Local Nasal Tolerability and Safety Study of 1146A in Healthy Adult Participants

Study Overview
=================
Brief Summary
-----------------
This will be a single-center, randomized, parallel-group, placebo-controlled study to assess the local nasal tolerability and safety of multiple administrations of topically (intranasally) administered 1146A delivered by a nasal spray applicator in healthy adult participants

Official Title
-----------------
A Randomized, Parallel-Group, Placebo-Controlled Study to Evaluate the Local Nasal Tolerability and Safety of 1146A in Healthy Adult Subjects

Conditions
-----------------
Common Cold

Intervention / Treatment
-----------------
* Drug: Carbomer 980
* Other: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Demonstrates understanding of the study procedures, restrictions and willingness to participate as evidenced by voluntary written informed consent and has received a signed and dated copy of the informed consent form. Willing to be confined for 9 days (8 nights) and acceptance of standardized food and beverages throughout the confined study period Aged between 18 and 55 years inclusive Male or female Good general and mental health with, in the opinion of the investigator or medically qualified designee, no clinically significant and relevant abnormalities in medical history or upon physical and nasal examinations Participant is free of any disease or concomitant treatment that could interfere with the interpretation of the study results as determined by the investigator or the sponsor's medical officer Females of childbearing potential who are, in the opinion of the investigator, practicing a reliable method of contraception. Adequate contraception is defined as abstinence, oral contraceptive, either combined or progestogen alone or injectable progestogen or implants of levonorgestrel or estrogenic vaginal ring or percutaneous contraceptive patches or intrauterine device or intrauterine system or double barrier method (condom or occlusive cap [diaphragm or cervical vault caps] plus spermicidal agent [foam, gel, film, cream, suppository]) or male partner sterilization prior to the female participant's entry into the study, and this male is the sole partner for that participant Exclusion Criteria: Women who have a positive urine pregnancy test Women who are breast-feeding History of malignancy or neoplastic disease of any organ system (except for localized basal cell skin carcinoma), treated or untreated, within the past 5 years prior to screening, regardless of whether there is evidence of local recurrence or metastases, clinically relevant chronic or acute infectious illnesses or febrile infections within two weeks prior to start of the study, History (within 5 years prior to study start) or any evidence of cardiovascular, pulmonary, renal, hepatic, gastrointestinal, hematological, endocrinological, metabolic, autoimmune, neurological, psychiatric or other diseases at screening, participants who have used medications or therapies that could interfere with study evaluations and have not had the proper washout period from these medications or therapies or are anticipated to require any concomitant intranasal medication during that period or at any time throughout the study, any condition that prohibits the participant from actuating nasal spray devices (severe rheumatoid arthritis; deformed hands and fingers; missing fingers), Nasal disease(s) likely to affect deposition of intranasal medication, such as acute or chronic sinusitis, rhinitis medicamentosa, clinically significant polyposis, or clinically significant nasal structural abnormalities Known or suspected intolerance or hypersensitivity to any of the study medications, excipients, investigational device material, or to medications of similar chemical classes, any history of drug hypersensitivity, asthma, urticaria, or other significant allergic diathesis, known or suspected contraindications, including history of allergy, or photosensitivity to study medication/s Participation in another clinical study (including cosmetic studies) or receipt of an investigational drug within 30 days of screening or 5 half-lives of the other clinical studies investigational drug, whichever is longer, Previously enrolled in the current study Current smoker or smoked or used nicotine containing products within 5 years of screening, history (within 5 years prior to study start) or evidence of illicit drug abuse or if the investigator suspects current drug use with drug classes that include but are not limited to barbiturates, amphetamines, benzodiazepines, cocaine, opiates, cannabis or any other illicit drugs (verified by urine drug screening or other reliable evidence), history or evidence of current alcohol abuse or if participant reports a regular average alcohol consumption exceeding 18 g (women) or 35 g (men) of pure alcohol per day, i.e. 1 drink/day for women or 2 drinks/day for men (1 drink = 150 mL of wine or 360 mL of beer or 45 mL of hard liquor) within 6 months of screening Non-acceptance of standardized food and beverages throughout each confined study period, Ingestion of food containing poppy seeds (muffins, bagels, cakes, etc) within 24 hours of admission to the study site Persons directly or indirectly involved in the execution of this protocol, including employees of the contract research organization (CRO) and persons related to them, an employee of the sponsor or the study site or members of their immediate family On nasal examination, the presence of any superficial or moderate nasal mucosal erosion, nasal mucosal ulceration, or nasal septum perforation (Grade 1B - 4) during the screening visit or Day -1, Participants with difficulty in using the nasal spray applicator, Vulnerable individual (as defined by the Institutional Review Board (IRB) e.g. incarcerated person), any condition not identified in the protocol that in the opinion of the investigator would confound the evaluation and interpretation of the study data or may put the participant at risk, no consumption of alcohol-containing products within 24 hours before confinement and throughout confined study period

