Study In Postmenopausal Women With Type 2 Diabetes Looking At Approved Diabetes Drugs And How They Affect Bone Health

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00679939
First received: May 15, 2008
Last updated: April 5, 2013
Last verified: April 2013
Results First Received: January 7, 2011  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Pharmacodynamics Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Condition: Diabetes Mellitus, Type 2
Interventions: Drug: Rosiglitazone
Drug: Metformin

  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
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Rosiglitazone in DB Period; Metformin in OL Period Rosiglitazone (RSG) initiated at a total daily dose of 4 milligrams (mg) in the 52-week DB Period. RSG could be uptitrated to a total daily dose of 8 mg at Week 4. At Week 52, all participants were switched to open-label (OL) Metformin (MET) therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.
Metformin in DB Period; Metformin in OL Period Metformin (MET) initiated at a total daily dose of 1000 mg in the 52-week DB Period. MET could be uptitrated to 1500 mg/day at Week 2 and to 2000 mg/day at Week 4. At Week 52, all participants were switched to open-label MET therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.

Participant Flow for 2 periods

Period 1:   52-Week Double-Blind (DB) Period
    Rosiglitazone in DB Period; Metformin in OL Period     Metformin in DB Period; Metformin in OL Period  
STARTED     114     112  
COMPLETED     77     85  
NOT COMPLETED     37     27  
Withdrew Consent                 17                 13  
Adverse Event                 14                 12  
Investigator Discretion                 5                 0  
Protocol Violation                 1                 0  
Lost to Follow-up                 0                 2  

Period 2:   24-Week Open-Label (OL) Period
    Rosiglitazone in DB Period; Metformin in OL Period     Metformin in DB Period; Metformin in OL Period  
STARTED     76 [1]   84 [1]
COMPLETED     69     80  
NOT COMPLETED     7     4  
Adverse Event                 0                 1  
Protocol Violation                 1                 1  
Met Stopping Criteria                 3                 1  
Physician Decision                 1                 0  
Withdrawal by Subject                 2                 1  
[1] One participant who completed the DB Period did not receive the OL dose of MET.



  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
Rosiglitazone in DB Period; Metformin in OL Period Rosiglitazone (RSG) initiated at a total daily dose of 4 milligrams (mg) in the 52-week DB Period. RSG could be uptitrated to a total daily dose of 8 mg at Week 4. At Week 52, all participants were switched to open-label (OL) Metformin (MET) therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.
Metformin in DB Period; Metformin in OL Period Metformin (MET) initiated at a total daily dose of 1000 mg in the 52-week DB Period. MET could be uptitrated to 1500 mg/day at Week 2 and to 2000 mg/day at Week 4. At Week 52, all participants were switched to open-label MET therapy for 24 weeks during the follow-up phase; all participants were force-titrated from 1000 mg/day to 2000 mg/day over a 4-week period. However, participants could be down-titrated to alleviate any MET-related tolerability issues.
Total Total of all reporting groups

Baseline Measures
    Rosiglitazone in DB Period; Metformin in OL Period     Metformin in DB Period; Metformin in OL Period     Total  
Number of Participants  
[units: participants]
  114     111     225  
Age [1]
[units: Years]
Mean ± Standard Deviation
     
Years     63.6  ± 6.61     64.0  ± 6.46     63.8  ± 6.52  
Gender [1]
[units: Participants]
     
Female     114     111     225  
Male     0     0     0  
Race/Ethnicity, Customized [1]
[units: participants]
     
White – White/Caucasian/European     82     78     160  
African American/African     2     8     10  
American Indian or Alaskan Native     6     5     11  
Asian - Central/South Asian     13     10     23  
South East Asian     4     6     10  
Mixed Race     3     2     5  
East Asia     4     2     6  
[1] Baseline Characteristics were summarized for all participants in the Safety Population, comprised of all randomized participants who received at least one dose of study medication. One participant in the Metformin arm did not receive study medication and was not included in the Safety Population.



