of birth control during the study from the day of the first dose administration to 30 days after the last administration of study drug For the purpose of this study the following are considered acceptable methods of birth control: oral contraceptives, contraceptive patches, contraceptive implant, vaginal contraceptive, double barrier methods (e.g., condom and spermicide), contraceptive injection (Depo-provera®), intrauterine device (IUD), hormonal IUD (Mirena®) and abstinence with a documented second acceptable method of birth control, should the patient become sexually active. Patients on hormonal contraception must be stabilized on the same type for at least three months prior to enrollment in the study and must not change the hormonal contraception during the study. Patients who had used hormonal contraception and stopped must have stopped no less than three months prior to the study. A sterile sexual partner is NOT considered an adequate form of birth control.

• All male patients must agree to use accepted methods of birth control with their partners, from the day of the first dose administration to 30 days after the last administration of study drug. Abstinence is an acceptable method of birth control. Female partners should use an acceptable method of birth control as described in the above Item Number 10.

• Patients who use make-up must have used the same brands/types of make-up for a minimum period of 14 days prior to study entry and must agree to use the same make-up, brand/type, or frequency of use, throughout the study.

Exclusion Criteria:

• Pregnant or lactating or planning to become pregnant during the study period.

• Presence of any skin condition on the face that would interfere with the diagnosis or assessment of rosacea.

• Excessive facial hair (e.g. beards, sideburns, moustaches, etc.) that would interfere with diagnosis or assessment of rosacea.

• History of hypersensitivity or allergy to azelaic acid, propylene glycol or any other component of the formulation.

• The use within 6 months prior to baseline of oral retinoids (e.g. Accutane®) or therapeutic vitamin A supplements of greater than 10,000 units/day (multivitamins are allowed).

• The use of estrogens or oral contraceptives for less than 3 months prior to baseline.

• The use within 1 month prior to baseline of:

1. topical retinoids to the face;

2. systemic antibiotics known to have an impact on the severity of facial rosacea (e.g., containing tetracycline and its derivatives, erythromycin and its derivatives, sulfamethoxazole, or trimethoprim);

3. systemic corticosteroids (Note: intranasal and inhalational corticosteroids do not require a washout and maybe used throughout the trial if the subject is on a stable dose).

• Use within 2 weeks prior to baseline of:

1. topical corticosteroids;

2. topical antibiotics;

3. topical medications for rosacea (e.g., metronidazole).

• Patients with moderate or severe rhinophyma, dense telangiectases (score 3, severe), or plaque-like facial edema.

• Patients with a severe irritation grade for erythema, dryness, scaling, pruritus, stinging/burning, and edema.

• Ocular rosacea (e.g., conjunctivitis, blepharitis, or keratitis) of sufficient severity to require topical or systemic antibiotics.

• A patient who has used a sauna during the 2 weeks prior to study entry and during the study.

• Patients who have performed wax epilation of the face within 14 days prior to baseline

• A patient who has a history of being unresponsive to topical azelaic acid therapy.

• A patient with bacterial folliculitis.

• A patient who consumes excessive alcohol, abuses licit or illicit drugs, or has a condition that could compromise the patient's ability to comply with study requirements.

• Patients who engage in activities that involve excessive or prolonged exposure to sunlight or weather extremes, such as wind or cold.

• A patient who has any clinically significant condition or situation, other than the condition being studied that, in the opinion of the Investigator, would interfere with the study evaluations or optimal participation in the study.

• A patient who has used any topical azelaic acid therapy within 30 days of baseline visit.

• Patients who have participated in an investigational drug study (i.e., patients have been treated with an Investigational Drug) within 30 days prior to baseline will be excluded from study participation. Patients who are participating in non-treatment studies such as observational studies or registry studies can be considered for inclusion.

• Patients who have been previously enrolled in this study.

• Patients who have had laser therapy (for telangiectasia or other conditions), electrodessication and phototherapy (e.g., ClearLight®) to the facial area within 180 days prior to study entry.

