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A Study to Compare the Efficacy and Safety of Fluticasone Furoate (FF) 100 mcg Once Daily With Fluticasone Propionate (FP) 250 mcg Twice Daily (BD) and FP 100 mcg BD in Well-controlled Asthmatic Japanese Subjects

Information source: GlaxoSmithKline
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Asthma

Intervention: Fluticasone Furoate/Vilanterol (Drug); Fluticasone Furoate 100 mcg (Drug); Fluticasone Propionate 250 mcg (Drug); Fluticasone Propionate 100 mcg (Drug); Fluticasone Furoate Placebo (Drug); Fluticasone Propionate Placebo (Drug)

Phase: Phase 3

Status: Active, not recruiting

Sponsored by: GlaxoSmithKline

Official(s) and/or principal investigator(s):
GSK Clinical Trials, Study Director, Affiliation: GlaxoSmithKline

Summary

The primary aim of this study is to clarify the position of FF and FF/Vilanterol (VI) 100/25 micrograms (mcg) compared with existing therapies by assessing FF dosage equivalent to low to middle-dose inhaled corticosteroids (ICS). The study is divided into Run-in period, Period 1 (open-label treatment), Period 2 (double blind treatment) and Follow-up. Subjects with well controlled asthma after completing a run-in period of 4 weeks will be switched from middle-dose ICS/long acting beta 2 agonist (LABA) equivalent dose to once-daily FF/VI 100/25 mcg for an 8 weeks treatment period (Period 1). After this, subjects will be randomized in a 1: 1:1 ratio to receive either FP 250 mcg twice daily, FP 100 mcg twice daily or FF 100 mcg once daily in a 12 week double blind treatment period (Period 2). There will be a 1 week Follow-up Period following completion of the double-blind treatment period, or early withdrawal from the study. Overall , the total duration of subject's participation in the study will be for 25 weeks. RELVAR is a registered trademark of the GSK group of companies.

Clinical Details

Official title: 201135 : A Randomised, Double-blind, Multicenter, Parallel-group Study to Compare the Efficacy and Safety of Fluticasone Furoate (FF) 100 mcg Once Daily With Fluticasone Propionate (FP) 250 mcg Twice Daily (BD) and FP 100 mcg BD in Well-controlled Asthmatic Subjects Stepped Down From a Maintenance Therapy With RELVARŪ Inhaler (FF/VI) 100/25 mcg Once-daily in Japanese Subjects

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Primary outcome:

Time to withdrawal due to poorly -controlled (requires step-up) asthma during Period-2

Proportion of subjects with well-controlled asthma at the end of Period-2

Secondary outcome:

Mean change from baseline in clinic visit trough FEV1 at the end of Period-2

Mean change from baseline in daily morning and evening peak expiratory flow (PEF) averaged during Period-2

Mean change from baseline in the percentage of symptom-free 24-hour periods during Period-2

Mean change from baseline in the percentage of rescue-free 24-hour periods during Period-2

Mean change from baseline in Asthma Control Test (ACT) score during Period-2

Proportion of subjects with ACT score >=20 at the end of the Period-2

Eligibility

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Informed consent: Subjects must give their signed and dated written informed consent

to participate.

- Type of Subject: Outpatients 18 years of age or older at Visit 1. Subjects must have

a diagnosis of asthma as defined by the National Institutes of Health at least 1 year prior to Visit 1.

- Gender: Male or Eligible Female, defined as non-childbearing potential or

childbearing potential using an acceptable method of birth control consistently and correctly, as defined by the following: Male partner who is sterile prior to the female subject's entry into the study and is the sole sexual partner for that female subject; Oral contraceptive (either combined estrogen/progestin); Any intrauterine device (IUD) with a documented failure rate of less than 1% per year; Double barrier

method - spermacide plus a mechanical barrier (e. g., spermacide plus a male condom or

a spermacide and female diaphragm); Females of childbearing potential who are not sexually active must commit to complete abstinence from intercourse throughout the clinical trial and for a period after the trial to account for elimination of the drug (minimum of six days); Female subjects should not be enrolled if they are pregnant, lactating or plan to become pregnant during the time of study participation. A serum pregnancy test is required for females of childbearing potential at the initial screening visit (Visit 1) and Visit 11 or Early Withdrawal. In addition a urine pregnancy test will be performed on all females of childbearing potential at Visit 2, Visit 5 and Visit 12.

- Severity of Disease: A best pre-bronchodilator FEV1 of >=80% of the predicted normal

value at the screening visit (Visit 1). Predicted values will be based upon National Health and Nutrition Examination Survey (NHANES) III. As subjects are Asian, the Asian adjustment will be used.

- Stable Asthma: Subjects must have stable asthma, as judged by the Investigator. This

includes no change in asthma medication for at least 8 weeks prior to Visit 1 and an ACT score of >=20 at Visit 1.

- Current Anti-Asthma Therapy: All subjects must be using the middle-dose ICS/LABA

which is equivalent to twice-daily combination of fluticasone propionate and salmeterol 250 mcg for at least 12 weeks prior to the registration visit. In addition, the prescription of the middle-dose ICS/LABA shouldn't be changed at least 8 weeks prior to Visit 1.

- Short-Acting Beta2-Agonists (SABA): All subjects must be able to use salbutamol

aerosol inhaler which will be provided as a rescue medication at Visit 1 during the study as needed. Subjects must be able to avoid using salbutamol for at least 6 hours prior to study visits.

- 12-lead electrocardiogram (ECG): Evidence of significant normality in the 12-lead ECG

performed at Visit 1, as judged by the investigator Selected specific ECG findings that are not considered to be significant and will not exclude the subject from study participation include, but are not limited to, the following: T interval corrected for heart rate (QTc) <450 milliseconds (msec) or QTc <480 msec for patients with bundle branch block. The QTc is the QT interval corrected for heart rate according to Fridericia's formula (QTcF), machine overread. The QTc should be based on single or averaged QTc values of triplicate electrocardiograms (ECGs) obtained over a brief recording period. If there are any clinically significant abnormalities including but not limited to a T interval for heart rate (QT) prolonged, confirm with two additional ECGs taken. Other inclusion criteria at Visit 2 and Visit 5:

- Subjects whose asthma meets the criterion of "well-controlled" (as defined in the

protocol), and in the Investigators judgement it is acceptable for subject to "switch (Visit 2)" and "step-down (Visit 5)" in one week prior to Visit 2 or Visit 5.

- Compliance rate of the middle-dose ICS/LABA which is equivalent to twice-daily

combination of fluticasone propionate and salmeterol 250 mcg (Visit1- Visit 2) and

FF/VI 100/25 mcg (Visit 2 - Visit5) should be achieved >=80%

- Compliance with completion of both morning and evening eDairy data fulfils >=5days in

one week prior to Visit 2 and Visit 5. Exclusion Criteria:

- History of Life-threatening asthma: Defined for this protocol as an asthma episode

that required intubation and/or was associated with hypercapnia, respiratory arrest or hypoxic seizures within the last 10 years.

- Respiratory Infection: Culture-documented or suspected bacterial or viral infection

of the upper or lower respiratory tract, sinus or middle ear that is not resolved within 8 weeks of Visit 1 and led to a change in asthma management or, in the opinion of the Investigator, is expected to affect the subject's asthma status or the subject's ability to participate in the study.

- Asthma Exacerbation: Any asthma exacerbation requiring systemic corticosteroids or

injection within 12 weeks of Visit 1 or that resulted in overnight hospitalization requiring additional treatment for asthma within 6 months prior to Visit 1.

- Concurrent Respiratory Disease: A subject must not have current evidence of

pneumonia, pneumothorax, atelectasis, pulmonary fibrotic disease, bronchopulmonary dysplasia, chronic bronchitis, emphysema, chronic obstructive pulmonary disease, or other respiratory abnormalities other than asthma.

- Other Concurrent Diseases/Abnormalities: A subject must not have any clinically

significant, uncontrolled condition or disease state that, in the opinion of the investigator, would put the safety of the subject at risk through study participation or would confound the interpretation of the efficacy results if the condition/disease exacerbated during the study. The list of additional excluded conditions/diseases includes, but is not limited to the following: congestive heart failure, known aortic aneurysm, clinically significant coronary heart disease, clinically significant cardiac arrhythmia, stroke within 3 months of Visit 1, uncontrolled hypertension (two or more measurements with systolic BP >160 millimeters of mercury (mmHg), or diastolic BP >100mmHg), recent or poorly controlled peptic ulcer, haematologic, hepatic, or renal disease, immunologic compromise, current malignancy (history of malignancy is acceptable only if subject has been in remission for one year prior to Visit 1 (remission = no current evidence of malignancy and no treatment for the malignancy in the 12 months prior to Visit 1)), tuberculosis (current or untreated) [Subjects with a history of tuberculosis infection who have completed an appropriate course of antituberculous treatment may be suitable for study entry provided that there is no clinical suspicion of active or recurrent disease], Cushing's disease, Addison's disease, uncontrolled diabetes mellitus, uncontrolled thyroid disorder, recent history of drug or alcohol abuse

- Oropharyngeal Examination: A subject will not be eligible for the run-in if he/she

has clinical visual evidence of candidiasis at Visit 1.

- Investigational Medications: A subject must not have used any investigational drug

within 30 days prior to Visit 1 or within five half-lives (t1/2) of the prior investigational study (whichever is longer of the two).

- Allergies: Drug Allergy: Any adverse reaction including immediate or delayed

hypersensitivity to any beta2-agonist, sympathomimetic drug, or any intranasal, inhaled, or systemic corticosteroid therapy. Known or suspected sensitivity to the constituents of the investigational product (i. e., lactose or magnesium stearate); Milk Protein Allergy: History of severe milk protein allergy.

