The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03064113




Registration number
NCT03064113
Ethics application status
Date submitted
20/01/2017
Date registered
24/02/2017
Date last updated
24/02/2017

Titles & IDs
Public title
Effects of TD-4208 on FEV1 in Subjects With Chronic Obstructive Pulmonary Disease (COPD)
Scientific title
A Phase 2, Randomized, Double-Blind, Crossover Study to Examine the Pharmacodynamics, Safety and Tolerability, and Pharmacokinetics of Single Doses of TD-4208 in Subjects Diagnosed With Chronic Obstructive Pulmonary Disease
Secondary ID [1] 0 0
ACTRN12611000482965
Secondary ID [2] 0 0
0059
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Obstructive Pulmonary Disease, COPD 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Chronic obstructive pulmonary disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Placebo
Treatment: Drugs - TD-4208 700 µg
Treatment: Drugs - TD-4208 350 µg
Treatment: Drugs - Ipratropium 500 µg

Placebo Comparator: Placebo - Sequence 1:
Period 1 = Placebo; Period 2 = TD-4208 700 µg; Period 3 = TD-4208 350 µg; Period 4 = Ipratropium 500 µg

Experimental: TD-4208 700 µg - Sequence 2:
Period 1 = TD-4208 700 µg; Period 2 = Ipratropium 500 µg; Period 3 = Placebo; Period 4 = TD-4208 350 µg

Experimental: TD-4208 350 µg - Sequence 3:
Period 1 = TD-4208 350 µg; Period 2 = Placebo; Period 3 = Ipratropium 500 µg; Period 4 = TD-4208 700 µg

Active Comparator: Ipratropium 500 µg - Sequence 4:
Period 1 = Ipratropium 500 µg; Period 2 = TD-4208 350 µg; Period 3 = TD-4208 700 µg; Period 4 = Placebo


Treatment: Drugs: Placebo


Treatment: Drugs: TD-4208 700 µg


Treatment: Drugs: TD-4208 350 µg


Treatment: Drugs: Ipratropium 500 µg


Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change in peak forced expiratory volume in one second (FEV1) relative to baseline
Timepoint [1] 0 0
From predose to 25 hours postdose
Secondary outcome [1] 0 0
Area under the FEV1 vs. time curve, time-matched difference from placebo
Timepoint [1] 0 0
From predose to 25 hours postdose
Secondary outcome [2] 0 0
Area under the FEV1 vs. peak FEV1, time-matched difference from placebo
Timepoint [2] 0 0
From predose to 25 hours postdose
Secondary outcome [3] 0 0
Peak Expiratory Flow Rate (PEFR) from 25% to 75% of vital capacity (FEF25-75), as related to FEV1
Timepoint [3] 0 0
From predose to 25 hours postdose
Secondary outcome [4] 0 0
Forced Expiratory flow from 25% to 75% of vital capacity (FEF25-75), as related to FEV1
Timepoint [4] 0 0
From predose to 25 hours postdose
Secondary outcome [5] 0 0
Forced Vital Capacity (FVC)
Timepoint [5] 0 0
From predose to 25 hours postdose
Secondary outcome [6] 0 0
Area under the forced vital capacity (FVC) vs. time curve
Timepoint [6] 0 0
From predose to 25 hours postdose
Secondary outcome [7] 0 0
Safety and tolerability endpoints: adverse events
Timepoint [7] 0 0
From randomization to the Period 4 Post-Study Follow-up Visit (up to 84 days)
Secondary outcome [8] 0 0
Safety and tolerability endpoints: vital signs
Timepoint [8] 0 0
From predose to 24 hours postdose
Secondary outcome [9] 0 0
Safety and tolerability endpoints: ECG parameters
Timepoint [9] 0 0
From predose to 24 hours postdose
Secondary outcome [10] 0 0
Safety and tolerability endpoints: physical exam results
Timepoint [10] 0 0
From predose to 24 hours postdose
Secondary outcome [11] 0 0
Safety and tolerability endpoints: clinical lab results
Timepoint [11] 0 0
From predose to 24 hours postdose
Secondary outcome [12] 0 0
Plasma PK parameters: Cmax
Timepoint [12] 0 0
From predose to 24 hours postdose
Secondary outcome [13] 0 0
Plasma PK parameters: Area under the concentration-versus-time curve calculated from time zero to the last detectable time point (AUC0-t)
Timepoint [13] 0 0
From predose to 24 hours postdose
Secondary outcome [14] 0 0
Plasma PK parameters: terminal half-life (t½)
Timepoint [14] 0 0
From predose to 24 hours postdose
Secondary outcome [15] 0 0
Plasma PK parameters: Renal clearance calculated as Ae/AUC0-t (CLrenal)
Timepoint [15] 0 0
From predose to 24 hours postdose
Secondary outcome [16] 0 0
Urine PK parameters: Cmax
Timepoint [16] 0 0
From predose to 24 hours postdose
Secondary outcome [17] 0 0
Urine PK parameters: Area under the concentration-versus-time curve calculated from time zero to the last detectable time point (AUC0-t)
Timepoint [17] 0 0
From predose to 24 hours postdose
Secondary outcome [18] 0 0
Urine PK parameters: terminal half-life (t½)
Timepoint [18] 0 0
From predose to 24 hours postdose
Secondary outcome [19] 0 0
Urine PK parameters: Renal clearance calculated as Ae/AUC0-t (CLrenal)
Timepoint [19] 0 0
From predose to 24 hours postdose
Secondary outcome [20] 0 0
Metabolite profiling performed using plasma and urine samples
Timepoint [20] 0 0
From predose to 24 hours postdose
Secondary outcome [21] 0 0
Pharmacokinetic parameters (including Time to maximum concentration [Tmax])
Timepoint [21] 0 0
From predose to 24 hours postdose
Secondary outcome [22] 0 0
Observed maximum concentration (Cmax)
Timepoint [22] 0 0
From predose to 24 hours postdose
Secondary outcome [23] 0 0
Elimination half-life (t1/2)
Timepoint [23] 0 0
From predose to 24 hours postdose
Secondary outcome [24] 0 0
Area Under the Concentration-time curve (AUC) for TD-4208 in blood
Timepoint [24] 0 0
From predose to 24 hours postdose
Secondary outcome [25] 0 0
Area Under the Concentration-time curve (AUC) for TD-4208 in urine
Timepoint [25] 0 0
From predose to 24 hours postdose

Eligibility
Key inclusion criteria
- Diagnosis of moderate stable Chronic Obstructive Pulmonary.

- Disease with FEV1/FVC <0.7 at screening.

- Woman of non-childbearing potential.

- Female participants of childbearing potential must test negative for pregnancy and
must be using a highly effective method of birth control during the study and for at
least 1 month after completion of study dosing.

- Female participants must not be breastfeeding.

- Men must agree to use a highly effective method of birth control with partners of
childbearing potential during the study and for 1 month after completion of study
dosing.

- Current or past smoking history >10 pack-years.

- Must be capable of performing reproducible spirometry maneuvers.
Minimum age
40 Years
Maximum age
75 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- History of significant respiratory disease other than COPD, and/ or requires daily
long-term oxygen therapy.

- Exacerbation of COPD, lung infection within 6 weeks prior to study.

- Start of or change in dose of COPD treatment 4 weeks before study.

- Daily using of maintenance systemic/inhaled corticosteroids (>1000 microgram of
fluticasone propionate equivalent or >5 mg prednisone).

- Use of bronchodilators or medication for the treatment of COPD, aspirin,
anti-inflammatories for a specific time, prior to the first dose or is not willing to
abstain from their use for the specified time periods prior to study dose
administration.

- Symptomatic prostrate hypertrophy, bladder neck obstruction, active cancer, narrow
angle glaucoma.

- Clinical significant hypersensitivity to medications.

- Participants have an uncontrolled hematologic, immunologic, renal, neurologic,
hepatic, endocrine or other disease that may place participant at risk.

- Cerebrovascular, cardiovascular disease or abnormal ECG.

- History of drug or alcohol abuse.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Crossover
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
New Zealand
State/province [1] 0 0
Wellington

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Theravance Biopharma
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Thirty-two subjects diagnosed with COPD were enrolled, received each study treatment and
completed the follow-up assessments. During each of the four study periods, subjects were
admitted to the clinic on Day -1 and housed overnight until after the last spirometry
measurement. Serial pulmonary function tests were performed and PK (pharmacokinetics) samples
collected up to 25 hours. Subjects were discharged from the clinic on Day 2 after
evaluations.
Trial website
https://clinicaltrials.gov/show/NCT03064113
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Glenn Crater, M.D.
Address 0 0
Theravance Biopharma, US, Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications