A Single-Dose, Bioequivalence Study of FMXIN001 4 mg Microspheres Powder

Study Overview
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Brief Summary
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A Single-Dose, Bioequivalence Study of FMXIN001 4 mg Microspheres Nasal Powder.

Detailed Description
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A comparison between FMXIN001 4 mg and Narcan® 4 mg/0.1 mL Nasal Spray under Fasting Conditions. A pharmacokinetic study in healthy volunteers

Official Title
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A Single-Dose, Bioequivalence Study of FMXIN001 4 mg Microspheres Powder and Narcan® 4 mg/0.1 mL Nasal Spray Under Fasting Conditions

Conditions
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Opioid Overdose

Intervention / Treatment
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* Combination Product: Nasus Pharma FMXIN001
* Combination Product: Nasal Naloxone liquid spray


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy, non-smoking, male and female subjects, 18 years of age or older. BMI ≥18 and ≤30 kg/m2. Females may be of childbearing or non-childbearing potential: Childbearing potential: o Physically capable of becoming pregnant Non-childbearing potential: Surgically sterile (i.e., both ovaries removed, uterus removed, or bilateral tubal ligation); and/or Postmenopausal (no menstrual period for at least 12 consecutive months without any other medical cause). Willing to use acceptable, effective methods of contraception. Able to tolerate venipuncture. Be informed of the nature of the study and give written consent prior to any study procedure. Exclusion Criteria: The following exclusion criteria will be assessed at screening (within 28 days prior to the first drug administration): Known history or presence of clinically significant neurologic, hematologic, endocrine, oncologic, pulmonary, immunologic, genitourinary, psychiatric, or cardiovascular disease or any other condition which, in the opinion of the Investigator, would jeopardize the safety of the subject or impact the validity of the study results. Known or suspected carcinoma. Known history or presence of hypersensitivity or idiosyncratic reaction to naloxone or any other drug substances with similar activity. Known history or presence of clinically significant lactose, galactose, or fructose intolerance. Presence of hepatic or renal dysfunction. Presence of nostril or septum piercing. Presence of abnormal nasal anatomy. Presence of hay fever/seasonal allergy/rhinitis. Presence of sinusitis. Presence of nasal symptoms (e.g., blocked and/or runny nose, nasal polyps). Presence of nasal septum ulcers or perforations, or nasal trauma within 30 days prior to drug administration. History of nasal surgery. History of malabsorption within the last year or presence of clinically significant gastrointestinal disease. History of atopic allergy (e.g., asthma, urticaria, eczematous dermatitis). Presence of a medical condition requiring regular medication (prescription and/or over-the-counter) with systemic absorption. History of drug or alcohol addiction requiring treatment. Any acute illness (e.g., cold/ rhinitis, acute infection) which is considered significant by the Investigator and that has not resolved within 7 days before the first drug administration. Positive test result for HIV, Hepatitis B surface antigen, or Hepatitis C antibody. Positive test result for urine drugs of abuse (amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, methadone, opiates, phencyclidine, and tricyclic antidepressants) or urine cotinine. Difficulty fasting or consuming standard meals. Inability to communicate well with the Investigators and staff (i.e., language problem, poor mental development or impaired cerebral function). Use of tobacco or nicotine-containing products within 6 months prior to drug administration. Females who: Have discontinued or changed the use of implanted, intrauterine, intravaginal, or injected hormonal contraceptives within 6 months prior to drug administration; Have discontinued or changed the use of oral or patch hormonal contraceptives within 1 month prior to drug administration; Are pregnant (serum hCG consistent with pregnancy); or Are lactating. Donation or loss of whole blood (including clinical trials): ≥50 mL and <500 mL within 30 days prior to drug administration; ≥500 mL within 56 days prior to drug administration. Participation in a clinical trial that involved administration of an investigational medicinal product within 30 days prior to drug administration, or recent participation in a clinical investigation that, in the opinion of the Investigator, would jeopardize subject safety or the integrity of the study results. On a special diet within 30 days prior to drug administration (e.g., liquid, protein, raw food diet). Have had a tattoo or body piercing within 30 days prior to drug administration. Have clinically significant findings in vital signs measurements. Systolic blood pressure increase or decrease in value by more than 20 mmHg and/or diastolic blood pressure decrease in value by more than 10 mmHg from supine or sitting to standing position. Have clinically significant findings in a 12-lead ECG. Have clinically significant abnormal laboratory values. Have significant diseases. Have clinically significant findings from a physical examination. Use of any enzyme-modifying drugs known to induce/inhibit hepatic drug metabolism or alter gastrointestinal pH/movement (e.g., omeprazole, ranitidine) within 30 days prior to drug administration.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Open-label, single-dose, randomized, two-period, two treatment, two-sequence, crossover, comparative bioavailability study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FMXIN001 4 mg Naloxone microspheres powder,<br>Naloxone powder nasal spray from Nasus Pharma, Israel | Combination Product: Nasus Pharma FMXIN001<br>* A nasal spray of 4mg Naloxone Hydrochloride powder in a unit dose device<br>Combination Product: Nasal Naloxone liquid spray<br>* A nasal spray of 4mg/0.1mL Naloxone Hydrochloride solution in a unit dose device<br>* Other names: Narcan;|
| Active Comparator: Narcan® 4 mg/0.1 mL nasal spray<br>Naloxone solution nasal spray from Adapt Pharma, Inc., USA | Combination Product: Nasus Pharma FMXIN001<br>* A nasal spray of 4mg Naloxone Hydrochloride powder in a unit dose device<br>Combination Product: Nasal Naloxone liquid spray<br>* A nasal spray of 4mg/0.1mL Naloxone Hydrochloride solution in a unit dose device<br>* Other names: Narcan;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Unconjugated naloxone in plasma - Cmax | Pharmacokinetic Parameters | 0 to 8 hours post dose | 
| Unconjugated naloxone in plasma - AUC | Pharmacokinetic Parameters | 0 to 8 hours post dose | 
| Unconjugated naloxone in plasma - Tmax | Pharmacokinetic Parameters | 0 to 8 hours post dose | 
| Unconjugated naloxone in plasma - K el | Pharmacokinetic Parameters | 0 to 8 hours post dose | 
| Unconjugated naloxone in plasma- T half | Pharmacokinetic Parameters | 0 to 8 hours post dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood pressure | Safety Monitoring: Vital signs | pre-dose | 
| Pulse | Safety Monitoring: Vital signs | pre-dose | 
| Blood pressure | Safety Monitoring: Vital signs | 1 hour post dose | 
| Pulse | Safety Monitoring: Vital signs | 1 hour post dose | 
| Blood pressure | Safety Monitoring: Vital signs | 2 hour post dose | 
| Pulse | Safety Monitoring: Vital signs | 2 hour post dose | 
| Blood pressure | Safety Monitoring: Vital signs | 4 hour post dose | 
| Pulse | Safety Monitoring: Vital signs | 4 hour post dose | 
| Blood pressure | Safety Monitoring: Vital signs | 12 hour post dose | 
| Pulse | Safety Monitoring: Vital signs | 12 hour post dose | 
| 12-Lead ECG | Safety Monitoring | pre-dose | 
| 12-Lead ECG | Safety Monitoring | 0.5 hours | 
| 12-Lead ECG | Safety Monitoring | 2 hours | 
| 12-Lead ECG | Safety Monitoring | 12 hours | 
| 4-item NHANES Pocket Smell Test | Safety Monitoring | pre-dose | 
| 4-item NHANES Pocket Smell Test | Safety Monitoring | 24 hours post dose | 
| Nasal examination | Safety Monitoring | pre-dose | 
| Nasal examination | Safety Monitoring | 1 hour | 
| Nasal examination | Safety Monitoring | 23 hour | 
| Adverse events | Safety Monitoring | 0 to 24 hour post dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Naloxone, Nasal, Powder