A Study Comparing Diclofenac Sodium Gel 3% to Solaraze® (Diclofenac Sodium) Gel 3% in the Treatment of Actinic Keratosis

• Sponsor: Actavis Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01962987
• Collaborator: (none)
• Enrollment: 476
• Locations: 31
• Arms: 3
• Duration (Months): 6
• Patients Per Site: 15.4
• Patients Per Site Per Month: 2.5

Study Details

Study Description

Brief Summary

To compare the relative efficacy and safety of the test formulation diclofenac sodium gel 3% (Actavis) to the marketed formulation Solaraze® (diclofenac sodium) Gel 3% (Fougera Pharms) in the treatment of the actinic keratosis

Condition or Disease	Intervention/Treatment	Phase
Actinic Keratosis	Drug: Diclofenac sodium; Other: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 476 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind, Multiple-Site, Placebo-Controlled, Parallel Design Study Comparing Diclofenac Sodium Gel 3% (Actavis) to Solaraze ® (Diclofenac Sodium) Gel 3% (Fougera Pharms) in the Treatment of Actinic Keratosis
• Study Start Date: Mar 1, 2013
• Actual Primary Completion Date: Sep 1, 2013
• Actual Study Completion Date: Sep 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Diclofenac Sodium 3% gel - Test The diclofenac sodium 3% test gel is applied to lesion areas twice daily. It is to be smoothed onto the affected skin gently. The amount needed depends upon the size of the lesion site. Assure that enough Test Gel is applied to adequately cover each lesion. Normally 0.5 g of gel is used on each 5 cm x 5 cm lesion site.	Drug: Diclofenac sodium; Topical administration of approximately 0.5g twice daily to the 25 sq cm treatment area for 60 days.; Other Names: Solaraze
Active Comparator: Diclofenac Sodium 3% gel - Reference The Reference diclofenac sodium 3% gel (Solaraze®) is applied to lesion areas twice daily. It is to be smoothed onto the affected skin gently. The amount needed depends upon the size of the lesion site. Assure that enough Reference (Solaraze®) Gel is applied to adequately cover each lesion. Normally 0.5 g of gel is used on each 5 cm x 5 cm lesion site.	Drug: Diclofenac sodium; Topical administration of approximately 0.5g twice daily to the 25 sq cm treatment area for 60 days.; Other Names: Solaraze
Placebo Comparator: Placebo gel The placebo gel (contains no active ingredient) is applied to lesion areas twice daily. It is to be smoothed onto the affected skin gently. The amount needed depends upon the size of the lesion site. Assure that enough placebo gel 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: Placebo; Topical administration of approximately 0.5g twice daily to the 25 sq cm treatment area for 60 days.; Other Names: Vehicle base

Outcome Measures

Primary Outcome Measures

1. Percentage of Patients With 100% Clearance of All AK Lesions Within the Treatment Area Assessed at Day 90 [90 days]

   The primary measure of bioequivalence will be evaluated using those patients who complete the study according to the (PP) population.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Signed informed consent form, which meets all criteria of current FDA and HIPAA regulations.

2. Immunocompetent male or non-pregnant, non-lactating female at least 18 years of age.

3. Diagnosis of AK with ≥ 5 and < 10 clinically typical, visible, discrete, nonhyperkeratotic, nonhypertrophic AK lesions each at least 4 mm in diameter on the face and/or bald scalp contained within a 25cm2 treatment area.

4. Women either must be 1 year post-menopausal (no menstrual periods for at least 12 months), surgically sterile, or if they are of child-bearing potential, they must:

5. Have been using systemic birth control, IUD, or Norplant for at least 28 days prior to the start of treatment period of the study, or used barrier methods such as diaphragm plus spermicide or condom plus spermicide consistently, at least 14 days before study gel administration.

6. Had a normal menstrual cycle for the month prior to the start of treatment.

7. Have a negative urine pregnancy test result upon entry into the study.

8. Agree to use a medically accepted form of birth control (oral, implant, injectable or transdermal contraceptives, intrauterine device, condom plus spermicide, diaphragm plus spermicide) or practice abstinence throughout the study period.

9. Free from any systemic or dermatologic disorder that, in the opinion of the Investigator, will interfere with the study results or increase the risk of AEs.

10. Any skin type or race, providing the skin pigmentation will allow discernment of erythema.

11. Willingness and capability to cooperate to the extent and degree required by the protocol.

Exclusion Criteria:

1. Active gastrointestinal ulceration or bleeding.

2. Current or history of severe renal or hepatic impairment.

3. Presence of atopic dermatitis, basal cell carcinoma, squamous cell carcinoma, eczema, psoriasis, rosacea, sunburn or other possible skin conditions on the face or bald scalp that in the investigator's opinion would interfere with the study assessments.

4. Use within six months prior to randomization of oral isotretinoin.

5. Use within six months prior to randomization on the face or bald scalp of 1) chemical peel, 2) dermabrasion, 3) laser abrasion, 4) PUVA (psoralen plus ultraviolet A) therapy, or 5) UVB therapy

6. Use within one month prior to randomization on the face or bald scalp of 1) cryodestruction or chemodestruction, 2)curettage, 3) photodynamic therapy, 4) surgical excision, 5)topical 5-fluorouracil, 6) topical corticosteroids, 7) topical diclofenac,

1. topical Imiquimod, 9) topical retinoids, or 10) other treatments for actinic keratosis including glycolic acids or over-the-counter products containing retinol, alpha or beta hydroxy acids.

1. Use within one month prior to randomization of 1)immunomodulators or immunosuppressive therapies, 2)interferon, 3) systemic corticosteroids or 4) cytotoxic drugs. (The occasional use of ophthalmic, nasal or inhaled steroids is acceptable and not reason for exclusion)

2. Known allergies to diclofenac sodium, benzyl alcohol, polyethylene glycol monomethyl ether 359, hyaluronate sodium or any excipients in the test or reference gels.

3. Receiving 5-Fluorouracil or other systemic cancer chemotherapy within 6 months prior to randomization.

4. Any condition, medical, psychological, or social, that, in the Investigator's opinion, would interfere with participation in the study.

5. Women who are pregnant, planning pregnancy or lactating.

6. Participation in any investigational drug study within 30 days of randomization or previous participation in this study.

7. Employees of the research center or Investigator.

8. Family members of employees of the research center or Investigator.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Investigator Site 23	Fremont	California	United States
2	Investigator Site 9	Long Beach	California	United States
3	Investigator Site 12	Newport Beach	California	United States
4	Investigator Site 2	San Diego	California	United States
5	Investigator Site 24	San Ramon	California	United States
6	Investigator Site 14	Denver	Colorado	United States
7	Investigator Site 17	Denver	Colorado	United States
8	Investigator Site 21	Brandon	Florida	United States
9	Investigator Site 25	Dunedin	Florida	United States
10	Investigator Site 20	Fort Myers	Florida	United States
11	Investigator Site 15	Jacksonville	Florida	United States
12	Investigator Site 16	Miami	Florida	United States
13	Investigator Site 6	Ormond Beach	Florida	United States
14	Investigator Site 19	Winter Park	Florida	United States
15	Investigator Site 22	Atlanta	Georgia	United States
16	Investigator Site 11	Boise	Idaho	United States
17	Investigator Site 8	Arlington Heights	Illinois	United States
18	Investigator Site 28	Plainfield	Indiana	United States
19	Investigator Site 31	Louisville	Kentucky	United States
20	Investigator Site 27	Fridley	Minnesota	United States
21	Investigator Site 13	Bozeman	Montana	United States
22	Investigator Site 26	New Bern	North Carolina	United States
23	Investigator Site 3	Raleigh	North Carolina	United States
24	Investigator Site 18	Wilmington	North Carolina	United States
25	Investigator Site 30	Cincinnati	Ohio	United States
26	Investigator Site 1	Hazleton	Pennsylvania	United States
27	Investigator Site 5	Clinton	South Carolina	United States
28	Investigator Site 4	Johnson City	Tennessee	United States
29	Investigator Site 10	Nashville	Tennessee	United States
30	Investigator Site 7	West Jordan	Utah	United States
31	Investigator Site 29	Midlothian	Virginia	United States

Sponsors and Collaborators

• Actavis Inc.

Investigators

• Study Director: Henry Lau, PhD, Actavis Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Actavis Inc.
• ClinicalTrials.gov Identifier: NCT01962987
• Other Study ID Numbers: 71204901
• First Posted: Oct 16, 2013
• Last Update Posted: Jul 20, 2020
• Last Verified: Jul 1, 2020

• Additional relevant MeSH terms: Keratosis, Actinic; Keratosis; Diclofenac

Study Results

Participant Flow

Arm/Group Title	Diclofenac Sodium 3% Gel	Solaraze( Diclofenac Sodium) 3% Gel	Vehicle Gel
Arm/Group Description	The test product diclofenac sodium 3% test gel is applied to lesion areas twice daily. It is to be smoothed onto the affected skin gently. The amount needed depends upon the size of the lesion site. Assure that enough Test Gel is applied to adequately cover each lesion. Normally 0.5 g of gel is used on each 5 cm x 5 cm lesion site. Diclofenac sodium: Topical administration of approximately 0.5g twice daily to the 25 sq cm treatment area for 60 days.	The Reference diclofenac sodium 3% gel (Solaraze®) is applied to lesion areas twice daily. It is to be smoothed onto the affected skin gently. The amount needed depends upon the size of the lesion site. Assure that enough Reference (Solaraze®) Gel is applied to adequately cover each lesion. Normally 0.5 g of gel is used on each 5 cm x 5 cm lesion site. Diclofenac sodium: Topical administration of approximately 0.5g twice daily to the 25 sq cm treatment area for 60 days.	The vehicle (placebo) gel (contains no active ingredient) is applied to lesion areas twice daily. It is to be smoothed onto the affected skin gently. The amount needed depends upon the size of the lesion site. Assure that enough placebo gel 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: Topical administration of approximately 0.5g twice daily to the 25 sq cm treatment area for 60 days.
Period Title: Overall Study
STARTED	190	191	95
COMPLETED	160	163	83
NOT COMPLETED	30	28	12

Baseline Characteristics

Arm/Group Title	Diclofenac Sodium 3% Gel	Solaraze( Diclofenac Sodium) 3% Gel	Vehicle Gel	Total
Arm/Group Description	The test product diclofenac sodium 3% test gel is applied to lesion areas twice daily. It is to be smoothed onto the affected skin gently. The amount needed depends upon the size of the lesion site. Assure that enough Test Gel is applied to adequately cover each lesion. Normally 0.5 g of gel is used on each 5 cm x 5 cm lesion site. Diclofenac sodium: Topical administration of approximately 0.5g twice daily to the 25 sq cm treatment area for 60 days.	The Reference diclofenac sodium 3% gel (Solaraze®) is applied to lesion areas twice daily. It is to be smoothed onto the affected skin gently. The amount needed depends upon the size of the lesion site. Assure that enough Reference (Solaraze®) Gel is applied to adequately cover each lesion. Normally 0.5 g of gel is used on each 5 cm x 5 cm lesion site. Diclofenac sodium: Topical administration of approximately 0.5g twice daily to the 25 sq cm treatment area for 60 days.	The vehicle (placebo) gel (contains no active ingredient) is applied to lesion areas twice daily. It is to be smoothed onto the affected skin gently. The amount needed depends upon the size of the lesion site. Assure that enough placebo gel 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: Topical administration of approximately 0.5g twice daily to the 25 sq cm treatment area for 60 days.	Total of all reporting groups
Overall Participants	188	189	93	470
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	65.34 (11.42)	66.24 (11.37)	65.55 (11.00)	65.71 (11.26)
Sex: Female, Male (Count of Participants)
Female	56 29.8%	54 28.6%	26 28%	136 28.9%
Male	132 70.2%	135 71.4%	67 72%	334 71.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	21 11.2%	19 10.1%	8 8.6%	48 10.2%
Not Hispanic or Latino	167 88.8%	170 89.9%	85 91.4%	422 89.8%
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	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%	0 0%
White	188 100%	189 100%	93 100%	470 100%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Percentage of Patients With 100% Clearance of All AK Lesions Within the Treatment Area Assessed at Day 90
Description	The primary measure of bioequivalence will be evaluated using those patients who complete the study according to the (PP) population.
Time Frame	90 days

Outcome Measure Data

Analysis Population Description

Analysis provided using the Per-Protocol Population.

Arm/Group Title	Diclofenac Sodium 3% Gel	Solaraze( Diclofenac Sodium) 3% Gel	Vehicle Gel
Arm/Group Description	The test product diclofenac sodium 3% test gel is applied to lesion areas twice daily. It is to be smoothed onto the affected skin gently. The amount needed depends upon the size of the lesion site. Assure that enough Test Gel is applied to adequately cover each lesion. Normally 0.5 g of gel is used on each 5 cm x 5 cm lesion site. Diclofenac sodium: Topical administration of approximately 0.5g twice daily to the 25 sq cm treatment area for 60 days.	The Reference diclofenac sodium 3% gel (Solaraze®) is applied to lesion areas twice daily. It is to be smoothed onto the affected skin gently. The amount needed depends upon the size of the lesion site. Assure that enough Reference (Solaraze®) Gel is applied to adequately cover each lesion. Normally 0.5 g of gel is used on each 5 cm x 5 cm lesion site. Diclofenac sodium: Topical administration of approximately 0.5g twice daily to the 25 sq cm treatment area for 60 days.	The vehicle (placebo) gel (contains no active ingredient) is applied to lesion areas twice daily. It is to be smoothed onto the affected skin gently. The amount needed depends upon the size of the lesion site. Assure that enough placebo gel 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: Topical administration of approximately 0.5g twice daily to the 25 sq cm treatment area for 60 days.
Measure Participants	139	148	81
Cure - 100% clearance of all AK lesions at Day 90	31 16.5%	32 16.9%	7 7.5%
No Cure - Not 100% Clearance of lesions at Day 90	108 57.4%	116 61.4%	74 79.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Diclofenac Sodium 3% Gel, Solaraze( Diclofenac Sodium) 3% Gel
	Comments
	Type of Statistical Test	Equivalence
	Comments	90% confidence interval of the difference in the percentage of patients between Test and Reference to be contained within -20%, + 20%, using the Per-Protocol Population.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	(Test-Ref) Difference
	Estimated Value	0.68
	Confidence Interval	(2-Sided) 90%; -8.06 to 9.42
	Parameter Dispersion	Type: Value:
	Estimation Comments	Applicable to Percentage of Subjects with Cure (100% complete AK clearance at day 90)

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Diclofenac Sodium 3% Gel, Vehicle Gel
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0010
	Comments
	Method	ANOVA
	Comments

Adverse Events

Time Frame	3 months
Arm/Group Title	Diclofenac Sodium 3% Gel		Solaraze( Diclofenac Sodium) 3% Gel		Vehicle Gel
Arm/Group Description	The test product diclofenac sodium 3% test gel is applied to lesion areas twice daily. It is to be smoothed onto the affected skin gently. The amount needed depends upon the size of the lesion site. Assure that enough Test Gel is applied to adequately cover each lesion. Normally 0.5 g of gel is used on each 5 cm x 5 cm lesion site. Diclofenac sodium: Topical administration of approximately 0.5g twice daily to the 25 sq cm treatment area for 60 days.		The Reference diclofenac sodium 3% gel (Solaraze®) is applied to lesion areas twice daily. It is to be smoothed onto the affected skin gently. The amount needed depends upon the size of the lesion site. Assure that enough Reference (Solaraze®) Gel is applied to adequately cover each lesion. Normally 0.5 g of gel is used on each 5 cm x 5 cm lesion site. Diclofenac sodium: Topical administration of approximately 0.5g twice daily to the 25 sq cm treatment area for 60 days.		The vehicle (placebo) gel (contains no active ingredient) is applied to lesion areas twice daily. It is to be smoothed onto the affected skin gently. The amount needed depends upon the size of the lesion site. Assure that enough placebo gel 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: Topical administration of approximately 0.5g twice daily to the 25 sq cm treatment area for 60 days.
All Cause Mortality
	Diclofenac Sodium 3% Gel		Solaraze( Diclofenac Sodium) 3% Gel		Vehicle Gel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/188 (0%)		0/189 (0%)		0/93 (0%)
Serious Adverse Events
	Diclofenac Sodium 3% Gel		Solaraze( Diclofenac Sodium) 3% Gel		Vehicle Gel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/188 (3.7%)		4/189 (2.1%)		2/93 (2.2%)
Cardiac disorders
Cardiac disorder	1/188 (0.5%)		0/189 (0%)		0/93 (0%)
Ear and labyrinth disorders
Vertigo	0/188 (0%)		0/189 (0%)		1/93 (1.1%)
Gastrointestinal disorders
Intestinal obstruction	0/188 (0%)		2/189 (1.1%)		0/93 (0%)
Nausea	1/188 (0.5%)		0/189 (0%)		0/93 (0%)
Infections and infestations
Bacteraemia	0/188 (0%)		1/189 (0.5%)		0/93 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cardiac myxoma	1/188 (0.5%)		0/189 (0%)		0/93 (0%)
Nervous system disorders
Cerebrovascular accident	1/188 (0.5%)		0/189 (0%)		0/93 (0%)
Presyncope	1/188 (0.5%)		0/189 (0%)		0/93 (0%)
Syncope	1/188 (0.5%)		0/189 (0%)		0/93 (0%)
Psychiatric disorders
Alcoholism	1/188 (0.5%)		0/189 (0%)		0/93 (0%)
Renal and urinary disorders
Nephrolithiasis	0/188 (0%)		1/189 (0.5%)		0/93 (0%)
Surgical and medical procedures
Angioplasty	0/188 (0%)		0/189 (0%)		1/93 (1.1%)
Other (Not Including Serious) Adverse Events
	Diclofenac Sodium 3% Gel		Solaraze( Diclofenac Sodium) 3% Gel		Vehicle Gel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	102/188 (54.3%)		91/189 (48.1%)		35/93 (37.6%)
Blood and lymphatic system disorders
Leukocytosis	0/188 (0%)	0	1/189 (0.5%)	1	0/93 (0%)	0
Lymphadenopathy	1/188 (0.5%)	1	0/189 (0%)	0	0/93 (0%)	0
Cardiac disorders
Arteriosclerosis coronary artery	0/188 (0%)	0	1/189 (0.5%)	1	0/93 (0%)	0
Atrial fibrillation	3/188 (1.6%)	3	0/189 (0%)	0	0/93 (0%)	0
Atrial flutter	0/188 (0%)	0	1/189 (0.5%)	1	0/93 (0%)	0
Atrioventricular block first degree	1/188 (0.5%)	1	0/189 (0%)	0	0/93 (0%)	0
Bradycardia	0/188 (0%)	0	0/189 (0%)	0	1/93 (1.1%)	1
Bundle branch block right	0/188 (0%)	0	1/189 (0.5%)	1	0/93 (0%)	0
Cardiac disorder	1/188 (0.5%)	1	0/189 (0%)	0	0/93 (0%)	0
Coronary artery disease	0/188 (0%)	0	1/189 (0.5%)	1	0/93 (0%)	0
Mitral valce incompetence	1/188 (0.5%)	1	0/189 (0%)	0	0/93 (0%)	0
Sinus arrhythmia	1/188 (0.5%)	1	0/189 (0%)	0	0/93 (0%)	0
Tricuspid valve incompetence	1/188 (0.5%)	1	0/189 (0%)	0	0/93 (0%)	0
Vertigo	1/188 (0.5%)	2	0/189 (0%)	0	1/93 (1.1%)	1
Ear and labyrinth disorders
Cerumen impaction	1/188 (0.5%)	1	0/189 (0%)	0	0/93 (0%)	0
Ear discomfort	0/188 (0%)	0	1/189 (0.5%)	1	0/93 (0%)	0
Eye disorders
Cataract	1/188 (0.5%)	1	0/189 (0%)	0	0/93 (0%)	0
Eye Swelling	0/188 (0%)	0	1/189 (0.5%)	1	0/93 (0%)	0
Periorbital oedema	1/188 (0.5%)	1	0/189 (0%)	0	0/93 (0%)	0
Gastrointestinal disorders
Abdominal discomfort	1/188 (0.5%)	1	0/189 (0%)	0	0/93 (0%)	0
Colitis	1/188 (0.5%)	1	0/189 (0%)	0	0/93 (0%)	0
Diarrhoea	0/188 (0%)	0	1/189 (0.5%)	1	1/93 (1.1%)	1
Dry mouth	1/188 (0.5%)	1	1/189 (0.5%)	1	0/93 (0%)	0
Dyspepsia	1/188 (0.5%)	1	0/189 (0%)	0	0/93 (0%)	0
Dysphagia	1/188 (0.5%)	1	0/189 (0%)	0	0/93 (0%)	0
Gastric ulcer	1/188 (0.5%)	1	0/189 (0%)	0	0/93 (0%)	0
Gastrooesophageal reflux	0/188 (0%)	0	0/189 (0%)	0	1/93 (1.1%)	1
Haematochezia	0/188 (0%)	0	0/189 (0%)	0	1/93 (1.1%)	1
Haemorrhoidal heamorrhage	1/188 (0.5%)	1	0/189 (0%)	0	0/93 (0%)	0
Hiatus hernia	0/188 (0%)	0	1/189 (0.5%)	1	0/93 (0%)	0
Intestinal obstruction	0/188 (0%)	0	2/189 (1.1%)	2	1/93 (1.1%)	1
Nausea	2/188 (1.1%)	2	1/189 (0.5%)	1	2/93 (2.2%)	3
Oral discomfort	0/188 (0%)	0	1/189 (0.5%)	1	0/93 (0%)	0
Toothache	1/188 (0.5%)	1	0/189 (0%)	0	0/93 (0%)	0
Vomiting	0/188 (0%)	0	0/189 (0%)	0	1/93 (1.1%)	1
General disorders
Application site alopecia	0/188 (0%)	0	0/189 (0%)	0	1/93 (1.1%)	1
Application site burn	1/188 (0.5%)	1	0/189 (0%)	0	0/93 (0%)	0
Application site dermatitis	6/188 (3.2%)	6	3/189 (1.6%)	3	0/93 (0%)	0
Application site dryness	1/188 (0.5%)	1	0/189 (0%)	0	1/93 (1.1%)	2
Application site exfoliation	0/188 (0%)	0	3/189 (1.6%)	5	0/93 (0%)	0
Application site haemorrhage	0/188 (0%)	0	1/189 (0.5%)	1	0/93 (0%)	0
Application site irritation	1/188 (0.5%)	1	0/189 (0%)	0	0/93 (0%)	0
Application site pain	2/188 (1.1%)	2	1/189 (0.5%)	1	2/93 (2.2%)	2
Application site pruritus	2/188 (1.1%)	2	2/189 (1.1%)	2	1/93 (1.1%)	1
Application site rash	1/188 (0.5%)	3	0/189 (0%)	0	0/93 (0%)	0
Application site reaction	1/188 (0.5%)	1	1/189 (0.5%)	1	0/93 (0%)	0
Application site scab	1/188 (0.5%)	3	0/189 (0%)	0	0/93 (0%)	0
Application site swelling	0/188 (0%)	0	3/189 (1.6%)	3	0/93 (0%)	0
Application site urticaria	0/188 (0%)	0	1/189 (0.5%)	1	0/93 (0%)	0
Application site vesicles	0/188 (0%)	0	1/189 (0.5%)	1	0/93 (0%)	0
Chest discomfort	0/188 (0%)	0	1/189 (0.5%)	1	0/93 (0%)	0
Chills	0/188 (0%)	0	2/189 (1.1%)	2	0/93 (0%)	0
Fatigue	0/188 (0%)	0	1/189 (0.5%)	1	0/93 (0%)	0
Pain	2/188 (1.1%)	2	0/189 (0%)	0	0/93 (0%)	0
Pyrexia	0/188 (0%)	0	1/189 (0.5%)	1	0/93 (0%)	0
Thirst	1/188 (0.5%)	1	0/189 (0%)	0	0/93 (0%)	0
Hepatobiliary disorders
Cholelithiasis	0/188 (0%)	0	1/189 (0.5%)	1	0/93 (0%)	0
Immune system disorders
Seasonal allergy	2/188 (1.1%)	2	0/189 (0%)	0	0/93 (0%)	0
Infections and infestations
Acarodermatitis	0/188 (0%)	0	1/189 (0.5%)	1	0/93 (0%)	0
Application site infection	1/188 (0.5%)	1	0/189 (0%)	0	0/93 (0%)	0
Bacteraemia	0/188 (0%)	0	1/189 (0.5%)	1	0/93 (0%)	0
Bronchitis	0/188 (0%)	0	1/189 (0.5%)	1	3/93 (3.2%)	3
Clostridium difficile colitis	0/188 (0%)	0	1/189 (0.5%)	1	0/93 (0%)	0
Diverticulitis	0/188 (0%)	0	1/189 (0.5%)	1	0/93 (0%)	0
Ear infection	0/188 (0%)	0	1/189 (0.5%)	1	0/93 (0%)	0
Eye infection	0/188 (0%)	0	0/189 (0%)	0	1/93 (1.1%)	1
Gastoenteritis viral	0/188 (0%)	0	1/189 (0.5%)	1	0/93 (0%)	0
Herpes zoster	1/188 (0.5%)	1	1/189 (0.5%)	1	0/93 (0%)	0
Hordeolum	1/188 (0.5%)	1	0/189 (0%)	0	0/93 (0%)	0
Influenza	1/188 (0.5%)	1	1/189 (0.5%)	1	0/93 (0%)	0
Localized infection	0/188 (0%)	0	0/189 (0%)	0	1/93 (1.1%)	3
Nasopharyngitis	2/188 (1.1%)	2	1/189 (0.5%)	1	0/93 (0%)	0
Oral herpes	1/188 (0.5%)	1	1/189 (0.5%)	1	0/93 (0%)	0
Pharyngitis	1/188 (0.5%)	1	0/189 (0%)	0	0/93 (0%)	0
Pharyngitis streptococcal	0/188 (0%)	0	1/189 (0.5%)	1	0/93 (0%)	0
Sinusitis	0/188 (0%)	0	1/189 (0.5%)	1	0/93 (0%)	0
Staphylococcal infection	0/188 (0%)	0	1/189 (0.5%)	1	0/93 (0%)	0
Tooth abscess	1/188 (0.5%)	1	0/189 (0%)	0	0/93 (0%)	0
Upper respiratory tract infection	0/188 (0%)	0	1/189 (0.5%)	1	0/93 (0%)	0
Urinary tract infection	0/188 (0%)	0	1/189 (0.5%)	1	0/93 (0%)	0
Injury, poisoning and procedural complications
Ankle fracture	0/188 (0%)	0	1/189 (0.5%)	1	0/93 (0%)	0
Excoriation	1/188 (0.5%)	1	0/189 (0%)	0	0/93 (0%)	0
Fall	1/188 (0.5%)	1	0/189 (0%)	0	0/93 (0%)	0
Foot fracture	1/188 (0.5%)	1	0/189 (0%)	0	0/93 (0%)	0
Head injury	0/188 (0%)	0	1/189 (0.5%)	1	0/93 (0%)	0
Muscle strain	1/188 (0.5%)	1	0/189 (0%)	0	0/93 (0%)	0
Wound	0/188 (0%)	0	1/189 (0.5%)	1	0/93 (0%)	0
Investigations
Blood pressure increased	0/188 (0%)	0	2/189 (1.1%)	2	0/93 (0%)	0
Blood uric acid increased	0/188 (0%)	0	1/189 (0.5%)	1	0/93 (0%)	0
Respiratory rate decreased	1/188 (0.5%)	1	0/189 (0%)	0	0/93 (0%)	0
Metabolism and nutrition disorders
Decreased appetite	0/188 (0%)	0	1/189 (0.5%)	1	0/93 (0%)	0
Gout	2/188 (1.1%)	2	1/189 (0.5%)	1	0/93 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	1/188 (0.5%)	1	1/189 (0.5%)	1	1/93 (1.1%)	1
Back pain	1/188 (0.5%)	1	0/189 (0%)	0	0/93 (0%)	0
Foot deformity	1/188 (0.5%)	1	0/189 (0%)	0	0/93 (0%)	0
Muscle spasms	1/188 (0.5%)	1	0/189 (0%)	0	0/93 (0%)	0
Musculoskeletal stiffness	1/188 (0.5%)	1	0/189 (0%)	0	0/93 (0%)	0
Myalgia	1/188 (0.5%)	1	1/189 (0.5%)	1	0/93 (0%)	0
Neck pain	1/188 (0.5%)	1	0/189 (0%)	0	0/93 (0%)	0
Osteitis	0/188 (0%)	0	1/189 (0.5%)	1	0/93 (0%)	0
Pain in jaw	0/188 (0%)	0	1/189 (0.5%)	1	1/93 (1.1%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acrochordon	0/188 (0%)	0	1/189 (0.5%)	1	0/93 (0%)	0
Cardiac myxoma	1/188 (0.5%)	1	0/189 (0%)	0	0/93 (0%)	0
Melanoma recurrent	0/188 (0%)	0	1/189 (0.5%)	1	0/93 (0%)	0
Neoplasm	1/188 (0.5%)	1	0/189 (0%)	0	0/93 (0%)	0
Neoplasm skin	0/188 (0%)	0	0/189 (0%)	0	1/93 (1.1%)	1
Squamous cell carcinoma	0/188 (0%)	0	0/189 (0%)	0	2/93 (2.2%)	2
Nervous system disorders
Balance disorder	0/188 (0%)	0	1/189 (0.5%)	1	0/93 (0%)	0
Carotid artery stenosis	1/188 (0.5%)	1	0/189 (0%)	0	0/93 (0%)	0
Cerebrovascular accident	1/188 (0.5%)	1	0/189 (0%)	0	0/93 (0%)	0
Dementia	1/188 (0.5%)	1	0/189 (0%)	0	0/93 (0%)	0
Dizziness	2/188 (1.1%)	2	2/189 (1.1%)	2	2/93 (2.2%)	2
Headache	5/188 (2.7%)	10	7/189 (3.7%)	9	3/93 (3.2%)	4
Hyperaesthesia	1/188 (0.5%)	1	0/189 (0%)	0	0/93 (0%)	0
Migraine	0/188 (0%)	0	2/189 (1.1%)	2	1/93 (1.1%)	1
Presyncope	1/188 (0.5%)	1	0/189 (0%)	0	0/93 (0%)	0
Sciatica	1/188 (0.5%)	1	1/189 (0.5%)	1	0/93 (0%)	0
Syncope	1/188 (0.5%)	1	0/189 (0%)	0	0/93 (0%)	0
Psychiatric disorders
Alcoholism	1/188 (0.5%)	1	0/189 (0%)	0	0/93 (0%)	0
Anxiety	1/188 (0.5%)	1	0/189 (0%)	0	0/93 (0%)	0
Depression	2/188 (1.1%)	2	0/189 (0%)	0	0/93 (0%)	0
Renal and urinary disorders
Nephrolithiasis	0/188 (0%)	0	2/189 (1.1%)	4	0/93 (0%)	0
Renal cyst	0/188 (0%)	0	1/189 (0.5%)	1	0/93 (0%)	0
Reproductive system and breast disorders
Dysmenorrhoea	0/188 (0%)	0	0/189 (0%)	0	1/93 (1.1%)	2
Respiratory, thoracic and mediastinal disorders
Cough	2/188 (1.1%)	2	0/189 (0%)	0	0/93 (0%)	0
Nasal congestion	0/188 (0%)	0	1/189 (0.5%)	1	0/93 (0%)	0
Nasal ulcer	1/188 (0.5%)	1	0/189 (0%)	0	0/93 (0%)	0
Oropharyngeal pain	0/188 (0%)	0	1/189 (0.5%)	1	0/93 (0%)	0
Pulmonary hypertention	1/188 (0.5%)	1	0/189 (0%)	0	0/93 (0%)	0
Rhinorrhoea	0/188 (0%)	0	1/189 (0.5%)	1	0/93 (0%)	0
Sinus congestion	0/188 (0%)	0	0/189 (0%)	0	1/93 (1.1%)	1
Wheezing	1/188 (0.5%)	1	0/189 (0%)	0	0/93 (0%)	0
Skin and subcutaneous tissue disorders
Actinic keratosis	1/188 (0.5%)	2	0/189 (0%)	0	1/93 (1.1%)	1
Blister	1/188 (0.5%)	1	0/189 (0%)	0	0/93 (0%)	0
Dermatitis	0/188 (0%)	0	1/189 (0.5%)	1	0/93 (0%)	0
Dermatitis acneiform	0/188 (0%)	0	1/189 (0.5%)	1	0/93 (0%)	0
Dermatitis contact	2/188 (1.1%)	3	1/189 (0.5%)	1	0/93 (0%)	0
Pruritus	0/188 (0%)	0	1/189 (0.5%)	1	0/93 (0%)	0
Rash	0/188 (0%)	0	0/189 (0%)	0	1/93 (1.1%)	1
Rosacea	1/188 (0.5%)	1	0/189 (0%)	0	0/93 (0%)	0
Seborrhoeic dermatitis	1/188 (0.5%)	1	1/189 (0.5%)	1	0/93 (0%)	0
Sunburn	1/188 (0.5%)	1	0/189 (0%)	0	0/93 (0%)	0
Surgical and medical procedures
Anal fissure excision	1/188 (0.5%)	1	0/189 (0%)	0	0/93 (0%)	0
Angioplasty	0/188 (0%)	0	0/189 (0%)	0	1/93 (1.1%)	1
Malignant tumour excision	1/188 (0.5%)	1	0/189 (0%)	0	0/93 (0%)	0
Skin neoplasm excision	0/188 (0%)	0	1/189 (0.5%)	1	0/93 (0%)	0
Vascular disorders
Hypertention	1/188 (0.5%)	1	0/189 (0%)	0	0/93 (0%)	0

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.