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Trial registered on ANZCTR


Registration number
ACTRN12611000482965
Ethics application status
Approved
Date submitted
5/05/2011
Date registered
10/05/2011
Date last updated
8/03/2012
Type of registration
Prospectively registered

Titles & IDs
Public 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
Scientific title
Effects of TD-4208 on FEV1 in Subjects with COPD
Secondary ID [1] 260111 0
NIL
Universal Trial Number (UTN)
U1111-1120-8290
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Obstructive Pulmonary Disease 265790 0
Condition category
Condition code
Respiratory 265941 265941 0 0
Chronic obstructive pulmonary disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Single doses of 2 dose levels (350 and 700 micrograms) of TD 4208 by inhalation via a nebulizer: 7-12 days apart.
Comparators are single doses of ipratropium bromide (500 micrograms) and placebo.
Subjects crossover to single doses of all four treatments.
The washout is a minium of 7 days and a maximum of 12 days between each single dose.
The 7-12 day period is determined by the clinic's schedule, the availability of the subjects and the re-assessment of eligibility criteria prior to each of the subsequent single doses.
Intervention code [1] 264527 0
Treatment: Drugs
Comparator / control treatment
Ipratropium bromide (500 micrograms) will be administered as single doses and a placebo solution will be administered as positive and negative controls, respectively.
The placebo solution is made of cytric acid monohydrate, sodium citrate, and normal saline.
Control group
Active

Outcomes
Primary outcome [1] 266694 0
Change in peak forced expiratory volume in one second (FEV1) relative to baseline will be assessed using Spirometry.
Timepoint [1] 266694 0
In each of the four treatment periods, spirometry assessments will be obtained predose and at specified intervals through approximately 25 hours postdose; 15, 30, and 45 minutes postdose; and 1, 2, 3, 4, 6, 8, 10, 11, 12, 14, 22, 23, 24, and 25 hours postdose.
Secondary outcome [1] 276206 0
To evaluate additional lung function parameters and duration of bronchodilatory effect, spirometry will be used to obtain data to evaluate area under the FEV1 vs. time curve, FEV1 at 12 and 24 hours postdose, peak expiratory flow rate (PEFR) ,forced expiratory flow from 25% to 75% of vital capacity (FEF25 to 75), forced vital capacity (FVC) and area under the FVC vs time curve.
Timepoint [1] 276206 0
In each of the four treatment periods, spirometry assessments will be obtained predose and at specified intervals through approximately 25 hours postdose.
Secondary outcome [2] 276207 0
Safety and tolerability of single doses of TD-4208 will be evaluated using physical exams, ECGs, vital signs, clinical safety labs, and adverse events. The most frequently observed adverse events in the Phase 2 study include dysgeusia (taste disorder) and headaches. Adverse Events will be assessed through physical examinations.
Timepoint [2] 276207 0
Physical exams and safety labs will be done at baseline and in each period before dosing and at a follow-up visit. Vital signs and ECGs will be collected at baseline and in each period before dosing and at specified times through 24 hours postdose. Adverse events will be evaluated throughout the study.
Secondary outcome [3] 276209 0
Pharmacokinetic parameters (including time to maximum concentration [Tmax], maximum concentration [Cmax], elimination half-life [t1/2], area under the concentration-time curve[AUC]) for TD-4208 in blood and in urine will be determined for each dose level of TD-4208.
Timepoint [3] 276209 0
A total of 14 blood samples will be collected in each period predose and at specified times through 24 hours postdose. Subjects will collect all urine for 24 hours postdose in each period.

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 hypertorphy, 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, cardiovacular 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)
After providing written informed consent, subjects are screened against enrollment criteria. Those meeting all criteria will be assigned sequentially a treatment number from the randomization schedule by unblinded site staff. The treatment number specifies the order in which a subject will receive TD 4208 (2 dose levels), ipratropium bromide, and placebo in each of the four treatment periods. In each treatment period, unblinded staff will prepare and dispense the study treatment in a nebulizer that is labeled with the subject’s treatment number. Blinded site staff will then administer the study treatment to the study subject.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
A statistical programmer at Theravance who is not involved in the study was responsible for preparing the randomization schedule using a computer program. The randomization schedule specifies the treatment sequence for each treatment number.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Phase 2
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
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 outside Australia
Country [1] 3578 0
South Africa
State/province [1] 3578 0
Country [2] 3579 0
New Zealand
State/province [2] 3579 0

Funding & Sponsors
Funding source category [1] 265015 0
Commercial sector/Industry
Name [1] 265015 0
Theravance, Inc.
Address [1] 265015 0
901 Gateway Blvd
South San Francisco, CA 94080
Country [1] 265015 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Theravance, Inc.
Address
901 Gateway Blvd
South San Francisco, CA 94080
Country
United States of America
Secondary sponsor category [1] 264109 0
None
Name [1] 264109 0
Address [1] 264109 0
Country [1] 264109 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 266990 0
Central Regional Ethics Committee
Ethics committee address [1] 266990 0
Ministry of Health, Level 1, 1-3 The Terrace, PO Box 5013, Wellington 6011
Ethics committee country [1] 266990 0
New Zealand
Date submitted for ethics approval [1] 266990 0
22/03/2011
Approval date [1] 266990 0
05/04/2011
Ethics approval number [1] 266990 0
CEN/11/04/029

Summary
Brief summary
Thirty-two subjects diagnosed with COPD will be enrolled with the goal of at least 28 subjects receiving each study treatment and completing the follow-up assessments. During each of the four study periods, subjects will be admitted to the clinic on Day -1 and housed overnight until after the last spirometry measurement. Serial pulmonary function tests will be performed and PK samples collected up to 25 hours. Subjects will be discharged from the clinic on Day 2 after evaluations.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 32571 0
Address 32571 0
Country 32571 0
Phone 32571 0
Fax 32571 0
Email 32571 0
Contact person for public queries
Name 15818 0
Dr. Dean Quinn
Address 15818 0
P3 Research
P.O. Box 7366
1st Floor 121 Adelaide Rd
Newton
Wellington 6021
Country 15818 0
New Zealand
Phone 15818 0
+64 0 4 801 0002
Fax 15818 0
Email 15818 0
dean@p3research.co.nz
Contact person for scientific queries
Name 6746 0
Peter Potgieter, M.D., Ph.D.
Address 6746 0
Theravance, Inc.
901 Gateway Boulevard
South San Francisco, California 94080 USA
Country 6746 0
United States of America
Phone 6746 0
+1 650 808 3726
Fax 6746 0
Email 6746 0
ppotgieter@theravance.com

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary