Pharmacokinetics/Pharmacodynamics of Albiglutide

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01357889
First received: May 19, 2011
Last updated: May 29, 2014
Last verified: April 2014
Results First Received: April 24, 2014  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Pharmacokinetics/Dynamics Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Condition: Diabetes Mellitus, Type 2
Intervention: Biological: albiglutide (GSK716155)

  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
The enrollment number reflects the 283 participants starting the Multiple-dose Phase.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
This study was comprised of a Screening Period (up to 2 weeks), a Run-in Period (4 weeks), a Treatment Period (TP: 17 weeks), and a Follow-up (8 weeks) Period. The TP had a Single-dose Phase (Bioequivalence [BE] Phase: 28 days) and a 12-week Multiple-dose Phase. In the BE Phase, 186 participants were randomized; 167 received >=1 treatment dose.

Reporting Groups
  Description
Albiglutide Process 2 During the BE Phase, participants received a single dose of albiglutide 30 milligrams (mg) from the Process 2 drug product, injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen. After completing the BE phase, participants progressed into the Multiple-dose Phase of the study, beginning at Week 5, during which participants received 12 weekly injections of albiglutide 30 mg from the Process 2 drug product, injected subcutaneously into the abdomen, alternating between the right and left sides of the body, using a fixed-dose, prefilled, single-use injector pen. Additional participants (other than those completing the BE Phase and progressing to the Multiple-dose Phase) were randomized into the Multiple-dose Phase of the study. All participants returned for the 8-week post-treatment follow-up visit.
Albiglutide Process 3 During the BE Phase, participants received a single dose of albiglutide 30 mg from the Process 3 drug product, injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen. After completing the BE phase, participants progressed into the Multiple-dose Phase of the study, beginning at Week 5, during which participants received 12 weekly injections of albiglutide 30 mg from the Process 3 drug product, injected subcutaneously into the abdomen, alternating between the right and left sides of the body, using a fixed-dose, prefilled, single-use injector pen. Additional participants (other than those completing the BE Phase and progressing to the Multiple-dose Phase) were randomized into the Multiple-dose Phase of the study. All participants returned for the 8-week post-treatment follow-up visit.

Participant Flow for 3 periods

Period 1:   Single-dose Phase (BE Phase: 28 Days)
    Albiglutide Process 2     Albiglutide Process 3  
STARTED     86     81  
COMPLETED     82     79  
NOT COMPLETED     4     2  
Withdrawal by Subject                 2                 1  
Persistent Hyperglycemia                 1                 1  
Physician Decision                 1                 0  

Period 2:   Multiple-dose Phase (MDP) (Overall)
    Albiglutide Process 2     Albiglutide Process 3  
STARTED     141 [1]   142 [1]
COMPLETED     125     126  
NOT COMPLETED     16     16  
Adverse Event                 2                 2  
Noncompliance                 0                 2  
Lost to Follow-up                 0                 2  
Withdrawal by Subject                 5                 2  
Physician Decision                 2                 1  
Withdrawn Due to Hyperglycemia                 7                 7  
[1] After completion of the BE Phase, additional participants were randomized to the Overall Phase.

Period 3:   Follow-up Phase (FUP) (8 Weeks)
    Albiglutide Process 2     Albiglutide Process 3  
STARTED     141 [1]   142 [1]
COMPLETED     138     138  
NOT COMPLETED     3     4  
Noncompliance                 1                 0  
Lost to Follow-up                 0                 4  
Withdrawal by Subject                 1                 0  
Hyperglycemia                 1                 0  
[1] All participants who started the MDP entered the FUP, regardless of MDP completion status.



