A Drug-Drug Interaction Study of ENV-101 (Taladegib) on Nintedanib Pharmacokinetics in Healthy Subjects

Study Overview
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Brief Summary
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The goal of this clinical trial is to learn about the potential effect of ENV-101 (taladegib) on the pharmacokinetics of nintedanib (an approved treatment for idiopathic pulmonary fibrosis) when the two compounds are dosed together in healthy subjects. Participants in this study will receive ENV-101 and/or nintedanib on various days throughout a 10-day period during which they will reside at the clinical trial site.

Official Title
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A Phase 1, Single-Center, Fixed Sequence, Drug-Drug Interaction Study of ENV-101 (Taladegib) on Nintedanib Pharmacokinetics in Healthy Subjects

Conditions
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Idiopathic Pulmonary Fibrosis

Intervention / Treatment
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* Drug: taladegib
* Drug: nintedanib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body Mass Index (BMI) ≥18 and ≤32 kg/m^2 Body weight ≤120kg Subjects must be willing to be sequestered for 10 consecutive days. Exclusion Criteria: Chronic or current use of any prescription medications or acute use within the preceding 30 days or 5 half-lives, whichever is longer, with the exception of contraceptives, prior to study start Subject has an active infection of hepatitis B or C, or human immunodeficiency virus (HIV) at study start Subject has a 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 the screening visit, or planned participation in any such trial at time of study start Subject has a pulse <45 or >100 bpm; systolic blood pressure >160 mmHg, or diastolic blood pressure >95 mmHg at study start Subject has pacemaker; is not in sinus rhythm; has a corrected QT interval (QTc; using Fridericia's [QTcF] formula) of >450 ms (for males) and >470 ms (for females) during the Screening Period; or has a left bundle branch block or bifascicular block. Females and males of reproductive potential who are sexually active and unwilling to use birth control for the duration of the study and for 90 days after their final study dose Females that are pregnant or lactating Females and males that are unwilling to refrain from blood or blood product donation for the duration of the study and for 30 days after their final study dose Males who are unwilling to refrain from sperm donation for the duration of the study and for 90 days after their final study dose Females who are unwilling to refrain from egg donation for the duration of the study and for 90 days after their final study dose Subjects with a history of a severe allergic reaction or anaphylactic reaction or known hypersensitivity to any component of ENV-101 (taladegib) or nintedanib Subjects 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental<br> | Drug: taladegib<br>* 100 mg per tablet, dosed once daily<br>* Other names: ENV-101;Drug: nintedanib<br>* 100 mg per capsule, dosed once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Nintedanib maximum blood concentration (Cmax) after administration alone and after coadministration with ENV-101 (taladegib) |  | Day 1 and Day 7 | 
| Time of nintedanib maximum blood concentration (Tmax) after coadministration alone and after coadministration with ENV-101 (taladegib) |  | Day 1 and Day 7 | 
| Nintedanib absorption to time t (AUC0-t) after administration alone and after coadministration with ENV-101 (taladegib) | AUC represents area under the concentration-time curve and measures the amount of drug that is present in the blood from the time of administration to a given time t | Day 1 and Day 7 | 
| Nintedanib total absorption (AUC0-inf) after administration alone and after coadministration with ENV-101 (taladegib) |  | Day 1 and Day 7 | 
| Nintedanib half-life in the blood (T1/2) after administration alone and after coadministration with ENV-101 (taladegib) |  | Day 1 and Day 7 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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smoothened, hedgehog, pulmonary fibrosis