Children and Adolescent With Type 2 Diabetes
Conditions
Keywords
exenatide, type 2 diabetes, GLP-1 receptor agonist
Brief summary
The study examines the Safety and efficacy study of exenatide once weekly in children and adolescents with type 2 diabetes
Detailed description
This Phase 3, double-blind (controlled assessment period), randomized, multicenter, placebo-controlled parallel study is designed to examine the efficacy and safety of EQW compared to placebo (PBO) in adolescents with type 2 diabetes for 24 weeks. This study will assess safety and efficacy of EQW (as monotherapy and adjunctive therapy to oral antidiabetic agents and/or insulin). At least 40% and not more than 60% of the randomized patients must be females. At least 40% of patients should be recruited from areas with similar ethnicity and lifestyle to those of the European Union member states. Long term safety and efficacy of EQW will subsequently be monitored for 28 weeks in the open-label, uncontrolled extension period (through Week 52). The study will be terminated at Visit 11 (Week 62/Study Termination) which will be a follow-up visit occurring 10 weeks after the last dose administration at Visit 10 (Week 52). This study will be conducted in 77 patients with type 2 diabetes treated with diet and exercise alone or in combination with a stable dose of oral antidiabetic agents and/or insulin for at least 2 months prior to screening. During the controlled assessment period, approximately 77 patients will be randomly assigned in a 5:2 ratio to either EQW 2 mg (Group A) or PBO (Group B), to yield at least 70 evaluable patients: at least 50 patients in the exenatide and at least 20 patients in the PBO group. Following the 24-week controlled assessment period, patients assigned to the EQW 2 mg treatment (Group A) will continue to be treated with EQW 2 mg during the extension period (through Week 52). Patients randomized to PBO (Group B) will receive EQW 2 mg beginning at the start of the extension period, Week 25 through Week 52. In addition to receiving study medications, all patients will participate in a lifestyle intervention program encompassing diet and physical activity modifications following the signing of the informed consent and assent forms (Visit 1 \[Week -2\]) through the end of the extension period (Week 52). Following Visit 11 (Week 62/Study Termination), patients whose height increase is at least 5 mm between Visit 8 (Week 28) and Visit 11 (Week 62/Study Termination) will participate in a long-term safety follow-up period. Patients who discontinue study medication prior to Visit 11 (Week 62/Study Termination) will also participate in the Extended Safety Follow-up Period, unless they have a height increase of less than 5 mm over a 6-month interval at study site visits prior to discontinuation of study medication. Patients who do not have height assessments at study-site visits over a 6-month interval prior to discontinuation of study medication will enter the Extended Safety Follow-up Period. The Extended Safety Follow Up Period will continue for up to 3 years or until the difference between two 6-month interval visits is less than a 5 mm increase (whichever comes first). No study medication will be administered during the Extended Safety Follow-up Period. Blood samples will be collected for calcitonin and carcinoembryonic antigen (CEA) laboratory measurements.
Interventions
2 mg exenatide once weekly
DRUGPlacebo
Placebo
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
10 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
Each patient must meet the following criteria to be enrolled in this study. 1. Is a child or an adolescent of 10 to \<18 years old, at Visit 1 (Screening) 2. Has been diagnosed with type 2 diabetes mellitus per American Diabetes Association diagnostic criteria 3. HbA1c of 6.5% to 11.0%, inclusive, in patients not taking insulin/SU, and of 6.5% to 12.0%, inclusive, in patients taking insulin/SU, at Visit 1 (Screening) 4. Has a C-peptide of \>0.6 ng/L at Visit 1 (Screening) 5. Has been treated with diet and exercise alone or in combination with a stable dose of an oral antidiabetic agent (e.g., metformin and/or SU) and/or insulin for their type 2 diabetes for at least 2 months prior to Visit 1 (Screening) 6. Has a fasting plasma glucose concentration \<280 mg/dL (15.5 mmol/L) at Visit 1 (Screening) Patients who meet any of the following criteria will be excluded from the study. 1. Has a clinically significant medical condition that could potentially affect study participation and/or personal well-being, as judged by the Investigator, including but not limited to the following conditions: 1. Hepatic disease (defined by aspartate or alanine transaminase \>3.0 times the upper limit of normal (ULN) 2. Renal disease or serum creatinine \>1.5 mg/dL (132.6 µmol/L) (males) or 1.4 mg/dL (123.8 µmol/L) (females) 3. Gastrointestinal disease deemed significant by the Investigator 4. Organ transplantation 5. Chronic infection (e.g., tuberculosis, human immunodeficiency virus, hepatitis B virus, or hepatitis C virus) 6. Clinically significant malignant disease (with the exception of basal and squamous cell carcinoma of the skin) within 5 years of Visit 1 (Screening) 2. Has positive antibody titers to glutamic acid decarboxylase (GAD65) or islet cell antigen (ICA512) at Visit 1 (Screening) 3. Has a personal or family history of elevated calcitonin, calcitonin \>100 ng/L, medullary thyroid carcinoma, or multiple endocrine neoplasia-2 4. Has ever used exenatide (exenatide once weekly \[exenatide LAR\], exenatide BID, BYETTA, or any other formulation) or any glucagon-like peptide-1 (GLP-1) receptor agonist (e.g., liraglutide \[Victoza®\]) 5. Is pregnant
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Glycosylated Hemoglobin A1c (HbA1c) to Week 24 (Controlled Assessment Period) | Baseline (Week 0) and Week 24 | Change from baseline in HbA1c (%) to Week 24 during the controlled assessment period is reported as adjusted least square (LS) mean values. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. A mixed model with repeated measures (MMRM) analysis was performed, excluding data collected after initiation of rescue medication or premature discontinuation of study medication. |
| Percentage of Patients With On-Treatment Adverse Events (AEs) up to Week 24 (Controlled Assessment Period) | Day 1 (Week 0) up to Week 24, plus up to a maximum of 90 days follow up | A controlled assessment period AE was defined as an AE starting on or after day of first dose of study medication up to but not including Week 24 for patients entering the extension period. For patients not entering the extension period, the period was defined up to and including last dose of study medication + 7 days (+ 90 days for serious AEs \[SAEs\] and other clinically significant or related AEs). The Investigator assessed AEs for causal relationship to study drug medication. |
| Percentage of Patients Positive for Anti-Drug Antibodies (ADAs) to Exenatide up to Week 24 | Samples were collected on Day 1 (Week 0), Week 4, Week 8, Week 12 and Week 24 | Percentage of patients positive for ADAs up to Week 24 for the exenatide treatment group is reported. Baseline was the antibody measurement at Week 0 (Day 1). A negative or missing antibody measurement was considered negative at baseline. High positive = antibody titers ≥ 625, including baseline assessment. Low positive = antibody titers \< 625, including baseline assessment. A patient was said to have treatment-emergent ADA positive at a visit if the antibody test was positive after the first dose of exenatide following a negative or missing antibody measurement, or the titer increased by at least 1 titration category from a detectable measurement prior to first dose of randomized study medication. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients Achieving HbA1c Goals of < 6.5%, ≤ 6.5%, and < 7.0% at Week 24 (Controlled Assessment Period) | At Week 24 | The percentage of patients achieving HbA1c goals of \< 6.5%, ≤ 6.5%, and \< 7.0% at Week 24 during the controlled assessment period is reported. A Cochran-Mantel-Haenszel (CMH) analysis was performed with missing data treated as non-responder, and excluding data collected after initiation of rescue medication or after premature discontinuation of study medication. |
| Change From Baseline in Lipid Profiles to Week 24 (Controlled Assessment Period) | Baseline (Week 0) and Week 24 | Change from baseline in lipid profiles to Week 24 during the controlled assessment period is reported as mean values (Standard International \[SI\] units). The following lipids were assessed: total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides. All lipids presented were taken in a fasted state. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. Data collected after initiation of rescue medication or after premature discontinuation of study medication were excluded. |
| Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) to Week 24 (Controlled Assessment Period) | Baseline (Week 0) and Week 24 | Change from baseline in SBP and DBP to Week 24 during the controlled assessment period is reported as adjusted LS mean values. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. A MMRM analysis was performed, excluding data collected after initiation of rescue medication or after premature discontinuation of study medication. |
| Number of Patients Needing Rescue Medication Due to Failure to Maintain Glycemic Control up to Week 24 (Controlled Assessment Period) | At Week 4, Week 8, Week 12, Week 18 and Week 24 | Number of patients needing rescue medication at Week 24 and at each intermediate visit during the controlled assessment period is reported. Patients with a loss of glycemic control, defined as either an increase from baseline in HbA1c values by ≥ 1.0% at 2 consecutive clinic visits that were at least 1 month apart, or a fasting plasma glucose value ≥ 250 mg/dL or random blood glucose value \> 300 mg/dL for 4 days during a 7 day period, received rescue medication. Data collected after premature discontinuation of study medication were excluded. |
| Change From Baseline in Homeostasis Model Assessments - Beta-Cell Function (HOMA-B) and Insulin Sensitivity (HOMA-S) to Week 24 (Controlled Assessment Period) | Baseline (Week 0) and Week 24 | Change from baseline in HOMA-B and HOMA-S in patients who were not taking insulin to Week 24 during the controlled assessment period is reported as adjusted LS mean values. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. A MMRM analysis was performed, excluding data collected after initiation of rescue medication or after premature discontinuation of study medication. |
| Percentage of Patients Reporting AEs of Injection Site Reactions up to Week 24 (Controlled Assessment Period) | At Week 4, Week 8, Week 12, Week 18 and Week 24 | Percentage of patients reporting injection site reactions at Week 24 and at each intermediate visit during the controlled assessment period is reported. Injection site reactions were presented from the AE case report form (CRF), based on the Injection site reactions higher level term. A controlled assessment period AE was defined as an AE starting on or after day of first dose of study medication up to but not including Week 24 for patients entering the extension period. For patients not entering the extension period, the period was defined up to and including last dose of study medication + 7 days (+ 90 days for SAEs and other clinically significant or related AEs). |
| Change From Baseline in HbA1c to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) | Baseline (Week 0) and Week 52 | Change from baseline in HbA1c (%) to Week 52 among patients who received open-label exenatide during the treatment period is reported as mean values. The treatment period was defined as the controlled assessment period and extension period combined. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. Data collected after initiation of rescue medication or after premature discontinuation of study medication were excluded. |
| Change From Baseline in FPG Concentration to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) | Baseline (Week 0) and Week 52 | Change from baseline in FPG to Week 52 among patients who received open-label exenatide during the treatment period is reported as mean values. The treatment period was defined as the controlled assessment period and extension period combined. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. Data collected after initiation of rescue medication or after premature discontinuation of study medication were excluded. |
| Change From Baseline in Fasting Plasma Glucose (FPG) Concentration to Week 24 (Controlled Assessment Period) | Baseline (Week 0) and Week 24 | Change from baseline in FPG to Week 24 during the controlled assessment period is reported as adjusted LS mean values. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. A MMRM analysis was performed, excluding data collected after initiation of rescue medication or after premature discontinuation of study medication. |
| Change From Baseline in Fasting Insulin to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) | Baseline (Week 0) and Week 52 | Change from baseline in fasting insulin to Week 52 among patients who received open-label exenatide during the treatment period is reported as mean values. The treatment period was defined as the controlled assessment period and extension period combined. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. Data collected after initiation of rescue medication or after premature discontinuation of study medication were excluded. |
| Percentage of Participants Achieving HbA1c Goals of < 6.5%, ≤ 6.5%, and < 7.0% to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) | At Week 52 | The percentage of patients achieving HbA1c goals of \< 6.5%, ≤ 6.5%, and \< 7.0% at Week 52 among patients who received open-label exenatide during the treatment period is reported. The treatment period was defined as the controlled assessment period and extension period combined. Data collected after initiation of rescue medication or after premature discontinuation of study medication were excluded. |
| Change From Baseline in Lipids Profiles to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) | Baseline (Week 0) and Week 52 | Change from baseline in lipid profiles to Week 52 among patients who received open-label exenatide during the treatment period is reported as mean values (SI units). The treatment period was defined as the controlled assessment period and extension period combined. The following lipids were assessed: total cholesterol, HDL-C, LDL-C, and triglycerides. All lipids presented were taken in a fasted state. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. Data collected after initiation of rescue medication or after premature discontinuation of study medication were excluded. |
| Change From Baseline in Blood Pressure (Systolic and Diastolic) to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) | Baseline (Week 0) and Week 52 | Change from baseline in SBP and DBP to Week 52 among patients who received open-label exenatide during the treatment period is reported as mean values. The treatment period was defined as the controlled assessment period and extension period combined. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. Data collected after initiation of rescue medication or after premature discontinuation of study medication were excluded. |
| Number of Patients Needing Rescue Medication Due to Failure to Maintain Glycemic Control up to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) | At Week 4, Week 8, Week 12, Week 18, Week 24, Week 28, Week 40 and Week 52 | Number of patients needing rescue medication at Week 52 and at each intermediate visit during the treatment period is reported. The treatment period was defined as the controlled assessment period and extension period combined. Patients with a loss of glycemic control, defined as either an increase from baseline in HbA1c values by ≥ 1.0% at 2 consecutive clinic visits that were at least 1 month apart, or a fasting plasma glucose value ≥ 250 mg/dL or random blood glucose value \> 300 mg/dL for 4 days during a 7 day period, received rescue medication. Data collected after premature discontinuation of study medication were excluded. |
| Change From Baseline in HOMA-B and HOMA-S to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) | Baseline (Week 0) and Week 52 | Change from baseline in HOMA-B and HOMA-S to Week 52 among patients who received open-label exenatide during the treatment period is reported as mean values. The treatment period was defined as the controlled assessment period and extension period combined. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. Data collected after initiation of rescue medication or after premature discontinuation of study medication were excluded. |
| Percentage of Patients Reporting AEs of Injection Site Reactions up to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) | At Week 4, Week 8, Week 12, Week 18, Week 24, Week 28, Week 40 and Week 52 | Percentage of patients reporting injection site reactions at Week 52 and at each intermediate visit among patients who received open-label exenatide during the treatment period is reported. The treatment period was defined as the controlled assessment period and extension period combined. Injection site reactions were presented from the AE CRF, based on the Injection site reactions higher level term. An Extension Period AE was defined as an AE starting on or after day of first dose of open-label exenatide to last dose + 7 days (+ 90 days for SAEs and other clinically significant or related AEs). |
| Plasma Exenatide Concentrations to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) | Samples were collected on Day 1 (Week 0), Week 4, Week 8, Week 12, Week 24 and Week 52 | Geometric mean plasma exenatide concentrations up to Week 52 during the treatment period are reported (for the placebo then exenatide treatment group, only Weeks 24 and 52 were applicable). The treatment period was defined as the controlled assessment period and extension period combined. Data collected after initiation of rescue medication were included. Data collected after discontinuation of study medication were excluded. |
| Change From Baseline in Body Weight to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) | Baseline (Week 0) and Week 52 | Change from baseline in body weight to Week 52 among patients who received open-label exenatide during the treatment period is reported as mean values. The treatment period was defined as the controlled assessment period and extension period combined. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. Data collected after initiation of rescue medication or after premature discontinuation of study medication were excluded. |
| Change From Baseline in Body Weight to Week 24 (Controlled Assessment Period) | Baseline (Week 0) and Week 24 | Change from baseline in body weight to Week 24 during the controlled assessment period is reported as adjusted LS mean values. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. A MMRM analysis was performed, excluding data collected after initiation of rescue medication or after premature discontinuation of study medication. |
| Change From Baseline in Fasting Insulin to Week 24 (Controlled Assessment Period) | Baseline (Week 0) and Week 24 | Change from baseline in fasting insulin to Week 24 during the controlled assessment period is reported as adjusted LS mean values. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. A MMRM analysis was performed, excluding data collected after initiation of rescue medication or after premature discontinuation of study medication. |
Countries
Bulgaria, Hungary, Israel, Kuwait, Mexico, Ukraine, United States
Participant flow
Recruitment details
This study was conducted in adolescents (aged 10 to 17 years inclusive) with type 2 diabetes treated with diet and exercise alone or in combination with a stable dose of oral antidiabetic agents and/or insulin for at least 2 months prior to screening. 27 study centers in 6 countries randomized patients during the study.
Pre-assignment details
Study had a screening period (5 weeks), controlled assessment period (24 weeks; patients randomized 5:2 to exenatide or placebo), open-label extension period (28 weeks) and post-treatment follow-up period (10 weeks). 84 patients were randomized but 1 due to clinical error and immediately discontinued, thus, 83 patients were included in the study.
Participants by arm
| Arm | Count |
|---|---|
| Exenatide Controlled assessment period: Patients received exenatide 2 mg SC injection once weekly for 24 weeks.
Extension period: Patients continued to receive exenatide 2 mg SC once weekly during the open-label extension period for 28 weeks (through Week 52). | 58 |
| Placebo Controlled assessment period: Patients received placebo (matching with exenatide) SC injection once weekly for 24 weeks.
Extension period: Patients then received exenatide 2 mg SC once weekly beginning at the start of the open-label extension period for 28 weeks (from Week 25 to Week 52). | 24 |
| Total | 82 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Controlled Assessment Period | Lost to Follow-up | 2 | 1 |
| Controlled Assessment Period | Withdrawal by Subject | 6 | 0 |
| Open-Label Extension Period | Lost to Follow-up | 1 | 1 |
| Open-Label Extension Period | Physician Decision | 0 | 1 |
| Open-Label Extension Period | Withdrawal by Subject | 2 | 3 |
| Randomized Through Start of Treatment | Adverse Event | 1 | 0 |
Baseline characteristics
| Characteristic | Exenatide | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 14.9 years STANDARD_DEVIATION 1.88 | 15.6 years STANDARD_DEVIATION 1.66 | 15.1 years STANDARD_DEVIATION 1.84 |
| Age, Customized < 10 | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized ≥ 10 to ≤ 12 | 8 Participants | 3 Participants | 11 Participants |
| Age, Customized ≥ 13 to ≤ 16 | 36 Participants | 12 Participants | 48 Participants |
| Age, Customized > 16 | 14 Participants | 9 Participants | 23 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 25 Participants | 8 Participants | 33 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 29 Participants | 13 Participants | 42 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 4 Participants | 3 Participants | 7 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 4 Participants | 1 Participants | 5 Participants |
| Race/Ethnicity, Customized Asian | 2 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized Black or African American | 17 Participants | 8 Participants | 25 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 12 Participants | 2 Participants | 14 Participants |
| Race/Ethnicity, Customized White | 23 Participants | 12 Participants | 35 Participants |
| Region of Enrollment Bulgaria | 1 Participants | 0 Participants | 1 Participants |
| Region of Enrollment Hungary | 3 Participants | 1 Participants | 4 Participants |
| Region of Enrollment Israel | 4 Participants | 3 Participants | 7 Participants |
| Region of Enrollment Kuwait | 2 Participants | 1 Participants | 3 Participants |
| Region of Enrollment Mexico | 13 Participants | 2 Participants | 15 Participants |
| Region of Enrollment United States | 35 Participants | 17 Participants | 52 Participants |
| Sex: Female, Male Female | 31 Participants | 17 Participants | 48 Participants |
| Sex: Female, Male Male | 27 Participants | 7 Participants | 34 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 59 | 0 / 23 | 0 / 50 | 0 / 22 |
| other Total, other adverse events | 25 / 59 | 10 / 23 | 10 / 50 | 4 / 22 |
| serious Total, serious adverse events | 2 / 59 | 1 / 23 | 3 / 50 | 1 / 22 |
Outcome results
Primary
Change From Baseline in Glycosylated Hemoglobin A1c (HbA1c) to Week 24 (Controlled Assessment Period)
Change from baseline in HbA1c (%) to Week 24 during the controlled assessment period is reported as adjusted least square (LS) mean values. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. A mixed model with repeated measures (MMRM) analysis was performed, excluding data collected after initiation of rescue medication or premature discontinuation of study medication.
Time frame: Baseline (Week 0) and Week 24
Population: The Evaluable Analysis Set consisted of all randomized patients who received at least 1 dose of randomized study medication and had at least 1 baseline and post-baseline HbA1c assessment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Controlled Assessment Period - Exenatide | Change From Baseline in Glycosylated Hemoglobin A1c (HbA1c) to Week 24 (Controlled Assessment Period) | -0.36 percentage (% HbA1c) | Standard Error 0.184 |
| Controlled Assessment Period - Placebo | Change From Baseline in Glycosylated Hemoglobin A1c (HbA1c) to Week 24 (Controlled Assessment Period) | 0.49 percentage (% HbA1c) | Standard Error 0.273 |
Comparison: Adjusted LS mean and treatment group difference in the change from baseline at Week 24 were modeled using a MMRM including treatment group, region, visit, and treatment group by visit interaction, baseline HbA1c value (continuous) and baseline HbA1c by visit interaction as fixed effects, using an unstructured covariance matrix.p-value: 0.01295% CI: [-1.51, -0.19]Mixed Models Analysis
Primary
Percentage of Patients Positive for Anti-Drug Antibodies (ADAs) to Exenatide up to Week 24
Percentage of patients positive for ADAs up to Week 24 for the exenatide treatment group is reported. Baseline was the antibody measurement at Week 0 (Day 1). A negative or missing antibody measurement was considered negative at baseline. High positive = antibody titers ≥ 625, including baseline assessment. Low positive = antibody titers \< 625, including baseline assessment. A patient was said to have treatment-emergent ADA positive at a visit if the antibody test was positive after the first dose of exenatide following a negative or missing antibody measurement, or the titer increased by at least 1 titration category from a detectable measurement prior to first dose of randomized study medication.
Time frame: Samples were collected on Day 1 (Week 0), Week 4, Week 8, Week 12 and Week 24
Population: The Safety Analysis Set consisted of all patients who received at least 1 dose of study medication. Only patients receiving exenatide in the controlled assessment period were included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Controlled Assessment Period - Exenatide | Percentage of Patients Positive for Anti-Drug Antibodies (ADAs) to Exenatide up to Week 24 | Week 4: Low Positive | 30.2 percentage of participants |
| Controlled Assessment Period - Exenatide | Percentage of Patients Positive for Anti-Drug Antibodies (ADAs) to Exenatide up to Week 24 | Week 4: Treatment-Emergent ADA Positive | 45.3 percentage of participants |
| Controlled Assessment Period - Exenatide | Percentage of Patients Positive for Anti-Drug Antibodies (ADAs) to Exenatide up to Week 24 | Week 8: High Positive | 53.8 percentage of participants |
| Controlled Assessment Period - Exenatide | Percentage of Patients Positive for Anti-Drug Antibodies (ADAs) to Exenatide up to Week 24 | Week 8: Low Positive | 38.5 percentage of participants |
| Controlled Assessment Period - Exenatide | Percentage of Patients Positive for Anti-Drug Antibodies (ADAs) to Exenatide up to Week 24 | Week 8: Treatment-Emergent ADA Positive | 92.3 percentage of participants |
| Controlled Assessment Period - Exenatide | Percentage of Patients Positive for Anti-Drug Antibodies (ADAs) to Exenatide up to Week 24 | Week 12: High Positive | 60.0 percentage of participants |
| Controlled Assessment Period - Exenatide | Percentage of Patients Positive for Anti-Drug Antibodies (ADAs) to Exenatide up to Week 24 | Week 12: Low Positive | 38.0 percentage of participants |
| Controlled Assessment Period - Exenatide | Percentage of Patients Positive for Anti-Drug Antibodies (ADAs) to Exenatide up to Week 24 | Week 12: Treatment-Emergent ADA Positive | 98.0 percentage of participants |
| Controlled Assessment Period - Exenatide | Percentage of Patients Positive for Anti-Drug Antibodies (ADAs) to Exenatide up to Week 24 | Week 24: High Positive | 40.8 percentage of participants |
| Controlled Assessment Period - Exenatide | Percentage of Patients Positive for Anti-Drug Antibodies (ADAs) to Exenatide up to Week 24 | Week 24: Low Positive | 55.1 percentage of participants |
| Controlled Assessment Period - Exenatide | Percentage of Patients Positive for Anti-Drug Antibodies (ADAs) to Exenatide up to Week 24 | Week 24: Treatment-Emergent ADA Positive | 95.9 percentage of participants |
| Controlled Assessment Period - Exenatide | Percentage of Patients Positive for Anti-Drug Antibodies (ADAs) to Exenatide up to Week 24 | Week 4: High Positive | 17.0 percentage of participants |
Primary
Percentage of Patients With On-Treatment Adverse Events (AEs) up to Week 24 (Controlled Assessment Period)
A controlled assessment period AE was defined as an AE starting on or after day of first dose of study medication up to but not including Week 24 for patients entering the extension period. For patients not entering the extension period, the period was defined up to and including last dose of study medication + 7 days (+ 90 days for serious AEs \[SAEs\] and other clinically significant or related AEs). The Investigator assessed AEs for causal relationship to study drug medication.
