Trial Outcomes & Findings for A Comparison of Adding Exenatide With Switching to Exenatide in Patients With Type 2 Diabetes Experiencing Inadequate Glycemic Control With Sitagliptin Plus Metformin (NCT NCT00870194)

NCT ID: NCT00870194

Last Updated: 2015-04-09

Results Overview

Change in HbA1c from baseline to endpoint (Week 20); difference of base percent values \[X% - Y%\]

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 255 participants
• Primary outcome timeframe: Baseline to 20 Weeks
• Results posted on: 2015-04-09

Participant Flow

Participant milestones

Measure	Exenatide + Placebo Exenatide-subcutaneous injection, 5mcg (4 weeks) followed by 10mcg (16 weeks), twice a day; Placebo-tablet orally once a day.	Exenatide + Sitagliptin Exenatide-subcutaneous injection, 5mcg (4 weeks) followed by 10mcg (16 weeks), twice a day; Sitagliptin-100mg tablet orally once a day.
Overall Study STARTED	127	128
Overall Study Per Protocol Set	97	111
Overall Study COMPLETED	101	114
Overall Study NOT COMPLETED	26	14

Reasons for withdrawal

Measure	Exenatide + Placebo Exenatide-subcutaneous injection, 5mcg (4 weeks) followed by 10mcg (16 weeks), twice a day; Placebo-tablet orally once a day.	Exenatide + Sitagliptin Exenatide-subcutaneous injection, 5mcg (4 weeks) followed by 10mcg (16 weeks), twice a day; Sitagliptin-100mg tablet orally once a day.
Overall Study Adverse Event	10	5
Overall Study Lack of Efficacy	0	1
Overall Study Lost to Follow-up	2	0
Overall Study Physician Decision	3	1
Overall Study Protocol Violation	3	3
Overall Study Entry Criteria Not Met	1	2
Overall Study Subject Decision	7	2

Baseline Characteristics

A Comparison of Adding Exenatide With Switching to Exenatide in Patients With Type 2 Diabetes Experiencing Inadequate Glycemic Control With Sitagliptin Plus Metformin

Baseline characteristics by cohort

Measure	Exenatide + Placebo n=97 Participants Exenatide-subcutaneous injection, 5mcg (4 weeks) followed by 10mcg (16 weeks), twice a day; Placebo-tablet orally once a day.	Exenatide + Sitagliptin n=111 Participants Exenatide-subcutaneous injection, 5mcg (4 weeks) followed by 10mcg (16 weeks), twice a day; Sitagliptin-100mg tablet orally once a day.	Total n=208 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	81 Participants n=5 Participants	97 Participants n=7 Participants	178 Participants n=5 Participants
Age, Categorical >=65 years	16 Participants n=5 Participants	14 Participants n=7 Participants	30 Participants n=5 Participants
Age, Continuous	54.8 years STANDARD_DEVIATION 10.97 • n=5 Participants	54.6 years STANDARD_DEVIATION 9.66 • n=7 Participants	54.7 years STANDARD_DEVIATION 10.27 • n=5 Participants
Sex: Female, Male Female	46 Participants n=5 Participants	58 Participants n=7 Participants	104 Participants n=5 Participants
Sex: Female, Male Male	51 Participants n=5 Participants	53 Participants n=7 Participants	104 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline to 20 Weeks

Population: Per Protocol Set: the set of data generated by the subset of patients who sufficiently complied with the protocol to ensure that these data would be likely to exhibit the effects of treatment, according to the underlying scientific model.

Change in HbA1c from baseline to endpoint (Week 20); difference of base percent values [X% - Y%]

Outcome measures

Measure	Exenatide + Placebo n=97 Participants Exenatide-subcutaneous injection, 5mcg (4 weeks) followed by 10mcg (16 weeks), twice a day; Placebo-tablet orally once a day.	Exenatide + Sitagliptin n=111 Participants Exenatide-subcutaneous injection, 5mcg (4 weeks) followed by 10mcg (16 weeks), twice a day; Sitagliptin-100mg tablet orally once a day.
Change in HbA1c (Percent)	-0.38 Percent HbA1c Standard Error 0.09	-0.68 Percent HbA1c Standard Error 0.08

SECONDARY outcome

Timeframe: Baseline to 20 Weeks

Population: Patients in the Per Protocol Set whose baseline HbA1c was \> 7.0%; Last Observation Carried Forward.Per Protocol Set: the set of data generated by the subset of patients who sufficiently complied with the protocol to ensure that these data would be likely to exhibit the effects of treatment, according to the underlying scientific model.

