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

May 1, 2017 updated by: University of Aberdeen

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

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

299

Phase

  • Phase 2

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of patients with complete clearance of target warts in Intention to treat (ITT) population
Time Frame: 24 weeks
  • 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
Time Frame: 12 weeks
12 weeks
Patient assessment of efficacy
Time Frame: 12 weeks
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
Time Frame: 12 weeks
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
Time Frame: 12
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
Time Frame: 12 weeks
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
Time Frame: 12 weeks and followed up
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

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Investigator assessment of staining
Time Frame: 12 weeks
Investigator assessment of staining (present or absent) at treatment site at Weeks 1, 2, 4, 6, 8, 10 and 12/withdrawal/early completion
12 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Aberdeen

Collaborators

Erasmus Medical Center
Prostrakan Pharmaceuticals

Investigators

  • Principal Investigator: Willem I Van der Meijden, Erasmus Medical Centre

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2001

Primary Completion (Actual)

May 1, 2003

Study Completion (Actual)

May 1, 2003

Study Registration Dates

First Submitted

August 6, 2013

First Submitted That Met QC Criteria

December 12, 2013

First Posted (Estimate)

December 19, 2013

Study Record Updates

Last Update Posted (Actual)

May 3, 2017

Last Update Submitted That Met QC Criteria

May 1, 2017

Last Verified

December 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ANA/2/C

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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