A Trial of the Efficacy and Safety of Topical Nitric Oxide in Patients With Anogenital Warts

Study Overview
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Brief Summary
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Objective To assess the efficacy of the topical application of Nitric Oxide, delivered using acidified nitrite. Design Multicentre, randomized, controlled, dose ranging trial. A control arm and three doses of acidified nitrite applied topically for 12 weeks with a further 12 weeks of follow up. Setting The trial setting was in European genitourinary medicine clinics Participants Male and female volunteers over 18 years of age with between 2 and 50 ano-genital warts, 328 were screened for eligibility and 299 subjects from 40 centres were randomised. Exclusions Pregnancy; concomitant Sexually Transmitted Disease; internal warts requiring treatment other than surgery /laser; diabetes ; Human Immunodeficiency Virus-positive, immunosuppressed and/or using immunosuppressive therapies; drug abuse. interventions compared Control Placebo nitrite cream and placebo citric acid cream twice daily A) 3% sodium nitrite + 4.5% citric acid creams twice daily B) 6% sodium nitrite + 9% citric acid creams once daily C) 6% sodium nitrite + 9% citric acid creams twice daily Outcomes Primary proportion of patients with complete clearance of target warts Secondary Time to clearance Wart area Wart count Patient and investigator assessment of efficacy Safety Tolerability Adherence

Official Title
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A Randomised, Multicentre, Double-blind, Placebo-controlled, Dose-ranging Trial to Evaluate the Efficacy, Safety and Tolerability of Three Dose Regimens of Topical Nitric Oxide in Patients With Anogenital Warts

Conditions
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Anogenital Warts, Condylomata Acuminata

Intervention / Treatment
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* Drug: Topical NO
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females over 18 years of age 2-50 warts in the anogenital region. Female patients of child-bearing potential had to be willing to use a non-barrier method of contraception at entry and for the duration of the study. all patients had to be willing to use barrier protection for the duration of the study. All patients had to be able to comply with the requirements of the protocol and be likely to return for follow-up visits and had to be contactable for the duration of the study. Exclusion Criteria: Patients with clinically relevant abnormal haematology or biochemistry results (determined from the sample taken at Visit 1). Patients who had used an active therapy for anogenital warts within 2 weeks of randomisation to study drug, i.e. Visit 2. Patients who had used any local supportive medication, including topical corticosteroids or beta-interferon, within 2 weeks of study entry. Patients who had used medication known to adversely affect their haematology profile, including local anaesthetics (benzocaine, lidocaine, etc), nitrofurantoin, sulphonylureas and sulphonamides within 2 weeks of study entry. [Word 'adversely' added by Protocol Amendment 2, 7 May 2002.] Patients with abnormal anogenital skin, such as eczema, or skin that had not healed following surgery (cryosurgery, laser ablation or similar). Patients who were known to have a concomitant sexually transmitted disease that inhibited accurate assessment of their warts. Patients who required treatment other than surgery or laser for internal warts. Male patients with intra-urethral warts [deleted by Protocol Amendment 2, 7 May 2002]. Patients with diabetes (Type I or Type II diabetes). Patients who were known to be HIV-positive. Patients who were known to be immunosuppressed and/or using immunosuppressive therapies. Patients known to abuse alcohol and/or drugs or with a history of chronic alcohol or drug abuse.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: placebo<br>placebo 0% nitrite cream and placebo 0% citric acid cream | Drug: Placebo<br>* Placebo<br>* Other names: Placebo nitrite cream and placebo citric acid cream;|
| Active Comparator: Topical NO Dose A<br>3% sodium nitrite + 4.5% citric acid twice daily | Drug: Topical NO<br>* Varying doses of sodium nitrite and citric acid co-applied to warts<br>* Other names: Acidified Nitrite vs Placebo;|
| Active Comparator: Topical NO Dose B<br>6% sodium nitrite + 9% citric acid once daily | Drug: Topical NO<br>* Varying doses of sodium nitrite and citric acid co-applied to warts<br>* Other names: Acidified Nitrite vs Placebo;|
| Active Comparator: Topical NO Dose C<br>6% sodium nitrite + 9% citric acid twice daily | Drug: Topical NO<br>* Varying doses of sodium nitrite and citric acid co-applied to warts<br>* Other names: Acidified Nitrite vs Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with complete clearance of target warts in Intention to treat (ITT) population | Number of and area of target warts (up to 10 selected) at Baseline and Week 1, 2, 4, 6, 8, 10 and 12/withdrawal/early completion and at follow-up (Weeks 4, 8 and 12 after end of treatment) Number of warts at Baseline (Week 0) and of remaining baseline warts at Week 1, 2, 4, 6, 8, 10 and 12/withdrawal/early completion and at Weeks 4, 8 and 12 of follow-up | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total number of warts (baseline and new) at end of treatment |  | 12 weeks | 
| Patient assessment of efficacy | Patient assessment of efficacy (categorised as complete clearance, significant improvement, partial improvement, no change or worsening) at Week 12/withdrawal/early completion | 12 weeks | 
| Investigator assessment of efficacy | Investigator assessment of efficacy (categorised as complete clearance, significant improvement, partial improvement, no change or worsening) at Week 12/withdrawal/early completion | 12 weeks | 
| Patient assessment of tolerability | Patient assessment of itching, pain and burning (categorised as none, mild, moderate or severe) at treatment site at Screening and Weeks 1, 2, 4, 6, 8, 10 and 12/withdrawal/early completion | 12 | 
| Investigator assessment of tolerability | Investigator assessment of erythema/eschar and oedema (using modified Draize scales from 0 to 4) at Baseline (Week 0), Weeks 1, 2, 4, 6, 8, 10 and 12/withdrawal/early completion and at follow-up (Weeks 4, 8 and 12 after end of treatment) | 12 weeks | 
| Safety of treatment | Adverse events throughout treatment period; unresolved events at end of treatment were followed up Heart rate and blood pressure at each visit during treatment Laboratory tests at Screening and Week 12/withdrawal/early completion Physical examination at Screening and at Week 12/withdrawal/early completion. | 12 weeks and followed up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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human papilloma virus infection, Anogenital warts, condylomata acuminata