Study Comparing GDC 695 and Diclofenac Sodium Gel, 3% in Subjects With Actinic Keratoses

• Sponsor: Gage Development Company, LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02952898
• Collaborator: (none)
• Enrollment: 665
• Locations: 16
• Arms: 3
• Actual Duration (Months): 10.3
• Patients Per Site: 41.6
• Patients Per Site Per Month: 4

Study Details

Study Description

Brief Summary

This research study is being done to compare the safety and effectiveness of GDC 695 (test drug) against the currently marketed reference drug (diclofenac sodium gel, 3%) and to establish that these two drugs work better than placebo in the treatment of actinic keratosis.

Condition or Disease	Intervention/Treatment	Phase
Actinic Keratosis	Drug: GDC 695; Drug: Diclofenac Sodium Gel, 3%; Drug: Vehicle gel	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 665 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Comparison Study to Determine the Therapeutic Equivalence of GDC 695 and Diclofenac Sodium Gel, 3% in Subjects With Actinic Keratoses
• Actual Study Start Date: Oct 27, 2016
• Actual Primary Completion Date: Jul 11, 2017
• Actual Study Completion Date: Sep 6, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Test Drug GDC 695 gel applied topically as directed.	Drug: GDC 695; GDC 695 is a topical gel.
Active Comparator: Reference Drug Diclofenac sodium gel, 3% applied topically as directed.	Drug: Diclofenac Sodium Gel, 3%; Diclofenac sodium gel, 3% is an FDA-approved drug.
Placebo Comparator: Placebo Vehicle gel applied topically as directed.	Drug: Vehicle gel; Vehicle topical gel contains 0.0% of active drug and is color matched to the other two active test drugs.

Outcome Measures

Primary Outcome Measures

1. Number of Subjects With Complete Clearance of AK Lesions [Day 90 (30 days after completion of 60 days of treatment)]

   Complete Clearance was defined as 100% clearance of all Actinic Keratosis (AK) lesions (having a count of zero AKs) in the treatment area (face or bald scalp) at the Day 90 visit (30 Days Post Treatment).

Other Outcome Measures

1. Adverse Events (AEs) [Day 0 through Day 90]

   AEs will be assessed by the investigator and the incidence (severity and causality) of any local and systemic AEs will be reported.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Has provided written informed consent.

• Immunocompetent male and/or non-pregnant female, 18 years of age or older.

• Willing and able to apply the test article(s) as directed, comply with study instructions, and commit to all follow-up visits for the duration of the study.

• Clinical diagnosis of actinic keratosis.

• In good general health and free of any disease state or physical condition.

• Women, must be post-menopausal, surgically sterile, or use an effective method of birth control with a negative urine pregnancy test (UPT) at the Baseline Visit (Day 1).

Exclusion Criteria:

• Women who are pregnant, breastfeeding, or are planning to become pregnant or breastfeed during the study.

• Is currently enrolled in another investigational drug or device study or has used an investigational drug or investigational device within 30 days prior to the Baseline Visit (Day 1).

• Has the need or plans to be exposed to artificial tanning devices or excessive sunlight during the study.

• Is immunosuppressed (e.g., human immunodeficiency virus [ HIV], systemic malignancy, graft host disease, etc.) or is taking medications that suppress the immune system.

• Has experienced an unsuccessful outcome from previous topical diclofenac sodium therapy.

• Has a history of sensitivity to any of the ingredients in the test articles or other excipients in the test or reference drug.

• Has signs or symptoms consistent with the aspirin (ASA) triad.

• Has used topical medications: corticosteroids, alpha hydroxy acids (e.g., glycolic acid, lactic acid, etc. >5%), beta hydroxy acid (salicylic acid >2%), urea >2%, 5-fluorouracil, diclofenac, imiquimod, ingenol mebutate, aminolevulinic acid (ALA) or prescription retinoids (e.g., tazarotene, adapalene, tretinoin), over-the-counter (OTC) products labeled as scrubs of any kind which are used to smooth the skin (as they contain some form of exfoliant such as nut shells, coffee grounds, polymer particles, etc.) within the selected treatment area (face or bald scalp) within one month prior to the Baseline Visit.

• Has had cryodestruction or chemodestruction, curettage, photodynamic therapy (PDT), surgical excision, or other treatments for AK within the selected treatment area (face or bald scalp) within one month prior to the Baseline Visit.

• Has used oral corticosteroid therapy, interferon, cytotoxic drugs, immunomodulators, immunosuppressive therapies, or retinoids within one month prior to the Baseline Visit.

• Has used oral isotretinoin within six months prior to the Baseline Visit.

• Has used chemical peels, including but not limited to alphahydroxy acid, betahydroxy acid, bichloroacetic acid, trichloroacetic acid, and phenol within the selected treatment area (face or bald scalp) within six months prior to the Baseline Visit.

• Has had dermatologic procedures or surgeries such as: laser resurfacing, PUVA (Psoralen + ultraviolet A) therapy, ultraviolet B (UVB) therapy, ALA-PDT, or dermabrasion within the selected treatment area (face or bald scalp) within six months prior to the Baseline Visit.

• Has lesions suspicious for skin cancer (skin cancer not ruled out by biopsy) or untreated skin cancers within the selected treatment area (face or bald scalp).

• Has active gastrointestinal ulceration or bleeding or has a history of gastrointestinal bleeds due to use of aspirin or other NSAIDs.

• Has severe renal or hepatic impairment.

• Has any condition which, in the investigator's opinion, could interfere with the evaluation of the test drugs or that could make it unsafe or preclude the subject's ability to fully participate in this research study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Site 07	Fort Smith	Arkansas	United States	72916
2	Site 14	San Diego	California	United States	92117
3	Site 24	San Ramon	California	United States	94582
4	Site 22	Clearwater	Florida	United States	33756
5	Site 01	North Miami Beach	Florida	United States	33162
6	Site 27	Ocala	Florida	United States	34471
7	Site 12	Tampa	Florida	United States	33609
8	Site 05	Carmel	Indiana	United States	46032
9	Site 02	Plainfield	Indiana	United States	46168
10	Site 25	Saint Joseph	Missouri	United States	64506
11	Site 21	Albuquerque	New Mexico	United States	87106
12	Site 03	Warwick	Rhode Island	United States	02886
13	Site 26	Anderson	South Carolina	United States	29621
14	Site 04	Greenville	South Carolina	United States	29607
15	Site 28	Norfolk	Virginia	United States	23507
16	Site 10	Spokane	Washington	United States	99202

Sponsors and Collaborators

• Gage Development Company, LLC

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Jan 26, 2017
• Statistical Analysis Plan - Mar 14, 2017

More Information

Publications

None provided.

• Responsible Party: Gage Development Company, LLC
• ClinicalTrials.gov Identifier: NCT02952898
• Other Study ID Numbers: GDC-695-001
• First Posted: Nov 2, 2016
• Last Update Posted: Jan 7, 2020
• Last Verified: Jan 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Gage Development Company, LLC: solar keratoses
• Additional relevant MeSH terms: Keratosis, Actinic; Keratosis; Diclofenac

Study Results

Participant Flow

Recruitment Details	Recruitment Period: October 2016 to July 2017 The location of clinical sites included dermatology clinics and clinical research centers.
Pre-assignment Detail	All subjects who met the entry criteria and were randomized and enrolled into the study.

Arm/Group Title	GDC 695 Gel	Diclofenac Sodium Gel	Placebo
Arm/Group Description	The test drug is GDC 695 gel applied topically as directed. GDC 695: GDC 695 is a topical gel.	The reference drug is Diclofenac sodium gel, 3% applied topically as directed. Diclofenac Sodium Gel, 3%: Diclofenac sodium gel, 3% is an FDA-approved drug.	Vehicle gel applied topically as directed. Vehicle gel: Vehicle topical gel contains 0.0% of active drug and is color matched to the other two active test drugs.
Period Title: Overall Study
STARTED	220	221	224
COMPLETED	198	202	209
NOT COMPLETED	22	19	15

Baseline Characteristics

Arm/Group Title	GDC 695 Gel	Diclofenac Sodium Gel	Placebo	Total
Arm/Group Description	GDC 695 gel applied topically as directed. GDC 695: GDC 695 is a topical gel.	Diclofenac sodium gel, 3% applied topically as directed. Diclofenac Sodium Gel, 3%: Diclofenac sodium gel, 3% is an FDA-approved drug.	Vehicle gel applied topically as directed. Vehicle gel: Vehicle topical gel contains 0.0% of active drug and is color matched to the other two active test drugs.	Total of all reporting groups
Overall Participants	218	220	223	661
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	70.2 (9.4)	69.6 (9.8)	69.1 (9.3)	69.6 (9.5)
Sex: Female, Male (Count of Participants)
Female	31 14.2%	45 20.5%	36 16.1%	112 16.9%
Male	187 85.8%	175 79.5%	187 83.9%	549 83.1%
Race/Ethnicity, Customized (Count of Participants)
Hispanic or Latino	14 6.4%	13 5.9%	16 7.2%	43 6.5%
Not Hispanic or Latino	204 93.6%	207 94.1%	207 92.8%	618 93.5%
Race/Ethnicity, Customized (Count of Participants)
American Indian or Alaska Native	1 0.5%	2 0.9%	1 0.4%	4 0.6%
White	217 99.5%	218 99.1%	222 99.6%	657 99.4%
Region of Enrollment (participants) [Number]
United States	218 100%	220 100%	223 100%	661 100%

Outcome Measures

1. Primary Outcome

Title	Number of Subjects With Complete Clearance of AK Lesions
Description	Complete Clearance was defined as 100% clearance of all Actinic Keratosis (AK) lesions (having a count of zero AKs) in the treatment area (face or bald scalp) at the Day 90 visit (30 Days Post Treatment).
Time Frame	Day 90 (30 days after completion of 60 days of treatment)

Outcome Measure Data

Analysis Population Description

Analysis shown is based on the modified Intent-to-Treat (mITT) population, defined as all randomized subjects who met the following requirements, 1) met all inclusion/exclusion criteria; 2) applied at least one dose of test article; 3) and returned for at least one post-baseline evaluation clinic visit (Visits 3, 5, or 6).

Arm/Group Title	GDC 695 Gel	Diclofenac Sodium Gel	Placebo
Arm/Group Description	GDC 695 gel applied topically as directed. GDC 695: GDC 695 is a topical gel.	Diclofenac sodium gel, 3% applied topically as directed. Diclofenac Sodium Gel, 3%: Diclofenac sodium gel, 3% is an FDA-approved drug.	Vehicle gel applied topically as directed. Vehicle gel: Vehicle topical gel contains 0.0% of active drug and is color matched to the other two active test drugs.
Measure Participants	215	218	221
Number [percentage of participants]	30.2 13.9%	25.7 11.7%	9.5 4.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GDC 695 Gel, Placebo
	Comments	Two-sided, continuity-corrected Chi-square tests was used to evaluate the superiority of GDC 695 gel's complete clearance proportion over that of the Vehicle treatment in the mITT population using LOCF.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Chi-squared, Corrected
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Diclofenac Sodium Gel, Placebo
	Comments	Two-sided, continuity-corrected Chi-square tests was used to evaluate the superiority of Diclofenac sodium gel's complete clearance proportion over that of the Vehicle treatment in the mITT population using LOCF.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Chi-squared, Corrected
	Comments

2. Other Pre-specified Outcome

Title	Adverse Events (AEs)
Description	AEs will be assessed by the investigator and the incidence (severity and causality) of any local and systemic AEs will be reported.
Time Frame	Day 0 through Day 90

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	Treatment Emergent Adverse Events (TEAEs) were collected from study Day 1 (enrollment/first dose) to study completion (Day 90) or participant termination. AEs that continued beyond completion/termination were followed until resolution or stabilization.
Adverse Event Reporting Description	There were a total of four (4) Serious Adverse Events (SAEs) in three (3) subjects in the Reference group (Diclofenac sodium gel); one of these subjects experienced two (2) SAEs: (1) Bladder transitional cell carcinoma and (2) Haematuria. There were a total of six (6) SAEs in the five (5) subjects in the Placebo group (Vehicle gel); one of these subjects experienced two (2) SAEs: (1) Flank pain and (2) Lung infiltration.
Arm/Group Title	GDC 695		Diclofenac Sodium Gel		Placebo
Arm/Group Description	GDC 695 gel applied topically as directed. GDC 695: GDC 695 is a topical gel.		Diclofenac sodium gel, 3% applied topically as directed. Diclofenac Sodium Gel, 3%: Diclofenac sodium gel, 3% is an FDA-approved drug.		Vehicle gel applied topically as directed. Vehicle gel: Vehicle topical gel contains 0.0% of active drug and is color matched to the other two active test drugs.
All Cause Mortality
	GDC 695		Diclofenac Sodium Gel		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/218 (0%)		0/220 (0%)		0/223 (0%)
Serious Adverse Events
	GDC 695		Diclofenac Sodium Gel		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/218 (0.5%)		3/220 (1.4%)		5/223 (2.2%)
Cardiac disorders
Cardiac disorder	0/218 (0%)	0	1/220 (0.5%)	1	0/223 (0%)	0
Cardiac failure acute	1/218 (0.5%)	1	0/220 (0%)	0	0/223 (0%)	0
Coronary artery disease	0/218 (0%)	0	0/220 (0%)	0	1/223 (0.4%)	1
Gastrointestinal disorders
Diverticulum	0/218 (0%)	0	1/220 (0.5%)	1	0/223 (0%)	0
Infections and infestations
Sepsis syndrome	0/218 (0%)	0	0/220 (0%)	0	1/223 (0.4%)	1
Urinary tract infection	0/218 (0%)	0	0/220 (0%)	0	1/223 (0.4%)	1
Musculoskeletal and connective tissue disorders
Flank pain	0/218 (0%)	0	0/220 (0%)	0	1/223 (0.4%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder transitional cell carcinoma	0/218 (0%)	0	1/220 (0.5%)	1	0/223 (0%)	0
Nervous system disorders
Subarachnoid haemorrhage	0/218 (0%)	0	0/220 (0%)	0	1/223 (0.4%)	1
Renal and urinary disorders
Haematuria	0/218 (0%)	0	1/220 (0.5%)	1	0/223 (0%)	0
Respiratory, thoracic and mediastinal disorders
Lung infiltration	0/218 (0%)	0	0/220 (0%)	0	1/223 (0.4%)	1
Other (Not Including Serious) Adverse Events
	GDC 695		Diclofenac Sodium Gel		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	19/218 (8.7%)		14/220 (6.4%)		6/223 (2.7%)
General disorders
Application site erythema	4/218 (1.8%)	4	3/220 (1.4%)	3	1/223 (0.4%)	1
Application site oedema	3/218 (1.4%)	3	2/220 (0.9%)	2	0/223 (0%)	0
Application site pain	3/218 (1.4%)	3	1/220 (0.5%)	1	1/223 (0.4%)	1
Application site pruritus	3/218 (1.4%)	3	0/220 (0%)	0	2/223 (0.9%)	2
Infections and infestations
Sinusitis	3/218 (1.4%)	3	4/220 (1.8%)	4	0/223 (0%)	0
Upper respiratory tract infection	3/218 (1.4%)	3	4/220 (1.8%)	4	2/223 (0.9%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The Institution and Investigator, including all employees and coworkers involved with this study, agree not to publish the results of this study without the prior written consent of Sponsor.