  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
Albiglutide Process 2 During the BE Phase, participants received a single dose of albiglutide 30 mg from the Process 2 drug product, injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen. After completing the BE phase, participants progressed into the Multiple-dose Phase of the study, beginning at Week 5, during which participants received 12 weekly injections of albiglutide 30 mg from the Process 2 drug product, injected subcutaneously into the abdomen, alternating between the right and left sides of the body, using a fixed-dose, prefilled, single-use injector pen. Additional participants (other than those completing the BE Phase and progressing to the Multiple-dose Phase) were randomized into the Multiple-dose Phase of the study. All participants returned for the 8-week post-treatment follow-up visit.
Albiglutide Process 3 During the BE Phase, participants received a single dose of albiglutide 30 mg from the Process 3 drug product, injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen. After completing the BE phase, participants progressed into the Multiple-dose Phase of the study, beginning at Week 5, during which participants received 12 weekly injections of albiglutide 30 mg from the Process 3 drug product, injected subcutaneously into the abdomen, alternating between the right and left sides of the body, using a fixed-dose, prefilled, single-use injector pen. Additional participants (other than those completing the BE Phase and progressing to the Multiple-dose Phase) were randomized into the Multiple-dose Phase of the study. All participants returned for the 8-week post-treatment follow-up visit.
Total Total of all reporting groups

Baseline Measures
    Albiglutide Process 2     Albiglutide Process 3     Total  
Number of Participants  
[units: participants]
  141     142     283  
Age [1]
[units: Years]
Mean ± Standard Deviation
  52.6  ± 11.18     54.4  ± 10.53     53.5  ± 10.88  
Gender [1]
[units: Participants]
     
Female     78     76     154  
Male     63     66     129  
Race/Ethnicity, Customized [1]
[units: Participants]
     
African American/African Heritage     15     20     35  
American Indian or Alaskan Native     0     1     1  
Asian - Central/South Asian Heritage     2     0     2  
Asian - East Asian Heritage     1     2     3  
Asian - South East Asian Heritage     3     1     4  
Native Hawaiian or Other Pacific Islander     0     1     1  
White - White/Caucasian/European Heritage     120     117     237  
[1] Baseline data are reported for participants randomized to the Single- and Multiple-dose Phases (Overall).



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Area Under the Plasma Concentration Versus Time Curve (AUC) From Time Zero to Infinity (0-inf) of Albiglutide in the Bioequivalence (BE) Phase   [ Time Frame: Pre-dose at Baseline; 24 hours (hr), 48 hr, 96 hr, 216 hr, 312 hr, 480 hr, and 672 hr post-dose ]

2.  Primary:   Maximum Observed Plasma Concentration (Cmax) of Albiglutide in the BE Phase   [ Time Frame: Pre-dose at Baseline; 24 hr, 48 hr, 96 hr, 216 hr, 312 hr, 480 hr, and 672 hr post-dose ]

3.  Secondary:   Trough (Pre-dose) Plasma Concentrations of Albiglutide in the Mutiple-dose Phase (MDP)   [ Time Frame: Immediately pre-dose at Week 5, Week 9, Week 13, Week 17 (End of Treatment [EOT]), and Week 25 (Follow-up) ]

4.  Secondary:   Number of Participants With Anti-albiglutide Antibody Formation at Baseline and Weeks 5, 9, 13, 17, and 25 in the Multiple-dose Phase   [ Time Frame: Baseline, Week 5, Week 9, Week 13, Week 17, and Week 25 (Follow-up) ]

5.  Secondary:   AUC (0-last) and AUC (0-inf) of Albiglutide in the BE Phase   [ Time Frame: Pre-dose at Baseline; 24 hr, 48 hr, 96 hr, 216 hr, 312 hr, 480 hr, and 672 hr post-dose ]

6.  Secondary:   Tmax and Tlag of Albiglutide in the BE Phase   [ Time Frame: Pre-dose at Baseline; 24 hr, 48 hr, 96 hr, 216 hr, 312 hr, 480 hr, and 672 hr post-dose ]

7.  Secondary:   Cmax of Albiglutide in the BE Phase   [ Time Frame: Pre-dose at Baseline; 24 hr, 48 hr, 96 hr, 216 hr, 312 hr, 480 hr, and 672 hr post-dose ]

8.  Secondary:   t1/2 of Albiglutide in the BE Phase   [ Time Frame: Pre-dose at Baseline; 24 hr, 48 hr, 96 hr, 216 hr, 312 hr, 480 hr, and 672 hr post-dose ]

9.  Secondary:   Apparent Clearance of Albiglutide in the BE Phase   [ Time Frame: Pre-dose at Baseline; 24 hr, 48 hr, 96 hr, 216 hr, 312 hr, 480 hr, and 672 hr post-dose ]

10.  Secondary:   Apparent Volume of Distribution in the Terminal Phase of Albiglutide in BE Phase   [ Time Frame: Pre-dose at Baseline; 24 hr, 48 hr, 96 hr, 216 hr, 312 hr, 480 hr, and 672 hr post-dose ]

11.  Secondary:   Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 17   [ Time Frame: Baseline and Week 17 ]

12.  Secondary:   Change From Baseline in Fasting Plasma Glucose (FPG) at Week 17   [ Time Frame: Baseline and Week 17 ]

13.  Secondary:   Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE)   [ Time Frame: From the time the participant consented to participate in the study through Visit 28 (Week 25) or the final follow-up visit, for participants who discontinued active participation in the study ]

14.  Secondary:   Number of Participants With Indicated Adverse Events of Special Interest   [ Time Frame: From the time the participant consented to participate in the study through Visit 28 (Week 25) or the final follow-up visit, for participants who discontinue active participation in the study ]

15.  Secondary:   Number of Participants With a Change From Baseline of Clinical Concern in Hematology Values by Any On-therapy Visit   [ Time Frame: Week 1 through Week 25 ]
  Hide Outcome Measure 15

Measure Type Secondary
Measure Title Number of Participants With a Change From Baseline of Clinical Concern in Hematology Values by Any On-therapy Visit
Measure Description Criteria for values of potential concern were determined by the medical monitors. For hematocrit, a >0.1 decrease from Baseline was considered to be of clinical concern. For hemoglobin, a >25 grams per liter (g/L) decrease from Baseline was considered to be of clinical concern.
Time Frame Week 1 through Week 25  
Safety Issue No  

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.
Safety Population. Only those participants available at the specified time points were analyzed.

Reporting Groups
  Description
Albiglutide Process 2 During the BE Phase, participants received a single dose of albiglutide 30 mg from the Process 2 drug product, injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen. After completing the BE phase, participants progressed into the Multiple-dose Phase of the study, beginning at Week 5, during which participants received 12 weekly injections of albiglutide 30 mg from the Process 2 drug product, injected subcutaneously into the abdomen, alternating between the right and left sides of the body, using a fixed-dose, prefilled, single-use injector pen. Additional participants (other than those completing the BE Phase and progressing to the Multiple-dose Phase) were randomized into the Multiple-dose Phase of the study. All participants returned for the 8-week post-treatment follow-up visit.
Albiglutide Process 3 During the BE Phase, participants received a single dose of albiglutide 30 mg from the Process 3 drug product, injected subcutaneously into the abdomen using a fixed-dose, prefilled, single-use injector pen. After completing the BE phase, participants progressed into the Multiple-dose Phase of the study, beginning at Week 5, during which participants received 12 weekly injections of albiglutide 30 mg from the Process 3 drug product, injected subcutaneously into the abdomen, alternating between the right and left sides of the body, using a fixed-dose, prefilled, single-use injector pen. Additional participants (other than those completing the BE Phase and progressing to the Multiple-dose Phase) were randomized into the Multiple-dose Phase of the study. All participants returned for the 8-week post-treatment follow-up visit.

Measured Values
    Albiglutide Process 2     Albiglutide Process 3  
Number of Participants Analyzed  
[units: participants]
  140     140  
Number of Participants With a Change From Baseline of Clinical Concern in Hematology Values by Any On-therapy Visit  
[units: Participants]
   
Hematocrit >0.1 decrease     1     0  
Hemoglobin >25 g/L     1     1  

No statistical analysis provided for Number of Participants With a Change From Baseline of Clinical Concern in Hematology Values by Any On-therapy Visit



16.  Secondary:   Number of Participants With a Change From Baseline of Clinical Concern in Vital Signs by Any On-therapy Visit   [ Time Frame: Week 1 through Week 25 ]

17.  Secondary:   Number of Participants With the Indicated Change From the Screening Assessment in Physical Examination at Week 17   [ Time Frame: Screening and Week 17 ]

18.  Secondary:   Number of Participants With a Change From Baseline of Clinical Concern in Electrocardiogram (ECG) Values by Any On-therapy Visit   [ Time Frame: Week 1 through Week 25 ]


  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


No publications provided


Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01357889     History of Changes
Other Study ID Numbers: 114856
Study First Received: May 19, 2011
Results First Received: April 24, 2014
Last Updated: May 29, 2014
Health Authority: United States: Food and Drug Administration