Treatment of airway inflammation, initially in asthma MedDRA version: 20.0 Level: PT Classification code 10003553 Term: Asthma System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
Conditions
Interventions
Product Name: TD-8236 150µg
Product Code: TD-8236
Pharmaceutical Form: Inhalation powder, hard capsule
INN or Proposed INN: TD-8236
Current Sponsor code: TD-8236
Other descriptive name: TD-8236
Concen
Sponsors
Theravance Biopharma Ireland Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Male or female, 18 to 65 years of age, inclusive, at Screening. 2.BMI = 18.0 and = 35.0 kg/m2 at Screening and weighs = 50 kg at Screening. 3.Documented physician-diagnosed asthma for = 4 months prior to Screening. 4.Pre-bronchodilator FEV1 = 70% predicted at Screening and prior to Day 1 dosing in Treatment Period 1. 5.Documented allergy to at least one common allergen as confirmed by the skin prick test, with wheal diameter =3mm greater than the negative control. Historical data up to one year can be used. 6.Subject should be a dual responder to inhaled bronchial allergen challenges as manifested by positive allergen-induced early (LAR) and late airway bronchoconstriction (LAR) at screening, defined as follows: •EAR is defined as a fall in FEV1 of at least 20% from pre-challenge post diluent baseline values during the 30 minutes after inhaled bronchial allergen challenge. •LAR is defined by a fall from post diluent value of FEV1 of at least 15% on at least 3 occasions, 2 of which must be consecutive, between 3 to 8 hours after inhaled allergen challenge. 7.Able to correctly use the DPI inhaler and to generate sufficient peak inspiratory flow rate (PIFR) (at least 40 L/min) using the In-Check DIAL device at Screening and prior to dosing on Day 1 of Treatment Period 1. 8.Subject has no clinically significant abnormalities as determined by the PI in the results of laboratory evaluations at Screening, including: •Liver function tests (i.e., ALT, AST, ALP, GGT, and bilirubin) = upper limit of normal or deemed medically acceptable at the discretion of the PI and Sponsor’s Medical Monitor •Absolute lymphocyte counts within normal range or should be deemed medically acceptable at the discretion of the PI and Sponsor’s Medical Monitor 9.Subject must have a negative QuantiFeron® Test result at Screening. 10.Pregnancy concerns: •Female subjects must be either of non-childbearing potential or if of childbearing potential use a highly effective birth control method (see Section 6.3.10) during the study and through 30 days after the last dose of TD-8236. •Male subjects (with partners of child-bearing potential) must use acceptable contraception (see Section 6.3.10) during the study and through 30 days after the last dose of study medication •Male subjects must agree not to donate semen during the study and for 30 days after the last dose of study medication 11.Understands the study procedures in the ICF, and is willing and able to comply with the protocol-defined study procedures and expectations. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 21 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: 1.Is mentally or legally incapacitated at the time of Screening or Day 1 TP1, or expected during the conduct of the study that in the opinion of the PI/designee indicates the subject is inappropriate for the study 2.Have abnormal ECG measurements at Screening or pre-dose Day 1 TP1 indicating: •2nd or 3rd-degree AV block •QRS>120 msec •QTcF>450 msec(male) or >460msec(female) •PR interval >220msec 3.Subject has a known personal or family history of congenital long QT syndrome or known family history of sudden death 4.Subject has a resting bradycardia (pulse 100 bpm) at Screening or Day 1 TP1 5.Lung disease other than stable, mild asthma; worsening of asthma that requires a change in asthma therapy or is deemed clinically significant by the PI or Medical Monitor 6.History of clinically significant hypotensive episodes or symptoms of fainting, dizziness, or light-headedness 7.History of lymphoma, leukemia, or other types of malignancy (except for completely resected squamous or basal cell cancer) 8.Any signs of RTI within 6 weeks of screening or prior to Day 1 TP1 that are deemed clinically significant by the PI or Medical Monitor. 9.Subject who has a current bacterial, parasitic, fungal, or viral infection; any infection requiring hospitalization or IV antibiotics within 6 months prior to Screening; any infection requiring oral or topical antimicrobial treatment within 2 weeks prior to Screening or prior to Day 1 TP1; a history of > 1 episode of herpes zoster infection 10.Any evidence of current or previous clinically significant disease (with the exception of stable, mild asthma) 11.History of life-threatening asthma, defined as an asthma episode that required intubation and/or was associated with hypercapnoea, respiratory arrest and/or hypoxic seizures or hospitalisation (including emergency room visits) for the treatment of asthma within 3 months of Screening, or have been hospitalized or have attended emergency room visits for asthma > twice in last 12 months 12.Subject has any condition of the oro-laryngeal or respiratory tract (incl. but not limited to, prior surgery) that could