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Dose Ranging Pharmacokinetics and Pharmacodynamics Study With Mepolizumab in Asthma Patients With Elevated Eosinophils

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01366521
First received: May 12, 2011
Last updated: January 14, 2016
Last verified: November 2015
Results First Received: November 5, 2015  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Pharmacokinetics/Dynamics Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Asthma
Intervention: Biological: Mepolizumab

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Participants (par.) were on a stable dose of their current asthma medications for 12 weeks prior to screening. Par. who met the eligibility criteria at screening were randomized to one of the four possible treatment arms. Total duration of participation in the study was up to approximately 22 weeks including screening, dosing and follow-up.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
A total of 70 participants were enrolled into the study and 66 participants completed the study.

Reporting Groups
  Description
Mepolizumab 12.5 mg SC Participants received mepolizumab 12.5 milligrams (mg) administered subcutaneously (SC) (two injections of the same volume) once every 4 weeks (for a total of three doses on Day 1, Day 28 and Day 56). Maintenance asthma therapy was continued unchanged throughout the study, unless medically indicated.
Mepolizumab 125 mg SC Participants received mepolizumab 125 mg administered SC (two injections of the same volume) once every 4 weeks (for a total of three doses on Day 1, Day 28 and Day 56). Maintenance asthma therapy was continued unchanged throughout the study, unless medically indicated.
Mepolizumab 250 mg SC Participants received mepolizumab 250 mg administered SC (two injections of the same volume) once every 4 weeks (for a total of three doses on Day 1, Day 28 and Day 56). Maintenance asthma therapy was continued unchanged throughout the study, unless medically indicated.
Mepolizumab 75 mg IV Participants received mepolizumab 75 mg administered intravenously (IV) once every 4 weeks (for a total of three doses on Day 1, Day 28 and Day 56). Maintenance asthma therapy was continued unchanged throughout the study, unless medically indicated.

Participant Flow:   Overall Study
    Mepolizumab 12.5 mg SC   Mepolizumab 125 mg SC   Mepolizumab 250 mg SC   Mepolizumab 75 mg IV
STARTED   21   15   23   11 
COMPLETED   20   14   21   11 
NOT COMPLETED   1   1   2   0 
Adverse Event                1                0                0                0 
Protocol Violation                0                0                1                0 
Physician Decision                0                0                1                0 
Withdrawal by Subject                0                1                0                0 



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Mepolizumab 12.5 mg SC Participants received mepolizumab 12.5 milligrams (mg) administered subcutaneously (SC) (two injections of the same volume) once every 4 weeks (for a total of three doses on Day 1, Day 28 and Day 56). Maintenance asthma therapy was continued unchanged throughout the study, unless medically indicated.
Mepolizumab 125 mg SC Participants received mepolizumab 125 mg administered SC (two injections of the same volume) once every 4 weeks (for a total of three doses on Day 1, Day 28 and Day 56). Maintenance asthma therapy was continued unchanged throughout the study, unless medically indicated.
Mepolizumab 250 mg SC Participants received mepolizumab 250 mg administered SC (two injections of the same volume) once every 4 weeks (for a total of three doses on Day 1, Day 28 and Day 56). Maintenance asthma therapy was continued unchanged throughout the study, unless medically indicated.
Mepolizumab 75 mg IV Participants received mepolizumab 75 mg administered intravenously (IV) once every 4 weeks (for a total of three doses on Day 1, Day 28 and Day 56). Maintenance asthma therapy was continued unchanged throughout the study, unless medically indicated.
Total Total of all reporting groups

Baseline Measures
   Mepolizumab 12.5 mg SC   Mepolizumab 125 mg SC   Mepolizumab 250 mg SC   Mepolizumab 75 mg IV   Total 
Overall Participants Analyzed 
[Units: Participants]
 21   15   23   11   70 
Age 
[Units: Years]
Mean (Standard Deviation)
 43.1  (11.53)   37.0  (17.80)   43.9  (13.42)   44.8  (12.55)   42.3  (13.83) 
Gender 
[Units: Participants]
         
Female   13   5   14   5   37 
Male   8   10   9   6   33 
Race/Ethnicity, Customized 
[Units: Participants]
         
African American/African Heritage   1   0   1   0   2 
Asian-South East Asian Heritage   0   1   1   0   2 
White-White/Caucasian/European Heritage   20   14   21   11   66 


  Outcome Measures
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1.  Primary:   Change From Baseline in Blood Eosinophil Levels at Week 12 (Day 84)   [ Time Frame: Baseline (Day 1 pre-dose) and Week 12 ]

2.  Primary:   Area Under the Blood Eosinophil Time Curve (AUEC) up to Day 84   [ Time Frame: Days 1, 3, 7, 28, 56, 70 and 84 ]

3.  Primary:   Maximum Change From Baseline in Blood Eosinophils (Emax)   [ Time Frame: Days 1, 3, 7, 28, 56, 70, 84, 112 and 140 ]

4.  Primary:   Time to Maximum Change in Blood Eosinophils Levels (Tmaxeos)   [ Time Frame: Days 1, 3, 7, 28, 56, 70, 84, 112 and 140 ]

5.  Primary:   Number of Participants Who Achieved >=50% Eosinophil Repletion by Day 140   [ Time Frame: Days 1, 3, 7, 28, 56, 70, 84, 112 and 140 ]

6.  Primary:   Mean Area Under the Plasma-concentration Time Curve (AUC) Following SC and IV Administration of Mepolizumab   [ Time Frame: Days 1, 3, 7, 28, 56, 70, 84, 112 and 140 ]

7.  Primary:   Maximum Plasma Concentration (Cmax) From Pre-dose (Day 1) to Day 140 for Mepolizumab   [ Time Frame: Days 1, 3, 7, 28, 56, 70, 84, 112 and 140 ]

8.  Primary:   Time to Maximum Plasma Concentration (Tmax) From Pre-dose (Day 1) to Day 140 for Mepolizumab   [ Time Frame: Days 1, 3, 7, 28, 56, 70, 84, 112 and 140 ]

9.  Primary:   Terminal Half-life (t½) From Pre-dose (Day 1) to Day 140 for Mepolizumab   [ Time Frame: Days 1, 3, 7, 28, 56, 70, 84, 112 and 140 ]

10.  Secondary:   Number of Participants With Clinical Chemistry Parameters Outside the Normal Range Following Treatment   [ Time Frame: Baseline (Day 1 pre-dose), Weeks 4, 8, 12 and 20 ]

11.  Secondary:   Number of Participants With Hematology Laboratory Parameters Outside the Normal Range at Following Treatment   [ Time Frame: Days 1, 3, 7, 28, 56, 70, 84, 112 and 140 (follow-up visit) ]

12.  Secondary:   Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure Assessed at Baseline, Day 1, Day 28, Day 56, Day 84, Day 112 and Day 140   [ Time Frame: Baseline (Day 1 pre-dose) and at Day 1, Day 28, Day 56, Day 84, Day 112 and Day 140 ]

13.  Secondary:   Change From Baseline in Heart Rate Assessed at Baseline, Day 1, Day 28, Day 56, Day 84, Day 112 and Day 140   [ Time Frame: Baseline (Day 1 pre-dose) and at Day 1, Day 28, Day 56, Day 84, Day 112 and Day 140 ]

14.  Secondary:   Number of Participants With Levels of Anti-mepolizumab Antibodies at Indicated Time Points   [ Time Frame: Day 1, Day 112 and Day 140 ]

15.  Secondary:   Number of Participants With the Indicated Electrocardiogram (ECG) Findings at Screening and Day 3   [ Time Frame: Screening (SCR) and at Day 3 ]

16.  Secondary:   Mean AUC to Assess the Absolute Bioavailability of SC Mepolizumab   [ Time Frame: Days 1, 3, 7, 28, 56, 70, 84, 112 and 140 ]

17.  Secondary:   Mean Dose Normalized Cmax Ratio to Assess the Relative Bioavailability of SC Mepolizumab as Compared With IV Mepolizumab   [ Time Frame: Days 1, 3, 7, 28, 56, 70, 84, 112 and 140 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: GSK Response Center
Organization: GlaxoSmithKline
phone: 866-435-7343



Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01366521     History of Changes
Other Study ID Numbers: 114092
Study First Received: May 12, 2011
Results First Received: November 5, 2015
Last Updated: January 14, 2016
Health Authority: Estonia: State Agency of Medicines
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
United States: Food and Drug Administration
Germany: Pau-Ehrlich Institute