Clinical trial NCT03652038: Single and Multiple Ascending Dose Study of TD-8236 by Inhalation
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Asthma
Keywords: Single ascending dose
SAD
Multiple ascending dose
MAD
Phase 1
first-in-human
TD-8236
asthma
Lead sponsor: Theravance Biopharma
Sponsor class: INDUSTRY
First posted: 2018-08-29
Enrollment: 94
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: To assess the safety and tolerability of SAD of TD-8236 by assessing the number, severity and type of treatment emergent adverse events
timeFrame: Day 1 through Day 8
measure: To assess the safety and tolerability of MAD of TD-8236 by assessing the number, severity and type of treatment emergent adverse events
timeFrame: Day 1 through Day 14
Secondary outcomes:
measure: Pharmacokinetics (PK) of TD-8236 when given as a Single Ascending Dose (SAD): Area under the plasma concentration-time curve (AUC)
timeFrame: Day 1 through Day 4
measure: Pharmacokinetics (PK) of TD-8236 when given as a Single Ascending Dose (SAD): Maximum observed concentration (Cmax)
timeFrame: Day 1 through Day 4
measure: Pharmacokinetics (PK) of TD-8236 when given as a Single Ascending Dose (SAD): Time to reach maximum observed concentration (Tmax)
timeFrame: Day 1 through Day 4
measure: Pharmacokinetics (PK) of TD-8236 when given as a Multiple Ascending Dose (MAD): Area under the plasma concentration-time curve (AUC)
timeFrame: Day 1 through Day 9
measure: Pharmacokinetics (PK) of TD-8236 when given as a Multiple Ascending Dose (MAD): Maximum observed concentration (Cmax)
timeFrame: Day 1 through Day 9
measure: Pharmacokinetics (PK) of TD-8236 when given as a Multiple Ascending Dose (MAD): Time to reach maximum observed concentration (Tmax)
timeFrame: Day 1 through Day 9
Other outcomes:
Locations:
city: Manchester
country: United Kingdom
facility: Theravance Biopharma Investigational Site
state: England
city: Belfast
country: United Kingdom
facility: Theravance Biopharma Investigational Site
state: Northern Ireland
Study officials:
affiliation: Theravance Biopharma
name: Medical Monitor
role: STUDY_DIRECTOR
References: