Type 2 Diabetes Mellitus
Conditions
Keywords
exenatide, Byetta, antibodies, Amylin, Lilly
Brief summary
The primary purpose of this study is to assess the anti-exenatide-antibody response to exenatide re-exposure as measured by anti-exenatide antibodies and incidence of treatment-emergent allergy and hypersensitivity reactions following a period of treatment interruption, in patients previously exposed to exenatide.
Interventions
DRUGexenatide
subcutaneous injection, 5mcg or 10mcg, twice a day
Sponsors
Eli Lilly and Company
AstraZeneca
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosed with type 2 diabetes. * Have been exposed to exenatide for at least 3 months in previous Amylin/Lilly Studies H8O-MC-GWAO, H8O-MC-GWAP, H8O-MC-GWAT, or H8O-MC-GWBA. * Have interrupted exenatide treatment for a period of at least 2 months. * HbA1c of ≤10.5%.
Exclusion criteria
* Have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry. * Have previously completed or withdrawn from this study. * Have taken marketed exenatide (Byetta) during the interim period between studies GWAO, GWAP, GWAT, or GWBA and the current study. * Used drugs for weight loss (for example, Xenical® \[orlistat\], Meridia® \[sibutramine\], Acutrim® \[phenylpropanolamine\], Accomplia® \[rimonabant\], or similar over-the-counter medications) within 3 months of screening. * Are currently treated with any of the following excluded medications: Drugs that directly affect gastrointestinal motility, including, but not limited to: Reglan® (metoclopramide), Propulsid® (cisapride), and chronic macrolide antibiotics. * Use insulin with daily dosage exceeding 1 U/kg.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Treatment-emergent Antibody Status (Maximum Titer Level Experienced) | 24 weeks | Patients who experienced specified treatment-emergent antibody status at any point during the study (grouped by maximum titer level experienced) |
| Incidence of Potentially Immune-related Treatment-emergent Adverse Events | 24 weeks | Number of patients experiencing a potentially immune-related treatment-emergent adverse event at any point during the study |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Hemoglobin A1c (HbA1c) From Baseline to Endpoint | 24 weeks | Change in HbA1c from baseline (Week 0) to endpoint (Week 24) by treatment-emergent antibody status |
Countries
Australia, Canada, Hungary, Italy, South Korea
Participant flow
Recruitment details
Following a period of treatment interruption of at least 2 months, patients for this study were recruited from among patients who were previously exposed to exenatide for at least 3 months in Amylin/Lilly studies GWAO, GWAP, GWAT, and GWBA.
Participants by arm
| Arm | Count |
|---|---|
| Negative Baseline (Week 0) Antibody Status Patients assessed as negative for antibodies to exenatide at baseline (Week 0). | 50 |
| Positive Baseline (Week 0) Antibody Status Patients assessed as positive for antibodies to exenatide at baseline (Week 0). | 8 |
| Total | 58 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 0 | 0 | 1 |
| Overall Study | Subject Decision | 0 | 2 | 0 |
Baseline characteristics
| Characteristic | Negative Baseline (Week 0) Antibody Status | Positive Baseline (Week 0) Antibody Status | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 19 Participants | 0 Participants | 19 Participants |
| Age, Categorical Between 18 and 65 years | 31 Participants | 8 Participants | 39 Participants |
| Age, Continuous | 60.65 years STANDARD_DEVIATION 8.95 | 49.88 years STANDARD_DEVIATION 9.84 | 59.17 years STANDARD_DEVIATION 9.74 |
| Sex: Female, Male Female | 20 Participants | 5 Participants | 25 Participants |
| Sex: Female, Male Male | 30 Participants | 3 Participants | 33 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 7 / — | 11 / — | 0 / — |
| serious Total, serious adverse events | 0 / — | 1 / — | 1 / — |
Outcome results
Primary
Incidence of Potentially Immune-related Treatment-emergent Adverse Events
Number of patients experiencing a potentially immune-related treatment-emergent adverse event at any point during the study
Time frame: 24 weeks
Population: Intent to Treat
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Exenatide:Treatment-Emergent Antibody Negative | Incidence of Potentially Immune-related Treatment-emergent Adverse Events | Arthralgia | 1 participants |
| Exenatide:Treatment-Emergent Antibody Negative | Incidence of Potentially Immune-related Treatment-emergent Adverse Events | Spinal osteoarthritis | 1 participants |
| Exenatide:Treatment-Emergent Antibody Negative | Incidence of Potentially Immune-related Treatment-emergent Adverse Events | Injection site pruritis | 0 participants |
| Exenatide:Treatment-Emergent Antibody Negative | Incidence of Potentially Immune-related Treatment-emergent Adverse Events | Injection site rash | 0 participants |
| Exenatide:Treatment-Emergent Antibody Negative | Incidence of Potentially Immune-related Treatment-emergent Adverse Events | Rash | 0 participants |
| Exenatide:Treatment-Emergent Antibody Negative | Incidence of Potentially Immune-related Treatment-emergent Adverse Events | Eye allergy | 0 participants |
| Exenatide: Treatment-Emergent Antibody Positive | Incidence of Potentially Immune-related Treatment-emergent Adverse Events | Eye allergy | 1 participants |
| Exenatide: Treatment-Emergent Antibody Positive | Incidence of Potentially Immune-related Treatment-emergent Adverse Events | Arthralgia | 0 participants |
| Exenatide: Treatment-Emergent Antibody Positive | Incidence of Potentially Immune-related Treatment-emergent Adverse Events | Injection site rash | 1 participants |
| Exenatide: Treatment-Emergent Antibody Positive | Incidence of Potentially Immune-related Treatment-emergent Adverse Events | Rash | 1 participants |
| Exenatide: Treatment-Emergent Antibody Positive | Incidence of Potentially Immune-related Treatment-emergent Adverse Events | Spinal osteoarthritis | 0 participants |
| Exenatide: Treatment-Emergent Antibody Positive | Incidence of Potentially Immune-related Treatment-emergent Adverse Events | Injection site pruritis | 2 participants |
| Enrolled But Withdrew Before Receiving Treatment | Incidence of Potentially Immune-related Treatment-emergent Adverse Events | Spinal osteoarthritis | 0 participants |
| Enrolled But Withdrew Before Receiving Treatment | Incidence of Potentially Immune-related Treatment-emergent Adverse Events | Injection site pruritis | 0 participants |
| Enrolled But Withdrew Before Receiving Treatment | Incidence of Potentially Immune-related Treatment-emergent Adverse Events | Eye allergy | 0 participants |
| Enrolled But Withdrew Before Receiving Treatment | Incidence of Potentially Immune-related Treatment-emergent Adverse Events | Injection site rash | 0 participants |
| Enrolled But Withdrew Before Receiving Treatment | Incidence of Potentially Immune-related Treatment-emergent Adverse Events | Arthralgia | 0 participants |
| Enrolled But Withdrew Before Receiving Treatment | Incidence of Potentially Immune-related Treatment-emergent Adverse Events | Rash | 0 participants |
Primary
Treatment-emergent Antibody Status (Maximum Titer Level Experienced)
Patients who experienced specified treatment-emergent antibody status at any point during the study (grouped by maximum titer level experienced)
Time frame: 24 weeks
Population: Intent to Treat
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Exenatide:Treatment-Emergent Antibody Negative | Treatment-emergent Antibody Status (Maximum Titer Level Experienced) | Low titer antibodies | 0 Participants |
| Exenatide:Treatment-Emergent Antibody Negative | Treatment-emergent Antibody Status (Maximum Titer Level Experienced) | Antibody negative | 15 Participants |
| Exenatide:Treatment-Emergent Antibody Negative | Treatment-emergent Antibody Status (Maximum Titer Level Experienced) | Higher titer antibodies | 0 Participants |
| Exenatide: Treatment-Emergent Antibody Positive | Treatment-emergent Antibody Status (Maximum Titer Level Experienced) | Low titer antibodies | 25 Participants |
| Exenatide: Treatment-Emergent Antibody Positive | Treatment-emergent Antibody Status (Maximum Titer Level Experienced) | Antibody negative | 0 Participants |
| Exenatide: Treatment-Emergent Antibody Positive | Treatment-emergent Antibody Status (Maximum Titer Level Experienced) | Higher titer antibodies | 17 Participants |
| Enrolled But Withdrew Before Receiving Treatment | Treatment-emergent Antibody Status (Maximum Titer Level Experienced) | Antibody negative | 0 Participants |
| Enrolled But Withdrew Before Receiving Treatment | Treatment-emergent Antibody Status (Maximum Titer Level Experienced) | Higher titer antibodies | 0 Participants |
| Enrolled But Withdrew Before Receiving Treatment | Treatment-emergent Antibody Status (Maximum Titer Level Experienced) | Low titer antibodies | 0 Participants |
Secondary
Change in Hemoglobin A1c (HbA1c) From Baseline to Endpoint
Change in HbA1c from baseline (Week 0) to endpoint (Week 24) by treatment-emergent antibody status
Time frame: 24 weeks
Population: Intent to Treat; Last Observation Carried Forward
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Exenatide:Treatment-Emergent Antibody Negative | Change in Hemoglobin A1c (HbA1c) From Baseline to Endpoint | Baseline HbA1c (Week 0) | 8.13 percent | Standard Deviation 0.66 |
| Exenatide:Treatment-Emergent Antibody Negative | Change in Hemoglobin A1c (HbA1c) From Baseline to Endpoint | Change in HbA1c at endpoint (Week 24) | -1.03 percent | Standard Deviation 0.74 |
| Exenatide: Treatment-Emergent Antibody Positive | Change in Hemoglobin A1c (HbA1c) From Baseline to Endpoint | Baseline HbA1c (Week 0) | 8.05 percent | Standard Deviation 1 |
| Exenatide: Treatment-Emergent Antibody Positive | Change in Hemoglobin A1c (HbA1c) From Baseline to Endpoint | Change in HbA1c at endpoint (Week 24) | -0.30 percent | Standard Deviation 0.94 |
| Enrolled But Withdrew Before Receiving Treatment | Change in Hemoglobin A1c (HbA1c) From Baseline to Endpoint | Baseline HbA1c (Week 0) | 0 percent | Standard Deviation 0 |
| Enrolled But Withdrew Before Receiving Treatment | Change in Hemoglobin A1c (HbA1c) From Baseline to Endpoint | Change in HbA1c at endpoint (Week 24) | 0 percent | Standard Deviation 0 |