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Carbomer 980<br>Participants will be administered test product (nasal spray) containing 0.5% carbomer 980, 4 times per day (i.e. 3 actuations per nostril per dose; each actuation will be 140 mcL, equivalent to 140 mg). | Drug: Carbomer 980<br>* Test product containing 0.5% carbomer 980 gel<br>|
| Placebo Comparator: Placebo<br>Participants will be administered reference product (nasal spray) containing vehicle without carbomer 980, 4 times per day (i.e. 3 actuations per nostril per dose; each actuation will be 140 mcL, equivalent to 140 mg). | Other: Placebo<br>* Reference product containing vehicle without 0.5% carbomer 980 gel<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidences of nasal mucosal changes of ≥ Grade 1B | The investigators will perform a thorough examination using nasal mucosal grading scale: Grade 0 = No abnormal findings, Grade 1A = focal nasal mucosal irritation (inflammation, erythema or hyperemia), Grade 1B = superficial nasal mucosal erosion, Grade 2 = moderate nasal mucosal erosion | Baseline to Day 8 | 
| Incidence of moderate or severe mucosal bleeding | The investigators will perform a thorough examination using mucosal bleeding scale: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe | Baseline to Day 8 | 
| Incidence of moderate or severe crusting of mucosa | The investigators will perform a thorough examination using crusting of mucosa scale: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe | Baseline to Day 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events | All adverse events reported by participants will be recorded. | Baseline to Day 8 | 
| Change from baseline in Blood pressure | Systolic and diastolic BP will be measured three times after the participant has been sitting for 5 minutes using an automated validated device, e.g. OMRON, with an appropriately sized cuff. The repeat sitting measurements will be made at 1-2 minute intervals and the mean/average of the three measurements will be recorded. | Baseline to Day 8 | 
| Change from baseline in pulse | Pulse will be measured three times after the participant has been sitting for 5 minutes using an automated validated device, e.g. OMRON, with an appropriately sized cuff. The repeat sitting measurements will be made at 1-2 minute intervals and the mean/average of the three measurements will be recorded. | Baseline to Day 8 | 
| Change from baseline in respiration rate | The rate will be measured by counting the number of breaths for one minute (counting how many times the chest rises). | Baseline to Day 8 | 
| Change from baseline in oral body temperature | Oral body temperature will be measured. Reference range (Oral body temperature between 35.0 º Celsius (C) and 37.5 ºC) | Baseline to Day 8 | 
| Change from baseline in Hematology | Hemoglobin (Hb), hematocrit (Ht), red blood cell (RBC) count (including mean corpuscular hemoglobin (MCH), mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC), white blood cell (WBC) count with differential and platelet count will be measured. | Baseline to Day 8 | 
| Change from baseline in clinical Chemistry | Electrolytes (sodium, potassium, chloride, calcium, phosphorous), substrates (Blood Urea Nitrogen [BUN], creatinine, total bilirubin, total protein, albumin, uric acid, and C-reactive protein), and enzymes (aspartate amino transferase [AST], alanine amino transferase [ALT], alkaline phosphatase (ALP), gamma glutamyl transferase [GGT], creatine kinase [CK]) will be measured. | Baseline to Day 8 | 
| Change from baseline in virus Serology | Serology will be performed only for Hepatitis B Surface Antigen (HBs Ag), Hepatitis B core antibody [anti-HBc] (Immunoglobulin G [IgG] + Immunoglobulin M [IgM]), anti-HCV Ab [Hepatitis C Virus antibody], Human Immunodeficiency Virus [HIV] 1 and HIV 2 antibodies. | Baseline to Day 8 | 
| Change from baseline in urinalysis | Specific gravity, nitrite, protein including microalbuminuria, glucose, ketones as well as blood WBC and RBC sediments will be assessed. ( | Baseline to Day 8 | 
| Change from baseline in urine drug & cotinine screen | : Urine will be collected and tested for cotinine and the following drugs or illicit substances: barbiturates, benzodiazepines, amphetamines, cocaine, opiates, and cannabis. | Baseline to Day 8 | 
| Change from baseline in pregnancy and assessments of fertility | A urine dipsick test will be performed. | Baseline to Day 8 |