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A Study To Assess The Safety And Tolerability Of GW642444 In Subjects With Chronic Obstructive Pulmonary Disease (COPD)

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ClinicalTrials.gov Identifier: NCT00372112
Recruitment Status : Completed
First Posted : September 6, 2006
Results First Posted : February 22, 2018
Last Update Posted : April 2, 2018
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Brief Summary:
The compound GW642444 has previously been found to be well tolerated with no significant side effects in subjects with asthma and healthy volunteers. This study will assess the safety and tolerability of GW642444 in subjects with COPD in order to obtain information to support dosing in a broader population of subjects with COPD

Condition or disease Intervention/treatment Phase
Pulmonary Disease, Chronic Obstructive Drug: GW642444 Other: Placebo Phase 2

Detailed Description:
A multicentre, randomised, placebo-controlled, double-blind, 4-arm parallel-group, 2-week study to evaluate the safety, tolerability, pharmacodynamics and pharmacokinetics of GW642444H (100 administered once daily in the morning via DISKUS™ dry-powder inhaler) compared with SEREVENT (salmeterol) (50mcg administered twice daily via DISKUS dry-powder inhaler) and placebo in subjects with moderate COPD.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 68 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A 2-wk Study to Evaluate the Safety, Tolerability,Pharmacodynamics and Pharmacokinetics of GW642444H(100 Administered Once Daily in the Morning Via DISKUS™ Dry-powder Inhaler)Compared With SEREVENT(Salmeterol)(50mcg Administered Twice Daily Via DISKUS Dry-powder Inhaler)and Placebo in Subject w/COPD
Actual Study Start Date : November 3, 2006
Actual Primary Completion Date : May 1, 2007
Actual Study Completion Date : May 10, 2007

Resource links provided by the National Library of Medicine

MedlinePlus related topics: COPD Lung Diseases

Arm Intervention/treatment
Active Comparator: 100 mcg GW642444H
Twice daily in the morning.
Drug: GW642444
GW642444H

Active Comparator: 400 mcg GW642444H
Twice daily in the morning.
Drug: GW642444
GW642444H

Active Comparator: 50 mcg salmeterol
Twice daily.
Drug: GW642444
GW642444H

Placebo Comparator: placebo
Twice daily
Drug: GW642444
GW642444H

Other: Placebo
Placebo administered twice daily




Primary Outcome Measures :
  1. Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) [ Time Frame: Up to Follow-up (17 days) ]
    An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An 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, may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in this definition.


Secondary Outcome Measures :
  1. Change From Baseline in Pre-dose Weighted Mean Heart Rate (HR) Derived From 28.5 Hour (h) Ambulatory Blood Pressure Monitoring (ABPM) at Day 7 and 14 [ Time Frame: Baseline (Day 1, pre-dose) up to Day 14 ]
    HR was measured using 28.5h ABPM on Day 1, Day 7 and Day 14. Baseline was defined as the pre-dose weighted mean of Day 1. Weighted mean was calculated by calculating the area under curve (AUC) of measurements made pre-dose on each day, and then dividing by the relevant time interval. AUC was calculated using the trapezoidal rule. The weighted mean change from Baseline was the average AUC minus Baseline (AAUCMB).

  2. Change From Baseline in 0-4 h Weighted Mean HR Derived From 28.5 h ABPM at Day 1, 2, 7, 8, 14 and 15 [ Time Frame: Baseline (Day 1, pre-dose) up to Day 15 ]
    HR was measured using 28.5 h ABPM on Day 1 (continued till Day 2), Day 7 (continued till Day 8) and Day 14 (continued till Day 15). Baseline was defined as the pre-dose weighted mean of Day 1. Weighted mean was calculated by calculating the AUC of measurements made 0-4 h post-dose on Day 1, 2, 7, 8, 14 and 15 and then dividing by the relevant time interval. AUC was calculated using the trapezoidal rule. The weighted mean change from Baseline was the AAUCMB.

  3. Change From Baseline in 0-24 h Weighted Mean HR Derived From 28.5 ABPM at Day 7 and 14 [ Time Frame: Baseline (Day 1, pre-dose) up to Day 15 ]
    HR was measured using 28.5 h ABPM on Day 1, Day 7 and Day 14. Baseline was defined as the pre-dose weighted mean of Day 1. Weighted mean was calculated by calculating the AUC of measurements made 0-24 h post-dose on Day 7 and 14, and then dividing by the relevant time interval. AUC was calculated using the trapezoidal rule. The weighted mean change from Baseline was the AAUCMB.

  4. Change From Baseline in Maximum HR During 0-4 h Derived From 28.5 h ABPM at Day 1, 2, 7, 8, 14 and 15 [ Time Frame: Baseline (Day 1, pre-dose) up to Day 15 ]
    HR was measured using 28.5 h ABPM on Day 1 (continued till Day 2), Day 7 (continued till Day 8) and Day 14 (continued till Day 15). For the calculation of 0-4 h maximum change from Baseline, measurements post-dose up to 6 h (actual time) was included. Baseline was defined as the pre-dose weighted mean of Day 1. Maximum change from Baseline was calculated by subtracting the Baseline value (weighted mean pre-dose Day 1) from the maximum assessment value (during 0-4 h) of the individual post-Baseline time points.

  5. Mean Weighted Mean HR at 0-4 h, Weighted Mean HR at 0-24 h and Maximum HR at 0-4 h Derived From 28.5 h ABPM [ Time Frame: Day 1 up to Day 15 ]
    HR was measured using 28.5 h ABPM. Weighted mean HR at 0-4 h was obtained from measurements made over 0-4 h post-dose on Day 1, 2, 7, 8, 14 and 15. Weighted mean HR at 0-24 h was obtained from measurements made 0-24 h post-dose on Day 1, 7 and 14. Maximum HR at 0-4 h was obtained from measurements made over 0-4 h post-dose on Day 1, 2, 7, 8, 14 and 15. Baseline was defined as the pre-dose weighted mean of Day 1.

  6. Mean Hourly HR 0-24 h at Day 1, 7 and 14 [ Time Frame: Day 1 up to Day 14 ]
    HR was measured using 28.5 h ABPM. The assessments were analyzed hourly as 0-1 h, 1-2 h, 2-3 h, 3-4 h, 4-5 h, 5-6 h, 6-7 h, 7-8 h, 8-9 h, 9-10 h, 10-11 h, 11-12 h, 12-13 h, 13-14 h, 14-15 h, 15-16 h, 16-17 h, 17-18 h, 18-19 h, 19-20 h, 20-21 h, 21-22 h, 22-23 h and 23-24 h at Day 1, Day 7 and Day 14.

  7. Mean Maximum Hourly HR 0-24 h at Day 1, 7 and 14 [ Time Frame: Day 1 up to Day 14 ]
    HR was measured using 28.5 h ABPM. The assessments for maximum HR were analyzed hourly as 0-1 h, 1-2 h, 2-3 h, 3-4 h, 4-5 h, 5-6 h, 6-7 h, 7-8 h, 8-9 h, 9-10 h, 10-11 h, 11-12 h, 12-13 h, 13-14 h, 14-15 h, 15-16 h, 16-17 h, 17-18 h, 18-19 h, 19-20 h, 20-21 h, 21-22 h, 22-23 h and 23-24 h at Day 1, Day 7 and Day 14.

  8. Change From Baseline in Weighted Mean Systolic and Diastolic Blood Pressure (SBP and DBP) Derived From 28.5 h ABPM Over Time [ Time Frame: Baseline (Day 1, pre-dose) up to Day 15 ]
    BP was measured using 28.5 h ABPM. Weighted mean SBP and DBP at 0-4 h post-dose was obtained on Day 1, 2, 7, 8, 14 and 15. Weighted mean SBP and DBP at 0-24 h post-dose was obtained on Day 1, 7 and 14. Weighted mean was calculated by calculating the AUC, and then dividing by the relevant time interval. AUC was calculated using the trapezoidal rule. Baseline was defined as the weighted mean SBP and DBP on pre-dose Day 1. The weighted mean change from Baseline was the AAUCMB. Data is reported for change from Baseline in weighted mean pre-dose values at Day 7 and Day 14; change from Baseline in weighted mean over 0-4 h at Day 1, 2, 7, 8, 14 and 15; and change from Baseline in weighted mean over 0-24 h at Day 1, 7 and 14.

  9. Change From Baseline in Maximum SBP and Minimum DBP Derived From 28.5 h ABPM Over Time [ Time Frame: Baseline (Day 1, pre-dose) up to Day 15 ]
    BP was measured using 28.5 h ABPM. Maximum SBP and minimum DBP at 0-4 h post-dose was obtained on Day 1, 2, 7, 8, 14 and 15. For the calculation of 0-4 h maximum/minimum change from Baseline, measurements post-dose up to 6 h (actual time) was included. Baseline was defined as the pre-dose weighted mean of Day 1 for SBP and DBP. Maximum/minimum change from Baseline was calculated by subtracting the Baseline value (weighted mean pre-dose Day 1 for SBP and DBP) from the maximum/minimum assessment value (during 0-4 h) of the individual post-Baseline time points.

  10. Mean Weighted Mean SBP and DBP at 0-4 h, Weighted Mean SBP and DBP at 0-24 h and Maximum SBP and Minimum DBP at 0-4 h Derived From 28.5 h ABPM [ Time Frame: Day 1 up to Day 15 ]
    BP was measured using 28.5 h ABPM. Weighted mean SBP and DBP at 0-4 h post-dose was obtained on Day 1, 2, 7, 8, 14 and 15. Weighted mean SBP and DBP at 0-24 h post-dose was obtained on Day 1, 7 and 14. Maximum SBP and minimum DBP at 0-4 h post-dose was obtained on Day 1, 2, 7, 8, 14 and 15. Baseline was defined as the pre-dose weighted mean of Day 1.

  11. Change From Baseline in QTc by Federicia's Method (F) and QTc Bazett's Method (B) Values at Pre-dose, Weighted Mean 0-4 h and Maximum 0-4 h Derived From 12-lead Electrocardiogram (ECG) Over Time [ Time Frame: Baseline (Day 1, pre-dose) up to Day 15 ]
    A 12-lead ECG was recorded on Day 1, 2, 7, 8, 14 and 15 with the participant in a supine position having rested in that position for at least 5 min before each reading. A total of 3 measurements separated by at least 1 min was taken at each visit and the mean recorded. The Baseline for pre-dose QTcF and QTcB measurements was the pre-dose assessment on Day 1. Weighted mean at 0-4 h for QTcF and QTcB was calculated by calculating the AUC, and then dividing by the relevant time interval. AUC was calculated using the trapezoidal rule. The weighted mean change from Baseline was the AAUCMB. The change from Baseline in maximum QTcF and QTcB at 0-4 h was calculated by subtracting the Baseline (pre-dose Day 1) value from the individual post-Baseline values.

  12. Mean QTcF and QTcB Values at Pre-dose, Weighted Mean 0-4 h and Maximum 0-4 h Derived From 12-lead ECG Over Time [ Time Frame: Day 1 up to Day 15 ]
    A 12-lead ECG was recorded on Day 1, 2, 7, 8, 14 and 15 with the participant in a supine position having rested in that position for at least 5 min before each reading. A total of 3 measurements separated by at least 1 min was taken at each visit and the mean recorded. The pre-dose QTcF and QTcB assessment was done at Day 1, 7 and 14. Weighted mean at 0-4 h for QTcF and QTcB at Day 1, 2, 7, 8, 14 and 15 was calculated by calculating the AUC, and then dividing by the relevant time interval. AUC was calculated using the trapezoidal rule. The maximum QTcF and QTcB at 0-4 h was obtained at Day 1, 2, 7, 8, 14 and 15.

  13. Mean of Hourly Maximums QTcF and QTcB Derived From 24 h 3-lead Holter ECG Monitoring Over Time [ Time Frame: Day 1 up to Day 14 ]
    A holter monitor is a machine that continuously records the heart's electrical activity. A 3-lead holter ECG monitoring device was used. The monitor was worn for 24 h during normal activity to record the ECG intervals. The assesmment for hourly maximums QTcF and QTcB was done on Day 1, Day 7 and Day 14. For each h of holter monitoring the maximum QTcF for that h was calculated using the maximum QT and mean HR of that given h as Maximum QT divided by (60/Mean HR)^1/3. For each h of holter monitoring the maximum QTcB for that h was calculated using the maximum QT and mean HR of that given h as Maximum QT divided by (60/Mean HR)^1/2.

  14. Number of Events of Supra Ventricular Ectopics, Ventricular Ectopics and Ventricular Runs Per 24 h Derived From 3-lead Holter ECG Monitoring Over Time [ Time Frame: Day 1 up to Day 14 ]
    A holter monitor is a machine that continuously records the heart's electrical activity. A 3-lead holter ECG monitoring device was used. The monitor was worn for 24 h during normal activity to record the heart's rhythm. The assessment for the events of supra ventricular ectopics, ventricular ectopics and ventricular runs per 24 h was done on Day 1, Day 7 and Day 14.

  15. Number of Participants With Biochemistry Abnormal Change From Baseline Values Relative to the Normal Range at Day 7 and 14 [ Time Frame: Baseline (Day 1) up to Day 14 ]
    The parameters of biochemistry with their normal range included: alanine amino transferase ([ALT] 0-48 international units per liter [IU/L]), albumin (32-50 gram [g]/L), alkaline phosphatase ([ALP] 20-125 IU/L), aspartate amino transferase ([AST] 0-42 IU/L), calcium (2.12-2.56 millimole [mmol]/L, chloride (95-108 mmol/L), creatine kinase ([CK] 0-235 IU/L), creatinine (44-124 micromole [µmol]/L), direct bilirubin (0-6 µmol/L), gamma glutamyl transferase ([GGT] 0-65 IU/L), glucose (3.9-6.9 mmol/L), lactate dehydrogenase ([LDH] 0-250 IU/L), potassium (3.5-5.3 mmol/L), sodium (135-146 mmol/L), total bilirubin (0-22 µmol/L), total protein (60-85 g/L), urea (2.5-9 mmol/L) and uric acid (250-510 µmol/L). The assessments were performed on Day 1, Day 7 and Day 14. Baseline was defined as the assessment done on Day 1. Only those parameters for which at least one value of abnormality (to low or to high) change from Baseline, relative to normal ranges were reported are summarized.

  16. Number of Participants With Hematology Abnormal Change From Baseline Values Relative to the Normal Range at Day 7 and 14 [ Time Frame: Baseline (Day 1) up to Day 14 ]
    The parameters of biochemistry with their normal range included: basophils (0-0.2 giga cells [GI]/L), eosinophils (0.05-0.55 GI/L), haematocrit (0.41-0.5 ratio), hemoglobin (138-172 g/L), lymphocytes (0.85-4.1 GI/L), mean corpuscle hemoglobin ([MCH] 27-33 picogram [pg]), mean corpuscle hemoglobin concentration ([MCHC] 320-360 g/L), mean corpuscle volume ([MCV] 80-100 femtoliter [fl]), monocytes (0.2-1.1 GI/L), segmented neutrophils (1.8-8 GI/L), total neutrophils (1.8-8 GI/L), platelet count (130-400 GI/L), red blood cell ([RBC] 4.4-5.8 trillion cells [TI]/L) count and white blood cell ([WBC] 3.8-10.8 GI/L) count. The assessments were performed on Day 1, Day 7 and Day 14. Baseline was defined as the assessment done on Day 1. Only those parameters for which at least one value of abnormality (to low or to high) change from Baseline, relative to normal ranges were reported are summarized.

  17. Change From Baseline in Forced Expiratory Volume in One Second (FEV1) at Pre-dose, Weighted Mean FEV1 at 0-4 h and Maximum FEV1 0-4 h Over Time [ Time Frame: Baseline (Day 1, pre-dose) up to Day 15 ]
    FEV1 is defined as the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. FEV1 was assessed pre-dose at Day 1, 2, 7, 8, 14 and 15. FEV1 was assessed post-dose at Day 1, 2, 7, 8 and 14. Lung function test of FEV1 was performed at the approximately same time at each visit in the morning and highest of the 3 measurements were recorded. Baseline was defined as the assessment done on pre-dose Day 1. The change from Baseline pre-dose was calculated by subtracting the Baseline value (pre-dose Day 1) from the individual post Baseline (Day 2, 7, 8, 14 and 15) values. Weighted mean was calculated by calculating the AUC, and then dividing by the relevant time interval. AUC was calculated using the trapezoidal rule. The weighted mean FEV1 0-4 h change from Baseline was the AAUCMB obtained at Day 1, 2, 7, 8, 14 and 15. The maximum FEV1 0-4 h change from Baseline was obtained at Day 1, Day 2, Day 7, Day 8, Day 14 and Day 15.

  18. Mean FEV1 Weighted Mean FEV1 at 0-4 h and Maximum FEV1 at 0-4 h Over Time [ Time Frame: Day 1 up to Day 15 ]
    FEV1 is defined as the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. FEV1 was assessed pre-dose and post-dose at Day 1, 2, 7, 8, 14 and 15. Lung function test of FEV1 was performed at the approximately same time at each visit in the morning and highest of the 3 measurements were recorded. Weighted mean was calculated by calculating the AUC, and then dividing by the relevant time interval. AUC was calculated using the trapezoidal rule. The weighted mean FEV1 0-4 h and maximum FEV1 0-4 h was obtained at Day 1, 2, 7, 8, 14 and 15.

  19. Change From Baseline in Weighted Mean FEV1 Over 22- 24 h on Days 1, 7 and 14 [ Time Frame: Baseline (Day 1, pre-dose) up to Day 15 ]
    FEV1 is defined as the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. Lung function test of FEV1 was performed at the approximately same time at each visit in the morning and highest of the 3 measurements were recorded. Weighted mean was calculated by calculating the AUC, and then dividing by the relevant time interval. AUC was calculated using the trapezoidal rule. The weighted mean FEV1 over 22-24 h was obtained at Day 1, Day 7 and Day 14 which was recorded up to Day 2, Day 8 and Day 15. Baseline was defined as the assessment on Day 1 pre-dose. Change from Baseline was calculated by subtracting the Baseline (Day 1, pre-dose) value from the individual post Baseline (Day 1, Day 7 and Day 14) values.

  20. Mean Morning and Evening Peak Expiratory Flow Rate (PEFR) Over Time [ Time Frame: Up to Follow-up (Day 17) ]
    PEF is a measure of lung function and measures how fast a person can breathe out. It was measured using a peak flow meter by the participants and recorded on daily record cards each day in the morning and evening from Screening up to Follow-up. The morning measurements were performed prior to the participant taking the morning dose of study medication or rescue medication. The evening measurements were performed prior to the participant taking the evening dose of study medication or rescue medication. The highest of the 3 values of morning and evening PEF were recorded on the diary card. The mean of 7 days of each morning and evening measurements were reported for the Run-in Week, Week 1, Week 2 and Follow-up.

  21. Mean Use of Rescue Medication Over Period [ Time Frame: Up to Follow-up (Day 17) ]
    Ipratropium bromide was provided as the rescue medication. The use of rescue medication was recorded by the participants on daily record cards each day in the morning and evening from Screening up to Follow-up. The mean of 7 days (puffs per 24 h) were reported for the Run-in Week, Week 1, Week 2 and Follow-up.

  22. Number of Participants With Rescue Free Days [ Time Frame: Up to Follow-up (Day 17) ]
    Ipratropium bromide was provided as the rescue medication. The use of rescue medication was recorded by the participants on daily record cards each day in the morning and evening from Screening up to Follow-up. The percentage of rescue free days during the Run-in week, Week 1, Week 2 and Follow-up Week were assessed. Data is reported for number of participants with < 20%, >=20 to <40%, >=40 to <60%, >=60 to <80% and >=80% rescue free days.

  23. Change From Baseline in Pre-dose Fasting Glucose and Potassium at Day 7 and 14 [ Time Frame: Baseline (Day 1, pre-dose) up to Day 14 ]
    Blood samples were collected at pre-dose on Day 1, Day 7 and Day 14. Baseline was defined as the assessment done on pre-dose, Day 1. Change from Baseline was calculated by subtracting the Baseline (Day 1, pre-dose) value from the individual post Baseline (Day 7 and Day 14) values.

  24. Change From Baseline in Weighted Mean Glucose and Potassium 0-4 h, Maximum Glucose 0-4 h and Minimum Potassium 0-4 h Over Time [ Time Frame: Baseline (Day 1, pre-dose) up to Day 15 ]
    Blood samples were collected at pre-dose and 4 h post-dose on Day 1, Day 2, Day 7, Day 8, Day 14 and Day 15. Weighted mean was calculated by calculating the AUC, and then dividing by the relevant time interval. AUC was calculated using the trapezoidal rule. Baseline was defined as the assessment on Day 1 pre-dose. The weighted mean change from Baseline was the AAUCMB. Change from Baseline in maximum glucose 0-4 h and minimum potassium 0-4 h was calculated by subtracting the Baseline (Day 1, pre-dose) value from the individual post Baseline (Day 1 to Day 15) values.

  25. Mean Weighted Mean 0-4 h of Glucose and Potassium, Maximum Glucose 0-4 h and Minimum Potassium 0-4 h Over Time [ Time Frame: Day 1 up to Day 15 ]
    Blood samples were collected at pre-dose and 4 h post-dose on Day 1, Day 2, Day 7, Day 8, Day 14 and Day 15. Weighted mean was calculated by calculating the AUC, and then dividing by the relevant time interval. AUC was calculated using the trapezoidal rule.

  26. AUC of GW642444H Over 0 to 4 h (AUC [0-4]) on Day 1, 7 and 14 [ Time Frame: Day 1 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose), Day 7 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose) and Day 14 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose) ]
    Blood samples were collected on Day 1 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose), Day 7 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose) and Day 14 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose). The pre-dose sample was collected within 5 min prior to study medication administration. The AUC over 4 h as AUC from zero (pre-dose) to 2 h post-dose (AUC [0-2]), AUC from zero (pre-dose) to 4 h post-dose (AUC [0-4]) and AUC from zero (pre-dose) to time of last quantifiable concentration (AUC [0-t]) was determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations.

  27. Maximum Concentration (Cmax) of GW642444H at Day 1, 7 and 14 [ Time Frame: Day 1 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose), Day 7 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose) and Day 14 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose) ]
    Blood samples were collected on Day 1 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose), Day 7 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose) and Day 14 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose). The pre-dose sample was collected within 5 min prior to study medication administration. The first occurrence of the Cmax was determined directly from the raw concentration-time data.

  28. Time to Maximum Concentration (Tmax) and Time of Last Quantifiable Concentration (Tlast) of GW642444H at Day 1, 7 and 14 [ Time Frame: Day 1 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose), Day 7 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose) and Day 14 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose) ]
    Blood samples were collected on Day 1 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose), Day 7 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose) and Day 14 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose). The pre-dose sample was collected within 5 min prior to study medication administration. The time at which Cmax was observed and tlast was determined directly from the raw concentration-time data.

  29. AUC (0-4) of CCI2189 at Day 1, 7 and 14 [ Time Frame: Day 1 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose), Day 7 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose) and Day 14 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose) ]
    CCI2189 is a counterion of GW642444H. Blood samples were collected on Day 1 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose), Day 7 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose) and Day 14 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose). The pre-dose sample was collected within 5 min prior to study medication administration. The AUC (0-4) was determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations.

  30. Cmax of CCI2189 at Day 1, 7 and 14 [ Time Frame: Day 1 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose), Day 7 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose) and Day 14 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose) ]
    CCI2189 is a counterion of GW642444H. Blood samples were collected on Day 1 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose), Day 7 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose) and Day 14 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose). The pre-dose sample was collected within 5 min prior to study medication administration. The first occurrence of the Cmax was determined directly from the raw concentration-time data.

  31. AUC (0-4) of GW630200 and GSK932009 at Day 1, 7 and 14 [ Time Frame: Day 1 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose), Day 7 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose) and Day 14 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose) ]
    GW630200 and GSK932009 are metabolites of GW642444H. Blood samples were collected on Day 1 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose), Day 7 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose) and Day 14 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose). The pre-dose sample was collected within 5 min prior to study medication administration. The AUC (0-4) was determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations.

  32. Cmax of GW630200 and GSK932009 at Day 1, 7 and 14 [ Time Frame: Day 1 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose), Day 7 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose) and Day 14 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose) ]
    GW630200 and GSK932009 are metabolites of GW642444H. Blood samples were collected on Day 1 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose), Day 7 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose) and Day 14 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose). The pre-dose sample was collected within 5 min prior to study medication administration. The first occurrence of the Cmax was determined directly from the raw concentration-time data.

  33. Time to Maximum Concentration (Tmax) of CCI2189, GW630200 and GSK932009 at Day 1, 7 and 14 [ Time Frame: Day 1 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose), Day 7 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose) and Day 14 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose) ]
    GW630200 and GSK932009 are metabolites of GW642444H. CCI2189 is a counterion of GW642444H. Blood samples were collected on Day 1 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose), Day 7 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose) and Day 14 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose). The pre-dose sample was collected within 5 min prior to study medication administration. The time at which Cmax was observed was determined directly from the raw concentration-time data.

  34. AUC (0-4) of Salmeterol at Day 1, 7 and 14 [ Time Frame: Day 1 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose), Day 7 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose) and Day 14 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose) ]
    Blood samples were collected on Day 1 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose), Day 7 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose) and Day 14 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose). The pre-dose sample was collected within 5 min prior to study medication administration. The AUC (0-4) was determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations.

  35. Cmax of Salmeterol at Day 1, 7 and 14 [ Time Frame: Day 1 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose), Day 7 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose) and Day 14 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose) ]
    Blood samples were collected on Day 1 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose), Day 7 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose) and Day 14 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose). The pre-dose sample was collected within 5 min prior to study medication administration. The first occurrence of the Cmax was determined directly from the raw concentration-time data.

  36. Tmax of Salmeterol at Day 1, 7 and 14 [ Time Frame: Day 1 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose), Day 7 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose) and Day 14 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose) ]
    Blood samples were collected on Day 1 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose), Day 7 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose) and Day 14 (pre-dose, 5 min, 1 h, 2 h and 4 h post-dose). The pre-dose sample was collected within 5 min prior to study medication administration. The time at which Cmax was observed was determined directly from the raw concentration-time data.



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.


Ages Eligible for Study:   40 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  • females must be of non-childbearing potential
  • moderately severe COPD

Exclusion criteria:

  • Subjects with a main diagnosis of asthma
  • subjects with poorly controlled COPD
  • subjects with significant heart, renal, endocrine, psychiatric, immunological or neurological disease.

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): NCT00372112


Locations
Australia, New South Wales
GSK Investigational Site
Camperdown, New South Wales, Australia, 2050
Australia, Western Australia
GSK Investigational Site
Nedlands, Western Australia, Australia, 6009
Bulgaria
GSK Investigational Site
Ruse, Bulgaria, 7000
GSK Investigational Site
Sofia, Bulgaria, 1431
GSK Investigational Site
Sofia, Bulgaria, 1606
Germany
GSK Investigational Site
Weinheim, Baden-Wuerttemberg, Germany, 69469
GSK Investigational Site
Hannover, Niedersachsen, Germany, 30159
GSK Investigational Site
Geesthacht, Schleswig-Holstein, Germany, 21502
Netherlands
GSK Investigational Site
Breda, Netherlands, 4819 EV
GSK Investigational Site
Hoorn, Netherlands, 1624 NP
New Zealand
GSK Investigational Site
Auckland, New Zealand, 1005
GSK Investigational Site
Tauranga, New Zealand
Romania
GSK Investigational Site
Bucharest, Romania, 050159
GSK Investigational Site
Iasi, Romania, 700506
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline

Additional Information:
Study Data/Documents: Individual Participant Data Set  This link exits the ClinicalTrials.gov site
Identifier: B2C108562
For additional information about this study please refer to the GSK Clinical Study Register
Study Protocol  This link exits the ClinicalTrials.gov site
Identifier: B2C108562
For additional information about this study please refer to the GSK Clinical Study Register
Dataset Specification  This link exits the ClinicalTrials.gov site
Identifier: B2C108562
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: B2C108562
For additional information about this study please refer to the GSK Clinical Study Register
Statistical Analysis Plan  This link exits the ClinicalTrials.gov site
Identifier: B2C108562
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: B2C108562
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: B2C108562
For additional information about this study please refer to the GSK Clinical Study Register

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00372112     History of Changes
Other Study ID Numbers: B2C108562
First Posted: September 6, 2006    Key Record Dates
Results First Posted: February 22, 2018
Last Update Posted: April 2, 2018
Last Verified: March 2018
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:
Chronic Obstructive Pulmonary Disease (COPD)
COPD

Additional relevant MeSH terms:
Lung Diseases
Lung Diseases, Obstructive
Pulmonary Disease, Chronic Obstructive
Chronic Disease
Respiratory Tract Diseases
Disease Attributes
Pathologic Processes
Salmeterol Xinafoate
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action