Trial Outcomes & Findings for A Study to Examine the Efficacy, Safety and Tolerability, and Pharmacokinetics of Exenatide Once Monthly Suspension (NCT NCT01104701)

Last Updated: 2015-08-20

Results Overview

HbA1c was measured as a percent of total hemoglobin at screening, Baseline, and during treatment on Weeks 4, 8, 12, 16, and 20. Baseline was Day 1, or last measurement prior to first dose of study drug. The Evaluable population was defined as participants who completed study procedures in compliance with the protocol and had adequate exposure to the study drug.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

121 participants

Primary outcome timeframe

Baseline (Day 1) to 20 weeks

Results posted on

2015-08-20

Participant Flow

Study initiated 22-May-2010; completed 27-Dec-2010. Once weekly arm: first dose of exenatide administered at study-site on Day 1; self-administered on a weekly basis over subsequent 20 weeks. Once monthly arm: first dose of exenatide administered at study-site on Day 1;self-administered on monthly basis by participants over next 20 weeks.

Participant milestones

Participant milestones
Measure	2 mg Exenatide Weekly 2 milligrams (mg) exenatide microspheres in aqueous diluent were administered once a week as a subcutaneous injection (SC) over 20 weeks.	5 mg Exenatide Monthly 5 mg exenatide microspheres in Miglyol 812 were administered once a month SC over 20 weeks. Miglyol is a clear oil mixture of medium chain triglycerides.	8 mg Exenatide Monthly 8 mg exenatide microspheres in Miglyol 812 were administered once a month SC over 20 weeks. Miglyol is a clear oil mixture of medium chain triglycerides.	11 mg Exenatide Monthly 11 mg exenatide microspheres in Miglyol 812 were administered once a month SC over 20 weeks. Miglyol is a clear oil mixture of medium chain triglycerides.
Overall Study STARTED	30	30	31	30
Overall Study COMPLETED	30	27	29	28
Overall Study NOT COMPLETED	0	3	2	2

Reasons for withdrawal

Reasons for withdrawal
Measure	5 mg Exenatide Monthly 5 mg exenatide microspheres in Miglyol 812 were administered once a month SC over 20 weeks. Miglyol is a clear oil mixture of medium chain triglycerides.	8 mg Exenatide Monthly 8 mg exenatide microspheres in Miglyol 812 were administered once a month SC over 20 weeks. Miglyol is a clear oil mixture of medium chain triglycerides.	11 mg Exenatide Monthly 11 mg exenatide microspheres in Miglyol 812 were administered once a month SC over 20 weeks. Miglyol is a clear oil mixture of medium chain triglycerides.
Overall Study Withdrawal by Subject	1	2	1
Overall Study Adverse Event	0	0	1
Overall Study Physician Decision	2	0	0

Baseline Characteristics

A Study to Examine the Efficacy, Safety and Tolerability, and Pharmacokinetics of Exenatide Once Monthly Suspension

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	2 mg Exenatide Weekly n=30 Participants 2 milligrams (mg) exenatide microspheres in aqueous diluent were administered once a week as a subcutaneous injection (SC).	5 mg Exenatide Monthly n=30 Participants 5 mg exenatide microspheres in Miglyol 812 were administered once a month SC. Miglyol is a clear oil mixture of medium chain triglycerides.	8 mg Exenatide Monthly n=31 Participants 8 mg exenatide microspheres in Miglyol 812 were administered once a month SC. Miglyol is a clear oil mixture of medium chain triglycerides. .	11 mg Exenatide Monthly n=30 Participants 11 mg exenatide microspheres in Miglyol 812 were administered once a month SC. Miglyol is a clear oil mixture of medium chain triglycerides.	Total n=121 Participants Total of all reporting groups
Age, Customized Less than (<) 65 years of age	28 participants n=5 Participants	29 participants n=7 Participants	26 participants n=5 Participants	27 participants n=4 Participants	110 participants n=21 Participants
Age, Customized Greater than, equal to (≥) 65 years of age	2 participants n=5 Participants	1 participants n=7 Participants	5 participants n=5 Participants	3 participants n=4 Participants	11 participants n=21 Participants
Sex: Female, Male Female	10 Participants n=5 Participants	13 Participants n=7 Participants	7 Participants n=5 Participants	13 Participants n=4 Participants	43 Participants n=21 Participants
Sex: Female, Male Male	20 Participants n=5 Participants	17 Participants n=7 Participants	24 Participants n=5 Participants	17 Participants n=4 Participants	78 Participants n=21 Participants
Race/Ethnicity, Customized Asian	0 participants n=5 Participants	1 participants n=7 Participants	0 participants n=5 Participants	2 participants n=4 Participants	3 participants n=21 Participants
Race/Ethnicity, Customized Black or African American	1 participants n=5 Participants	4 participants n=7 Participants	2 participants n=5 Participants	5 participants n=4 Participants	12 participants n=21 Participants
Race/Ethnicity, Customized White	28 participants n=5 Participants	24 participants n=7 Participants	29 participants n=5 Participants	23 participants n=4 Participants	104 participants n=21 Participants
Race/Ethnicity, Customized Other	1 participants n=5 Participants	1 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants	2 participants n=21 Participants
Region of Enrollment United States	30 participants n=5 Participants	30 participants n=7 Participants	31 participants n=5 Participants	30 participants n=4 Participants	121 participants n=21 Participants
Mean Hemoglobin A1c (HbA1c)	8.64 Percent of hemoglobin STANDARD_DEVIATION 1.19 • n=5 Participants	8.54 Percent of hemoglobin STANDARD_DEVIATION 1.18 • n=7 Participants	8.54 Percent of hemoglobin STANDARD_DEVIATION 1.18 • n=5 Participants	8.37 Percent of hemoglobin STANDARD_DEVIATION 1.34 • n=4 Participants	8.52 Percent of hemoglobin STANDARD_DEVIATION 1.21 • n=21 Participants
Category of HbA1c HbA1c < 9.0%	20 participants n=5 Participants	18 participants n=7 Participants	19 participants n=5 Participants	21 participants n=4 Participants	78 participants n=21 Participants
Category of HbA1c HbA1c ≥ 9.0%	10 participants n=5 Participants	12 participants n=7 Participants	12 participants n=5 Participants	9 participants n=4 Participants	43 participants n=21 Participants

PRIMARY outcome

Timeframe: Baseline (Day 1) to 20 weeks

Population: All participants who received at least one dose of study drug, complied with the protocol, had adequate study drug exposure, and had a measurement value on the specified week were included in the analysis of the evaluable population. n=number of participants with measurement value.

Outcome measures

Outcome measures
Measure	2 mg Exenatide Weekly n=29 Participants 2 milligrams (mg) exenatide microspheres in aqueous diluent were administered once a week as a subcutaneous injection (SC) over 20 weeks.	5 mg Exenatide Monthly n=26 Participants 5 mg exenatide microspheres in Miglyol 812 were administered once a month SC over 20 weeks. Miglyol is a clear oil mixture of medium chain triglycerides.	8 mg Exenatide Monthly n=28 Participants 8 mg exenatide microspheres in Miglyol 812 were administered once a month SC over 20 weeks. Miglyol is a clear oil mixture of medium chain triglycerides. .	11 mg Exenatide Monthly n=27 Participants 11 mg exenatide microspheres in Miglyol 812 were administered once a month SC over 20 weeks. Miglyol is a clear oil mixture of medium chain triglycerides.
Mean Change in HbA1c From Baseline to End of Treatment (Week 20) - Evaluable Population Change from baseline at Week 4 (n=29, 26, 28, 27)	-0.52 Percent of Hemoglobin Standard Error 0.095	-0.33 Percent of Hemoglobin Standard Error 0.127	-0.24 Percent of Hemoglobin Standard Error 0.139	-0.34 Percent of Hemoglobin Standard Error 0.074
Mean Change in HbA1c From Baseline to End of Treatment (Week 20) - Evaluable Population Change from baseline at Week 8 (n=25, 22, 25, 27)	-1.15 Percent of Hemoglobin Standard Error 0.157	-0.89 Percent of Hemoglobin Standard Error 0.200	-1.03 Percent of Hemoglobin Standard Error 0.218	-0.91 Percent of Hemoglobin Standard Error 0.110
Mean Change in HbA1c From Baseline to End of Treatment (Week 20) - Evaluable Population Change from baseline at Week 12 (n=29, 26, 28, 27)	-1.43 Percent of Hemoglobin Standard Error 0.223	-1.30 Percent of Hemoglobin Standard Error 0.209	-1.19 Percent of Hemoglobin Standard Error 0.246	-1.26 Percent of Hemoglobin Standard Error 0.156
Mean Change in HbA1c From Baseline to End of Treatment (Week 20) - Evaluable Population Change from baseline at Week 16 (n=29, 26, 28, 27)	-1.58 Percent of Hemoglobin Standard Error 0.216	-1.40 Percent of Hemoglobin Standard Error 0.215	-1.41 Percent of Hemoglobin Standard Error 0.271	-1.43 Percent of Hemoglobin Standard Error 0.177
Mean Change in HbA1c From Baseline to End of Treatment (Week 20) - Evaluable Population Change from baseline at Week 20 (n=29, 26, 28, 27)	-1.54 Percent of Hemoglobin Standard Error 0.234	-1.29 Percent of Hemoglobin Standard Error 0.210	-1.31 Percent of Hemoglobin Standard Error 0.313	-1.45 Percent of Hemoglobin Standard Error 0.179