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Adjusted Percent Change From Baseline in Femoral Neck (FN) Bone Mineral Density (BMD) Via Dual-energy X-ray Absorptiometry (DXA) at Week 52   [ Time Frame: Baseline and Week 52 ]

2.  Primary:   Adjusted Percent Change From Baseline in Femoral Neck (FN) Bone Mineral Density (BMD) Via Dual-energy X-ray Absorptiometry (DXA) at Week 76+10 Days   [ Time Frame: Baseline and Week 76+10 days ]

3.  Primary:   Adjusted Percent Change in Femoral Neck (FN) Bone Mineral Density (BMD) Via Dual-energy X-ray Absorptiometry (DXA) From Week 52 +10 Days to Week 76+10 Days   [ Time Frame: Week 52+10 days and Week 76+10 days ]

4.  Secondary:   Adjusted Percent Change From Baseline in Femoral Neck, Total Hip, Trochanter, and Lumbar Spine BMD Via DXA at Week 52   [ Time Frame: Baseline and Week 52 ]

5.  Secondary:   Adjusted Percent Change in Femoral Neck, Total Hip, Trochanter, and Lumbar Spine BMD Via DXA From Week 52+10 Days to Week 76 + 10 Days   [ Time Frame: Week 52 + 10 days and Week 76 + 10 days ]

6.  Secondary:   Adjusted Percent Change in Femoral Neck, Total Hip, Trochanter, and Lumbar Spine BMD Via DXA From Week 52+30 Days to Week 76 + 30 Days   [ Time Frame: Week 52 + 30 days and Week 76 + 30 days ]

7.  Secondary:   Adjusted Percent Change From Baseline in Bone Specific Alkaline Phosphatase (BSAP) and Procollagen Type 1 N-propeptide (P1NP) at Week 52 and Week 76   [ Time Frame: Baseline, Week 52, and Week 76 ]

8.  Secondary:   Adjusted Percent Change in Bone Specific Alkaline Phosphatase (BSAP) and Procollagen Type 1 N-propeptide (P1NP) From Week 52 to Week 76   [ Time Frame: Week 52 and Week 76 ]

9.  Secondary:   Adjusted Percent Change From Baseline in Carboxyterminal Cross-linked Telopeptide of Type 1 Collagen (CTX) at Week 52 and Week 76   [ Time Frame: Baseline, Week 52, and Week 76 ]

10.  Secondary:   Adjusted Percent Change in Carboxyterminal Cross-linked Telopeptide of Type 1 Collagen (CTX) From Week 52 to Week 76   [ Time Frame: Week 52 and Week 76 ]

11.  Secondary:   Adjusted Percent Change From Baseline in 25-Hydroxyvitamin D (Vitamin D) at Week 52 and Week 76   [ Time Frame: Baseline, Week 52, and Week 76 ]

12.  Secondary:   Adjusted Percent Change in 25-Hydroxyvitamin D (Vitamin D) From Week 52 to Week 76   [ Time Frame: Week 52 and Week 76 ]

13.  Secondary:   Adjusted Percent Change From Baseline in Intact Parathyroid Hormone (PTH) at Week 52 and Week 76   [ Time Frame: Baseline, Week 52, and Week 76 ]

14.  Secondary:   Adjusted Percent Change in Intact Parathyroid Hormone (PTH) From Week 52 to Week 76   [ Time Frame: Week 52 and Week 76 ]

15.  Secondary:   Percent Change From Baseline in Serum Estradiol at Week 52 and Week 76   [ Time Frame: Baseline, Week 52, and Week 76 ]

16.  Secondary:   Percent Change in Serum Estradiol From Week 52 to Week 76   [ Time Frame: Week 52 and Week 76 ]

17.  Secondary:   Percent Change From Baseline in Total Testosterone at Week 52 and Week 76   [ Time Frame: Baseline, Week 52, and Week 76 ]

18.  Secondary:   Percent Change in Total Testosterone From Week 52 to Week 76   [ Time Frame: Week 52 and Week 76 ]

19.  Secondary:   Percent Change From Baseline in Free Testosterone at Week 52 and Week 76   [ Time Frame: Baseline, Week 52, and Week 76 ]

20.  Secondary:   Percent Change in Free Testosterone From Week 52 to Week 76   [ Time Frame: Week 52 and Week 76 ]

21.  Secondary:   Percent Change From Baseline in Sex Hormone Binding Globulin (SHBG) at Week 52 and Week 76   [ Time Frame: Baseline, Week 52, and Week 76 ]

22.  Secondary:   Percent Change in Sex Hormone Binding Globulin (SHBG) From Week 52 to Week 76   [ Time Frame: Week 52 and Week 76 ]

23.  Post-Hoc:   Adjusted Percent Change From Baseline in Femoral Neck, Total Hip, Trochanter, and Lumbar Spine BMD Via DXA at Week 52 + 10 Days and Week 76 + 10 Days   [ Time Frame: Baseline, Week 52 + 10 days, and Week 76 + 10 days ]

24.  Post-Hoc:   Adjusted Percent Change From Baseline in Femoral Neck, Total Hip, Trochanter, and Lumbar Spine BMD Via DXA at Week 52 + 30 Days and Week 76 + 30 Days   [ Time Frame: Baseline, Week 52 + 30 days, and Week 76 + 30 days ]

25.  Post-Hoc:   Adjusted Percent Change From Baseline in Femoral Neck, Total Hip, Trochanter, and Intertrochanter Areal BMD Via Quantitative Computed Tomography (QCT) at Week 52 + 30 Days and Week 76 + 30 Days   [ Time Frame: Baseline, Week 52 + 30 days, and Week 76 + 30 days ]

26.  Post-Hoc:   Adjusted Percent Change in Femoral Neck, Total Hip, Trochanter, and Intertrochanter Areal BMD Via Quantitative Computed Tomography (QCT) From Week 52+30 Days to Week 76 + 30 Days   [ Time Frame: Week 52 + 30 days and Week 76 + 30 days ]

27.  Post-Hoc:   Adjusted Percent Change From Baseline in Total Hip (TH) Integral, TH Trabecular, and TH Cortical vBMD Via QCT at Week 52 + 30 Days and at Week 76 + 30 Days   [ Time Frame: Baseline, Week 52 + 30 days, and Week 76 + 30 days ]

28.  Post-Hoc:   Adjusted Percent Change in Total Hip (TH) Integral, TH Trabecular, and TH Cortical vBMD Via QCT From Week 52+30 Days to Week 76 + 30 Days   [ Time Frame: Week 52 + 30 days and Week 76 + 30 days ]

29.  Post-Hoc:   Adjusted Percent Change From Baseline in Femoral Neck (FN) Integral, FN Trabecular, and FN Cortical vBMD Via QCT at Week 52 + 30 Days and Week 76 + 30 Days   [ Time Frame: Baseline, Week 52 + 30 days, and Week 76 + 30 days ]

30.  Post-Hoc:   Adjusted Percent Change in Femoral Neck (FN) Integral, FN Trabecular, and FN Cortical vBMD Via QCT From Week 52+30 Days to Week 76 + 30 Days   [ Time Frame: Week 52 + 30 days and Week 76 + 30 days ]

31.  Post-Hoc:   Adjusted Percent Change From Baseline in Trochanter Integral, Trochanter Trabecular, and Trochanter Cortical vBMD Via QCT at Week 52 + 30 Days and Week 76 + 30 Days   [ Time Frame: Baseline, Week 52 + 30 days, and Week 76 + 30 days ]

32.  Post-Hoc:   Adjusted Percent Change in Trochanter Integral, Trochanter Trabecular, and Trochanter Cortical vBMD Via QCT From Week 52+30 Days to Week 76 + 30 Days   [ Time Frame: Week 52 + 30 days and Week 76 + 30 days ]

33.  Post-Hoc:   Adjusted Percent Change From Baseline in Intertrochanter Integral, Intertrochanter Trabecular, and Intertrochanter Cortical vBMD Via QCT at Week 52 + 30 Days and Week 76 + 30 Days   [ Time Frame: Baseline, Week 52 + 30 days, and Week 76 + 30 days ]

34.  Post-Hoc:   Adjusted Percent Change in Intertrochanter Integral, Intertrochanter Trabecular, and Intertrochanter Cortical vBMD Via QCT From Week 52+30 Days to Week 76 + 30 Days   [ Time Frame: Week 52 + 30 days and Week 76 + 30 days ]

35.  Post-Hoc:   Adjusted Percent Change From Baseline in Vertebral Trabecular vBMD Via QCT at Week 52 + 30 Days and Week 76 + 30 Days   [ Time Frame: Baseline, Week 52 + 30 days, and Week 76 + 30 days ]

36.  Post-Hoc:   Adjusted Percent Change in Vertebral Trabecular vBMD Via QCT From Week 52+30 Days to Week 76 + 30 Days   [ Time Frame: Week 52 + 30 days and Week 76 + 30 days ]

37.  Post-Hoc:   Adjusted Percent Change From Baseline in Femoral Neck (FN) Supero-posterior Integral, Trabecular, and Cortical vBMD Via QCT at Week 52 + 30 Days and Week 76 + 30 Days   [ Time Frame: Baseline, Week 52 + 30 days, and Week 76 + 30 days ]

38.  Post-Hoc:   Adjusted Change From Baseline in Femoral Neck (FN) Supero-posterior and Cortical vBMD Via QCT at Week 76 + 30 Days   [ Time Frame: Baseline and Week 76 + 30 days ]

39.  Post-Hoc:   Adjusted Percent Change in Femoral Neck (FN) Supero-posterior Integral, Trabecular, and Cortical vBMD Via QCT From Week 52+30 Days to Week 76 + 30 Days   [ Time Frame: Week 52 + 30 days and Week 76 + 30 days ]

40.  Post-Hoc:   Adjusted Change in Femoral Neck (FN) Supero-posterior Cortical vBMD Via QCT From Week 52 + 30 Days to Week 76 + 30 Days   [ Time Frame: Week 52 + 30 days and Week 76 + 30 days ]

41.  Post-Hoc:   Adjusted Percent Change From Baseline in Femoral Neck (FN) Supero-posterior Cortical Thickness Via QCT at Week 52 + 30 Days and Week 76 + 30 Days   [ Time Frame: Baseline, Week 52 + 30 days, and Week 76 + 30 days ]

42.  Post-Hoc:   Adjusted Change From Baseline in Femoral Neck (FN) Supero-posterior Cortical Thickness Via QCT at Week 76 + 30 Days   [ Time Frame: Baseline and Week 76 + 30 days ]

43.  Post-Hoc:   Adjusted Percent Change in Femoral Neck (FN) Supero-posterior Cortical Thickness Via QCT From Week 52+30 Days to Week 76 + 30 Days   [ Time Frame: Week 52 + 30 days and Week 76 + 30 days ]

44.  Post-Hoc:   Adjusted Change in Femoral Neck (FN) Supero-posterior Cortical Thickness Via QCT From Week 52 + 30 Days to Week 76 + 30 Days   [ Time Frame: Week 52 + 30 days and Week 76 + 30 days ]

45.  Post-Hoc:   Adjusted Percent Change From Baseline in Femoral Neck (FN) Supero-anterior Integral, Trabecular, and Cortical vBMD Via QCT at Week 52 + 30 Days and Week 76 + 30 Days   [ Time Frame: Baseline, Week 52 plus 30 days, and Week 76 + 30 days ]

46.  Post-Hoc:   Adjusted Change From Baseline in Femoral Neck (FN) Supero-anterior Cortical vBMD Via QCT at Week 76 + 30 Days   [ Time Frame: Baseline and Week 76 + 30 days ]

47.  Post-Hoc:   Adjusted Percent Change in Femoral Neck (FN) Supero-anterior Integral, Trabecular, and Cortical vBMD Via QCT From Week 52+30 Days to Week 76 + 30 Days   [ Time Frame: Week 52 + 30 days and Week 76 + 30 days ]

48.  Post-Hoc:   Adjusted Change in Femoral Neck (FN) Supero-anterior Cortical vBMD Via QCT From Week 52+30 Days to Week 76 + 30 Days   [ Time Frame: Week 52 + 30 days and Week 76 + 30 days ]

49.  Post-Hoc:   Adjusted Percent Change From Baseline in Femoral Neck (FN) Supero-anterior Cortical Thickness Via QCT at Week 52 + 30 Days and Week 76 + 30 Days   [ Time Frame: Baseline, Week 52 + 30 days, and Week 76 + 30 days ]

50.  Post-Hoc:   Adjusted Change From Baseline in Femoral Neck (FN) Supero-anterior Cortical Thickness Via QCT at Week 76 + 30 Days   [ Time Frame: Baseline and Week 76 + 30 days ]

51.  Post-Hoc:   Adjusted Percent Change in Femoral Neck (FN) Supero-anterior Cortical Thickness Via QCT From Week 52 + 30 Days to Week 76 + 30 Days   [ Time Frame: Week 52 + 30 days and Week 76 + 30 days ]

52.  Post-Hoc:   Adjusted Change in Femoral Neck (FN) Supero-anterior Cortical Thickness Via QCT From Week 52+30 Days to Week 76 + 30 Days   [ Time Frame: Week 52 + 30 days and Week 76 + 30 days ]

53.  Post-Hoc:   Adjusted Percent Change From Baseline in Femoral Neck (FN) Infero-posterior Integral, Trabecular, and Cortical vBMD Via QCT at Week 52 + 30 Days and Week 76 + 30 Days   [ Time Frame: Baseline, Week 52 + 30 days, and Week 76 + 30 days ]

54.  Post-Hoc:   Adjusted Change From Baseline in Femoral Neck (FN) Infero-posterior Cortical vBMD Via QCT at Week 76 + 30 Days   [ Time Frame: Baseline and Week 76 + 30 days ]

55.  Post-Hoc:   Adjusted Percent Change in Femoral Neck (FN) Infero-posterior Integral, Trabecular, and Cortical vBMD Via QCT From Week 52+30 Days to Week 76 + 30 Days   [ Time Frame: Week 52 + 30 days and Week 76 + 30 days ]

56.  Post-Hoc:   Adjusted Change in Femoral Neck (FN) Infero-posterior Cortical vBMD Via QCT From Week 52 + 30 Days to Week 76 + 30 Days   [ Time Frame: Week 52 + 30 days and Week 76 + 30 days ]

57.  Post-Hoc:   Adjusted Percent Change From Baseline in Femoral Neck (FN) Infero-posterior Cortical Thickness Via QCT at Week 52 + 30 Days and Week 76 + 30 Days   [ Time Frame: Baseline, Week 52 + 30 days, and Week 76 + 30 days ]

58.  Post-Hoc:   Adjusted Change From Baseline in Femoral Neck (FN) Infero-posterior Cortical Thickness Via QCT at Week 76 + 30 Days   [ Time Frame: Baseline and Week 76 + 30 days ]

59.  Post-Hoc:   Adjusted Percent Change in Femoral Neck (FN) Infero-posterior Cortical Thickness Via QCT From Week 52 + 30 Days to Week 76 + 30 Days   [ Time Frame: Week 52 + 30 days and Week 76 + 30 days ]

60.  Post-Hoc:   Adjusted Change in Femoral Neck (FN) Infero-posterior Cortical Thickness Via QCT From Week 52 + 30 Days to Week 76 + 30 Days   [ Time Frame: Week 52 + 30 days and Week 76 + 30 days ]

61.  Post-Hoc:   Adjusted Percent Change From Baseline in Femoral Neck (FN) Infero-anterior Integral, Trabecular, and Cortical vBMD Via QCT at Week 52 + 30 Days and Week 76 + 30 Days   [ Time Frame: Baseline, Week 52 + 30 days, and Week 76 + 30 days ]

62.  Post-Hoc:   Adjusted Change From Baseline in Femoral Neck (FN) Infero-anterior Cortical vBMD Via QCT at Week 76 + 30 Days   [ Time Frame: Baseline and Week 76 + 30 days ]

63.  Post-Hoc:   Adjusted Percent Change in Femoral Neck (FN) Infero-anterior Integral, Trabecular, and Cortical vBMD Via QCT From Week 52+30 Days to Week 76 + 30 Days   [ Time Frame: Week 52 + 30 days and Week 76 + 30 days ]

64.  Post-Hoc:   Adjusted Change in Femoral Neck (FN) Infero-anterior Cortical vBMD Via QCT From Week 52 + 30 Days to Week 76 + 30 Days   [ Time Frame: Week 52 + 30 days and Week 76 + 30 days ]

65.  Post-Hoc:   Adjusted Percent Change From Baseline in Femoral Neck (FN) Infero-anterior Cortical Thickness Via QCT at Week 52 + 30 Days and Week 76 + 30 Days   [ Time Frame: Baseline, Week 52 + 30 days, and Week 76 + 30 days ]

66.  Post-Hoc:   Adjusted Change From Baseline in Femoral Neck (FN) Infero-anterior Cortical Thickness Via QCT at Week 76 + 30 Days   [ Time Frame: Baseline and Week 76 + 30 days ]

67.  Post-Hoc:   Adjusted Percent Change in Femoral Neck (FN) Infero-anterior Cortical Thickness Via QCT From Week 52 + 30 Days to Week 76 + 30 Days   [ Time Frame: Week 52 + 30 days and Week 76 + 30 days ]

68.  Post-Hoc:   Adjusted Change in Femoral Neck (FN) Infero-anterior Cortical Thickness Via QCT From Week 52 + 30 Days to Week 76 + 30 Days   [ Time Frame: Week 52 + 30 days and Week 76 + 30 days ]

69.  Post-Hoc:   Adjusted Change From Baseline in Albumin-adjusted Serum Calcium (AASC) at Week 52 and Week 76   [ Time Frame: Baseline, Week 52, and Week 76 ]

70.  Post-Hoc:   Adjusted Change in Albumin-adjusted Serum Calcium (AASC) From Week 52 to Week 76   [ Time Frame: Week 52 and Week 76 ]

71.  Other Pre-specified:   Percent Change in Percentage of Free Estradiol From Week 52 to Week 76   [ Time Frame: Week 52 and Week 76 ]

72.  Other Pre-specified:   Percent Change in Free Estradiol From Week 52 to Week 76   [ Time Frame: Week 52 and Week 76 ]


  Serious Adverse Events


  Other Adverse Events


  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.


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


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Publications automatically indexed to this study:

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00679939     History of Changes
Other Study ID Numbers: AVD111179
Study First Received: May 15, 2008
Results First Received: January 7, 2011
Last Updated: April 5, 2013
Health Authority: Canada: Health Canada
United States: Food and Drug Administration