A Randomized, Single-Dose and Multiple Dose Dose-Ranging Safety and Pharmacokinetics Study of Tacrolimus Powder for Inhalation in Healthy Adult Subjects
TFF Pharmaceuticals Australia Pty Limited
64 participants
Jun 29, 2020
Interventional
Conditions
Summary
TFF Pharmaceuticals Australia Pty Limited is developing the study drug TFF tacrolimus as a potential new treatment to lower the risk of rejection for lung transplantations. Tacrolimus is an immunosuppressive drug used mainly after an organ transplant to lower the risk of organ rejection. Immunosuppression has been a key factor for the success of organ transplants. Tacrolimus as inhalation therapy (TFF tacrolimus) is being investigated specifically to lower the risk of rejection for lung transplantations. Tacrolimus is available as oral capsules and as intravenous injections (into the vein). The purpose of this study is to determine safe and tolerable inhaled doses that will be investigated further in future human studies.
Eligibility
Inclusion Criteria5
- Healthy, adult, male or female (women of non-child bearing potential only),
- Continuous non smoker who has not used nicotine containing products (including e vaping) for at least 3 months prior to the first dosing and throughout the study, based on subject’s self-reporting and urine cotinine levels at screening.
- Medically healthy with no clinically significant medical history, physical and neurologic examination, laboratory profiles, vital signs or ECGs, as deemed by the PI or designee.
- A CKD-EPI Creatinine 2009 estimated creatinine clearance of >=80 mL/min
- A non vasectomized, male subject must agree to use a highly effective method of birth control with female partners of childbearing potential during the study and for 120 days following dosing.
Exclusion Criteria10
- History or presence of clinically significant medical or psychiatric condition or disease in the opinion of the PI or designee.
- History of any illness that, in the opinion of the PI or designee, 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 hypersensitivity or idiosyncratic reaction to tacrolimus, cyclosporine, or any chemically related compound (everolimus, sirolimus).
- History of lactase deficiency
- 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 with a positive pregnancy test or who are lactating.
- Positive results at screening for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV).
- ECG findings are abnormal.
- Blood pressure is abnormal.
- Seated heart rate is lower than 40 bpm or higher than 99 bpm at screening.
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Interventions
Part A: This is a double-blinded, placebo-controlled, randomized, dose-ranging study evaluating five different dose levels (0.5, 1.0, 2.5, 5, and 10 mg). On Day 1 of each period, subjects will receive a single dose of either TFF tacrolimus inhalation powder or a matching placebo. Participants will receive only one dose level of TFF tacrolimus. Participants will be required to fast overnight prior to dosing and for 2 hours following dosing, and will be domiciled at the clinical research center. Treatments will be administered by the clinic staff. For the 2.5 mg dose level, subjects will be given two administrations, one fasted and one with a high fat meal (50%-60% fat), in a fixed sequence fashion separated by one week. Safety and PK will be monitored on both occasions. Part B: This is a double-blinded, placebo-controlled, randomized, multi-dose study evaluating three different dose levels (1.0, 2.5, and 5.0 mg BID). Participants who enrolled in Part A are not eligible to enroll in Part B. Tacrolimus inhalation powder or matching placebo will be administered twice per day for 6.5 days for a total of 13 doses. Participants will receive only one dose level of TFF tacrolimus. Participants will be domiciled at the clinical research center and treatments will be administered by the clinic staff.
Locations(2)
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ACTRN12620000192987