SECONDARY outcome

Timeframe: Week 20

Population: All participants who received at least one dose of study drug, complied with the protocol, had adequate study drug exposure, and had a measurement value for Week 20 were included in the analysis of the evaluable population. n=number of participants with measurement value.

HbA1c was measured as a percent (%) of total hemoglobin. The Target values for HbA1c were \<7% and ≤ 6.5% at Week 20. Evaluable population was defined as participants who completed study procedures in compliance with the protocol and had adequate exposure to the study drug.

Outcome measures

Outcome measures
Measure	2 mg Exenatide Weekly n=29 Participants 2 milligrams (mg) exenatide microspheres in aqueous diluent were administered once a week as a subcutaneous injection (SC) over 20 weeks.	5 mg Exenatide Monthly n=26 Participants 5 mg exenatide microspheres in Miglyol 812 were administered once a month SC over 20 weeks. Miglyol is a clear oil mixture of medium chain triglycerides.	8 mg Exenatide Monthly n=28 Participants 8 mg exenatide microspheres in Miglyol 812 were administered once a month SC over 20 weeks. Miglyol is a clear oil mixture of medium chain triglycerides. .	11 mg Exenatide Monthly n=27 Participants 11 mg exenatide microspheres in Miglyol 812 were administered once a month SC over 20 weeks. Miglyol is a clear oil mixture of medium chain triglycerides.
Percentage of Participants Achieving HbA1c Target Values at Week 20 - Evaluable Population < 7.0% HbA1c	48.3 percentage of Participants	50.0 percentage of Participants	57.1 percentage of Participants	70.4 percentage of Participants
Percentage of Participants Achieving HbA1c Target Values at Week 20 - Evaluable Population ≤ 6.5% HbA1c	44.8 percentage of Participants	26.9 percentage of Participants	39.3 percentage of Participants	48.1 percentage of Participants

SECONDARY outcome

Timeframe: Baseline (Day 1) to Week 20

Body weight was measured in kilograms (kg) at Baseline, and during treatment at Weeks 2, 4, 6, 8, 9-11, 12, 13, 14, 15, 16, 17-19, and 20. Baseline was Day 1, or last measurement prior to first dose of study drug. Evaluable population was defined as all participants who completed study procedures in compliance with the protocol and had adequate exposure to the study drug.

Outcome measures

Outcome measures
Measure	2 mg Exenatide Weekly n=29 Participants 2 milligrams (mg) exenatide microspheres in aqueous diluent were administered once a week as a subcutaneous injection (SC) over 20 weeks.	5 mg Exenatide Monthly n=26 Participants 5 mg exenatide microspheres in Miglyol 812 were administered once a month SC over 20 weeks. Miglyol is a clear oil mixture of medium chain triglycerides.	8 mg Exenatide Monthly n=28 Participants 8 mg exenatide microspheres in Miglyol 812 were administered once a month SC over 20 weeks. Miglyol is a clear oil mixture of medium chain triglycerides. .	11 mg Exenatide Monthly n=27 Participants 11 mg exenatide microspheres in Miglyol 812 were administered once a month SC over 20 weeks. Miglyol is a clear oil mixture of medium chain triglycerides.
Mean Change in Body Weight From Baseline to Week 20 - Evaluable Population Change from baseline to Week 2 (n=29,26,28,27)	-0.31 kg Standard Error 0.274	0.32 kg Standard Error 0.232	0.31 kg Standard Error 0.234	0.35 kg Standard Error 0.204
Mean Change in Body Weight From Baseline to Week 20 - Evaluable Population Change from baseline to Week 4 (n=29,26,28,27)	-0.66 kg Standard Error 0.321	-0.04 kg Standard Error 0.249	0.32 kg Standard Error 0.299	0.03 kg Standard Error 0.226
Mean Change in Body Weight From Baseline to Week 20 - Evaluable Population Change from baseline to Week 6 (n=29,26,28,27)	-1.26 kg Standard Error 0.359	-0.74 kg Standard Error 0.304	-0.45 kg Standard Error 0.409	-0.74 kg Standard Error 0.326
Mean Change in Body Weight From Baseline to Week 20 - Evaluable Population Change from baseline to Week 8 (n=28,26,28,27)	-1.36 kg Standard Error 0.455	-0.85 kg Standard Error 0.395	-0.33 kg Standard Error 0.482	-0.70 kg Standard Error 0.466
Mean Change in Body Weight From Baseline to Week 20 - Evaluable Population Change from baseline to Weeks 9-11 (n=29,26,28,27)	-1.73 kg Standard Error 0.565	-0.57 kg Standard Error 0.469	-0.49 kg Standard Error 0.498	-0.83 kg Standard Error 0.563
Mean Change in Body Weight From Baseline to Week 20 - Evaluable Population Change from baseline to Week 12 (n=28,26,28,27)	-1.49 kg Standard Error 0.573	-0.91 kg Standard Error 0.453	-0.33 kg Standard Error 0.578	-0.76 kg Standard Error 0.502
Mean Change in Body Weight From Baseline to Week 20 - Evaluable Population Change from baseline to Week 13 (n=29,26,28,27)	-1.96 kg Standard Error 0.505	-1.20 kg Standard Error 0.572	-0.56 kg Standard Error 0.591	-0.97 kg Standard Error 0.551
Mean Change in Body Weight From Baseline to Week 20 - Evaluable Population Change from baseline to Week 14 (n=29,26,28,27)	-1.91 kg Standard Error 0.643	-0.96 kg Standard Error 0.611	-0.76 kg Standard Error 0.589	-0.81 kg Standard Error 0.563
Mean Change in Body Weight From Baseline to Week 20 - Evaluable Population Change from baseline to Week 15 (n=29,26,28,26)	-1.84 kg Standard Error 0.511	-1.34 kg Standard Error 0.648	-0.80 kg Standard Error 0.581	-1.24 kg Standard Error 0.581
Mean Change in Body Weight From Baseline to Week 20 - Evaluable Population Change from baseline to Week 16 (n=29,26,28,27)	-1.85 kg Standard Error 0.590	-1.33 kg Standard Error 0.673	-0.26 kg Standard Error 0.551	-1.02 kg Standard Error 0.574
Mean Change in Body Weight From Baseline to Week 20 - Evaluable Population Change from baseline to Weeks 17-19(n=29,26,28,27)	-1.63 kg Standard Error 0.592	-1.17 kg Standard Error 0.697	-0.58 kg Standard Error 0.629	-1.72 kg Standard Error 0.700
Mean Change in Body Weight From Baseline to Week 20 - Evaluable Population Change from baseline to Week 20 (n=29,26,28,27)	-1.36 kg Standard Error 0.641	-1.10 kg Standard Error 0.774	-0.41 kg Standard Error 0.559	-1.14 kg Standard Error 0.676

SECONDARY outcome

Timeframe: Baseline (Day 1) to Week 20

Fasting glucose was measured in milligrams per deciliter (mg/dL) at screening, Baseline, and during treatment at Weeks 2, 4, 6, 8, 9-11, 12, 13, 14, 15, 16, 17-19, and 20. Baseline was Day 1, or last measurement prior to first dose of study drug. Evaluable population was defined as all participants who completed study procedures in compliance with the protocol and had adequate exposure to the study drug.

Outcome measures

Outcome measures
Measure	2 mg Exenatide Weekly n=29 Participants 2 milligrams (mg) exenatide microspheres in aqueous diluent were administered once a week as a subcutaneous injection (SC) over 20 weeks.	5 mg Exenatide Monthly n=26 Participants 5 mg exenatide microspheres in Miglyol 812 were administered once a month SC over 20 weeks. Miglyol is a clear oil mixture of medium chain triglycerides.	8 mg Exenatide Monthly n=28 Participants 8 mg exenatide microspheres in Miglyol 812 were administered once a month SC over 20 weeks. Miglyol is a clear oil mixture of medium chain triglycerides. .	11 mg Exenatide Monthly n=27 Participants 11 mg exenatide microspheres in Miglyol 812 were administered once a month SC over 20 weeks. Miglyol is a clear oil mixture of medium chain triglycerides.
Mean Change in Fasting Glucose From Baseline to Week 20 - Evaluable Population Change from baseline to Week 2 (n=29, 26, 28,27)	-1.16 mg/dL Standard Error 8.54	-12.9 mg/dL Standard Error 7.57	-14.6 mg/dL Standard Error 6.36	-23.5 mg/dL Standard Error 5.17
Mean Change in Fasting Glucose From Baseline to Week 20 - Evaluable Population Change from baseline to Week 4 (n=29, 25, 28,27)	-21.7 mg/dL Standard Error 7.97	-18.0 mg/dL Standard Error 5.96	-14.2 mg/dL Standard Error 8.57	-23.1 mg/dL Standard Error 7.83
Mean Change in Fasting Glucose From Baseline to Week 20 - Evaluable Population Change from baseline to Week 6 (n=28, 26, 28,27)	-32.8 mg/dL Standard Error 8.58	-42.6 mg/dL Standard Error 5.72	-39.5 mg/dL Standard Error 9.49	-48.8 mg/dL Standard Error 7.67
Mean Change in Fasting Glucose From Baseline to Week 20 - Evaluable Population Change from baseline to Week 8 (n=28, 26, 28,27)	-40.8 mg/dL Standard Error 8.70	-45.7 mg/dL Standard Error 6.44	-36.8 mg/dL Standard Error 7.45	-44.0 mg/dL Standard Error 7.24
Mean Change in Fasting Glucose From Baseline to Week 20 - Evaluable Population Change from baseline to Weeks 9-11 (n=29,26,27,27)	-32.8 mg/dL Standard Error 8.77	-40.2 mg/dL Standard Error 8.25	-44.3 mg/dL Standard Error 7.71	-48.1 mg/dL Standard Error 7.60
Mean Change in Fasting Glucose From Baseline to Week 20 - Evaluable Population Change from baseline to Weeks 12 (n=29,26,27,27)	-44.8 mg/dL Standard Error 10.28	-37.4 mg/dL Standard Error 8.61	-45.4 mg/dL Standard Error 6.78	-44.9 mg/dL Standard Error 7.53
Mean Change in Fasting Glucose From Baseline to Week 20 - Evaluable Population Change from baseline to Weeks 13 (n=29,26,28,27)	-42.0 mg/dL Standard Error 8.60	-38.0 mg/dL Standard Error 7.52	-48.6 mg/dL Standard Error 6.21	-45.7 mg/dL Standard Error 8.60
Mean Change in Fasting Glucose From Baseline to Week 20 - Evaluable Population Change from baseline to Weeks 14 (n=29,26,28,27)	-36.3 mg/dL Standard Error 10.51	-37.3 mg/dL Standard Error 7.75	-47.5 mg/dL Standard Error 7.83	-51.6 mg/dL Standard Error 8.68
Mean Change in Fasting Glucose From Baseline to Week 20 - Evaluable Population Change from baseline to Weeks 15 (n=29,26,28,26)	-38.0 mg/dL Standard Error 11.09	-37.3 mg/dL Standard Error 7.65	-46.9 mg/dL Standard Error 7.35	-53.1 mg/dL Standard Error 8.96
Mean Change in Fasting Glucose From Baseline to Week 20 - Evaluable Population Change from baseline to Weeks 16 (n=29,26,28,27)	-34.5 mg/dL Standard Error 9.96	-31.6 mg/dL Standard Error 9.24	-43.3 mg/dL Standard Error 10.14	-46.3 mg/dL Standard Error 7.90
Mean Change in Fasting Glucose From Baseline to Week 20 - Evaluable Population Change from baseline to Weeks17-19 (n=29,26,28,27)	-33.3 mg/dL Standard Error 8.58	-42.4 mg/dL Standard Error 7.16	-34.6 mg/dL Standard Error 9.32	-55.1 mg/dL Standard Error 8.92
Mean Change in Fasting Glucose From Baseline to Week 20 - Evaluable Population Change from baseline to Week 20 (n=29,26,28,27)	-34.2 mg/dL Standard Error 8.99	-25.1 mg/dL Standard Error 8.49	-29.8 mg/dL Standard Error 9.88	-48.9 mg/dL Standard Error 9.35

SECONDARY outcome

Timeframe: Day 1 to Week 20

Population: PK Evaluable- Steady-State: from trough to trough following Week 12 through Week 16, 3 or more values.

All participants received an initial blood draw prior to the first dose and a single blood sample was collected at all other subsequent visits, for plasma exenatide assessments and the characterization of pharmacokinetic (PK) parameters following multiple monthly doses over the study period. Exenatide was measured using a validated enzyme-linked immunosorbent assay (ELISA). Time weighted average concentration (Cave (2016-2688 h) and Peak to Trough were measured in picograms per milliliter (pg/mL).

Outcome measures

Outcome measures
Measure	2 mg Exenatide Weekly n=25 Participants 2 milligrams (mg) exenatide microspheres in aqueous diluent were administered once a week as a subcutaneous injection (SC) over 20 weeks.	5 mg Exenatide Monthly n=24 Participants 5 mg exenatide microspheres in Miglyol 812 were administered once a month SC over 20 weeks. Miglyol is a clear oil mixture of medium chain triglycerides.	8 mg Exenatide Monthly n=25 Participants 8 mg exenatide microspheres in Miglyol 812 were administered once a month SC over 20 weeks. Miglyol is a clear oil mixture of medium chain triglycerides. .	11 mg Exenatide Monthly n=23 Participants 11 mg exenatide microspheres in Miglyol 812 were administered once a month SC over 20 weeks. Miglyol is a clear oil mixture of medium chain triglycerides.
Time Weighted Average Concentration and Peak to Trough of Exenatide From Week 12 Through Week 16 - Pharmacokinetic Evaluable - Steady State Population Cave(2016-2688h) pg/mL	262.92 pg/mL Geometric Coefficient of Variation 83.54	127.13 pg/mL Geometric Coefficient of Variation 69.34	247.38 pg/mL Geometric Coefficient of Variation 81.63	218.07 pg/mL Geometric Coefficient of Variation 73.77
Time Weighted Average Concentration and Peak to Trough of Exenatide From Week 12 Through Week 16 - Pharmacokinetic Evaluable - Steady State Population Peak-Trough (2016-2688h) pg/mL	171.27 pg/mL Geometric Coefficient of Variation 73.85	198.06 pg/mL Geometric Coefficient of Variation 86.76	424.47 pg/mL Geometric Coefficient of Variation 70.27	328.52 pg/mL Geometric Coefficient of Variation 86.30

SECONDARY outcome

Timeframe: Baseline (Day 1), Week 20

Population: Participants who received at least one dose of study drug were analyzed in the Intent to Treat (ITT) population.

Baseline was Day 1, or last measurement prior to first dose of study drug. Vital signs were measured after the participant had rested for approximately 5 minutes and with the participant in a sitting position. Measurement was recorded in millimeters of mercury (mmHg). The blood pressure measurement was repeated after at least 30 seconds and the average of the two readings recorded. ITT population was defined as all participants who received at least one dose of the study drug.

Outcome measures

Outcome measures
Measure	2 mg Exenatide Weekly n=30 Participants 2 milligrams (mg) exenatide microspheres in aqueous diluent were administered once a week as a subcutaneous injection (SC) over 20 weeks.	5 mg Exenatide Monthly n=30 Participants 5 mg exenatide microspheres in Miglyol 812 were administered once a month SC over 20 weeks. Miglyol is a clear oil mixture of medium chain triglycerides.	8 mg Exenatide Monthly n=31 Participants 8 mg exenatide microspheres in Miglyol 812 were administered once a month SC over 20 weeks. Miglyol is a clear oil mixture of medium chain triglycerides. .	11 mg Exenatide Monthly n=30 Participants 11 mg exenatide microspheres in Miglyol 812 were administered once a month SC over 20 weeks. Miglyol is a clear oil mixture of medium chain triglycerides.
Mean Change From Baseline in Diastolic and Systolic Blood Pressure at Week 20 - Intent to Treat (ITT) Population Diastolic Blood Pressure	-1.7 mmHg Standard Deviation 8.55	3.4 mmHg Standard Deviation 8.54	1.8 mmHg Standard Deviation 9.61	1.9 mmHg Standard Deviation 8.17
Mean Change From Baseline in Diastolic and Systolic Blood Pressure at Week 20 - Intent to Treat (ITT) Population Systolic Blood Pressure	-2.3 mmHg Standard Deviation 13.64	4.4 mmHg Standard Deviation 18.68	0.5 mmHg Standard Deviation 13.97	5.0 mmHg Standard Deviation 12.04