possibly affect drug administration, deposition, or absorption, or ability to perform lung function, allergen challenge, sputum induction as determined by the PI or Sponsor Medical Monitor 13.Positive alcohol results at Screening or Day 1 TP1, or history or presence of alcoholism within the past 2 years prior to dosing on Day 1 TP1 14.Alcohol consumption >21 units per week (males) or >14 units per week (females) 15.Positive drugs of abuse test result (unless in the opinion of the investigator this can be explained by the patient’s current medications) at Screening or Day 1 TP1 16.Positive urine cotinine test result at Screening or Day 1 TP1 17.Uses or has used tobacco or nicotine-containing products within 6 months prior to Screening, or has history of >5 pack-years 18.History of hypersensitivity to drugs, latex allergy, band aids, adhesive dressing, or medical tape, with a clinically significant reaction as determined by the PI or designee 19.History of serious adverse reaction, severe hypersensitivity or allergy to any drug or in any other circumstance 20.Female subjects with a positive pregnancy test at Screening or Day 1 TP1, or who are breastfeeding or lactating 21.Subjects who have had a live viral vaccine within 8 weeks prior to Screening and/or are unwilling to avoid live viral vaccines for until at-least 8
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Characterize the late asthmatic response (LAR) in terms of area under the FEV1 (Forced expiratory volume in one second) curve after inhaled allergen challenge (breathing in a fine mist of the allergen that the participant is sensitive to) in mild asthmatic subjects receiving 14 days of TD-8236 or placebo (dummy drug containing no active ingredient);Secondary Objective: Secondary: •Characterize the late asthmatic response (LAR) in terms of maximum decline in FEV1 (Forced expiratory volume in one second) and area under the percent change FEV1 curve after inhaled allergen challenge (breathing in a fine mist of the allergen that the participant is sensitive to) in mild asthmatic subjects receiving 14 days of TD-8236 or placebo (dummy drug containing no active ingredient) •Assess the pharmacokinetics (PK - the levels of study medication in the body and the time it takes the body to break it down) of TD-8236 in subjects with asthma •Evaluate the safety and tolerability of inhaled TD-8236 administered for 14 days in subjects with mild asthma Exploratory: •Characterize the early asthmatic response (EAR) after inhaled allergen challenge in mild asthmatic subjects receiving 14 days of TD-8236 or placebo •Characterize the overall asthmatic response from 0-8 hours after inhaled allergen challenge in mild asthmatic subjects receiving 14 days of TD-8236 or placeb;Primary end point(s): •Area under the curve (AUC) of change from baseline FEV1 from 3 to 8 hours after inhaled allergen challenge at Day 14;Timepoint(s) of evaluation of this end point: FEV1 measured at Day 14 of each treatment period from pre-allergen challenge and the period beginning 3 hours and ending 8 hours after the allergen challenge. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary 1. AUC of percentage change from baseline in FEV1 from 3 to 8 hours after inhaled allergen challenge at Day 14 2. Maximum decline in FEV1 from 3 to 8 hours after inhaled allergen challenge at Day 14 3. Maximum percentage decline in FEV1 from 3 to 8 hours after inhaled allergen challenge at Day 14 4. Day 14 plasma PK parameters of TD-8236 in subjects with mild asthma 5. Safety and tolerability of TD-8236 over 14 days of dosing, including frequency and severity of adverse events, vital signs, clinical laboratory evaluations, and 12-lead ECG changes from baseline Exploratory 1. AUC of change from baseline FEV1 from 0 to 2 hours after inhaled allergen challenge at Day 14 2. AUC of percentage change from baseline in FEV1 from 0 to 2 hours after inhaled allergen challenge at Day 14 3. Maximum decline in FEV1 from 0 to 2 hours after inhaled allergen challenge at Day 14 4. Maximum percentage decline in FEV1 from 0 to 2 hours after inhaled allergen challenge at Day 14 5. AUC of change from baseline FEV1 from 0 to 8 hours after inhaled allergen challenge 6. AUC of percentage change from baseline FEV1 from 0 to 8 hours after inhaled allergen challenge 7. Change in pre-dose FEV1 from Day 1 to Day 14 for each treatment period 8. Change over time (change and percent change; pre-dose over 14 days, and pre-/post allergen challenge) in fraction exhaled nitric oxide (FeNO) 9. Total and differential cell counts in induced sputum and blood PD biomarker samples 10. Known or potential asthma-related biomarkers in induced sputum samples, including but not limited to: eosinophilic cationic protein (ECP), periostin, and various cytokines 11. Change from baseline in Total ACQ-5 score;Timepoint(s) of evaluation of this end point: Secondary 1,2,3. Pre-BAC & between 3 & 8 hrs post-BAC (Day 14 of each TP) 4. Days 1,7 pre-dose. Day 14 pre-dose,0.5,1,2,4,6,8 & 24 hrs post-dose (each TP) 5. AEs: From signing of consent to follow-up. Vital signs & ECG: SV1,pre-dose | — |
Countries
United Kingdom
Contacts
Public ContactNathan Pfeifer
Theravance Biopharma Ireland Limited
Outcome results
None listed