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

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)

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.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: TD-8236; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 94
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • England
    • Manchester, England, United Kingdom, M23 9QZ
      • Theravance Biopharma Investigational Site
  • Northern Ireland
    • Belfast, Northern Ireland, United Kingdom
      • Theravance Biopharma Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

6

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Theravance Biopharma

Study record dates

Study Major Dates

• Study Start (Actual): November 7, 2018
• Primary Completion (Actual): July 13, 2020
• Study Completion (Actual): July 13, 2020

Study Registration Dates

• First Submitted: August 20, 2018
• First Submitted That Met QC Criteria: August 27, 2018
• First Posted (Actual): August 29, 2018

Study Record Updates

• Last Update Posted (Actual): September 30, 2021
• Last Update Submitted That Met QC Criteria: September 28, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: asthma; Phase 1; SAD; MAD; first-in-human; Multiple ascending dose; Single ascending dose; TD-8236
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma
• Other Study ID Numbers: 0175; 2018-001260-38 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Theravance Biopharma, Inc. will not be sharing individual de-identified participant data or other relevant study documents.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes