Single Ascending Dose and Multiple Ascending Dose Study of Voriconazole Inhalation Powder in Healthy Adult Subjects

• Status: Completed
• Trial end date: 2020-08-26
• Target enrollment: 0
• Participant gender: All

Summary

This is a Phase 1 (healthy adult volunteers), 2-part, double-blind, randomized, placebo controlled trial to evaluate the safety and pharmacokinetic (PK) profiles of escalating single doses of Voriconazole Inhalation Powder versus placebo (SAD part) and escalating multiple doses of Voriconazole Inhalation Powder versus placebo (MAD part). SAD part will be initiated first and includes a sentinel design. MAD part will not utilize a sentinel design and will be initiated once the lowest doses from SAD part are deemed safe.

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

Details

• Lead Sponsor: TFF Pharmaceuticals, Inc.
• Treatments: Voriconazole

Criteria

Inclusion Criteria:

1. Provide written informed consent to participate.

2. Healthy, adult males or females (women of non-childbearing potential only).

3. Body mass index (BMI) ≥ 18.0 and ≤ 32.0 kg/m2 at Screening.

4. Medically healthy with no clinically significant abnormalities in medical history, physical and visual examination, laboratory profiles, vital signs or ECGs, as deemed by the PI or designee.

5. Agree to abstain from recreational drug use throughout the study.

6. Must be willing and able to comply with the protocol.

7. Succeed in training on the use of the device for maximum of 12 inhalations in total, with demonstration of at-least 8 successful inhalations of empty capsules during training.

8. Have had a forced expiratory volume in one second (FEV1) ≥80%.

Exclusion Criteria:

1. Is mentally or legally incapacitated or has significant emotional problems in the opinion of the PI.

2. History or presence of clinically significant medical or psychiatric condition or disease in the opinion of the PI.

3. History of any illness that, in the opinion of the PI, might confound the results of the study or poses an additional risk to the subject by their participation in the study.

4. History or presence of alcoholism or drug abuse within the past 2 years.

5. History or presence of hypersensitivity or idiosyncratic reaction to voriconazole or any triazole antifungal.

6. Has had surgery or any medical condition within 6 months prior to first dosing which may affect the absorption, distribution, metabolism, or elimination of the study drug, in the opinion of the PI or designee.

7. Female subjects of childbearing potential.

8. Female subjects with a positive pregnancy test or who are lactating.

9. Positive urine drug or alcohol results at screening or first check-in.

10. Positive cotinine results at screening.

11. Diagnosis of asthma.

12. Use of albuterol or a similar bronchodilator

13. Positive results at screening for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV).

14. QTcF interval is >450 msec or has ECG findings deemed abnormal with clinical significance by the PI at screening.

15. Seated blood pressure with systolic less than 90 mmHg or diastolic less than 60 mm/Hg or with a systolic greater than 140 mmHg or diastolic greater than 90 mmHg at screening.

16. Seated heart rate is lower than 60 bpm or higher than 100 bpm at screening.

17. Using any exclusionary medication.

18. Donation or loss of 50 to 499 mL whole blood within 30 days or more than 499 mL whole blood within 56 days prior to the first dosing.

19. Plasma donation within 7 days prior to the first dosing.

20. Has coagulation test outside of normal ranges.

21. Has platelet, hemoglobin, and hematocrit that are below the lower limit of normal.

22. Has liver function tests including alanine aminotransferase (ALT), aspartate aminotransferase (AST), ALP and total bilirubin that are greater than the upper limit of normal. Estimated creatinine clearance <90 mL/min at screening.

23. Participation in another clinical study within 30 days prior to the first dosing.

24. Had a treatment with other investigational drug within 5 times the elimination half- life, if known (e.g., a marketed product) or within 30 days (if the elimination half-life is unknown) prior to first dosing.

25. Demonstrates an inability to operate the inhalation device after training.

26. Allergy or sensitivity to lactose or milk products.