Time frame: Day 1 (Week 0) up to Week 24, plus up to a maximum of 90 days follow up
Population: The Safety Analysis Set consisted of all patients who received at least 1 dose of study medication. One patient who was randomized to placebo received a dose of exenatide in error and was subsequently reassigned to the exenatide treatment group for analyses based on actual treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Controlled Assessment Period - Exenatide | Percentage of Patients With On-Treatment Adverse Events (AEs) up to Week 24 (Controlled Assessment Period) | Any AE with outcome of death | 0 percentage of participants |
| Controlled Assessment Period - Exenatide | Percentage of Patients With On-Treatment Adverse Events (AEs) up to Week 24 (Controlled Assessment Period) | Any AE leading to discontinuation from study | 0 percentage of participants |
| Controlled Assessment Period - Exenatide | Percentage of Patients With On-Treatment Adverse Events (AEs) up to Week 24 (Controlled Assessment Period) | Any AE related to treatment | 25.4 percentage of participants |
| Controlled Assessment Period - Exenatide | Percentage of Patients With On-Treatment Adverse Events (AEs) up to Week 24 (Controlled Assessment Period) | Any AE | 61.0 percentage of participants |
| Controlled Assessment Period - Exenatide | Percentage of Patients With On-Treatment Adverse Events (AEs) up to Week 24 (Controlled Assessment Period) | Any SAE | 3.4 percentage of participants |
| Controlled Assessment Period - Exenatide | Percentage of Patients With On-Treatment Adverse Events (AEs) up to Week 24 (Controlled Assessment Period) | Any AE leading to discontinuation of treatment | 0 percentage of participants |
| Controlled Assessment Period - Placebo | Percentage of Patients With On-Treatment Adverse Events (AEs) up to Week 24 (Controlled Assessment Period) | Any AE related to treatment | 21.7 percentage of participants |
| Controlled Assessment Period - Placebo | Percentage of Patients With On-Treatment Adverse Events (AEs) up to Week 24 (Controlled Assessment Period) | Any AE with outcome of death | 0 percentage of participants |
| Controlled Assessment Period - Placebo | Percentage of Patients With On-Treatment Adverse Events (AEs) up to Week 24 (Controlled Assessment Period) | Any SAE | 4.3 percentage of participants |
| Controlled Assessment Period - Placebo | Percentage of Patients With On-Treatment Adverse Events (AEs) up to Week 24 (Controlled Assessment Period) | Any AE | 73.9 percentage of participants |
| Controlled Assessment Period - Placebo | Percentage of Patients With On-Treatment Adverse Events (AEs) up to Week 24 (Controlled Assessment Period) | Any AE leading to discontinuation from study | 0 percentage of participants |
| Controlled Assessment Period - Placebo | Percentage of Patients With On-Treatment Adverse Events (AEs) up to Week 24 (Controlled Assessment Period) | Any AE leading to discontinuation of treatment | 0 percentage of participants |
Secondary
Change From Baseline in Blood Pressure (Systolic and Diastolic) to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period)
Change from baseline in SBP and DBP to Week 52 among patients who received open-label exenatide during the treatment period is reported as mean values. The treatment period was defined as the controlled assessment period and extension period combined. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. Data collected after initiation of rescue medication or after premature discontinuation of study medication were excluded.
Time frame: Baseline (Week 0) and Week 52
Population: The ITT Analysis Set consisted of all randomized patients who received at least 1 dose of randomized study medication. Only patients with observed baseline and Week 52 values, and who received open-label exenatide were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Controlled Assessment Period - Exenatide | Change From Baseline in Blood Pressure (Systolic and Diastolic) to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) | SBP | -0.7 mmHg | Standard Deviation 13.09 |
| Controlled Assessment Period - Exenatide | Change From Baseline in Blood Pressure (Systolic and Diastolic) to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) | DBP | 1.1 mmHg | Standard Deviation 8.65 |
| Controlled Assessment Period - Placebo | Change From Baseline in Blood Pressure (Systolic and Diastolic) to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) | SBP | -0.6 mmHg | Standard Deviation 8.73 |
| Controlled Assessment Period - Placebo | Change From Baseline in Blood Pressure (Systolic and Diastolic) to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) | DBP | -2.5 mmHg | Standard Deviation 10.65 |
Secondary
Change From Baseline in Body Weight to Week 24 (Controlled Assessment Period)
Change from baseline in body weight to Week 24 during the controlled assessment period is reported as adjusted LS mean values. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. A MMRM analysis was performed, excluding data collected after initiation of rescue medication or after premature discontinuation of study medication.
Time frame: Baseline (Week 0) and Week 24
Population: The ITT Analysis Set consisted of all randomized patients who received at least 1 dose of randomized study medication.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Controlled Assessment Period - Exenatide | Change From Baseline in Body Weight to Week 24 (Controlled Assessment Period) | -0.59 kilogram (kg) | Standard Error 0.665 |
| Controlled Assessment Period - Placebo | Change From Baseline in Body Weight to Week 24 (Controlled Assessment Period) | 0.63 kilogram (kg) | Standard Error 0.982 |
Comparison: Adjusted LS mean and treatment group difference in the change from baseline at Week 24 were modeled using a MMRM including treatment group, region, visit, and treatment group by visit interaction, baseline body weight, screening HbA1c (\< 9.0% or ≥ 9.0%), and baseline body weight by visit interaction as fixed effects, using an unstructured covariance matrix.p-value: 0.30795% CI: [-3.59, 1.15]Mixed Models Analysis
Secondary
Change From Baseline in Body Weight to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period)
Change from baseline in body weight to Week 52 among patients who received open-label exenatide during the treatment period is reported as mean values. The treatment period was defined as the controlled assessment period and extension period combined. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. Data collected after initiation of rescue medication or after premature discontinuation of study medication were excluded.
Time frame: Baseline (Week 0) and Week 52
Population: The ITT Analysis Set consisted of all randomized patients who received at least 1 dose of randomized study medication. Only patients with observed baseline and Week 52 values, and who received open-label exenatide were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Controlled Assessment Period - Exenatide | Change From Baseline in Body Weight to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) | 0.04 kg | Standard Deviation 6.088 |
| Controlled Assessment Period - Placebo | Change From Baseline in Body Weight to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) | -0.04 kg | Standard Deviation 4.687 |
Secondary
Change From Baseline in Fasting Insulin to Week 24 (Controlled Assessment Period)
Change from baseline in fasting insulin to Week 24 during the controlled assessment period is reported as adjusted LS mean values. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. A MMRM analysis was performed, excluding data collected after initiation of rescue medication or after premature discontinuation of study medication.
Time frame: Baseline (Week 0) and Week 24
Population: The ITT Analysis Set consisted of all randomized patients who received at least 1 dose of randomized study medication.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Controlled Assessment Period - Exenatide | Change From Baseline in Fasting Insulin to Week 24 (Controlled Assessment Period) | 79.6 picomoles per liter (pmol/L) | Standard Error 52.28 |
| Controlled Assessment Period - Placebo | Change From Baseline in Fasting Insulin to Week 24 (Controlled Assessment Period) | -15.3 picomoles per liter (pmol/L) | Standard Error 78.49 |
Comparison: Adjusted LS mean and treatment group difference in the change from baseline at Week 24 were modeled using a MMRM including treatment group, region, visit, treatment group by visit interaction, baseline fasting insulin, screening HbA1c (\< 9.0% or ≥ 9.0%), and baseline fasting insulin by visit interaction as fixed effects, using an unstructured covariance matrix.p-value: 0.32395% CI: [-95.6, 285.5]Mixed Models Analysis
Secondary
Change From Baseline in Fasting Insulin to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period)
Change from baseline in fasting insulin to Week 52 among patients who received open-label exenatide during the treatment period is reported as mean values. The treatment period was defined as the controlled assessment period and extension period combined. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. Data collected after initiation of rescue medication or after premature discontinuation of study medication were excluded.
Time frame: Baseline (Week 0) and Week 52
Population: The ITT Analysis Set consisted of all randomized patients who received at least 1 dose of randomized study medication. Only patients with observed baseline and Week 52 values, and who received open-label exenatide were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Controlled Assessment Period - Exenatide | Change From Baseline in Fasting Insulin to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) | -32.4 pmol/L | Standard Deviation 273.57 |
| Controlled Assessment Period - Placebo | Change From Baseline in Fasting Insulin to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) | 121.5 pmol/L | Standard Deviation 379.13 |
Secondary
Change From Baseline in Fasting Plasma Glucose (FPG) Concentration to Week 24 (Controlled Assessment Period)
Change from baseline in FPG to Week 24 during the controlled assessment period is reported as adjusted LS mean values. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. A MMRM analysis was performed, excluding data collected after initiation of rescue medication or after premature discontinuation of study medication.
Time frame: Baseline (Week 0) and Week 24
Population: The ITT Analysis Set consisted of all randomized patients who received at least 1 dose of randomized study medication.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Controlled Assessment Period - Exenatide | Change From Baseline in Fasting Plasma Glucose (FPG) Concentration to Week 24 (Controlled Assessment Period) | -5.2 milligrams per deciliter (mg/dL) | Standard Error 7.65 |
| Controlled Assessment Period - Placebo | Change From Baseline in Fasting Plasma Glucose (FPG) Concentration to Week 24 (Controlled Assessment Period) | 16.5 milligrams per deciliter (mg/dL) | Standard Error 11.32 |
Comparison: Adjusted LS mean and treatment group difference in the change from baseline at Week 24 were modeled using a MMRM including treatment group, region, visit, and treatment group by visit interaction, baseline fasting plasma glucose value, screening HbA1c (\< 9.0% or ≥ 9.0%), and baseline fasting plasma glucose by visit interaction as fixed effects, using an unstructured covariance matrix.p-value: 0.11995% CI: [-49, 5.7]Mixed Models Analysis
Secondary
Change From Baseline in FPG Concentration to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period)
Change from baseline in FPG to Week 52 among patients who received open-label exenatide during the treatment period is reported as mean values. The treatment period was defined as the controlled assessment period and extension period combined. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. Data collected after initiation of rescue medication or after premature discontinuation of study medication were excluded.
Time frame: Baseline (Week 0) and Week 52
Population: The ITT Analysis Set consisted of all randomized patients who received at least 1 dose of randomized study medication. Only patients with observed baseline and Week 52 values, and who received open-label exenatide were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Controlled Assessment Period - Exenatide | Change From Baseline in FPG Concentration to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) | -1.8 mg/dL | Standard Deviation 62.64 |
| Controlled Assessment Period - Placebo | Change From Baseline in FPG Concentration to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) | 10.6 mg/dL | Standard Deviation 75.49 |
Secondary
Change From Baseline in HbA1c to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period)
Change from baseline in HbA1c (%) to Week 52 among patients who received open-label exenatide during the treatment period is reported as mean values. The treatment period was defined as the controlled assessment period and extension period combined. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. Data collected after initiation of rescue medication or after premature discontinuation of study medication were excluded.
Time frame: Baseline (Week 0) and Week 52
Population: The Evaluable Analysis Set consisted of all randomized patients who received at least 1 dose of randomized study medication and had at least 1 baseline and post-baseline HbA1c assessment. Only patients with observed baseline and Week 52 values, and who received open-label exenatide were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Controlled Assessment Period - Exenatide | Change From Baseline in HbA1c to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) | -0.10 percentage (% HbA1c) | Standard Deviation 1.711 |
| Controlled Assessment Period - Placebo | Change From Baseline in HbA1c to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) | 0.53 percentage (% HbA1c) | Standard Deviation 2.123 |
Secondary
Change From Baseline in HOMA-B and HOMA-S to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period)
Change from baseline in HOMA-B and HOMA-S to Week 52 among patients who received open-label exenatide during the treatment period is reported as mean values. The treatment period was defined as the controlled assessment period and extension period combined. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. Data collected after initiation of rescue medication or after premature discontinuation of study medication were excluded.
Time frame: Baseline (Week 0) and Week 52
Population: The ITT Analysis Set consisted of all randomized patients who received at least 1 dose of randomized study medication. Only patients with observed baseline and Week 52 values, and who received open-label exenatide were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Controlled Assessment Period - Exenatide | Change From Baseline in HOMA-B and HOMA-S to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) | HOMA-B | -2.58 percentage (%HOMA-B and %HOMA-S) | Standard Deviation 130.435 |
| Controlled Assessment Period - Exenatide | Change From Baseline in HOMA-B and HOMA-S to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) | HOMA-S | 9.85 percentage (%HOMA-B and %HOMA-S) | Standard Deviation 12.366 |
| Controlled Assessment Period - Placebo | Change From Baseline in HOMA-B and HOMA-S to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) | HOMA-B | 42.02 percentage (%HOMA-B and %HOMA-S) | Standard Deviation 183.869 |
| Controlled Assessment Period - Placebo | Change From Baseline in HOMA-B and HOMA-S to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) | HOMA-S | 2.36 percentage (%HOMA-B and %HOMA-S) | Standard Deviation 7.631 |
Secondary
Change From Baseline in Homeostasis Model Assessments - Beta-Cell Function (HOMA-B) and Insulin Sensitivity (HOMA-S) to Week 24 (Controlled Assessment Period)
Change from baseline in HOMA-B and HOMA-S in patients who were not taking insulin to Week 24 during the controlled assessment period is reported as adjusted LS mean values. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. A MMRM analysis was performed, excluding data collected after initiation of rescue medication or after premature discontinuation of study medication.
Time frame: Baseline (Week 0) and Week 24
Population: The ITT Analysis Set consisted of all randomized patients who received at least 1 dose of randomized study medication. Homeostasis model assessments were only performed in patients who were not taking insulin.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Controlled Assessment Period - Exenatide | Change From Baseline in Homeostasis Model Assessments - Beta-Cell Function (HOMA-B) and Insulin Sensitivity (HOMA-S) to Week 24 (Controlled Assessment Period) | HOMA-B | 63.98 percentage (%HOMA-B and %HOMA-S) | Standard Error 39.552 |
| Controlled Assessment Period - Exenatide | Change From Baseline in Homeostasis Model Assessments - Beta-Cell Function (HOMA-B) and Insulin Sensitivity (HOMA-S) to Week 24 (Controlled Assessment Period) | HOMA-S | 0.62 percentage (%HOMA-B and %HOMA-S) | Standard Error 3.607 |
| Controlled Assessment Period - Placebo | Change From Baseline in Homeostasis Model Assessments - Beta-Cell Function (HOMA-B) and Insulin Sensitivity (HOMA-S) to Week 24 (Controlled Assessment Period) | HOMA-B | -26.39 percentage (%HOMA-B and %HOMA-S) | Standard Error 56.138 |
| Controlled Assessment Period - Placebo | Change From Baseline in Homeostasis Model Assessments - Beta-Cell Function (HOMA-B) and Insulin Sensitivity (HOMA-S) to Week 24 (Controlled Assessment Period) | HOMA-S | 7.37 percentage (%HOMA-B and %HOMA-S) | Standard Error 4.914 |
Comparison: Treatment difference in HOMA-B:~Adjusted LS mean and treatment group difference in the change from baseline at Week 24 were modeled using a MMRM including treatment group, region, visit, treatment group by visit interaction, baseline HOMA-B, screening HbA1c (\< 9.0% or ≥ 9.0%), and baseline HOMA-B by visit interaction as fixed effects, using an unstructured covariance matrix.p-value: 0.21195% CI: [-57.27, 238]Mixed Models Analysis
Comparison: Treatment difference in HOMA-S:~Adjusted LS mean and treatment group difference in the change from baseline at Week 24 were modeled using a MMRM including treatment group, region, visit, treatment group by visit interaction, baseline HOMA-S, screening HbA1c (\< 9.0% or ≥ 9.0%), and baseline HOMA-S by visit interaction as fixed effects, using an unstructured covariance matrix.p-value: 0.28995% CI: [-19.8, 6.29]Mixed Models Analysis
Secondary
Change From Baseline in Lipid Profiles to Week 24 (Controlled Assessment Period)
Change from baseline in lipid profiles to Week 24 during the controlled assessment period is reported as mean values (Standard International \[SI\] units). The following lipids were assessed: total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides. All lipids presented were taken in a fasted state. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. Data collected after initiation of rescue medication or after premature discontinuation of study medication were excluded.
Time frame: Baseline (Week 0) and Week 24
Population: The ITT Analysis Set consisted of all randomized patients who received at least 1 dose of randomized study medication. Only patients with data available were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Controlled Assessment Period - Exenatide | Change From Baseline in Lipid Profiles to Week 24 (Controlled Assessment Period) | Total Cholesterol | -0.117 millimoles per liter (mmol/L) | Standard Deviation 0.7124 |
| Controlled Assessment Period - Exenatide | Change From Baseline in Lipid Profiles to Week 24 (Controlled Assessment Period) | HDL-C | -0.035 millimoles per liter (mmol/L) | Standard Deviation 0.195 |
| Controlled Assessment Period - Exenatide | Change From Baseline in Lipid Profiles to Week 24 (Controlled Assessment Period) | LDL-C | -0.050 millimoles per liter (mmol/L) | Standard Deviation 0.5618 |
| Controlled Assessment Period - Exenatide | Change From Baseline in Lipid Profiles to Week 24 (Controlled Assessment Period) | Triglycerides | -0.122 millimoles per liter (mmol/L) | Standard Deviation 1.0303 |
| Controlled Assessment Period - Placebo | Change From Baseline in Lipid Profiles to Week 24 (Controlled Assessment Period) | Triglycerides | 0.094 millimoles per liter (mmol/L) | Standard Deviation 0.6626 |
| Controlled Assessment Period - Placebo | Change From Baseline in Lipid Profiles to Week 24 (Controlled Assessment Period) | Total Cholesterol | -0.114 millimoles per liter (mmol/L) | Standard Deviation 0.5819 |
| Controlled Assessment Period - Placebo | Change From Baseline in Lipid Profiles to Week 24 (Controlled Assessment Period) | LDL-C | -0.110 millimoles per liter (mmol/L) | Standard Deviation 0.5983 |
| Controlled Assessment Period - Placebo | Change From Baseline in Lipid Profiles to Week 24 (Controlled Assessment Period) | HDL-C | -0.047 millimoles per liter (mmol/L) | Standard Deviation 0.1039 |
Secondary
Change From Baseline in Lipids Profiles to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period)
Change from baseline in lipid profiles to Week 52 among patients who received open-label exenatide during the treatment period is reported as mean values (SI units). The treatment period was defined as the controlled assessment period and extension period combined. The following lipids were assessed: total cholesterol, HDL-C, LDL-C, and triglycerides. All lipids presented were taken in a fasted state. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. Data collected after initiation of rescue medication or after premature discontinuation of study medication were excluded.
Time frame: Baseline (Week 0) and Week 52
Population: The ITT Analysis Set consisted of all randomized patients who received at least 1 dose of randomized study medication. Only patients with observed baseline and Week 52 values, and who received open-label exenatide were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Controlled Assessment Period - Exenatide | Change From Baseline in Lipids Profiles to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) | LDL-C | -0.175 mmol/L | Standard Deviation 0.4025 |
| Controlled Assessment Period - Exenatide | Change From Baseline in Lipids Profiles to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) | Total Cholesterol | -0.188 mmol/L | Standard Deviation 0.4199 |
| Controlled Assessment Period - Exenatide | Change From Baseline in Lipids Profiles to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) | Triglycerides | -0.155 mmol/L | Standard Deviation 1.1108 |
| Controlled Assessment Period - Exenatide | Change From Baseline in Lipids Profiles to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) | HDL-C | 0.004 mmol/L | Standard Deviation 0.174 |
| Controlled Assessment Period - Placebo | Change From Baseline in Lipids Profiles to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) | Triglycerides | -0.043 mmol/L | Standard Deviation 0.5971 |
| Controlled Assessment Period - Placebo | Change From Baseline in Lipids Profiles to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) | LDL-C | -0.152 mmol/L | Standard Deviation 0.7682 |
| Controlled Assessment Period - Placebo | Change From Baseline in Lipids Profiles to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) | HDL-C | -0.076 mmol/L | Standard Deviation 0.2327 |
| Controlled Assessment Period - Placebo | Change From Baseline in Lipids Profiles to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) | Total Cholesterol | -0.255 mmol/L | Standard Deviation 0.9075 |
Secondary
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) to Week 24 (Controlled Assessment Period)
Change from baseline in SBP and DBP to Week 24 during the controlled assessment period is reported as adjusted LS mean values. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of randomized study medication. A MMRM analysis was performed, excluding data collected after initiation of rescue medication or after premature discontinuation of study medication.
Time frame: Baseline (Week 0) and Week 24
Population: The ITT Analysis Set consisted of all randomized patients who received at least 1 dose of randomized study medication.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Controlled Assessment Period - Exenatide | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) to Week 24 (Controlled Assessment Period) | SBP | -0.7 millimeters mercury (mmHg) | Standard Error 1.48 |
| Controlled Assessment Period - Exenatide | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) to Week 24 (Controlled Assessment Period) | DBP | 0.2 millimeters mercury (mmHg) | Standard Error 1 |
| Controlled Assessment Period - Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) to Week 24 (Controlled Assessment Period) | SBP | 2.2 millimeters mercury (mmHg) | Standard Error 2.15 |
| Controlled Assessment Period - Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) to Week 24 (Controlled Assessment Period) | DBP | -1.3 millimeters mercury (mmHg) | Standard Error 1.45 |
Comparison: Treatment difference in SBP:~Adjusted LS mean and treatment group difference in the change from baseline at Week 24 were modeled using a MMRM including treatment group, region, visit, treatment group by visit interaction, baseline SBP, screening HbA1c (\< 9.0% or ≥ 9.0%), and baseline SBP by visit interaction as fixed effects, using an unstructured covariance matrix.p-value: 0.28495% CI: [-8, 2.4]Mixed Models Analysis
Comparison: Treatment difference in DBP:~Adjusted LS mean and treatment group difference in the change from baseline at Week 24 were modeled using a MMRM including treatment group, region, visit, treatment group by visit interaction, baseline DBP, screening HbA1c (\< 9.0% or ≥ 9.0%), and baseline DBP by visit interaction as fixed effects, using an unstructured covariance matrix.p-value: 0.37695% CI: [-2, 5.1]Mixed Models Analysis
Secondary
Number of Patients Needing Rescue Medication Due to Failure to Maintain Glycemic Control up to Week 24 (Controlled Assessment Period)
Number of patients needing rescue medication at Week 24 and at each intermediate visit during the controlled assessment period is reported. Patients with a loss of glycemic control, defined as either an increase from baseline in HbA1c values by ≥ 1.0% at 2 consecutive clinic visits that were at least 1 month apart, or a fasting plasma glucose value ≥ 250 mg/dL or random blood glucose value \> 300 mg/dL for 4 days during a 7 day period, received rescue medication. Data collected after premature discontinuation of study medication were excluded.
Time frame: At Week 4, Week 8, Week 12, Week 18 and Week 24
Population: The ITT Analysis Set consisted of all randomized patients who received at least 1 dose of randomized study medication. Only patients with data available at each specified visit were included in the analysis.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Controlled Assessment Period - Exenatide | Number of Patients Needing Rescue Medication Due to Failure to Maintain Glycemic Control up to Week 24 (Controlled Assessment Period) | Week 8 | 0 Participants |
| Controlled Assessment Period - Exenatide | Number of Patients Needing Rescue Medication Due to Failure to Maintain Glycemic Control up to Week 24 (Controlled Assessment Period) | Week 18 | 1 Participants |
| Controlled Assessment Period - Exenatide | Number of Patients Needing Rescue Medication Due to Failure to Maintain Glycemic Control up to Week 24 (Controlled Assessment Period) | Week 12 | 0 Participants |
| Controlled Assessment Period - Exenatide | Number of Patients Needing Rescue Medication Due to Failure to Maintain Glycemic Control up to Week 24 (Controlled Assessment Period) | Week 24 | 0 Participants |
| Controlled Assessment Period - Exenatide | Number of Patients Needing Rescue Medication Due to Failure to Maintain Glycemic Control up to Week 24 (Controlled Assessment Period) | Week 4 | 0 Participants |
| Controlled Assessment Period - Placebo | Number of Patients Needing Rescue Medication Due to Failure to Maintain Glycemic Control up to Week 24 (Controlled Assessment Period) | Week 24 | 0 Participants |
| Controlled Assessment Period - Placebo | Number of Patients Needing Rescue Medication Due to Failure to Maintain Glycemic Control up to Week 24 (Controlled Assessment Period) | Week 4 | 0 Participants |
| Controlled Assessment Period - Placebo | Number of Patients Needing Rescue Medication Due to Failure to Maintain Glycemic Control up to Week 24 (Controlled Assessment Period) | Week 8 | 0 Participants |
| Controlled Assessment Period - Placebo | Number of Patients Needing Rescue Medication Due to Failure to Maintain Glycemic Control up to Week 24 (Controlled Assessment Period) | Week 12 | 0 Participants |
| Controlled Assessment Period - Placebo | Number of Patients Needing Rescue Medication Due to Failure to Maintain Glycemic Control up to Week 24 (Controlled Assessment Period) | Week 18 | 0 Participants |
Secondary
Number of Patients Needing Rescue Medication Due to Failure to Maintain Glycemic Control up to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period)
Number of patients needing rescue medication at Week 52 and at each intermediate visit during the treatment period is reported. The treatment period was defined as the controlled assessment period and extension period combined. Patients with a loss of glycemic control, defined as either an increase from baseline in HbA1c values by ≥ 1.0% at 2 consecutive clinic visits that were at least 1 month apart, or a fasting plasma glucose value ≥ 250 mg/dL or random blood glucose value \> 300 mg/dL for 4 days during a 7 day period, received rescue medication. Data collected after premature discontinuation of study medication were excluded.
Time frame: At Week 4, Week 8, Week 12, Week 18, Week 24, Week 28, Week 40 and Week 52
Population: The ITT Analysis Set consisted of all randomized patients who received at least 1 dose of randomized study medication. Only patients who received open-label exenatide and with data available were included in the analysis.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Controlled Assessment Period - Exenatide | Number of Patients Needing Rescue Medication Due to Failure to Maintain Glycemic Control up to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) | Week 4 | 0 Participants |
| Controlled Assessment Period - Exenatide | Number of Patients Needing Rescue Medication Due to Failure to Maintain Glycemic Control up to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) | Week 8 | 0 Participants |
| Controlled Assessment Period - Exenatide | Number of Patients Needing Rescue Medication Due to Failure to Maintain Glycemic Control up to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) | Week 12 | 0 Participants |
| Controlled Assessment Period - Exenatide | Number of Patients Needing Rescue Medication Due to Failure to Maintain Glycemic Control up to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) | Week 18 | 1 Participants |
| Controlled Assessment Period - Exenatide | Number of Patients Needing Rescue Medication Due to Failure to Maintain Glycemic Control up to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) | Week 24 | 0 Participants |
| Controlled Assessment Period - Exenatide | Number of Patients Needing Rescue Medication Due to Failure to Maintain Glycemic Control up to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) | Week 28 | 2 Participants |
| Controlled Assessment Period - Exenatide | Number of Patients Needing Rescue Medication Due to Failure to Maintain Glycemic Control up to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) | Week 40 | 2 Participants |
| Controlled Assessment Period - Exenatide | Number of Patients Needing Rescue Medication Due to Failure to Maintain Glycemic Control up to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) | Week 52 | 0 Participants |
| Controlled Assessment Period - Placebo | Number of Patients Needing Rescue Medication Due to Failure to Maintain Glycemic Control up to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) | Week 52 | 0 Participants |
| Controlled Assessment Period - Placebo | Number of Patients Needing Rescue Medication Due to Failure to Maintain Glycemic Control up to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) | Week 4 | 0 Participants |
| Controlled Assessment Period - Placebo | Number of Patients Needing Rescue Medication Due to Failure to Maintain Glycemic Control up to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) | Week 24 | 0 Participants |
| Controlled Assessment Period - Placebo | Number of Patients Needing Rescue Medication Due to Failure to Maintain Glycemic Control up to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) | Week 8 | 0 Participants |
| Controlled Assessment Period - Placebo | Number of Patients Needing Rescue Medication Due to Failure to Maintain Glycemic Control up to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) | Week 40 | 0 Participants |
| Controlled Assessment Period - Placebo | Number of Patients Needing Rescue Medication Due to Failure to Maintain Glycemic Control up to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) | Week 12 | 0 Participants |
| Controlled Assessment Period - Placebo | Number of Patients Needing Rescue Medication Due to Failure to Maintain Glycemic Control up to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) | Week 28 | 1 Participants |
| Controlled Assessment Period - Placebo | Number of Patients Needing Rescue Medication Due to Failure to Maintain Glycemic Control up to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) | Week 18 | 0 Participants |
Secondary
Percentage of Participants Achieving HbA1c Goals of < 6.5%, ≤ 6.5%, and < 7.0% to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period)
The percentage of patients achieving HbA1c goals of \< 6.5%, ≤ 6.5%, and \< 7.0% at Week 52 among patients who received open-label exenatide during the treatment period is reported. The treatment period was defined as the controlled assessment period and extension period combined. Data collected after initiation of rescue medication or after premature discontinuation of study medication were excluded.
Time frame: At Week 52
Population: The Evaluable Analysis Set consisted of all randomized patients who received at least 1 dose of randomized study medication and had at least 1 baseline and post-baseline HbA1c assessment. Only patients who received open-label exenatide and with data available were included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Controlled Assessment Period - Exenatide | Percentage of Participants Achieving HbA1c Goals of < 6.5%, ≤ 6.5%, and < 7.0% to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) | HbA1c < 6.5% | 30.8 percentage of participants |
| Controlled Assessment Period - Exenatide | Percentage of Participants Achieving HbA1c Goals of < 6.5%, ≤ 6.5%, and < 7.0% to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) | HbA1c ≤ 6.5% | 30.8 percentage of participants |
| Controlled Assessment Period - Exenatide | Percentage of Participants Achieving HbA1c Goals of < 6.5%, ≤ 6.5%, and < 7.0% to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) | HbA1c < 7.0% | 35.9 percentage of participants |
| Controlled Assessment Period - Placebo | Percentage of Participants Achieving HbA1c Goals of < 6.5%, ≤ 6.5%, and < 7.0% to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) | HbA1c < 6.5% | 23.5 percentage of participants |
| Controlled Assessment Period - Placebo | Percentage of Participants Achieving HbA1c Goals of < 6.5%, ≤ 6.5%, and < 7.0% to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) | HbA1c ≤ 6.5% | 23.5 percentage of participants |
| Controlled Assessment Period - Placebo | Percentage of Participants Achieving HbA1c Goals of < 6.5%, ≤ 6.5%, and < 7.0% to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) | HbA1c < 7.0% | 29.4 percentage of participants |
Secondary
Percentage of Patients Achieving HbA1c Goals of < 6.5%, ≤ 6.5%, and < 7.0% at Week 24 (Controlled Assessment Period)
The percentage of patients achieving HbA1c goals of \< 6.5%, ≤ 6.5%, and \< 7.0% at Week 24 during the controlled assessment period is reported. A Cochran-Mantel-Haenszel (CMH) analysis was performed with missing data treated as non-responder, and excluding data collected after initiation of rescue medication or after premature discontinuation of study medication.
Time frame: At Week 24
Population: The Evaluable Analysis Set consisted of all randomized patients who received at least 1 dose of randomized study medication and had at least 1 baseline and post-baseline HbA1c assessment. Only patients with data available were included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Controlled Assessment Period - Exenatide | Percentage of Patients Achieving HbA1c Goals of < 6.5%, ≤ 6.5%, and < 7.0% at Week 24 (Controlled Assessment Period) | HbA1c ≤ 6.5% | 19.0 percentage of participants |
| Controlled Assessment Period - Exenatide | Percentage of Patients Achieving HbA1c Goals of < 6.5%, ≤ 6.5%, and < 7.0% at Week 24 (Controlled Assessment Period) | HbA1c <6 .5% | 19.0 percentage of participants |
| Controlled Assessment Period - Exenatide | Percentage of Patients Achieving HbA1c Goals of < 6.5%, ≤ 6.5%, and < 7.0% at Week 24 (Controlled Assessment Period) | HbA1c < 7.0% | 31.0 percentage of participants |
| Controlled Assessment Period - Placebo | Percentage of Patients Achieving HbA1c Goals of < 6.5%, ≤ 6.5%, and < 7.0% at Week 24 (Controlled Assessment Period) | HbA1c <6 .5% | 4.2 percentage of participants |
| Controlled Assessment Period - Placebo | Percentage of Patients Achieving HbA1c Goals of < 6.5%, ≤ 6.5%, and < 7.0% at Week 24 (Controlled Assessment Period) | HbA1c < 7.0% | 8.3 percentage of participants |
| Controlled Assessment Period - Placebo | Percentage of Patients Achieving HbA1c Goals of < 6.5%, ≤ 6.5%, and < 7.0% at Week 24 (Controlled Assessment Period) | HbA1c ≤ 6.5% | 4.2 percentage of participants |
Comparison: Treatment difference in HbA1c \< 6.5%:~Treatment group comparison was based on CMH test stratified by screening HbA1c (\<9.0% or \>=9.0%). P-value was from the general association statistic.p-value: 0.07795% CI: [1.9, 27.7]Cochran-Mantel-Haenszel
Comparison: Treatment difference in HbA1c ≤ 6.5%:~Treatment group comparison was based on CMH test stratified by screening HbA1c (\<9.0% or \>=9.0%). P-value was from the general association statistic.p-value: 0.07795% CI: [1.9, 27.7]Cochran-Mantel-Haenszel
Comparison: Treatment difference in HbA1c \< 7.0%:~Treatment group comparison was based on CMH test stratified by screening HbA1c (\<9.0% or \>=9.0%). P-value was from the general association statistic.p-value: 0.0295% CI: [6.5, 39]Cochran-Mantel-Haenszel
Secondary
Percentage of Patients Reporting AEs of Injection Site Reactions up to Week 24 (Controlled Assessment Period)
Percentage of patients reporting injection site reactions at Week 24 and at each intermediate visit during the controlled assessment period is reported. Injection site reactions were presented from the AE case report form (CRF), based on the Injection site reactions higher level term. A controlled assessment period AE was defined as an AE starting on or after day of first dose of study medication up to but not including Week 24 for patients entering the extension period. For patients not entering the extension period, the period was defined up to and including last dose of study medication + 7 days (+ 90 days for SAEs and other clinically significant or related AEs).