Percentage of patients whose baseline HbA1c was > 7.0% achieving HbA1c <=7.0% at endpoint (Week 20)

Outcome measures

Measure	Exenatide + Placebo n=88 Participants Exenatide-subcutaneous injection, 5mcg (4 weeks) followed by 10mcg (16 weeks), twice a day; Placebo-tablet orally once a day.	Exenatide + Sitagliptin n=106 Participants Exenatide-subcutaneous injection, 5mcg (4 weeks) followed by 10mcg (16 weeks), twice a day; Sitagliptin-100mg tablet orally once a day.
Percentage of Patients Achieving HbA1c <=7.0%	29.5 Percentage	44.3 Percentage

SECONDARY outcome

Timeframe: Baseline to 20 Weeks

Population: Patients in the Per Protocol Set whose baseline HbA1c was \>= 7.0%; Last Observation Carried Forward. Per Protocol Set: the set of data generated by the subset of patients who sufficiently complied with the protocol to ensure that these data would be likely to exhibit the effects of treatment, according to the underlying scientific model.

Percentage of patients whose baseline HbA1c was >=7.0% achieving HbA1c <7.0% at endpoint (Week 20)

Outcome measures

Measure	Exenatide + Placebo n=94 Participants Exenatide-subcutaneous injection, 5mcg (4 weeks) followed by 10mcg (16 weeks), twice a day; Placebo-tablet orally once a day.	Exenatide + Sitagliptin n=108 Participants Exenatide-subcutaneous injection, 5mcg (4 weeks) followed by 10mcg (16 weeks), twice a day; Sitagliptin-100mg tablet orally once a day.
Percentage of Patients Achieving HbA1c <7.0%	26.6 Percentage	41.7 Percentage

SECONDARY outcome

Timeframe: Baseline to 20 Weeks

Population: Patients in the Per Protocol Set whose baseline HbA1c was \> 6.5%; Last Observation Carried Forward. Per Protocol Set: the set of data generated by the subset of patients who sufficiently complied with the protocol to ensure that these data would be likely to exhibit the effects of treatment, according to the underlying scientific model.

Percentage of patients whose baseline HbA1c was > 6.5% achieving HbA1c <=6.5% at endpoint (Week 20)

Outcome measures

Measure	Exenatide + Placebo n=97 Participants Exenatide-subcutaneous injection, 5mcg (4 weeks) followed by 10mcg (16 weeks), twice a day; Placebo-tablet orally once a day.	Exenatide + Sitagliptin n=111 Participants Exenatide-subcutaneous injection, 5mcg (4 weeks) followed by 10mcg (16 weeks), twice a day; Sitagliptin-100mg tablet orally once a day.
Percentage of Patients Achieving HbA1c <=6.5%	16.5 Percentage	20.7 Percentage

SECONDARY outcome

Timeframe: Baseline to 20 Weeks

Population: Per Protocol Set: the set of data generated by the subset of patients who sufficiently complied with the protocol to ensure that these data would be likely to exhibit the effects of treatment, according to the underlying scientific model.

Change in fasting serum glucose (FSG) from baseline to endpoint (Week 20)

Outcome measures

Measure	Exenatide + Placebo n=93 Participants Exenatide-subcutaneous injection, 5mcg (4 weeks) followed by 10mcg (16 weeks), twice a day; Placebo-tablet orally once a day.	Exenatide + Sitagliptin n=106 Participants Exenatide-subcutaneous injection, 5mcg (4 weeks) followed by 10mcg (16 weeks), twice a day; Sitagliptin-100mg tablet orally once a day.
Change in FSG (mmol/L)	0.06 mmol/L Standard Error 0.23	-0.55 mmol/L Standard Error 0.21

SECONDARY outcome

Timeframe: Baseline to 20 Weeks

Population: Per Protocol Set: the set of data generated by the subset of patients who sufficiently complied with the protocol to ensure that these data would be likely to exhibit the effects of treatment, according to the underlying scientific model.

Change in body weight from baseline to endpoint (Week 20)

Outcome measures

Measure	Exenatide + Placebo n=97 Participants Exenatide-subcutaneous injection, 5mcg (4 weeks) followed by 10mcg (16 weeks), twice a day; Placebo-tablet orally once a day.	Exenatide + Sitagliptin n=111 Participants Exenatide-subcutaneous injection, 5mcg (4 weeks) followed by 10mcg (16 weeks), twice a day; Sitagliptin-100mg tablet orally once a day.
Change in Body Weight (kg)	-2.58 kg Standard Error 0.25	-2.20 kg Standard Error 0.24

SECONDARY outcome

Timeframe: Baseline to 20 Weeks

Population: Per Protocol Set: the set of data generated by the subset of patients who sufficiently complied with the protocol to ensure that these data would be likely to exhibit the effects of treatment, according to the underlying scientific model.

Change in waist circumference from baseline to endpoint (Week 20)

Outcome measures

Measure	Exenatide + Placebo n=96 Participants Exenatide-subcutaneous injection, 5mcg (4 weeks) followed by 10mcg (16 weeks), twice a day; Placebo-tablet orally once a day.	Exenatide + Sitagliptin n=111 Participants Exenatide-subcutaneous injection, 5mcg (4 weeks) followed by 10mcg (16 weeks), twice a day; Sitagliptin-100mg tablet orally once a day.
Change in Waist Circumference (cm)	-3.25 cm Standard Error 0.40	-2.36 cm Standard Error 0.37

SECONDARY outcome

Timeframe: Baseline to 20 Weeks

Population: Per Protocol Set: the set of data generated by the subset of patients who sufficiently complied with the protocol to ensure that these data would be likely to exhibit the effects of treatment, according to the underlying scientific model.

Change in waist-to-hip ratio from baseline to endpoint (Week20)

Outcome measures

Measure	Exenatide + Placebo n=96 Participants Exenatide-subcutaneous injection, 5mcg (4 weeks) followed by 10mcg (16 weeks), twice a day; Placebo-tablet orally once a day.	Exenatide + Sitagliptin n=111 Participants Exenatide-subcutaneous injection, 5mcg (4 weeks) followed by 10mcg (16 weeks), twice a day; Sitagliptin-100mg tablet orally once a day.
Waist-to-Hip Ratio	-0.01 Ratio Standard Error 0.00	-0.00 Ratio Standard Error 0.00

SECONDARY outcome

Timeframe: Baseline to 20 Weeks

Population: Per Protocol Set: the set of data generated by the subset of patients who sufficiently complied with the protocol to ensure that these data would be likely to exhibit the effects of treatment, according to the underlying scientific model.

7 point Self Monitored Blood Glucose Profiles - daily mean value (Week 20)

Outcome measures

Measure	Exenatide + Placebo n=50 Participants Exenatide-subcutaneous injection, 5mcg (4 weeks) followed by 10mcg (16 weeks), twice a day; Placebo-tablet orally once a day.	Exenatide + Sitagliptin n=71 Participants Exenatide-subcutaneous injection, 5mcg (4 weeks) followed by 10mcg (16 weeks), twice a day; Sitagliptin-100mg tablet orally once a day.
SMBG (mmol/L)	8.57 mmol/L Standard Error 0.26	8.16 mmol/L Standard Error 0.22

SECONDARY outcome

Timeframe: Baseline to 20 Weeks

Population: Per Protocol Set: the set of data generated by the subset of patients who sufficiently complied with the protocol to ensure that these data would be likely to exhibit the effects of treatment, according to the underlying scientific model.

Change in triglycerides from baseline to endpoint (Week 20)

Outcome measures

Measure	Exenatide + Placebo n=96 Participants Exenatide-subcutaneous injection, 5mcg (4 weeks) followed by 10mcg (16 weeks), twice a day; Placebo-tablet orally once a day.	Exenatide + Sitagliptin n=109 Participants Exenatide-subcutaneous injection, 5mcg (4 weeks) followed by 10mcg (16 weeks), twice a day; Sitagliptin-100mg tablet orally once a day.
Change in Triglycerides (mmol/L)	0.17 mmol/L Standard Error 0.10	-0.07 mmol/L Standard Error 0.09

SECONDARY outcome

Timeframe: Baseline to 20 Weeks

Population: Per Protocol Set: the set of data generated by the subset of patients who sufficiently complied with the protocol to ensure that these data would be likely to exhibit the effects of treatment, according to the underlying scientific model.

Change in high-density lipoprotein (HDL) cholesterol from baseline to endpoint (Week 20)

Outcome measures

Measure	Exenatide + Placebo n=96 Participants Exenatide-subcutaneous injection, 5mcg (4 weeks) followed by 10mcg (16 weeks), twice a day; Placebo-tablet orally once a day.	Exenatide + Sitagliptin n=109 Participants Exenatide-subcutaneous injection, 5mcg (4 weeks) followed by 10mcg (16 weeks), twice a day; Sitagliptin-100mg tablet orally once a day.
Change in HDL (mmol/L)	-0.03 mmol/L Standard Error 0.02	-0.01 mmol/L Standard Error 0.02

SECONDARY outcome

Timeframe: Baseline to 20 Weeks

Population: Per Protocol Set: the set of data generated by the subset of patients who sufficiently complied with the protocol to ensure that these data would be likely to exhibit the effects of treatment, according to the underlying scientific model.

Change in low-density lipoprotein (LDL) cholesterol from baseline to endpoint (Week 20)

Outcome measures

Measure	Exenatide + Placebo n=90 Participants Exenatide-subcutaneous injection, 5mcg (4 weeks) followed by 10mcg (16 weeks), twice a day; Placebo-tablet orally once a day.	Exenatide + Sitagliptin n=98 Participants Exenatide-subcutaneous injection, 5mcg (4 weeks) followed by 10mcg (16 weeks), twice a day; Sitagliptin-100mg tablet orally once a day.
Change in LDL (mmol/L)	0.06 mmol/L Standard Error 0.06	0.10 mmol/L Standard Error 0.06

SECONDARY outcome

Timeframe: Baseline to 20 Weeks

Population: Per Protocol Set: the set of data generated by the subset of patients who sufficiently complied with the protocol to ensure that these data would be likely to exhibit the effects of treatment, according to the underlying scientific model.

Change in total cholesterol from baseline to endpoint (Week 20)

Outcome measures

Measure	Exenatide + Placebo n=96 Participants Exenatide-subcutaneous injection, 5mcg (4 weeks) followed by 10mcg (16 weeks), twice a day; Placebo-tablet orally once a day.	Exenatide + Sitagliptin n=109 Participants Exenatide-subcutaneous injection, 5mcg (4 weeks) followed by 10mcg (16 weeks), twice a day; Sitagliptin-100mg tablet orally once a day.
Change in Total Cholesterol (mmol/L)	0.09 mmol/L Standard Error 0.07	0.08 mmol/L Standard Error 0.07

SECONDARY outcome

Timeframe: Baseline to 20 Weeks

Population: As Treated Patients; Hypoglycemia defined as: patient experiencing a sign or symptom associated with hypoglycemia that is either self-treated or resolves on its own; not confirmed with blood glucose values.

Incidence of hypoglycemic episodes experienced overall during the study

Outcome measures

Measure	Exenatide + Placebo n=127 Participants Exenatide-subcutaneous injection, 5mcg (4 weeks) followed by 10mcg (16 weeks), twice a day; Placebo-tablet orally once a day.	Exenatide + Sitagliptin n=128 Participants Exenatide-subcutaneous injection, 5mcg (4 weeks) followed by 10mcg (16 weeks), twice a day; Sitagliptin-100mg tablet orally once a day.
Incidence of Hypoglycemia (Overall)	5 Participants	10 Participants

SECONDARY outcome

Timeframe: Baseline to 20 Weeks

Population: As Treated Patients; Severe hypo:symptoms consistent with hypoglycemia resulting in loss of consciousness or seizure with prompt recovery in response to administration of glucagon or glucose;or documented hypoglycemia (BG\< 3.0 mmol/L \[54/mg/dL\]) requiring the assistance of another person because of severe impairment in consciousness or behavior

Incidence of severe hypoglycemia experienced overall during the study

Outcome measures

Measure	Exenatide + Placebo n=127 Participants Exenatide-subcutaneous injection, 5mcg (4 weeks) followed by 10mcg (16 weeks), twice a day; Placebo-tablet orally once a day.	Exenatide + Sitagliptin n=128 Participants Exenatide-subcutaneous injection, 5mcg (4 weeks) followed by 10mcg (16 weeks), twice a day; Sitagliptin-100mg tablet orally once a day.
Incidence of Severe Hypoglycemia(Overall)	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline to 20 Weeks

Population: As Treated Patients

Incidence of nocturnal hypoglycemia experienced overall during the study

Outcome measures

Measure	Exenatide + Placebo n=127 Participants Exenatide-subcutaneous injection, 5mcg (4 weeks) followed by 10mcg (16 weeks), twice a day; Placebo-tablet orally once a day.	Exenatide + Sitagliptin n=128 Participants Exenatide-subcutaneous injection, 5mcg (4 weeks) followed by 10mcg (16 weeks), twice a day; Sitagliptin-100mg tablet orally once a day.
Incidence of Nocturnal Hypoglycemia (Overall)	0 Participants	3 Participants

SECONDARY outcome

Timeframe: Baseline to 20 Weeks

Population: As Treated Patients; Hypoglycemia defined as: patient experiencing a sign or symptom associated with hypoglycemia that is either self-treated or resolves on its own; has a concurrent fingerstick blood glucose \<3.0 mmol/L (54 mg/dL).

Incidence of confirmed hypoglycemia experienced overall during the study

Outcome measures

Measure	Exenatide + Placebo n=127 Participants Exenatide-subcutaneous injection, 5mcg (4 weeks) followed by 10mcg (16 weeks), twice a day; Placebo-tablet orally once a day.	Exenatide + Sitagliptin n=128 Participants Exenatide-subcutaneous injection, 5mcg (4 weeks) followed by 10mcg (16 weeks), twice a day; Sitagliptin-100mg tablet orally once a day.
Incidence of Confirmed Hypoglycemia(Overall)	1 Participants	2 Participants

Adverse Events

Exenatide + Placebo

Serious events: 4 serious events

Other events: 36 other events

Deaths: 0 deaths

Exenatide + Sitagliptin

Serious events: 6 serious events

Other events: 28 other events

Deaths: 0 deaths

Serious adverse events

Measure	Exenatide + Placebo n=127 participants at risk Exenatide-subcutaneous injection, 5mcg (4 weeks) followed by 10mcg (16 weeks), twice a day; Placebo-tablet orally once a day.	Exenatide + Sitagliptin n=128 participants at risk Exenatide-subcutaneous injection, 5mcg (4 weeks) followed by 10mcg (16 weeks), twice a day; Sitagliptin-100mg tablet orally once a day.
Musculoskeletal and connective tissue disorders Arthralgia	0.79% 1/127	0.00% 0/128
Musculoskeletal and connective tissue disorders Back pain	0.79% 1/127	0.00% 0/128
Metabolism and nutrition disorders Hypoglycaemia	0.79% 1/127	0.78% 1/128
Gastrointestinal disorders Lumbar hernia	0.79% 1/127	0.00% 0/128
Musculoskeletal and connective tissue disorders Lumbar spinal stenosis	0.79% 1/127	0.00% 0/128
Skin and subcutaneous tissue disorders Urticaria	0.79% 1/127	0.00% 0/128
Cardiac disorders Angina unstable	0.00% 0/127	0.78% 1/128
Respiratory, thoracic and mediastinal disorders Asthma	0.00% 0/127	0.78% 1/128
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder cancer	0.00% 0/127	0.78% 1/128
Cardiac disorders Coronary artery disease	0.00% 0/127	0.78% 1/128
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/127	0.78% 1/128
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pancreatic carcinoma	0.00% 0/127	0.78% 1/128
Nervous system disorders Presyncope	0.00% 0/127	0.78% 1/128
Musculoskeletal and connective tissue disorders Rotator cuff syndrome	0.00% 0/127	0.78% 1/128
Infections and infestations Urosepsis	0.00% 0/127	0.78% 1/128

Other adverse events

Measure	Exenatide + Placebo n=127 participants at risk Exenatide-subcutaneous injection, 5mcg (4 weeks) followed by 10mcg (16 weeks), twice a day; Placebo-tablet orally once a day.	Exenatide + Sitagliptin n=128 participants at risk Exenatide-subcutaneous injection, 5mcg (4 weeks) followed by 10mcg (16 weeks), twice a day; Sitagliptin-100mg tablet orally once a day.
Gastrointestinal disorders Nausea	15.7% 20/127	10.2% 13/128
Gastrointestinal disorders Vomiting	10.2% 13/127	3.1% 4/128
Infections and infestations Nasopharyngitis	8.7% 11/127	7.8% 10/128
Nervous system disorders Headache	4.7% 6/127	7.0% 9/128

Additional Information

Peter Ohman, Medical Science Director

AstraZeneca

Email: ClinicalTrialTransparency@astrazeneca.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: GT60