SECONDARY outcome

Timeframe: Baseline (Day 1), Week 20

Population: Participants who received at least one dose of study drug were analyzed in the ITT population.

Baseline was Day 1, or last measurement prior to first dose of study drug. Heart rate was measured after the participant had rested for approximately 5 minutes and with the participant in a sitting position. Measurement was recorded in beats per minute (bpm). The measurement was repeated after at least 30 seconds and the average of the two readings recorded. ITT population was defined as all participants who received at least one dose of the study drug.

Outcome measures

Outcome measures
Measure	2 mg Exenatide Weekly n=30 Participants 2 milligrams (mg) exenatide microspheres in aqueous diluent were administered once a week as a subcutaneous injection (SC) over 20 weeks.	5 mg Exenatide Monthly n=30 Participants 5 mg exenatide microspheres in Miglyol 812 were administered once a month SC over 20 weeks. Miglyol is a clear oil mixture of medium chain triglycerides.	8 mg Exenatide Monthly n=31 Participants 8 mg exenatide microspheres in Miglyol 812 were administered once a month SC over 20 weeks. Miglyol is a clear oil mixture of medium chain triglycerides. .	11 mg Exenatide Monthly n=30 Participants 11 mg exenatide microspheres in Miglyol 812 were administered once a month SC over 20 weeks. Miglyol is a clear oil mixture of medium chain triglycerides.
Mean Change From Baseline in Heart Rate at Week 20 - Intent to Treat (ITT) Population	2.8 bpm Standard Deviation 9.58	3.9 bpm Standard Deviation 10.69	5.6 bpm Standard Deviation 10.84	-0.3 bpm Standard Deviation 11.55

SECONDARY outcome

Timeframe: Day 1 to Study Termination (24 Weeks) or early Termination

Population: All participants who received at least one dose of study drug were included in the ITT analysis.

AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. All participants who received at least one dose of study drug were included in the ITT analysis. Treatment-emergent (TE) adverse events were defined as those with onset at or after initiation of study medication on Day 1 through study termination or early termination.

Outcome measures

Outcome measures
Measure	2 mg Exenatide Weekly n=30 Participants 2 milligrams (mg) exenatide microspheres in aqueous diluent were administered once a week as a subcutaneous injection (SC) over 20 weeks.	5 mg Exenatide Monthly n=30 Participants 5 mg exenatide microspheres in Miglyol 812 were administered once a month SC over 20 weeks. Miglyol is a clear oil mixture of medium chain triglycerides.	8 mg Exenatide Monthly n=31 Participants 8 mg exenatide microspheres in Miglyol 812 were administered once a month SC over 20 weeks. Miglyol is a clear oil mixture of medium chain triglycerides. .	11 mg Exenatide Monthly n=30 Participants 11 mg exenatide microspheres in Miglyol 812 were administered once a month SC over 20 weeks. Miglyol is a clear oil mixture of medium chain triglycerides.
Number of Participants With Treatment-Emergent Adverse Events (AEs), Serious AEs (SAEs), and AEs Leading to Discontinuation - ITT Population Treatment-Emergent AES	27 participants	25 participants	20 participants	24 participants
Number of Participants With Treatment-Emergent Adverse Events (AEs), Serious AEs (SAEs), and AEs Leading to Discontinuation - ITT Population Treatment-Emergent SAEs	0 participants	2 participants	0 participants	0 participants
Number of Participants With Treatment-Emergent Adverse Events (AEs), Serious AEs (SAEs), and AEs Leading to Discontinuation - ITT Population Treatment-Emergent AEs Leading to Discontinuation	0 participants	0 participants	0 participants	1 participants

SECONDARY outcome

Timeframe: Day 1 through study termination (Week 24) or early termination.

Population: All participants who received at least one dose of study drug were analyzed in the ITT population.