Time frame: At Week 4, Week 8, Week 12, Week 18 and Week 24
Population: The Safety Analysis Set consisted of all patients who received at least 1 dose of study medication. Only patients with data available at each specified visit were included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Controlled Assessment Period - Exenatide | Percentage of Patients Reporting AEs of Injection Site Reactions up to Week 24 (Controlled Assessment Period) | Week 8 | 3.5 percentage of participants |
| Controlled Assessment Period - Exenatide | Percentage of Patients Reporting AEs of Injection Site Reactions up to Week 24 (Controlled Assessment Period) | Week 12 | 1.9 percentage of participants |
| Controlled Assessment Period - Exenatide | Percentage of Patients Reporting AEs of Injection Site Reactions up to Week 24 (Controlled Assessment Period) | Week 18 | 0 percentage of participants |
| Controlled Assessment Period - Exenatide | Percentage of Patients Reporting AEs of Injection Site Reactions up to Week 24 (Controlled Assessment Period) | Week 24 | 0 percentage of participants |
| Controlled Assessment Period - Exenatide | Percentage of Patients Reporting AEs of Injection Site Reactions up to Week 24 (Controlled Assessment Period) | Week 4 | 8.5 percentage of participants |
| Controlled Assessment Period - Placebo | Percentage of Patients Reporting AEs of Injection Site Reactions up to Week 24 (Controlled Assessment Period) | Week 24 | 0 percentage of participants |
| Controlled Assessment Period - Placebo | Percentage of Patients Reporting AEs of Injection Site Reactions up to Week 24 (Controlled Assessment Period) | Week 4 | 8.7 percentage of participants |
| Controlled Assessment Period - Placebo | Percentage of Patients Reporting AEs of Injection Site Reactions up to Week 24 (Controlled Assessment Period) | Week 8 | 4.3 percentage of participants |
| Controlled Assessment Period - Placebo | Percentage of Patients Reporting AEs of Injection Site Reactions up to Week 24 (Controlled Assessment Period) | Week 18 | 0 percentage of participants |
| Controlled Assessment Period - Placebo | Percentage of Patients Reporting AEs of Injection Site Reactions up to Week 24 (Controlled Assessment Period) | Week 12 | 0 percentage of participants |
Secondary
Percentage of Patients Reporting AEs of Injection Site Reactions up to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period)
Percentage of patients reporting injection site reactions at Week 52 and at each intermediate visit among patients who received open-label exenatide during the treatment period is reported. The treatment period was defined as the controlled assessment period and extension period combined. Injection site reactions were presented from the AE CRF, based on the Injection site reactions higher level term. An Extension Period AE was defined as an AE starting on or after day of first dose of open-label exenatide to last dose + 7 days (+ 90 days for SAEs and other clinically significant or related AEs).
Time frame: At Week 4, Week 8, Week 12, Week 18, Week 24, Week 28, Week 40 and Week 52
Population: The Safety Analysis Set consisted of all patients who received at least 1 dose of study medication. Only patients with data available at each specified visit were included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Controlled Assessment Period - Exenatide | Percentage of Patients Reporting AEs of Injection Site Reactions up to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) | Week 40 | 0 percentage of participants |
| Controlled Assessment Period - Exenatide | Percentage of Patients Reporting AEs of Injection Site Reactions up to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) | Week 8 | 4.0 percentage of participants |
| Controlled Assessment Period - Exenatide | Percentage of Patients Reporting AEs of Injection Site Reactions up to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) | Week 12 | 2.0 percentage of participants |
| Controlled Assessment Period - Exenatide | Percentage of Patients Reporting AEs of Injection Site Reactions up to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) | Week 18 | 0 percentage of participants |
| Controlled Assessment Period - Exenatide | Percentage of Patients Reporting AEs of Injection Site Reactions up to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) | Week 24 | 0 percentage of participants |
| Controlled Assessment Period - Exenatide | Percentage of Patients Reporting AEs of Injection Site Reactions up to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) | Week 52 | 0 percentage of participants |
| Controlled Assessment Period - Exenatide | Percentage of Patients Reporting AEs of Injection Site Reactions up to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) | Week 4 | 10.0 percentage of participants |
| Controlled Assessment Period - Exenatide | Percentage of Patients Reporting AEs of Injection Site Reactions up to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) | Week 28 | 4.0 percentage of participants |
| Controlled Assessment Period - Placebo | Percentage of Patients Reporting AEs of Injection Site Reactions up to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) | Week 4 | 9.1 percentage of participants |
| Controlled Assessment Period - Placebo | Percentage of Patients Reporting AEs of Injection Site Reactions up to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) | Week 52 | 0 percentage of participants |
| Controlled Assessment Period - Placebo | Percentage of Patients Reporting AEs of Injection Site Reactions up to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) | Week 8 | 4.5 percentage of participants |
| Controlled Assessment Period - Placebo | Percentage of Patients Reporting AEs of Injection Site Reactions up to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) | Week 28 | 0 percentage of participants |
| Controlled Assessment Period - Placebo | Percentage of Patients Reporting AEs of Injection Site Reactions up to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) | Week 12 | 0 percentage of participants |
| Controlled Assessment Period - Placebo | Percentage of Patients Reporting AEs of Injection Site Reactions up to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) | Week 18 | 0 percentage of participants |
| Controlled Assessment Period - Placebo | Percentage of Patients Reporting AEs of Injection Site Reactions up to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) | Week 24 | 0 percentage of participants |
| Controlled Assessment Period - Placebo | Percentage of Patients Reporting AEs of Injection Site Reactions up to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) | Week 40 | 0 percentage of participants |
Secondary
Plasma Exenatide Concentrations to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period)
Geometric mean plasma exenatide concentrations up to Week 52 during the treatment period are reported (for the placebo then exenatide treatment group, only Weeks 24 and 52 were applicable). The treatment period was defined as the controlled assessment period and extension period combined. Data collected after initiation of rescue medication were included. Data collected after discontinuation of study medication were excluded.
Time frame: Samples were collected on Day 1 (Week 0), Week 4, Week 8, Week 12, Week 24 and Week 52
Population: The Pharmacokinetic (PK) Analysis Set consisted of all patients who received at least 1 dose of exenatide, for whom any postdose data were available and who did not deviate from the protocol in ways that would significantly affect the PK analyses. Only patients who received open-label exenatide and with data available were included in the analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Controlled Assessment Period - Exenatide | Plasma Exenatide Concentrations to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) | Baseline | NA picograms per milliliter | — |
| Controlled Assessment Period - Exenatide | Plasma Exenatide Concentrations to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) | Week 4 | 41.51 picograms per milliliter | Geometric Coefficient of Variation 91.9 |
| Controlled Assessment Period - Exenatide | Plasma Exenatide Concentrations to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) | Week 8 | 130.60 picograms per milliliter | Geometric Coefficient of Variation 83.8 |
| Controlled Assessment Period - Exenatide | Plasma Exenatide Concentrations to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) | Week 12 | 163.58 picograms per milliliter | Geometric Coefficient of Variation 92.3 |
| Controlled Assessment Period - Exenatide | Plasma Exenatide Concentrations to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) | Week 24 | 140.81 picograms per milliliter | Geometric Coefficient of Variation 84 |
| Controlled Assessment Period - Exenatide | Plasma Exenatide Concentrations to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) | Week 52 | 88.88 picograms per milliliter | Geometric Coefficient of Variation 79.2 |
| Controlled Assessment Period - Placebo | Plasma Exenatide Concentrations to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) | Week 52 | 105.56 picograms per milliliter | Geometric Coefficient of Variation 154.9 |
| Controlled Assessment Period - Placebo | Plasma Exenatide Concentrations to Week 52 Among Patients Who Received Open-Label Exenatide (Treatment Period) | Week 24 | NA picograms per milliliter | — |