Phase 1 Study of SIAN Nasal Spray in Healthy Adults

• Status: Recruiting
• Trial end date: 2022-08-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Emergent BioSolutions
• Collaborator: Department of Health and Human Services

Criteria

Inclusion Criteria:

1. Able and willing to provide informed consent (and assent as applicable) voluntarily signed by subject/guardian/legally acceptable representative.

2. Generally healthy, in the opinion of the PI, medical history, physical examination, vital signs, electrocardiogram (ECG) and laboratory assessments at Screening.

3. Male or non-pregnant female.

4. Aged 18-45 years, inclusive, at the time of informed consent.

5. Have adequate venous access for phlebotomies.

6. 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)

7. Body mass index (BMI) between 18 and 34 kg/m2, inclusive.

Exclusion Criteria:

1. Acute disease not resolved at least 4 weeks before Baseline (Day -1).

2. 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.

3. Medical history of cardiovascular (including symptomatic or asymptomatic aortic or mitral valvular disease, hypertension), renal, pulmonary and neurological conditions.

4. Active treatment for erectile dysfunction, continuous or on demand, within 4 weeks of baseline.

5. Orthostatic hypotension (at any time prior to dosing) or history of syncope of any cause.

6. Any ocular condition, other than a requirement for corrective lenses.

7. Any cancer other than the following:

1. Any non-metastatic cancer (excluding hematologic malignancies) or melanoma of which the subject has been disease-free for at least five years; or

2. Localized skin cancer that has been resected at least 4 weeks prior to Screening (including squamous cell and basal cell carcinomas).

8. History of intolerance to nitrites, nitrates or IAN and/or any of the study drug components (including ELSO (Epoxidized linseed oil)).

9. Contraindication to methylene blue.

10. History of nasal disorders, chronic sinusitis, sinonasal surgery including rhinnoplasty, or significant abnormalities of the nasal anatomy including septum deviations.

11. Piercing of the nose that could interfere with study drug administration or absorption or study assessments, as judged by the investigator.

12. 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).

13. Red blood cell G6PD (glucose-6-phosphate dehydrogenase) deficiency, by laboratory testing at Screening.

14. Abnormal laboratory values Grade 1 or higher per the toxicity grading scale at Screening.

15. Hemoglobin (Hb) < 12.0 g/dL for females or < 13.5 g/dL for males at Screening.

16. Methemoglobin > 3% at Screening or Day -1.

17. Any history or family history of congenital methemoglobinemia.

18. Has a positive serology test for human immunodeficiency virus antibodies, hepatitis B virus surface antigen or hepatitis C virus antibodies at Screening.

19. Abnormal Screening or Day -1 ECG; however, abnormal readings for the following benign conditions will be acceptable for inclusion in the study: early repolarization, nonspecific ST-T wave pattern or changes, right axis deviation (axis ≤ 110°), first degree atrioventricular block (PR interval < 220 ms), nonspecific intraventricular conduction delay (QRS < 120 ms), indeterminate axis and short PR interval (no delta wave present).

20. Any scheduled or anticipated medical intervention or surgical procedure, including dental procedures, during study participation, from Screening through Day 8.

21. History of chronic or current tobacco use. Subjects with more than 10 years of tobacco cessation might be included if they are considered healthy according to Investigator's opinion and medical history.

22. History of significant alcohol abuse within 1 year prior to screening or regular use of alcohol within 6 months prior to the screening visit (more than 14 units of alcohol per week [1 unit = 150 mL of wine, 360 mL of beer, or 45 mL of 40% alcohol]) or positive alcohol breath test at Screening or Day -1.

23. Positive test result on urine drug screen (cocaine, marijuana, phencyclidine, amphetamine, methamphetamine, opioids including methadone, ecstasy), any evidence of ongoing drug abuse or dependence (including alcohol), or recent history (over the past five years) of treatment for alcohol or drug abuse within 1 year prior to screening or positive standard urine drug test at Screening or Day -1.

24. History of the use of poppers, (alkyl nitrites) or positive standard urine drug screen.

25. Has donated plasma or blood or intends to donate within 30 days prior to Day 1 or during the course of the study.

26. Has received any medication, either prescription or non-prescription, including dietary supplements or herbal medications (e.g., quercetin, Gingko Bilboa, palmetto, etc.), within 14 days prior to Baseline (Day -1) and is unable to refrain from any medication during study participation. The only allowed exception is hormonal birth control.

27. Psychological and/or emotional problems, which would render the informed consent invalid or limit the ability of the subject to comply with the study requirements.

28. Member or immediate family member of an investigative site or Sponsor team member.

29. Known lack of treatment compliance from prior studies or ongoing medical care based on medical records and Investigator's assessment.

30. Judged by the Investigator or Sponsor to be inappropriate/ineligible for the study for any other reason.