Diabetes Mellitus, Type 2
Conditions
Keywords
Extension, Long-term Safety, Pharmacodynamics, Albiglutide, Type 2 Diabetes Mellitus
Brief summary
Albiglutide has been developed for the treatment of type 2 diabetes mellitus (T2DM) as an adjunct to diet and exercise, as monotherapy, or in combination with existing therapies and has been approved by the United States (US) Food and Drug Administration (FDA), the European Medicines Agency (EMA) and other regulatory agencies. This is a 26 week, open-label, single group, multicenter, extension study to Study 200952. This extension study will provide extended safety, tolerability and immunogenicity data for the albiglutide liquid drug product. This extension study will comprise 2 study periods: treatment (26 weeks) and post-treatment follow-up (8 weeks). A maximum of 300 subjects will be eligible to take part in this extension study.
Interventions
DRUGAlbiglutide
Albiglutide liquid drug product is provided as a fixed-dose, disposable auto-injector containing albiglutide liquid drug product (50 mg). Subjects will receive albiglutide 50 mg through subcutaneous injection in the abdomen, thigh or upper arm region via auto-injector. Albiglutide is a glucagon-like peptide-1 agonist (GLP-1 agonist).
DEVICEAuto-injector
The auto-injector delivers the albiglutide liquid drug product in an injection volume of 1.0 mL for the 50 mg dose.
Sponsors
GlaxoSmithKline
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Subjects who have completed the 26 week Treatment Phase of Study 200952 * Male or female * Able and willing to provide informed consent.
Exclusion criteria
* Subject meets one or more of the withdrawal stopping criteria at Visit 1 (Week 26)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Up to Week 34 | An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product whether or not it is considered drug related. This would include any side effect, injury, toxicity, sensitivity reaction, abnormal or worsening of a laboratory value, concurrent illness or sudden death. Pre-existing conditions that worsen during a study will be reported as AEs. SAE is any AE that results in death, is life-threatening, requires inpatient hospitalization or extends a current hospital stay, results in an ongoing or significant incapacity or interferes substantially with normal life functions, or causes a congenital anomaly or birth defect, or is associated with liver injury or impaired liver function. Number of participants who reported any AE or SAE during this extension study or who had ongoing AE or SAE from study 200952 have been presented. |
| Number of Participants With Physical Examination Abnormalities | Up to Week 34 | A full physical examination was planned to be done, at a minimum, assessment of the skin (including injection site), head, eyes, ears, nose, throat, thyroid, respiratory system cardiovascular system, abdomen (liver and spleen), lymph nodes, central nervous system and extremities was planned. The evaluation of skin (including injection site), respiratory system, cardiovascular system, abdomen (liver, spleen), and central nervous system was planned; however, it was not performed due to early termination of the study. |
| Number of Participants With Hematology Values of Potential Clinical Importance (PCI) | Up to Week 34 | Blood samples were collected from the participants to evaluate the hematology paramaters. The following hematology parameters were measured: platelet count, red blood cell (RBC) count, hemoglobin, hematocrit, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), white blood cell (WBC) count, neutrophils, lymphocytes, monocytes, eosinophils, and basophils, at the specified timepoints (Week 0, 4, 10, 22, 26 and Week 34). Number of participants with hematology paramaters with PCI values has been reported. |
| Number of Participants With Clinical Chemistry Parameters of PCI | Up to Week 34 | The following clinical chemistry parameters were measured: blood urea nitrogen (BUN), creatinine, calcium, bicarbonate, potassium, sodium, chloride, uric acid, aspartate amino transferase (AST), alanine amino transferase (ALT), alkaline phosphatase, gamma glutamyl transferase (GGT), total and direct bilirubin, total protein, and albumin at the specified timepoints (Week 0, 4, 10, 22, 26 and Week 34). Number of participants with clinical chemistry paramaters with PCI values has been reported. |
| Number of Participants With Clinically Significant Urinalysis Abnormalities by Dipstick Method | Up to 26 weeks | Urine samples were collected early morning from the participants at specified timepoints (Weeks 26 to 52). The following urinalysis parameters were measured: specific gravity, power of hydrogen (pH), glucose, protein, blood and ketones by dipstick; microscopic examination (if blood or protein was abnormal). Number of participants with no clinically significant abnormalities in urinalysis dipstick results were reported. |
| Number of Participants With Pulse Rate Values of PCI | Up to Week 34 | The pulse rate, was measured after completion of the electrocardiogram (ECG) sampling at specified timepoints (Week 0, 4, 10, 22, 26 and Week 34). The participants were asked to be either in semi-recumbent or sitting position. During blood withdraws the vitals were performed prior to blood collection. Number of participants with pulse rate values of PCI has been reported. |
| Number of Participants With Systolic and Diastolic Blood Pressure of PCI | Up to Week 34 | The systolic and diastolic blood pressure, were measured after completion of the ECG sampling at specified timepoints (Week 0, 4, 10, 22, 26 and Week 34). The participants were asked to be either in semi-recumbent or sitting position. During blood withdraws the vitals were performed prior to blood collection. Number of participants with systolic and diastolic blood pressure values of PCI has been reported. |
| Number of Participants With Clinically Significant Findings for 12-lead ECG | Up to Week 34 | A single 12-lead ECG was performed at the specified timepoints (Weeks 0, 26 and 34) during the study where the participant was instructed to be in semi-recumbent position for 10 to 15 minutes before obtaining the ECG. An ECG machine that automatically calculated the heart rate and measures like the PR, QRS, QT, and corrected QT intervals. Number of participants with clinically significant findings in ECG results has been reported. |
| Number of Participant With Positive Results of Anti-albiglutide Antibody Production Over Time | Up to Week 34 | Anti-albiglutide antibodies were planned to be assessed using a validated enzyme-linked immunosorbent assay, which utilized a tiered testing approach. It was to be collected at specified timepoints at Week 0, Week 4, Week 10, Week 26 and Week 34 (follow-up). Confirmed positive samples were to be titrated to obtain the titer of anti-albiglutide antibodies. The number of participants with positive results of anti-albiglutide antibody production was to be reported. However, due to early termination only limited number of key safety data was analyzed. This study 204682 was planned as an extension of the main study, 200952 and was supposed to end well after the main study. However, the 204682 extension study was terminated prior to completion of the main study 200952, which is a double-blind study. To preserve the integrity of the main study 200952, results of anti-albiglutide antibody were not completed after the termination. |
Countries
United States
Participant flow
Recruitment details
A total of 8 participants with Diabetes Mellitus type II, were enrolled in the study from 3 centres in United States of America. The study was conducted from 07 October 2016 to 21 March 2017. The study was terminated prematurely as a reflection of GlaxoSmithKline business considerations.
Pre-assignment details
The participants who completed study 200952 and who were eligible, were included in this open-label extension study 204682. This was an extension study, hence visit 1 of this study was also a last treatment visit of study 200952 (NCT02683746).
Participants by arm
| Arm | Count |
|---|---|
| Albiglutide Liquid The participants in this arm, self-administered, albiglutide liquid drug product 50 mg at a volume of 1 mL as a single dose subcutaneous injection in the abdomen, thigh or upper arm region, once weekly, for 26-weeks. It was administered on the same day each week, anytime during the day without regards to meals. The first dose was self-administered by the participant in the supervision from clinic staff. All further doses of study treatment were self-administered by the participant. | 8 |
| Total | 8 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Study closed/terminated | 8 |
Baseline characteristics
| Characteristic | Albiglutide Liquid |
|---|---|
| Age, Continuous | 53.1 Years STANDARD_DEVIATION 7.86 |
| Race/Ethnicity, Customized American Indian or Alaskan native | 1 Participants |
| Race/Ethnicity, Customized White | 7 Participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 8 |
| other Total, other adverse events | 2 / 8 |
| serious Total, serious adverse events | 0 / 8 |
Outcome results
Primary
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product whether or not it is considered drug related. This would include any side effect, injury, toxicity, sensitivity reaction, abnormal or worsening of a laboratory value, concurrent illness or sudden death. Pre-existing conditions that worsen during a study will be reported as AEs. SAE is any AE that results in death, is life-threatening, requires inpatient hospitalization or extends a current hospital stay, results in an ongoing or significant incapacity or interferes substantially with normal life functions, or causes a congenital anomaly or birth defect, or is associated with liver injury or impaired liver function. Number of participants who reported any AE or SAE during this extension study or who had ongoing AE or SAE from study 200952 have been presented.
Time frame: Up to Week 34
Population: Safety Population comprised of all enrolled participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Albiglutide Liquid | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any SAE | 0 Participants |
| Albiglutide Liquid | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any AE | 2 Participants |
Primary
Number of Participants With Clinical Chemistry Parameters of PCI
The following clinical chemistry parameters were measured: blood urea nitrogen (BUN), creatinine, calcium, bicarbonate, potassium, sodium, chloride, uric acid, aspartate amino transferase (AST), alanine amino transferase (ALT), alkaline phosphatase, gamma glutamyl transferase (GGT), total and direct bilirubin, total protein, and albumin at the specified timepoints (Week 0, 4, 10, 22, 26 and Week 34). Number of participants with clinical chemistry paramaters with PCI values has been reported.
Time frame: Up to Week 34
Population: Safety population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Albiglutide Liquid | Number of Participants With Clinical Chemistry Parameters of PCI | 1 Participants |
Primary
Number of Participants With Clinically Significant Findings for 12-lead ECG
A single 12-lead ECG was performed at the specified timepoints (Weeks 0, 26 and 34) during the study where the participant was instructed to be in semi-recumbent position for 10 to 15 minutes before obtaining the ECG. An ECG machine that automatically calculated the heart rate and measures like the PR, QRS, QT, and corrected QT intervals. Number of participants with clinically significant findings in ECG results has been reported.
Time frame: Up to Week 34
Population: Safety population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Albiglutide Liquid | Number of Participants With Clinically Significant Findings for 12-lead ECG | 0 Participants |
Primary
Number of Participants With Clinically Significant Urinalysis Abnormalities by Dipstick Method
Urine samples were collected early morning from the participants at specified timepoints (Weeks 26 to 52). The following urinalysis parameters were measured: specific gravity, power of hydrogen (pH), glucose, protein, blood and ketones by dipstick; microscopic examination (if blood or protein was abnormal). Number of participants with no clinically significant abnormalities in urinalysis dipstick results were reported.
Time frame: Up to 26 weeks
Population: Safety Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Albiglutide Liquid | Number of Participants With Clinically Significant Urinalysis Abnormalities by Dipstick Method | 0 Participants |
Primary
Number of Participants With Hematology Values of Potential Clinical Importance (PCI)
Blood samples were collected from the participants to evaluate the hematology paramaters. The following hematology parameters were measured: platelet count, red blood cell (RBC) count, hemoglobin, hematocrit, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), white blood cell (WBC) count, neutrophils, lymphocytes, monocytes, eosinophils, and basophils, at the specified timepoints (Week 0, 4, 10, 22, 26 and Week 34). Number of participants with hematology paramaters with PCI values has been reported.
Time frame: Up to Week 34
Population: Safety Population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Albiglutide Liquid | Number of Participants With Hematology Values of Potential Clinical Importance (PCI) | 1 Participants |
Primary
Number of Participants With Physical Examination Abnormalities
A full physical examination was planned to be done, at a minimum, assessment of the skin (including injection site), head, eyes, ears, nose, throat, thyroid, respiratory system cardiovascular system, abdomen (liver and spleen), lymph nodes, central nervous system and extremities was planned. The evaluation of skin (including injection site), respiratory system, cardiovascular system, abdomen (liver, spleen), and central nervous system was planned; however, it was not performed due to early termination of the study.
Time frame: Up to Week 34
Population: Safety Population.
Primary
Number of Participants With Pulse Rate Values of PCI
The pulse rate, was measured after completion of the electrocardiogram (ECG) sampling at specified timepoints (Week 0, 4, 10, 22, 26 and Week 34). The participants were asked to be either in semi-recumbent or sitting position. During blood withdraws the vitals were performed prior to blood collection. Number of participants with pulse rate values of PCI has been reported.
Time frame: Up to Week 34
Population: Safety population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Albiglutide Liquid | Number of Participants With Pulse Rate Values of PCI | 0 Participants |
Primary
Number of Participants With Systolic and Diastolic Blood Pressure of PCI
The systolic and diastolic blood pressure, were measured after completion of the ECG sampling at specified timepoints (Week 0, 4, 10, 22, 26 and Week 34). The participants were asked to be either in semi-recumbent or sitting position. During blood withdraws the vitals were performed prior to blood collection. Number of participants with systolic and diastolic blood pressure values of PCI has been reported.
Time frame: Up to Week 34
Population: Safety population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Albiglutide Liquid | Number of Participants With Systolic and Diastolic Blood Pressure of PCI | 0 Participants |
Primary
Number of Participant With Positive Results of Anti-albiglutide Antibody Production Over Time
Anti-albiglutide antibodies were planned to be assessed using a validated enzyme-linked immunosorbent assay, which utilized a tiered testing approach. It was to be collected at specified timepoints at Week 0, Week 4, Week 10, Week 26 and Week 34 (follow-up). Confirmed positive samples were to be titrated to obtain the titer of anti-albiglutide antibodies. The number of participants with positive results of anti-albiglutide antibody production was to be reported. However, due to early termination only limited number of key safety data was analyzed. This study 204682 was planned as an extension of the main study, 200952 and was supposed to end well after the main study. However, the 204682 extension study was terminated prior to completion of the main study 200952, which is a double-blind study. To preserve the integrity of the main study 200952, results of anti-albiglutide antibody were not completed after the termination.
Time frame: Up to Week 34
Population: Safety population.