Fluticasone Furoate/GW642444 Inhalation Powder Long-Term Safety Study

Study at a glance

From the registry record, last updated by the sponsor on 15 Feb 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title

A Randomized, Double-Blind, Double Dummy, Active Comparator, Parallel Group, Multicenter Study to Evaluate the Safety of Once-Daily Fluticasone Furoate/GW642444 Inhalation Powder for 52 Weeks in Adolescent and Adult Subjects With Asthma

ClinicalTrials.gov ID

NCT01018186

Acronym / sponsor ID

106839

Conditions

Asthma

Phase

Phase 3

Study type

Interventional

Recruitment status

Completed

Enrolment

503 participants (actual)

Lead sponsor

GlaxoSmithKlineIndustry (pharma, biotech, devices)

Study start

19 Oct 2009

Primary completion

1 May 2011 (actual)

Study completion

12 May 2011 (actual)

First posted

23 Nov 2009 (estimated)

Results

Posted 29 Oct 2013

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose

Treatment

Allocation

Randomised

Intervention model

Parallel groups

Masking

Double blind (participant, investigator)

Number of arms

2

Who may qualify

Ages

12 years and older

Sex

All

Healthy volunteers

Not accepted

Age groups

Child, Adult, Older adult

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Primary outcome

1. Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) During the Treatment Period

   Time frame: From the start of study medication until Visit 11 (Week 52)/Early Withdrawal

   An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A serious adverse event (SAE) is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect. Medical or scientific judgment should be exercised in deciding whether reporting is appropriate in other situations. Refer to the General Adverse AE/SAE module for a complete list of AEs and SAEs.

2. Number of Participants With Severe Asthma Exacerbations During the Treatment Period

   Time frame: From the start of study medication until Visit 11 (Week 52)/Early Withdrawal

   A severe asthma exacerbation is defined as the deterioration of asthma requiring the use of systemic corticosteroids (tablets, suspension, or injection) for at least 3 days or an in-patient hospitalization or emergency department visit due to asthma that required systemic corticosteroids. Courses of corticosteroids separated by 1 week or more were treated as separate severe exacerbations.

3. Change From Baseline in Albumin and Total Protein at Week 12, Week 28, and Week 52/Early Withdrawal

   Time frame: Baseline; Week 12, Week 28, and Week 52/Early Withdrawal

   Blood samples were collected for the measurement of albumin and total protein values at the following scheduled time points: Baseline, Week 12, Week 28, and Week 52/Early Withdrawal. The Baseline value is defined as the most recent recorded value at Screening or prior to Day 1. Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.

4. Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Kinase (CK), and Gamma Glutamyltransferase (GGT) at Week 12, Week 28, and Week 52/Early Withdrawal

   Time frame: Baseline; Week 12, Week 28, and Week 52/Early Withdrawal

   Blood samples were collected for the measurement of ALP, ALT, AST, CK, and GGT values at the following scheduled time points: Baseline, Week 12, Week 28, and Week 52/Early Withdrawal. The Baseline value is defined as the most recent recorded value at Screening or prior to Day 1. Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.

5. Change From Baseline in Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, and Creatinine at Week 12, Week 28, and Week 52/Early Withdrawal

   Time frame: Baseline; Week 12, Week 28, and Week 52/Early Withdrawal

   Blood samples were collected for the measurement of direct bilirubin, indirect bilirubin, total bilirubin, and creatinine values at the following scheduled time points: Baseline, Week 12, Week 28, and Week 52/Early Withdrawal. The Baseline value is defined as the most recent recorded value at Screening or prior to Day 1. Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.

6. Change From Baseline in Chloride, Carbon Dioxide Content/Bicarbonate, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) at Week 12, Week 28, and Week 52/Early Withdrawal

   Time frame: Baseline; Week 12, Week 28, and Week 52/Early Withdrawal

   Blood samples were collected for the measurement of chloride, carbon dioxide (CO2) content/bicarbonate, glucose, potassium, sodium, and urea/BUN values at the following scheduled time points: Baseline, Week 12, Week 28, and Week 52/Early Withdrawal. The Baseline value is defined as the most recent recorded value at Screening or prior to Day 1. Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.

