A Ph 1, Rndmzd, Dbl-Blinded, Pbo-Controlled, 4-Part Study to Eval the Safety, Tolerability, PK, and PD of TD-1058 Admin by Inhalation of Single (A) and Multiple (B) Ascending Doses in Healthy Subjs and Subjs With IPF (C) and Following Admin Microtracer Doses (D)
Overview
- Phase
- Phase 1
- Intervention
- TD-1058
- Conditions
- Idiopathic Pulmonary Fibrosis (IPF)
- Sponsor
- Theravance Biopharma
- Enrollment
- 72
- Locations
- 1
- Primary Endpoint
- Part D (Microtracer) - Adverse Events
- Status
- Terminated
- Last Updated
- 4 years ago
Overview
Brief Summary
This is a Phase 1, 4-part, randomized, double-blinded, placebo-controlled study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of TD-1058 inhaled solution. Part A is a SAD study in healthy subjects, Part B is a MAD study in healthy subjects, Part C is a multiple-dose study in subjects with IPF, and Part D studies lung bioavailability and renal elimination in Healthy Subjects.
Detailed Description
A Phase 1, 3-part, randomized, double-blinded, placebo-controlled, first in human study. Part A is a single ascending dose (SAD) study in up to 5 cohorts of 8 healthy subjects (6 active and 2 placebo). Part B is a multiple ascending dose (MAD) study in up to 4 cohorts of 8 healthy subjects (6 active and 2 placebo). Part C is a 28 day multiple-dose study in up to 2 cohorts of 12 IPF subjects (8 active and 4 placebo). The dose levels administered in Part C will not exceed those previously administered in Part B which were shown to be well tolerated. Part D studies lung bioavailability and renal elimination in Healthy Subjects.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Parts A and B:
- •Healthy, adult, male or female, 18 to 60 years of age, inclusive, at Screening
- •Body mass index (BMI) ≥ 18.0 and ≤ 30.0 kg/m2 and weighs at least 50 kg at Screening
- •Medically healthy with no clinically significant medical history, physical examination, spirometry, vital signs or ECGs, as deemed by the Investigator or designee
- •Forced expiratory volume of 1 second (FEV1) ≥80% predicted at Screening and prior to dosing
- •No clinically significant abnormalities in the results of laboratory evaluations at Screening and the visit scheduled between Day -7 and Day -2, as applicable, and at the discretion of the Investigator and Sponsor's Medical Monitor.
- •Pregnancy concerns:
- •Female subjects must either of non-childbearing potential or if of childbearing potential, subject must not be pregnant or breastfeeding, and must agree to use a highly effective birth control method during the study and through 30 days after the last dose of study medication
- •Male subjects must agree to use condoms to prevent potential fetal or partner exposure through seminal fluid, in addition to the use of highly effective pregnancy prevention measures with female partners of childbearing potential during the study and through 30 days after the last dose of study medication
- •Subjects must agree to not donate ova or sperm through 30 days after the last dose of study medication
Exclusion Criteria
- •Parts A and B:
- •History or presence of clinically significant medical or psychiatric condition or disease in the opinion of the Investigator or designee
- •Abnormal ECG measurements at Screening (any of the three individual ECG measurements) or prior to dosing indicating a second- or third- degree atrioventricular block, or one or more of the following:
- •QRS \> 120 msec
- •QTcF \> 450 msec (males) or \> 460 msec (females)
- •PR interval \> 220 msec
- •Known personal or family history of congenital long QT syndrome or known family history of sudden death.
- •Supine resting bradycardia (pulse \< 40 beats per minute \[bpm\]) or a supine resting tachycardia (pulse \> 100 bpm) at Screening or prior to dosing on Day
- •Abnormal renal function as defined by estimated glomerular filtration rate (eGFR) \<90mL/min/1.73m\^2 at Screening
- •History of clinically significant hypotensive episodes or symptoms of fainting, dizziness, or light-headedness.
Arms & Interventions
TD-1058
Part A (SAD): 6 out of 8 subjects per cohort (up to 5 cohorts) will be randomized to receive a single dose of TD-1058 Part B (MAD): 6 out of 8 subjects per cohort (up to 4 cohorts) will be randomized to receive multiple dose of TD-1058 Part C (IPF subjects): 8 out of 12 subjects per cohort (up to 2 cohorts) will be randomized to receive multiple dose of TD-1058 Part D (Healthy Subjects): 6 subjects (1 cohort) will receive a single dose of TD-1058. After receipt of initial dose, subjects will recieve infusion of radiolabeled TD-1058 microtracer.
Intervention: TD-1058
Placebo
Part A (SAD): 2 out of 8 subjects per cohort (up to 5 cohorts) will be randomized to receive a single dose of placebo Part B (MAD): 2 out of 8 subjects per cohort (up to 4 cohorts) will be randomized to receive multiple dose of placebo Part C (IPF subjects): 4 out of 12 subjects per cohort (up to 2 cohorts) will be randomized to receive multiple dose of placebo
Intervention: Placebo
Outcomes
Primary Outcomes
Part D (Microtracer) - Adverse Events
Time Frame: Part D (Microtracer) Day 1 to Day 8
Number and severity of treatment emergent adverse events
Part C (IPF) - Adverse Events
Time Frame: Part C (IPF) Day 1 to Day 35
Number and severity of treatment emergent adverse events
Part A (SAD) - Adverse Events
Time Frame: Part A (SAD) Day 1 to Day 8
Number and severity of treatment emergent adverse events
Part B (MAD) - Adverse Events
Time Frame: Part B (MAD) Day 1 to Day 21
Number and severity of treatment emergent adverse events
Secondary Outcomes
- Pharmacokinetics (PK) of TD-1058: Tmax(Part A (SAD) Day 1 to Day 8 Part B (MAD) Day 1 to Day 21 Part C (IPF) Day 1 to Day 35 Part D (Microtracer) Day 1 to Day 8)
- Pharmacokinetics (PK) of TD-1058: AUC(Part A (SAD) Day 1 to Day 8 Part B (MAD) Day 1 to Day 21 Part C (IPF) Day 1 to Day 35 Part D (Microtracer) Day 1 to Day 8)
- Pharmacokinetics (PK) of TD-1058: Cmax(Part A (SAD) Day 1 to Day 8 Part B (MAD) Day 1 to Day 21 Part C (IPF) Day 1 to Day 35 Part D (Microtracer) Day 1 to Day 8)