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

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

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

Study Overview

• Status: Completed
• Conditions: Opioid Overdose
• Intervention / Treatment: Combination product: Nasus Pharma FMXIN001; Combination product: Nasal Naloxone liquid spray

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Mississauga, Ontario, Canada, L5R 0B7
      • Pharma Medica Research Inc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Healthy, non-smoking, male and female subjects, 18 years of age or older.
2. BMI ≥18 and ≤30 kg/m2.

3. 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).
4. Willing to use acceptable, effective methods of contraception.
5. Able to tolerate venipuncture.
6. 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):

  1. 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.
  2. Known or suspected carcinoma.
  3. Known history or presence of hypersensitivity or idiosyncratic reaction to naloxone or any other drug substances with similar activity.
  4. Known history or presence of clinically significant lactose, galactose, or fructose intolerance.
  5. Presence of hepatic or renal dysfunction.
  6. Presence of nostril or septum piercing.
  7. Presence of abnormal nasal anatomy.
  8. Presence of hay fever/seasonal allergy/rhinitis.
  9. Presence of sinusitis.
  10. Presence of nasal symptoms (e.g., blocked and/or runny nose, nasal polyps).
  11. Presence of nasal septum ulcers or perforations, or nasal trauma within 30 days prior to drug administration.
  12. History of nasal surgery.
  13. History of malabsorption within the last year or presence of clinically significant gastrointestinal disease.
  14. History of atopic allergy (e.g., asthma, urticaria, eczematous dermatitis).
  15. Presence of a medical condition requiring regular medication (prescription and/or over-the-counter) with systemic absorption.
  16. History of drug or alcohol addiction requiring treatment.
  17. 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.
  18. Positive test result for HIV, Hepatitis B surface antigen, or Hepatitis C antibody.
  19. Positive test result for urine drugs of abuse (amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, methadone, opiates, phencyclidine, and tricyclic antidepressants) or urine cotinine.
  20. Difficulty fasting or consuming standard meals.
  21. Inability to communicate well with the Investigators and staff (i.e., language problem, poor mental development or impaired cerebral function).
  22. Use of tobacco or nicotine-containing products within 6 months prior to drug administration.

  23. 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.

  24. 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.
  25. 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.
  26. On a special diet within 30 days prior to drug administration (e.g., liquid, protein, raw food diet).
  27. Have had a tattoo or body piercing within 30 days prior to drug administration.
  28. Have clinically significant findings in vital signs measurements.
  29. 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.
  30. Have clinically significant findings in a 12-lead ECG.
  31. Have clinically significant abnormal laboratory values.
  32. Have significant diseases.
  33. Have clinically significant findings from a physical examination.
  34. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Nasus Pharma
• Investigators: Principal Investigator: Janice Faulknor, MD, CCFP, Pharma Medica Research Inc. Canada

Publications and helpful links

General Publications

• Lapidot T, Bouhajib M, Faulknor J, Khan S, Krayz GT, Abrutzky C, Megiddo D. A Novel Faster-Acting, Dry Powder-Based, Naloxone Intranasal Formulation for Opioid Overdose. Pharm Res. 2022 May;39(5):963-975. doi: 10.1007/s11095-022-03247-5. Epub 2022 Apr 6.

Helpful Links

• Lapidot, Tair, et al. "A Novel Faster-Acting, Dry Powder-Based, Naloxone Intranasal Formulation for Opioid Overdose." Pharmaceutical Research (2022): 1-13.

Study record dates

Study Major Dates

• Study Start (Actual): January 31, 2021
• Primary Completion (Actual): March 30, 2021
• Study Completion (Actual): October 10, 2021

Study Registration Dates

• First Submitted: January 11, 2021
• First Submitted That Met QC Criteria: January 14, 2021
• First Posted (Actual): January 19, 2021

Study Record Updates

• Last Update Posted (Actual): May 2, 2022
• Last Update Submitted That Met QC Criteria: April 25, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: Naloxone; Nasal; Powder
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Narcotic-Related Disorders; Opioid-Related Disorders; Drug Overdose; Opiate Overdose; Physiological Effects of Drugs; Peripheral Nervous System Agents; Sensory System Agents; Narcotic Antagonists; Naloxone
• Other Study ID Numbers: NP-NAL-004

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: Yes
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes