- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01086410
Safety Study of the Effects of Inhaled Fluticasone Furoate/GW642444 on the Hypothalamic-Pituitary-Adrenal (HPA) Axis
November 30, 2016 updated by: GlaxoSmithKline
Study HZA106851: A Study of the Effects of Inhaled Fluticasone Furoate/GW642444 Versus Placebo on the HPA Axis of Adolescent and Adult Asthmatics
The purpose of this study is to assess the effect of six weeks' treatment with two once-daily strengths of Fluticasone Furoate/GW642444 Inhalation Powder on the HPA axis system
Study Overview
Status
Completed
Conditions
Study Type
Interventional
Enrollment (Actual)
185
Phase
- Phase 3
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Berlin, Germany, 10117
- GSK Investigational Site
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Berlin, Germany, 10787
- GSK Investigational Site
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Hamburg, Germany, 20253
- GSK Investigational Site
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Hessen
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Frankfurt, Hessen, Germany, 60596
- GSK Investigational Site
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Sachsen-Anhalt
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Magdeburg, Sachsen-Anhalt, Germany, 39112
- GSK Investigational Site
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Schleswig-Holstein
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Grosshansdorf, Schleswig-Holstein, Germany, 22927
- GSK Investigational Site
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Bialystok, Poland, 15-010
- GSK Investigational Site
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Gdansk, Poland, 80-405
- GSK Investigational Site
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Gidle, Poland, 97-540
- GSK Investigational Site
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Krakow, Poland, 31-023
- GSK Investigational Site
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Lodz, Poland, 93-513
- GSK Investigational Site
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Olsztyn, Poland, 10-357
- GSK Investigational Site
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Warszawa, Poland, 01-138
- GSK Investigational Site
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California
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Cypress, California, United States, 90630
- GSK Investigational Site
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Huntington Beach, California, United States, 92647
- GSK Investigational Site
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Oklahoma
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Oklahoma City, Oklahoma, United States, 73103
- GSK Investigational Site
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Texas
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San Antonio, Texas, United States, 78229
- GSK Investigational Site
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
12 years to 65 years (Child, Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Outpatient with ability to comply with study requirements and complete two 24-hour clinic visits
- Clinical diagnosis of asthma for greater than/equal to 12 weeks
- Reversibility FEV1 of at least twelve percent and two hundred milliliters
- FEV1 greater than or equal to fifty percent of predicted
Exclusion Criteria:
- History of life threatening asthma
- Respiratory infection or oral candidiasis
- Asthma exacerbation
- Uncontrolled disease or clinical abnormality
- Allergies to study drugs, study drugs' excipients, medications related to study drugs
- Taking another investigational medication or prohibited medication
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Active Comparator: FF/444 Dose B
Fluticasone furoate/GW642444 Dose B inhalation powder once daily for 6 weeks' treatment + 1 oral placebo capsule each day on the last 7 days of the study
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Dose B inhaled once daily for 6 weeks' treatment
Dose A inhaled once daily for 6 weeks' treatment
One placebo capsule taken each day on the last 7 days of the study
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Active Comparator: FF/444 Dose A
Fluticasone furoate/GW642444 Dose A inhalation powder once daily for 6 weeks' treatment + 1 oral placebo capsule each day on the last 7 days of the study
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Dose B inhaled once daily for 6 weeks' treatment
Dose A inhaled once daily for 6 weeks' treatment
One placebo capsule taken each day on the last 7 days of the study
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Placebo Comparator: Placebo
Placebo inhalation powder once daily for 6 weeks' treatment + 1 oral placebo capsule each day on the last 7 days of the study
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One placebo capsule taken each day on the last 7 days of the study
Placebo Inhalation powder inhaled once daily for 6 weeks' treatment
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Active Comparator: Prednisolone
Placebo inhalation powder once daily for 6 weeks' treatment + 1 oral prednisolone 10mg capsule each day on the last 7 days of the study
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Placebo Inhalation powder inhaled once daily for 6 weeks' treatment
Prednisolone 10mg oral capsule taken each day on the last 7 days of the study
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Ratio From Baseline of the Serum Cortisol Weighted Mean (0-24 Hours) on Day -1/1 (Baseline) and Day 42
Time Frame: Day -1/1 (Baseline) and Day 42
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Serum cortisol weighted mean was determined for each participant over the time period 0-12 hours on Day -1/1 (Baseline) and Day 42.
Serum cortisol weighted mean was derived by dividing the area under the concentration-time curve (AUC; defined as thearea under the concentration-time curve from time zero up to 24 hours) by the sample collection time interval.
The sample collection time interval is defined as the difference between the time of the last cortisol sample and the time of the first cortisol sample.
Samples were collected at the following time points: 0 (first blood draw/pre-dose); 2, 4, 9, 12, 14, 16, 20, 22, and 24 hours (relative to the "0" time point).
Because values are on a logged scale, the ratio of the endpoint to Baseline is presented, as it is a measure of the difference from Baseline.
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Day -1/1 (Baseline) and Day 42
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Ratio From Baseline of the Serum Cortisol Area Under the Concentration-time Curve (AUC) (0-24 Hour) on Day -1/1 (Baseline) and Day 42
Time Frame: Day -1/1 (Baseline) and Day 42
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Area under the plasma drug concentration-time (AUC[0-24 hour]) curve from time zero (pre-dose) to the last time of quantifiable serum cortisol concentration at 24 hours post-dose on Day -1/1 (Baseline) and Day 42 was measured.
AUC reflects the actual body exposure to drug over a specified period of time after administration of a dose.
Samples were collected at the following times: 0 (immediately pre-dose inhaled study drug); post-dose at 5 minutes (min), 15 min, 30 min, and 1 hour (hr), 2 hr, 4 hr, 9 hr, 12 hr, 16 hr, 20 hr, and 24 hr.
Because values are on a logged scale, the ratio of the endpoint to Baseline is presented, as it is a measure of the difference from Baseline.
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Day -1/1 (Baseline) and Day 42
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Ratio From Baseline of Serum Cortisol Trough (0-24 Hours) at Day -1/1 (Baseline) and Day 42
Time Frame: Day -1/1 (Baseline) and Day 42
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Serum cortisol trough is defined as the minimum value of serum cortisol measured over the 24-hour period.
Samples were collected at the following times: 0 (immediately pre-dose inhaled study drug); post-dose at 5 minutes (min), 15 min, 30 min, and 1 hour (hr), 2 hr, 4 hr, 9 hr, 12 hr, 16 hr, 20 hr, and 24 hr.
Because values are on a logged scale, the ratio of the endpoint to Baseline is presented, as it is a measure of the difference from Baseline.
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Day -1/1 (Baseline) and Day 42
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Ratio From Baseline of 0-24 Hour Urinary Free Cortisol Excretion on Day -1/1 (Baseline) and Day 42
Time Frame: Day -1/1 (Baseline) and Day 42
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A 24-hour urine sample was collected for the measurement of 24-hour urinary cortisol excretion at Day -1/1 (Baseline) and Day 42.
Only those participants available at the specified time points were analyzed.
Because values are on a logged scale, the ratio of the endpoint to Baseline is presented, as it is a measure of the difference from Baseline.
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Day -1/1 (Baseline) and Day 42
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Plasma FF and VI Pharmacokinetic (PK) Concentration
Time Frame: Day 42
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Plasma FF and VI Pharmacokinetic (PK) Concentration were estimates at the following time points:0 (immediately pre-dose inhaled study drug), and post-dose at 5 min, 15 min, 30 min, and 1 hr, 2 hr, 4 hr, 9 hr, 12 hr, 16 hr, 20 hr, 24 hr on Day 42.
Only those participants available at the specified time points were analyzed (represented by n=X, X, X, X in the category titles).
Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the Pharmacokinetic Population.
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Day 42
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AUC(0-t) and AUC(0-24) for FF on Day 42
Time Frame: Day 42
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Area under the plasma drug concentration-time (AUC[0-t]) curve from time zero (pre-dose) to the last time of quantifiable FF concentration and AUC(0-24) is the concentration time curve from zero (pre-dose) to 24 hours of quantifiable FF concentration on Day 42 was measured.
AUC reflects the actual body exposure to drug over a specified period of time after administration of a dose.
Samples were collected at the following times: 0 (immediately pre-dose inhaled study drug); post-dose at 5 minutes (min), 15 min, 30 min, and 1 hour (hr), 2 hr, 4 hr, 9 hr, 12 hr, 16 hr, 20 hr, and 24 hr post-dose on Day 42.
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Day 42
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Cmax for FF on Day 42
Time Frame: Day 42
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Cmax is defined as the maximum observed concentration on Day 42.
Samples were collected at the following times: 0 (immediately pre-dose inhaled study drug); post-dose at 5 minutes (min), 15 min, 30 min, and 1 hour (hr), 2 hr, 4 hr, 9 hr, 12 hr, 16 hr, 20 hr, and 24 hr post-dose on Day 42.
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Day 42
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Tmax and Tlast of FF at Day 42
Time Frame: Day 42
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tmax is defined as the time to reach the observed maximum concentration, and tlast is defined as the time of the last observed quantifiable concentration on Day 42.
Samples were collected at the following times: 0 (immediately pre-dose inhaled study drug); post-dose at 5 minutes (min), 15 min, 30 min, and 1hour (hr), 2 hr, 4 hr, 9 hr, 12 hr, 16 hr, 20 hr, and 24 hr post-dose on Day 42.
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Day 42
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AUC(0-t) for VI on Day 42
Time Frame: Day 42
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Area under the concentration-time (AUC[0-t]) curve from time zero (pre-dose) to the last time of quantifiable VI concentration on Day 42 was measured.
Samples were collected at the following times: 0 (immediately pre-dose inhaled study drug); post-dose at 5 minutes (min), 15 min, 30 min, and 1 hour (hr), 2 hr, 4 hr, 9 hr, 12 hr, 16 hr, 20 hr, and 24 hr post-dose on Day 42.
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Day 42
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Cmax for VI on Day 42
Time Frame: Day 42
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Cmax is defined as the maximum observed concentration on Day 42.
Samples were collected at the following times: 0 (immediately pre-dose inhaled study drug); post-dose at 5 minutes (min), 15 min, 30 min, and 1 hour (hr), 2 hr, 4 hr, 9 hr, 12 hr, 16 hr, 20 hr, and 24 hr post-dose on Day 42.
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Day 42
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Tmax and Tlast of VI at Day 42
Time Frame: Day 42
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tmax is defined as the time to reach the observed maximum concentration, and tlast is defined as the time of the last observed quantifiable VI concentration on Day 42.
Samples were collected at the following times: 0 (immediately pre-dose inhaled study drug); post-dose at 5 minutes (min), 15 min, 30 min, and 1hour (hr), 2 hr, 4 hr, 9 hr, 12 hr, 16 hr, 20 hr, and 24 hr post-dose on Day 42.
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Day 42
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Number of Participants With Any Adverse Event (AE) or Any Serious Adverse Event (SAE) During the Treatment Period
Time Frame: From the start of study medication until Day 42 (Visit 5)/Early Withdrawal
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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.
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From the start of study medication until Day 42 (Visit 5)/Early Withdrawal
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Change From Baseline in Basophil, Eosinophil, Lymphocyte, Monocyte, and Segmented Neutrophil Values at Day 42/Early Withdrawal (EW)
Time Frame: Baseline and Day 42/Early Withdrawal (EW)
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Blood samples were collected for the measurement of basophils, eosinophils, lymphocytes, monocytes, and segmented neutrophils at Baseline and Day 42/EW.
For all laboratory assessments, Baseline is the most recent recorded value at Screening or prior to Day -1/1.
Change from Baseline was calculated as the Day 42/EW value minus the Baseline value.
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Baseline and Day 42/Early Withdrawal (EW)
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Change From Baseline in Eosinophil, Total Neutrophil, Platelet, and White Blood Cell (WBC) Count Values at Day 42/EW
Time Frame: Baseline and Day 42/EW
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Blood samples were collected for the measurement of eosinophils, total neutrophils, platelets, and WBC count at Baseline and Day 42/EW.
For all laboratory assessments, Baseline is the most recent recorded value at Screening or prior to Day -1/1.
Change from Baseline was calculated as the Day 42/EW value minus the Baseline value.
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Baseline and Day 42/EW
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Change From Baseline in Hemoglobin Values at Day 42/EW
Time Frame: Baseline and Day 42/EW
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Blood samples were collected for the measurement of hemoglobin at Baseline and Day 42/EW.
For all laboratory assessments, Baseline is the most recent recorded value at Screening or prior to Day -1/1.
Change from Baseline was calculated as the Day 42/EW value minus the Baseline value.
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Baseline and Day 42/EW
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Change From Baseline in Hematocrit Values at Day 42/EW
Time Frame: Baseline and Day 42/EW
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Blood samples were collected for the measurement of hematocrit at Baseline and Day 42/EW.
For all laboratory assessments, Baseline is the most recent recorded value at Screening or prior to Day -1/1.
Change from Baseline was calculated as the Day 42/EW value minus the Baseline value.
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Baseline and Day 42/EW
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Change From Baseline in Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Creatine Kinase (CK), and Gamma Glutamyl Transferase (GGT) Values at Day 42/EW
Time Frame: Baseline and Day 42/EW
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Blood samples were collected for the measurement of ALT, ALP, AST, CK, and GGT at Baseline and Day 42/EW.
For all laboratory assessments, Baseline is the most recent recorded value at Screening or prior to Day -1/1.
Change from Baseline was calculated as the Day 42/EW value minus the Baseline value.
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Baseline and Day 42/EW
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Change From Baseline in Albumin and Total Protein Values at Day 42/EW
Time Frame: Baseline and Day 42/EW
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Blood samples were collected for the measurement of albumin and total protein at Baseline and Day 42/EW.
For all laboratory assessments, Baseline is the most recent recorded value at Screening or prior to Day -1/1.
Change from Baseline was calculated as the Day 42/EW value minus the Baseline value.
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Baseline and Day 42/EW
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Change From Baseline in Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, and Creatinine Values at Day 42/EW
Time Frame: Baseline and Day 42/EW
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Blood samples were collected for the measurement of direct bilirubin, indirect bilirubin, total bilirubin, and creatinine at Baseline and Day 42/EW.
For all laboratory assessments, Baseline is the most recent recorded value at Screening or prior to Day -1/1.
Change from Baseline was calculated as the Day 42/EW value minus the Baseline value.
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Baseline and Day 42/EW
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Change From Baseline in Chloride, Carbon Dioxide (CO2) Content/Bicarbonate, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values at Day 42/EW
Time Frame: Baseline and Day 42/EW
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Blood samples were collected for the measurement of chloride, carbon dioxide (CO2) content/bicarbonate, glucose, potassium, sodium, and urea/blood urea nitrogen (BUN) at Baseline and Day 42/EW.
For all laboratory assessments, Baseline is the most recent recorded value at Screening or prior to Day -1/1.
Change from Baseline was calculated as the Day 42/EW value minus the Baseline value.
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Baseline and Day 42/EW
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Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Days 14, 28, 42, and Maximum Post-Baseline
Time Frame: Days 14, 28, 42, and EW
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SBP and DBP were measured at Baseline and at Days 14, 28, 42, and EW.
Change from Baseline was calculated as the Day 42/EW value minus the Baseline value.
Scheduled, unscheduled, and early withdrawal visits were used for the maximum post-Baseline assessment.
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Days 14, 28, 42, and EW
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Change From Baseline in Pulse Rate at Days 14, 28, 42, and Maximum Post-Baseline
Time Frame: Days 14, 28, 42, and EW
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Heart rate was measured at Baseline and at Days 14, 28, 42, and EW.
Change from Baseline was calculated as the Day 42/EW value minus the Baseline value.
Scheduled, unscheduled, and early withdrawal visits were used for the maximum post-Baseline assessment.
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Days 14, 28, 42, and EW
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
March 1, 2010
Primary Completion (Actual)
September 1, 2010
Study Completion (Actual)
September 1, 2010
Study Registration Dates
First Submitted
March 11, 2010
First Submitted That Met QC Criteria
March 11, 2010
First Posted (Estimate)
March 15, 2010
Study Record Updates
Last Update Posted (Estimate)
January 18, 2017
Last Update Submitted That Met QC Criteria
November 30, 2016
Last Verified
November 1, 2016
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Physiological Effects of Drugs
- Autonomic Agents
- Peripheral Nervous System Agents
- Anti-Inflammatory Agents
- Antineoplastic Agents
- Glucocorticoids
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Antineoplastic Agents, Hormonal
- Dermatologic Agents
- Bronchodilator Agents
- Anti-Asthmatic Agents
- Respiratory System Agents
- Anti-Allergic Agents
- Prednisolone
- Fluticasone
- Xhance
Other Study ID Numbers
- 106851
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Yes
IPD Plan Description
Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
Study Data/Documents
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Statistical Analysis Plan
Information identifier: 106851Information comments: For additional information about this study please refer to the GSK Clinical Study Register
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Informed Consent Form
Information identifier: 106851Information comments: For additional information about this study please refer to the GSK Clinical Study Register
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Dataset Specification
Information identifier: 106851Information comments: For additional information about this study please refer to the GSK Clinical Study Register
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Individual Participant Data Set
Information identifier: 106851Information comments: For additional information about this study please refer to the GSK Clinical Study Register
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Clinical Study Report
Information identifier: 106851Information comments: For additional information about this study please refer to the GSK Clinical Study Register
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Study Protocol
Information identifier: 106851Information comments: For additional information about this study please refer to the GSK Clinical Study Register
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Annotated Case Report Form
Information identifier: 106851Information comments: For additional information about this study please refer to the GSK Clinical Study Register
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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