Trial Outcomes & Findings for Multicenter, Double-blind, Placebo Controlled Comparing Test Fluorouracil Cream to Carac Cream in Actinic Keratosis (NCT NCT02616601)

Last Updated: 2019-07-17

Results Overview

Percentage of participants with treatment success (complete clearance) at Week 6 (4 weeks after completion of 2 weeks of treatment). Complete clearance was defined as having no (zero) clinically visible actinic keratoses (AK) lesions in the treatment area at the Week 6/End Of Study visit. All AK lesions (baseline and new lesions) independent of size within the treatment area were treated and included in the efficacy lesion count.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

422 participants

Primary outcome timeframe

Week 6

Results posted on

2019-07-17

Participant Flow

The populations for this study included the Safety Population, the Per-Protocol (PP) Population, and the modified Intent-to-Treat (mITT) population.

Participant milestones

Participant milestones
Measure	Generic Fluorouracil Cream Participants applied up to 1 gram of generic fluorouracil 0.5% topical cream once daily for 2 weeks (wks) as a thin film to the skin of the treatment area and rub until the cream was no longer visible. Participants were instructed to apply the study drug 10 minutes after thoroughly washing, rinsing, and drying the entire treatment area and 1 to 2 hours before bedtime. Study drug was to have been left on the skin for approximately 8 hours and then removed by washing the area with mild soap and water. Treatment should have continued for the full treatment course even if the actinic keratoses lesions appeared to be gone.	Carac (Fluorouracil) Cream Participants applied up to 1 gram of Carac (fluorouracil) 0.5% topical cream once daily for 2 weeks as a thin film to the skin of the treatment area and rub until the cream was no longer visible. Participants were instructed to apply the study drug 10 minutes after thoroughly washing, rinsing, and drying the entire treatment area and 1 to 2 hours before bedtime. Study drug was to have been left on the skin for approximately 8 hours and then removed by washing the area with mild soap and water. Treatment should have continued for the full treatment course even if the actinic keratoses lesions appeared to be gone.	Vehicle Cream Participants applied up to 1 gram of vehicle topical cream once daily for 2 weeks as a thin film to the skin of the treatment area and rub until the cream was no longer visible. Participants were instructed to apply the study drug 10 minutes after thoroughly washing, rinsing, and drying the entire treatment area and 1 to 2 hours before bedtime. Study drug was to have been left on the skin for approximately 8 hours and then removed by washing the area with mild soap and water. Treatment should have continued for the full treatment course even if the actinic keratoses lesions appeared to be gone.
Overall Study STARTED	140	140	142
Overall Study Safety Population	140	140	142
Overall Study mITT Population	137	136	138
Overall Study PP Population	112	121	123
Overall Study COMPLETED	131	136	135
Overall Study NOT COMPLETED	9	4	7

Reasons for withdrawal

Reasons for withdrawal
Measure	Generic Fluorouracil Cream Participants applied up to 1 gram of generic fluorouracil 0.5% topical cream once daily for 2 weeks (wks) as a thin film to the skin of the treatment area and rub until the cream was no longer visible. Participants were instructed to apply the study drug 10 minutes after thoroughly washing, rinsing, and drying the entire treatment area and 1 to 2 hours before bedtime. Study drug was to have been left on the skin for approximately 8 hours and then removed by washing the area with mild soap and water. Treatment should have continued for the full treatment course even if the actinic keratoses lesions appeared to be gone.	Carac (Fluorouracil) Cream Participants applied up to 1 gram of Carac (fluorouracil) 0.5% topical cream once daily for 2 weeks as a thin film to the skin of the treatment area and rub until the cream was no longer visible. Participants were instructed to apply the study drug 10 minutes after thoroughly washing, rinsing, and drying the entire treatment area and 1 to 2 hours before bedtime. Study drug was to have been left on the skin for approximately 8 hours and then removed by washing the area with mild soap and water. Treatment should have continued for the full treatment course even if the actinic keratoses lesions appeared to be gone.	Vehicle Cream Participants applied up to 1 gram of vehicle topical cream once daily for 2 weeks as a thin film to the skin of the treatment area and rub until the cream was no longer visible. Participants were instructed to apply the study drug 10 minutes after thoroughly washing, rinsing, and drying the entire treatment area and 1 to 2 hours before bedtime. Study drug was to have been left on the skin for approximately 8 hours and then removed by washing the area with mild soap and water. Treatment should have continued for the full treatment course even if the actinic keratoses lesions appeared to be gone.
Overall Study Withdrawal by Subject	4	4	3
Overall Study Adverse Event	2	0	2
Overall Study Death	1	0	0
Overall Study Lost to Follow-up	1	0	1
Overall Study Non-Compliance with Test Article	1	0	1

Baseline Characteristics

Multicenter, Double-blind, Placebo Controlled Comparing Test Fluorouracil Cream to Carac Cream in Actinic Keratosis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Generic Fluorouracil Cream n=140 Participants Participants applied up to 1 gram of generic fluorouracil 0.5% topical cream once daily for 2 weeks as a thin film to the skin of the treatment area and rub until the cream was no longer visible. Participants were instructed to apply the study drug 10 minutes after thoroughly washing, rinsing, and drying the entire treatment area and 1 to 2 hours before bedtime. Study drug was to have been left on the skin for approximately 8 hours and then removed by washing the area with mild soap and water. Treatment should have continued for the full treatment course even if the actinic keratoses lesions appeared to be gone.	Carac (Fluorouracil) Cream n=140 Participants Participants applied up to 1 gram of Carac (fluorouracil) 0.5% topical cream once daily for 2 weeks as a thin film to the skin of the treatment area and rub until the cream was no longer visible. Participants were instructed to apply the study drug 10 minutes after thoroughly washing, rinsing, and drying the entire treatment area and 1 to 2 hours before bedtime. Study drug was to have been left on the skin for approximately 8 hours and then removed by washing the area with mild soap and water. Treatment should have continued for the full treatment course even if the actinic keratoses lesions appeared to be gone.	Vehicle Cream n=142 Participants Participants applied up to 1 gram of vehicle topical cream once daily for 2 weeks as a thin film to the skin of the treatment area and rub until the cream was no longer visible. Participants were instructed to apply the study drug 10 minutes after thoroughly washing, rinsing, and drying the entire treatment area and 1 to 2 hours before bedtime. Study drug was to have been left on the skin for approximately 8 hours and then removed by washing the area with mild soap and water. Treatment should have continued for the full treatment course even if the actinic keratoses lesions appeared to be gone.	Total n=422 Participants Total of all reporting groups
Age, Continuous	67.7 years STANDARD_DEVIATION 9.46 • n=5 Participants	67.4 years STANDARD_DEVIATION 9.43 • n=7 Participants	67.1 years STANDARD_DEVIATION 11.13 • n=5 Participants	67.4 years STANDARD_DEVIATION 10.02 • n=4 Participants
Sex: Female, Male Female	16 Participants n=5 Participants	18 Participants n=7 Participants	20 Participants n=5 Participants	54 Participants n=4 Participants
Sex: Female, Male Male	124 Participants n=5 Participants	122 Participants n=7 Participants	122 Participants n=5 Participants	368 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	4 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	139 Participants n=5 Participants	138 Participants n=7 Participants	141 Participants n=5 Participants	418 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) White	138 Participants n=5 Participants	140 Participants n=7 Participants	141 Participants n=5 Participants	419 Participants n=4 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants

PRIMARY outcome

Timeframe: Week 6

Population: Participants in mlTT population who met inclusion/exclusion criteria, applied 75%-125% applications of study drug, did not miss applications for more than 3 consecutive days, no evidence of dosing noncompliance, and completed evaluation at Week 6 within ±4 days with no protocol violations that would affect treatment evaluation (PP Population).

Outcome measures

Outcome measures
Measure	Generic Fluorouracil Cream n=112 Participants Participants applied up to 1 gram of generic fluorouracil 0.5% topical cream once daily for 2 weeks as a thin film to the skin of the treatment area and rub until the cream was no longer visible. Participants were instructed to apply the study drug 10 minutes after thoroughly washing, rinsing, and drying the entire treatment area and 1 to 2 hours before bedtime. Study drug was to have been left on the skin for approximately 8 hours and then removed by washing the area with mild soap and water. Treatment should have continued for the full treatment course even if the actinic keratoses lesions appeared to be gone.	Carac (Fluorouracil) Cream n=121 Participants Participants applied up to 1 gram of Carac (fluorouracil) 0.5% topical cream once daily for 2 weeks as a thin film to the skin of the treatment area and rub until the cream was no longer visible. Participants were instructed to apply the study drug 10 minutes after thoroughly washing, rinsing, and drying the entire treatment area and 1 to 2 hours before bedtime. Study drug was to have been left on the skin for approximately 8 hours and then removed by washing the area with mild soap and water. Treatment should have continued for the full treatment course even if the actinic keratoses lesions appeared to be gone.	Vehicle Cream n=123 Participants Participants applied up to 1 gram of vehicle topical cream once daily for 2 weeks as a thin film to the skin of the treatment area and rub until the cream was no longer visible. Participants were instructed to apply the study drug 10 minutes after thoroughly washing, rinsing, and drying the entire treatment area and 1 to 2 hours before bedtime. Study drug was to have been left on the skin for approximately 8 hours and then removed by washing the area with mild soap and water. Treatment should have continued for the full treatment course even if the actinic keratoses lesions appeared to be gone.
Percentage of Participants With Treatment Success (Complete Clearance) at Week 6	33.9 percentage of participants	33.9 percentage of participants	3.3 percentage of participants

Adverse Events

Generic Fluorouracil Cream

Serious events: 4 serious events

Other events: 21 other events

Deaths: 1 deaths

Carac (Fluorouracil) Cream

Serious events: 1 serious events

Other events: 13 other events

Deaths: 0 deaths

Vehicle Cream

Serious events: 2 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Generic Fluorouracil Cream n=140 participants at risk Participants applied up to 1 gram of generic fluorouracil 0.5% topical cream once daily for 2 weeks as a thin film to the skin of the treatment area and rub until the cream was no longer visible. Participants were instructed to apply the study drug 10 minutes after thoroughly washing, rinsing, and drying the entire treatment area and 1 to 2 hours before bedtime. Study drug was to have been left on the skin for approximately 8 hours and then removed by washing the area with mild soap and water. Treatment should have continued for the full treatment course even if the actinic keratoses lesions appeared to be gone.	Carac (Fluorouracil) Cream n=140 participants at risk Participants applied up to 1 gram of Carac (fluorouracil) 0.5% topical cream once daily for 2 weeks as a thin film to the skin of the treatment area and rub until the cream was no longer visible. Participants were instructed to apply the study drug 10 minutes after thoroughly washing, rinsing, and drying the entire treatment area and 1 to 2 hours before bedtime. Study drug was to have been left on the skin for approximately 8 hours and then removed by washing the area with mild soap and water. Treatment should have continued for the full treatment course even if the actinic keratoses lesions appeared to be gone.	Vehicle Cream n=142 participants at risk Participants applied up to 1 gram of vehicle topical cream once daily for 2 weeks as a thin film to the skin of the treatment area and rub until the cream was no longer visible. Participants were instructed to apply the study drug 10 minutes after thoroughly washing, rinsing, and drying the entire treatment area and 1 to 2 hours before bedtime. Study drug was to have been left on the skin for approximately 8 hours and then removed by washing the area with mild soap and water. Treatment should have continued for the full treatment course even if the actinic keratoses lesions appeared to be gone.
Infections and infestations Urinary tract infection	0.71% 1/140 • Baseline up to Week 6 Adverse events were collected from participants who were randomized and received the study drug.	0.00% 0/140 • Baseline up to Week 6 Adverse events were collected from participants who were randomized and received the study drug.	0.00% 0/142 • Baseline up to Week 6 Adverse events were collected from participants who were randomized and received the study drug.
Vascular disorders Aortic aneurysm	0.71% 1/140 • Baseline up to Week 6 Adverse events were collected from participants who were randomized and received the study drug.	0.00% 0/140 • Baseline up to Week 6 Adverse events were collected from participants who were randomized and received the study drug.	0.00% 0/142 • Baseline up to Week 6 Adverse events were collected from participants who were randomized and received the study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Acute myeloid leukaemia	0.71% 1/140 • Baseline up to Week 6 Adverse events were collected from participants who were randomized and received the study drug.	0.00% 0/140 • Baseline up to Week 6 Adverse events were collected from participants who were randomized and received the study drug.	0.00% 0/142 • Baseline up to Week 6 Adverse events were collected from participants who were randomized and received the study drug.
Gastrointestinal disorders Inguinal hernia strangulated	0.71% 1/140 • Baseline up to Week 6 Adverse events were collected from participants who were randomized and received the study drug.	0.00% 0/140 • Baseline up to Week 6 Adverse events were collected from participants who were randomized and received the study drug.	0.00% 0/142 • Baseline up to Week 6 Adverse events were collected from participants who were randomized and received the study drug.
Cardiac disorders Bradycardia	0.00% 0/140 • Baseline up to Week 6 Adverse events were collected from participants who were randomized and received the study drug.	0.71% 1/140 • Baseline up to Week 6 Adverse events were collected from participants who were randomized and received the study drug.	0.00% 0/142 • Baseline up to Week 6 Adverse events were collected from participants who were randomized and received the study drug.
Vascular disorders Aortic stenosis	0.00% 0/140 • Baseline up to Week 6 Adverse events were collected from participants who were randomized and received the study drug.	0.00% 0/140 • Baseline up to Week 6 Adverse events were collected from participants who were randomized and received the study drug.	0.70% 1/142 • Baseline up to Week 6 Adverse events were collected from participants who were randomized and received the study drug.
General disorders Asthenia	0.00% 0/140 • Baseline up to Week 6 Adverse events were collected from participants who were randomized and received the study drug.	0.00% 0/140 • Baseline up to Week 6 Adverse events were collected from participants who were randomized and received the study drug.	0.70% 1/142 • Baseline up to Week 6 Adverse events were collected from participants who were randomized and received the study drug.
Skin and subcutaneous tissue disorders Hyperhidrosis	0.00% 0/140 • Baseline up to Week 6 Adverse events were collected from participants who were randomized and received the study drug.	0.00% 0/140 • Baseline up to Week 6 Adverse events were collected from participants who were randomized and received the study drug.	0.70% 1/142 • Baseline up to Week 6 Adverse events were collected from participants who were randomized and received the study drug.

Other adverse events

Additional Information

Director, CE Studies

Teva Pharmaceuticals Inc. USA

Phone: 1-888-483-8279

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Sponsor has the right 60 days before submission for publication to review/provide comments. If the Sponsor's review shows that potentially patentable subject matter would be disclosed, publication or public disclosure shall be delayed for up to 90 additional days in order for the Sponsor, or Sponsor's designees, to file the necessary patent applications. In multicenter trials, each PI will postpone single center publications until after disclosure or publication of multicenter data.
Publication restrictions are in place

Restriction type: OTHER