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

University of Aberdeen

Status and phase: Completed; Phase 2

Conditions: Anogenital Warts; Condylomata Acuminata

Treatments: Drug: Topical NO; Drug: Placebo

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT02015260

ANA/2/C

Details and patient eligibility

About

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

Enrollment: 299 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

299 participants in 4 patient groups, including a placebo group

placebo

Placebo Comparator group

Description:

placebo 0% nitrite cream and placebo 0% citric acid cream

Treatment:

Drug: Placebo

Topical NO Dose A

Active Comparator group

Description:

3% sodium nitrite + 4.5% citric acid twice daily

Treatment:

Drug: Topical NO

Topical NO Dose B

Active Comparator group

Description:

6% sodium nitrite + 9% citric acid once daily

Treatment:

Drug: Topical NO

Topical NO Dose C

Active Comparator group

Description:

6% sodium nitrite + 9% citric acid twice daily

Treatment:

Drug: Topical NO