- Concomitant Medication: Administration of prescription or over the counter medication

that would significantly affect the course of asthma, or interact with study drug, such as: anticonvulsants (barbiturates, hydantoins, carbamazepine); polycyclic antidepressants; beta-adrenergic blocking agents; phenothiazines and monoamine oxidase (MAO) inhibitors; Immunosuppressive Medications: A subject must not be using or require use of immunosuppressive medications during the study. Note: Immunotherapy for the treatment of allergies is allowed during the study provided it was initiated at least 4 weeks prior to Visit 1 and subjects remain in the maintenance phase for the duration of the study; Cytochrome P450 3A4 (CYP3A4) inhibitors: Subjects who have received a potent CYP3A4 inhibitor within 4 weeks of Visit 1 (e. g.,Clarithromycin, atazanavir, indinavir, itraconazole, ketoconazole, nefazadone, nelfinavir; ritonavir; saquinavir; telithromycin, troleandomycin, voriconazole, mibefradil, cyclosporine, etc).

- Compliance: A subject will not be eligible if he/she or his/her parent or legal

guardian has any infirmity, disability, disease, or geographical location which seems likely (in the opinion of the Investigator) to impair compliance with any aspect of this study protocol, including visit schedule and completion of eDiaries and a paper medical conditions diary.

- Tobacco Use: Current smoker or a smoking history of 10 pack years (e. g., 20

cigarettes/day for 10 years). A subject may not have used inhaled tobacco products within the past 3 months (i. e., cigarettes, cigars or pipe tobacco).

- Affiliation with Investigator's Site: A subject will not be eligible for this study

if he/she is an immediate family member of the participating Investigator, sub-Investigator, study coordinator, or employee of the participating Investigator. Other exclusion criteria at Visit 2 and Visit 5:

- Evidence of clinically significant abnormal laboratory tests during Visit 1which are

still abnormal upon repeat analysis and are not believed to be due to disease(s) present. Each Investigator will use his/her own discretion in determining the clinical significance of the abnormality.

- Changes in asthma medication (excluding salbutamol inhalation aerosol provided at

Visit 1).

- Occurrence of a culture-documented or suspected bacterial or viral infection of the

upper or lower respiratory tract, sinus or middle ear during the run-in and the open-label treatment period that led to a change in asthma management or, in the opinion of the Investigator, is expected to affect the subject's asthma status or the subject's ability to participate in the study.

- Any asthma exacerbation requiring systemic corticosteroids or injection or that

resulted in overnight hospitalization requiring additional treatment for asthma. Clinical visual evidence of oral candidiasis at Visit 2 and Visit 5.

- Positive urine pregnancy test for all females of childbearing potential at Visit 2

and Visit 5

- Subjects that the investigator decides that it is impossible for subject to do

"switch (Visit 2)" and "step-down (Visit 5)".

Locations and Contacts

GSK Investigational Site, Aomori 036-8545, Japan

GSK Investigational Site, Fukuoka 832-0059, Japan

GSK Investigational Site, Fukuoka 811-1394, Japan

GSK Investigational Site, Fukuoka 816-0813, Japan

GSK Investigational Site, Fukuoka 802-0052, Japan

GSK Investigational Site, Gifu 509-6134, Japan

GSK Investigational Site, Hiroshima 732-0052, Japan

GSK Investigational Site, Hyogo 672-8064, Japan

GSK Investigational Site, Ibaraki 319-1113, Japan

GSK Investigational Site, Ibaraki 302-0022, Japan

GSK Investigational Site, Kagawa 762-0031, Japan

GSK Investigational Site, Kagawa 760-8538, Japan

GSK Investigational Site, Kagawa 761-8073, Japan

GSK Investigational Site, Kagawa 760-0018, Japan

GSK Investigational Site, Kanagawa 239-0821, Japan

GSK Investigational Site, Kanagawa 252-0143, Japan

GSK Investigational Site, Kochi 780-0901, Japan

GSK Investigational Site, Kyoto 612-0026, Japan

GSK Investigational Site, Mie 514-1101, Japan

GSK Investigational Site, Mie 515-8544, Japan

GSK Investigational Site, Oita 870-0921, Japan

GSK Investigational Site, Osaka 560-0005, Japan

GSK Investigational Site, Saitama 343-0808, Japan

GSK Investigational Site, Tokyo 204-8522, Japan

GSK Investigational Site, Tokyo 103-0027, Japan

GSK Investigational Site, Tokyo 140-0011, Japan

GSK Investigational Site, Tokyo 140-0013, Japan

GSK Investigational Site, Tokyo 145-0063, Japan

GSK Investigational Site, Tokyo 171-0014, Japan

GSK Investigational Site, Tokyo 187-0002, Japan

GSK Investigational Site, Tokyo 190-0014, Japan

GSK Investigational Site, Tokyo 191-0031, Japan

GSK Investigational Site, Tokyo 104-8560, Japan

Additional Information

Starting date: March 2014
Last updated: August 20, 2015

Page last updated: August 23, 2015

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