A Study to Evaluate Pharmacokinetics and Drug-drug Interactions of ENV-101 (Taladegib) in Healthy Participants

Official title

A Phase 1, Open-Label Study to Evaluate Pharmacokinetics and Drug-drug Interactions of ENV-101 in Healthy Participants

Overview

The purposes of this study are to: 1. evaluate potential interactions between taladegib (ENV-101) and current standard-of-care (SOC) therapies for idiopathic pulmonary fibrosis (IPF), including nintedanib and pirfenidone, and 2. more fully characterize the pharmacokinetics (PK) of taladegib (i.e., how the body absorbs, distributes, metabolizes and excretes taladegib). This study will enroll 4 cohorts (groups) of participants. Each cohort will experience a different duration of treatment and sequestering (being housed) at the clinical site, followed by a 14-day follow-up period for safety evaluation. The longest duration of treatment for any cohort is 30 days.

Interventions

• Drug taladegib
  low, medium or high dose tablet administered once, or once a day
• Drug nintedanib
  150 mg capsule administered twice a day
• Drug pirfenidone
  One, two or three 267 mg tablets administered three times a day
• Drug pirfenidone
  Three 267 mg tablets administered once

Primary outcome measures

• Cohort 1: Taladegib (ENV-101) maximum blood concentration (Cmax) after administration alone and after coadministration with nintedanib [Time frame: Day 1 and Day 13]
• Cohort 1: Time of taladegib maximum blood concentration (Tmax) after administration alone and after coadministration with nintedanib [Time frame: Day 1 and Day 13]
• Cohort 1: Taladegib absorption to time t (AUC[0-t]) after administration alone and after coadministration with nintedanib [Time frame: Day 1 and Day 13]
• Cohort 1: Taladegib total absorption (AUC[0-infinity]) after administration alone and after coadministration with nintedanib [Time frame: Day 1 and Day 13]
• Cohort 1: Taladegib extrapolated total absorption (AUC[extrapolated]) after administration alone and after coadministration with nintedanib [Time frame: Day 1 and Day 13]
• Cohort 1: Taladegib half-life in the blood (T1/2) after administration alone and after coadministration with nintedanib [Time frame: Day 1 and Day 13]
• Cohort 1: Elimination rate constant (K[el]) for taladegib after administration alone and after coadministration with nintedanib [Time frame: Day 1 and Day 13]
• Cohort 1: Apparent oral clearance (CL/F) of taladegib after administration alone and after coadministration with nintedanib [Time frame: Day 1 and Day 13]
• Cohort 1: Apparent volume of distribution (Vz/F) of taladegib after administration alone and after coadministration with nintedanib [Time frame: Day 1 and Day 13]
• Cohort 2: Taladegib maximum blood concentration (Cmax) after administration alone and after coadministration with pirfenidone [Time frame: Day 1 and Day 27]

Eligibility criteria

Inclusion criteria

• Participants are reproductively sterile.
• Body Mass Index (BMI) ≥ 18.5 and ≤ 32 kg/m2 and body weight ≥ 50 kg at study start.
• Medically healthy with no clinically significant medical history, physical examination, clinical laboratory profiles, vital signs, or electrocardiograms (ECGs) prior to dosing, as deemed by the Investigator.
• Able to swallow multiple capsules and tablets.
• Participants are willing to remain on study treatment for the duration of the study and comply with all study days and procedures.
• Participants willing to sign and have a full understanding of the informed consent.
• Participants must be willing to be sequestered for the time period indicated for their respective cohort.

Exclusion criteria

• Chronic or current use of any prescription or over the counter medications; or acute use of prescription medications within 14 days or 5 half-lives, whichever is longer, or over the counter medications within 7 days or 5 half-lives, whichever is longer, prior to study start, or planned use during all study periods.
• Participant is unwilling to refrain from fruits (including juices) that inhibit CYP3A4, including grapefruit, Seville orange, pomelo, or star fruit, beginning 7 days prior to study start through end of study.
• Active infection with hepatitis B or C, or human immunodeficiency virus (HIV) during screening.
• Current alcohol or drug abuse.
• Smoking or other nicotine use (including but not limited to vaping, nicotine patch, nicotine gum or nicotine lozenge) within 3 months prior to screening, current smoker, or unwillingness to refrain from smoking for the duration of the study.
• History or presence (per participant history) of:

• Autoimmune disease such as rheumatoid arthritis or systemic lupus erythematosus
• Thrombophlebitis or deep vein thrombosis
• Hematologic or coagulation disorders
• Liver disease or dysfunction; Gilbert's syndrome
• Renal dysfunction or glomerulonephritis
• Coronary artery disease
• Diverticular disease
• Congestive heart failure or ventricular dysfunction
• Clinically significant cardiovascular, gastrointestinal, pulmonary, endocrine, central nervous system disorders, or other major active and uncontrolled disease in the opinion of the Investigator.
• History of malignancy of any type, other than in situ cervical cancer or surgically excised non-melanomatous skin cancers, within 5 years before study start.
• Participation in a clinical research trial that included the receipt of an investigational agent or any experimental procedure within 30 days or 5 half-lives, whichever is longer, prior to screening, during screening, or planned participation in any such trial while participating in this study.
• Major surgery requiring hospitalization (according to the Investigator) performed within 3 months prior to screening, or planned during the course of the trial.
• Participants with clinically significant cardiac abnormalities including but not limited to: has pacemaker; or is not in sinus rhythm during screening; or has a left bundle branch block or bifascicular block during screening; or any prior history of ventricular arrhythmia or torsades de pointes.
• Participant is unwilling to adhere to the on-study diet provided by the clinical site during study participation.
• Females who are pregnant or nursing.
• Participants that are unwilling to refrain from blood or blood product donation for the duration of the study and for 30 days after their final dose of any study treatment.
• Males who are unwilling to refrain from sperm donation for the duration of the study and for 95 days after their final dose of any study treatment.
• Females who are unwilling to refrain from egg donation for the duration of the study and for 95 days after their final dose of any study treatment.
• Participants with a history of a severe allergic reaction or anaphylactic reaction or known hypersensitivity to any component of taladegib (all cohorts), nintedanib (Cohort 1), or pirfenidone (Cohorts 2 and 3).
• Participants who are immediate family members (spouse, parent, child, or sibling; biological or legally adopted) of personnel directly affiliated with the study investigative site or the study Sponsor.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Non-randomized

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Australia · 2 centers

• Research Site — Brisbane
• Research Site — Melbourne

Identifiers

NCT: NCT07454291 · ENV-IPF-104

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