Trial Outcomes & Findings for A Study to Determine the Safety and Efficacy of Albiglutide Administered in Combination With Insulin Glargine (NCT NCT00976391)

Last Updated: 2017-01-11

Results Overview

HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over a 2- to 3-month period. The BL HbA1c value is defined as the last non-missing value before the start of treatment. Change from BL was calculated as the value at Week 26 minus the value at BL. The analysis was performed using an Analysis of Covariance (ANCOVA) model with treatment group, region, history of prior myocardial infarction (yes versus no), and age category (\<65 years versus ≥65 years) as factors and Baseline HbA1c as a continuous covariate.The last observation carried forward (LOCF) method was used to impute missing post-BL HbA1c values; the last non-missing post-BL on-treatment measurement was used to impute the missing measurement. HbA1c values obtained after hyperglycemic rescue were treated as missing and were replaced with pre-rescue values.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

586 participants

Primary outcome timeframe

Baseline and Week 26

Results posted on

2017-01-11

Participant Flow

Participants (par.) who met eligibility criteria and completed a 4-8 week Run-in/Stabilization Period were then randomized to a 52-week Treatment Period, followed by 8 weeks of post-treatment follow-up. A total of 920 par. were screened; 586 par. were randomized, and 566 par. received \>=1 treatment dose.

Participant milestones

Participant milestones
Measure	Albiglutide 30 mg With Insulin Glargine Participants received albiglutide 30 milligrams (mg) as a subcutaneous injection weekly (with uptitration to 50 mg weekly if needed) via a fully disposable pen injector system combined with insulin glargine (with uptitration if needed) as prescribed by their physician. Participants did not receive investigational product during the Follow-up Period.	Preprandial Lispro Insulin With Insulin Glargine Participants received a combination of insulin glargine (with uptitration if needed) and preprandial lispro insulin (with uptitration as appropriate) as prescribed by their physician.Participants did not receive investigational product during the Follow-up Period.
Treatment Period (52 Weeks) STARTED	285	281
Treatment Period (52 Weeks) COMPLETED	243	242
Treatment Period (52 Weeks) NOT COMPLETED	42	39
Follow-up Period (8 Weeks) STARTED	285	281
Follow-up Period (8 Weeks) COMPLETED	256	247
Follow-up Period (8 Weeks) NOT COMPLETED	29	34

Reasons for withdrawal

Reasons for withdrawal
Measure	Albiglutide 30 mg With Insulin Glargine Participants received albiglutide 30 milligrams (mg) as a subcutaneous injection weekly (with uptitration to 50 mg weekly if needed) via a fully disposable pen injector system combined with insulin glargine (with uptitration if needed) as prescribed by their physician. Participants did not receive investigational product during the Follow-up Period.	Preprandial Lispro Insulin With Insulin Glargine Participants received a combination of insulin glargine (with uptitration if needed) and preprandial lispro insulin (with uptitration as appropriate) as prescribed by their physician.Participants did not receive investigational product during the Follow-up Period.
Treatment Period (52 Weeks) Adverse Event	16	2
Treatment Period (52 Weeks) Protocol Violation	1	1
Treatment Period (52 Weeks) Noncompliance	4	4
Treatment Period (52 Weeks) Lost to Follow-up	10	8
Treatment Period (52 Weeks) Withdrawal by Subject	9	19
Treatment Period (52 Weeks) Physician Decision	1	1
Treatment Period (52 Weeks) Termination of Study/Site by GSK	0	4
Treatment Period (52 Weeks) Pregnancy	1	0
Follow-up Period (8 Weeks) Adverse Event	3	1
Follow-up Period (8 Weeks) Noncompliance	2	2
Follow-up Period (8 Weeks) Lost to Follow-up	14	12
Follow-up Period (8 Weeks) Did not Entered Follow-up	6	8
Follow-up Period (8 Weeks) Withdrawal by Subject	4	7
Follow-up Period (8 Weeks) Termination of Study/Site by GSK	0	4

