Trial Outcomes & Findings for Safety and Effectiveness Study of Actinic Keratosis Treatment Following Cryosurgery (NCT NCT00894647)

Last Updated: 2010-08-31

Results Overview

The primary efficacy endpoint was a comparison between the active and placebo treatment groups of percent change from baseline in the total AK lesion count at Week 26. All AK lesions on the face were included in the analysis-treated and untreated AK lesions at baseline (defined as the AK lesion count just prior to cryosurgery) and new lesions that appeared post-baseline.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

247 participants

Primary outcome timeframe

Week 26

Results posted on

2010-08-31

Participant Flow

Subjects were screened in 20 sites-16 in the United States of America (U.S.A.) and 4 in Canada. Screening began on 01 Jun 2009 and the last subject was enrolled on 03 Aug 2009.

Subjects had to have ≥10 AK lesions in an area the face to participate in the study. At screening, at least 5 visible lesions were not treated with cryosurgery, and 5 to 14 visible lesions were treated with cryosurgery. Subjects needed at least 5 AK lesions after the skin healed sufficiently from the cryosurgery to be eligible for randomization.

Participant milestones

Participant milestones
Measure	Placebo Cream placebo cream in 250 mg/packet, up to 2 packets applied daily	Imiquimod Cream Imiquimod 3.75% cream, 250 mg single-use packets, up to 2 packets applied daily
Overall Study STARTED	121	126
Overall Study COMPLETED	111	112
Overall Study NOT COMPLETED	10	14

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Cream placebo cream in 250 mg/packet, up to 2 packets applied daily	Imiquimod Cream Imiquimod 3.75% cream, 250 mg single-use packets, up to 2 packets applied daily
Overall Study Adverse Event	5	4
Overall Study Withdrawal by Subject	4	4
Overall Study Lost to Follow-up	0	2
Overall Study Non-compliance with study procedures	0	2
Overall Study Other, not due to AE	1	2

Baseline Characteristics

Safety and Effectiveness Study of Actinic Keratosis Treatment Following Cryosurgery

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo Cream n=121 Participants placebo cream in 250 mg/packet, up to 2 packets applied daily	Imiquimod Cream n=126 Participants Imiquimod 3.75% cream, 250 mg single-use packets, up to 2 packets applied daily	Total n=247 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	48 Participants n=5 Participants	63 Participants n=7 Participants	111 Participants n=5 Participants
Age, Categorical >=65 years	73 Participants n=5 Participants	63 Participants n=7 Participants	136 Participants n=5 Participants
Age Continuous	67.3 years STANDARD_DEVIATION 10.05 • n=5 Participants	66.0 years STANDARD_DEVIATION 9.49 • n=7 Participants	66.7 years STANDARD_DEVIATION 9.77 • n=5 Participants
Sex: Female, Male Female	15 Participants n=5 Participants	18 Participants n=7 Participants	33 Participants n=5 Participants
Sex: Female, Male Male	106 Participants n=5 Participants	108 Participants n=7 Participants	214 Participants n=5 Participants
Region of Enrollment United States	90 participants n=5 Participants	91 participants n=7 Participants	181 participants n=5 Participants
Region of Enrollment Canada	31 participants n=5 Participants	35 participants n=7 Participants	66 participants n=5 Participants

PRIMARY outcome

Timeframe: Week 26

Population: Intent to treat population, Last Observation Carried Forward (LOCF)

Outcome measures

Outcome measures
Measure	Placebo Cream n=121 Participants placebo cream in 250 mg/packet, up to 2 packets applied daily	Imiquimod Cream n=126 Participants Imiquimod 3.75% cream, 250 mg single-use packets, up to 2 packets applied daily
Change From Baseline in Percentage of Lesion Count	-43.3 percentage of lesion count Standard Deviation 30.66	-77.4 percentage of lesion count Standard Deviation 27.54

SECONDARY outcome

Timeframe: Week 26

Population: Intent to treat (ITT) population, last observation carried forward (LOCF)

Proportion of subjects who achieved complete clearance of all AK lesions, cryosurgery-treated AK lesions, and non cryosurgery-treated AK lesions from baseline to Week 26/EOS in the ITT population.

Outcome measures

Outcome measures
Measure	Placebo Cream n=121 Participants placebo cream in 250 mg/packet, up to 2 packets applied daily	Imiquimod Cream n=126 Participants Imiquimod 3.75% cream, 250 mg single-use packets, up to 2 packets applied daily
Percent of Subjects With Complete Clearance	3 percentage of participants Interval 0.9 to 8.2	30 percentage of participants Interval 22.3 to 39.0

SECONDARY outcome

Timeframe: Weeks 2, 4, 6, 10, 14, 20, and 26

Population: Safety population: all randomized subjects were presumed to have applied at least one application of study medication and were included in the safety population. This population was used for all safety analyses. Subjects were analyzed as treated.

LSRs were assessed independently from AEs. The frequency and percentage of subjects, as well as the mean (SD) and median score for severity (none=0, mild=1, moderate=2, and severe=3), were summarized by treatment group and by visit for the following LSRs: erythema, edema, weeping/exudates, flaking/ scaling/dryness, and scabbing/crusting. Erosion and ulceration were also evaluated (none=0, erosion=1, and ulceration=2). A score of greater than 0 for the specified LSR was considered a "treatment site reaction".

Outcome measures

Outcome measures
Measure	Placebo Cream n=121 Participants placebo cream in 250 mg/packet, up to 2 packets applied daily	Imiquimod Cream n=126 Participants Imiquimod 3.75% cream, 250 mg single-use packets, up to 2 packets applied daily
Number of Participants With Any Post-baseline Local Skin Reactions (LSRs) Edema	9 participants	93 participants
Number of Participants With Any Post-baseline Local Skin Reactions (LSRs) Erythema	88 participants	125 participants
Number of Participants With Any Post-baseline Local Skin Reactions (LSRs) Weeping/Exudate	9 participants	64 participants
Number of Participants With Any Post-baseline Local Skin Reactions (LSRs) Flaking/Scaling/Dryness	3 participants	114 participants
Number of Participants With Any Post-baseline Local Skin Reactions (LSRs) Scabbing, crusting	81 participants	112 participants
Number of Participants With Any Post-baseline Local Skin Reactions (LSRs) Erosion/Ulceration	22 participants	60 participants

Adverse Events

Placebo Cream

Serious events: 2 serious events

Other events: 28 other events

Deaths: 0 deaths

Imiquimod Cream

Serious events: 6 serious events

Other events: 54 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo Cream n=121 participants at risk placebo cream in 250 mg/packet, up to 2 packets applied daily	Imiquimod Cream n=126 participants at risk Imiquimod 3.75% cream, 250 mg single-use packets, up to 2 packets applied daily
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine Cancer	0.00% 0/121 • Up to the end of study visit - Week 26 AEs were collected from Visit 1 to the end of the final study visit for each subject.	0.79% 1/126 • Number of events 1 • Up to the end of study visit - Week 26 AEs were collected from Visit 1 to the end of the final study visit for each subject.
Cardiac disorders Cardiac Arrest	0.00% 0/121 • Up to the end of study visit - Week 26 AEs were collected from Visit 1 to the end of the final study visit for each subject.	0.79% 1/126 • Number of events 1 • Up to the end of study visit - Week 26 AEs were collected from Visit 1 to the end of the final study visit for each subject.
Injury, poisoning and procedural complications Fractured Leg	0.00% 0/121 • Up to the end of study visit - Week 26 AEs were collected from Visit 1 to the end of the final study visit for each subject.	0.79% 1/126 • Number of events 1 • Up to the end of study visit - Week 26 AEs were collected from Visit 1 to the end of the final study visit for each subject.
Injury, poisoning and procedural complications Worsening of sciatic nerve	0.00% 0/121 • Up to the end of study visit - Week 26 AEs were collected from Visit 1 to the end of the final study visit for each subject.	0.79% 1/126 • Number of events 1 • Up to the end of study visit - Week 26 AEs were collected from Visit 1 to the end of the final study visit for each subject.
Injury, poisoning and procedural complications Deep right thigh bruise	0.00% 0/121 • Up to the end of study visit - Week 26 AEs were collected from Visit 1 to the end of the final study visit for each subject.	0.79% 1/126 • Number of events 1 • Up to the end of study visit - Week 26 AEs were collected from Visit 1 to the end of the final study visit for each subject.
Infections and infestations Possible viral syndrome	0.00% 0/121 • Up to the end of study visit - Week 26 AEs were collected from Visit 1 to the end of the final study visit for each subject.	0.79% 1/126 • Number of events 1 • Up to the end of study visit - Week 26 AEs were collected from Visit 1 to the end of the final study visit for each subject.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma right cheek	0.83% 1/121 • Number of events 1 • Up to the end of study visit - Week 26 AEs were collected from Visit 1 to the end of the final study visit for each subject.	0.00% 0/126 • Up to the end of study visit - Week 26 AEs were collected from Visit 1 to the end of the final study visit for each subject.
Cardiac disorders Death (Possible cardiac arrest)	0.83% 1/121 • Number of events 1 • Up to the end of study visit - Week 26 AEs were collected from Visit 1 to the end of the final study visit for each subject.	0.00% 0/126 • Up to the end of study visit - Week 26 AEs were collected from Visit 1 to the end of the final study visit for each subject.

Other adverse events

Other adverse events
Measure	Placebo Cream n=121 participants at risk placebo cream in 250 mg/packet, up to 2 packets applied daily	Imiquimod Cream n=126 participants at risk Imiquimod 3.75% cream, 250 mg single-use packets, up to 2 packets applied daily
Gastrointestinal disorders Nausea	0.00% 0/121 • Up to the end of study visit - Week 26 AEs were collected from Visit 1 to the end of the final study visit for each subject.	4.8% 6/126 • Number of events 6 • Up to the end of study visit - Week 26 AEs were collected from Visit 1 to the end of the final study visit for each subject.
General disorders Application site irritation	0.83% 1/121 • Number of events 1 • Up to the end of study visit - Week 26 AEs were collected from Visit 1 to the end of the final study visit for each subject.	5.6% 7/126 • Number of events 7 • Up to the end of study visit - Week 26 AEs were collected from Visit 1 to the end of the final study visit for each subject.
General disorders Application site pain	0.00% 0/121 • Up to the end of study visit - Week 26 AEs were collected from Visit 1 to the end of the final study visit for each subject.	4.8% 6/126 • Number of events 6 • Up to the end of study visit - Week 26 AEs were collected from Visit 1 to the end of the final study visit for each subject.
General disorders Application site pruritus	0.83% 1/121 • Number of events 1 • Up to the end of study visit - Week 26 AEs were collected from Visit 1 to the end of the final study visit for each subject.	9.5% 12/126 • Number of events 12 • Up to the end of study visit - Week 26 AEs were collected from Visit 1 to the end of the final study visit for each subject.
General disorders Fatigue	0.83% 1/121 • Number of events 1 • Up to the end of study visit - Week 26 AEs were collected from Visit 1 to the end of the final study visit for each subject.	4.0% 5/126 • Number of events 5 • Up to the end of study visit - Week 26 AEs were collected from Visit 1 to the end of the final study visit for each subject.
Infections and infestations Upper respiratory tract infection	7.4% 9/121 • Number of events 9 • Up to the end of study visit - Week 26 AEs were collected from Visit 1 to the end of the final study visit for each subject.	5.6% 7/126 • Number of events 7 • Up to the end of study visit - Week 26 AEs were collected from Visit 1 to the end of the final study visit for each subject.
Infections and infestations Bronchitis	4.1% 5/121 • Number of events 5 • Up to the end of study visit - Week 26 AEs were collected from Visit 1 to the end of the final study visit for each subject.	0.79% 1/126 • Number of events 1 • Up to the end of study visit - Week 26 AEs were collected from Visit 1 to the end of the final study visit for each subject.
Infections and infestations Sinusitis	4.1% 5/121 • Number of events 5 • Up to the end of study visit - Week 26 AEs were collected from Visit 1 to the end of the final study visit for each subject.	0.00% 0/126 • Up to the end of study visit - Week 26 AEs were collected from Visit 1 to the end of the final study visit for each subject.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	3.3% 4/121 • Number of events 4 • Up to the end of study visit - Week 26 AEs were collected from Visit 1 to the end of the final study visit for each subject.	1.6% 2/126 • Number of events 2 • Up to the end of study visit - Week 26 AEs were collected from Visit 1 to the end of the final study visit for each subject.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma	3.3% 4/121 • Number of events 4 • Up to the end of study visit - Week 26 AEs were collected from Visit 1 to the end of the final study visit for each subject.	1.6% 2/126 • Number of events 2 • Up to the end of study visit - Week 26 AEs were collected from Visit 1 to the end of the final study visit for each subject.
Musculoskeletal and connective tissue disorders Myalgia	0.83% 1/121 • Number of events 1 • Up to the end of study visit - Week 26 AEs were collected from Visit 1 to the end of the final study visit for each subject.	4.8% 6/126 • Number of events 6 • Up to the end of study visit - Week 26 AEs were collected from Visit 1 to the end of the final study visit for each subject.

Additional Information

Vice President Medical Affairs

Graceway Pharmaceuticals

Phone: 267-948-0400

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place