Trial Outcomes & Findings for Safety of Exenatide Once Weekly in Patients With Type 2 Diabetes Mellitus Treated With Thiazolidinedione Alone or Thiazolidinedione in Combination With Metformin (NCT NCT00753896)

Results Overview

Percentage of patients experiencing treatment-emergent adverse events over 52 weeks

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

134 participants

Primary outcome timeframe

Baseline to Week 52

Results posted on

2015-04-21

Participant Flow

Participant milestones

Participant milestones
Measure	Exenatide Once Weekly Subcutaneous injection, 2.0mcg, once weekly.
Overall Study STARTED	134
Overall Study COMPLETED	118
Overall Study NOT COMPLETED	16

Reasons for withdrawal

Reasons for withdrawal
Measure	Exenatide Once Weekly Subcutaneous injection, 2.0mcg, once weekly.
Overall Study Adverse Event	4
Overall Study Death	1
Overall Study Lost to Follow-up	2
Overall Study Protocol Violation	1
Overall Study Withdrawal by Subject	4
Overall Study Entry Criteria Not Met	4

Baseline Characteristics

Safety of Exenatide Once Weekly in Patients With Type 2 Diabetes Mellitus Treated With Thiazolidinedione Alone or Thiazolidinedione in Combination With Metformin

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Exenatide Once Weekly n=134 Participants Subcutaneous injection, 2.0mcg, once weekly.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	114 Participants n=5 Participants
Age, Categorical >=65 years	20 Participants n=5 Participants
Age, Continuous	55.0 years STANDARD_DEVIATION 9.74 • n=5 Participants
Sex: Female, Male Female	60 Participants n=5 Participants
Sex: Female, Male Male	74 Participants n=5 Participants
Glycosylated hemoglobin (HbA1c)	7.2 percentage of total hemoglobin STANDARD_DEVIATION 0.95 • n=5 Participants
Weight	98.1 kg STANDARD_DEVIATION 18.71 • n=5 Participants
Background Oral Antidiabetic Agent Metformin + Thiazolidinedione (TZD)	118 participants n=5 Participants
Background Oral Antidiabetic Agent TZD	16 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline to Week 52

Population: All enrolled patients who had taken at least one dose of study drug. Sample size based on FDA recommendation for safety exposure: a minimum of 100 patients completing at least 52 weeks of treatment is sought to assess long-term safety associated with exposure to exenatide once weekly.

Percentage of patients experiencing treatment-emergent adverse events over 52 weeks

Outcome measures

Outcome measures
Measure	Exenatide Once Weekly n=134 Participants Subcutaneous injection, 2.0mcg, once weekly.
Percentage of Patients Experiencing Adverse Events	73.1 percentage of patients

PRIMARY outcome

Timeframe: Baseline to Week 52

Population: All enrolled patients who had taken at least one dose of study drug. Sample size based on FDA recommendation for safety exposure: a minimum of 100 patients completing at least 52 weeks of treatment is sought to assess long-term safety associated with exposure to exenatide once weekly.

Major hypoglycemia: any episode with symptoms consistent with hypoglycemia that resulted in loss of consciousness or seizure with prompt recovery in response to administration of glucagon or glucose OR documented hypoglycemia (blood glucose \<3.0 mmol/L \[54 mg/dL\]) and required the assistance of another person. Minor hypoglycemia: any sign or symptom associated with hypoglycemia that is either self-treated by the patient or resolves on its own AND has a concurrent finger stick blood glucose \<3.0 mmol/L (54 mg/dL) and not classified as major hypoglycemia. Mean event rate = total number of events for all subjects in a treatment regimen / the total number of subject years of exposure for all subjects in that treatment. Standard error = square root of (total number of events / (subject years of exposure)\*\*2).

Outcome measures

Outcome measures
Measure	Exenatide Once Weekly n=134 Participants Subcutaneous injection, 2.0mcg, once weekly.
Assessment of Event Rate of Treatment-Emergent Hypoglycemic Events Major Hypoglycemia	0.00 events per subject-year Standard Error 0.000
Assessment of Event Rate of Treatment-Emergent Hypoglycemic Events Minor Hypoglycemia	0.02 events per subject-year Standard Error 0.014

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: All enrolled patients who had taken at least one dose of study drug. Last observation carried forward. Only patients with non-missing baseline value and at least one non-missing post-baseline value of the response variable were included in analysis.

Change in HbA1c from baseline to endpoint

Outcome measures

Outcome measures
Measure	Exenatide Once Weekly n=132 Participants Subcutaneous injection, 2.0mcg, once weekly.
Change in HbA1c From Baseline to Week 52	-0.78 percentage of total hemoglobin Standard Error 0.07

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: All enrolled patients who had taken at least one dose of study drug and whose baseline HbA1c was \> 7% . Last observation carried forward. Only patients with non-missing baseline value and at least one non-missing post-baseline value of the response variable were included in analysis.

Percentage of patients achieving HbA1c \<=7% at endpoint (for patients with HbA1c \>7% at baseline)

Outcome measures

Outcome measures
Measure	Exenatide Once Weekly n=64 Participants Subcutaneous injection, 2.0mcg, once weekly.
Percentage of Patients Achieving HbA1c <=7% at Week 52	68.8 percentage of patients

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: All enrolled patients who had taken at least one dose of study drug and whose baseline HbA1c was \> 6.5%. Last observation carried forward. Only patients with non-missing baseline value and at least one non-missing post-baseline value of the response variable were included in analysis.

Percentage of patients achieving HbA1c \<=6.5% at endpoint (for patients with HbA1c \>6.5% at baseline)

Outcome measures

Outcome measures
Measure	Exenatide Once Weekly n=96 Participants Subcutaneous injection, 2.0mcg, once weekly.
Percentage of Patients Achieving HbA1c <=6.5% at Week 52	54.2 percentage of patients

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: All enrolled patients who had taken at least one dose of study drug. Last observation carried forward. Only patients with non-missing baseline value and at least one non-missing post-baseline value of the response variable were included in analysis.

Change in fasting serum glucose from baseline to endpoint

Outcome measures

Outcome measures
Measure	Exenatide Once Weekly n=126 Participants Subcutaneous injection, 2.0mcg, once weekly.
Change in Fasting Serum Glucose From Baseline to Week 52	-1.59 mmol/L Standard Error 0.21

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: All enrolled patients who had taken at least one dose of study drug. Last observation carried forward. Only patients with non-missing baseline value and at least one non-missing post-baseline value of the response variable were included in analysis.

Change in body weight from baseline to endpoint

Outcome measures

Outcome measures
Measure	Exenatide Once Weekly n=134 Participants Subcutaneous injection, 2.0mcg, once weekly.
Change in Body Weight From Baseline to Week 52	-1.50 kg Standard Error 0.45

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: All enrolled patients who had taken at least one dose of study drug. Last observation carried forward. Only patients with non-missing baseline value and at least one non-missing post-baseline value of the response variable were included in analysis.

Change in Total Cholesterol from baseline to endpoint

Outcome measures

Outcome measures
Measure	Exenatide Once Weekly n=126 Participants Subcutaneous injection, 2.0mcg, once weekly.
Change in Total Cholesterol From Baseline to Week 52	-0.18 mmol/L Standard Error 0.08

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: All enrolled patients who had taken at least one dose of study drug. Last observation carried forward. Only patients with non-missing baseline value and at least one non-missing post-baseline value of the response variable were included in analysis.

Change in HDL from baseline to endpoint

Outcome measures

Outcome measures
Measure	Exenatide Once Weekly n=126 Participants Subcutaneous injection, 2.0mcg, once weekly.
Change in High-density Lipoprotein (HDL) From Baseline to Week 52	0.04 mmol/L Standard Error 0.02

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: All enrolled patients who had taken at least one dose of study drug. Last observation carried forward. Only patients with non-missing baseline value and at least one non-missing post-baseline value of the response variable were included in analysis.

Change in Triglycerides from baseline to endpoint

Outcome measures

Outcome measures
Measure	Exenatide Once Weekly n=126 Participants Subcutaneous injection, 2.0mcg, once weekly.
Change in Triglycerides From Baseline to Week 52	-0.19 mmol/L Standard Error 0.07

SECONDARY outcome

Timeframe: Baseline, Week 52

Population: All enrolled patients who had taken at least one dose of study drug. Last observation carried forward. Only patients with non-missing baseline value and at least one non-missing post-baseline value of the response variable were included in analysis.

Change in Systolic and Diastolic Blood Pressure from baseline to endpoint

Outcome measures

Outcome measures
Measure	Exenatide Once Weekly n=134 Participants Subcutaneous injection, 2.0mcg, once weekly.
Change in Blood Pressure From Baseline to Week 52 Systolic Blood Pressure	-1.69 mmHg Standard Error 1.12
Change in Blood Pressure From Baseline to Week 52 Diastolic Blood Pressure	-0.19 mmHg Standard Error 0.70

Adverse Events

Exenatide Once Weekly

Serious events: 9 serious events

Other events: 67 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Exenatide Once Weekly n=134 participants at risk Subcutaneous injection, 2.0mcg, once weekly.
Cardiac disorders Angina pectoris	0.75% 1/134
Infections and infestations Anorectal cellulitis	0.75% 1/134
Vascular disorders Aortic aneurysm	0.75% 1/134
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Brain neoplasm	0.75% 1/134
Renal and urinary disorders Calculus urinary	0.75% 1/134
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer stage II	0.75% 1/134
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.75% 1/134
Injury, poisoning and procedural complications Patella fracture	0.75% 1/134
Injury, poisoning and procedural complications Post procedural haemorrhage	0.75% 1/134
Nervous system disorders Presyncope	0.75% 1/134

Other adverse events

Other adverse events
Measure	Exenatide Once Weekly n=134 participants at risk Subcutaneous injection, 2.0mcg, once weekly.
Gastrointestinal disorders Nausea	16.4% 22/134
General disorders Injection site nodule	11.2% 15/134
Infections and infestations Nasopharyngitis	9.7% 13/134
Metabolism and nutrition disorders Decreased appetite	9.0% 12/134
Nervous system disorders Headache	9.0% 12/134
Infections and infestations Upper respiratory tract infection	7.5% 10/134
Gastrointestinal disorders Vomiting	7.5% 10/134
Gastrointestinal disorders Constipation	6.0% 8/134
Gastrointestinal disorders Dyspepsia	6.0% 8/134
Musculoskeletal and connective tissue disorders Arthralgia	5.2% 7/134
Gastrointestinal disorders Diarrhoea	5.2% 7/134
Infections and infestations Influenza	5.2% 7/134

Additional Information

Peter Ohman, Medical Science Director

AstraZeneca

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60