7. Change From Baseline in the Percentage of Basophils, Eosinophils, Hematocrit, Lymphocytes, Monocytes, and Segmented Neutrophils in the Blood at Week 12, Week 28, and Week 52/Early Withdrawal

   Time frame: Baseline; Week 12, Week 28, and Week 52/Early Withdrawal

   Blood samples were collected for the measurement of the percentage of basophils, eosinophils, hematocrit, lymphocytes, monocytes, and segmented neutrophils in the blood at the following scheduled time points: Baseline, Week 12, Week 28, and Week 52/Early Withdrawal. The Baseline value is defined as the most recent recorded value at Screening or prior to Day 1. Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.

8. Change From Baseline in Eosinophil Count, Total Absolute Neutrophil Count (ANC), Platelet Count, and White Blood Cell (WBC) Count at Week 12, Week 28, and Week 52/Early Withdrawal

   Time frame: Baseline; Week 12, Week 28, and Week 52/Early Withdrawal

   Blood samples were collected to determine the eosinophil count, total ANC, platelet count, and WBC count at the following scheduled time points: Baseline, Week 12, Week 28, and Week 52/Early Withdrawal. The Baseline value is defined as the most recent recorded value at Screening or prior to Day 1. Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.

9. Change From Baseline in Hematocrit at Week 12, Week 28, and Week 52/Early Withdrawal

   Time frame: Baseline; Week 12, Week 28, and Week 52/Early Withdrawal

   Blood samples were collected for the measurement of hematocrit values at the following scheduled time points: Baseline, Week 12, Week 28, and Week 52/Early Withdrawal. The Baseline value is defined as the most recent recorded value at Screening or prior to Day 1. Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.

10. Change From Baseline in Hemoglobin at Week 12, Week 28, and Week 52/Early Withdrawal

    Time frame: Baseline; Week 12, Week 28, and Week 52/Early Withdrawal

    Blood samples were collected for the measurement of hemoglobin values at the following scheduled time points: Baseline, Week 12, Week 28, and Week 52/Early Withdrawal. The Baseline value is defined as the most recent recorded value at Screening or prior to Day 1. Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.

11. Number of Participants With the Indicated Shift From Baseline to High, Normal or no Change, and Low Post-Baseline Values for Urinary Cortisol Excretion

    Time frame: Baseline; Week 12, Week 28, and Week 52/Early Withdrawal

    A 24-hour urine sample was collected for the measurement of 24-hour urinary cortisol excretion (UCE) at the following scheduled time points: Baseline, Week 12, Week 28, and Week 52/Early Withdrawal. Any visit post-baseline (AVPB) value was derived using laboratory assessments performed at scheduled, unscheduled, and Early Withdrawal visits. Participants who had a shift from Baseline in their post-Baseline UCE values relative to the normal range, are presented in the "To high and To low" categories. Participants whose post-Baseline UCE values were unchanged (e.g., High to High) or whose value became normal, are presented in the "To normal or no change" category. The normal range for UCE is defined as: 11 to 138 nanomoles per 24 hours (nmol/24 hr) for participants >=18 years of age, 8.3 to 151.7 nmol/24 hr for participants 14 to 17 years of age, and 2.8 to 124.2 nmol/24 hr for participants 12 and 13 years of age.

12. Ratio of 24-hour Urinary Cortisol Excretion at Week 12 to Baseline

    Time frame: Baseline and Week 12

    A 24-hour urine sample was collected, and the least square geometric mean (LSGM) for 24-hour urinary cortisol excretion (UCE) was calculated at Baseline and at Week 12. The ratio of the Week 12 LSGM to the Baseline LSGM was calculated as the value at Week 12 divided by the value at Baseline. Analysis was performed using analysis of covariance (ANCOVA) with covariates of region, sex, age, treatment, and the log of the Baseline values.

13. Ratio of 24-hour Urinary Cortisol Excretion at Week 28 to Baseline

    Time frame: Baseline and Week 28

    A 24-hour urine sample was collected, and the LSGM for 24-hour UCE was calculated at Baseline and at Week 28. The ratio of the Week 28 LSGM to the Baseline LSGM was calculated as the value at Week 28 divided by the value at Baseline. Analysis was performed using ANCOVA with covariates of region, sex, age, treatment, and the log of the Baseline values.

14. Ratio of 24-hour Urinary Cortisol Excretion at Week 52 to Baseline

    Time frame: Baseline and Week 52

    A 24-hour urine sample was collected, and the LSGM for 24-hour UCE was calculated at Baseline and at Week 52. The ratio of the Week 52 LSGM to the Baseline LSGM was calculated as the value at Week 52 divided by the value at Baseline. Analysis was performed using ANCOVA with covariates of region, sex, age, treatment, and the log of the Baseline values.

15. Number of Participants With Evidence of Oral Candidiasis at Any Time Post-Baseline

    Time frame: From Baseline until Visit 11/Early Withdrawal (52 weeks)

    A detailed oropharyngeal examination was done at all clinic visits for visual/clinical evidence of oral candidiasis over the entire Treatment Period (worst case any time post-Baseline). For participants with visual/clinical evidence of candidiasis during the Treatment Phase of the study, a culture swab was taken and analyzed for infection.

16. Maximum Change From Baseline in Systolic Blood Pressure (SBP) and Minimum Change From Baseline in Diastolic Blood Pressure (DBP)

    Time frame: From Baseline until Visit 11/Early Withdrawal (52 weeks)

    SBP and DBP were measured at the following scheduled time points: Screening, Day 1, Week 2, Week 4, Week 8, Week 12, Week 20, Week 28, Week 36, Week 44, and Week 52/Early Withdrawal. Baseline is defined as the Visit 1 (screening) value. Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline. Maximum and minimum change from Baseline for any post-Baseline visit was derived using all scheduled, unscheduled, and Early Withdrawal visits.

17. Maximum Change From Baseline in Pulse Rate

    Time frame: From Baseline until Visit 11/Early Withdrawal (52 weeks)

    Pulse rate was measured at the following scheduled time points: Screening, Day 1, Week 2, Week 4, Week 8, Week 12, Week 20,Week 28, Week 36, Week 44, and Week 52/Early Withdrawal. Baseline is defined as the Visit 1 (screening) value. Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline. Maximum change from Baseline for any post-Baseline visit was derived using all scheduled, unscheduled, and Early Withdrawal visits.

18. Number of Participants With the Indicated Change From Baseline in Lens Opacities Classification System, Version III (LOCS III) Posterior Subcapsular Opacity (P) at Week 28 and Week 52

    Time frame: Baseline; Week 28, and Week 52

    P is defined as the opacification at the back of the lens adjacent to the capsule (or bag) in which the lens sits. An event of P is defined as an increase of >=0.3 from Baseline in LOCS III grade for P in either eye at any time post-Baseline. Per LOC III, P ranges from 0.1 (clear or colorless) to 5.9 (very opaque). Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.

19. Number of Participants With the Indicated Change From Baseline in Intraocular Pressure (IOP) at Week 28 and Week 52

    Time frame: Baseline; Week 28 and Week 52

    Intraocular pressure (IOP) is the fluid pressure inside the eye. IOP was measured twice for each eye at Baseline, Week 28, and Week 52 using Goldmann Applanation tonometry. The second IOP reading was used for analysis. The number of participants with a change from Baseline in IOP of <0 mmHg, >=0 to <4 mmHg, >=4 to <7 mmHg, >=7 to <11 mmHg, and >=11 mmHg are presented. Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.

20. Change From Baseline in Horizontal Cup-to-disc Ratio at Week 28 and Week 52

    Time frame: Baseline; Week 28 and Week 52

    Funduscopic examination was performed at Baseline, Week 28, and Week 52 to measure the horizontal cup-to-disc ratio of both eyes. The horizontal cup-to-disc ratio is the ratio of the horizontal diameter of the physiological cup to that of the horizontal diameter of the optic disc. Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.

21. Number of Participants With the Indicated Change From Baseline in Lens Opacities Classification System, Version III (LOCS III) Cortical Opacity (C) at Week 28 and Week 52

    Time frame: Baseline; Week 28 and Week 52

    C is defined as the opacification of the cortex (outer layer) of the lens. Per LOC III, C ranges from 0.1 (clear or colorless) to 5.9 (very opaque). Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.

22. Change From Baseline in Lens Opacities Classification System, Version III (LOCS III) Nuclear Color (NC) at Week 28 and Week 52

    Time frame: Baseline; Week 28 and Week 52

    NC is the color of the nucleus (central layer) of the lens. Per LOC III, NC ranges from 0.1 (clear or colorless) to 6.9 (very opaque or brunescent). Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.

23. Change From Baseline in Lens Opacities Classification System, Version III (LOCS III) Nuclear Opalescence (NO) at Week 28 and Week 52

    Time frame: Baseline; Week 28 and Week 52

    NO is the opalescence of the nucleus (central layer) of the lens. Per LOC III, NO ranges from 0.1 (clear or colorless) to 6.9 (very opaque or brunescent). Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.

24. Change From Baseline in the Logarithm of the Minimum Angle of Resolution (LogMAR) Visual Acuity at Week 28 and Week 52

    Time frame: Baseline; Week 28 and Week 52

    Visual acuity is defined as the acuteness or clearness of vision. The minimum angle of resolution (MAR) is the angle a viewed object subtends at the eye, usually stated in degrees/minutes of arc. Visual acuity was measured using Early Treatment Diabetic Retinopathy Study (ETDRS) charts in decimal numbers. The LogMAR scale is used to express the visual acuity in a linear scale as the logarithm to base 10 of the MAR. A lower score indicates better visual acuity; visual acuity decreases with an increasing score. Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.

25. Maximum Change From Baseline in the QT Interval Using Bazett's Correction (QTcB) and QT Interval Using Fridericia's Correction (QTcF)

    Time frame: Baseline; Week 2, Week 12, Week 28, and Week 52/Early Withdrawal

    The QT interval is an electrocardiogram (ECG) parameter that represents the electrical depolarization and repolarization of the left and right ventricles of the heart. The QT interval is a measure of the time between the start of the Q wave and the end of the T wave in the ECG. Corrected QT (QTc) is the QT interval corrected for heart rate by using Bazett's formula (QTcB) and Fridericia's formula (QTcF). 12-lead ECG measurements were perfomed at the following scheduled time points: Baseline; Week 2, Week 12, Week 28, and Week 52/Early Withdrawal. The Baseline value is defined as the value taken pre-dose at screening. The maximum post-Baseline value was derived using all scheduled, unscheduled, and Early Withdrawal ECG assessments. Maximum change from Baseline was calculated as the maximum post-Baseline value minus the value at Baseline.

26. Mean 24 Hour Holter Heart Rate for Participants With at Least 16 Hours of Recorded Data

    Time frame: 0-24 hours at Screening, Day 1, Week 28, and Week 52

    Twenty-four hour Holter monitors were obtained using a 12-lead Holter monitor. The Holter monitor is worn by the participant for 24 hours, and the monitor continuously records the heart's rhythm while the monitor is worn. At the end of the 24 hour period, the data from the monitor are downloaded and transmitted to the centralized vendor for analysis and interpretation by a licensed cardiologist.

27. Maximum 24 Hour Holter Heart Rate for Participants With at Least 16 Hours of Recorded Data

    Time frame: 0-24 hours at Screening, Day 1, Week 28, and Week 52

    Twenty-four hour Holter monitors were obtained using a 12-lead Holter monitor. Holter monitor data were transmitted to a centralized vendor for analysis and interpretation by a licensed cardiologist.

Results and safety

Loading the posted results from ClinicalTrials.gov…

Research links

• Official record on ClinicalTrials.govLast updated by the sponsor 15 Feb 2018.
• Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
• Background: PubMed 23440247Busse WW, O'Byrne PM, Bleecker ER, Lotvall J, Woodcock A, Andersen L, Hicks W, Crawford J, Jacques L, Apoux L, Bateman ED. Safety and tolerability of the novel inhaled corticosteroid fluticasone furoate in combination with the beta2 agonist vilanterol administered once daily for 52 weeks in patients >=12 years old with asthma: a randomised trial. Thorax. 2013 Jun;68(6):513-20. doi: 10.1136/thoraxjnl-2012-202606. Epub 2013 Feb 25.
• Derived from this study: PubMed 36472162Oba Y, Anwer S, Maduke T, Patel T, Dias S. Effectiveness and tolerability of dual and triple combination inhaler therapies compared with each other and varying doses of inhaled corticosteroids in adolescents and adults with asthma: a systematic review and network meta-analysis. Cochrane Database Syst Rev. 2022 Dec 6;12(12):CD013799. doi: 10.1002/14651858.CD013799.pub2.
• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.Link provided by the sponsor.
• Individual participant dataSharing planned: Yes. Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

47 sites in 4 countries: see every site and its status.