Baseline Characteristics

A Study to Determine the Safety and Efficacy of Albiglutide Administered in Combination With Insulin Glargine

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Albiglutide 30 mg With Insulin Glargine n=285 Participants Participants received albiglutide 30 mg as a subcutaneous injection weekly (with uptitration to 50 mg weekly if needed) via a fully disposable pen injector system combined with insulin glargine (with uptitration if needed) as prescribed by their physician. Participants did not receive investigational product during the Follow-up Period.	Preprandial Lispro Insulin With Insulin Glargine n=281 Participants Participants received a combination of insulin glargine (with uptitration if needed) and preprandial lispro insulin (with uptitration as appropriate) as prescribed by their physician.Participants did not receive investigational product during the Follow-up Period.	Total n=566 Participants Total of all reporting groups
Age, Continuous	54.8 Years STANDARD_DEVIATION 9.10 • n=5 Participants	56.3 Years STANDARD_DEVIATION 8.87 • n=7 Participants	55.6 Years STANDARD_DEVIATION 9.01 • n=5 Participants
Gender Female	153 Participants n=5 Participants	145 Participants n=7 Participants	298 Participants n=5 Participants
Gender Male	132 Participants n=5 Participants	136 Participants n=7 Participants	268 Participants n=5 Participants
Race/Ethnicity, Customized African American/African Heritage	39 Participants n=5 Participants	34 Participants n=7 Participants	73 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaskan Native	29 Participants n=5 Participants	20 Participants n=7 Participants	49 Participants n=5 Participants
Race/Ethnicity, Customized Asian - Central/South Asian Heritage	17 Participants n=5 Participants	17 Participants n=7 Participants	34 Participants n=5 Participants
Race/Ethnicity, Customized Asian - East Asian Heritage	15 Participants n=5 Participants	17 Participants n=7 Participants	32 Participants n=5 Participants
Race/Ethnicity, Customized Asian - South East Asian Heritage	16 Participants n=5 Participants	16 Participants n=7 Participants	32 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Race/Ethnicity, Customized White - Arabic/North African Heritage	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Race/Ethnicity, Customized White - White/Caucasian/European Heritage	174 Participants n=5 Participants	171 Participants n=7 Participants	345 Participants n=5 Participants
Race/Ethnicity, Customized Other-Black	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Other-Native American	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Week 26

Population: Intent-to-Treat (ITT) Population with LOCF: all randomized par. who received \>=1 dose of study medication and who had a BL assessment and \>=1 post-BL assessment of HbA1c. Only par. with a value at BL and at the specified visit were analyzed. Values were carried forward for par. who were rescued or discontinued from active treatment before Week 26.

Outcome measures

Outcome measures
Measure	Albiglutide 30 mg With Insulin Glargine n=279 Participants Participants received albiglutide 30 mg as a subcutaneous injection weekly (with uptitration to 50 mg weekly if needed) via a fully disposable pen injector system combined with insulin glargine (with uptitration if needed) as prescribed by their physician. Participants did not receive investigational product during the Follow-up Period.	Preprandial Lispro Insulin With Insulin Glargine n=278 Participants Participants received a combination of insulin glargine (with uptitration if needed) and preprandial lispro insulin (with uptitration as appropriate) as prescribed by their physician.Participants did not receive investigational product during the Follow-up Period.
Change From Baseline (BL) in Glycosylated Hemoglobin (HbA1c) at Week 26	-0.82 Percentage of HbA1c in the blood Standard Error 0.058	-0.66 Percentage of HbA1c in the blood Standard Error 0.058

SECONDARY outcome

Timeframe: Baseline and Weeks 36, 48 and 52

Population: ITT Population with observed values. Only those participants with a value at Baseline and at the specified visit were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the ITT Population.

HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over a 2- to 3-month period. Baseline is defined as the last available assessment on or prior to the first dose of study drug. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. This analysis used observed HbA1c values, excluding those obtained after hyperglycemia rescue; no missing data imputation was performed.

Outcome measures

Outcome measures
Measure	Albiglutide 30 mg With Insulin Glargine n=250 Participants Participants received albiglutide 30 mg as a subcutaneous injection weekly (with uptitration to 50 mg weekly if needed) via a fully disposable pen injector system combined with insulin glargine (with uptitration if needed) as prescribed by their physician. Participants did not receive investigational product during the Follow-up Period.	Preprandial Lispro Insulin With Insulin Glargine n=254 Participants Participants received a combination of insulin glargine (with uptitration if needed) and preprandial lispro insulin (with uptitration as appropriate) as prescribed by their physician.Participants did not receive investigational product during the Follow-up Period.
Change From Baseline in HbA1c at Weeks 36, 48 and 52 Week 36, n=173, 182	-1.04 Percentage of HbA1c in the blood Standard Deviation 0.990	-0.88 Percentage of HbA1c in the blood Standard Deviation 0.924
Change From Baseline in HbA1c at Weeks 36, 48 and 52 Week 48, n=140, 153	-0.97 Percentage of HbA1c in the blood Standard Deviation 1.070	-0.81 Percentage of HbA1c in the blood Standard Deviation 0.961
Change From Baseline in HbA1c at Weeks 36, 48 and 52 Week 52, n=121, 141	-1.01 Percentage of HbA1c in the blood Standard Deviation 1.024	-0.84 Percentage of HbA1c in the blood Standard Deviation 0.925

SECONDARY outcome

Timeframe: Baseline and Week 26

Population: Intent-to-Treat (ITT) Population with LOCF. Only those participants with a value at Baseline and at the specified visit were analyzed. Values were carried forward for participants who were rescued or discontinued from active treatment before Week 26.

The FPG test measures blood sugar levels after the participant has not eaten (fasted) for 12 to 14 hours. The Baseline FPG value is the last non-missing value before the start of treatment. The LOCF method was used to impute missing post-Baseline FPG values. FPG values obtained after hyperglycemia rescue were treated as missing and replaced with pre-rescue values. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Based on ANCOVA: change = treatment + Baseline FPG + Baseline HbA1c category + region

Outcome measures

Outcome measures
Measure	Albiglutide 30 mg With Insulin Glargine n=282 Participants Participants received albiglutide 30 mg as a subcutaneous injection weekly (with uptitration to 50 mg weekly if needed) via a fully disposable pen injector system combined with insulin glargine (with uptitration if needed) as prescribed by their physician. Participants did not receive investigational product during the Follow-up Period.	Preprandial Lispro Insulin With Insulin Glargine n=279 Participants Participants received a combination of insulin glargine (with uptitration if needed) and preprandial lispro insulin (with uptitration as appropriate) as prescribed by their physician.Participants did not receive investigational product during the Follow-up Period.
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26	-0.99 Millimoles per liter (mmol/L) Standard Error 0.164	-0.71 Millimoles per liter (mmol/L) Standard Error 0.164

SECONDARY outcome

Timeframe: Baseline and Weeks 36, 48 and 52

Population: ITT Population with observed values. Only those participants with a value at Baseline and at the specified visit were analyzed (represented by n=X, X in the category title).

The FPG test measures blood sugar levels after the participant has not eaten (fasted) for 12 to 14 hours. The Baseline FPG value is the last non-missing value before the start of treatment. Change from Baseline was calculated as the post-Baseline FPG minus the Baseline FPG. This analysis used observed FPG values excluding those obtained after hyperglycemia rescue; no missing data imputation was performed.

Outcome measures

Outcome measures
Measure	Albiglutide 30 mg With Insulin Glargine n=171 Participants Participants received albiglutide 30 mg as a subcutaneous injection weekly (with uptitration to 50 mg weekly if needed) via a fully disposable pen injector system combined with insulin glargine (with uptitration if needed) as prescribed by their physician. Participants did not receive investigational product during the Follow-up Period.	Preprandial Lispro Insulin With Insulin Glargine n=182 Participants Participants received a combination of insulin glargine (with uptitration if needed) and preprandial lispro insulin (with uptitration as appropriate) as prescribed by their physician.Participants did not receive investigational product during the Follow-up Period.
Change From Baseline in Fasting Plasma Glucose (FPG) at Weeks 36, 48 and 52 Week 36, n=171, 182	-1.41 Millimoles per liter (mmol/L) Standard Deviation 2.905	-0.91 Millimoles per liter (mmol/L) Standard Deviation 3.039
Change From Baseline in Fasting Plasma Glucose (FPG) at Weeks 36, 48 and 52 Week 48, n=131, 151	-1.13 Millimoles per liter (mmol/L) Standard Deviation 3.078	-1.07 Millimoles per liter (mmol/L) Standard Deviation 2.965
Change From Baseline in Fasting Plasma Glucose (FPG) at Weeks 36, 48 and 52 Week 52, n=121, 139	-1.36 Millimoles per liter (mmol/L) Standard Deviation 3.054	-0.97 Millimoles per liter (mmol/L) Standard Deviation 3.305

SECONDARY outcome

Timeframe: Week 26

Population: ITT Population. Only those participants available at the indicated time point were assessed.

The number of participants who acheieved the HbA1c treatment goal (i.e., HbA1c response levels of \<6.5% and \<7.0% at Week 26) were assessed.

Outcome measures

Outcome measures
Measure	Albiglutide 30 mg With Insulin Glargine n=279 Participants Participants received albiglutide 30 mg as a subcutaneous injection weekly (with uptitration to 50 mg weekly if needed) via a fully disposable pen injector system combined with insulin glargine (with uptitration if needed) as prescribed by their physician. Participants did not receive investigational product during the Follow-up Period.	Preprandial Lispro Insulin With Insulin Glargine n=278 Participants Participants received a combination of insulin glargine (with uptitration if needed) and preprandial lispro insulin (with uptitration as appropriate) as prescribed by their physician.Participants did not receive investigational product during the Follow-up Period.
Number of Participants Who Achieved HbA1c Response Level of <6.5% and <7.0% at Week 26 HbA1c <6.5 %	31 Participants	23 Participants
Number of Participants Who Achieved HbA1c Response Level of <6.5% and <7.0% at Week 26 HbA1c <7.0 %	83 Participants	70 Participants

SECONDARY outcome

Timeframe: From the start of study medication until the end of the treatment (up to Week 52)

Population: ITT Population. Only those participants with a value at Baseline and at the specified visit were analyzed.

Participants who experienced persistent hyperglycemia (high blood glucose) could have qualified for hyperglycemia rescue. The conditions for hyperglycemia rescue were as follows: HbA1c \>9.0% and \<0.5% decrease from Baseline between \>=Week 4 and \<Week 8; HbA1c \>9.0% and \<0.5% decrease from Baseline between \>=Week 8 and \<Week 12; HbA1c \>8.5% and \>=4 weeks since uptitration between \>=Week 12 and \<Week 16; HbA1c \>8.0% and \>=4 weeks since uptitration; HbA1c \>7.5% and \>=4 weeks between \>Week 26 and \>=Week 48 since uptitration. Participants could have been rescued at any time after Week 4. Time to hyperglycemia rescue is the time between the date of first dose and the date of hyperglycemia rescue plus 1 day, or the time between the date of first dose and the date of last visit during active treatment period plus 1 day for participants not requiring rescue. This time is divided by 7 to express the result in weeks.

Outcome measures

Outcome measures
Measure	Albiglutide 30 mg With Insulin Glargine n=282 Participants Participants received albiglutide 30 mg as a subcutaneous injection weekly (with uptitration to 50 mg weekly if needed) via a fully disposable pen injector system combined with insulin glargine (with uptitration if needed) as prescribed by their physician. Participants did not receive investigational product during the Follow-up Period.	Preprandial Lispro Insulin With Insulin Glargine n=281 Participants Participants received a combination of insulin glargine (with uptitration if needed) and preprandial lispro insulin (with uptitration as appropriate) as prescribed by their physician.Participants did not receive investigational product during the Follow-up Period.
Time to Hyperglycemia Rescue	NA Weeks There were too few events of hyperglycemia rescue (\<50% of participants with events) to calculate the median and confidence interval.	NA Weeks There were too few events of hyperglycemia rescue (\<50% of participants with events) to calculate the median and confidence interval.

SECONDARY outcome

Timeframe: Baseline and Week 26

Population: ITT Population with LOCF. Only those participants with a value at Baseline and at the specified visit were analyzed. Values were carried forward for participants who were rescued or discontinued from active treatment before Week 26.

The Baseline value is the last non-missing value before the start of treatment. Change from Baseline was calculated as the post-Baseline weight minus the Baseline weight. The LOCF method was used to impute missing post-Baseline weight values. Weight values obtained after hyperglycemia rescue were treated as missing and replaced with prerescue values. Based on ANCOVA: change = treatment + Baseline weight + Baseline HbA1c category + prior myocardial infarction history + age category + region + current oral antidiabetic therapy.

Outcome measures

Outcome measures
Measure	Albiglutide 30 mg With Insulin Glargine n=282 Participants Participants received albiglutide 30 mg as a subcutaneous injection weekly (with uptitration to 50 mg weekly if needed) via a fully disposable pen injector system combined with insulin glargine (with uptitration if needed) as prescribed by their physician. Participants did not receive investigational product during the Follow-up Period.	Preprandial Lispro Insulin With Insulin Glargine n=280 Participants Participants received a combination of insulin glargine (with uptitration if needed) and preprandial lispro insulin (with uptitration as appropriate) as prescribed by their physician.Participants did not receive investigational product during the Follow-up Period.
Change From Baseline in Body Weight at Week 26	-0.73 Kilograms Standard Error 0.194	0.81 Kilograms Standard Error 0.195

SECONDARY outcome

Timeframe: Baseline and Weeks 36, 48 and 52

Population: ITT Population with observed values. Only those participants who were available at the indicated time points were analyzed (represented by n=X, X in the category title).

The Baseline value is the last non-missing value before the start of treatment. Change from Baseline was calculated as the post-Baseline weight minus the Baseline weight. This analysis used observed body weight values excluding those obtained after hyperglycemia rescue; no missing data imputation was performed.

Outcome measures

Outcome measures
Measure	Albiglutide 30 mg With Insulin Glargine n=172 Participants Participants received albiglutide 30 mg as a subcutaneous injection weekly (with uptitration to 50 mg weekly if needed) via a fully disposable pen injector system combined with insulin glargine (with uptitration if needed) as prescribed by their physician. Participants did not receive investigational product during the Follow-up Period.	Preprandial Lispro Insulin With Insulin Glargine n=182 Participants Participants received a combination of insulin glargine (with uptitration if needed) and preprandial lispro insulin (with uptitration as appropriate) as prescribed by their physician.Participants did not receive investigational product during the Follow-up Period.
Change From Baseline in Body Weight at Weeks 36, 48 and 52 Week 36, n=172, 182	-0.42 Kilograms Standard Deviation 3.656	1.31 Kilograms Standard Deviation 4.005
Change From Baseline in Body Weight at Weeks 36, 48 and 52 Week 48, n=142, 153	-0.60 Kilograms Standard Deviation 3.928	1.56 Kilograms Standard Deviation 3.846
Change From Baseline in Body Weight at Weeks 36, 48 and 52 Week 52, n=122, 141	-0.70 Kilograms Standard Deviation 4.023	1.44 Kilograms Standard Deviation 4.053

Adverse Events

Albiglutide 30 mg With Insulin Glargine

Serious events: 38 serious events

Other events: 188 other events

Deaths: 0 deaths

Preprandial Lispro Insulin With Insulin Glargine

Serious events: 29 serious events

Other events: 178 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER