Skin and Connective Tissue Diseases

All Conditions

Neoplasms

Skin Diseases

Keratosis, Actinic

Keratosis

Precancerous Conditions

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Imiquimod

Immunomodulating Agents

Immunologic Factors

Adjuvants, Immunologic

Interferons

placebo cream in 250mg/packet, up to 2 packets applied daily

Imiquimod 3.75% cream, 250 mg single-use packets, up to 2 packets applied daily

Imiquimod 3.75% cream (250 mg/packet) up to 2 packets applied daily Two 2-week treatment periods (Cycle 1 and Cycle 2) separated by a 2-week no-treatment period

imiquimod cream

cream applied once daily for two 2-week treatment periods (Cycle 1 and Cycle 2) separated by a 2-week no-treatment period

placebo cream

Sharon Levy, MD

The objective of this study is to evaluate the efficacy and safety of imiquimod cream versus placebo cream when used after cryosurgery in the treatment of actinic keratoses (AKs).

In this multicenter, randomized, double-blind, placebo-controlled study, the efficacy and safety of imiquimod 3.75% cream following cryosurgery to treat clinically typical visible or palpable AK lesions on the face was compared with that of placebo cream. Based on a 1:1 randomization, approximately 120 subjects applied imiquimod 3.75% cream daily (up to 500 mg cream daily \[18.75 mg imiquimod\]) and approximately 120 subjects applied placebo cream daily during two 2-week periods (Cycle 1 and Cycle 2) separated by 2 weeks of no treatment. Subjects visited the clinic 9 times-1 screening/cryosurgery visit (additional visits might be needed during the screening period to assess healing from the cryosurgery), 4 treatment visits(treatment initiation at Weeks 0 and 4 and treatment follow-up at the end of Weeks 2 and 6), and 4 posttreatment visits (4, 8, 14, and 20 weeks after the last administration of study treatment at the end of Week 6). The total study duration for a subject, including a 2-week screening period, was up to 28 weeks.

Prior to cryosurgery, subjects had to have ≥10 clinically typical visible or palpable AK lesions in an area that exceeded 25 cm\^2 on the face to be eligible for participation in the study. At screening, a minimum of 5 visible lesions were not treated with cryosurgery, and 5 to 14 visible lesions were treated with cryosurgery. Subjects had to have at least 5 AK lesions after the skin healed sufficiently from the cryosurgery to be eligible for randomization to either imiquimod 3.75% or placebo cream. Subjects applied up to 2 packets of study cream (500 mg total) as a thin layer to the entire face, avoiding the periocular areas, lips, and nares; ears were excluded from both assessment and treatment. Study cream was applied prior to normal sleeping hours and removed approximately 8 hours later with mild soap and water. Rest periods from daily treatment could be approved by the investigator as needed, with treatment resumption at the investigator's discretion.

Safety and Effectiveness Study of Actinic Keratosis Treatment Following Cryosurgery

A Phase 3b Randomized, Double-blinded, Placebo-controlled, Multicenter, Efficacy and Safety Study of Imiquimod Cream Following Cryosurgery for the Treatment of Actinic Keratoses

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.

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.

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".

Graceway Pharmaceuticals, LLC

AEs were collected from Visit 1 to the end of the final study visit for each subject.

placebo cream in 250 mg/packet, up to 2 packets applied daily

Placebo Cream

Imiquimod Cream

Total

Age, Categorical

Age Continuous

Sex: Female, Male

United States

Canada

Region of Enrollment

A treatment-emergent AE (TEAE) was an AE that began or worsened in severity after the first application of study drug. TEAEs were summarized for each treatment group by overall incidence, descending order, relationship to study drug, and severity.

Vice President Medical Affairs

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

Change From Baseline in Percentage of Lesion Count

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

Percent of Subjects With Complete Clearance

Edema

Erythema

Weeping/Exudate

Flaking/Scaling/Dryness

Scabbing, crusting

Erosion/Ulceration

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.

Number of Participants With Any Post-baseline Local Skin Reactions (LSRs)

Overall Study

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.

Imiquimod cream

Placebo cream

Sharon F Levy, MD

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 shown to be safe and effective for the treatment of AKs.

These were a randomized, double-blind, multicenter, placebo-controlled studies 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 AK of the face or balding scalp. Subjects were scheduled for a total of 11 visits (1 prestudy screening visit and 10 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 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. 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 21 weeks, including a 4-week maximum screening period and a 17-week study period. At the End of Study (EOS) visit, eligible subjects may have been invited to participate in a separate study evaluating AK recurrence.

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

A Phase 3, Randomized, Double-blinded, Placebo-controlled, Multicenter, Efficacy and Safety Study of Six Weeks of Treatment With Imiquimod Creams for Actinic Keratoses

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.

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.

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.

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).

Vice President, Clinical Development

Subjects were queried indirectly regarding AEs during each study visit.

3.75% Imiquimod Cream

2.5% Imiquimod Cream

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).

Number of Participants With Complete Clearance of AK Lesions

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

Number of Participants With Partial Clearance of AK Lesions

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

Percent Change From Baseline in AK Lesion Count

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.

Local Skin Reactions (LSR)

Infections

Symptoms and General Pathology

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Recurrence

Communicable Diseases

Condylomata Acuminata

Virus Diseases

Papillomavirus Infections

Papilloma

Sexually Transmitted Diseases

Sexually Transmitted Diseases, Viral

DNA Virus Infections

Tumor Virus Infections

Genital Diseases

Urogenital Diseases

Disease Attributes

Patients receive topical Imiquimod therapy for 12 weeks.

Imiquimod 5% cream

Patients receive topical Doritin therapy for 12 weeks

Surgical Excision and Fulguration of condyloma

Fulguration

Irmgard E Kronberger, MD

Sascha Czipin, MD

Dietmar Öfner-Velano, MD

AdAM is a prospective, randomized, controlled, double-blinded, monocentric trial in patients receiving surgical therapy due to anal HPV infection.

Aim of the study is to evaluate efficacy of combination therapy (surgical therapy + topical Imiquimod-therapy). It is planned to include 200 patients.

100 patients receive surgical therapy+ topical Imiquimod therapy, 100 patients receive surgical therapy + topical Placebo therapy

Adjuvant Anal Imiquimod Therapy in Anal HPV-lesions: AdAM-trial

Adjuvant Imiquimod Therapy to Reduce Recurrence Rate in Patients After Surgical Therapy of Anal HPV (Human Papilloma Virus)-Lesions

Recurrence is evaluated by clinical examination (proctoscopy)

Influence of CD4 cell count in the subgroup of HIV positive patients

Medical University Innsbruck

Leading Consultent

Warts

Skin Diseases, Viral

Skin Diseases, Infectious

2.5% imiquimod cream applied daily to wart area for up to 8 weeks

3.75% imiquimod cream applied daily to wart areas for up to 8 weeks.

placebo cream applied daily to wart areas for up to 8 weeks

daily topical application for up to 8 weeks

3.75% imiquimod cream

Jason Wu, MD

The purpose of this study is to determine whether imiquimod creams are effective in treating external genital warts (EGW). The secondary objective of this study is to provide information on recurrence of EGW. Additionally the study will also look at any adverse events associated with the use of the creams.

External genital and perianal warts are caused by the infection of human papillomavirus or HPV. HPV infection is a sexually transmitted disease (STD). External genital warts look like small flesh-colored, pink, or red growths on or around the external skin of sex organs or perianal area. The warts may look similar to the small parts of a cauliflower or they may be very tiny and difficult to see. They often appear in clusters of three or four, and may grow and spread rapidly. They usually are not painful, although they may cause mild pain, bleeding, and itching.

Safety and Effectiveness Study of Imiquimod Creams in the Treatment of External Genital Warts

A Phase 3, Randomized, Double-blind, Placebo-controlled, Multi-center, Efficacy and Safety Study of Imiquimod Creams in the Treatment of External Genital Warts

Proportion of subjects with complete clearance of all warts (both presented at Baseline and newly emerged warts) at End of Study. Primary analysis performed on the Intent to Treat population with imputation (Last Observation Carried Forward)for missing data points.

Local skin reactions in the treatment and/or immediate surrounding area were clinically identified as: erythema, edema, weeping/exudate, flaking/scaling/dryness, and erosion/ulceration. LSRs were visually assessed by investigator at each visit.

Rest period was a temporary interruption of dosing dur to intolerable LSRs.

Numbers of subjects in each treatment group reporting one or more adverse events

Jason Wu, MD / Exective Director, Product Development

The study duration included 5 month enrollment period, up to 28 week of study period, so total duration from first patient enrolled to the last patient completed study was approximately 12 months

2.5% imiquimod cream applied once daily to wart areas for up to 8 weeks

3.75% imiquimod cream applied once daily to wart areas for up to 8 weeks

Placebo cream applied once daily to wart areas for up to 8 weeks

Placebo

Robert Babilon, Vice President, Product Development

Adverse Reactions

Local Skin Reactions

Number of Subjects with Rest Period in Treatment

Safety Variables Include Adverse Reactions (AEs), Local Skin Reactions (LSRs), and Number of Subjects Who Took Rest Periods During the Treatment Period.

Proportion of Subjects With Complete Clearance of All Warts (Both Presented at Baseline and Newly Emerged Warts) at End of Study

Patients with adverse events considered probably related or related to the administration of the product.

Treatment Related Adverse Events

Fluorouracil

Antimetabolites

Immunosuppressive Agents

Treatment of actinic keratosis with active ingredient

treatment of actinic keratosis with placebo cream

Brand Carac

Generic 0.5% 5-fluorouracil cream

Melanie Appell, M.D.

