Trial Outcomes & Findings for Study Comparing GDC 695 and Diclofenac Sodium Gel, 3% in Subjects With Actinic Keratoses (NCT NCT02952898)

NCT ID: NCT02952898

Last Updated: 2020-01-07

Results Overview

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).

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 665 participants
• Primary outcome timeframe: Day 90 (30 days after completion of 60 days of treatment)
• Results posted on: 2020-01-07

Participant Flow

Recruitment Period: October 2016 to July 2017 The location of clinical sites included dermatology clinics and clinical research centers.

All subjects who met the entry criteria and were randomized and enrolled into the study.

Participant milestones

Measure	GDC 695 Gel The test drug is GDC 695 gel applied topically as directed. GDC 695: GDC 695 is a topical gel.	Diclofenac Sodium 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.	Placebo 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.
Overall Study STARTED	220	221	224
Overall Study COMPLETED	198	202	209
Overall Study NOT COMPLETED	22	19	15

Reasons for withdrawal

Measure	GDC 695 Gel The test drug is GDC 695 gel applied topically as directed. GDC 695: GDC 695 is a topical gel.	Diclofenac Sodium 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.	Placebo 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.
Overall Study Withdrawal by Subject	10	8	8
Overall Study Adverse Event	8	8	3
Overall Study Lost to Follow-up	3	2	2
Overall Study Non-compliance with study drug	1	1	2

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	GDC 695 Gel n=218 Participants GDC 695 gel applied topically as directed. GDC 695: GDC 695 is a topical gel.	Diclofenac Sodium Gel n=220 Participants Diclofenac sodium gel, 3% applied topically as directed. Diclofenac Sodium Gel, 3%: Diclofenac sodium gel, 3% is an FDA-approved drug.	Placebo n=223 Participants 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 n=661 Participants Total of all reporting groups
Age, Continuous	70.2 years STANDARD_DEVIATION 9.4 • n=5 Participants	69.6 years STANDARD_DEVIATION 9.8 • n=7 Participants	69.1 years STANDARD_DEVIATION 9.3 • n=5 Participants	69.6 years STANDARD_DEVIATION 9.5 • n=4 Participants
Sex: Female, Male Female	31 Participants n=5 Participants	45 Participants n=7 Participants	36 Participants n=5 Participants	112 Participants n=4 Participants
Sex: Female, Male Male	187 Participants n=5 Participants	175 Participants n=7 Participants	187 Participants n=5 Participants	549 Participants n=4 Participants
Race/Ethnicity, Customized Ethnicity · Hispanic or Latino	14 Participants n=5 Participants	13 Participants n=7 Participants	16 Participants n=5 Participants	43 Participants n=4 Participants
Race/Ethnicity, Customized Ethnicity · Not Hispanic or Latino	204 Participants n=5 Participants	207 Participants n=7 Participants	207 Participants n=5 Participants	618 Participants n=4 Participants
Race/Ethnicity, Customized Race · American Indian or Alaska Native	1 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	4 Participants n=4 Participants
Race/Ethnicity, Customized Race · White	217 Participants n=5 Participants	218 Participants n=7 Participants	222 Participants n=5 Participants	657 Participants n=4 Participants
Region of Enrollment United States	218 participants n=5 Participants	220 participants n=7 Participants	223 participants n=5 Participants	661 participants n=4 Participants

PRIMARY outcome

Timeframe: Day 90 (30 days after completion of 60 days of treatment)

Population: 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).

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).

Outcome measures

Measure	GDC 695 Gel n=215 Participants GDC 695 gel applied topically as directed. GDC 695: GDC 695 is a topical gel.	Diclofenac Sodium Gel n=218 Participants Diclofenac sodium gel, 3% applied topically as directed. Diclofenac Sodium Gel, 3%: Diclofenac sodium gel, 3% is an FDA-approved drug.	Placebo n=221 Participants 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.
Number of Subjects With Complete Clearance of AK Lesions	30.2 percentage of participants	25.7 percentage of participants	9.5 percentage of participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Outcome measures

