COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Safety Study of the Effects of Inhaled Fluticasone Furoate/GW642444 on the Hypothalamic-Pituitary-Adrenal (HPA) Axis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01086410
Recruitment Status : Completed
First Posted : March 15, 2010
Results First Posted : August 8, 2013
Last Update Posted : January 18, 2017
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Brief Summary:
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

Condition or disease Intervention/treatment Phase
Asthma Drug: Placebo Inhalation Powder Drug: Fluticasone Furoate/GW642444 Inhalation Powder Drug: Placebo Oral Capsule Drug: Prednisolone Oral Capsule Phase 3

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 185 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Study HZA106851: A Study of the Effects of Inhaled Fluticasone Furoate/GW642444 Versus Placebo on the HPA Axis of Adolescent and Adult Asthmatics
Study Start Date : March 2010
Actual Primary Completion Date : September 2010
Actual Study Completion Date : September 2010

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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
Drug: Fluticasone Furoate/GW642444 Inhalation Powder
Dose B inhaled once daily for 6 weeks' treatment

Drug: Placebo Oral Capsule
One placebo capsule taken each day on the last 7 days of the study

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
Drug: Fluticasone Furoate/GW642444 Inhalation Powder
Dose A inhaled once daily for 6 weeks' treatment

Drug: Placebo Oral Capsule
One placebo capsule taken each day on the last 7 days of the study

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
Drug: Placebo Inhalation Powder
Placebo Inhalation powder inhaled once daily for 6 weeks' treatment

Drug: Placebo Oral Capsule
One placebo capsule taken each day on the last 7 days of the study

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
Drug: Placebo Inhalation Powder
Placebo Inhalation powder inhaled once daily for 6 weeks' treatment

Drug: Prednisolone Oral Capsule
Prednisolone 10mg oral capsule taken each day on the last 7 days of the study




Primary Outcome Measures :
  1. 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 ]
    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.


Secondary Outcome Measures :
  1. 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 ]
    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.

  2. 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 ]
    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.

  3. 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 ]
    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.

  4. Plasma FF and VI Pharmacokinetic (PK) Concentration [ Time Frame: Day 42 ]
    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.

  5. AUC(0-t) and AUC(0-24) for FF on Day 42 [ Time Frame: Day 42 ]
    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.

  6. Cmax for FF on Day 42 [ Time Frame: Day 42 ]
    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.

  7. Tmax and Tlast of FF at Day 42 [ Time Frame: Day 42 ]
    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.

  8. AUC(0-t) for VI on Day 42 [ Time Frame: Day 42 ]
    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.

  9. Cmax for VI on Day 42 [ Time Frame: Day 42 ]
    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.

  10. Tmax and Tlast of VI at Day 42 [ Time Frame: Day 42 ]
    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.

  11. 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 ]
    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.

  12. 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) ]
    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.

  13. 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 ]
    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.

  14. Change From Baseline in Hemoglobin Values at Day 42/EW [ Time Frame: Baseline and Day 42/EW ]
    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.

  15. Change From Baseline in Hematocrit Values at Day 42/EW [ Time Frame: Baseline and Day 42/EW ]
    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.

  16. 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 ]
    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.

  17. Change From Baseline in Albumin and Total Protein Values at Day 42/EW [ Time Frame: Baseline and Day 42/EW ]
    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.

  18. Change From Baseline in Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, and Creatinine Values at Day 42/EW [ Time Frame: Baseline and Day 42/EW ]
    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.

  19. 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 ]
    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.

  20. 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 ]
    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.

  21. Change From Baseline in Pulse Rate at Days 14, 28, 42, and Maximum Post-Baseline [ Time Frame: Days 14, 28, 42, and EW ]
    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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   12 Years to 65 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01086410


Locations
Layout table for location information
United States, California
GSK Investigational Site
Cypress, California, United States, 90630
GSK Investigational Site
Huntington Beach, California, United States, 92647
United States, Oklahoma
GSK Investigational Site
Oklahoma City, Oklahoma, United States, 73103
United States, Texas
GSK Investigational Site
San Antonio, Texas, United States, 78229
Germany
GSK Investigational Site
Frankfurt, Hessen, Germany, 60596
GSK Investigational Site
Magdeburg, Sachsen-Anhalt, Germany, 39112
GSK Investigational Site
Grosshansdorf, Schleswig-Holstein, Germany, 22927
GSK Investigational Site
Berlin, Germany, 10117
GSK Investigational Site
Berlin, Germany, 10787
GSK Investigational Site
Hamburg, Germany, 20253
Poland
GSK Investigational Site
Bialystok, Poland, 15-010
GSK Investigational Site
Gdansk, Poland, 80-405
GSK Investigational Site
Gidle, Poland, 97-540
GSK Investigational Site
Krakow, Poland, 31-023
GSK Investigational Site
Lodz, Poland, 93-513
GSK Investigational Site
Olsztyn, Poland, 10-357
GSK Investigational Site
Warszawa, Poland, 01-138
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Layout table for investigator information
Study Director: GSK Clinical Trials GlaxoSmithKline
Additional Information:
Study Data/Documents: Statistical Analysis Plan  This link exits the ClinicalTrials.gov site
Identifier: 106851
For additional information about this study please refer to the GSK Clinical Study Register
Informed Consent Form  This link exits the ClinicalTrials.gov site
Identifier: 106851
For additional information about this study please refer to the GSK Clinical Study Register
Dataset Specification  This link exits the ClinicalTrials.gov site
Identifier: 106851
For additional information about this study please refer to the GSK Clinical Study Register
Individual Participant Data Set  This link exits the ClinicalTrials.gov site
Identifier: 106851
For additional information about this study please refer to the GSK Clinical Study Register
Clinical Study Report  This link exits the ClinicalTrials.gov site
Identifier: 106851
For additional information about this study please refer to the GSK Clinical Study Register
Study Protocol  This link exits the ClinicalTrials.gov site
Identifier: 106851
For additional information about this study please refer to the GSK Clinical Study Register
Annotated Case Report Form  This link exits the ClinicalTrials.gov site
Identifier: 106851
For additional information about this study please refer to the GSK Clinical Study Register

Layout table for additonal information
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01086410    
Other Study ID Numbers: 106851
First Posted: March 15, 2010    Key Record Dates
Results First Posted: August 8, 2013
Last Update Posted: January 18, 2017
Last Verified: November 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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.
Keywords provided by GlaxoSmithKline:
HPA axis
Additional relevant MeSH terms:
Layout table for MeSH terms
Fluticasone
Prednisolone
Anti-Inflammatory Agents
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Dermatologic Agents
Anti-Allergic Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents