Status and phase
Conditions
Treatments
About
The primary objective is to compare the efficacy of UMEC/VI Inhalation Powder (62.5/25 mcg) once-daily with tiotropium (18 mcg) once-daily over 12 weeks for the treatment of subjects with COPD who have received tiotropium and continue to have symptoms while on tiotropium.
Full description
This is a Phase IIIb multicentre, randomized, blinded, double-dummy, parallel group study to evaluate the efficacy and safety of UMEC/VI Inhalation Powder (62.5/25 mcg) when administered once-daily via ELLIPTA dry powder inhaler (DPI) [note: the ELLIPTA DPI may also be referred to as the Novel DPI (NDPI) or the DPI] compared with tiotropium (18 mcg) administered once-daily via the HandiHaler over a treatment period of 12 weeks in subjects with COPD who continue to have symptoms while on tiotropium.
The target population of the study will include those subjects who continue to have symptoms while on tiotropium. The study will screen approximately 650 subjects who continue to have symptoms whilst on tiotropium. After a 4 week run-in period on open label tiotropium, those subjects who continue to have symptoms and have adhered to the treatment schedule will progress into the treatment phase.
At the end of the run-in phase approximately 490 subjects will be randomised 1:1 to UMEC/VI Inhalation Powder (62.5/25 mcg), or tiotropium (18 mcg). During the treatment phase, each subject will receive two inhalers, a preloaded ELLIPTA DPI and a HandiHaler dry powder inhaler with capsules, for once-daily administration of one active treatment and one placebo treatment for 12 weeks.
There will be a total of 8 study visits. Subjects will sign the informed consent form (ICF) at either Visit 0 or Visit 1 and will be assigned a subject identifier. Subjects who meet the eligibility criteria at Screening (Visit 1) will enter the open label tiotropium run-in phase. After 4 weeks all subjects will be reviewed (Visit 2) and if they satisfy the randomisation criteria they will be randomised and enter the treatment phase.
After Visit 2, there will be a further 6 study clinic visits. Further visits are scheduled at Day 2, Week 4, Week 8, Week 12 and Week 12 +1 day (Visits 3 to 7 respectively). Vital signs (blood pressure and pulse rate) will be obtained at all clinic visits.
Trough FEV₁and trough FVC will be performed at Visit 3 and Visit 7. Pre-dose and post dose FEV₁and FVC measurement at 5 and 15 mins and 1 and 3 hrs will also be performed at Visit 2, Visit 4, Visit 5 and Visit 6.
At selected study sites, a subset of approximately 200 subjects will perform 24-hour serial spirometry at Visit 2 and Visit 6 for evaluation of lung function over the dosing period.
An assessment of dyspnea will be obtained using the Baseline and Transition Dyspnea Index (BDI/TDI). At Visit 2, the severity of dyspnea at baseline will be assessed using the BDI. Change from baseline will be assessed using the TDI at Visit 4, Visit 5 and Visit 6.
In addition to the baseline assessment at Visit 2, health status will be captured using the St. George Respiratory Questionnaire for COPD (SGRQ-C) scale at Visit 4 and Visit 6.
The impact of COPD on the subject's wellbeing and daily life will be measured using the COPD Assessment Test (CAT) and the the Euroqol-5D (EQ5D).. In addition to the baseline assessment at Visit 2, the CAT and the EQ-5D will also completed at Visit 4 and Visit 6. Furthermore, the CAT is also completed during screening.
The Patient Global Rating of COPD Severity and Change of COPD Severity is a selfreported global assessment of severity of illness will be performed at Baseline during Visit 2 and at Visit 4 and Visit 6.
Visits 0/1 through 7 will be clinic visits conducted on an outpatient basis. A safety Follow-Up assessment (Visit 8) will be conducted either by phone call or clinic visit where required approximately 7 days after the end of the study treatment (Visit 7 or Early Withdrawal, if applicable). The total duration of subject participation, including follow-up, will be approximately 18 weeks. All subjects will be provided with albuterol/salbutamol for use on an "as-needed" basis throughout the run-in and study treatment periods.
For determination of subject disposition, subjects will be considered to have completed the study upon completion of Visit 7 (the last on-treatment clinic visit). There are no plans for compassionate use of the study medications.
Enrollment
Sex
Ages
Volunteers
Inclusion criteria
Non-child bearing potential (i.e. physiologically incapable of becoming pregnant, including any female who is post-menopausal or surgically sterile). Surgically sterile females are defined as those with a documented hysterectomy and/or bilateral oophorectomy or tubal ligation. Post-menopausal females are defined as being amenorrhoeic for greater than 1 year with an appropriate clinical profile, e.g. age appropriate, >45 years, in the absence of hormone replacement therapy.
OR
Child bearing potential, has a negative pregnancy test at screening, and agrees to one of the following acceptable contraceptive methods used consistently and correctly (i.e. in accordance with the approved product label and the instructions of the physician for the duration of the study - screening to follow-up contact):
Abstinence
Oral Contraceptive, either combined or progestogen alone
Injectable progestogen
Implants of levonorgestrel
Estrogenic vaginal ring
Percutaneous contraceptive patches
Intrauterine device (IUD) or intrauterine system (IUS) that meets the SOP effectiveness criteria as stated in the product label
Male partner sterilization (vasectomy with documentation of azoospermia) prior to the female subject's entry into the study, and this male is the sole partner for that subject. For this definition, "documented" refers to the outcome of the investigator's/designee's medical examination of the subject or review of the subject's medical history for study eligibility, as obtained via a verbal interview with the subject or from the subject's medical records.
Double barrier method: condom and an occlusive cap (diaphragm or cervical/vault caps) with a vaginal spermicidal agent (foam/gel/film/cream/suppository)
Note: Pipe and/or cigar use cannot be used to calculate pack-year history
Exclusion criteria
A moderate COPD exacerbation is defined as worsening symptoms of COPD that require treatment with oral/systemic corticosteroids and/or antibiotics. A severe exacerbation is defined as worsening symptoms of COPD that require in-patient hospitalization.
Appendix 3:
Sinus tachycardia ≥120 bpm. *Note: sinus tachycardia ≥120bpm should be confirmed by two additional readings at least 5 minutes apart.
Sinus bradycardia <45bpm. *Note: Sinus bradycardia <45bpm should be confirmed by two additional readings at least 5 minutes apart.
Multifocal atrial tachycardia.
Supraventricular tachycardia (>100bpm).
Atrial fibrillation with rapid ventricular response (rate >120bpm).
Atrial flutter with rapid ventricular response (rate >120bpm).
Ventricular tachycardias (non sustained, sustained, polymorphic, or monomorphic).
Ventricular flutter.
Ventricular fibrillation.
Torsades de Pointes.
Evidence of Mobitz type II second degree or third degree atrioventricular (AV) block.
AV dissociation.
2:1 AV block.
Trifascicular Block.
For subjects with QRS duration <120 ms: QTc(F) ≥450msec or an ECG that is unsuitable for QT measurements (e.g., poor defined termination of the T wave).
For subjects with QRS duration≥120: QTc(F) ≥480msec or an ECG that is unsuitable for QT measurements (e.g., poor defined termination of the T wave).
Myocardial infarction (acute or recent) * Note: Evidence of an old (resolved) myocardial infarction is not exclusionary
Use as maintenance treatment in the 3 months prior to Visit 1 is not permitted. Maintenance treatment is defined as use for ≥ 14 consecutive days (at any time in the 3 months prior to Visit 1).
Any other investigational medication use within 30 days or within 5 drug half-lives (whichever is longer) is not permitted
Note: if a LABA, LAMA (non-tiotropium), ICS/LABA, LAMA/LABA, theophylline, oral beta-agonist,or PDE4 inhibitor was taken on a non-maintenance basis (i.e., < 14 consecutive days over the 3 months prior to screening) the following minimum washouts must be observed prior to visit 1: twice-daily LABAs and ICS/LABAs = 48 hours; once-daily LABAs and ICS/LABAs= 14 days; LAMAs (excluding tiotropium) = 7 days; once-daily LAMA/LABA = 14 days, twice-daily LAMA/LABA = 7days; theophyllines = 48 hours; oral beta2 agonists = 48 hours; PDE4 inhibitor = 14 days.
Primary purpose
Allocation
Interventional model
Masking
497 participants in 2 patient groups
Loading...
Data sourced from clinicaltrials.gov
Clinical trials
Research sites
Resources
Legal