Actinic Keratoses
Conditions
Keywords
Actinic keratosis, Skin disease
Brief summary
The purpose of this study is to determine whether imiquimod creams are effective in treating Actinic Keratoses when applied to the face or balding scalp. Actinic keratosis (AK) is a skin condition that shows up on skin routinely exposed to the sun, such as the face, scalp, shoulders, chest, back, arms, and hands. The active ingredient contained in the study cream for this study is the same as that of the approved product Aldara, which has been shown to be safe and effective for the treatment of AKs.
Detailed description
This was a randomized, double-blind, multicenter, placebo-controlled study that compared the efficacy and safety of 2.5% imiquimod cream and 3.75% imiquimod cream with that of placebo in the treatment of typical visible or palpable AKs of the face or balding scalp. Subjects were scheduled for a total of 9 visits (1 prestudy screening visit and 8 on-study visits). Subjects determined to be eligible during the screening phase were randomized in a 1:1:1 ratio to 2.5% imiquimod cream, 3.75% imiquimod cream, or placebo cream. The creams were applied daily for 2 treatment cycles. The first treatment cycle consisted of 2 weeks of daily treatment followed by 2 weeks of no treatment, and the second treatment cycle consisted of an additional 2 weeks of daily treatment followed by 8 weeks of no treatment. The investigator selected the treatment area for the study (either the entire face or the entire balding scalp, but not both). Subjects applied a thin layer of cream to the treatment area (up to 2 packets, or 500 mg of product, per application), avoiding the periocular areas, lips, and nares. Study medication was applied prior to normal sleeping hours and removed approximately 8 hours later with mild soap and water. Ears were excluded from both assessment and treatment. Rest periods from daily treatment were instituted by the investigator as needed to manage local skin reactions (LSRs) or application site reactions, with resumption of treatment upon adequate resolution as determined by the investigator. The duration of each subject's study participation was approximately 18 weeks, including a 4-week maximum screening period and a 14-week study period.
Interventions
DRUGimiquimod cream
cream, 250 mg/packet, up to 2 packets applied daily for 2 treatment cycles. The first treatment cycle consisted of 2 weeks of daily treatment followed by 2 weeks of no treatment, and the second treatment cycle consisted of an additional 2 weeks of daily treatment followed by 8 weeks of no treatment.
DRUGPlacebo
cream, 250 mg/packet, up to 2 packets applied daily for 2 treatment cycles. The first treatment cycle consisted of 2 weeks of daily treatment followed by 2 weeks of no treatment, and the second treatment cycle consisted of an additional 2 weeks of daily treatment followed by 8 weeks of no treatment.
Sponsors
Graceway Pharmaceuticals, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* In good general health * Have 5 to 20 AKs on the face or balding scalp * Negative urine pregnancy test (for women who are able to become pregnant) * Willing to make frequent visits to the study center during treatment and follow-up periods.
Exclusion criteria
* Women who are pregnant, lactating or planning to become pregnant during the study. * Have had a medical event within 90 days of the first visit (such as; stroke, heart attack). * Have any skin condition in the treatment area that may be made worse by treatment with imiquimod (e.g., rosacea, psoriasis, atopic dermatitis, eczema). * Have received specific treatments/medications in the treatment area(s) within the designated time period prior to study treatment initiation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Complete Clearance of AK Lesions | End of Study the Week 14 visit | Subject status with respect to complete clearance of AK lesions at End of Study (EOS), ie, the Week 14 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Partial Clearance of AK Lesions | End of Study the Week 14 visit | Subject status with respect to partial 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. |
| Percent Change From Baseline in AK Lesion Count | From baseline to End of Study the Week 14 visit | Percent change from Baseline to end of study (EOS) in investigator counts of AK lesions. |
| Local Skin Reactions | At all visits - from Baseline to End of study (Week 14) | Six local skin reaction (LSR) signs were predefined and were assessed for presence and intensity at each study 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. Mean scores were summated over time (14 weeks) to yield a mean LSR AUC (area under the curve) |
Countries
United States
Participant flow
Recruitment details
Recruitment started on January 15, 2008 all subjects were randomized by March 17, 2008. The studies were performed at 26 investigational centers in the United States.
Pre-assignment details
Subjects were screened and had to meet eligibility requirements for randomization. The most frequent reason for screen failure (104 of screen failures) was that the subject did not have between 5 and 20 visible or palpable Actinic Keratosis (AK) lesions on either the face or the balding scalp.
Participants by arm
| Arm | Count |
|---|---|
| 3.75% Imiquimod Cream 250 mg/packet, up to 2 packets applied daily for 2 treatment cycles. The first treatment cycle consisted of 2 weeks of daily treatment followed by 2 weeks of no treatment, and the second treatment cycle consisted of an additional 2 weeks of daily treatment followed by 8 weeks of no treatment. | 160 |
| 2.5% Imiquimod Cream 250 mg/packet, up to 2 packets applied daily for 2 treatment cycles. The first treatment cycle consisted of 2 weeks of daily treatment followed by 2 weeks of no treatment, and the second treatment cycle consisted of an additional 2 weeks of daily treatment followed by 8 weeks of no treatment. | 160 |
| Placebo Cream 250 mg/packet, up to 2 packets applied daily for 2 treatment cycles. The first treatment cycle consisted of 2 weeks of daily treatment followed by 2 weeks of no treatment, and the second treatment cycle consisted of an additional 2 weeks of daily treatment followed by 8 weeks of no treatment. | 159 |
| Total | 479 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 1 | 3 |
| Overall Study | Lost to Follow-up | 2 | 2 | 1 |
| Overall Study | Non-complicance with study procedures | 1 | 0 | 0 |
| Overall Study | Other (not due to AE) | 1 | 1 | 0 |
| Overall Study | Use of concomitant therapy | 1 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 4 | 2 | 4 |
Baseline characteristics
| Characteristic | 2.5% Imiquimod Cream | Placebo Cream | 3.75% Imiquimod Cream | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 72 Participants | 69 Participants | 78 Participants | 219 Participants |
| Age, Categorical Between 18 and 65 years | 88 Participants | 90 Participants | 82 Participants | 260 Participants |
| Age Continuous | 64.3 years STANDARD_DEVIATION 10.5 | 64.3 years STANDARD_DEVIATION 8.9 | 64.5 years STANDARD_DEVIATION 10.6 | 64.4 years STANDARD_DEVIATION 10 |
| Region of Enrollment United States | 160 participants | 159 participants | 160 participants | 479 participants |
| Sex: Female, Male Female | 33 Participants | 29 Participants | 28 Participants | 90 Participants |
| Sex: Female, Male Male | 127 Participants | 130 Participants | 132 Participants | 389 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 14 / 160 | 7 / 160 | 13 / 159 |
| serious Total, serious adverse events | 5 / 160 | 5 / 160 | 2 / 159 |
Outcome results
Primary
Number of Participants With Complete Clearance of AK Lesions
Subject status with respect to complete clearance of AK lesions at End of Study (EOS), ie, the Week 14 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.
Time frame: End of Study the Week 14 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).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 3.75% Imiquimod Cream | Number of Participants With Complete Clearance of AK Lesions | 57 participants |
| 2.5% Imiquimod Cream | Number of Participants With Complete Clearance of AK Lesions | 49 participants |
| Placebo Cream | Number of Participants With Complete Clearance of AK Lesions | 10 participants |
Secondary
Local Skin Reactions
Six local skin reaction (LSR) signs were predefined and were assessed for presence and intensity at each study 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. Mean scores were summated over time (14 weeks) to yield a mean LSR AUC (area under the curve)
Time frame: At all visits - from Baseline to End of study (Week 14)
Population: All participants were evaluated for local skin reactions (LSR) at every visit. Summary of LSR - area under the curve (AUC) of sum of LSR Scores (days). ITT population. The time period for the AUC extends to 8 weeks after the end of treatment (Week 14). Only subjects who received treatment in both treatment cycles are included in this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 3.75% Imiquimod Cream | Local Skin Reactions | 272.0 units on a scale * days | Standard Deviation 123 |
| 2.5% Imiquimod Cream | Local Skin Reactions | 242.5 units on a scale * days | Standard Deviation 126.2 |
| Placebo Cream | Local Skin Reactions | 139.8 units on a scale * days | Standard Deviation 104.1 |
Secondary
Number of Participants With Partial Clearance of AK Lesions
Subject status with respect to partial 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.
Time frame: End of Study the Week 14 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).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 3.75% Imiquimod Cream | Number of Participants With Partial Clearance of AK Lesions | 95 participants |
| 2.5% Imiquimod Cream | Number of Participants With Partial Clearance of AK Lesions | 77 participants |
| Placebo Cream | Number of Participants With Partial Clearance of AK Lesions | 36 participants |
Secondary
Percent Change From Baseline in AK Lesion Count
Percent change from Baseline to end of study (EOS) in investigator counts of AK lesions.
Time frame: From baseline to End of Study the Week 14 visit
Population: Intent to treat (ITT) Last Observation Carried Forward (LOCF)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 3.75% Imiquimod Cream | Percent Change From Baseline in AK Lesion Count | -81.8 percent change |
| 2.5% Imiquimod Cream | Percent Change From Baseline in AK Lesion Count | -71.8 percent change |
| Placebo Cream | Percent Change From Baseline in AK Lesion Count | -25.0 percent change |