A Randomized, Double-Blind, Placebo Controlled, Single-Dose and Multiple Dose Dose-Ranging Study of Voriconazole Inhalation Powder in Healthy Adult Subjects
Overview
- Phase
- Phase 1
- Intervention
- Voriconazole Inhalation Powder
- Conditions
- Healthy
- Sponsor
- TFF Pharmaceuticals, Inc.
- Enrollment
- 65
- Locations
- 1
- Primary Endpoint
- Number of participants who experience laboratory test abnormalities
- Status
- Completed
- Last Updated
- 4 years ago
Overview
Brief 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.
Detailed Description
This is a Phase 1, randomized, 2 part double-blind, placebo-controlled trial to evaluate the safety and PK profiles of Voriconazole Inhalation Powder (VIP) in a SAD/MAD study design. Part A is a double-blinded, placebo-controlled, randomized, dose- ranging single dose study evaluating four different dose levels. On Day 1 of each group, two selected subjects (sentinel subjects) will receive either Voriconazole Inhalation Powder or a matching placebo. Blood and sputum samples and safety measurements including Adverse Events (AEs) will be collected over 24 hour period following the drug administration. The safety results to be evaluated include AEs, concomitant medications, out of specification clinical laboratory results, vital signs, Electrocardiograms (ECGs), visual examinations, pulmonary function tests, pulse oximetry results and any new findings on physical examinations. If the administration is safe as deemed by Principal Investigator \& Medical Monitor, the remaining six subjects will be dosed, with identical safety and PK procedures performed after minimum of 3 days interval. A minimum of 3 days will separate each dose escalation, with the remaining dose groups dosed in a sentinel fashion. Part B is a double-blinded, placebo-controlled, randomized, dose- ranging multi-dose study evaluating four different dose levels. Dose level 1 of Part B can begin in parallel once safety assessments of Part A dose level 2 are complete and indicate safety is present. Voriconazole Inhalation Powder will be administered twice daily (BID) × 13 doses. Blood samples for safety and PK will be collected over 12 hours after the first dose and 24 hours after the last dose. A minimum of 1 week will separate the start of each dose escalation, with the remaining dose groups.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Provide written informed consent to participate.
- •Healthy, adult males or females (women of non-childbearing potential only).
- •Body mass index (BMI) ≥ 18.0 and ≤ 32.0 kg/m2 at Screening.
- •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.
- •Agree to abstain from recreational drug use throughout the study.
- •Must be willing and able to comply with the protocol.
- •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.
- •Have had a forced expiratory volume in one second (FEV1) ≥80%.
Exclusion Criteria
- •Is mentally or legally incapacitated or has significant emotional problems in the opinion of the PI.
- •History or presence of clinically significant medical or psychiatric condition or disease in the opinion of the PI.
- •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.
- •History or presence of alcoholism or drug abuse within the past 2 years.
- •History or presence of hypersensitivity or idiosyncratic reaction to voriconazole or any triazole antifungal.
- •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.
- •Female subjects of childbearing potential.
- •Female subjects with a positive pregnancy test or who are lactating.
- •Positive urine drug or alcohol results at screening or first check-in.
- •Positive cotinine results at screening.
Arms & Interventions
Voriconazole Inhalation Powder
Investigational drug will be supplied as capsules, each capsule contains 10 mg of Voriconazole Inhalation Powder. The capsules will be administered with the provided breath actuated Plastiape RS00 Model 8 Dry Powder Inhaler device.
Intervention: Voriconazole Inhalation Powder
Placebo
Placebo will be supplied as capsules, each capsule will contain no active ingredient. The capsules will be administered with the provided breath actuated Plastiape RS00 Model 8 Dry Powder Inhaler device.
Intervention: Placebo
Outcomes
Primary Outcomes
Number of participants who experience laboratory test abnormalities
Time Frame: Baseline through study completion, an average of 14 days
Number of participants with potentially clinically significant laboratory test results
PK of VIP in plasma: Maximum observed concentration (Cmax)
Time Frame: Predose Day 1 and through 12 hours post last dose (day 6)
Blood samples will be collected for analysis
Mean change from baseline in forced expiratory volume (FEV1)
Time Frame: Baseline through study completion, an average of 14 days
Spirometry used to measure FEV1 lung function
Mean change from baseline in forced vital capacity (FVC)
Time Frame: Baseline through study completion, an average of 14 days
Spirometry used to measure FVC lung function
Number of participants who experience vital sign abnormalities
Time Frame: Baseline through study completion, an average of 14 days
Number of participants with potentially clinically significant vital sign values
Mean change from baseline in QTcF changes via ECG
Time Frame: Baseline through study completion, an average of 14 days
Number of participants with potentially clinically significant ECG values
Number of participants who experience physical examination abnormalities
Time Frame: Baseline through study completion, an average of 14 days
Number of participants with potentially clinically significant physical examination findings
PK of VIP in plasma: Area under the plasma-concentration time curve (AUC)
Time Frame: Predose Day 1 and through 12 hours post last dose (day 6)
Blood samples will be collected for plasma analysis
PK of VIP in plasma: Area under the concentration time curve, from time 0 to the last observed non-zero concentration (AUC0-tlast)
Time Frame: Predose Day 1 and through 12 hours post last dose (day 6)
Blood samples will be collected for analysis
PK of VIP in plasma: Area under the concentration time curve from time 0 extrapolated to infinity (AUC∞)
Time Frame: Predose Day 1 and through 12 hours post last dose (day 6)
Blood samples will be collected for analysis
PK of VIP in plasma: Termination elimination half-life (t½)
Time Frame: Predose Day 1 and through 12 hours post last dose (day 6)
Blood samples will be collected for analysis
Number of participants who experience pulse oximetry abnormalities
Time Frame: Baseline through study completion, an average of 14 days
Number of participants with potentially clinically significant pulse oximetry values
PK of VIP in plasma: Area under the plasma-concentration time curve over the first 12 hours after dosing (AUC0-12)
Time Frame: Predose Day 1 and through 12 hours post last dose (day 6)
Blood samples will be collected for analysis
Number of participants who experience Adverse Events (AEs), Serious Adverse Events (SAEs) and withdrawals due to AEs
Time Frame: Through study completion, an average of 14 days
Number of AEs, SAEs, and discontinuations due to AEs
Mean change from baseline in FEV1/FVC ratio
Time Frame: Baseline through study completion, an average of 14 days
Spirometry used to measure FEV1 and FVC lung function
PK of VIP in plasma: Time to maximal observed concentration (tmax)
Time Frame: Predose Day 1 and through 12 hours post last dose (day 6)
Blood samples will be collected for analysis
PK of VIP in plasma: Apparent total body clearance (CL/F)
Time Frame: Predose Day 1 and through 12 hours post last dose (day 6)
Blood samples will be collected for analysis
PK of VIP in plasma: Apparent volume of distribution during the terminal elimination phase (Vz/F)
Time Frame: Predose Day 1 and through 12 hours post last dose (day 6)
Blood samples will be collected for analysis