• Patients who have had cosmetic procedures (e.g., facials) which may affect the efficacy and safety profile of the Investigational Product within 14 days prior to study entry.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Site 24	Fremont	California	United States
2	Site 22	Santa Monica	California	United States
3	Site 1	Brandon	Florida	United States
4	Site 3	Fort Myers	Florida	United States
5	Site 27	Jacksonville	Florida	United States
6	Site 19	Miami	Florida	United States
7	Site 9	Miami	Florida	United States
8	Site 29	Miramar	Florida	United States
9	Site 2	Tampa	Florida	United States
10	Site 15	Chicago	Illinois	United States
11	Site 4	Plainfield	Indiana	United States
12	Site 14	Lake Charles	Louisiana	United States
13	Site 17	Glenn Dale	Maryland	United States
14	Site 6	Bay City	Michigan	United States
15	Site 30	Clinton Township	Michigan	United States
16	Site 16	Las Vegas	Nevada	United States
17	Site 11	Raleigh	North Carolina	United States
18	Site 23	Winston-Salem	North Carolina	United States
19	Site 26	Philadelphia	Pennsylvania	United States
20	Site 12	Warwick	Rhode Island	United States
21	Site 28	Simpsonville	South Carolina	United States
22	Site 20	Nashville	Tennessee	United States
23	Site 21	College Station	Texas	United States
24	Site 5	Dallas	Texas	United States
25	Site 8	El Paso	Texas	United States
26	Site 13	Houston	Texas	United States
27	Site 7	Katy	Texas	United States
28	Site 18	Salt Lake City	Utah	United States
29	Site 10	Norfolk	Virginia	United States
30	Site 25	University Place	Virginia	United States

Sponsors and Collaborators

• Actavis Inc.

Investigators

• Study Director: John Capicchioni, Akesis, LLC

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Actavis Inc.
• ClinicalTrials.gov Identifier: NCT02120924
• Other Study ID Numbers: 13-1014
• First Posted: Apr 23, 2014
• Last Update Posted: Jun 2, 2020
• Last Verified: May 1, 2020

• Keywords provided by Actavis Inc.: Moderate facial rosacea; Azelaic acid; Rosacea
• Additional relevant MeSH terms: Rosacea; Azelaic acid

Study Results

Participant Flow

Arm/Group Title	Azelaic Acid, 15% Topical Gel	Finacea® (Azelaic Acid) Gel, 15% (Intendis)	Gel Vehicle
Arm/Group Description	Test product: Azelaic Acid, 15% topical gel (Watson Laboratories, Inc.) Azelaic acid: Dosage form: Topical gel Dosage: Apply gel to the affected areas of the face twice daily for 12 weeks. The amount needed depends upon the size of the lesion site. Assure that enough is applied to adequately cover each lesion. Normally 0.5 g of gel is used on each 5 cm x 5 cm lesion site.	Reference product: Finacea® (azelaic acid) Gel, 15% (Intendis) Azelaic acid: Dosage form: Topical gel Dosage: Apply gel to the affected areas of the face twice daily for 12 weeks. The amount needed depends upon the size of the lesion site. Assure that enough is applied to adequately cover each lesion. Normally 0.5 g of gel is used on each 5 cm x 5 cm lesion site.	Placebo product: Gel Vehicle of the test product (Watson Laboratories, Inc.) Azelaic acid: Dosage form: Topical gel Dosage: Apply gel to the affected areas of the face twice daily for 12 weeks. The amount needed depends upon the size of the lesion site. Assure that enough is applied to adequately cover each lesion. Normally 0.5 g of gel is used on each 5 cm x 5 cm lesion site.
Period Title: Overall Study
STARTED	404	403	202
COMPLETED	362	357	173
NOT COMPLETED	42	46	29

Baseline Characteristics

Arm/Group Title	Azelaic Acid, 15% Topical Gel	Finacea® (Azelaic Acid) Gel, 15%	Gel Vehicle	Total
Arm/Group Description	Test product: Azelaic Acid, 15% topical gel (Watson Laboratories, Inc.) Azelaic acid: Dosage form: Topical gel Dosage: Apply gel to the affected areas of the face twice daily for 12 weeks. The amount needed depends upon the size of the lesion site. Assure that enough is applied to adequately cover each lesion. Normally 0.5 g of gel is used on each 5 cm x 5 cm lesion site.	Reference product: Finacea® (azelaic acid) Gel, 15% (Intendis) Azelaic acid: Dosage form: Topical gel Dosage: Apply gel to the affected areas of the face twice daily for 12 weeks. The amount needed depends upon the size of the lesion site. Assure that enough is applied to adequately cover each lesion. Normally 0.5 g of gel is used on each 5 cm x 5 cm lesion site.	Placebo product: Gel Vehicle of the test product (Watson Laboratories, Inc.) Azelaic acid: Dosage form: Topical gel Dosage: Apply gel to the affected areas of the face twice daily for 12 weeks. The amount needed depends upon the size of the lesion site. Assure that enough is applied to adequately cover each lesion. Normally 0.5 g of gel is used on each 5 cm x 5 cm lesion site.	Total of all reporting groups
Overall Participants	293	274	127	694
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	51.4 (12.71)	50.0 (12.42)	51.4 (11.73)	50.8 (12.42)
Sex: Female, Male (Count of Participants)
Female	195 66.6%	195 71.2%	89 70.1%	479 69%
Male	98 33.4%	79 28.8%	38 29.9%	215 31%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	118 40.3%	126 46%	59 46.5%	303 43.7%
Not Hispanic or Latino	175 59.7%	148 54%	68 53.5%	391 56.3%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	3 1%	2 0.7%	1 0.8%	6 0.9%
Native Hawaiian or Other Pacific Islander	0 0%	1 0.4%	0 0%	1 0.1%
Black or African American	0 0%	0 0%	0 0%	0 0%
White	280 95.6%	263 96%	124 97.6%	667 96.1%
More than one race	10 3.4%	8 2.9%	2 1.6%	20 2.9%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Percent Change From Baseline to Week 12 in the Inflammatory (Papules and Pustules) Lesion Counts.
Description	Percent change from baseline to Week 12 in the inflammatory (papules and pustules) lesion counts in PP population.
Time Frame	Baseline to Week 12

Outcome Measure Data

Analysis Population Description

Per protocol population

Arm/Group Title	Azelaic Acid, 15% Topical Gel	Finacea® (Azelaic Acid) Gel, 15%	Gel Vehicle
Arm/Group Description	Test product: Azelaic Acid, 15% topical gel (Watson Laboratories, Inc.) Azelaic acid: Dosage form: Topical gel Dosage: Apply gel to the affected areas of the face twice daily for 12 weeks. The amount needed depends upon the size of the lesion site. Assure that enough is applied to adequately cover each lesion. Normally 0.5 g of gel is used on each 5 cm x 5 cm lesion site.	Reference product: Finacea® (azelaic acid) Gel, 15% (Intendis) Azelaic acid: Dosage form: Topical gel Dosage: Apply gel to the affected areas of the face twice daily for 12 weeks. The amount needed depends upon the size of the lesion site. Assure that enough is applied to adequately cover each lesion. Normally 0.5 g of gel is used on each 5 cm x 5 cm lesion site.	Placebo product (Watson Laboratories, Inc.) Azelaic acid: Dosage form: Topical gel Dosage: Apply gel to the affected areas of the face twice daily for 12 weeks. The amount needed depends upon the size of the lesion site. Assure that enough is applied to adequately cover each lesion. Normally 0.5 g of gel is used on each 5 cm x 5 cm lesion site.
Measure Participants	293	274	127
Mean (Standard Deviation) [Percent change in lesion counts]	-66.96 (29.394)	-68.62 (27.415)	-38.64 (46.845)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azelaic Acid, 15% Topical Gel, Finacea® (Azelaic Acid) Gel, 15%
	Comments	The primary endpoint was the percent change from baseline to Week 12 in the inflammatory (papules and pustules) lesion counts in PP population.
	Type of Statistical Test	Equivalence
	Comments	Bioequivalence was established if the 90% CI for the ratio of Test/Reference means was contained within the interval [0.80, 1.25].
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.98
	Confidence Interval	(2-Sided) 90%; 0.92 to 1.05
	Parameter Dispersion	Type: Value:
	Estimation Comments	Bioequivalence was established if the 90% CI for the ratio of Test/Reference means was contained within the interval [0.80, 1.25].

2. Secondary Outcome

Title	The Percentage of Subjects With a Clinical Response of "Success" at Week 12 Using Investigator Global Evaluation (IGE)
Description	The secondary endpoint is the clinical response of "success" or "failure" at Week 12 on the IGE. Success is defined as an IGE score of 0 (clear) or 1 (almost clear). Any subject who is not considered to be a success will be considered to be a failure. Score-Grade-Definition 0 - Clear - No inflammatory lesions present; at most, mild erythema. - Almost Clear - Very mild erythema present. Very few small papules/pustules. - Mild - Mild erythema. Several small papules/pustules. - Moderate - Moderate erythema. Several small or large papules/pustules, and up to two nodules. - Severe - Severe erythema. Numerous small and/or large papules/pustules, up to several nodules.
Time Frame	Baseline to 12 weeks

Outcome Measure Data

Analysis Population Description

Analysis of Treatment Success Based on IGE Score at Week 12 in PP Population.

Arm/Group Title	Azelaic Acid, 15% Topical Gel	Finacea® (Azelaic Acid) Gel, 15%	Gel Vehicle
Arm/Group Description	Test product: Azelaic Acid, 15% topical gel (Watson Laboratories, Inc.) Azelaic acid: Dosage form: Topical gel Dosage: Apply gel to the affected areas of the face twice daily for 12 weeks. The amount needed depends upon the size of the lesion site. Assure that enough is applied to adequately cover each lesion. Normally 0.5 g of gel is used on each 5 cm x 5 cm lesion site.	Reference product: Finacea® (azelaic acid) Gel, 15% (Intendis) Azelaic acid: Dosage form: Topical gel Dosage: Apply gel to the affected areas of the face twice daily for 12 weeks. The amount needed depends upon the size of the lesion site. Assure that enough is applied to adequately cover each lesion. Normally 0.5 g of gel is used on each 5 cm x 5 cm lesion site.	Placebo product: Gel Vehicle of the test product (Watson Laboratories, Inc.) Azelaic acid: Dosage form: Topical gel Dosage: Apply gel to the affected areas of the face twice daily for 12 weeks. The amount needed depends upon the size of the lesion site. Assure that enough is applied to adequately cover each lesion. Normally 0.5 g of gel is used on each 5 cm x 5 cm lesion site.
Measure Participants	293	274	127
Success	138 47.1%	117 42.7%	40 31.5%
Failure	155 52.9%	157 57.3%	87 68.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Azelaic Acid, 15% Topical Gel, Finacea® (Azelaic Acid) Gel, 15%
	Comments
	Type of Statistical Test	Equivalence
	Comments	A two-sided, continuity-corrected, 90% CI on the Test-to-Reference difference for the proportion of subjects with treatment success on the IGE was constructed.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.044
	Confidence Interval	(2-Sided) 90%; -0.028 to 0.116
	Parameter Dispersion	Type: Value:
	Estimation Comments	Bioequivalence was established if the 90% CI for the difference was contained within the interval [-0.20, +0.20].

Adverse Events

Time Frame	Adverse events were monitored and collected over a period of at least 12 weeks, through to study completion.
Arm/Group Title	Azelaic Acid, 15% Topical Gel		Finacea® (Azelaic Acid) Gel, 15%		Gel Vehicle
Arm/Group Description	Test product: Azelaic Acid, 15% topical gel (Watson Laboratories, Inc.) Azelaic acid: Dosage form: Topical gel Dosage: Apply gel to the affected areas of the face twice daily for 12 weeks. The amount needed depends upon the size of the lesion site. Assure that enough is applied to adequately cover each lesion. Normally 0.5 g of gel is used on each 5 cm x 5 cm lesion site.		Reference product: Finacea® (azelaic acid) Gel, 15% (Intendis) Azelaic acid: Dosage form: Topical gel Dosage: Apply gel to the affected areas of the face twice daily for 12 weeks. The amount needed depends upon the size of the lesion site. Assure that enough is applied to adequately cover each lesion. Normally 0.5 g of gel is used on each 5 cm x 5 cm lesion site.		Placebo product: Gel Vehicle of the test product (Watson Laboratories, Inc.) Azelaic acid: Dosage form: Topical gel Dosage: Apply gel to the affected areas of the face twice daily for 12 weeks. The amount needed depends upon the size of the lesion site. Assure that enough is applied to adequately cover each lesion. Normally 0.5 g of gel is used on each 5 cm x 5 cm lesion site.
All Cause Mortality
	Azelaic Acid, 15% Topical Gel		Finacea® (Azelaic Acid) Gel, 15%		Gel Vehicle
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/390 (0.3%)		0/386 (0%)		0/190 (0%)
Serious Adverse Events
	Azelaic Acid, 15% Topical Gel		Finacea® (Azelaic Acid) Gel, 15%		Gel Vehicle
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/390 (0.3%)		0/386 (0%)		0/190 (0%)
Cardiac disorders
Cardiac failure congestive	1/390 (0.3%)		0/386 (0%)		0/190 (0%)
Other (Not Including Serious) Adverse Events
	Azelaic Acid, 15% Topical Gel		Finacea® (Azelaic Acid) Gel, 15%		Gel Vehicle
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	109/390 (27.9%)		98/386 (25.4%)		47/190 (24.7%)
Blood and lymphatic system disorders
Anaemia	0/390 (0%)		1/386 (0.3%)		0/190 (0%)
Cardiac disorders
Cardiac failure congestive	1/390 (0.3%)		0/386 (0%)		0/190 (0%)
Ear and labyrinth disorders
Ear pain	1/390 (0.3%)		0/386 (0%)		1/190 (0.5%)
Vertigo	1/390 (0.3%)		0/386 (0%)		0/190 (0%)
Endocrine disorders
Hypothyroidism	0/390 (0%)		0/386 (0%)		1/190 (0.5%)
Eye disorders
Blepharospasm	1/390 (0.3%)		0/386 (0%)		0/190 (0%)
Eye irritation	1/390 (0.3%)		0/386 (0%)		0/190 (0%)
Eye pain	1/390 (0.3%)		0/386 (0%)		0/190 (0%)
Eye pruritus	0/390 (0%)		1/386 (0.3%)		0/190 (0%)
Foreign body sensation in eye	1/390 (0.3%)		0/386 (0%)		0/190 (0%)
Lacrimation increased	1/390 (0.3%)		1/386 (0.3%)		0/190 (0%)
Vision blurred	1/390 (0.3%)		0/386 (0%)		0/190 (0%)
Gastrointestinal disorders
Abdominal discomfort	0/390 (0%)		0/386 (0%)		2/190 (1.1%)
Abdominal pain	1/390 (0.3%)		1/386 (0.3%)		0/190 (0%)
Abdominal pain lower	1/390 (0.3%)		0/386 (0%)		1/190 (0.5%)
Abdominal pain upper	3/390 (0.8%)		3/386 (0.8%)		0/190 (0%)
Aphthous stomatitis	0/390 (0%)		1/386 (0.3%)		0/190 (0%)
Diarrhoea	2/390 (0.5%)		5/386 (1.3%)		2/190 (1.1%)
Dyspepsia	1/390 (0.3%)		5/386 (1.3%)		0/190 (0%)
Gastroesophageal reflux disease	1/390 (0.3%)		1/386 (0.3%)		1/190 (0.5%)
Haemorrhoids	0/390 (0%)		1/386 (0.3%)		1/190 (0.5%)
Mouth ulceration	1/390 (0.3%)		0/386 (0%)		0/190 (0%)
Nausea	5/390 (1.3%)		1/386 (0.3%)		0/190 (0%)
Tooth crowding	1/390 (0.3%)		0/386 (0%)		0/190 (0%)
Toothache	0/390 (0%)		2/386 (0.5%)		1/190 (0.5%)
Vomiting	1/390 (0.3%)		4/386 (1%)		0/190 (0%)
General disorders
Adverse drug reaction	0/390 (0%)		0/386 (0%)		1/190 (0.5%)
Application site pain	2/390 (0.5%)		1/386 (0.3%)		1/190 (0.5%)
Application site pruritus	1/390 (0.3%)		0/386 (0%)		0/190 (0%)
Chills	0/390 (0%)		1/386 (0.3%)		1/190 (0.5%)
Fatigue	2/390 (0.5%)		2/386 (0.5%)		0/190 (0%)
Feeling hot	1/390 (0.3%)		0/386 (0%)		0/190 (0%)
Influenza like illness	0/390 (0%)		3/386 (0.8%)		1/190 (0.5%)
Local swelling	1/390 (0.3%)		0/386 (0%)		0/190 (0%)
Malaise	0/390 (0%)		1/386 (0.3%)		0/190 (0%)
Pain	2/390 (0.5%)		3/386 (0.8%)		1/190 (0.5%)
Pyrexia	2/390 (0.5%)		0/386 (0%)		0/190 (0%)
Hepatobiliary disorders
Biliary colic	1/390 (0.3%)		0/386 (0%)		0/190 (0%)
Cholelithiasis	1/390 (0.3%)		0/386 (0%)		0/190 (0%)
Immune system disorders
Hypersensitivity	1/390 (0.3%)		0/386 (0%)		1/190 (0.5%)
Seasonal allergy	0/390 (0%)		1/386 (0.3%)		0/190 (0%)
Infections and infestations
Acute sinusitis	1/390 (0.3%)		0/386 (0%)		0/190 (0%)
Alveolar osteitis	0/390 (0%)		1/386 (0.3%)		0/190 (0%)
Atypical pnuemonia	0/390 (0%)		0/386 (0%)		1/190 (0.5%)
Bacterial infection	0/390 (0%)		1/386 (0.3%)		0/190 (0%)
Bronchitis	0/390 (0%)		3/386 (0.8%)		1/190 (0.5%)
Cellulitis	0/390 (0%)		0/386 (0%)		1/190 (0.5%)
Conjunctivitis bacterial	1/390 (0.3%)		0/386 (0%)		0/190 (0%)
Conjunctivitis infective	0/390 (0%)		1/386 (0.3%)		0/190 (0%)
Ear infection	2/390 (0.5%)		0/386 (0%)		0/190 (0%)
Eye infection	0/390 (0%)		1/386 (0.3%)		0/190 (0%)
Fungal infection	0/390 (0%)		1/386 (0.3%)		0/190 (0%)
Gastroenteritis	0/390 (0%)		1/386 (0.3%)		0/190 (0%)
Gastroenteritis viral	0/390 (0%)		3/386 (0.8%)		0/190 (0%)
Herpes simplex	0/390 (0%)		1/386 (0.3%)		0/190 (0%)
Hordeolum	0/390 (0%)		1/386 (0.3%)		0/190 (0%)
Influenza	6/390 (1.5%)		4/386 (1%)		1/190 (0.5%)
Kidney infection	0/390 (0%)		1/386 (0.3%)		0/190 (0%)
Lyme disease	0/390 (0%)		0/386 (0%)		1/190 (0.5%)
Nasopharyngitis	27/390 (6.9%)		19/386 (4.9%)		9/190 (4.7%)
Oral herpes	0/390 (0%)		1/386 (0.3%)		0/190 (0%)
Pertussis	1/390 (0.3%)		1/386 (0.3%)		0/190 (0%)
Pharyngitis	0/390 (0%)		1/386 (0.3%)		0/190 (0%)
Pharyngitis streptococcal	1/390 (0.3%)		0/386 (0%)		0/190 (0%)
Sinusitis	6/390 (1.5%)		7/386 (1.8%)		1/190 (0.5%)
Skin infection	0/390 (0%)		0/386 (0%)		1/190 (0.5%)
Subcutaneous abscess	1/390 (0.3%)		0/386 (0%)		0/190 (0%)
Tonsillitus	0/390 (0%)		1/386 (0.3%)		0/190 (0%)
Tooth abscess	0/390 (0%)		0/386 (0%)		1/190 (0.5%)
Upper respiratory tract infection	3/390 (0.8%)		5/386 (1.3%)		3/190 (1.6%)
Urinary tract infection	0/390 (0%)		1/386 (0.3%)		0/190 (0%)
Injury, poisoning and procedural complications
Foot fracture	0/390 (0%)		1/386 (0.3%)		0/190 (0%)
Foreign body	1/390 (0.3%)		0/386 (0%)		0/190 (0%)
Post procedural complication	0/390 (0%)		1/386 (0.3%)		0/190 (0%)
Spinal column injury	1/390 (0.3%)		0/386 (0%)		0/190 (0%)
Sunburn	0/390 (0%)		1/386 (0.3%)		0/190 (0%)
Investigations
Blood cholesterol increased	0/390 (0%)		1/386 (0.3%)		0/190 (0%)
Heart rate increased	0/390 (0%)		1/386 (0.3%)		0/190 (0%)
Metabolism and nutrition disorders
Hypercholesterolaemia	1/390 (0.3%)		0/386 (0%)		0/190 (0%)
Vitamin D deficiency	1/390 (0.3%)		0/386 (0%)		0/190 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	2/390 (0.5%)		1/386 (0.3%)		1/190 (0.5%)
Back pain	4/390 (1%)		5/386 (1.3%)		0/190 (0%)
Invertebral disc protrusion	1/390 (0.3%)		0/386 (0%)		0/190 (0%)
Muscle spasms	0/390 (0%)		1/386 (0.3%)		2/190 (1.1%)
Muscoloskeletal pain	1/390 (0.3%)		0/386 (0%)		0/190 (0%)
Myalgia	2/390 (0.5%)		1/386 (0.3%)		0/190 (0%)
Osteoarthritis	1/390 (0.3%)		0/386 (0%)		0/190 (0%)
Rotator cuff syndrome	0/390 (0%)		1/386 (0.3%)		0/190 (0%)
Nervous system disorders
Burning sensation	4/390 (1%)		5/386 (1.3%)		0/190 (0%)
Dizziness	1/390 (0.3%)		0/386 (0%)		0/190 (0%)
Dizziness exertional	0/390 (0%)		1/386 (0.3%)		0/190 (0%)
Headache	23/390 (5.9%)		23/386 (6%)		11/190 (5.8%)
Migraine	3/390 (0.8%)		2/386 (0.5%)		3/190 (1.6%)
Nerve compression	0/390 (0%)		1/386 (0.3%)		0/190 (0%)
Neuropathy peripheral	0/390 (0%)		1/386 (0.3%)		0/190 (0%)
Paraesthesia	0/390 (0%)		1/386 (0.3%)		0/190 (0%)
Sinus headache	0/390 (0%)		1/386 (0.3%)		1/190 (0.5%)
Tension headache	0/390 (0%)		1/386 (0.3%)		0/190 (0%)
Transient ischaemic attack	1/390 (0.3%)		0/386 (0%)		0/190 (0%)
Psychiatric disorders
Anxiety	1/390 (0.3%)		1/386 (0.3%)		0/190 (0%)
Renal and urinary disorders
Hypertonic bladder	0/390 (0%)		1/386 (0.3%)		0/190 (0%)
Nephrolithiasis	1/390 (0.3%)		0/386 (0%)		0/190 (0%)
Reproductive system and breast disorders
Dysmenorrhoea	6/390 (1.5%)		2/386 (0.5%)		2/190 (1.1%)
Premenstrual headache	0/390 (0%)		1/386 (0.3%)		0/190 (0%)
Respiratory, thoracic and mediastinal disorders
Allergic sinusitis	0/390 (0%)		1/386 (0.3%)		0/190 (0%)
Asthma	0/390 (0%)		1/386 (0.3%)		0/190 (0%)
Cough	2/390 (0.5%)		2/386 (0.5%)		2/190 (1.1%)
Epistaxis	0/390 (0%)		0/386 (0%)		1/190 (0.5%)
Nasal congestion	1/390 (0.3%)		2/386 (0.5%)		1/190 (0.5%)
Oropharyngeal pain	3/390 (0.8%)		5/386 (1.3%)		0/190 (0%)
Respiratory tract congestion	3/390 (0.8%)		2/386 (0.5%)		0/190 (0%)
Rhinitis allergic	0/390 (0%)		1/386 (0.3%)		0/190 (0%)
Rhinorrhoea	1/390 (0.3%)		1/386 (0.3%)		3/190 (1.6%)
Sinus congestion	5/390 (1.3%)		2/386 (0.5%)		0/190 (0%)
Sneezing	0/390 (0%)		1/386 (0.3%)		0/190 (0%)
Skin and subcutaneous tissue disorders
Acne	0/390 (0%)		1/386 (0.3%)		0/190 (0%)
Blister	0/390 (0%)		2/386 (0.5%)		0/190 (0%)
Dermal cyst	0/390 (0%)		1/386 (0.3%)		0/190 (0%)
Dry skin	2/390 (0.5%)		2/386 (0.5%)		2/190 (1.1%)
Erythema	5/390 (1.3%)		4/386 (1%)		4/190 (2.1%)
Pain of skin	0/390 (0%)		1/386 (0.3%)		0/190 (0%)
Pruritus	6/390 (1.5%)		3/386 (0.8%)		2/190 (1.1%)
Rash	0/390 (0%)		4/386 (1%)		0/190 (0%)
Rosacea	0/390 (0%)		0/386 (0%)		4/190 (2.1%)
Skin burning sensation	1/390 (0.3%)		2/386 (0.5%)		0/190 (0%)
Skin exfoliation	0/390 (0%)		1/386 (0.3%)		1/190 (0.5%)
Skin irritation	2/390 (0.5%)		0/386 (0%)		0/190 (0%)
Urticaria	1/390 (0.3%)		1/386 (0.3%)		1/190 (0.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The results of the study may be published or presented by the Investigator(s) after the review by, and in consultation and agreement with the Sponsor, and such that confidential or proprietary information is not disclosed.