Trial Outcomes & Findings for Safety and Effectiveness Study of Imiquimod Creams for the Treatment of Actinic Keratoses (AKs) (NCT NCT00603798)

Last Updated: 2010-06-29

Results Overview

Subject status with respect to complete clearance of AK lesions at End of Study (EOS), ie, the Week 17 visit. Complete clearance was defined as the absence of clinically visible or palpable AK lesions in the treatment area. All lesions within the identified treatment area were included in the count, even if the lesion was a new lesion or "subclinical" lesion that had not been identified at Baseline.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

490 participants

Primary outcome timeframe

End of Study the Week 17 visit

Results posted on

2010-06-29

Participant Flow

Recruitment started on January 15, 2008 and all subjects were randomized by March 6, 2008. The studies were performed at 26 investigational centers in the United States.

Subjects were screened and had to meet eligibility requirements for randomization. The most frequent reason for screen failure (44 of screen failures) was that the subject did not have between 5 and 20 visible or palpable lesions on either the face or the balding scalp.

Participant milestones

Participant milestones
Measure	3.75% Imiquimod Cream 250 mg/packet, up to 2 packets applied daily for 2 treatment cycles. The first treatment cycle consisted of 3 weeks of daily treatment followed by 3 weeks of no treatment, and the second treatment cycle consisted of an additional 3 weeks of daily treatment followed by 8 weeks of no treatment.	2.5% Imiquimod Cream 250 mg/packet, up to 2 packets applied daily for 2 treatment cycles. The first treatment cycle consisted of 3 weeks of daily treatment followed by 3 weeks of no treatment, and the second treatment cycle consisted of an additional 3 weeks of daily treatment followed by 8 weeks of no treatment.	Placebo Cream 250 mg/packet, up to 2 packets applied daily for 2 treatment cycles. The first treatment cycle consisted of 3 weeks of daily treatment followed by 3 weeks of no treatment, and the second treatment cycle consisted of an additional 3 weeks of daily treatment followed by 8 weeks of no treatment.
Overall Study STARTED	162	164	164
Overall Study COMPLETED	152	157	154
Overall Study NOT COMPLETED	10	7	10

Reasons for withdrawal

Reasons for withdrawal
Measure	3.75% Imiquimod Cream 250 mg/packet, up to 2 packets applied daily for 2 treatment cycles. The first treatment cycle consisted of 3 weeks of daily treatment followed by 3 weeks of no treatment, and the second treatment cycle consisted of an additional 3 weeks of daily treatment followed by 8 weeks of no treatment.	2.5% Imiquimod Cream 250 mg/packet, up to 2 packets applied daily for 2 treatment cycles. The first treatment cycle consisted of 3 weeks of daily treatment followed by 3 weeks of no treatment, and the second treatment cycle consisted of an additional 3 weeks of daily treatment followed by 8 weeks of no treatment.	Placebo Cream 250 mg/packet, up to 2 packets applied daily for 2 treatment cycles. The first treatment cycle consisted of 3 weeks of daily treatment followed by 3 weeks of no treatment, and the second treatment cycle consisted of an additional 3 weeks of daily treatment followed by 8 weeks of no treatment.
Overall Study Adverse Event	4	2	1
Overall Study Withdrawal by Subject	4	3	4
Overall Study Lost to Follow-up	1	0	1
Overall Study Non-compliance with study procedures	0	1	0
Overall Study Not due to AE	1	1	4

Baseline Characteristics

Safety and Effectiveness Study of Imiquimod Creams for the Treatment of Actinic Keratoses (AKs)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	3.75% Imiquimod Cream n=162 Participants 250 mg/packet, up to 2 packets applied daily for 2 treatment cycles. The first treatment cycle consisted of 3 weeks of daily treatment followed by 3 weeks of no treatment, and the second treatment cycle consisted of an additional 3 weeks of daily treatment followed by 8 weeks of no treatment.	2.5% Imiquimod Cream n=164 Participants 250 mg/packet, up to 2 packets applied daily for 2 treatment cycles. The first treatment cycle consisted of 3 weeks of daily treatment followed by 3 weeks of no treatment, and the second treatment cycle consisted of an additional 3 weeks of daily treatment followed by 8 weeks of no treatment.	Placebo Cream n=164 Participants 250 mg/packet, up to 2 packets applied daily for 2 treatment cycles. The first treatment cycle consisted of 3 weeks of daily treatment followed by 3 weeks of no treatment, and the second treatment cycle consisted of an additional 3 weeks of daily treatment followed by 8 weeks of no treatment.	Total n=490 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	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	94 Participants n=5 Participants	75 Participants n=7 Participants	86 Participants n=5 Participants	255 Participants n=4 Participants
Age, Categorical >=65 years	68 Participants n=5 Participants	89 Participants n=7 Participants	78 Participants n=5 Participants	235 Participants n=4 Participants
Age Continuous	64.3 years STANDARD_DEVIATION 10.2 • n=5 Participants	66.0 years STANDARD_DEVIATION 10.2 • n=7 Participants	63.7 years STANDARD_DEVIATION 10.9 • n=5 Participants	64.7 years STANDARD_DEVIATION 10.4 • n=4 Participants
Sex: Female, Male Female	39 Participants n=5 Participants	36 Participants n=7 Participants	29 Participants n=5 Participants	104 Participants n=4 Participants
Sex: Female, Male Male	123 Participants n=5 Participants	128 Participants n=7 Participants	135 Participants n=5 Participants	386 Participants n=4 Participants
Region of Enrollment United States	162 participants n=5 Participants	164 participants n=7 Participants	164 participants n=5 Participants	490 participants n=4 Participants

PRIMARY outcome

Timeframe: End of Study the Week 17 visit

Population: Efficacy analyses were conducted on the intent-to-treat (ITT) population. For the primary efficacy variable, imputations were made for missing data points using last observation carried forward (LOCF), primary analysis), taking all missed observations as failure (sensitivity analysis), and using observed cases only (supportive analysis).

Outcome measures

Outcome measures
Measure	3.75% Imiquimod Cream n=162 Participants 250 mg/packet, up to 2 packets applied daily for 2 treatment cycles. The first treatment cycle consisted of 3 weeks of daily treatment followed by 3 weeks of no treatment, and the second treatment cycle consisted of an additional 3 weeks of daily treatment followed by 8 weeks of no treatment.	2.5% Imiquimod Cream n=164 Participants 250 mg/packet, up to 2 packets applied daily for 2 treatment cycles. The first treatment cycle consisted of 3 weeks of daily treatment followed by 3 weeks of no treatment, and the second treatment cycle consisted of an additional 3 weeks of daily treatment followed by 8 weeks of no treatment.	Placebo Cream n=164 Participants 250 mg/packet, up to 2 packets applied daily for 2 treatment cycles. The first treatment cycle consisted of 3 weeks of daily treatment followed by 3 weeks of no treatment, and the second treatment cycle consisted of an additional 3 weeks of daily treatment followed by 8 weeks of no treatment.
Number of Participants With Complete Clearance of AK Lesions	55 participants	41 participants	9 participants

SECONDARY outcome

Timeframe: End of Study the Week 17 visit

Population: Efficacy analyses were conducted on the intent-to-treat (ITT) population. Imputations were made for missing data points using last observation carried forward (LOCF).

Subject status with respect to complete clearance of AK lesions at End of Study (EOS), defined as at least a 75% reduction in the number of AK lesions in the treatment area compared with Baseline.

Outcome measures

Outcome measures
Measure	3.75% Imiquimod Cream n=162 Participants 250 mg/packet, up to 2 packets applied daily for 2 treatment cycles. The first treatment cycle consisted of 3 weeks of daily treatment followed by 3 weeks of no treatment, and the second treatment cycle consisted of an additional 3 weeks of daily treatment followed by 8 weeks of no treatment.	2.5% Imiquimod Cream n=164 Participants 250 mg/packet, up to 2 packets applied daily for 2 treatment cycles. The first treatment cycle consisted of 3 weeks of daily treatment followed by 3 weeks of no treatment, and the second treatment cycle consisted of an additional 3 weeks of daily treatment followed by 8 weeks of no treatment.	Placebo Cream n=164 Participants 250 mg/packet, up to 2 packets applied daily for 2 treatment cycles. The first treatment cycle consisted of 3 weeks of daily treatment followed by 3 weeks of no treatment, and the second treatment cycle consisted of an additional 3 weeks of daily treatment followed by 8 weeks of no treatment.
Number of Participants With Partial Clearance of AK Lesions	87 participants	70 participants	21 participants

SECONDARY outcome

Timeframe: At all visits - Baseline through the Week 17 EOS visit

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

Percent change from Baseline to end of study (EOS) in investigator counts of AK lesions. A negative percent change is better than a positive percent change.

Outcome measures

Outcome measures
Measure	3.75% Imiquimod Cream n=162 Participants 250 mg/packet, up to 2 packets applied daily for 2 treatment cycles. The first treatment cycle consisted of 3 weeks of daily treatment followed by 3 weeks of no treatment, and the second treatment cycle consisted of an additional 3 weeks of daily treatment followed by 8 weeks of no treatment.	2.5% Imiquimod Cream n=164 Participants 250 mg/packet, up to 2 packets applied daily for 2 treatment cycles. The first treatment cycle consisted of 3 weeks of daily treatment followed by 3 weeks of no treatment, and the second treatment cycle consisted of an additional 3 weeks of daily treatment followed by 8 weeks of no treatment.	Placebo Cream n=164 Participants 250 mg/packet, up to 2 packets applied daily for 2 treatment cycles. The first treatment cycle consisted of 3 weeks of daily treatment followed by 3 weeks of no treatment, and the second treatment cycle consisted of an additional 3 weeks of daily treatment followed by 8 weeks of no treatment.
Percent Change From Baseline in AK Lesion Count	-80.0 percentage of participants Interval -100.0 to 160.0	-66.7 percentage of participants Interval -100.0 to 183.3	-23.6 percentage of participants Interval -100.0 to 200.0

SECONDARY outcome

Timeframe: The time period for the AUC extends to 8 weeks after the end of treatment (Week 17)

Population: All participants were evaluated for local skin reactions (LSR) at every visit. The ITT population was used. Only subjects who received treatment in both cycles are included in the analysis.

Six local skin reaction (LSR) signs were predefined and were assessed for presence and intensity at each visit. These included: Erythema, edema, Weeping/Exudate, Flaking/Scaling/Dryness, Scabbing/Crusting and Erosion/Ulceration. The LSRs were scored as 0=none, 1=mild, 2=moderate, 3=severe. Summary of LSR - area under the curve (AUC) of sum of LSR scores (days).

Outcome measures

Outcome measures
Measure	3.75% Imiquimod Cream n=152 Participants 250 mg/packet, up to 2 packets applied daily for 2 treatment cycles. The first treatment cycle consisted of 3 weeks of daily treatment followed by 3 weeks of no treatment, and the second treatment cycle consisted of an additional 3 weeks of daily treatment followed by 8 weeks of no treatment.	2.5% Imiquimod Cream n=155 Participants 250 mg/packet, up to 2 packets applied daily for 2 treatment cycles. The first treatment cycle consisted of 3 weeks of daily treatment followed by 3 weeks of no treatment, and the second treatment cycle consisted of an additional 3 weeks of daily treatment followed by 8 weeks of no treatment.	Placebo Cream n=160 Participants 250 mg/packet, up to 2 packets applied daily for 2 treatment cycles. The first treatment cycle consisted of 3 weeks of daily treatment followed by 3 weeks of no treatment, and the second treatment cycle consisted of an additional 3 weeks of daily treatment followed by 8 weeks of no treatment.
Local Skin Reactions (LSR)	413.5 units on a scale * days Standard Deviation 187.7	372.0 units on a scale * days Standard Deviation 180.6	188.6 units on a scale * days Standard Deviation 136.7

Adverse Events

3.75% Imiquimod Cream

Serious events: 10 serious events

Other events: 39 other events

Deaths: 0 deaths

2.5% Imiquimod Cream

Serious events: 5 serious events

Other events: 29 other events

Deaths: 0 deaths

Placebo Cream

Serious events: 3 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	3.75% Imiquimod Cream n=162 participants at risk 250 mg/packet, up to 2 packets applied daily for 2 treatment cycles. The first treatment cycle consisted of 3 weeks of daily treatment followed by 3 weeks of no treatment, and the second treatment cycle consisted of an additional 3 weeks of daily treatment followed by 8 weeks of no treatment.	2.5% Imiquimod Cream n=164 participants at risk 250 mg/packet, up to 2 packets applied daily for 2 treatment cycles. The first treatment cycle consisted of 3 weeks of daily treatment followed by 3 weeks of no treatment, and the second treatment cycle consisted of an additional 3 weeks of daily treatment followed by 8 weeks of no treatment.	Placebo Cream n=164 participants at risk 250 mg/packet, up to 2 packets applied daily for 2 treatment cycles. The first treatment cycle consisted of 3 weeks of daily treatment followed by 3 weeks of no treatment, and the second treatment cycle consisted of an additional 3 weeks of daily treatment followed by 8 weeks of no treatment.
General disorders Application site pruritus	9.3% 15/162 • Number of events 15 • From study screening through the last study visit. From Day 1 up to Week 17 Subjects were queried indirectly regarding AEs during each study visit.	7.3% 12/164 • Number of events 12 • From study screening through the last study visit. From Day 1 up to Week 17 Subjects were queried indirectly regarding AEs during each study visit.	0.61% 1/164 • Number of events 1 • From study screening through the last study visit. From Day 1 up to Week 17 Subjects were queried indirectly regarding AEs during each study visit.
General disorders Application site irritation	5.6% 9/162 • Number of events 9 • From study screening through the last study visit. From Day 1 up to Week 17 Subjects were queried indirectly regarding AEs during each study visit.	3.7% 6/164 • Number of events 6 • From study screening through the last study visit. From Day 1 up to Week 17 Subjects were queried indirectly regarding AEs during each study visit.	0.61% 1/164 • Number of events 1 • From study screening through the last study visit. From Day 1 up to Week 17 Subjects were queried indirectly regarding AEs during each study visit.
General disorders Application site pain	9.3% 15/162 • Number of events 15 • From study screening through the last study visit. From Day 1 up to Week 17 Subjects were queried indirectly regarding AEs during each study visit.	6.7% 11/164 • Number of events 11 • From study screening through the last study visit. From Day 1 up to Week 17 Subjects were queried indirectly regarding AEs during each study visit.	0.00% 0/164 • From study screening through the last study visit. From Day 1 up to Week 17 Subjects were queried indirectly regarding AEs during each study visit.

Additional Information

Sharon F Levy, MD

Graceway Pharmaceuticals

Phone: 267-948-0400

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	3.75% Imiquimod Cream n=162 participants at risk 250 mg/packet, up to 2 packets applied daily for 2 treatment cycles. The first treatment cycle consisted of 3 weeks of daily treatment followed by 3 weeks of no treatment, and the second treatment cycle consisted of an additional 3 weeks of daily treatment followed by 8 weeks of no treatment.	2.5% Imiquimod Cream n=164 participants at risk 250 mg/packet, up to 2 packets applied daily for 2 treatment cycles. The first treatment cycle consisted of 3 weeks of daily treatment followed by 3 weeks of no treatment, and the second treatment cycle consisted of an additional 3 weeks of daily treatment followed by 8 weeks of no treatment.	Placebo Cream n=164 participants at risk 250 mg/packet, up to 2 packets applied daily for 2 treatment cycles. The first treatment cycle consisted of 3 weeks of daily treatment followed by 3 weeks of no treatment, and the second treatment cycle consisted of an additional 3 weeks of daily treatment followed by 8 weeks of no treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.62% 1/162 • Number of events 1 • From study screening through the last study visit. From Day 1 up to Week 17 Subjects were queried indirectly regarding AEs during each study visit.	0.00% 0/164 • From study screening through the last study visit. From Day 1 up to Week 17 Subjects were queried indirectly regarding AEs during each study visit.	0.00% 0/164 • From study screening through the last study visit. From Day 1 up to Week 17 Subjects were queried indirectly regarding AEs during each study visit.
Surgical and medical procedures Surgery	0.62% 1/162 • Number of events 1 • From study screening through the last study visit. From Day 1 up to Week 17 Subjects were queried indirectly regarding AEs during each study visit.	0.00% 0/164 • From study screening through the last study visit. From Day 1 up to Week 17 Subjects were queried indirectly regarding AEs during each study visit.	0.00% 0/164 • From study screening through the last study visit. From Day 1 up to Week 17 Subjects were queried indirectly regarding AEs during each study visit.
Respiratory, thoracic and mediastinal disorders Dyspnea	0.62% 1/162 • Number of events 1 • From study screening through the last study visit. From Day 1 up to Week 17 Subjects were queried indirectly regarding AEs during each study visit.	0.00% 0/164 • From study screening through the last study visit. From Day 1 up to Week 17 Subjects were queried indirectly regarding AEs during each study visit.	0.00% 0/164 • From study screening through the last study visit. From Day 1 up to Week 17 Subjects were queried indirectly regarding AEs during each study visit.
Injury, poisoning and procedural complications Hip fracture	0.62% 1/162 • Number of events 1 • From study screening through the last study visit. From Day 1 up to Week 17 Subjects were queried indirectly regarding AEs during each study visit.	0.00% 0/164 • From study screening through the last study visit. From Day 1 up to Week 17 Subjects were queried indirectly regarding AEs during each study visit.	0.00% 0/164 • From study screening through the last study visit. From Day 1 up to Week 17 Subjects were queried indirectly regarding AEs during each study visit.
Musculoskeletal and connective tissue disorders Arthralgia	0.62% 1/162 • Number of events 1 • From study screening through the last study visit. From Day 1 up to Week 17 Subjects were queried indirectly regarding AEs during each study visit.	0.00% 0/164 • From study screening through the last study visit. From Day 1 up to Week 17 Subjects were queried indirectly regarding AEs during each study visit.	0.00% 0/164 • From study screening through the last study visit. From Day 1 up to Week 17 Subjects were queried indirectly regarding AEs during each study visit.
Infections and infestations Wound infection staphylococcal	0.62% 1/162 • Number of events 1 • From study screening through the last study visit. From Day 1 up to Week 17 Subjects were queried indirectly regarding AEs during each study visit.	0.00% 0/164 • From study screening through the last study visit. From Day 1 up to Week 17 Subjects were queried indirectly regarding AEs during each study visit.	0.00% 0/164 • From study screening through the last study visit. From Day 1 up to Week 17 Subjects were queried indirectly regarding AEs during each study visit.
Cardiac disorders Coronary artery disease	0.62% 1/162 • Number of events 1 • From study screening through the last study visit. From Day 1 up to Week 17 Subjects were queried indirectly regarding AEs during each study visit.	0.00% 0/164 • From study screening through the last study visit. From Day 1 up to Week 17 Subjects were queried indirectly regarding AEs during each study visit.	0.00% 0/164 • From study screening through the last study visit. From Day 1 up to Week 17 Subjects were queried indirectly regarding AEs during each study visit.
Infections and infestations Pneumonia staphylococcal	0.62% 1/162 • Number of events 1 • From study screening through the last study visit. From Day 1 up to Week 17 Subjects were queried indirectly regarding AEs during each study visit.	0.00% 0/164 • From study screening through the last study visit. From Day 1 up to Week 17 Subjects were queried indirectly regarding AEs during each study visit.	0.00% 0/164 • From study screening through the last study visit. From Day 1 up to Week 17 Subjects were queried indirectly regarding AEs during each study visit.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Non-Hodgkin's lymphoma	0.62% 1/162 • Number of events 1 • From study screening through the last study visit. From Day 1 up to Week 17 Subjects were queried indirectly regarding AEs during each study visit.	0.00% 0/164 • From study screening through the last study visit. From Day 1 up to Week 17 Subjects were queried indirectly regarding AEs during each study visit.	0.00% 0/164 • From study screening through the last study visit. From Day 1 up to Week 17 Subjects were queried indirectly regarding AEs during each study visit.
Blood and lymphatic system disorders Pancytopenia	0.62% 1/162 • Number of events 1 • From study screening through the last study visit. From Day 1 up to Week 17 Subjects were queried indirectly regarding AEs during each study visit.	0.00% 0/164 • From study screening through the last study visit. From Day 1 up to Week 17 Subjects were queried indirectly regarding AEs during each study visit.	0.00% 0/164 • From study screening through the last study visit. From Day 1 up to Week 17 Subjects were queried indirectly regarding AEs during each study visit.
Cardiac disorders Aortic valve stenosis	0.00% 0/162 • From study screening through the last study visit. From Day 1 up to Week 17 Subjects were queried indirectly regarding AEs during each study visit.	0.61% 1/164 • Number of events 1 • From study screening through the last study visit. From Day 1 up to Week 17 Subjects were queried indirectly regarding AEs during each study visit.	0.00% 0/164 • From study screening through the last study visit. From Day 1 up to Week 17 Subjects were queried indirectly regarding AEs during each study visit.
Nervous system disorders Syncope	0.00% 0/162 • From study screening through the last study visit. From Day 1 up to Week 17 Subjects were queried indirectly regarding AEs during each study visit.	0.61% 1/164 • Number of events 1 • From study screening through the last study visit. From Day 1 up to Week 17 Subjects were queried indirectly regarding AEs during each study visit.	0.00% 0/164 • From study screening through the last study visit. From Day 1 up to Week 17 Subjects were queried indirectly regarding AEs during each study visit.
Infections and infestations Pneumonia	0.00% 0/162 • From study screening through the last study visit. From Day 1 up to Week 17 Subjects were queried indirectly regarding AEs during each study visit.	0.61% 1/164 • Number of events 1 • From study screening through the last study visit. From Day 1 up to Week 17 Subjects were queried indirectly regarding AEs during each study visit.	0.00% 0/164 • From study screening through the last study visit. From Day 1 up to Week 17 Subjects were queried indirectly regarding AEs during each study visit.
General disorders Chest pain	0.00% 0/162 • From study screening through the last study visit. From Day 1 up to Week 17 Subjects were queried indirectly regarding AEs during each study visit.	0.61% 1/164 • Number of events 1 • From study screening through the last study visit. From Day 1 up to Week 17 Subjects were queried indirectly regarding AEs during each study visit.	0.61% 1/164 • Number of events 1 • From study screening through the last study visit. From Day 1 up to Week 17 Subjects were queried indirectly regarding AEs during each study visit.
Infections and infestations Bronchitis	0.00% 0/162 • From study screening through the last study visit. From Day 1 up to Week 17 Subjects were queried indirectly regarding AEs during each study visit.	0.61% 1/164 • Number of events 1 • From study screening through the last study visit. From Day 1 up to Week 17 Subjects were queried indirectly regarding AEs during each study visit.	0.00% 0/164 • From study screening through the last study visit. From Day 1 up to Week 17 Subjects were queried indirectly regarding AEs during each study visit.
Psychiatric disorders Mental status changes	0.00% 0/162 • From study screening through the last study visit. From Day 1 up to Week 17 Subjects were queried indirectly regarding AEs during each study visit.	0.00% 0/164 • From study screening through the last study visit. From Day 1 up to Week 17 Subjects were queried indirectly regarding AEs during each study visit.	0.61% 1/164 • Number of events 1 • From study screening through the last study visit. From Day 1 up to Week 17 Subjects were queried indirectly regarding AEs during each study visit.
Vascular disorders Orthostatic hypotension	0.00% 0/162 • From study screening through the last study visit. From Day 1 up to Week 17 Subjects were queried indirectly regarding AEs during each study visit.	0.00% 0/164 • From study screening through the last study visit. From Day 1 up to Week 17 Subjects were queried indirectly regarding AEs during each study visit.	0.61% 1/164 • Number of events 1 • From study screening through the last study visit. From Day 1 up to Week 17 Subjects were queried indirectly regarding AEs during each study visit.