Single and Multiple Ascending Dose Study of TD-8236 by Inhalation

Study Overview
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Brief Summary
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This is a Phase 1, randomized, double-blinded, placebo controlled study. The study consists of 3 parts: Part A is a single ascending dose (SAD) study in healthy subjects, Part B is a multiple ascending dose (MAD) study in subjects with stable, mild asthma, and Part C (Biomarker) is a multiple dose study in subjects with stable, moderate-to-severe asthma.

Official Title
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A Phase 1, Randomized, Double-Blinded, Placebo-Controlled, 3-Part Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of TD-8236 by Inhalation of Single Ascending Doses in Healthy Subjects (Part A) and Multiple Ascending Doses in Subjects With Stable, Mild Asthma (Part B), and Stable, Moderate-to-Severe Asthma (Part C)

Conditions
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Asthma

Intervention / Treatment
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* Drug: TD-8236
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, 18 - 60 years old Willing and able to give informed consent and comply with the study Body mass index (BMI) 18 to 32 kg/m2 and weighs at least 50 kg Women of child bearing potential must have a negative pregnancy test and use a highly efficient birth control method Pre-bronchodilator FEV ≥ 70% predicted for MAD cohorts and >40% predicted for biomarker cohorts Treatment with inhaled corticosteroids with or without long acting beta agonists Additional inclusion criteria apply Exclusion Criteria: Positive for hepatitis A, B or C, HIV or tuberculosis Clinically significant abnormalities of laboratory evaluations Have abnormal ECG measurements Any sign of respiratory tract infection within 6 weeks of screening Have a current bacterial, parasitic, fungal or viral infection Uses or have used tobacco or nicotine-containing products within 6 months prior to screening Additional exclusion criteria apply

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TD-8236 for SAD (Part A)<br>6 out of 8 subjects per cohort (up to 5 cohorts) will be randomized to receive TD-8236 | Drug: TD-8236<br>* Study drug to be administered via inhaler device<br>|
| Placebo Comparator: Placebo for SAD (Part A)<br>2 out of 8 subjects per cohort (up to 5 cohorts) will be randomized to receive placebo | Drug: Placebo<br>* Placebo to be administered via inhaler device<br>|
| Experimental: TD-8236 for MAD (Part B)<br>6 out of 8 subjects per cohort (up to 6 cohorts) will be randomized to receive TD-8236. | Drug: TD-8236<br>* Study drug to be administered via inhaler device<br>|
| Placebo Comparator: Placebo for MAD (Part B)<br>2 out of 8 subjects per cohort (up to 6 cohorts) will be randomized to receive placebo. | Drug: Placebo<br>* Placebo to be administered via inhaler device<br>|
| Experimental: TD-8236 for Biomarker (Part C)<br>8 subjects in each of 2 biomarker cohorts will be randomized to receive TD-8236. | Drug: TD-8236<br>* Study drug to be administered via inhaler device<br>|
| Placebo Comparator: Placebo for Biomarker (Part C)<br>8 subjects in 1 biomarker cohort will be randomized to receive placebo. | Drug: Placebo<br>* Placebo to be administered via inhaler device<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the safety and tolerability of SAD of TD-8236 by assessing the number, severity and type of treatment emergent adverse events |  | Day 1 through Day 8 | 
| To assess the safety and tolerability of MAD of TD-8236 by assessing the number, severity and type of treatment emergent adverse events |  | Day 1 through Day 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK) of TD-8236 when given as a Single Ascending Dose (SAD): Area under the plasma concentration-time curve (AUC) | Multiple PK variables of TD-8236 will be assessed during SAD and may include, but are not limited to: Area under the plasma concentration-time curve (AUC) | Day 1 through Day 4 | 
| Pharmacokinetics (PK) of TD-8236 when given as a Single Ascending Dose (SAD): Maximum observed concentration (Cmax) | Multiple PK variables of TD-8236 will be assessed during SAD and may include, but are not limited to: Maximum observed concentration (Cmax) | Day 1 through Day 4 | 
| Pharmacokinetics (PK) of TD-8236 when given as a Single Ascending Dose (SAD): Time to reach maximum observed concentration (Tmax) | Multiple PK variables of TD-8236 will be assessed during SAD and may include, but are not limited to: Time to reach maximum observed concentration (Tmax) | Day 1 through Day 4 | 
| Pharmacokinetics (PK) of TD-8236 when given as a Multiple Ascending Dose (MAD): Area under the plasma concentration-time curve (AUC) | Multiple PK variables of TD-8236 will be assessed during MAD and may include, but are not limited to: Area under the plasma concentration-time curve (AUC) | Day 1 through Day 9 | 
| Pharmacokinetics (PK) of TD-8236 when given as a Multiple Ascending Dose (MAD): Maximum observed concentration (Cmax) | Multiple PK variables of TD-8236 will be assessed during MAD and may include, but are not limited to: Maximum observed concentration (Cmax) | Day 1 through Day 9 | 
| Pharmacokinetics (PK) of TD-8236 when given as a Multiple Ascending Dose (MAD): Time to reach maximum observed concentration (Tmax) | Multiple PK variables of TD-8236 will be assessed during MAD and may include, but are not limited to: Time to reach maximum observed concentration (Tmax) | Day 1 through Day 9 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SAD, Single ascending dose, Multiple ascending dose, MAD, Phase 1, first-in-human, TD-8236, asthma