Clinical trial NCT02015260: A Trial of the Efficacy and Safety of Topical Nitric Oxide in Patients With Anogenital Warts
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Anogenital Warts
Condylomata Acuminata
Keywords: human papilloma virus infection
Anogenital warts
condylomata acuminata
Lead sponsor: University of Aberdeen
Sponsor class: OTHER
Collaborators: name: Kyowa Kirin Co., Ltd.
name: Erasmus Medical Center
First posted: 2013-12-19
Enrollment: 299
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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


Eligibility criteria: 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.

Primary outcomes:
measure: Proportion of patients with complete clearance of target warts in Intention to treat (ITT) population
timeFrame: 24 weeks
Secondary outcomes:
measure: Total number of warts (baseline and new) at end of treatment
timeFrame: 12 weeks
measure: Patient assessment of efficacy
timeFrame: 12 weeks
measure: Investigator assessment of efficacy
timeFrame: 12 weeks
measure: Patient assessment of tolerability
timeFrame: 12
measure: Investigator assessment of tolerability
timeFrame: 12 weeks
measure: Safety of treatment
timeFrame: 12 weeks and followed up
Other outcomes:
measure: Investigator assessment of staining
timeFrame: 12 weeks
Locations:
Study officials:
affiliation: Erasmus Medical Centre
name: Willem I Van der Meijden
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ormerod AD, van Voorst Vader PC, Majewski S, Vanscheidt W, Benjamin N, van der Meijden W. Evaluation of the Efficacy, Safety, and Tolerability of 3 Dose Regimens of Topical Sodium Nitrite With Citric Acid in Patients With Anogenital Warts: A Randomized Clinical Trial. JAMA Dermatol. 2015 Aug;151(8):854-61. doi: 10.1001/jamadermatol.2015.0381.