Effect of Albiglutide, When Added to Standard Blood Glucose Lowering Therapies, on Major Cardiovascular Events in Subjects With Type 2 Diabetes Mellitus

Sponsor
GlaxoSmithKline (Industry)
Overall Status
Completed
CT.gov ID
NCT02465515
Collaborator
Duke Clinical Research Institute (Other)
9,463
608
2
32.4
15.6
0.5

Study Details

Study Description

Brief Summary

Albiglutide is an analogue of glucagon-like peptide-1 (GLP-1), used to treat type 2 diabetes This study will test whether albiglutide affects the occurrence of major cardiovascular events such as heart attacks or strokes and other important medical outcomes in persons with type 2 diabetes, when used alone or added to other diabetes treatments.

Condition or Disease Intervention/Treatment Phase
  • Biological: Albiglutide 30 mg
  • Biological: Albiglutide 50 mg
  • Biological: Albiglutide matching placebo
Phase 4

Study Design

Study Type:
Interventional
Actual Enrollment :
9463 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Long Term, Randomised, Double Blind, Placebo-controlled Study to Determine the Effect of Albiglutide, When Added to Standard Blood Glucose Lowering Therapies, on Major Cardiovascular Events in Patients With Type 2 Diabetes Mellitus
Actual Study Start Date :
Jul 1, 2015
Actual Primary Completion Date :
Feb 20, 2018
Actual Study Completion Date :
Mar 14, 2018

Arms and Interventions

Arm Intervention/Treatment
Experimental: Albiglutide

Albiglutide once weekly by subcutaneous injection. Starting dose 30 mg may be increased to 50 mg if needed. Albiglutide will be administered in addition to standard therapy for diabetes and cardiovascular health.

Biological: Albiglutide 30 mg
Once weekly subcutaneous injection. Starting dose 30 mg may be increased to 50 mg if needed.

Biological: Albiglutide 50 mg
Once weekly subcutaneous injection. Starting dose 30 mg may be increased to 50 mg if needed.

Placebo Comparator: Placebo

Placebo once weekly by subcutaneous injection. Placebo will be administered in addition to standard therapy for diabetes and cardiovascular health.

Biological: Albiglutide matching placebo
Once weekly subcutaneous injection. Matched to 30 mg and 50 mg albiglutide.

Outcome Measures

Primary Outcome Measures

  1. Time to First Occurrence of Major Adverse Cardiovascular Events (MACE) During Cardiovascular (CV) Follow-up Time Period [Median of 1.65 person years for CV follow-up time period]

    Time to MACE defined as the time to first occurrence of Cardiovascular Endpoint Committee (CEC)-adjudicated MACE (CV death, myocardial infarction [MI] or stroke) was analyzed using a Cox Proportional Hazards regression model with treatment group as the only covariate. The incidence rate per 100 person years (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% confidence interval. First event person-years=(cumulative total time to first event for participants who have the event+cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period. The analysis was performed on the Intent to Treat (ITT) Population which comprised of all randomized participants excluding participants who did not provide consent.

Secondary Outcome Measures

  1. Time to First Occurrence of MACE or Urgent Revascularization for Unstable Angina [Median of 1.65 person years for CV follow-up time period]

    Time to first occurrence of CEC-adjudicated MACE (CV death, MI or stroke) or urgent revascularization for unstable angina was analyzed using a Cox Proportional Hazards regression model with treatment group as the only covariate. The incidence rate per 100 person years (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% confidence interval. First event person-years=(cumulative total time to first event for participants who have the event+cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period.

  2. Time to Adjudicated CV Death [Median of 1.65 person years for the CV follow-up time period]

    Time to adjudicated CV death was analyzed using a Cox Proportional Hazards regression model with treatment group as the only covariate. The incidence rate per 100 person years (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% confidence interval. First event person-years=(cumulative total time to first event for participants who have the event+cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period.

  3. Time to First Occurrence of Adjudicated MI [Median of 1.65 person years for CV follow-up time period]

    Time to first occurrence of adjudicated MI was analyzed using a Cox Proportional Hazards regression model with treatment group as the only covariate. The incidence rate per 100 person years (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% confidence interval. First event person-years=(cumulative total time to first event for participants who have the event+cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period.

  4. Time to First Occurrence of Adjudicated Stroke [Median of 1.65 person years for CV follow-up time period]

    Time to first occurrence of adjudicated stroke was analyzed using a Cox Proportional Hazards regression model with treatment group as the only covariate. The incidence rate per 100 person years (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% confidence interval. First event person-years=(cumulative total time to first event for participants who have the event+cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period.

  5. Time to First Occurrence of Adjudicated CV Death or Hospitalization for Heart Failure (HF) [Median of 1.65 person years for CV follow-up time period]

    Time to first occurrence of adjudicated CV death or hospitalization for HF was analyzed using a Cox Proportional Hazards regression model with treatment group as the only covariate. The incidence rate per 100 person years (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% confidence interval. First event person-years=(cumulative total time to first event for participants who have the event+cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period.

  6. Time to Initiation of Insulin of More Than 3 Months Duration for Those Participants Not Treated With Insulin at Study Start [Up to 2.7 years]

    Time to initiation of insulin of more than 3 months duration in participants not treated with insulin at study start was analyzed using a Cox Proportional Hazards regression model with treatment group as the only covariate. The incidence rate per 100 person years (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% confidence interval. First event person-years=(cumulative total time to first event for participants who have the event+cumulative total of censored time for participants without the event)/365.25, based on the on-therapy and post-therapy AE time period. The analysis was performed on Non-Insulin Population which comprised of participants in the ITT Population who were not on insulin at Baseline.

  7. Time to Initiation of Prandial Insulin in Those Participants on Basal Insulin at Study Start [Up to 2.7 years]

    Time to initiation of prandial insulin in those participants on basal insulin at study start was analyzed using a Cox Proportional Hazards regression model with treatment group as the only covariate. The incidence rate per 100 person years (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% confidence interval. First event person-years=(cumulative total time to first event for participants who have the event+cumulative total of censored time for participants without the event)/365.25, based on the on-therapy and post-therapy AE time period. The analysis was performed on Basal Insulin Population which comprised of participants in the ITT Population who were on basal insulin but not on other insulin at Baseline (i.e., will not include a participant on a mixed insulin or on a prandial-only insulin).

  8. Percentage of Participants Achieving Composite Metabolic Endpoint [Months 8, 16, 24 and final assessment (up to 2.7 years)]

    Percentage of participants achieving composite metabolic endpoint defined as the percentage of participants achieving glycemic control (glycated hemoglobin [HbA1c] <=7% ) with no severe hypoglycemic incidents and weight gain < 5%. Final Assessment is the latest post-Baseline assessment of both HbA1c and weight.

  9. Time to First Occurrence of a Clinically Important Microvascular Event [Up to 2.7 years]

    Clinically important microvascular events were defined as the following: need for renal transplant or dialysis, new diabetes-related blindness, and procedures (laser photocoagulation or anti-vascular endothelial growth factor treatment or vitrectomy for diabetic retinopathy/eye disease). Time to first occurrence of a clinically important microvascular event was analyzed using a Cox Proportional Hazards regression model with treatment group as the only covariate. The incidence rate per 100 person years (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% confidence interval. First event person-years=(cumulative total time to first event for participants who have the event+cumulative total of censored time for participants without the event)/365.25, based on the on-therapy and post-therapy AE time period.

  10. Change From Baseline in HbA1c [Baseline and Months 8 and 16]

    Change from Baseline in HbA1c was analyzed using mixed model repeated measures (MMRM) including observed case data (does not impute any missing data). Baseline is the last non-missing value assessed on or before treatment start date. Change from Baseline is the value at specified time point minus the Baseline value. Change from Baseline in HbA1c using Baseline data from Local or Central Laboratory, and post-Baseline Central Laboratory data is presented.

  11. Change From Baseline in Body Weight [Baseline and Months 8 and 16]

    Change from Baseline in body weight was analyzed using mixed model repeated measures including observed case data (does not impute any missing data). Baseline is the last non-missing value assessed on or before treatment start date. Change from Baseline is the value at specified time point minus the Baseline value.

  12. Change From Baseline in Treatment Related Impact Measures-Diabetes (TRIM-D) Total Score [Baseline and Months 8 and 16]

    The TRIM-D is a 28 item treatment satisfaction measure with 5 domains assessing Treatment Burden, Daily Life, Diabetes Management, Compliance and Psychological Health. The raw score ranges for each subscale were: treatment burden (6 to 30), daily life (5 to 25), diabetes management (5 to 25), compliance (4 to 20) and psychological health (8 to 40), higher scores indicating better health state. Total raw score was determined by summing the raw scores for each of the subscales and the total score (transformed) was determined as [(raw score minus lowest possible raw score)/possible raw score range] x100. The possible total (transformed) score range is 0-100, where higher scores indicated better health state. Baseline is the last non-missing value assessed on or before treatment start date. Change from Baseline is the value at specified time point minus the Baseline value.

  13. Change From Baseline in EuroQol- 5 Dimension (EQ-5D) Visual Analogue Scale (VAS) Score [Baseline and Months 8 and 16]

    The EQ-5D is a standardized instrument used to evaluate generic health-related quality of life, comprising 5 domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. It provides a simple descriptive profile and a single index value for health status. The EQ-5D self-reported questionnaire includes a visual analog scale (VAS), which records the respondent's self-rated health status on a graduated (0-100) scale, where 0 represents the worst imaginable health state and 100 represents the best imaginable health state. Baseline is the last non-missing value assessed on or before treatment start date. Change from Baseline is the value at specified time point minus the Baseline value.

  14. Time to Death [Median of 1.73 years for the Vital Status follow-up time period]

    Time to death was analyzed using a Cox Proportional Hazards regression model with treatment group as the only covariate. The incidence rate per 100 person years (100*number of participants who died/endpoint person-years) is presented along with 95% confidence interval. Endpoint person-years=(cumulative total time to event for participants who have the event+cumulative total of censored time for participants without the event)/365.25, based on the Vital Status follow-up time period.

  15. Number of Participants With Non-fatal Serious Adverse Events (SAEs) [Up to 2.7 years]

    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; is a congenital anomaly/birth defect; other important medical events that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed before; is associated with liver injury and impaired liver function. Number of participants with on-therapy non-fatal SAEs are presented. Safety Population comprised of all randomized participants who received at least one dose of study treatment.

  16. Number of Participants With Adverse Events (AEs) Leading to Discontinuation of Investigational Product (AELD) [Up to 2.7 years]

    The number of participants with on-therapy AEs leading to discontinuation of investigational product is reported.

  17. Number of Participants With AEs of Special Interest [Up to 2.7 years]

    The protocol defined AEs of special interest included: development of thyroid cancer; hematologic malignancy; pancreatic cancer; pancreatitis (investigator reported and pancreatitis positively adjudicated by the Pancreatic Adjudication Committee [PAC]); investigational product injection site reactions; immunological reactions; severe hypoglycemic events; hepatic events; hepatic enzyme elevations (including gamma glutamyl transferase [GGT]); serious gastrointestinal (GI) events; appendicitis; atrial fibrillation/flutter; pneumonia; worsening renal function and diabetic retinopathy. The number of participants with on-therapy AEs of special interest is reported.

  18. Change in Estimated Glomerular Filtration Rate (eGFR) Calculated Using Modification of Diet in Renal Disease (MDRD) Formula [Baseline and Months 8 and 16]

    Blood samples were collected for the measurement of serum creatinine. Serum creatinine values were used to calculate eGFR using the MDRD formula, eGFR=175 x (serum creatinine)^-1.154 x (Age)^-0.203 x (0.742 if female) x (1.212 if African American). Baseline is the last non-missing value assessed on or before treatment start date. Change from Baseline is the value at specified time point minus the Baseline value. Change from Baseline in eGFR using Baseline data from Local or Central Laboratory, and post-Baseline Central Laboratory data for the on-treatment time period is presented.

  19. Change From Baseline in Blood Pressure [Baseline and Months 8,16,24 and end of study (up to 2.7 years)]

    Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were taken with the participant in a semi-recumbent or seated position after at least a 5-minute rest period. Baseline is the last non-missing value assessed on or before treatment start date. Change from Baseline is the value at specified time point minus the Baseline value.

  20. Change From Baseline in Heart Rate [Baseline and Months 8, 16, 24 and end of study (up to 2.7 years)]

    Heart rate was measured with the participant in a semi-recumbent or seated position after at least a 5-minute rest period. Baseline is the last non-missing value assessed on or before treatment start date. Change from Baseline is the value at specified time point minus the Baseline value.

Eligibility Criteria

Criteria

Ages Eligible for Study:
40 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
  • Men or women at least 40 years old. Women must be post-menopausal or using a highly effective method for avoidance of pregnancy.

  • Diagnosis of type 2 diabetes.

  • Established cardiovascular disease with at least one of the following: coronary artery disease, cerebrovascular disease, or peripheral arterial disease.

  • HbA1c >7.0% (53 mmol/mol) (based on the most recent documented laboratory measurement within 6 months).

  • Able and willing to provide informed consent.

Exclusion Criteria:
  • Severely reduced kidney function: eGFR <30 ml/min/1.73 m^2 (based on the last measured and documented laboratory measurement within 6 months) or renal replacement therapy.

  • Use of a GLP-1 receptor agonist at Screening.

  • Severe gastroparesis

  • History of pancreatitis or considered clinically at significant risk of developing pancreatitis during the course of the study.

  • Personal or family history of medullary carcinoma of the thyroid or subject with multiple endocrine neoplasia type 2 (MEN-2). Personal history of pancreatic neuroendocrine tumours.

  • Medical history which might limit the subject's ability to take trial treatments for the duration of the study or to otherwise complete the study.

  • Breastfeeding, pregnancy, or planning a pregnancy during the course of the study. Note: a pregnancy test will be performed on all women of child bearing potential prior to study entry.

  • Known allergy to any GLP-1 receptor agonist or excipients of albiglutide.

  • Use of another investigational product within 30 days or according to local regulations, or currently enrolled in a study of an investigational device.

  • Any other reason the investigator deems the subject to be unsuitable for the study.

Contacts and Locations

Locations

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260 GSK Investigational Site Freiburg Baden-Wuerttemberg Germany 79106
261 GSK Investigational Site Gueglingen Baden-Wuerttemberg Germany 74363
262 GSK Investigational Site Karlsruhe Baden-Wuerttemberg Germany 76199
263 GSK Investigational Site Ludwigsburg Baden-Wuerttemberg Germany 71640
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266 GSK Investigational Site Villingen-Schwenningen Baden-Wuerttemberg Germany 78048
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268 GSK Investigational Site Aschaffenburg Bayern Germany 63739
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277 GSK Investigational Site Floersheim Hessen Germany 65439
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280 GSK Investigational Site Stuhr Niedersachsen Germany 28816
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285 GSK Investigational Site Essen Nordrhein-Westfalen Germany 45136
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292 GSK Investigational Site Bad Kreuznach Rheinland-Pfalz Germany 55545
293 GSK Investigational Site Ludwigshafen am Rhein Rheinland-Pfalz Germany 67059
294 GSK Investigational Site Mainz Rheinland-Pfalz Germany 55116
295 GSK Investigational Site Sankt Ingbert Saarland Germany 66386
296 GSK Investigational Site Hohenmoelsen Sachsen-Anhalt Germany 06679
297 GSK Investigational Site Jerichow Sachsen-Anhalt Germany 39319
298 GSK Investigational Site Magdeburg Sachsen-Anhalt Germany 39112
299 GSK Investigational Site Chemnitz Sachsen Germany 09113
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302 GSK Investigational Site Dresden Sachsen Germany 01219
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306 GSK Investigational Site Leipzig Sachsen Germany 04109
307 GSK Investigational Site Leipzig Sachsen Germany 04249
308 GSK Investigational Site Oschatz Sachsen Germany 04758
309 GSK Investigational Site Pirna Sachsen Germany 01796
310 GSK Investigational Site Riesa Sachsen Germany 01587
311 GSK Investigational Site Schkeuditz Sachsen Germany 04435
312 GSK Investigational Site Berlin Germany 10117
313 GSK Investigational Site Berlin Germany 10409
314 GSK Investigational Site Berlin Germany 10789
315 GSK Investigational Site Berlin Germany 12157
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317 GSK Investigational Site Dortmund Germany 44137
318 GSK Investigational Site Hamburg Germany 20099
319 GSK Investigational Site Hamburg Germany 21073
320 GSK Investigational Site Hamburg Germany 22041
321 GSK Investigational Site Mannheim Germany 68163
322 GSK Investigational Site Muenchen Germany 80809
323 GSK Investigational Site Alexandroupolis Greece 68 100
324 GSK Investigational Site Athens, Greece 11 527
325 GSK Investigational Site Athens Greece 11521
326 GSK Investigational Site Athens Greece 11528
327 GSK Investigational Site Haidari, Athens Greece 12462
328 GSK Investigational Site Heraklion, Crete Greece 71409
329 GSK Investigational Site Ioannina Greece 45500
330 GSK Investigational Site Lamia Greece 35100
331 GSK Investigational Site Nikaia Piraeus Greece 184 54
332 GSK Investigational Site Pireas Greece 18536
333 GSK Investigational Site Thessaloniki Greece 546 36
334 GSK Investigational Site Thessaloniki Greece 546 42
335 GSK Investigational Site Thessaloniki Greece 54642
336 GSK Investigational Site Thessaloniki Greece 564 29
337 GSK Investigational Site Thessaloniki Greece 570 01
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339 GSK Investigational Site Hong Kong Hong Kong
340 GSK Investigational Site Shatin Hong Kong
341 GSK Investigational Site Baja Hungary 6500
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352 GSK Investigational Site Chieti Abruzzo Italy 66100
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354 GSK Investigational Site Napoli Campania Italy 80131
355 GSK Investigational Site Napoli Campania Italy 80138
356 GSK Investigational Site Bologna Emilia-Romagna Italy 40138
357 GSK Investigational Site Parma Emilia-Romagna Italy 43100
358 GSK Investigational Site Ravenna Emilia-Romagna Italy 48121
359 GSK Investigational Site Roma Lazio Italy 00133
360 GSK Investigational Site Roma Lazio Italy 00168
361 GSK Investigational Site Roma Lazio Italy 00186
362 GSK Investigational Site Arenzano (GE) Liguria Italy 16011
363 GSK Investigational Site Bergamo Lombardia Italy 24127
364 GSK Investigational Site Milano Lombardia Italy 20122
365 GSK Investigational Site Milano Lombardia Italy 20132
366 GSK Investigational Site Milano Lombardia Italy 20142
367 GSK Investigational Site Vigevano (PV) Lombardia Italy 27029
368 GSK Investigational Site Ancona Marche Italy 60131
369 GSK Investigational Site Ascoli Piceno Marche Italy 63100
370 GSK Investigational Site Bari Puglia Italy 70124
371 GSK Investigational Site San Giovanni Rotondo (FG) Puglia Italy 71013
372 GSK Investigational Site Olbia (OT) Sardegna Italy 07026
373 GSK Investigational Site Siena Toscana Italy 53100
374 GSK Investigational Site S.Andrea Delle Fratte - S. Sisto (PG) Umbria Italy 06132
375 GSK Investigational Site Padova Veneto Italy 35128
376 GSK Investigational Site Daegu Korea, Republic of 42415
377 GSK Investigational Site Daegu Korea, Republic of 700-71
378 GSK Investigational Site Gyeonggi-do Korea, Republic of 463-70
379 GSK Investigational Site Gyeonggido Korea, Republic of 420-717
380 GSK Investigational Site Kangwondo Korea, Republic of 220-701
381 GSK Investigational Site Pusan Korea, Republic of 602-73
382 GSK Investigational Site Seoul Korea, Republic of 110-744
383 GSK Investigational Site Seoul Korea, Republic of 120-752
384 GSK Investigational Site Seoul Korea, Republic of 134-72
385 GSK Investigational Site Seoul Korea, Republic of 135-71
386 GSK Investigational Site Seoul Korea, Republic of 135-72
387 GSK Investigational Site Seoul Korea, Republic of 137-70
388 GSK Investigational Site Seoul Korea, Republic of 150-95
389 GSK Investigational Site Seoul Korea, Republic of 152-703
390 GSK Investigational Site Seoul Korea, Republic of 411-70
391 GSK Investigational Site Suwon, Kyonggi-do Korea, Republic of 443-72
392 GSK Investigational Site Suwon Korea, Republic of 442-723
393 GSK Investigational Site Aguascalientes, Ags Aguascalientes Mexico 20127
394 GSK Investigational Site Guadalajara Jalisco Mexico 44150
395 GSK Investigational Site Guadalajara Jalisco Mexico 44600
396 GSK Investigational Site Guadalajara Jalisco Mexico 45116
397 GSK Investigational Site Tlaquepaque Jalisco Mexico 45510
398 GSK Investigational Site Monterrey NL Nuevo León Mexico 64718
399 GSK Investigational Site Monterrey Nuevo León Mexico 64460
400 GSK Investigational Site Queretaro Querétaro Mexico 76000
401 GSK Investigational Site Mazatlán Sinaloa Mexico 82126
402 GSK Investigational Site Mazatlán Sinaloa Mexico
403 GSK Investigational Site Mérida Yucatán Mexico 97129
404 GSK Investigational Site Aguascalientes Mexico 20230
405 GSK Investigational Site Mexico, D.F. Mexico 11650
406 GSK Investigational Site Alkmaar Netherlands 1815 JD
407 GSK Investigational Site Amsterdam Netherlands 1061 A
408 GSK Investigational Site Eindhoven Netherlands 5631 BM
409 GSK Investigational Site Gouda Netherlands 2803 H
410 GSK Investigational Site Hardenberg Netherlands 7772 SE
411 GSK Investigational Site Heerlen Netherlands 6419 PC
412 GSK Investigational Site Hoogeveen Netherlands 7909 A
413 GSK Investigational Site Meppel Netherlands 7943 K
414 GSK Investigational Site Rotterdam Netherlands 3051 G
415 GSK Investigational Site Sneek Netherlands 8601 Z
416 GSK Investigational Site Hoenefoss Norway 3513
417 GSK Investigational Site Kolbjørnsvik Norway 4816
418 GSK Investigational Site Oslo Norway 0319
419 GSK Investigational Site Oslo Norway 0586
420 GSK Investigational Site Stavanger Norway 4011
421 GSK Investigational Site Trujillo La Libertad Peru 13001
422 GSK Investigational Site Callao Lima Peru Callao 2
423 GSK Investigational Site San Martin de Porres Lima Peru Lima 33
424 GSK Investigational Site Arequipa Peru
425 GSK Investigational Site Lima Peru 01
426 GSK Investigational Site Lima Peru 17
427 GSK Investigational Site Lima Peru Lima 14
428 GSK Investigational Site Lima Peru Lima 29
429 GSK Investigational Site Lima Peru Lima 32
430 GSK Investigational Site Piura Peru 20001
431 GSK Investigational Site Cebu City Philippines 6000
432 GSK Investigational Site Iloilo City Philippines 5000
433 GSK Investigational Site Laoag City Philippines 2900
434 GSK Investigational Site Bialystok Poland 15-435
435 GSK Investigational Site Bydgoszcz Poland 85-231
436 GSK Investigational Site Bydgoszcz Poland 85-863
437 GSK Investigational Site Gdansk Poland 80-858
438 GSK Investigational Site Gniewkowo Poland 88-140
439 GSK Investigational Site Katowice Poland 40-081
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441 GSK Investigational Site Krakow Poland 30-539
442 GSK Investigational Site Krakow Poland 31-261
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444 GSK Investigational Site Lublin Poland 20-538
445 GSK Investigational Site Poznan Poland 60-111
446 GSK Investigational Site Poznan Poland 61-655
447 GSK Investigational Site Sopot Poland 81- 71
448 GSK Investigational Site Warszawa Poland 00-465
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450 GSK Investigational Site Wroclaw Poland 50-127
451 GSK Investigational Site Wroclaw Poland 50-981
452 GSK Investigational Site Wroclaw Poland 54-239
453 GSK Investigational Site Arkhangelsk Russian Federation 163045
454 GSK Investigational Site Barnaul Russian Federation 656 045
455 GSK Investigational Site Chelyabinsk Russian Federation 454021
456 GSK Investigational Site Chelyabinsk Russian Federation 454047
457 GSK Investigational Site Ekaterinburg Russian Federation 620039
458 GSK Investigational Site Ekaterinburg Russian Federation 620149
459 GSK Investigational Site Ivanovo Russian Federation 153005
460 GSK Investigational Site Kemerovo Russian Federation 650000
461 GSK Investigational Site Kemerovo Russian Federation 650002
462 GSK Investigational Site Krasnodar Russian Federation 350086
463 GSK Investigational Site Moscow Russian Federation 117 036
464 GSK Investigational Site Moscow Russian Federation 117 03
465 GSK Investigational Site Moscow Russian Federation 117292
466 GSK Investigational Site Moscow Russian Federation 119435
467 GSK Investigational Site Moscow Russian Federation 119992
468 GSK Investigational Site Moscow Russian Federation 127411
469 GSK Investigational Site Moscow Russian Federation 129110
470 GSK Investigational Site Nizhniy Novgorod Russian Federation 603126
471 GSK Investigational Site Nizhny Novgorod Russian Federation 603003
472 GSK Investigational Site Novosibirsk Russian Federation 630047
473 GSK Investigational Site Novosibirsk Russian Federation 630091
474 GSK Investigational Site Perm Russian Federation 614097
475 GSK Investigational Site Rostov-on-Don Russian Federation 344022
476 GSK Investigational Site Ryazan Russian Federation 390039
477 GSK Investigational Site Saint Petersburg Russian Federation 195257
478 GSK Investigational Site Samara Russian Federation 443067
479 GSK Investigational Site Saratov Russian Federation 410053
480 GSK Investigational Site Tomsk Russian Federation 634012
481 GSK Investigational Site Tomsk Russian Federation 634041
482 GSK Investigational Site Tomsk Russian Federation 634050
483 GSK Investigational Site Voronezh Russian Federation 394018
484 GSK Investigational Site Yaroslavl Russian Federation 150000
485 GSK Investigational Site Yaroslavl Russian Federation 150003
486 GSK Investigational Site Yaroslavl Russian Federation 150010
487 GSK Investigational Site Yaroslavl Russian Federation 150030
488 GSK Investigational Site Bloemfontein Free State South Africa 9301
489 GSK Investigational Site Tongaat KwaZulu- Natal South Africa 4400
490 GSK Investigational Site Bloemfontein South Africa 9301
491 GSK Investigational Site Cape Town South Africa 7500
492 GSK Investigational Site Houghton South Africa 2198
493 GSK Investigational Site Kuilsrivier South Africa 7580
494 GSK Investigational Site Paarl South Africa 7646
495 GSK Investigational Site Pinelands South Africa 7405
496 GSK Investigational Site Umhlanga South Africa 4319
497 GSK Investigational Site Alicante Spain 03004
498 GSK Investigational Site Almeria Spain 4001
499 GSK Investigational Site Alzira/Valencia Spain 46600
500 GSK Investigational Site Badalona / Barcelona Spain 08917
501 GSK Investigational Site Badalona Spain 08916
502 GSK Investigational Site Barcelona Spain 08003
503 GSK Investigational Site Barcelona Spain 08006
504 GSK Investigational Site Barcelona Spain 08026
505 GSK Investigational Site Barcelona Spain 08907
506 GSK Investigational Site Boadilla Del Monte (Madrid) Spain 28660
507 GSK Investigational Site Canet De Mar - Barcelona Spain 08360
508 GSK Investigational Site Cangas Del Narcea/Asturias Spain 33800
509 GSK Investigational Site Centelles (Barcelona) Spain 08540
510 GSK Investigational Site Córdoba Spain 14004
511 GSK Investigational Site Elche Spain 03293
512 GSK Investigational Site Granada Spain 18012
513 GSK Investigational Site La Coruña Spain 15006
514 GSK Investigational Site León Spain 24071
515 GSK Investigational Site Madrid Spain 28006
516 GSK Investigational Site Madrid Spain 28034
517 GSK Investigational Site Madrid Spain 28040
518 GSK Investigational Site Madrid Spain 28046
519 GSK Investigational Site Madrid Spain 28050
520 GSK Investigational Site Malaga Spain 29010
521 GSK Investigational Site Málaga Spain 29010
522 GSK Investigational Site Palma de Mallorca Spain 07010
523 GSK Investigational Site Palma de Mallorca Spain 07198
524 GSK Investigational Site Pontevedra Spain 36071
525 GSK Investigational Site Pozuelo De Alarcón/Madrid Spain 28223
526 GSK Investigational Site Sagunto/Valencia Spain 46520
527 GSK Investigational Site San Juan (Alicante) Spain 03550
528 GSK Investigational Site Sanlucar De Barrameda - Cádiz Spain 11540
529 GSK Investigational Site Santa Coloma De Gramanet (Barcelona) Spain 08923
530 GSK Investigational Site Santiago De Compostela Spain 15706
531 GSK Investigational Site Sevilla Spain 41014
532 GSK Investigational Site Tarrasa, Barcelona Spain 08221
533 GSK Investigational Site Valencia Spain 46010
534 GSK Investigational Site Valencia Spain 46017
535 GSK Investigational Site Valencia Spain 46026
536 GSK Investigational Site Vigo-Pontevedra Spain 36312
537 GSK Investigational Site Borås Sweden SE-506
538 GSK Investigational Site Eksjö Sweden SE-575 35
539 GSK Investigational Site Göteborg Sweden SE-413 45
540 GSK Investigational Site Helsingborg Sweden SE-252
541 GSK Investigational Site Härnösand Sweden SE-871
542 GSK Investigational Site Karlskrona Sweden SE-371 41
543 GSK Investigational Site Kristianstad Sweden SE-291 85
544 GSK Investigational Site Linköping Sweden SE-587 58
545 GSK Investigational Site Ljungby Sweden SE-341
546 GSK Investigational Site Malmö Sweden SE-205 02
547 GSK Investigational Site Rättvik Sweden SE-795 30
548 GSK Investigational Site Stockholm Sweden SE-111
549 GSK Investigational Site Stockholm Sweden SE-113 61
550 GSK Investigational Site Stockholm Sweden SE-182 88
551 GSK Investigational Site Umeå Sweden SE-901 85
552 GSK Investigational Site Uppsala Sweden SE-752
553 GSK Investigational Site Örebro Sweden SE-703 62
554 GSK Investigational Site Changhua Taiwan 500
555 GSK Investigational Site Hualien Taiwan 970
556 GSK Investigational Site Kaohsiung Taiwan 833
557 GSK Investigational Site Taichung Taiwan 433
558 GSK Investigational Site Tainan Taiwan 71004
559 GSK Investigational Site Taipei Taiwan 10002
560 GSK Investigational Site Taipei Taiwan 112
561 GSK Investigational Site Bangkok Thailand 10330
562 GSK Investigational Site Bangkok Thailand 10400
563 GSK Investigational Site Chiangmai Thailand 50200
564 GSK Investigational Site Pathumthani Thailand 12120
565 GSK Investigational Site Songkla Thailand 90110
566 GSK Investigational Site Chernivtsi Ukraine 58022
567 GSK Investigational Site Dnipropetrovsk Ukraine 49038
568 GSK Investigational Site Kharkiv Ukraine 61058
569 GSK Investigational Site Kharkiv Ukraine 61070
570 GSK Investigational Site Kherson Ukraine 73000
571 GSK Investigational Site Kyiv Ukraine 01004
572 GSK Investigational Site Kyiv Ukraine 01021
573 GSK Investigational Site Kyiv Ukraine 02091
574 GSK Investigational Site Kyiv Ukraine 03049
575 GSK Investigational Site Kyiv Ukraine 04050
576 GSK Investigational Site Kyiv Ukraine 04114
577 GSK Investigational Site Mykolaiv Ukraine 54003
578 GSK Investigational Site Odesa Ukraine 65025
579 GSK Investigational Site Poltava Ukraine 36011
580 GSK Investigational Site Uzhgorod Ukraine 88000
581 GSK Investigational Site Vinnytsia Ukraine 21010
582 GSK Investigational Site Zaporizhzhya Ukraine 69001
583 GSK Investigational Site Soham Cambridgeshire United Kingdom CB7 5J
584 GSK Investigational Site Chesterfield Derbyshire United Kingdom S40 4AAA
585 GSK Investigational Site Romford Essex United Kingdom RM1 3P
586 GSK Investigational Site Northwood Middlesex United Kingdom HA6 2R
587 GSK Investigational Site Edinburgh Midlothian United Kingdom EH4 2XU
588 GSK Investigational Site Trowbridge Wiltshire United Kingdom BA14 8
589 GSK Investigational Site Aberdeen United Kingdom AB25 2
590 GSK Investigational Site Axbridge, Somerset United Kingdom BS26 2
591 GSK Investigational Site Ayr United Kingdom KA6 6D
592 GSK Investigational Site Blackpool United Kingdom FY3 8NR
593 GSK Investigational Site Bristol United Kingdom BS10 5
594 GSK Investigational Site Dumfries United Kingdom DG1 4AP
595 GSK Investigational Site Dundee United Kingdom DD1 9S
596 GSK Investigational Site Dundee United Kingdom DD4 6Q
597 GSK Investigational Site Dundee United Kingdom DD5 4LX
598 GSK Investigational Site Fife United Kingdom KY14 7AW
599 GSK Investigational Site Fife United Kingdom KY2 5A
600 GSK Investigational Site Gloucester United Kingdom GL1 3N
601 GSK Investigational Site Lancaster United Kingdom LA1 4R
602 GSK Investigational Site Manchester United Kingdom M23 9LT
603 GSK Investigational Site Newport United Kingdom PO30 5
604 GSK Investigational Site Oxford United Kingdom OX3 7L
605 GSK Investigational Site Rotherham United Kingdom S60 2UD
606 GSK Investigational Site Sidcup, Kent United Kingdom DA14 6
607 GSK Investigational Site Trowbridge United Kingdom BA14 9
608 GSK Investigational Site Wigan United Kingdom WN1 2NN

Sponsors and Collaborators

  • GlaxoSmithKline
  • Duke Clinical Research Institute

Investigators

  • Study Director: GSK Clinical Trials, GlaxoSmithKline (for GlaxoSmithKline; Human Genome Sciences Inc., a GSK Company; Sirtris, a GSK Company; Stiefel, a GSK Company; ViiV Healthcare)

Study Documents (Full-Text)

More Information

Publications

Responsible Party:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT02465515
Other Study ID Numbers:
  • 116174
  • 2014-001824-32
First Posted:
Jun 8, 2015
Last Update Posted:
Mar 6, 2019
Last Verified:
Feb 1, 2019

Study Results

Participant Flow

Recruitment Details This was a randomized, double-blind, parallel group, placebo-controlled study in participants with Type 2 diabetes having a previous history of cardiovascular disease and not having optimal glycemic control.
Pre-assignment Detail A total of 10793 participants were screened of which 1330 failed screening and 9463 participants were randomized in a 1:1 ratio to receive either once weekly albiglutide or matching placebo subcutaneous injections. The study was conducted in 28 countries
Arm/Group Title Placebo Albiglutide
Arm/Group Description Albiglutide matching placebo was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region in addition to the standard of care therapy for diabetes and cardiovascular health. Albiglutide was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region. Participants were administered albiglutide at a dose of 30 milligrams (mg) or 50 mg once weekly in addition to the standard of care therapy for diabetes and cardiovascular health.
Period Title: Overall Study
STARTED 4732 4731
COMPLETED 4578 4620
NOT COMPLETED 154 111

Baseline Characteristics

Arm/Group Title Placebo Albiglutide Total
Arm/Group Description Albiglutide matching placebo was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region in addition to the standard of care therapy for diabetes and cardiovascular health. Albiglutide was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region. Participants were administered albiglutide at a dose of 30 milligrams (mg) or 50 mg once weekly in addition to the standard of care therapy for diabetes and cardiovascular health.. Total of all reporting groups
Overall Participants 4732 4731 9463
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]
64.2
(8.65)
64.1
(8.71)
64.1
(8.68)
Sex: Female, Male (Count of Participants)
Female
1467
31%
1427
30.2%
2894
30.6%
Male
3265
69%
3304
69.8%
6569
69.4%
Race/Ethnicity, Customized (Count of Participants)
American Indian (Amer. Ind.) or Alaska Native
238
5%
280
5.9%
518
5.5%
Central/South Asian Heritage (Her.)
27
0.6%
25
0.5%
52
0.5%
Japanese Her./East Asian Her/South East Asian Her.
215
4.5%
204
4.3%
419
4.4%
Black or African American (Amer.)
118
2.5%
121
2.6%
239
2.5%
Native Hawaiian or Other Pacific Islander
2
0%
3
0.1%
5
0.1%
White
4024
85%
4006
84.7%
8030
84.9%
Amer Ind. or Alaska Native & Black or African Amer
1
0%
3
0.1%
4
0%
Asian & Black or African Amer.
1
0%
0
0%
1
0%
Asian & White
0
0%
1
0%
1
0%
Black or African Amer. & White
81
1.7%
67
1.4%
148
1.6%
Unknown
1
0%
1
0%
2
0%
Amer. Ind. or Alaska Native & White
24
0.5%
20
0.4%
44
0.5%

Outcome Measures

1. Primary Outcome
Title Time to First Occurrence of Major Adverse Cardiovascular Events (MACE) During Cardiovascular (CV) Follow-up Time Period
Description Time to MACE defined as the time to first occurrence of Cardiovascular Endpoint Committee (CEC)-adjudicated MACE (CV death, myocardial infarction [MI] or stroke) was analyzed using a Cox Proportional Hazards regression model with treatment group as the only covariate. The incidence rate per 100 person years (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% confidence interval. First event person-years=(cumulative total time to first event for participants who have the event+cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period. The analysis was performed on the Intent to Treat (ITT) Population which comprised of all randomized participants excluding participants who did not provide consent.
Time Frame Median of 1.65 person years for CV follow-up time period

Outcome Measure Data

Analysis Population Description
ITT Population
Arm/Group Title Placebo Albiglutide
Arm/Group Description Albiglutide matching placebo was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region in addition to the standard of care therapy for diabetes and cardiovascular health. Albiglutide was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region. Participants were administered albiglutide at a dose of 30 milligrams (mg) or 50 mg once weekly in addition to the standard of care therapy for diabetes and cardiovascular health.
Measure Participants 4732 4731
Number (95% Confidence Interval) [Events per 100 person years]
5.87
4.57
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Albiglutide
Comments
Type of Statistical Test Non-Inferiority
Comments Non-inferiority was determined by testing the hypothesis that the observed hazard ratio is significantly different from the null margin of 1.3 (a one-sided p <0.025 for such a test with result in appropriate direction being equivalent to the upper 95% confidence limit for the hazard ratio being less than 1.3)
Statistical Test of Hypothesis p-Value <0.0001
Comments One-sided p-value based on Wald test of hazard ratio (HR) >=1.3 versus HR <1.3.
Method Wald test
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.78
Confidence Interval (2-Sided) 95%
0.68 to 0.90
Parameter Dispersion Type:
Value:
Estimation Comments Hazard ratio is estimated using a Cox proportional hazard regression model with treatment as the only covariate
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Albiglutide
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments Two-sided p-value based on Wald test of HR=1 versus HR not equal to 1
Method Wald test
Comments
2. Secondary Outcome
Title Time to First Occurrence of MACE or Urgent Revascularization for Unstable Angina
Description Time to first occurrence of CEC-adjudicated MACE (CV death, MI or stroke) or urgent revascularization for unstable angina was analyzed using a Cox Proportional Hazards regression model with treatment group as the only covariate. The incidence rate per 100 person years (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% confidence interval. First event person-years=(cumulative total time to first event for participants who have the event+cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period.
Time Frame Median of 1.65 person years for CV follow-up time period

Outcome Measure Data

Analysis Population Description
ITT Population
Arm/Group Title Placebo Albiglutide
Arm/Group Description Albiglutide matching placebo was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region in addition to the standard of care therapy for diabetes and cardiovascular health. Albiglutide was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region. Participants were administered albiglutide at a dose of 30 milligrams (mg) or 50 mg once weekly in addition to the standard of care therapy for diabetes and cardiovascular health.
Measure Participants 4732 4731
Number (95% Confidence Interval) [Events per 100 person years]
6.45
5.06
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Albiglutide
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments Two-sided p-value based on the Wald statistic.
Method Wald statistic
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.78
Confidence Interval (2-Sided) 95%
0.69 to 0.90
Parameter Dispersion Type:
Value:
Estimation Comments Hazard ratio is estimated using a Cox proportional hazard regression model with treatment as the only covariate.
3. Secondary Outcome
Title Time to Adjudicated CV Death
Description Time to adjudicated CV death was analyzed using a Cox Proportional Hazards regression model with treatment group as the only covariate. The incidence rate per 100 person years (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% confidence interval. First event person-years=(cumulative total time to first event for participants who have the event+cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period.
Time Frame Median of 1.65 person years for the CV follow-up time period

Outcome Measure Data

Analysis Population Description
ITT Population
Arm/Group Title Placebo Albiglutide
Arm/Group Description Albiglutide matching placebo was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region in addition to the standard of care therapy for diabetes and cardiovascular health. Albiglutide was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region. Participants were administered albiglutide at a dose of 30 milligrams (mg) or 50 mg once weekly in addition to the standard of care therapy for diabetes and cardiovascular health.
Measure Participants 4732 4731
Number (95% Confidence Interval) [Events per 100 person years]
1.72
1.61
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Albiglutide
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value 0.578
Comments Two-sided p-value based on the Wald statistic
Method Wald statistic
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.93
Confidence Interval (2-Sided) 95%
0.73 to 1.19
Parameter Dispersion Type:
Value:
Estimation Comments Hazard ratio is estimated using a Cox proportional hazard regression model with treatment as the only covariate
4. Secondary Outcome
Title Time to First Occurrence of Adjudicated MI
Description Time to first occurrence of adjudicated MI was analyzed using a Cox Proportional Hazards regression model with treatment group as the only covariate. The incidence rate per 100 person years (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% confidence interval. First event person-years=(cumulative total time to first event for participants who have the event+cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period.
Time Frame Median of 1.65 person years for CV follow-up time period

Outcome Measure Data

Analysis Population Description
ITT Population
Arm/Group Title Placebo Albiglutide
Arm/Group Description Albiglutide matching placebo was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region in addition to the standard of care therapy for diabetes and cardiovascular health. Albiglutide was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region. Participants were administered albiglutide at a dose of 30 milligrams (mg) or 50 mg once weekly in addition to the standard of care therapy for diabetes and cardiovascular health.
Measure Participants 4732 4731
Number (95% Confidence Interval) [Events per 100 person years]
3.26
2.43
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Albiglutide
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value 0.003
Comments Two-sided p-value based on the Wald statistic.
Method Wald statistic
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.75
Confidence Interval (2-Sided) 95%
0.61 to 0.90
Parameter Dispersion Type:
Value:
Estimation Comments Hazard ratio is estimated using a Cox proportional hazard regression model with treatment as the only covariate.
5. Secondary Outcome
Title Time to First Occurrence of Adjudicated Stroke
Description Time to first occurrence of adjudicated stroke was analyzed using a Cox Proportional Hazards regression model with treatment group as the only covariate. The incidence rate per 100 person years (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% confidence interval. First event person-years=(cumulative total time to first event for participants who have the event+cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period.
Time Frame Median of 1.65 person years for CV follow-up time period

Outcome Measure Data

Analysis Population Description
ITT Population
Arm/Group Title Placebo Albiglutide
Arm/Group Description Albiglutide matching placebo was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region in addition to the standard of care therapy for diabetes and cardiovascular health. Albiglutide was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region. Participants were administered albiglutide at a dose of 30 milligrams (mg) or 50 mg once weekly in addition to the standard of care therapy for diabetes and cardiovascular health.
Measure Participants 4732 4731
Number (95% Confidence Interval) [Events per 100 person years]
1.45
1.25
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Albiglutide
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value 0.300
Comments Two-sided p-value based on the Wald statistic.
Method Wald statistic
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.86
Confidence Interval (2-Sided) 95%
0.66 to 1.14
Parameter Dispersion Type:
Value:
Estimation Comments Hazard ratio is estimated using a Cox proportional hazard regression model with treatment as the only covariate.
6. Secondary Outcome
Title Time to First Occurrence of Adjudicated CV Death or Hospitalization for Heart Failure (HF)
Description Time to first occurrence of adjudicated CV death or hospitalization for HF was analyzed using a Cox Proportional Hazards regression model with treatment group as the only covariate. The incidence rate per 100 person years (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% confidence interval. First event person-years=(cumulative total time to first event for participants who have the event+cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period.
Time Frame Median of 1.65 person years for CV follow-up time period

Outcome Measure Data

Analysis Population Description
ITT Population
Arm/Group Title Placebo Albiglutide
Arm/Group Description Albiglutide matching placebo was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region in addition to the standard of care therapy for diabetes and cardiovascular health. Albiglutide was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region. Participants were administered albiglutide at a dose of 30 milligrams (mg) or 50 mg once weekly in addition to the standard of care therapy for diabetes and cardiovascular health.
Measure Participants 4732 4731
Number (95% Confidence Interval) [Events per 100 person years]
2.92
2.49
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Albiglutide
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value 0.113
Comments Two-sided p-value based on the Wald statistic.
Method Wald statistic
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.85
Confidence Interval (2-Sided) 95%
0.70 to 1.04
Parameter Dispersion Type:
Value:
Estimation Comments Hazard ratio is estimated using a Cox proportional hazard regression model with treatment as the only covariate.
7. Secondary Outcome
Title Time to Initiation of Insulin of More Than 3 Months Duration for Those Participants Not Treated With Insulin at Study Start
Description Time to initiation of insulin of more than 3 months duration in participants not treated with insulin at study start was analyzed using a Cox Proportional Hazards regression model with treatment group as the only covariate. The incidence rate per 100 person years (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% confidence interval. First event person-years=(cumulative total time to first event for participants who have the event+cumulative total of censored time for participants without the event)/365.25, based on the on-therapy and post-therapy AE time period. The analysis was performed on Non-Insulin Population which comprised of participants in the ITT Population who were not on insulin at Baseline.
Time Frame Up to 2.7 years

Outcome Measure Data

Analysis Population Description
Non-Insulin Population
Arm/Group Title Placebo Albiglutide
Arm/Group Description Albiglutide matching placebo was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region in addition to the standard of care therapy for diabetes and cardiovascular health. Albiglutide was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region. Participants were administered albiglutide at a dose of 30 milligrams (mg) or 50 mg once weekly in addition to the standard of care therapy for diabetes and cardiovascular health.
Measure Participants 1995 1871
Number (95% Confidence Interval) [Events per 100 person years]
8.58
3.56
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Albiglutide
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments Two-sided p-value based on Wald test of HR=1 versus HR not equal to 1.
Method Wald test
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.42
Confidence Interval (2-Sided) 95%
0.33 to 0.53
Parameter Dispersion Type:
Value:
Estimation Comments Hazard ratio is estimated using a Cox proportional hazard regression model with treatment as the only covariate.
8. Secondary Outcome
Title Time to Initiation of Prandial Insulin in Those Participants on Basal Insulin at Study Start
Description Time to initiation of prandial insulin in those participants on basal insulin at study start was analyzed using a Cox Proportional Hazards regression model with treatment group as the only covariate. The incidence rate per 100 person years (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% confidence interval. First event person-years=(cumulative total time to first event for participants who have the event+cumulative total of censored time for participants without the event)/365.25, based on the on-therapy and post-therapy AE time period. The analysis was performed on Basal Insulin Population which comprised of participants in the ITT Population who were on basal insulin but not on other insulin at Baseline (i.e., will not include a participant on a mixed insulin or on a prandial-only insulin).
Time Frame Up to 2.7 years

Outcome Measure Data

Analysis Population Description
Basal Insulin Population
Arm/Group Title Placebo Albiglutide
Arm/Group Description Albiglutide matching placebo was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region in addition to the standard of care therapy for diabetes and cardiovascular health. Albiglutide was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region. Participants were administered albiglutide at a dose of 30 milligrams (mg) or 50 mg once weekly in addition to the standard of care therapy for diabetes and cardiovascular health.
Measure Participants 1040 1028
Number (95% Confidence Interval) [Events per 100 person years]
5.09
3.59
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Albiglutide
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.043
Comments Two-sided p-value based on Wald test of HR=1 versus HR not equal to 1.
Method Wald test
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.71
Confidence Interval (2-Sided) 95%
0.51 to 0.99
Parameter Dispersion Type:
Value:
Estimation Comments Hazard ratio is estimated using a Cox proportional hazard regression model with treatment as the only covariate.
9. Secondary Outcome
Title Percentage of Participants Achieving Composite Metabolic Endpoint
Description Percentage of participants achieving composite metabolic endpoint defined as the percentage of participants achieving glycemic control (glycated hemoglobin [HbA1c] <=7% ) with no severe hypoglycemic incidents and weight gain < 5%. Final Assessment is the latest post-Baseline assessment of both HbA1c and weight.
Time Frame Months 8, 16, 24 and final assessment (up to 2.7 years)

Outcome Measure Data

Analysis Population Description
ITT Population. Only those participants with HbA1c and weight values at Baseline and at the specified visits were analyzed (represented by n=X in category titles)
Arm/Group Title Placebo Albiglutide
Arm/Group Description Albiglutide matching placebo was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region in addition to the standard of care therapy for diabetes and cardiovascular health. Albiglutide was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region. Participants were administered albiglutide at a dose of 30 milligrams (mg) or 50 mg once weekly in addition to the standard of care therapy for diabetes and cardiovascular health.
Measure Participants 4732 4731
Month 8, n=4127, 4195
15.4
0.3%
32.2
0.7%
Month 16, n=3026, 3118
16.5
0.3%
28.7
0.6%
Month 24, n=1119, 1173
17.8
0.4%
28.6
0.6%
Final assessment, n=4401, 4455
15.1
0.3%
26.0
0.5%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Albiglutide
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments P-value based on the covariate-adjusted extended Mantel-Haenszel test. Covariates include Baseline HbA1c (<8.0% versus >= 8.0%) and Baseline diabetes therapy (diet and exercise alone versus all other therapies).
Method Mantel Haenszel
Comments Month 8
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Albiglutide
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments P-value based on the covariate-adjusted extended Mantel-Haenszel test. Covariates include Baseline HbA1c (<8.0% versus >= 8.0%) and Baseline diabetes therapy (diet and exercise alone versus all other therapies).
Method Mantel Haenszel
Comments Month 16
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Albiglutide
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments P-value based on the covariate-adjusted extended Mantel-Haenszel test. Covariates include Baseline HbA1c (<8.0% versus >= 8.0%) and Baseline diabetes therapy (diet and exercise alone versus all other therapies).
Method Mantel Haenszel
Comments Month 24
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Albiglutide
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments P-value based on the covariate-adjusted extended Mantel-Haenszel test. Covariates include Baseline HbA1c (<8.0% versus >= 8.0%) and Baseline diabetes therapy (diet and exercise alone versus all other therapies).
Method Mantel Haenszel
Comments Final assessment
10. Secondary Outcome
Title Time to First Occurrence of a Clinically Important Microvascular Event
Description Clinically important microvascular events were defined as the following: need for renal transplant or dialysis, new diabetes-related blindness, and procedures (laser photocoagulation or anti-vascular endothelial growth factor treatment or vitrectomy for diabetic retinopathy/eye disease). Time to first occurrence of a clinically important microvascular event was analyzed using a Cox Proportional Hazards regression model with treatment group as the only covariate. The incidence rate per 100 person years (100*number of participants with at least 1 event)/first event person-years) is presented along with 95% confidence interval. First event person-years=(cumulative total time to first event for participants who have the event+cumulative total of censored time for participants without the event)/365.25, based on the on-therapy and post-therapy AE time period.
Time Frame Up to 2.7 years

Outcome Measure Data

Analysis Population Description
ITT Population
Arm/Group Title Placebo Albiglutide
Arm/Group Description Albiglutide matching placebo was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region in addition to the standard of care therapy for diabetes and cardiovascular health. Albiglutide was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region. Participants were administered albiglutide at a dose of 30 milligrams (mg) or 50 mg once weekly in addition to the standard of care therapy for diabetes and cardiovascular health.
Measure Participants 4732 4731
Number (95% Confidence Interval) [Events per 100 person years]
0.69
0.46
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Albiglutide
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.055
Comments Two-sided p-value based on Wald test of HR=1 versus HR not equal to 1
Method Wald test
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.66
Confidence Interval (2-Sided) 95%
0.43 to 1.01
Parameter Dispersion Type:
Value:
Estimation Comments Hazard ratio is estimated using a Cox proportional hazard regression model with treatment as the only covariate.
11. Secondary Outcome
Title Change From Baseline in HbA1c
Description Change from Baseline in HbA1c was analyzed using mixed model repeated measures (MMRM) including observed case data (does not impute any missing data). Baseline is the last non-missing value assessed on or before treatment start date. Change from Baseline is the value at specified time point minus the Baseline value. Change from Baseline in HbA1c using Baseline data from Local or Central Laboratory, and post-Baseline Central Laboratory data is presented.
Time Frame Baseline and Months 8 and 16

Outcome Measure Data

Analysis Population Description
ITT Population. Only those participants with value at Baseline and at the specified visit is presented (represented by n=X in category titles)
Arm/Group Title Placebo Albiglutide
Arm/Group Description Albiglutide matching placebo was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region in addition to the standard of care therapy for diabetes and cardiovascular health. Albiglutide was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region. Participants were administered albiglutide at a dose of 30 milligrams (mg) or 50 mg once weekly in addition to the standard of care therapy for diabetes and cardiovascular health.
Measure Participants 4732 4731
Month 8, n=4211, 4289
-0.28
(0.020)
-0.92
(0.019)
Month 16, n=3066, 3163
-0.31
(0.023)
-0.83
(0.022)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Albiglutide
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments P-value from a two-sided t-test to test whether the difference of least square means (Albiglutide - Placebo) is equal to zero
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.63
Confidence Interval (2-Sided) 95%
-0.69 to -0.58
Parameter Dispersion Type:
Value:
Estimation Comments Based on MMRM model: Change=Baseline HbA1c+Treatment+Visit+Treatment-by-Visit Interaction+Baseline HbA1c-by-Visit Interaction. Difference of least squares means (Albiglutide-Placebo) is from MMRM model for Month 8
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Albiglutide
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments P-value from a two-sided t-test to test whether the difference of least square means (Albiglutide - Placebo) is equal to zero
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.52
Confidence Interval (2-Sided) 95%
-0.58 to -0.45
Parameter Dispersion Type:
Value:
Estimation Comments Based on MMRM model: Change=Baseline HbA1c+Treatment+Visit+Treatment-by-Visit Interaction+Baseline HbA1c-by-Visit Interaction. Difference of least squares means (Albiglutide-Placebo) is from MMRM model for Month 16
12. Secondary Outcome
Title Change From Baseline in Body Weight
Description Change from Baseline in body weight was analyzed using mixed model repeated measures including observed case data (does not impute any missing data). Baseline is the last non-missing value assessed on or before treatment start date. Change from Baseline is the value at specified time point minus the Baseline value.
Time Frame Baseline and Months 8 and 16

Outcome Measure Data

Analysis Population Description
ITT Population. Only those participants with value at Baseline and at the specified visit is presented (represented by n=X in category titles)
Arm/Group Title Placebo Albiglutide
Arm/Group Description Albiglutide matching placebo was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region in addition to the standard of care therapy for diabetes and cardiovascular health. Albiglutide was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region. Participants were administered albiglutide at a dose of 30 milligrams (mg) or 50 mg once weekly in addition to the standard of care therapy for diabetes and cardiovascular health.
Measure Participants 4732 4731
Month 8, n=4217, 4286
-0.36
(0.062)
-1.02
(0.061)
Month 16, n=3068, 3173
-0.53
(0.084)
-1.36
(0.083)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Albiglutide
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments P-value from a two-sided t-test to test whether the difference of least square means (Albiglutide-Placebo) is equal to zero
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.66
Confidence Interval (2-Sided) 95%
-0.83 to -0.49
Parameter Dispersion Type:
Value:
Estimation Comments Based on MMRM model: Change=Baseline Body Weight+Treatment+Visit+Treatment-by-Visit Interaction+Baseline Body Weight-by-Visit Interaction. Difference of least squares means (Albiglutide-Placebo) is from MMRM model for Month 8
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Albiglutide
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments P-value from a two-sided t-test to test whether the difference of least square means (Albiglutide - Placebo) is equal to zero
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.83
Confidence Interval (2-Sided) 95%
-1.06 to -0.60
Parameter Dispersion Type:
Value:
Estimation Comments Based on MMRM model: Change=Baseline Body Weight+Treatment+Visit+Treatment-by-Visit Interaction+Baseline Body weight-by-Visit Interaction. Difference of least squares means (Albiglutide-Placebo) is from MMRM model for Month 16
13. Secondary Outcome
Title Change From Baseline in Treatment Related Impact Measures-Diabetes (TRIM-D) Total Score
Description The TRIM-D is a 28 item treatment satisfaction measure with 5 domains assessing Treatment Burden, Daily Life, Diabetes Management, Compliance and Psychological Health. The raw score ranges for each subscale were: treatment burden (6 to 30), daily life (5 to 25), diabetes management (5 to 25), compliance (4 to 20) and psychological health (8 to 40), higher scores indicating better health state. Total raw score was determined by summing the raw scores for each of the subscales and the total score (transformed) was determined as [(raw score minus lowest possible raw score)/possible raw score range] x100. The possible total (transformed) score range is 0-100, where higher scores indicated better health state. Baseline is the last non-missing value assessed on or before treatment start date. Change from Baseline is the value at specified time point minus the Baseline value.
Time Frame Baseline and Months 8 and 16

Outcome Measure Data

Analysis Population Description
ITT Population. Only those participants with value at Baseline and at the specified visit is presented (represented by n=X in category titles)
Arm/Group Title Placebo Albiglutide
Arm/Group Description Albiglutide matching placebo was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region in addition to the standard of care therapy for diabetes and cardiovascular health. Albiglutide was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region. Participants were administered albiglutide at a dose of 30 milligrams (mg) or 50 mg once weekly in addition to the standard of care therapy for diabetes and cardiovascular health.
Measure Participants 4732 4731
Month 8, n=3013, 3041
4.53
(0.194)
6.92
(0.193)
Month 16, n=1738, 1840
4.80
(0.247)
7.13
(0.241)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Albiglutide
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments P-value from a two-sided t-test to test whether the difference of least square means (Albiglutide - Placebo) is equal to zero.
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 2.39
Confidence Interval (2-Sided) 95%
1.85 to 2.93
Parameter Dispersion Type:
Value:
Estimation Comments Based on MMRM model: Change=Baseline Total Score+Treatment+Visit+Treatment-by-Visit Interaction+Baseline Total Score-by-Visit Interaction. Difference of least squares means (Albiglutide-Placebo) is from MMRM model for Month 8
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Albiglutide
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments P-value from a two-sided t-test to test whether the difference of least square means (Albiglutide-Placebo) is equal to zero
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 2.33
Confidence Interval (2-Sided) 95%
1.66 to 3.01
Parameter Dispersion Type:
Value:
Estimation Comments Based on MMRM model: Change=Baseline Total Score+Treatment+Visit+Treatment-by-Visit Interaction+Baseline Total Score-by-Visit Interaction. Difference of least squares means (Albiglutide-Placebo) is from MMRM model for Month 16
14. Secondary Outcome
Title Change From Baseline in EuroQol- 5 Dimension (EQ-5D) Visual Analogue Scale (VAS) Score
Description The EQ-5D is a standardized instrument used to evaluate generic health-related quality of life, comprising 5 domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. It provides a simple descriptive profile and a single index value for health status. The EQ-5D self-reported questionnaire includes a visual analog scale (VAS), which records the respondent's self-rated health status on a graduated (0-100) scale, where 0 represents the worst imaginable health state and 100 represents the best imaginable health state. Baseline is the last non-missing value assessed on or before treatment start date. Change from Baseline is the value at specified time point minus the Baseline value.
Time Frame Baseline and Months 8 and 16

Outcome Measure Data

Analysis Population Description
ITT Population. Only those participants with value at Baseline and at the specified visit is presented (represented by n=X in category titles)
Arm/Group Title Placebo Albiglutide
Arm/Group Description Albiglutide matching placebo was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region in addition to the standard of care therapy for diabetes and cardiovascular health. Albiglutide was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region. Participants were administered albiglutide at a dose of 30 milligrams (mg) or 50 mg once weekly in addition to the standard of care therapy for diabetes and cardiovascular health.
Measure Participants 4732 4731
Month 8, n=3982, 4014
1.36
(0.217)
2.83
(0.216)
Month 16, n=2347, 2481
1.87
(0.287)
2.39
(0.279)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Albiglutide
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments P-value from a two-sided t-test to test whether the difference of least square means (Albiglutide-Placebo) is equal to zero.
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.47
Confidence Interval (2-Sided) 95%
0.87 to 2.07
Parameter Dispersion Type:
Value:
Estimation Comments Based on MMRM model: Change=Baseline Score+Treatment+Visit+Treatment-by-Visit Interaction+Baseline Score-by-Visit Interaction. Difference of least squares means (Albiglutide-Placebo) is from MMRM model for Month 8.
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Albiglutide
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value 0.192
Comments P-value from a two-sided t-test to test whether the difference of least square means (Albiglutide - Placebo) is equal to zero
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.52
Confidence Interval (2-Sided) 95%
-0.26 to 1.31
Parameter Dispersion Type:
Value:
Estimation Comments Based on MMRM model: Change=Baseline Score+Treatment+Visit+Treatment-by-Visit Interaction+Baseline Score-by-Visit Interaction. Difference of least squares means (Albiglutide - Placebo) is from MMRM model for Month 16
15. Secondary Outcome
Title Time to Death
Description Time to death was analyzed using a Cox Proportional Hazards regression model with treatment group as the only covariate. The incidence rate per 100 person years (100*number of participants who died/endpoint person-years) is presented along with 95% confidence interval. Endpoint person-years=(cumulative total time to event for participants who have the event+cumulative total of censored time for participants without the event)/365.25, based on the Vital Status follow-up time period.
Time Frame Median of 1.73 years for the Vital Status follow-up time period

Outcome Measure Data

Analysis Population Description
ITT Population
Arm/Group Title Placebo Albiglutide
Arm/Group Description Albiglutide matching placebo was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region in addition to the standard of care therapy for diabetes and cardiovascular health. Albiglutide was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region. Participants were administered albiglutide at a dose of 30 milligrams (mg) or 50 mg once weekly in addition to the standard of care therapy for diabetes and cardiovascular health.
Measure Participants 4732 4731
Number (95% Confidence Interval) [Events per 100 person years]
2.56
2.44
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Albiglutide
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value 0.644
Comments Two-sided p-value based on Wald test of HR=1 versus HR not equal to 1.
Method Wald test
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.95
Confidence Interval (2-Sided) 95%
0.79 to 1.16
Parameter Dispersion Type:
Value:
Estimation Comments Hazard ratio is estimated using a Cox proportional hazard regression model with treatment as the only covariate.
16. Secondary Outcome
Title Number of Participants With Non-fatal Serious Adverse Events (SAEs)
Description 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; is a congenital anomaly/birth defect; other important medical events that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed before; is associated with liver injury and impaired liver function. Number of participants with on-therapy non-fatal SAEs are presented. Safety Population comprised of all randomized participants who received at least one dose of study treatment.
Time Frame Up to 2.7 years

Outcome Measure Data

Analysis Population Description
Safety Population
Arm/Group Title Placebo Albiglutide
Arm/Group Description Albiglutide matching placebo was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region in addition to the standard of care therapy for diabetes and cardiovascular health. Albiglutide was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region. Participants were administered albiglutide at a dose of 30 milligrams (mg) or 50 mg once weekly in addition to the standard of care therapy for diabetes and cardiovascular health.
Measure Participants 4715 4717
Count of Participants [Participants]
974
20.6%
891
18.8%
17. Secondary Outcome
Title Number of Participants With Adverse Events (AEs) Leading to Discontinuation of Investigational Product (AELD)
Description The number of participants with on-therapy AEs leading to discontinuation of investigational product is reported.
Time Frame Up to 2.7 years

Outcome Measure Data

Analysis Population Description
Safety Population
Arm/Group Title Placebo Albiglutide
Arm/Group Description Albiglutide matching placebo was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region in addition to the standard of care therapy for diabetes and cardiovascular health. Albiglutide was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region. Participants were administered albiglutide at a dose of 30 milligrams (mg) or 50 mg once weekly in addition to the standard of care therapy for diabetes and cardiovascular health.
Measure Participants 4715 4717
Count of Participants [Participants]
334
7.1%
427
9%
18. Secondary Outcome
Title Number of Participants With AEs of Special Interest
Description The protocol defined AEs of special interest included: development of thyroid cancer; hematologic malignancy; pancreatic cancer; pancreatitis (investigator reported and pancreatitis positively adjudicated by the Pancreatic Adjudication Committee [PAC]); investigational product injection site reactions; immunological reactions; severe hypoglycemic events; hepatic events; hepatic enzyme elevations (including gamma glutamyl transferase [GGT]); serious gastrointestinal (GI) events; appendicitis; atrial fibrillation/flutter; pneumonia; worsening renal function and diabetic retinopathy. The number of participants with on-therapy AEs of special interest is reported.
Time Frame Up to 2.7 years

Outcome Measure Data

Analysis Population Description
Safety Population
Arm/Group Title Placebo Albiglutide
Arm/Group Description Albiglutide matching placebo was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region in addition to the standard of care therapy for diabetes and cardiovascular health. Albiglutide was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region. Participants were administered albiglutide at a dose of 30 milligrams (mg) or 50 mg once weekly in addition to the standard of care therapy for diabetes and cardiovascular health.
Measure Participants 4715 4717
Thyroid cancer diagnosis
0
0%
0
0%
Hematologic malignancy
5
0.1%
9
0.2%
Pancreatic cancer
5
0.1%
6
0.1%
Investigational product injection site reaction
29
0.6%
86
1.8%
Hypersensitivity
48
1%
45
1%
Severe hypoglycemic events
55
1.2%
31
0.7%
Hepatic events
74
1.6%
98
2.1%
Hepatic enzyme elevations (including GGT)
34
0.7%
51
1.1%
Serious GI Events
87
1.8%
92
1.9%
Appendicitis
8
0.2%
3
0.1%
Atrial fibrillation/atrial flutter
131
2.8%
108
2.3%
Pneumonia
138
2.9%
131
2.8%
Renal impairment
319
6.7%
279
5.9%
Diabetic retinopathy
89
1.9%
78
1.6%
Investigator-reported pancreatitis
13
0.3%
14
0.3%
Pancreatitis positively adjudicated by PAC
7
0.1%
10
0.2%
19. Secondary Outcome
Title Change in Estimated Glomerular Filtration Rate (eGFR) Calculated Using Modification of Diet in Renal Disease (MDRD) Formula
Description Blood samples were collected for the measurement of serum creatinine. Serum creatinine values were used to calculate eGFR using the MDRD formula, eGFR=175 x (serum creatinine)^-1.154 x (Age)^-0.203 x (0.742 if female) x (1.212 if African American). Baseline is the last non-missing value assessed on or before treatment start date. Change from Baseline is the value at specified time point minus the Baseline value. Change from Baseline in eGFR using Baseline data from Local or Central Laboratory, and post-Baseline Central Laboratory data for the on-treatment time period is presented.
Time Frame Baseline and Months 8 and 16

Outcome Measure Data

Analysis Population Description
Safety Population. Only those participants with a value at Baseline and specified visit were analyzed (represented by n=X in category titles)
Arm/Group Title Placebo Albiglutide
Arm/Group Description Albiglutide matching placebo was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region in addition to the standard of care therapy for diabetes and cardiovascular health. Albiglutide was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region. Participants were administered albiglutide at a dose of 30 milligrams (mg) or 50 mg once weekly in addition to the standard of care therapy for diabetes and cardiovascular health.
Measure Participants 4715 4717
Month 8; n=3977,4008
1.22
(0.264)
0.10
(0.262)
Month 16; n=2354,2496
-0.90
(0.303)
-1.33
(0.296)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Albiglutide
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value 0.003
Comments P-value from a two-sided t-test to test whether the difference of least square means (Albiglutide-Placebo) is equal to zero.
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.11
Confidence Interval (2-Sided) 95%
-1.84 to -0.39
Parameter Dispersion Type:
Value:
Estimation Comments Based on MMRM model: Change=Baseline eGFR+Treatment+Visit+Treatment-by-Visit Interaction+Baseline eGFR-by-Visit Interaction. Difference of least squares means (Albiglutide-Placebo) is from MMRM model for Month 8.
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Albiglutide
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value 0.315
Comments P-value from a two-sided t-test to test whether the difference of least square means (Albiglutide-Placebo) is equal to zero
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.43
Confidence Interval (2-Sided) 95%
-1.26 to 0.41
Parameter Dispersion Type:
Value:
Estimation Comments Based on MMRM model: Change=Baseline eGFR+Treatment+Visit+Treatment-by-Visit Interaction+Baseline eGFR-by-Visit Interaction. Difference of least squares means (Albiglutide-Placebo) is from MMRM model for Month 16.
20. Secondary Outcome
Title Change From Baseline in Blood Pressure
Description Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were taken with the participant in a semi-recumbent or seated position after at least a 5-minute rest period. Baseline is the last non-missing value assessed on or before treatment start date. Change from Baseline is the value at specified time point minus the Baseline value.
Time Frame Baseline and Months 8,16,24 and end of study (up to 2.7 years)

Outcome Measure Data

Analysis Population Description
Safety Population. Only those participants with a value at Baseline and specified visit were analyzed (represented n=X in category titles)
Arm/Group Title Placebo Albiglutide
Arm/Group Description Albiglutide matching placebo was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region in addition to the standard of care therapy for diabetes and cardiovascular health. Albiglutide was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region. Participants were administered albiglutide at a dose of 30 milligrams (mg) or 50 mg once weekly in addition to the standard of care therapy for diabetes and cardiovascular health.
Measure Participants 4715 4717
SBP, Month 8; n=4241, 4319
-0.5
(17.33)
-1.0
(16.80)
SBP, Month 16; n=3082, 3187
-0.5
(17.45)
-0.9
(17.58)
SBP, Month 24; n=1133, 1198
-0.9
(18.62)
-1.2
(17.51)
SBP, End of study; n=3897, 4015
0.0
(17.68)
-0.4
(17.58)
DBP, Month 8; n=4241, 4319
-0.5
(10.26)
-0.4
(10.12)
DBP, Month 16; n=3082, 3187
-0.9
(10.74)
-0.5
(10.39)
DBP, Month 24; n=1133, 1198
-1.1
(10.87)
-1.0
(10.29)
DBP, End of study; n=3897, 4015
-0.7
(10.66)
-0.6
(10.57)
21. Secondary Outcome
Title Change From Baseline in Heart Rate
Description Heart rate was measured with the participant in a semi-recumbent or seated position after at least a 5-minute rest period. Baseline is the last non-missing value assessed on or before treatment start date. Change from Baseline is the value at specified time point minus the Baseline value.
Time Frame Baseline and Months 8, 16, 24 and end of study (up to 2.7 years)

Outcome Measure Data

Analysis Population Description
Safety Population. Only those participants with a value at Baseline and specified visit were analyzed (represented n=X in category titles)
Arm/Group Title Placebo Albiglutide
Arm/Group Description Albiglutide matching placebo was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region in addition to the standard of care therapy for diabetes and cardiovascular health. Albiglutide was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region. Participants were administered albiglutide at a dose of 30 milligrams (mg) or 50 mg once weekly in addition to the standard of care therapy for diabetes and cardiovascular health.
Measure Participants 4715 4717
Month 8; n=4239, 4312
0.2
(9.99)
1.6
(10.07)
Month 16; n=3078, 3181
0.3
(10.19)
1.6
(10.16)
Month 24; n=1131, 1195
0.6
(10.84)
1.7
(10.32)
End of study; n=3892, 4005
0.8
(10.64)
1.8
(10.50)

Adverse Events

Time Frame On-therapy non-SAEs and SAEs were reported on or after treatment start date and within 56 days after treatment stop date (Up to 2.7 years)
Adverse Event Reporting Description SAEs, non-SAELDs and non-SAEs of pre-specified interest were reported systematically in the Safety Population. Some investigators collected other non-SAEs for some participants (i.e. non-systematically). CV events referred for adjudication as study endpoints were not duplicate reported as AEs. Deaths were reported for ITT Population.
Arm/Group Title Albiglutide Placebo
Arm/Group Description Albiglutide was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region. Participants were administered albiglutide at a dose of 30 milligrams (mg) or 50 mg once weekly in addition to the standard of care therapy for diabetes and cardiovascular health.. Albiglutide matching placebo was administered once weekly as subcutaneous injection in the abdomen, thigh or upper arm region in addition to the standard of care therapy for diabetes and cardiovascular health.
All Cause Mortality
Albiglutide Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 196/4731 (4.1%) 205/4732 (4.3%)
Serious Adverse Events
Albiglutide Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 932/4717 (19.8%) 1022/4715 (21.7%)
Blood and lymphatic system disorders
Anaemia 7/4717 (0.1%) 8 10/4715 (0.2%) 10
Iron deficiency anaemia 5/4717 (0.1%) 5 3/4715 (0.1%) 3
Haemorrhagic anaemia 5/4717 (0.1%) 5 1/4715 (0%) 1
Lymphadenopathy mediastinal 2/4717 (0%) 2 0/4715 (0%) 0
Microcytic anaemia 0/4717 (0%) 0 2/4715 (0%) 2
Anaemia of chronic disease 0/4717 (0%) 0 1/4715 (0%) 1
Coagulopathy 0/4717 (0%) 0 1/4715 (0%) 1
Haemolysis 1/4717 (0%) 1 0/4715 (0%) 0
Lymph node fibrosis 0/4717 (0%) 0 1/4715 (0%) 1
Normochromic anaemia 0/4717 (0%) 0 1/4715 (0%) 1
Normocytic anaemia 0/4717 (0%) 0 1/4715 (0%) 1
Pancytopenia 1/4717 (0%) 1 0/4715 (0%) 0
Thrombocytopenia 1/4717 (0%) 1 0/4715 (0%) 0
Cardiac disorders
Atrial fibrillation 45/4717 (1%) 48 41/4715 (0.9%) 47
Angina pectoris 37/4717 (0.8%) 38 36/4715 (0.8%) 39
Coronary artery disease 24/4717 (0.5%) 24 31/4715 (0.7%) 31
Atrial flutter 6/4717 (0.1%) 6 14/4715 (0.3%) 15
Atrioventricular block complete 11/4717 (0.2%) 11 5/4715 (0.1%) 5
Ventricular tachycardia 6/4717 (0.1%) 7 9/4715 (0.2%) 10
Cardiac failure 10/4717 (0.2%) 10 4/4715 (0.1%) 4
Cardiogenic shock 9/4717 (0.2%) 9 4/4715 (0.1%) 4
Myocardial ischaemia 6/4717 (0.1%) 6 7/4715 (0.1%) 7
Bradycardia 8/4717 (0.2%) 8 4/4715 (0.1%) 4
Cardiac failure congestive 3/4717 (0.1%) 3 9/4715 (0.2%) 10
Cardio-respiratory arrest 5/4717 (0.1%) 5 5/4715 (0.1%) 6
Arteriosclerosis coronary artery 4/4717 (0.1%) 4 5/4715 (0.1%) 5
Cardiac arrest 4/4717 (0.1%) 4 5/4715 (0.1%) 5
Coronary artery stenosis 3/4717 (0.1%) 3 6/4715 (0.1%) 6
Sinus node dysfunction 2/4717 (0%) 2 6/4715 (0.1%) 6
Atrioventricular block second degree 3/4717 (0.1%) 3 4/4715 (0.1%) 4
Ventricular fibrillation 4/4717 (0.1%) 4 3/4715 (0.1%) 3
Aortic valve stenosis 3/4717 (0.1%) 3 3/4715 (0.1%) 3
Acute coronary syndrome 4/4717 (0.1%) 4 1/4715 (0%) 1
Pericarditis 1/4717 (0%) 1 4/4715 (0.1%) 5
Supraventricular tachycardia 3/4717 (0.1%) 3 2/4715 (0%) 2
Angina unstable 2/4717 (0%) 2 2/4715 (0%) 2
Atrioventricular block 1/4717 (0%) 1 3/4715 (0.1%) 3
Ventricular arrhythmia 1/4717 (0%) 1 3/4715 (0.1%) 3
Arrhythmia 1/4717 (0%) 1 2/4715 (0%) 2
Bundle branch block left 1/4717 (0%) 1 2/4715 (0%) 2
Cardiopulmonary failure 1/4717 (0%) 1 2/4715 (0%) 2
Ischaemic cardiomyopathy 0/4717 (0%) 0 3/4715 (0.1%) 3
Aortic valve disease 0/4717 (0%) 0 2/4715 (0%) 2
Aortic valve incompetence 1/4717 (0%) 1 1/4715 (0%) 1
Arrhythmia supraventricular 1/4717 (0%) 1 1/4715 (0%) 1
Cardiac asthma 1/4717 (0%) 1 1/4715 (0%) 1
Cardiac failure chronic 2/4717 (0%) 2 0/4715 (0%) 0
Cardiomegaly 1/4717 (0%) 1 1/4715 (0%) 1
Cardiomyopathy 1/4717 (0%) 1 1/4715 (0%) 1
Cardiovascular disorder 0/4717 (0%) 0 2/4715 (0%) 2
Coronary artery occlusion 1/4717 (0%) 1 1/4715 (0%) 1
Left ventricular failure 2/4717 (0%) 2 0/4715 (0%) 0
Myocardial fibrosis 0/4717 (0%) 0 2/4715 (0%) 2
Sinus tachycardia 2/4717 (0%) 2 0/4715 (0%) 0
Acute left ventricular failure 1/4717 (0%) 1 0/4715 (0%) 0
Acute myocardial infarction 1/4717 (0%) 1 0/4715 (0%) 0
Atrial thrombosis 0/4717 (0%) 0 1/4715 (0%) 1
Brugada syndrome 1/4717 (0%) 2 0/4715 (0%) 0
Cardiorenal syndrome 0/4717 (0%) 0 1/4715 (0%) 1
Coronary artery dissection 1/4717 (0%) 1 0/4715 (0%) 0
Coronary no-reflow phenomenon 1/4717 (0%) 1 0/4715 (0%) 0
Coronary ostial stenosis 1/4717 (0%) 1 0/4715 (0%) 0
Hypertensive heart disease 1/4717 (0%) 1 0/4715 (0%) 0
Intracardiac thrombus 1/4717 (0%) 1 0/4715 (0%) 0
Mitral valve incompetence 1/4717 (0%) 1 0/4715 (0%) 0
Myocarditis 0/4717 (0%) 0 1/4715 (0%) 1
Palpitations 1/4717 (0%) 1 0/4715 (0%) 0
Pericardial effusion 1/4717 (0%) 1 0/4715 (0%) 0
Right ventricular failure 0/4717 (0%) 0 1/4715 (0%) 1
Sinoatrial block 0/4717 (0%) 0 1/4715 (0%) 1
Sinus arrest 0/4717 (0%) 0 1/4715 (0%) 1
Sinus bradycardia 1/4717 (0%) 1 0/4715 (0%) 0
Tachycardia 1/4717 (0%) 1 0/4715 (0%) 0
Torsade de pointes 0/4717 (0%) 0 1/4715 (0%) 1
Ventricular extrasystoles 1/4717 (0%) 1 0/4715 (0%) 0
Congenital, familial and genetic disorders
Adenomatous polyposis coli 1/4717 (0%) 1 0/4715 (0%) 0
Haemorrhagic arteriovenous malformation 0/4717 (0%) 0 1/4715 (0%) 1
Hypertrophic cardiomyopathy 0/4717 (0%) 0 1/4715 (0%) 1
Phimosis 0/4717 (0%) 0 1/4715 (0%) 1
Ear and labyrinth disorders
Vertigo 2/4717 (0%) 2 5/4715 (0.1%) 6
Deafness 0/4717 (0%) 0 1/4715 (0%) 1
Deafness unilateral 0/4717 (0%) 0 1/4715 (0%) 1
Vertigo positional 1/4717 (0%) 1 0/4715 (0%) 0
Endocrine disorders
Adrenal mass 1/4717 (0%) 1 0/4715 (0%) 0
Goitre 0/4717 (0%) 0 1/4715 (0%) 1
Hyperparathyroidism 1/4717 (0%) 1 0/4715 (0%) 0
Eye disorders
Cataract 7/4717 (0.1%) 7 5/4715 (0.1%) 6
Glaucoma 1/4717 (0%) 1 6/4715 (0.1%) 6
Vitreous haemorrhage 5/4717 (0.1%) 5 2/4715 (0%) 2
Diabetic retinopathy 1/4717 (0%) 1 3/4715 (0.1%) 3
Eyelid ptosis 1/4717 (0%) 1 1/4715 (0%) 1
Macular degeneration 1/4717 (0%) 1 1/4715 (0%) 1
Blindness 1/4717 (0%) 1 0/4715 (0%) 0
Choroidal detachment 1/4717 (0%) 1 0/4715 (0%) 0
Diplopia 0/4717 (0%) 0 1/4715 (0%) 1
Eye pain 1/4717 (0%) 1 0/4715 (0%) 0
Hypotony of eye 1/4717 (0%) 1 0/4715 (0%) 0
Posterior capsule rupture 1/4717 (0%) 1 0/4715 (0%) 0
Retinal artery occlusion 1/4717 (0%) 1 0/4715 (0%) 0
Retinal detachment 0/4717 (0%) 0 1/4715 (0%) 1
Retinopathy 0/4717 (0%) 0 1/4715 (0%) 1
Retinopathy proliferative 1/4717 (0%) 1 0/4715 (0%) 0
Gastrointestinal disorders
Gastrointestinal haemorrhage 8/4717 (0.2%) 12 10/4715 (0.2%) 10
Gastritis 5/4717 (0.1%) 5 8/4715 (0.2%) 8
Small intestinal obstruction 5/4717 (0.1%) 5 5/4715 (0.1%) 6
Pancreatitis acute 6/4717 (0.1%) 7 3/4715 (0.1%) 3
Inguinal hernia 6/4717 (0.1%) 6 2/4715 (0%) 2
Colitis 3/4717 (0.1%) 3 4/4715 (0.1%) 4
Upper gastrointestinal haemorrhage 4/4717 (0.1%) 4 3/4715 (0.1%) 4
Abdominal pain 2/4717 (0%) 2 4/4715 (0.1%) 4
Abdominal pain upper 3/4717 (0.1%) 3 3/4715 (0.1%) 4
Diarrhoea 4/4717 (0.1%) 4 2/4715 (0%) 2
Vomiting 5/4717 (0.1%) 5 1/4715 (0%) 1
Duodenal ulcer 1/4717 (0%) 1 4/4715 (0.1%) 4
Gastric ulcer 3/4717 (0.1%) 3 2/4715 (0%) 2
Large intestine polyp 2/4717 (0%) 2 3/4715 (0.1%) 3
Abdominal hernia 3/4717 (0.1%) 3 1/4715 (0%) 1
Constipation 3/4717 (0.1%) 3 1/4715 (0%) 1
Dyspepsia 2/4717 (0%) 2 2/4715 (0%) 2
Impaired gastric emptying 1/4717 (0%) 1 3/4715 (0.1%) 3
Gastric ulcer haemorrhage 1/4717 (0%) 1 2/4715 (0%) 2
Gastritis erosive 2/4717 (0%) 2 1/4715 (0%) 1
Gastrooesophageal reflux disease 2/4717 (0%) 2 1/4715 (0%) 1
Lower gastrointestinal haemorrhage 2/4717 (0%) 5 1/4715 (0%) 1
Oesophagitis 1/4717 (0%) 1 2/4715 (0%) 2
Pancreatitis 1/4717 (0%) 1 2/4715 (0%) 2
Chronic gastritis 0/4717 (0%) 0 2/4715 (0%) 2
Diverticulum intestinal 2/4717 (0%) 2 0/4715 (0%) 0
Duodenal ulcer haemorrhage 0/4717 (0%) 0 2/4715 (0%) 2
Enteritis 0/4717 (0%) 0 2/4715 (0%) 2
Haemorrhoidal haemorrhage 1/4717 (0%) 1 1/4715 (0%) 1
Hiatus hernia 1/4717 (0%) 1 1/4715 (0%) 1
Intestinal obstruction 2/4717 (0%) 2 0/4715 (0%) 0
Melaena 1/4717 (0%) 1 1/4715 (0%) 1
Nausea 2/4717 (0%) 2 0/4715 (0%) 0
Oesophageal varices haemorrhage 0/4717 (0%) 0 2/4715 (0%) 2
Pancreatitis chronic 1/4717 (0%) 1 1/4715 (0%) 1
Peptic ulcer 2/4717 (0%) 2 0/4715 (0%) 0
Rectal haemorrhage 1/4717 (0%) 1 1/4715 (0%) 1
Strangulated umbilical hernia 0/4717 (0%) 0 2/4715 (0%) 2
Abdominal discomfort 0/4717 (0%) 0 1/4715 (0%) 1
Alcoholic pancreatitis 1/4717 (0%) 1 0/4715 (0%) 0
Anal fistula 1/4717 (0%) 1 0/4715 (0%) 0
Aortoenteric fistula 0/4717 (0%) 0 1/4715 (0%) 1
Ascites 0/4717 (0%) 0 1/4715 (0%) 1
Biliary ascites 0/4717 (0%) 0 1/4715 (0%) 1
Colitis ischaemic 0/4717 (0%) 0 1/4715 (0%) 1
Colitis ulcerative 1/4717 (0%) 1 0/4715 (0%) 0
Crohn's disease 1/4717 (0%) 1 0/4715 (0%) 0
Diabetic gastroparesis 1/4717 (0%) 1 0/4715 (0%) 0
Duodenal ulcer perforation 0/4717 (0%) 0 1/4715 (0%) 1
Duodenitis 0/4717 (0%) 0 1/4715 (0%) 1
Dysphagia 1/4717 (0%) 1 0/4715 (0%) 0
Epiploic appendagitis 1/4717 (0%) 1 0/4715 (0%) 0
Erosive oesophagitis 0/4717 (0%) 0 1/4715 (0%) 1
Faecaloma 1/4717 (0%) 1 0/4715 (0%) 0
Gastric antral vascular ectasia 1/4717 (0%) 1 0/4715 (0%) 0
Gastric haemorrhage 0/4717 (0%) 0 1/4715 (0%) 1
Gastroenteritis eosinophilic 1/4717 (0%) 1 0/4715 (0%) 0
Gastrointestinal disorder 1/4717 (0%) 1 0/4715 (0%) 0
Gastrointestinal necrosis 1/4717 (0%) 1 0/4715 (0%) 0
Haematemesis 0/4717 (0%) 0 1/4715 (0%) 1
Haemorrhoids 1/4717 (0%) 1 0/4715 (0%) 0
Hypoaesthesia oral 1/4717 (0%) 1 0/4715 (0%) 0
Ileus 1/4717 (0%) 1 0/4715 (0%) 0
Intestinal perforation 1/4717 (0%) 1 0/4715 (0%) 0
Intestinal polyp 0/4717 (0%) 0 1/4715 (0%) 1
Irritable bowel syndrome 0/4717 (0%) 0 1/4715 (0%) 1
Lip oedema 0/4717 (0%) 0 1/4715 (0%) 1
Oesophageal stenosis 0/4717 (0%) 0 1/4715 (0%) 1
Oesophageal ulcer 0/4717 (0%) 0 1/4715 (0%) 1
Palatal ulcer 0/4717 (0%) 0 1/4715 (0%) 1
Pancreatic duct stenosis 0/4717 (0%) 0 1/4715 (0%) 1
Peptic ulcer perforation 1/4717 (0%) 1 0/4715 (0%) 0
Proctalgia 0/4717 (0%) 0 1/4715 (0%) 1
Rectal polyp 1/4717 (0%) 1 0/4715 (0%) 0
Retroperitoneal haematoma 1/4717 (0%) 1 0/4715 (0%) 0
Umbilical hernia 0/4717 (0%) 0 1/4715 (0%) 1
Uvulitis 1/4717 (0%) 1 0/4715 (0%) 0
Varices oesophageal 1/4717 (0%) 1 0/4715 (0%) 0
General disorders
Non-cardiac chest pain 15/4717 (0.3%) 19 22/4715 (0.5%) 23
Death 10/4717 (0.2%) 10 14/4715 (0.3%) 14
Chest pain 8/4717 (0.2%) 8 10/4715 (0.2%) 10
Multiple organ dysfunction syndrome 6/4717 (0.1%) 6 6/4715 (0.1%) 6
Asthenia 4/4717 (0.1%) 4 4/4715 (0.1%) 4
Sudden death 2/4717 (0%) 2 3/4715 (0.1%) 3
Vascular stent stenosis 3/4717 (0.1%) 3 2/4715 (0%) 2
Impaired healing 1/4717 (0%) 1 3/4715 (0.1%) 4
Catheter site haemorrhage 1/4717 (0%) 1 1/4715 (0%) 1
Generalised oedema 0/4717 (0%) 0 2/4715 (0%) 2
Pyrexia 2/4717 (0%) 2 0/4715 (0%) 0
Sudden cardiac death 2/4717 (0%) 2 0/4715 (0%) 0
Systemic inflammatory response syndrome 0/4717 (0%) 0 2/4715 (0%) 2
Accidental death 0/4717 (0%) 0 1/4715 (0%) 1
Cardiac complication associated with device 1/4717 (0%) 1 0/4715 (0%) 0
Complication associated with device 1/4717 (0%) 1 0/4715 (0%) 0
Condition aggravated 0/4717 (0%) 0 1/4715 (0%) 1
Discomfort 0/4717 (0%) 0 1/4715 (0%) 1
Drug withdrawal syndrome 1/4717 (0%) 1 0/4715 (0%) 0
Fatigue 1/4717 (0%) 1 0/4715 (0%) 0
Incarcerated hernia 1/4717 (0%) 1 0/4715 (0%) 0
Inflammation 0/4717 (0%) 0 1/4715 (0%) 1
Mass 1/4717 (0%) 1 0/4715 (0%) 0
Necrobiosis 1/4717 (0%) 1 0/4715 (0%) 0
Necrosis 0/4717 (0%) 0 1/4715 (0%) 1
Pain 0/4717 (0%) 0 1/4715 (0%) 1
Soft tissue inflammation 0/4717 (0%) 0 1/4715 (0%) 1
Treatment noncompliance 0/4717 (0%) 0 1/4715 (0%) 1
Vascular stent occlusion 0/4717 (0%) 0 1/4715 (0%) 1
Vascular stent thrombosis 0/4717 (0%) 0 1/4715 (0%) 1
Hepatobiliary disorders
Cholelithiasis 12/4717 (0.3%) 12 7/4715 (0.1%) 7
Cholecystitis 7/4717 (0.1%) 7 5/4715 (0.1%) 5
Cholecystitis acute 7/4717 (0.1%) 7 4/4715 (0.1%) 4
Bile duct stone 2/4717 (0%) 2 1/4715 (0%) 1
Hepatic cirrhosis 1/4717 (0%) 1 2/4715 (0%) 2
Hepatic failure 0/4717 (0%) 0 3/4715 (0.1%) 3
Biliary colic 2/4717 (0%) 2 0/4715 (0%) 0
Cholecystitis chronic 0/4717 (0%) 0 2/4715 (0%) 2
Hepatitis acute 0/4717 (0%) 0 2/4715 (0%) 2
Ischaemic hepatitis 1/4717 (0%) 1 1/4715 (0%) 1
Acute hepatic failure 0/4717 (0%) 0 1/4715 (0%) 1
Drug-induced liver injury 0/4717 (0%) 0 1/4715 (0%) 1
Hepatic steatosis 0/4717 (0%) 0 1/4715 (0%) 1
Hepatotoxicity 0/4717 (0%) 0 1/4715 (0%) 1
Jaundice cholestatic 0/4717 (0%) 0 1/4715 (0%) 1
Liver disorder 0/4717 (0%) 0 1/4715 (0%) 1
Liver injury 1/4717 (0%) 1 0/4715 (0%) 0
Non-alcoholic steatohepatitis 1/4717 (0%) 1 0/4715 (0%) 0
Immune system disorders
Anaphylactic reaction 2/4717 (0%) 2 0/4715 (0%) 0
Contrast media reaction 1/4717 (0%) 1 0/4715 (0%) 0
Drug hypersensitivity 0/4717 (0%) 0 1/4715 (0%) 1
Hypersensitivity 0/4717 (0%) 0 1/4715 (0%) 1
Infections and infestations
Pneumonia 74/4717 (1.6%) 79 77/4715 (1.6%) 81
Sepsis 23/4717 (0.5%) 23 28/4715 (0.6%) 29
Urinary tract infection 26/4717 (0.6%) 27 23/4715 (0.5%) 27
Cellulitis 20/4717 (0.4%) 22 20/4715 (0.4%) 20
Bronchitis 10/4717 (0.2%) 10 11/4715 (0.2%) 12
Erysipelas 9/4717 (0.2%) 9 12/4715 (0.3%) 14
Osteomyelitis 6/4717 (0.1%) 6 14/4715 (0.3%) 14
Gangrene 6/4717 (0.1%) 6 13/4715 (0.3%) 14
Gastroenteritis 8/4717 (0.2%) 8 8/4715 (0.2%) 8
Urosepsis 6/4717 (0.1%) 6 8/4715 (0.2%) 8
Diabetic foot infection 4/4717 (0.1%) 6 9/4715 (0.2%) 9
Septic shock 4/4717 (0.1%) 4 7/4715 (0.1%) 7
Postoperative wound infection 6/4717 (0.1%) 6 4/4715 (0.1%) 4
Respiratory tract infection 5/4717 (0.1%) 5 5/4715 (0.1%) 5
Appendicitis 2/4717 (0%) 2 7/4715 (0.1%) 7
Influenza 3/4717 (0.1%) 3 5/4715 (0.1%) 5
Localised infection 3/4717 (0.1%) 3 4/4715 (0.1%) 4
Endocarditis 1/4717 (0%) 1 5/4715 (0.1%) 5
Infected skin ulcer 5/4717 (0.1%) 5 1/4715 (0%) 1
Pyelonephritis 2/4717 (0%) 2 4/4715 (0.1%) 4
Staphylococcal infection 2/4717 (0%) 2 4/4715 (0.1%) 4
Subcutaneous abscess 2/4717 (0%) 2 4/4715 (0.1%) 4
Upper respiratory tract infection 2/4717 (0%) 2 4/4715 (0.1%) 4
Abscess limb 2/4717 (0%) 2 3/4715 (0.1%) 3
Anal abscess 0/4717 (0%) 0 5/4715 (0.1%) 5
Bacteraemia 3/4717 (0.1%) 4 2/4715 (0%) 2
Cystitis 3/4717 (0.1%) 3 2/4715 (0%) 2
Infective exacerbation of chronic obstructive airways disease 2/4717 (0%) 2 3/4715 (0.1%) 3
Lower respiratory tract infection 1/4717 (0%) 1 4/4715 (0.1%) 5
Escherichia urinary tract infection 3/4717 (0.1%) 3 1/4715 (0%) 1
Gastroenteritis viral 3/4717 (0.1%) 3 1/4715 (0%) 1
Osteomyelitis acute 2/4717 (0%) 2 2/4715 (0%) 2
Wound infection 1/4717 (0%) 1 3/4715 (0.1%) 3
Arthritis bacterial 3/4717 (0.1%) 3 0/4715 (0%) 0
Diabetic gangrene 1/4717 (0%) 1 2/4715 (0%) 2
Diverticulitis 1/4717 (0%) 2 2/4715 (0%) 3
Epididymitis 1/4717 (0%) 1 2/4715 (0%) 2
Groin abscess 2/4717 (0%) 2 1/4715 (0%) 1
Staphylococcal sepsis 0/4717 (0%) 0 3/4715 (0.1%) 3
Viral infection 2/4717 (0%) 2 1/4715 (0%) 1
Abscess soft tissue 2/4717 (0%) 2 0/4715 (0%) 0
Acute sinusitis 1/4717 (0%) 1 1/4715 (0%) 1
Bronchitis bacterial 0/4717 (0%) 0 2/4715 (0%) 2
Clostridium difficile infection 1/4717 (0%) 1 1/4715 (0%) 1
Device related infection 0/4717 (0%) 0 2/4715 (0%) 2
Graft infection 0/4717 (0%) 0 2/4715 (0%) 2
Hepatitis C 1/4717 (0%) 1 1/4715 (0%) 1
Infection 1/4717 (0%) 1 1/4715 (0%) 1
Intervertebral discitis 0/4717 (0%) 0 2/4715 (0%) 2
Liver abscess 2/4717 (0%) 2 0/4715 (0%) 0
Perirectal abscess 2/4717 (0%) 3 0/4715 (0%) 0
Pneumonia viral 2/4717 (0%) 2 0/4715 (0%) 0
Post procedural sepsis 1/4717 (0%) 1 1/4715 (0%) 1
Pulmonary sepsis 2/4717 (0%) 2 0/4715 (0%) 0
Sinusitis 2/4717 (0%) 2 0/4715 (0%) 0
Staphylococcal bacteraemia 0/4717 (0%) 0 2/4715 (0%) 2
Wound sepsis 0/4717 (0%) 0 2/4715 (0%) 2
Abdominal abscess 1/4717 (0%) 1 0/4715 (0%) 0
Abdominal sepsis 1/4717 (0%) 1 0/4715 (0%) 0
Abdominal wall abscess 0/4717 (0%) 0 1/4715 (0%) 1
Abscess neck 0/4717 (0%) 0 1/4715 (0%) 1
Abscess oral 1/4717 (0%) 1 0/4715 (0%) 0
Arthritis infective 0/4717 (0%) 0 1/4715 (0%) 2
Beta haemolytic streptococcal infection 0/4717 (0%) 0 1/4715 (0%) 1
Brain abscess 0/4717 (0%) 0 1/4715 (0%) 1
Campylobacter gastroenteritis 1/4717 (0%) 1 0/4715 (0%) 0
Candiduria 1/4717 (0%) 1 0/4715 (0%) 0
Cellulitis gangrenous 1/4717 (0%) 1 0/4715 (0%) 0
Cellulitis of male external genital organ 0/4717 (0%) 0 1/4715 (0%) 1
Cholecystitis infective 1/4717 (0%) 1 0/4715 (0%) 0
Chronic sinusitis 1/4717 (0%) 1 0/4715 (0%) 0
Citrobacter infection 1/4717 (0%) 1 0/4715 (0%) 0
Citrobacter sepsis 1/4717 (0%) 1 0/4715 (0%) 0
Clostridial infection 1/4717 (0%) 1 0/4715 (0%) 0
Clostridium difficile colitis 1/4717 (0%) 1 0/4715 (0%) 0
Cystitis klebsiella 0/4717 (0%) 0 1/4715 (0%) 1
Dacryocystitis 0/4717 (0%) 0 1/4715 (0%) 1
Dengue fever 1/4717 (0%) 1 0/4715 (0%) 0
Dengue haemorrhagic fever 0/4717 (0%) 0 1/4715 (0%) 1
Emphysematous pyelonephritis 1/4717 (0%) 1 0/4715 (0%) 0
Empyema 1/4717 (0%) 1 0/4715 (0%) 0
Enterobacter sepsis 0/4717 (0%) 0 1/4715 (0%) 1
Enterococcal bacteraemia 0/4717 (0%) 0 1/4715 (0%) 1
Enterocolitis infectious 1/4717 (0%) 1 0/4715 (0%) 0
Extradural abscess 0/4717 (0%) 0 1/4715 (0%) 1
Gas gangrene 1/4717 (0%) 1 0/4715 (0%) 0
Gastroenteritis salmonella 1/4717 (0%) 1 0/4715 (0%) 0
H1N1 influenza 0/4717 (0%) 0 1/4715 (0%) 1
Haematoma infection 1/4717 (0%) 1 0/4715 (0%) 0
Helicobacter gastritis 1/4717 (0%) 1 0/4715 (0%) 0
Helicobacter infection 0/4717 (0%) 0 1/4715 (0%) 1
Hepatitis E 1/4717 (0%) 1 0/4715 (0%) 0
Herpes zoster 1/4717 (0%) 1 0/4715 (0%) 0
Herpes zoster infection neurological 1/4717 (0%) 1 0/4715 (0%) 0
Infected bite 0/4717 (0%) 0 1/4715 (0%) 1
Infectious pleural effusion 1/4717 (0%) 1 0/4715 (0%) 0
Lower respiratory tract infection bacterial 1/4717 (0%) 1 0/4715 (0%) 0
Medical device site infection 1/4717 (0%) 1 0/4715 (0%) 0
Meningitis pneumococcal 0/4717 (0%) 0 1/4715 (0%) 1
Meningitis viral 1/4717 (0%) 1 0/4715 (0%) 0
Nasopharyngitis 1/4717 (0%) 1 0/4715 (0%) 0
Oesophageal candidiasis 1/4717 (0%) 1 0/4715 (0%) 0
Oral candidiasis 1/4717 (0%) 1 0/4715 (0%) 0
Osteomyelitis chronic 0/4717 (0%) 0 1/4715 (0%) 1
Otitis externa 1/4717 (0%) 1 0/4715 (0%) 0
Otitis media 1/4717 (0%) 1 0/4715 (0%) 0
Parotitis 1/4717 (0%) 1 0/4715 (0%) 0
Pharyngeal abscess 0/4717 (0%) 0 1/4715 (0%) 1
Pneumonia bacterial 0/4717 (0%) 0 1/4715 (0%) 1
Pneumonia haemophilus 0/4717 (0%) 0 1/4715 (0%) 1
Pneumonia influenzal 1/4717 (0%) 1 0/4715 (0%) 0
Pneumonia moraxella 1/4717 (0%) 1 0/4715 (0%) 0
Post procedural cellulitis 1/4717 (0%) 1 0/4715 (0%) 0
Post procedural infection 0/4717 (0%) 0 1/4715 (0%) 1
Prostatic abscess 0/4717 (0%) 0 1/4715 (0%) 1
Psoas abscess 0/4717 (0%) 0 1/4715 (0%) 1
Pyelonephritis acute 1/4717 (0%) 1 0/4715 (0%) 0
Pyonephrosis 1/4717 (0%) 2 0/4715 (0%) 0
Renal abscess 1/4717 (0%) 1 0/4715 (0%) 0
Respiratory syncytial virus infection 1/4717 (0%) 1 0/4715 (0%) 0
Retroperitoneal abscess 0/4717 (0%) 0 1/4715 (0%) 1
Septic embolus 1/4717 (0%) 1 0/4715 (0%) 0
Soft tissue infection 1/4717 (0%) 1 0/4715 (0%) 0
Sternitis 1/4717 (0%) 1 0/4715 (0%) 0
Streptococcal bacteraemia 1/4717 (0%) 1 0/4715 (0%) 0
Streptococcal endocarditis 1/4717 (0%) 1 0/4715 (0%) 0
Streptococcal sepsis 0/4717 (0%) 0 1/4715 (0%) 1
Systemic candida 0/4717 (0%) 0 1/4715 (0%) 1
Systemic infection 0/4717 (0%) 0 1/4715 (0%) 1
Tongue abscess 1/4717 (0%) 1 0/4715 (0%) 0
Tonsillitis 0/4717 (0%) 0 1/4715 (0%) 1
Tuberculosis 1/4717 (0%) 1 0/4715 (0%) 0
Viral diarrhoea 1/4717 (0%) 1 0/4715 (0%) 0
Viral upper respiratory tract infection 1/4717 (0%) 1 0/4715 (0%) 0
Vulval abscess 0/4717 (0%) 0 1/4715 (0%) 1
Injury, poisoning and procedural complications
Fall 7/4717 (0.1%) 8 6/4715 (0.1%) 7
Hip fracture 6/4717 (0.1%) 6 2/4715 (0%) 2
Road traffic accident 3/4717 (0.1%) 3 4/4715 (0.1%) 4
Upper limb fracture 4/4717 (0.1%) 4 3/4715 (0.1%) 3
Rib fracture 2/4717 (0%) 2 4/4715 (0.1%) 4
Ankle fracture 2/4717 (0%) 2 3/4715 (0.1%) 3
Contusion 2/4717 (0%) 2 3/4715 (0.1%) 4
Humerus fracture 3/4717 (0.1%) 3 2/4715 (0%) 2
Joint dislocation 2/4717 (0%) 2 3/4715 (0.1%) 3
Tibia fracture 3/4717 (0.1%) 3 2/4715 (0%) 2
Craniocerebral injury 4/4717 (0.1%) 4 0/4715 (0%) 0
Femur fracture 1/4717 (0%) 1 3/4715 (0.1%) 3
Meniscus injury 2/4717 (0%) 2 2/4715 (0%) 2
Peripheral artery restenosis 0/4717 (0%) 0 4/4715 (0.1%) 4
Tendon rupture 2/4717 (0%) 2 2/4715 (0%) 2
Coronary artery restenosis 0/4717 (0%) 0 3/4715 (0.1%) 4
Fibula fracture 1/4717 (0%) 1 2/4715 (0%) 2
Incisional hernia 3/4717 (0.1%) 3 0/4715 (0%) 0
Limb injury 1/4717 (0%) 1 2/4715 (0%) 2
Post procedural haematoma 1/4717 (0%) 1 2/4715 (0%) 2
Post procedural haemorrhage 1/4717 (0%) 1 2/4715 (0%) 3
Spinal fracture 1/4717 (0%) 1 2/4715 (0%) 2
Wound dehiscence 0/4717 (0%) 0 3/4715 (0.1%) 3
Cardiac procedure complication 0/4717 (0%) 0 2/4715 (0%) 2
Concussion 0/4717 (0%) 0 2/4715 (0%) 2
Femoral neck fracture 1/4717 (0%) 1 1/4715 (0%) 1
Hand fracture 0/4717 (0%) 0 2/4715 (0%) 2
Head injury 1/4717 (0%) 1 1/4715 (0%) 1
Lower limb fracture 1/4717 (0%) 1 1/4715 (0%) 1
Lumbar vertebral fracture 0/4717 (0%) 0 2/4715 (0%) 2
Postoperative thoracic procedure complication 2/4717 (0%) 2 0/4715 (0%) 0
Postoperative wound complication 1/4717 (0%) 2 1/4715 (0%) 1
Spinal compression fracture 2/4717 (0%) 2 0/4715 (0%) 0
Subdural haematoma 2/4717 (0%) 2 0/4715 (0%) 0
Vascular pseudoaneurysm 2/4717 (0%) 2 0/4715 (0%) 0
Accidental overdose 0/4717 (0%) 0 1/4715 (0%) 1
Adjacent segment degeneration 1/4717 (0%) 1 0/4715 (0%) 0
Anastomotic stenosis 1/4717 (0%) 1 0/4715 (0%) 0
Animal bite 1/4717 (0%) 1 0/4715 (0%) 0
Arterial restenosis 0/4717 (0%) 0 1/4715 (0%) 1
Carbon monoxide poisoning 1/4717 (0%) 1 0/4715 (0%) 0
Cartilage injury 1/4717 (0%) 1 0/4715 (0%) 0
Chest injury 0/4717 (0%) 0 1/4715 (0%) 1
Fractured coccyx 0/4717 (0%) 0 1/4715 (0%) 1
Fractured sacrum 1/4717 (0%) 1 0/4715 (0%) 0
Gastrointestinal disorder postoperative 0/4717 (0%) 0 1/4715 (0%) 1
Graft thrombosis 1/4717 (0%) 1 0/4715 (0%) 0
Gun shot wound 1/4717 (0%) 1 0/4715 (0%) 0
Intentional overdose 1/4717 (0%) 1 0/4715 (0%) 0
Joint injury 0/4717 (0%) 0 1/4715 (0%) 1
Kidney contusion 0/4717 (0%) 0 1/4715 (0%) 1
Ligament injury 1/4717 (0%) 1 0/4715 (0%) 0
Ligament sprain 0/4717 (0%) 0 1/4715 (0%) 1
Limb traumatic amputation 1/4717 (0%) 1 0/4715 (0%) 0
Lip injury 0/4717 (0%) 0 1/4715 (0%) 1
Multiple injuries 1/4717 (0%) 1 0/4715 (0%) 0
Muscle rupture 1/4717 (0%) 1 0/4715 (0%) 0
Open globe injury 0/4717 (0%) 0 1/4715 (0%) 1
Overdose 1/4717 (0%) 1 0/4715 (0%) 0
Patella fracture 1/4717 (0%) 1 0/4715 (0%) 0
Perirenal haematoma 1/4717 (0%) 1 0/4715 (0%) 0
Post procedural haematuria 1/4717 (0%) 1 0/4715 (0%) 0
Post-traumatic pain 1/4717 (0%) 1 0/4715 (0%) 0
Postoperative delirium 0/4717 (0%) 0 1/4715 (0%) 1
Procedural pneumothorax 0/4717 (0%) 0 1/4715 (0%) 1
Radius fracture 1/4717 (0%) 1 0/4715 (0%) 0
Shunt stenosis 1/4717 (0%) 1 0/4715 (0%) 0
Sternal fracture 1/4717 (0%) 1 0/4715 (0%) 0
Subarachnoid haemorrhage 1/4717 (0%) 1 0/4715 (0%) 0
Suture related complication 1/4717 (0%) 1 0/4715 (0%) 0
Suture rupture 1/4717 (0%) 1 0/4715 (0%) 0
Thoracic vertebral fracture 0/4717 (0%) 0 1/4715 (0%) 1
Traumatic haematoma 1/4717 (0%) 1 0/4715 (0%) 0
Traumatic intracranial haemorrhage 0/4717 (0%) 0 1/4715 (0%) 1
Ulnar nerve injury 1/4717 (0%) 1 0/4715 (0%) 0
Vascular graft occlusion 1/4717 (0%) 1 0/4715 (0%) 0
Vascular graft thrombosis 0/4717 (0%) 0 1/4715 (0%) 1
Wound evisceration 0/4717 (0%) 0 1/4715 (0%) 1
Investigations
Electrocardiogram QT prolonged 4/4717 (0.1%) 4 0/4715 (0%) 0
Blood creatinine increased 1/4717 (0%) 1 2/4715 (0%) 2
Hepatic enzyme increased 3/4717 (0.1%) 3 0/4715 (0%) 0
Liver function test increased 2/4717 (0%) 2 1/4715 (0%) 1
Glomerular filtration rate decreased 0/4717 (0%) 0 2/4715 (0%) 2
Troponin increased 1/4717 (0%) 1 1/4715 (0%) 1
Alanine aminotransferase increased 0/4717 (0%) 0 1/4715 (0%) 1
Anticoagulation drug level above therapeutic 1/4717 (0%) 1 0/4715 (0%) 0
Aspiration bronchial 1/4717 (0%) 1 0/4715 (0%) 0
Blood alkaline phosphatase increased 0/4717 (0%) 0 1/4715 (0%) 1
Blood glucose abnormal 0/4717 (0%) 0 1/4715 (0%) 1
Blood ketone body increased 1/4717 (0%) 1 0/4715 (0%) 0
Gamma-glutamyltransferase increased 0/4717 (0%) 0 1/4715 (0%) 1
Myocardial necrosis marker increased 1/4717 (0%) 1 0/4715 (0%) 0
Thyroid function test normal 0/4717 (0%) 0 1/4715 (0%) 1
Weight decreased 1/4717 (0%) 1 0/4715 (0%) 0
Weight increased 1/4717 (0%) 1 0/4715 (0%) 0
Metabolism and nutrition disorders
Hyperglycaemia 16/4717 (0.3%) 16 30/4715 (0.6%) 42
Hypoglycaemia 12/4717 (0.3%) 12 30/4715 (0.6%) 34
Diabetes mellitus inadequate control 4/4717 (0.1%) 4 13/4715 (0.3%) 13
Dehydration 3/4717 (0.1%) 3 9/4715 (0.2%) 9
Diabetic ketoacidosis 5/4717 (0.1%) 5 6/4715 (0.1%) 6
Diabetic metabolic decompensation 2/4717 (0%) 2 8/4715 (0.2%) 9
Hyperkalaemia 5/4717 (0.1%) 5 5/4715 (0.1%) 5
Type 2 diabetes mellitus 4/4717 (0.1%) 4 6/4715 (0.1%) 6
Diabetes mellitus 2/4717 (0%) 2 6/4715 (0.1%) 6
Hypokalaemia 1/4717 (0%) 1 4/4715 (0.1%) 4
Metabolic acidosis 1/4717 (0%) 1 4/4715 (0.1%) 4
Obesity 2/4717 (0%) 2 3/4715 (0.1%) 3
Hyperglycaemic hyperosmolar nonketotic syndrome 2/4717 (0%) 2 2/4715 (0%) 3
Lactic acidosis 0/4717 (0%) 0 3/4715 (0.1%) 3
Hypocalcaemia 1/4717 (0%) 1 1/4715 (0%) 1
Hypomagnesaemia 1/4717 (0%) 1 1/4715 (0%) 1
Decreased appetite 1/4717 (0%) 1 0/4715 (0%) 0
Failure to thrive 1/4717 (0%) 1 0/4715 (0%) 0
Fluid overload 0/4717 (0%) 0 1/4715 (0%) 1
Food intolerance 0/4717 (0%) 0 1/4715 (0%) 1
Gout 0/4717 (0%) 0 1/4715 (0%) 1
Hypercalcaemia 1/4717 (0%) 1 0/4715 (0%) 0
Hyperosmolar state 0/4717 (0%) 0 1/4715 (0%) 1
Hypoalbuminaemia 0/4717 (0%) 0 1/4715 (0%) 1
Hyponatraemia 0/4717 (0%) 0 1/4715 (0%) 1
Hypovolaemia 1/4717 (0%) 1 0/4715 (0%) 0
Insulin-requiring type 2 diabetes mellitus 1/4717 (0%) 1 0/4715 (0%) 0
Iron deficiency 1/4717 (0%) 1 0/4715 (0%) 0
Ketoacidosis 1/4717 (0%) 1 0/4715 (0%) 0
Ketosis 1/4717 (0%) 1 0/4715 (0%) 0
Musculoskeletal and connective tissue disorders
Osteoarthritis 7/4717 (0.1%) 9 16/4715 (0.3%) 16
Musculoskeletal chest pain 4/4717 (0.1%) 6 6/4715 (0.1%) 6
Lumbar spinal stenosis 4/4717 (0.1%) 4 4/4715 (0.1%) 4
Rotator cuff syndrome 6/4717 (0.1%) 6 2/4715 (0%) 2
Back pain 4/4717 (0.1%) 4 3/4715 (0.1%) 4
Intervertebral disc protrusion 4/4717 (0.1%) 4 2/4715 (0%) 2
Spinal column stenosis 1/4717 (0%) 1 3/4715 (0.1%) 3
Muscle haemorrhage 2/4717 (0%) 2 1/4715 (0%) 1
Muscular weakness 0/4717 (0%) 0 3/4715 (0.1%) 4
Musculoskeletal pain 2/4717 (0%) 2 1/4715 (0%) 1
Arthralgia 2/4717 (0%) 2 0/4715 (0%) 0
Intervertebral disc degeneration 0/4717 (0%) 0 2/4715 (0%) 2
Osteitis 2/4717 (0%) 2 0/4715 (0%) 0
Osteonecrosis 1/4717 (0%) 1 1/4715 (0%) 1
Pain in extremity 1/4717 (0%) 1 1/4715 (0%) 1
Rheumatoid arthritis 1/4717 (0%) 1 1/4715 (0%) 1
Spinal osteoarthritis 1/4717 (0%) 1 1/4715 (0%) 1
Spinal pain 0/4717 (0%) 0 2/4715 (0%) 2
Arthritis 0/4717 (0%) 0 1/4715 (0%) 1
Arthropathy 0/4717 (0%) 0 1/4715 (0%) 1
Articular calcification 0/4717 (0%) 0 1/4715 (0%) 1
Bursitis 1/4717 (0%) 1 0/4715 (0%) 0
Cervical spinal stenosis 1/4717 (0%) 1 0/4715 (0%) 0
Costochondritis 1/4717 (0%) 1 0/4715 (0%) 0
Fibromyalgia 0/4717 (0%) 0 1/4715 (0%) 1
Fracture nonunion 0/4717 (0%) 0 1/4715 (0%) 1
Intervertebral disc disorder 0/4717 (0%) 0 1/4715 (0%) 1
Myalgia 0/4717 (0%) 0 1/4715 (0%) 1
Neuropathic arthropathy 1/4717 (0%) 2 0/4715 (0%) 0
Osteochondrosis 0/4717 (0%) 0 1/4715 (0%) 1
Osteolysis 1/4717 (0%) 1 0/4715 (0%) 0
Osteoporosis 0/4717 (0%) 0 1/4715 (0%) 1
Osteoporotic fracture 0/4717 (0%) 0 1/4715 (0%) 1
Rhabdomyolysis 1/4717 (0%) 1 0/4715 (0%) 0
Sjogren's syndrome 1/4717 (0%) 2 0/4715 (0%) 0
Spondylolisthesis 1/4717 (0%) 1 0/4715 (0%) 0
Tendonitis 1/4717 (0%) 1 0/4715 (0%) 0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer 5/4717 (0.1%) 5 12/4715 (0.3%) 12
Lung neoplasm malignant 9/4717 (0.2%) 9 2/4715 (0%) 2
Breast cancer 4/4717 (0.1%) 4 5/4715 (0.1%) 5
Bladder cancer 1/4717 (0%) 1 7/4715 (0.1%) 7
Adenocarcinoma of colon 2/4717 (0%) 2 5/4715 (0.1%) 5
Pancreatic carcinoma metastatic 4/4717 (0.1%) 4 2/4715 (0%) 2
Lung cancer metastatic 3/4717 (0.1%) 3 2/4715 (0%) 2
Metastases to liver 2/4717 (0%) 2 3/4715 (0.1%) 3
Pancreatic carcinoma 2/4717 (0%) 2 3/4715 (0.1%) 3
Breast cancer metastatic 1/4717 (0%) 1 3/4715 (0.1%) 3
Colon cancer 1/4717 (0%) 1 3/4715 (0.1%) 3
Metastases to central nervous system 2/4717 (0%) 2 2/4715 (0%) 2
Adenocarcinoma 0/4717 (0%) 0 3/4715 (0.1%) 3
Basal cell carcinoma 2/4717 (0%) 2 1/4715 (0%) 1
Bronchial carcinoma 2/4717 (0%) 2 1/4715 (0%) 1
Colon cancer metastatic 0/4717 (0%) 0 3/4715 (0.1%) 3
Hepatocellular carcinoma 1/4717 (0%) 1 2/4715 (0%) 2
Malignant melanoma 2/4717 (0%) 2 1/4715 (0%) 1
Renal neoplasm 2/4717 (0%) 2 1/4715 (0%) 1
Salivary gland neoplasm 2/4717 (0%) 2 1/4715 (0%) 1
Squamous cell carcinoma 2/4717 (0%) 2 1/4715 (0%) 1
Uterine cancer 0/4717 (0%) 0 3/4715 (0.1%) 3
Uterine leiomyoma 2/4717 (0%) 2 1/4715 (0%) 1
Acute myeloid leukaemia 2/4717 (0%) 2 0/4715 (0%) 0
Adenocarcinoma gastric 2/4717 (0%) 2 0/4715 (0%) 0
B-cell lymphoma 1/4717 (0%) 1 1/4715 (0%) 1
Bladder neoplasm 1/4717 (0%) 1 1/4715 (0%) 1
Cholangiocarcinoma 1/4717 (0%) 1 1/4715 (0%) 1
Gastric cancer 2/4717 (0%) 2 0/4715 (0%) 0
Hepatic cancer 2/4717 (0%) 2 0/4715 (0%) 0
Intraductal proliferative breast lesion 0/4717 (0%) 0 2/4715 (0%) 2
Laryngeal cancer 1/4717 (0%) 1 1/4715 (0%) 1
Laryngeal papilloma 1/4717 (0%) 1 1/4715 (0%) 1
Lung adenocarcinoma 0/4717 (0%) 0 2/4715 (0%) 2
Lung neoplasm 0/4717 (0%) 0 2/4715 (0%) 2
Lymphoproliferative disorder 2/4717 (0%) 2 0/4715 (0%) 0
Malignant neoplasm of unknown primary site 2/4717 (0%) 2 0/4715 (0%) 0
Meningioma 0/4717 (0%) 0 2/4715 (0%) 2
Metastases to bone 1/4717 (0%) 1 1/4715 (0%) 1
Metastatic gastric cancer 0/4717 (0%) 0 2/4715 (0%) 2
Prostatic adenoma 1/4717 (0%) 1 1/4715 (0%) 1
Rectal cancer 2/4717 (0%) 2 0/4715 (0%) 0
Squamous cell carcinoma of lung 0/4717 (0%) 0 2/4715 (0%) 2
Squamous cell carcinoma of skin 1/4717 (0%) 1 1/4715 (0%) 1
Squamous cell carcinoma of the oral cavity 0/4717 (0%) 0 2/4715 (0%) 2
Adrenal adenoma 0/4717 (0%) 0 1/4715 (0%) 1
Benign gastric neoplasm 0/4717 (0%) 0 1/4715 (0%) 1
Benign neoplasm of bladder 1/4717 (0%) 1 0/4715 (0%) 0
Benign salivary gland neoplasm 1/4717 (0%) 1 0/4715 (0%) 0
Bladder cancer recurrent 0/4717 (0%) 0 1/4715 (0%) 1
Bladder cancer stage 0, with cancer in situ 0/4717 (0%) 0 1/4715 (0%) 1
Bladder cancer stage III 1/4717 (0%) 1 0/4715 (0%) 0
Bone cancer 0/4717 (0%) 0 1/4715 (0%) 1
Brain neoplasm malignant 0/4717 (0%) 0 1/4715 (0%) 1
Breast cancer stage II 0/4717 (0%) 0 1/4715 (0%) 1
Breast fibroma 1/4717 (0%) 1 0/4715 (0%) 0
Breast neoplasm 1/4717 (0%) 1 0/4715 (0%) 0
Bronchial neoplasm 0/4717 (0%) 0 1/4715 (0%) 1
Cardiac myxoma 0/4717 (0%) 0 1/4715 (0%) 1
Chromophobe renal cell carcinoma 0/4717 (0%) 0 1/4715 (0%) 1
Chronic lymphocytic leukaemia 0/4717 (0%) 0 1/4715 (0%) 1
Chronic myeloid leukaemia 1/4717 (0%) 1 0/4715 (0%) 0
Colon cancer stage 0 1/4717 (0%) 1 0/4715 (0%) 0
Colon cancer stage IV 0/4717 (0%) 0 1/4715 (0%) 1
Colorectal adenocarcinoma 1/4717 (0%) 1 0/4715 (0%) 0
Corneoconjunctival intraepithelial neoplasia 0/4717 (0%) 0 1/4715 (0%) 1
Dermatofibrosarcoma protuberans 0/4717 (0%) 0 1/4715 (0%) 1
Diffuse large B-cell lymphoma 1/4717 (0%) 1 0/4715 (0%) 0
Endometrial adenocarcinoma 1/4717 (0%) 1 0/4715 (0%) 0
Glioblastoma 0/4717 (0%) 0 1/4715 (0%) 1
Hypopharyngeal cancer 0/4717 (0%) 0 1/4715 (0%) 1
Intestinal adenocarcinoma 0/4717 (0%) 0 1/4715 (0%) 1
Intestinal metastasis 1/4717 (0%) 1 0/4715 (0%) 0
Invasive ductal breast carcinoma 1/4717 (0%) 1 0/4715 (0%) 0
Laryngeal squamous cell carcinoma 1/4717 (0%) 1 0/4715 (0%) 0
Lip squamous cell carcinoma 0/4717 (0%) 0 1/4715 (0%) 1
Lymphocytic leukaemia 0/4717 (0%) 0 1/4715 (0%) 1
Malignant melanoma in situ 1/4717 (0%) 1 0/4715 (0%) 0
Metastases to adrenals 0/4717 (0%) 0 1/4715 (0%) 1
Metastases to lung 1/4717 (0%) 1 0/4715 (0%) 0
Metastases to peritoneum 1/4717 (0%) 1 0/4715 (0%) 0
Metastatic bronchial carcinoma 0/4717 (0%) 0 1/4715 (0%) 1
Metastatic neoplasm 1/4717 (0%) 1 0/4715 (0%) 0
Nervous system neoplasm benign 0/4717 (0%) 0 1/4715 (0%) 1
Neuroendocrine carcinoma 0/4717 (0%) 0 1/4715 (0%) 1
Neuroendocrine carcinoma metastatic 1/4717 (0%) 1 0/4715 (0%) 0
Non-small cell lung cancer metastatic 0/4717 (0%) 0 1/4715 (0%) 1
Non-small cell lung cancer stage II 0/4717 (0%) 0 1/4715 (0%) 1
Oesophageal cancer metastatic 0/4717 (0%) 0 1/4715 (0%) 1
Oesophageal carcinoma 0/4717 (0%) 0 1/4715 (0%) 1
Oesophageal squamous cell carcinoma 0/4717 (0%) 0 1/4715 (0%) 1
Oral papilloma 0/4717 (0%) 0 1/4715 (0%) 1
Osteoma 0/4717 (0%) 0 1/4715 (0%) 1
Osteosarcoma metastatic 1/4717 (0%) 1 0/4715 (0%) 0
Ovarian adenoma 1/4717 (0%) 1 0/4715 (0%) 0
Ovarian cancer stage I 0/4717 (0%) 0 1/4715 (0%) 1
Papillary cystadenoma lymphomatosum 1/4717 (0%) 1 0/4715 (0%) 0
Plasma cell myeloma 1/4717 (0%) 1 0/4715 (0%) 0
Polycythaemia vera 0/4717 (0%) 0 1/4715 (0%) 1
Prostate cancer metastatic 1/4717 (0%) 1 0/4715 (0%) 0
Prostate cancer recurrent 0/4717 (0%) 0 1/4715 (0%) 1
Rectal adenocarcinoma 1/4717 (0%) 1 0/4715 (0%) 0
Rectosigmoid cancer stage II 1/4717 (0%) 1 0/4715 (0%) 0
Renal adenoma 0/4717 (0%) 0 1/4715 (0%) 1
Renal cancer 0/4717 (0%) 0 1/4715 (0%) 1
Renal cancer metastatic 1/4717 (0%) 1 0/4715 (0%) 0
Renal cell carcinoma 1/4717 (0%) 1 0/4715 (0%) 0
Retroperitoneal neoplasm 0/4717 (0%) 0 1/4715 (0%) 1
Small cell lung cancer 0/4717 (0%) 0 1/4715 (0%) 1
Small intestine carcinoma 0/4717 (0%) 0 1/4715 (0%) 1
Squamous cell carcinoma of the tongue 0/4717 (0%) 0 1/4715 (0%) 1
Squamous cell carcinoma of the vulva 0/4717 (0%) 0 1/4715 (0%) 1
Testicular neoplasm 1/4717 (0%) 1 0/4715 (0%) 0
Vulval cancer 1/4717 (0%) 1 0/4715 (0%) 0
Nervous system disorders
Syncope 14/4717 (0.3%) 17 13/4715 (0.3%) 15
Carotid artery stenosis 9/4717 (0.2%) 11 7/4715 (0.1%) 7
Presyncope 5/4717 (0.1%) 5 3/4715 (0.1%) 3
Metabolic encephalopathy 5/4717 (0.1%) 5 1/4715 (0%) 1
Carotid artery occlusion 3/4717 (0.1%) 3 2/4715 (0%) 2
Diabetic neuropathy 2/4717 (0%) 2 3/4715 (0.1%) 3
Dizziness 2/4717 (0%) 2 3/4715 (0.1%) 3
Seizure 1/4717 (0%) 1 4/4715 (0.1%) 4
Headache 2/4717 (0%) 2 2/4715 (0%) 2
Brain injury 3/4717 (0.1%) 3 0/4715 (0%) 0
Dementia 0/4717 (0%) 0 3/4715 (0.1%) 3
Encephalopathy 1/4717 (0%) 1 2/4715 (0%) 2
Facial paralysis 1/4717 (0%) 1 2/4715 (0%) 2
Migraine 3/4717 (0.1%) 3 0/4715 (0%) 0
Vertebrobasilar insufficiency 2/4717 (0%) 2 1/4715 (0%) 1
Carotid arteriosclerosis 1/4717 (0%) 1 1/4715 (0%) 1
Carpal tunnel syndrome 1/4717 (0%) 1 1/4715 (0%) 1
Cerebral arteriosclerosis 0/4717 (0%) 0 2/4715 (0%) 2
Cerebral haemorrhage 1/4717 (0%) 1 1/4715 (0%) 1
Cervicobrachial syndrome 1/4717 (0%) 1 1/4715 (0%) 1
Dizziness postural 0/4717 (0%) 0 2/4715 (0%) 2
Epilepsy 0/4717 (0%) 0 2/4715 (0%) 2
Facial paresis 1/4717 (0%) 1 1/4715 (0%) 1
IIIrd nerve paresis 2/4717 (0%) 2 0/4715 (0%) 0
Loss of consciousness 0/4717 (0%) 0 2/4715 (0%) 2
Myelopathy 0/4717 (0%) 0 2/4715 (0%) 2
Neuropathy peripheral 0/4717 (0%) 0 2/4715 (0%) 2
Peripheral sensory neuropathy 1/4717 (0%) 1 1/4715 (0%) 1
Acoustic neuritis 1/4717 (0%) 1 0/4715 (0%) 0
Aphasia 0/4717 (0%) 0 1/4715 (0%) 1
Autonomic neuropathy 0/4717 (0%) 0 1/4715 (0%) 1
Basilar artery aneurysm 0/4717 (0%) 0 1/4715 (0%) 1
Carotid artery disease 0/4717 (0%) 0 1/4715 (0%) 1
Cauda equina syndrome 1/4717 (0%) 1 0/4715 (0%) 0
Cerebral infarction 1/4717 (0%) 1 0/4715 (0%) 0
Cerebral ischaemia 0/4717 (0%) 0 1/4715 (0%) 1
Cerebrovascular accident 0/4717 (0%) 0 1/4715 (0%) 1
Cognitive disorder 0/4717 (0%) 0 1/4715 (0%) 1
Dementia Alzheimer's type 1/4717 (0%) 1 0/4715 (0%) 0
Depressed level of consciousness 0/4717 (0%) 0 1/4715 (0%) 1
Diabetic mononeuropathy 1/4717 (0%) 1 0/4715 (0%) 0
Dysarthria 1/4717 (0%) 1 0/4715 (0%) 0
Facial nerve disorder 1/4717 (0%) 1 0/4715 (0%) 0
Hemiparesis 1/4717 (0%) 1 0/4715 (0%) 0
Hydrocephalus 1/4717 (0%) 1 0/4715 (0%) 0
Hypoaesthesia 0/4717 (0%) 0 1/4715 (0%) 1
Hypoglycaemic coma 1/4717 (0%) 1 0/4715 (0%) 0
Hypoglycaemic unconsciousness 0/4717 (0%) 0 1/4715 (0%) 1
IIIrd nerve disorder 1/4717 (0%) 1 0/4715 (0%) 0
Intensive care unit acquired weakness 1/4717 (0%) 1 0/4715 (0%) 0
Intracranial aneurysm 0/4717 (0%) 0 1/4715 (0%) 1
Lacunar infarction 0/4717 (0%) 0 1/4715 (0%) 1
Lumbosacral radiculopathy 1/4717 (0%) 1 0/4715 (0%) 0
Memory impairment 1/4717 (0%) 1 0/4715 (0%) 0
Mixed dementia 0/4717 (0%) 0 1/4715 (0%) 1
Mononeuritis 0/4717 (0%) 0 1/4715 (0%) 1
Mononeuropathy multiplex 1/4717 (0%) 1 0/4715 (0%) 0
Multiple system atrophy 0/4717 (0%) 0 1/4715 (0%) 1
Myasthenia gravis 1/4717 (0%) 1 0/4715 (0%) 0
Nerve degeneration 0/4717 (0%) 0 1/4715 (0%) 1
Neuromyopathy 1/4717 (0%) 1 0/4715 (0%) 0
Normal pressure hydrocephalus 1/4717 (0%) 1 0/4715 (0%) 0
Orthostatic intolerance 1/4717 (0%) 1 0/4715 (0%) 0
Partial seizures 0/4717 (0%) 0 1/4715 (0%) 1
Post stroke seizure 0/4717 (0%) 0 1/4715 (0%) 1
Radial nerve compression 0/4717 (0%) 0 1/4715 (0%) 1
Sciatica 1/4717 (0%) 1 0/4715 (0%) 0
Sinus headache 0/4717 (0%) 0 1/4715 (0%) 1
Spinal cord compression 0/4717 (0%) 0 1/4715 (0%) 1
Spinal cord herniation 1/4717 (0%) 1 0/4715 (0%) 0
Spinal cord ischaemia 0/4717 (0%) 0 1/4715 (0%) 1
Toxic encephalopathy 0/4717 (0%) 0 1/4715 (0%) 1
Transient ischaemic attack 1/4717 (0%) 1 0/4715 (0%) 0
Tremor 0/4717 (0%) 0 1/4715 (0%) 1
Vertebral artery dissection 0/4717 (0%) 0 1/4715 (0%) 1
Vertebral artery stenosis 0/4717 (0%) 0 1/4715 (0%) 1
Vocal cord paralysis 1/4717 (0%) 1 0/4715 (0%) 0
Product Issues
Device malfunction 1/4717 (0%) 1 3/4715 (0.1%) 3
Device failure 2/4717 (0%) 2 1/4715 (0%) 1
Device extrusion 1/4717 (0%) 1 0/4715 (0%) 0
Device issue 0/4717 (0%) 0 1/4715 (0%) 1
Psychiatric disorders
Depression 2/4717 (0%) 2 3/4715 (0.1%) 3
Mental status changes 0/4717 (0%) 0 5/4715 (0.1%) 5
Suicide attempt 1/4717 (0%) 1 2/4715 (0%) 2
Delirium 0/4717 (0%) 0 2/4715 (0%) 2
Suicidal ideation 1/4717 (0%) 4 1/4715 (0%) 1
Adjustment disorder 0/4717 (0%) 0 1/4715 (0%) 1
Affective disorder 1/4717 (0%) 1 0/4715 (0%) 0
Alcoholism 0/4717 (0%) 0 1/4715 (0%) 1
Anxiety disorder 1/4717 (0%) 1 0/4715 (0%) 0
Bipolar disorder 1/4717 (0%) 1 0/4715 (0%) 0
Breathing-related sleep disorder 1/4717 (0%) 1 0/4715 (0%) 0
Completed suicide 1/4717 (0%) 1 0/4715 (0%) 0
Hallucination 1/4717 (0%) 1 0/4715 (0%) 0
Impulse-control disorder 1/4717 (0%) 1 0/4715 (0%) 0
Psychotic disorder 0/4717 (0%) 0 1/4715 (0%) 1
Renal and urinary disorders
Acute kidney injury 42/4717 (0.9%) 46 47/4715 (1%) 52
Renal impairment 17/4717 (0.4%) 17 12/4715 (0.3%) 13
Renal failure 9/4717 (0.2%) 10 7/4715 (0.1%) 7
Chronic kidney disease 5/4717 (0.1%) 5 7/4715 (0.1%) 7
Haematuria 5/4717 (0.1%) 5 3/4715 (0.1%) 3
Nephrolithiasis 2/4717 (0%) 2 6/4715 (0.1%) 6
Ureterolithiasis 3/4717 (0.1%) 3 4/4715 (0.1%) 4
Hydronephrosis 1/4717 (0%) 1 2/4715 (0%) 2
Renal artery stenosis 2/4717 (0%) 2 1/4715 (0%) 1
Renal colic 1/4717 (0%) 1 2/4715 (0%) 2
Renal tubular necrosis 2/4717 (0%) 2 1/4715 (0%) 1
Urinary tract obstruction 1/4717 (0%) 1 1/4715 (0%) 1
Bladder neck obstruction 1/4717 (0%) 1 0/4715 (0%) 0
Calculus urinary 0/4717 (0%) 0 1/4715 (0%) 1
Diabetic nephropathy 0/4717 (0%) 0 1/4715 (0%) 1
Glomerulonephritis acute 1/4717 (0%) 1 0/4715 (0%) 0
Hypertonic bladder 1/4717 (0%) 1 0/4715 (0%) 0
Lower urinary tract symptoms 0/4717 (0%) 0 1/4715 (0%) 1
Nephropathy 0/4717 (0%) 0 1/4715 (0%) 1
Nephropathy toxic 1/4717 (0%) 1 0/4715 (0%) 0
Nephrotic syndrome 0/4717 (0%) 0 1/4715 (0%) 1
Renal cyst 0/4717 (0%) 0 1/4715 (0%) 1
Renal disorder 1/4717 (0%) 1 0/4715 (0%) 0
Renal haematoma 0/4717 (0%) 0 1/4715 (0%) 1
Renal injury 1/4717 (0%) 1 0/4715 (0%) 0
Renal mass 1/4717 (0%) 1 0/4715 (0%) 0
Urethral obstruction 0/4717 (0%) 0 1/4715 (0%) 1
Urethral stenosis 1/4717 (0%) 1 0/4715 (0%) 0
Urinary incontinence 0/4717 (0%) 0 1/4715 (0%) 1
Urinary retention 1/4717 (0%) 1 0/4715 (0%) 0
Reproductive system and breast disorders
Benign prostatic hyperplasia 3/4717 (0.1%) 3 6/4715 (0.1%) 6
Prostatitis 3/4717 (0.1%) 3 2/4715 (0%) 2
Endometrial hyperplasia 0/4717 (0%) 0 3/4715 (0.1%) 3
Breast haematoma 0/4717 (0%) 0 1/4715 (0%) 1
Cervical dysplasia 1/4717 (0%) 1 0/4715 (0%) 0
Cystocele 1/4717 (0%) 1 0/4715 (0%) 0
Dysfunctional uterine bleeding 1/4717 (0%) 1 0/4715 (0%) 0
Ovarian cyst 0/4717 (0%) 0 1/4715 (0%) 1
Prostatic varices 1/4717 (0%) 1 0/4715 (0%) 0
Uterine polyp 0/4717 (0%) 0 1/4715 (0%) 1
Uterine prolapse 1/4717 (0%) 1 0/4715 (0%) 0
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease 21/4717 (0.4%) 30 21/4715 (0.4%) 33
Acute respiratory failure 7/4717 (0.1%) 7 14/4715 (0.3%) 16
Respiratory failure 10/4717 (0.2%) 10 6/4715 (0.1%) 6
Pleural effusion 4/4717 (0.1%) 5 10/4715 (0.2%) 11
Pulmonary oedema 5/4717 (0.1%) 5 7/4715 (0.1%) 9
Pulmonary embolism 6/4717 (0.1%) 6 4/4715 (0.1%) 4
Dyspnoea 5/4717 (0.1%) 5 4/4715 (0.1%) 4
Acute pulmonary oedema 3/4717 (0.1%) 4 5/4715 (0.1%) 5
Asthma 2/4717 (0%) 2 5/4715 (0.1%) 6
Pneumonia aspiration 4/4717 (0.1%) 4 3/4715 (0.1%) 3
Pulmonary hypertension 5/4717 (0.1%) 5 1/4715 (0%) 1
Hypoxia 1/4717 (0%) 2 3/4715 (0.1%) 4
Respiratory distress 0/4717 (0%) 0 4/4715 (0.1%) 4
Sleep apnoea syndrome 3/4717 (0.1%) 4 1/4715 (0%) 1
Atelectasis 1/4717 (0%) 1 2/4715 (0%) 2
Dyspnoea exertional 1/4717 (0%) 1 2/4715 (0%) 2
Cough 0/4717 (0%) 0 2/4715 (0%) 2
Epistaxis 0/4717 (0%) 0 2/4715 (0%) 2
Haemothorax 2/4717 (0%) 2 0/4715 (0%) 0
Respiratory arrest 2/4717 (0%) 2 0/4715 (0%) 0
Bronchiectasis 1/4717 (0%) 1 0/4715 (0%) 0
Chronic respiratory failure 1/4717 (0%) 1 0/4715 (0%) 0
Epiglottic cyst 1/4717 (0%) 1 0/4715 (0%) 0
Hydrothorax 0/4717 (0%) 0 1/4715 (0%) 1
Hypercapnia 0/4717 (0%) 0 1/4715 (0%) 2
Hyperventilation 0/4717 (0%) 0 1/4715 (0%) 1
Idiopathic pulmonary fibrosis 0/4717 (0%) 0 1/4715 (0%) 1
Lower respiratory tract congestion 0/4717 (0%) 0 1/4715 (0%) 1
Nasal septum deviation 0/4717 (0%) 0 1/4715 (0%) 1
Nasal ulcer 0/4717 (0%) 0 1/4715 (0%) 1
Obstructive airways disorder 1/4717 (0%) 1 0/4715 (0%) 0
Pharyngeal cyst 1/4717 (0%) 1 0/4715 (0%) 0
Pleuritic pain 0/4717 (0%) 0 1/4715 (0%) 1
Pneumothorax 0/4717 (0%) 0 1/4715 (0%) 1
Pulmonary arterial hypertension 0/4717 (0%) 0 1/4715 (0%) 1
Pulmonary congestion 0/4717 (0%) 0 1/4715 (0%) 1
Pulmonary fibrosis 0/4717 (0%) 0 1/4715 (0%) 1
Pulmonary mass 1/4717 (0%) 1 0/4715 (0%) 0
Respiratory depression 0/4717 (0%) 0 1/4715 (0%) 1
Rhinitis hypertrophic 0/4717 (0%) 0 1/4715 (0%) 1
Vocal cord leukoplakia 1/4717 (0%) 1 0/4715 (0%) 0
Skin and subcutaneous tissue disorders
Diabetic foot 14/4717 (0.3%) 16 22/4715 (0.5%) 26
Skin ulcer 9/4717 (0.2%) 9 7/4715 (0.1%) 7
Urticaria 1/4717 (0%) 1 3/4715 (0.1%) 3
Angioedema 1/4717 (0%) 1 1/4715 (0%) 1
Actinic keratosis 1/4717 (0%) 1 0/4715 (0%) 0
Dermatitis allergic 0/4717 (0%) 0 1/4715 (0%) 1
Diabetic neuropathic ulcer 1/4717 (0%) 1 0/4715 (0%) 0
Hidradenitis 0/4717 (0%) 0 1/4715 (0%) 1
Hyperhidrosis 0/4717 (0%) 0 1/4715 (0%) 1
Panniculitis 0/4717 (0%) 0 1/4715 (0%) 1
Psoriasis 1/4717 (0%) 1 0/4715 (0%) 0
Pustular psoriasis 1/4717 (0%) 1 0/4715 (0%) 0
Rash papular 0/4717 (0%) 0 1/4715 (0%) 1
Skin necrosis 1/4717 (0%) 1 0/4715 (0%) 0
Umbilical discharge 0/4717 (0%) 0 1/4715 (0%) 1
Surgical and medical procedures
Finger amputation 1/4717 (0%) 1 0/4715 (0%) 0
Vascular disorders
Peripheral arterial occlusive disease 33/4717 (0.7%) 37 41/4715 (0.9%) 48
Hypertension 11/4717 (0.2%) 12 12/4715 (0.3%) 12
Peripheral ischaemia 7/4717 (0.1%) 11 13/4715 (0.3%) 13
Hypertensive crisis 8/4717 (0.2%) 8 11/4715 (0.2%) 11
Hypotension 10/4717 (0.2%) 10 7/4715 (0.1%) 7
Peripheral vascular disorder 3/4717 (0.1%) 3 13/4715 (0.3%) 19
Extremity necrosis 7/4717 (0.1%) 7 5/4715 (0.1%) 6
Deep vein thrombosis 9/4717 (0.2%) 9 2/4715 (0%) 2
Orthostatic hypotension 4/4717 (0.1%) 5 6/4715 (0.1%) 6
Peripheral artery stenosis 4/4717 (0.1%) 6 5/4715 (0.1%) 6
Aortic stenosis 4/4717 (0.1%) 4 4/4715 (0.1%) 4
Peripheral artery occlusion 2/4717 (0%) 2 6/4715 (0.1%) 6
Aortic aneurysm 4/4717 (0.1%) 4 3/4715 (0.1%) 3
Embolism arterial 5/4717 (0.1%) 5 1/4715 (0%) 1
Haematoma 5/4717 (0.1%) 5 1/4715 (0%) 1
Arteriosclerosis 0/4717 (0%) 0 4/4715 (0.1%) 4
Intermittent claudication 2/4717 (0%) 3 2/4715 (0%) 2
Peripheral artery thrombosis 3/4717 (0.1%) 3 1/4715 (0%) 1
Aortic dissection 3/4717 (0.1%) 3 0/4715 (0%) 0
Arterial disorder 0/4717 (0%) 0 3/4715 (0.1%) 3
Hypertensive emergency 3/4717 (0.1%) 3 0/4715 (0%) 0
Hypovolaemic shock 0/4717 (0%) 0 3/4715 (0.1%) 3
Subclavian artery stenosis 1/4717 (0%) 1 2/4715 (0%) 2
Diabetic vascular disorder 2/4717 (0%) 2 0/4715 (0%) 0
Essential hypertension 1/4717 (0%) 1 1/4715 (0%) 1
Leriche syndrome 0/4717 (0%) 0 2/4715 (0%) 2
Venous thrombosis 2/4717 (0%) 2 0/4715 (0%) 0
Accelerated hypertension 1/4717 (0%) 1 0/4715 (0%) 0
Arterial haemorrhage 0/4717 (0%) 0 1/4715 (0%) 1
Bleeding varicose vein 1/4717 (0%) 1 0/4715 (0%) 0
Blood pressure inadequately controlled 1/4717 (0%) 1 0/4715 (0%) 0
Circulatory collapse 1/4717 (0%) 1 0/4715 (0%) 0
Diabetic microangiopathy 1/4717 (0%) 1 0/4715 (0%) 0
Dry gangrene 0/4717 (0%) 0 1/4715 (0%) 1
Femoral artery embolism 0/4717 (0%) 0 1/4715 (0%) 1
Granulomatosis with polyangiitis 1/4717 (0%) 1 0/4715 (0%) 0
Haemorrhage 0/4717 (0%) 0 1/4715 (0%) 1
Iliac artery occlusion 0/4717 (0%) 0 1/4715 (0%) 1
Lymphorrhoea 0/4717 (0%) 0 1/4715 (0%) 1
Lymphostasis 1/4717 (0%) 1 0/4715 (0%) 0
Malignant hypertension 1/4717 (0%) 1 0/4715 (0%) 0
Peripheral venous disease 0/4717 (0%) 0 1/4715 (0%) 1
Subclavian artery occlusion 1/4717 (0%) 1 0/4715 (0%) 0
Varicose vein 0/4717 (0%) 0 1/4715 (0%) 1
Venous occlusion 0/4717 (0%) 0 1/4715 (0%) 1
Other (Not Including Serious) Adverse Events
Albiglutide Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 0/4717 (0%) 0/4715 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.

Results Point of Contact

Name/Title GSK Response Center
Organization GlaxoSmithKline
Phone 866-435-7343
Email GSKClinicalSupportHD@gsk.com
Responsible Party:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT02465515
Other Study ID Numbers:
  • 116174
  • 2014-001824-32
First Posted:
Jun 8, 2015
Last Update Posted:
Mar 6, 2019
Last Verified:
Feb 1, 2019