This is a double-blind, randomized, placebo-controlled, three treatment parallel study in which normal, healthy men and women (age 45-85) with actinic keratosis will be treated on the face once daily for two weeks with 5-Fluorouracil Cream 0.5%, Spear Pharmaceuticals (Generic), Carac® Cream 0.5% (Brand), or Cream Vehicle (Placebo). Actinic keratoses will be counted at the baseline visit and at the visit four weeks following cessation of treatment.

Bioequivalence Study of Generic Fluorouracil 0.5% Cream and 0.5% Carac® and Placebo

Phase 3 Study of Brand Generic and Placebo in Treatment of Actinic Keratosis

Spear Pharmaceuticals

2.5% imiquimod cream applied daily to wart areas for up to 8 weeks

Placebo cream applied daily to wart areas for up to 8 weeks.

2.5% imiquimod cream applied daily to wart areas for up to 8 weeks.

2.5% imiquimod cream

3.75% imiquimod cream applied daily to wart areas for up to 8 weeks

Placebo cream applied daily to wart areas for up to 8 weeks

Phase 3 Study of Imiquimod Creams in the Treatment of External Genital Warts

A Safety and Effectiveness Study of Imiquimod Creams in the Treatment of External Genital Warts

The complete clearance was defined as completely cleared all warts including baseline and newly emerged during the study at all anatomic areas.

Treatment related defined as "probably related" or "related" by investigator. Local skin reactions (LSRs)were part of the treatment related adverse events and assessed by the investigators.

Rest periods defined as temporary interruption of dosing due to intolerable local skin reaction.

Jason Wu, MD / Executive Director, Product Development

The study period included 4 month enrollment, maximum 28 weeks of study phase, so total length of the study from first patient enrolled to last patient completed the study is about 11 months.

2.5% imiquimod cream applied once daily to wart areas for up to 8 weeks.

3.75% imiquimod cream applied once daily to wart areas for up to 8 weeks.

Placebo cream applied once daily to wart areas for up to 8 weeks.

There was a high percentage of lost to follow up in this study. Since the disease studied in this study can be wait and watch, typically a high lost to follow up rate were seen in these kind of trials.

Proportion of Subjects Achieving Complete Clearance of All Warts (Baseline and New) at the End of Study.

Subjects with and Adverse Reactions (ARs)

Subjects with Any Local Skin Reactions (LSRs)

Number of Subjects who Took a Rest Period

Analysis population was based on safety population which defined as for all subjects randomized and received at lease one dose. There was one subject who randomized to the 2.5% group but received one treatment kit of 3.75% imiq cream, so this subject was assigned to 3.75% for the safety analysis.

Number of Subjects With Any Treatment Related Adverse Reactions (AEs), Any Local Skin Reactions (LSRs), and Number of Subjects Who Took Rest Periods During the Treatment Period

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Safety and Effectiveness Study of Actinic Keratosis Treatment Following Cryosurgery	NCT00894647	Actinic Keratos...	imiquimod cream placebo cream	18 Years -	Graceway Pharmaceuticals, LLC
Safety and Effectiveness Study of Imiquimod Creams for the Treatment of Actinic Keratoses (AKs)	NCT00603798	Actinic Keratos...	Imiquimod cream Placebo cream Imiquimod cream	18 Years -	Graceway Pharmaceuticals, LLC
Adjuvant Anal Imiquimod Therapy in Anal HPV-lesions: AdAM-trial	NCT03289260	Anogenital Huma... Condyloma Anal	Imiquimod 5% cr... Placebo cream Fulguration	18 Years -	Medical University Innsbruck
Safety and Effectiveness Study of Imiquimod Creams in the Treatment of External Genital Warts	NCT00674739	Genital Warts	Imiquimod 3.75% imiquimod... placebo cream	12 Years -	Graceway Pharmaceuticals, LLC
Safety and Effectiveness Study of Imiquimod Creams in the Treatment of External Genital Warts	NCT00674739	Genital Warts	Imiquimod 3.75% imiquimod... placebo cream	12 Years -	Graceway Pharmaceuticals, LLC
Bioequivalence Study of Generic Fluorouracil 0.5% Cream and 0.5% Carac® and Placebo	NCT01354717	Actinic Keratos...	Brand Carac Generic 0.5% 5-... Placebo cream	45 Years - 85 Years	Spear Pharmaceuticals
Phase 3 Study of Imiquimod Creams in the Treatment of External Genital Warts	NCT00735462	Genital Warts	2.5% imiquimod ... 3.75% imiquimod... Placebo cream	12 Years -	Graceway Pharmaceuticals, LLC
Phase 3 Study of Imiquimod Creams in the Treatment of External Genital Warts	NCT00735462	Genital Warts	2.5% imiquimod ... 3.75% imiquimod... Placebo cream	12 Years -	Graceway Pharmaceuticals, LLC

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