Outcome data not reported

Adverse Events

GDC 695

Serious events: 1 serious events

Other events: 19 other events

Deaths: 0 deaths

Diclofenac Sodium Gel

Serious events: 3 serious events

Other events: 14 other events

Deaths: 0 deaths

Placebo

Serious events: 5 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Measure	GDC 695 n=218 participants at risk GDC 695 gel applied topically as directed. GDC 695: GDC 695 is a topical gel.	Diclofenac Sodium Gel n=220 participants at risk Diclofenac sodium gel, 3% applied topically as directed. Diclofenac Sodium Gel, 3%: Diclofenac sodium gel, 3% is an FDA-approved drug.	Placebo n=223 participants at risk 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.
Cardiac disorders Cardiac disorder	0.00% 0/218 • 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. 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.	0.45% 1/220 • Number of events 1 • 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. 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.	0.00% 0/223 • 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. 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.
Cardiac disorders Cardiac failure acute	0.46% 1/218 • Number of events 1 • 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. 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.	0.00% 0/220 • 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. 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.	0.00% 0/223 • 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. 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.
Cardiac disorders Coronary artery disease	0.00% 0/218 • 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. 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.	0.00% 0/220 • 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. 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.	0.45% 1/223 • Number of events 1 • 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. 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.
Gastrointestinal disorders Diverticulum	0.00% 0/218 • 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. 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.	0.45% 1/220 • Number of events 1 • 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. 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.	0.00% 0/223 • 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. 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.
Infections and infestations Sepsis syndrome	0.00% 0/218 • 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. 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.	0.00% 0/220 • 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. 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.	0.45% 1/223 • Number of events 1 • 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. 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.
Infections and infestations Urinary tract infection	0.00% 0/218 • 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. 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.	0.00% 0/220 • 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. 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.	0.45% 1/223 • Number of events 1 • 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. 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.
Musculoskeletal and connective tissue disorders Flank pain	0.00% 0/218 • 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. 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.	0.00% 0/220 • 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. 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.	0.45% 1/223 • Number of events 1 • 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. 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder transitional cell carcinoma	0.00% 0/218 • 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. 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.	0.45% 1/220 • Number of events 1 • 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. 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.	0.00% 0/223 • 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. 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.
Nervous system disorders Subarachnoid haemorrhage	0.00% 0/218 • 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. 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.	0.00% 0/220 • 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. 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.	0.45% 1/223 • Number of events 1 • 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. 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.
Renal and urinary disorders Haematuria	0.00% 0/218 • 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. 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.	0.45% 1/220 • Number of events 1 • 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. 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.	0.00% 0/223 • 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. 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.
Respiratory, thoracic and mediastinal disorders Lung infiltration	0.00% 0/218 • 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. 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.	0.00% 0/220 • 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. 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.	0.45% 1/223 • Number of events 1 • 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. 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.

Other adverse events

Measure	GDC 695 n=218 participants at risk GDC 695 gel applied topically as directed. GDC 695: GDC 695 is a topical gel.	Diclofenac Sodium Gel n=220 participants at risk Diclofenac sodium gel, 3% applied topically as directed. Diclofenac Sodium Gel, 3%: Diclofenac sodium gel, 3% is an FDA-approved drug.	Placebo n=223 participants at risk 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.
General disorders Application site erythema	1.8% 4/218 • Number of events 4 • 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. 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.	1.4% 3/220 • Number of events 3 • 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. 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.	0.45% 1/223 • Number of events 1 • 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. 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.
General disorders Application site oedema	1.4% 3/218 • Number of events 3 • 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. 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.	0.91% 2/220 • Number of events 2 • 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. 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.	0.00% 0/223 • 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. 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.
General disorders Application site pain	1.4% 3/218 • Number of events 3 • 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. 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.	0.45% 1/220 • Number of events 1 • 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. 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.	0.45% 1/223 • Number of events 1 • 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. 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.
General disorders Application site pruritus	1.4% 3/218 • Number of events 3 • 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. 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.	0.00% 0/220 • 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. 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.	0.90% 2/223 • Number of events 2 • 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. 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.
Infections and infestations Sinusitis	1.4% 3/218 • Number of events 3 • 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. 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.	1.8% 4/220 • Number of events 4 • 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. 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.	0.00% 0/223 • 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. 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.
Infections and infestations Upper respiratory tract infection	1.4% 3/218 • Number of events 3 • 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. 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.	1.8% 4/220 • Number of events 4 • 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. 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.	0.90% 2/223 • Number of events 2 • 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. 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.

Additional Information

Gage Development Company

Gage Development Company

Phone: 1-847-999-0600

Email: clinicalinfo@capstonedevservices.com

Results disclosure agreements

• Principal investigator is a sponsor employee 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.
• Publication restrictions are in place

Restriction type: OTHER