Extension to Study 200952 to Evaluate the Long-term Safety, Tolerability and Pharmacodynamics of Albiglutide Liquid Drug Product in Type 2 Diabetes Mellitus Subjects

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT02750930
• Collaborator: (none)
• Enrollment: 8
• Locations: 27
• Arm: 1
• Actual Duration (Months): 5.4
• Patients Per Site: 0.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus, Type 2	Drug: Albiglutide; Device: Auto-injector	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 8 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-label Extension to Study 200952 to Evaluate the Long-term Safety, Tolerability and Pharmacodynamics of Albiglutide Liquid Drug Product in Subjects With Type 2 Diabetes Mellitus
• Actual Study Start Date: Oct 7, 2016
• Actual Primary Completion Date: Mar 21, 2017
• Actual Study Completion Date: Mar 21, 2017

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Albiglutide arm Subjects will receive 50 milligrams (mg) albiglutide liquid drug product once weekly via auto-injector for 26 weeks.

Drug: Albiglutide; 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).; Device: Auto-injector; The auto-injector delivers the albiglutide liquid drug product in an injection volume of 1.0 mL for the 50 mg dose.

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

6. 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.

7. 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.

8. 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.

9. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts 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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Phoenix	Arizona	United States	85018
2	GSK Investigational Site	Fresno	California	United States	93720
3	GSK Investigational Site	Lomita	California	United States	90717
4	GSK Investigational Site	Sacramento	California	United States	95831
5	GSK Investigational Site	Spring Valley	California	United States	91978
6	GSK Investigational Site	Tustin	California	United States	92780
7	GSK Investigational Site	West Hills	California	United States	91307
8	GSK Investigational Site	Littleton	Colorado	United States	80128
9	GSK Investigational Site	Bradenton	Florida	United States	34201
10	GSK Investigational Site	Clearwater	Florida	United States	33765
11	GSK Investigational Site	Hallandale Beach	Florida	United States	33009
12	GSK Investigational Site	Miami	Florida	United States	33156
13	GSK Investigational Site	Miami	Florida	United States	33176
14	GSK Investigational Site	Orlando	Florida	United States	32825
15	GSK Investigational Site	Conyers	Georgia	United States	30094
16	GSK Investigational Site	Evansville	Indiana	United States	47714
17	GSK Investigational Site	Kalamazoo	Michigan	United States	49009
18	GSK Investigational Site	Chesterfield	Missouri	United States	63017
19	GSK Investigational Site	Columbia	North Carolina	United States	28150
20	GSK Investigational Site	Columbus	Ohio	United States	43201
21	GSK Investigational Site	Columbia	South Carolina	United States	29204
22	GSK Investigational Site	Arlington	Texas	United States	76012
23	GSK Investigational Site	Dallas	Texas	United States	75230
24	GSK Investigational Site	Houston	Texas	United States	77036
25	GSK Investigational Site	Houston	Texas	United States	77058
26	GSK Investigational Site	Schertz	Texas	United States	782154
27	GSK Investigational Site	Shavano Prk	Texas	United States	78231

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

• Study Protocol - Oct 28, 2015
• Statistical Analysis Plan - Mar 6, 2017

More Information

Publications

None provided.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT02750930
• Other Study ID Numbers: 204682
• First Posted: Apr 26, 2016
• Last Update Posted: Jul 12, 2019
• Last Verified: Jul 1, 2019

• Keywords provided by GlaxoSmithKline: Extension; Long-term Safety; Pharmacodynamics; Albiglutide; Type 2 Diabetes Mellitus
• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; rGLP-1 protein

Study Results

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 Detail	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).

Arm/Group Title	Albiglutide Liquid
Arm/Group Description	The participants in this arm, self-administered, albiglutide liquid drug product 50 milligram (mg) at a volume of 1 millilitre (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.
Period Title: Overall Study
STARTED	8
COMPLETED	0
NOT COMPLETED	8

Baseline Characteristics

Arm/Group Title	Albiglutide Liquid
Arm/Group Description	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.
Overall Participants	8
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	53.1 (7.86)
Sex: Female, Male (Count of Participants)
Female	3 37.5%
Male	5 62.5%
Race/Ethnicity, Customized (Number) [Number]
White	7 87.5%
American Indian or Alaskan native	1 12.5%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description	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

Outcome Measure Data

Analysis Population Description

Safety Population comprised of all enrolled participants who received at least 1 dose of study medication.

Arm/Group Title	Albiglutide Liquid
Arm/Group Description	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.
Measure Participants	8
Any SAE	0 0%
Any AE	2 25%

2. Primary Outcome

Title	Number of Participants With Physical Examination Abnormalities
Description	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

Outcome Measure Data

Analysis Population Description

Safety Population.

Arm/Group Title	Albiglutide Liquid
Arm/Group Description	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.
Measure Participants	0

3. Primary Outcome

Title	Number of Participants With Hematology Values of Potential Clinical Importance (PCI)
Description	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

Outcome Measure Data

Analysis Population Description

Safety Population.

Arm/Group Title	Albiglutide Liquid
Arm/Group Description	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.
Measure Participants	8
Number [Participants]	1 12.5%

4. Primary Outcome

Title	Number of Participants With Clinical Chemistry Parameters of PCI
Description	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

Outcome Measure Data

Analysis Population Description

Safety population

Arm/Group Title	Albiglutide Liquid
Arm/Group Description	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.
Measure Participants	8
Number [Participants]	1 12.5%

5. Primary Outcome

Title	Number of Participants With Clinically Significant Urinalysis Abnormalities by Dipstick Method
Description	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

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Albiglutide Liquid
Arm/Group Description	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.
Measure Participants	8
Number [Participants]	0 0%

6. Primary Outcome

Title	Number of Participants With Pulse Rate Values of PCI
Description	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

Outcome Measure Data

Analysis Population Description

Safety population

Arm/Group Title	Albiglutide Liquid
Arm/Group Description	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.
Measure Participants	8
Number [Participants]	0 0%

7. Primary Outcome

Title	Number of Participants With Systolic and Diastolic Blood Pressure of PCI
Description	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

Outcome Measure Data

Analysis Population Description

Safety population

Arm/Group Title	Albiglutide Liquid
Arm/Group Description	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.
Measure Participants	8
Number [Participants]	0 0%

8. Primary Outcome

Title	Number of Participants With Clinically Significant Findings for 12-lead ECG
Description	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

Outcome Measure Data

Analysis Population Description

Safety population.

Arm/Group Title	Albiglutide Liquid
Arm/Group Description	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.
Measure Participants	8
Number [Participants]	0 0%

9. Primary Outcome

Title	Number of Participant With Positive Results of Anti-albiglutide Antibody Production Over Time
Description	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

Outcome Measure Data

Analysis Population Description

Safety population.

Arm/Group Title	Albiglutide Liquid
Arm/Group Description	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.
Measure Participants	0

Adverse Events

Time Frame	From start of study treatment (Week 1 of this extension study) to upto follow-up (Up to Week 34)
Adverse Event Reporting Description	Safety population was used. On treatment AEs and SAEs were reported.
Arm/Group Title	Albiglutide Liquid
Arm/Group Description	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.
All Cause Mortality
	Albiglutide Liquid
	Affected / at Risk (%)	# Events
Total	0/8 (0%)
Serious Adverse Events
	Albiglutide Liquid
	Affected / at Risk (%)	# Events
Total	0/8 (0%)
Other (Not Including Serious) Adverse Events
	Albiglutide Liquid
	Affected / at Risk (%)	# Events
Total	2/8 (25%)
Infections and infestations
Tooth abscess	1/8 (12.5%)
Metabolism and nutrition disorders
Vitamin D deficiency	1/8 (12.5%)
Respiratory, thoracic and mediastinal disorders
Sleep apnoea syndrome	1/8 (12.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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