Study of SIAN Nasal Spray in Healthy Adults

NCT05194358 | Completed Phase 1 FDA Drug

• 1 other identifier: EBS-SIN-001
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 2

Brief Summary

This study is designed to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of single ascending doses of Stabilized Isoamyl Nitrite (SIAN) nasal spray in healthy subjects.

Conditions

Cyanide Poisoning

Keywords

Cyanide Exposure; Cyanide; Stabilized Isoamyl Nitrite (SIAN); Isoamyl Nitrite (IAN)

Outcome Measures

Primary Outcomes (2)

• Related Serious Adverse Events (SAEs)

  Incidence of related SAEs

  Through Day 8

• Methemoglobin (MetHb) level

  To determine the dose that will result in a 6-10% MetHb level

  Through 360 minutes post-dose

Secondary Outcomes (26)

• PK Endpoint: Maximum observed concentration (Cmax) of Isoamyl Alcohol (IAA metabolite)

  Through 59 minutes post-dose

• PK Endpoint: Time at which Cmax occurs (Tmax) of IAA

  Through 59 minutes post-dose

• PK Endpoint: Apparent first order terminal elimination half-life (t 1/2) of IAA

  Through 59 minutes post-dose

• PK Endpoint: Area under the concentration-time curve from time 0 to 10 minutes post-dose (AUC 0-10min) of IAA

  Through 59 minutes post-dose

• PK Endpoint: Area under the concentration-time curve from time 0 to the last quantifiable concentration (AUC 0-last) of IAA

  Through 59 minutes post-dose

Study Arms (7)

Cohort 1 SIAN

EXPERIMENTAL

SIAN dose of 0.28 mg/kg (20 μL) will be administered from a single syringe-based spray device into left nostril.

Drug: Stabilized Isoamyl Nitrite (SIAN)

Cohort 2 SIAN

EXPERIMENTAL

SIAN dose of 0.73 mg/kg (50 μL) will be administered from a single syringe-based spray device into left nostril.

Drug: Stabilized Isoamyl Nitrite (SIAN)

Cohort 3 SIAN

EXPERIMENTAL

SIAN dose of 1.45 mg/kg (100 μL) will be administered from a single syringe-based spray device into left nostril.

Drug: Stabilized Isoamyl Nitrite (SIAN)

Cohort 4 SIAN

EXPERIMENTAL

SIAN dose of 2.18 mg/kg (150 μL) will be administered from a single syringe-based spray device into left nostril.

Drug: Stabilized Isoamyl Nitrite (SIAN)

Cohort 5 SIAN

EXPERIMENTAL

SIAN dose of 2.90 mg/kg (200 μL) will be administered in two syringe-based spray devices, each containing 100 μL, with dose administered in left then right nostril, one device per nostril. For doses of 2.90 milligram/kilogram (200 microliter) and higher, the dose will be split equally between the two nostrils to avoid drug overflow from the nose (using two syringe-based spray devices one immediately followed by the other). Lower doses will be administered by a single device to one nostril.

Drug: Stabilized Isoamyl Nitrite (SIAN)

Cohort 6 SIAN

EXPERIMENTAL

SIAN dose of 3.63 mg/kg (250 μL) will be administered in two syringe-based spray devices, each containing 125 μL, with dose administered in left then right nostril, one device per nostril.

Drug: Stabilized Isoamyl Nitrite (SIAN)

Cohort 7 SIAN

EXPERIMENTAL

SIAN dose of 4.35 mg/kg (300 μL) will be administered in two syringe-based spray devices, each containing 150 μL, with dose administered in left then right nostril, one device per nostril.

Drug: Stabilized Isoamyl Nitrite (SIAN)

Interventions

Stabilized Isoamyl Nitrite (SIAN) DRUG

SIAN is comprised of isoamyl nitrite (IAN) stabilized with 4% by weight epoxidized linseed oil (ELSO) and administered by intranasal (IN) delivery as a nasal spray. A syringe-based spray device will be used to administer the SIAN product. This syringe-based spray device, consists of a Hamilton type syringe connected to a tip that functions as an atomizer, to provide an optimal spray plume for nasal absorption while minimizing exposure to lungs.

Cohort 1 SIAN; Cohort 2 SIAN; Cohort 3 SIAN; Cohort 4 SIAN; Cohort 5 SIAN; Cohort 6 SIAN; Cohort 7 SIAN

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Able and willing to provide informed consent (and assent as applicable) voluntarily signed by subject/guardian/legally acceptable representative.
• Generally healthy, in the opinion of the PI, medical history, physical examination, vital signs, ECG and laboratory assessments at Screening.
• Male or non-pregnant female.
• Aged 18-45 years, inclusive, at the time of informed consent.
• Have adequate venous access for phlebotomies.
• For Women who are EITHER A or B:
• A. Not of childbearing potential: surgically sterile (at least six weeks post bilateral tubal ligation, bilateral oophorectomy or hysterectomy); or post-menopausal (defined as ≥50 years of age with a history of ≥12 consecutive months without menses prior to randomization in the absence of other pathologic or physiologic causes and screening follicle-stimulating hormone \[FSH\] \> 30 mIU/mL)
• B. Women of childbearing potential who are not planning to be pregnant during the study period and who meet criteria i - iv: i. Negative serum pregnancy test at Screening Visit ii. Negative urine pregnancy test prior to dosing at Day -1 (Baseline) iii. Not currently breastfeeding iv. Using one of the following highly effective methods of contraception during the study period:
• Combined estrogen and progestogen, or progestogen-only hormonal contraception associated with inhibition of ovulation (e.g. implants, pills, patches) initiated ≥30 days prior to Day 1
• Intrauterine device (IUD) inserted ≥30 days prior to Day 1
• Double barrier type of birth control (e.g. female condom, diaphragm or cervical cap and spermicidal foam/gel/cream/suppository, or male condom with diaphragm, male condom with cervical cap)
• Body mass index (BMI) between 18 and 34 kg/m2, inclusive.

You may not qualify if:

• Acute disease not resolved at least 4 weeks before Baseline (Day -1).
• Any chronic clinical condition that requires active treatment of any kind. However, subjects that are on thyroid hormone replacement therapy are eligible if clinically euthyroid and on a stable dose of thyroxine for at least 2 years.
• Medical history of cardiovascular (including symptomatic or asymptomatic aortic or mitral valvular disease, hypertension), renal, pulmonary and neurological conditions.
• Active treatment for erectile dysfunction, continuous or on demand, within 4 weeks of baseline.
• Orthostatic hypotension (at any time prior to dosing) or history of syncope of any cause.
• Clinically significant ocular condition, other than a requirement for corrective lenses.
• Any cancer other than the following:
• Any non-metastatic cancer (excluding hematologic malignancies) or melanoma of which the subject has been disease-free for at least five years; or
• Localized skin cancer that has been resected at least 4 weeks prior to Screening (including squamous cell and basal cell carcinomas).
• History of intolerance to nitrites, nitrates or IAN and/or any of the study drug components (including ELSO (Epoxidized linseed oil)).
• Contraindication to methylene blue as per the medical history of the subject.
• History of nasal disorders, chronic sinusitis, sinonasal surgery including rhinoplasty, or significant abnormalities of the nasal anatomy including septum deviations.
• Piercing of the nose that could interfere with study drug administration or absorption or study assessments, as judged by the investigator.
• Participation in another clinical study and/or use of any drug, vaccine, device or combination product in the context of a clinical research study within 30 days prior to Baseline (Day -1) or administration of a biological product in the context of a clinical research study within 90 days prior to Baseline (Day -1).
• Red blood cell G6PD (glucose-6-phosphate dehydrogenase) deficiency, by laboratory testing at Screening.

Sponsors & Collaborators

• Emergent BioSolutions: lead
• Biomedical Advanced Research and Development Authority: collaborator

Study Sites (2)

Alliance for Multispecialty Research, LLC

Knoxville, Tennessee, 37920, United States

Location

Austin Clinical Research Unit - PPD Phase I Clinic

Austin, Texas, 78744, United States

Location

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 4, 2022
• First Posted: January 18, 2022
• Study Start: December 21, 2021
• Primary Completion: September 29, 2023
• Study Completion: October 13, 2023
• Last Updated: June 3, 2025

Record last verified: 2025-05

Locations

US (2)