Nitric Oxide Releasing Mouthwash (NORM) for the Management of Oropharyngeal Candidiasis

Phase 1 Single Centre, Open-labeled Clinical Trial to Evaluate the Safety and Tolerability of Topical Nitric Oxide Releasing Mouthwash (NORM) for the Management of Oropharyngeal Candidiasis

Phase 1 Single Centre, open-labeled Clinical Trial to Evaluate the Safety and Tolerability of Topical Nitric Oxide Releasing Mouthwash (NORM) for the Management of Oropharyngeal Candidiasis.

Participants that meet all inclusion and exclusion criteria will be enrolled to receive open label NORM 3 doses/day for three weeks.

Study Overview

• Status: Completed
• Conditions: Candidiasis, Oral
• Intervention / Treatment: Drug: Nitric Oxide

Detailed Description

This is a single-center, open-label phase 1 clinical trial to evaluate NORM safety, tolerance and ability to eliminate Candida sp from the oropharyngeal cavity.

Adult volunteer patients with dry mouth and confirmed presence of candida (by oral smear due to any cause will be eligible, including autoimmune disease, idiopathic (aging, tobacco, approved inhaled recreational drug, or alcohol use), and medical management including chemotherapy-induced, radiotherapy-induced, bone marrow transplantation-induced, medication use including antibiotics, anti-inflammatories, etc.

Sufficient participants will be enrolled to achieve 10 evaluable participants. Participants who are currently pursuing other forms of treatment (within 2 weeks prior to enrollment) will be excluded from the study (unless participant agrees to a two weeks wash out period).

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 4T1
      • Atlantis Dental Cambie

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. At least 19 years old at the time of consent.
2. Participants must be diagnosed with clinical candidiasis.
3. Have no acute illnesses or hospitalizations within 30 days prior to enrollment, no planned procedures during the anticipated study participation, and no newly diagnosed chronic illnesses that are not deemed stable by the participant's primary care physician), in the opinion of the Investigator, based on medical history (i.e., absence of any clinically relevant abnormality) during Screening.
4. Participants must not have been part of any clinical trial for the past 30 days and may not be taking any other investigational therapy related to treatment of candidiasis.
5. If female, be surgically sterile or post-menopausal (no menses for at least 12 months), or if of childbearing potential, must be using an acceptable method of contraception such as a combination estrogen/progestin hormonal contraceptive (oral or injected) for at least 1 month prior to Day -14, or such items as an intrauterine device (IUD), intrauterine system (IUS), transdermal hormonal implant, vaginal hormonal ring, or 2 forms of the following: diaphragm, cervical cap, patch, condom, spermicide, or sponge. Total abstinence is permitted. If local regulations deviate from the previously listed contraception methods to prevent pregnancy, local requirements will apply. In addition, females of childbearing potential must agree to continue to use their method of birth control for the duration of the study.
6. If male, be surgically sterile, or agree to use appropriate contraception (latex condom with spermicide) when engaging in sexual activity and agree to not donate sperm for the duration of the study.
7. Be able to understand and provide written, informed consent.
8. Must be willing and able to manage a treatment regimen and attend assessment study visits.

Exclusion Criteria:

1. Participants with mucosal/oral ulceration
2. No prior antifungal therapies for a minimum 2-week prior to enrollment
3. Participants with other conditions considered by the investigator to be reasons for disqualification that may jeopardize patient safety or interfere with the objectives of the trial (e.g., acute illness or exacerbation of chronic illness, lack of motivation, history of poor compliance, neurologically or mentally disabled)
4. Females who are breastfeeding, pregnant, or attempting to become pregnant.
5. Participants with hypersensitivity to any of the product's ingredients.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Nitric Oxide Releasing Mouthwash; Nitric Oxide Releasing Mouthwash (NORM) liquid producing NO at 266 ppm*min in 20mL

Drug: Nitric Oxide; Nitric Oxide Releasing Mouthwash will be self-administered by the participant three times throughout the day for 21 days. The intervention solution will be poured into their mouth from a medication cup containing 20 mL of the solution. Total exposure to study intervention will be a maximum of 63 treatments totaling 1,260 mL. All participants will be monitored for 7 days post-last treatment dose (to Day 28).; Other Names: Nitric Oxide Releasing Mouthwash

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess the tolerability of NORM in participants with candidiasis.	Intolerance (i.e., oral cavity, dental, and/or lingual irritation or sensitivity (pain, swelling, erythema, discharge)), dysgeusia, or discoloration of oral cavity/teeth/tongue) as assessed by number of patients that terminate NORM treatment.	21 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess the effectiveness of NORM to resolve oral fungal infection	Assess the number of participants who experience clearing of the infection by negative smear/culture	21 days
To assess the effectiveness of NORM to resolve clinical symptoms of candidiasis	Mean time to achieve clearing of clinical infection (no symptoms [0] or mild [1]) from Baseline until Day 21	21 days
To assess the effectiveness of NORM to reduce the need for an oral antifungal agent	Proportion of participants that require nystatin intervention	21 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
To categorize the major reasons impacting the tolerance of NORM during oral administration	Tolerance as assessed by number of patient reported outcomes (PRO) of irritation and dysgeusia of the rinse, dental sensitivity while willing to continue to use the rinse	21 days
Determine incidence and severity of adverse reactions	Safety as assessed by number and severity of adverse events	21 days
To assess reoccurrence of candidiasis	Proportion of participants with reemergence of candidiasis infection	28 days
To assess of exacerbation of candidiasis	Proportion of participants with an increased Candida sp. associated with their lesions (determined as an increase of 2 or more semi-quantitative steps (e.g., scant to moderate or light to heavy))	28 days

Collaborators and Investigators

• Sponsor: Sanotize Research and Development corp.
• Investigators: Study Director: Keith Moore, PHARMMD, SaNOtize R&D Corp; Principal Investigator: Joel Epstein, Atlantis Dental Cambie

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): January 20, 2024
• Primary Completion (Actual): May 25, 2024
• Study Completion (Actual): May 25, 2024

Study Registration Dates

• First Submitted: November 1, 2023
• First Submitted That Met QC Criteria: November 1, 2023
• First Posted (Actual): November 7, 2023

Study Record Updates

• Last Update Posted (Actual): July 10, 2024
• Last Update Submitted That Met QC Criteria: July 9, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: oral candidiasis
• Additional Relevant MeSH Terms: Infections; Stomatognathic Diseases; Mouth Diseases; Bacterial Infections and Mycoses; Mycoses; Candidiasis; Candidiasis, Oral; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Protective Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Antioxidants; Free Radical Scavengers; Endothelium-Dependent Relaxing Factors; Gasotransmitters; Nitric Oxide
• Other Study ID Numbers: NORM-POC-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No