AE is any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. Injection site related adverse events were defined as the adverse events with 'injection site' phrase in preferred term excluding 'injection site nodule'. The following events were Injection Site Reaction AEs: erythema, hematoma, hemorrhage, site pain, site papule, site pruritus, site warmth. Participants receiving study drug monthly received 5 injections with last injection at Week 16; Participants receiving study drug weekly received 20 injections with last injection at Week 19. .

Outcome measures

Outcome measures
Measure	2 mg Exenatide Weekly n=30 Participants 2 milligrams (mg) exenatide microspheres in aqueous diluent were administered once a week as a subcutaneous injection (SC) over 20 weeks.	5 mg Exenatide Monthly n=30 Participants 5 mg exenatide microspheres in Miglyol 812 were administered once a month SC over 20 weeks. Miglyol is a clear oil mixture of medium chain triglycerides.	8 mg Exenatide Monthly n=31 Participants 8 mg exenatide microspheres in Miglyol 812 were administered once a month SC over 20 weeks. Miglyol is a clear oil mixture of medium chain triglycerides. .	11 mg Exenatide Monthly n=30 Participants 11 mg exenatide microspheres in Miglyol 812 were administered once a month SC over 20 weeks. Miglyol is a clear oil mixture of medium chain triglycerides.
Number of Participants With Injection Site Reaction Treatment Emergent Adverse Events - ITT Population	6 participants	8 participants	3 participants	6 participants

SECONDARY outcome

Timeframe: Day 1 to Study Termination (24 weeks) or early termination

Population: n=all participants who received at least one dose of study drug and had available titer.

Serum titers of antibodies to exenatide were evaluated using a validated enzyme-linked immunosorbent assay (Covance Method No. ELISA-0308). Positive antibody to exenatide titer: observed at the indicated visit following a negative or missing titer at baseline, or a positive titer that has increased by at least 3 dilutions at the indicated visit from a detectable baseline. Baseline=Day 1.

Outcome measures

Outcome measures
Measure	2 mg Exenatide Weekly n=30 Participants 2 milligrams (mg) exenatide microspheres in aqueous diluent were administered once a week as a subcutaneous injection (SC) over 20 weeks.	5 mg Exenatide Monthly n=30 Participants 5 mg exenatide microspheres in Miglyol 812 were administered once a month SC over 20 weeks. Miglyol is a clear oil mixture of medium chain triglycerides.	8 mg Exenatide Monthly n=30 Participants 8 mg exenatide microspheres in Miglyol 812 were administered once a month SC over 20 weeks. Miglyol is a clear oil mixture of medium chain triglycerides. .	11 mg Exenatide Monthly n=30 Participants 11 mg exenatide microspheres in Miglyol 812 were administered once a month SC over 20 weeks. Miglyol is a clear oil mixture of medium chain triglycerides.
Participants Negative or Positive for Anti-exenatide Antibodies - ITT Population Week 2 Negative (n=30,30,30,30)	27 participants	30 participants	30 participants	29 participants
Participants Negative or Positive for Anti-exenatide Antibodies - ITT Population Week 2 Low Titer (<625)(n=30,30,30,30)	3 participants	0 participants	0 participants	1 participants
Participants Negative or Positive for Anti-exenatide Antibodies - ITT Population Week 2 High Titer (≥625)(n=30,30,30,30)	0 participants	0 participants	0 participants	0 participants
Participants Negative or Positive for Anti-exenatide Antibodies - ITT Population Week 20 Negative (n=30,26,29,28)	7 participants	8 participants	9 participants	9 participants
Participants Negative or Positive for Anti-exenatide Antibodies - ITT Population Week 20 Low Titer (<625)(n=30,26,29,28)	15 participants	10 participants	15 participants	15 participants
Participants Negative or Positive for Anti-exenatide Antibodies - ITT Population Week 20 High Titer (≥625)(n=30,26,29,28)	8 participants	8 participants	5 participants	4 participants

SECONDARY outcome

Timeframe: Day 1 to study termination (24 weeks) or early termination

Population: n= all participants who received at least one dose of study drug and had available laboratory measurements.

Potential clinical importance are the following: Hematocrit values for males less than (\<) 36%, females \< 30%; hemoglobin for males \<12 grams per deciliter (g/dL), females \< 10 g/dL; low platelet values \<75,000/micro liter (µL), high values greater than (\>) 500,000 µL. Laboratory samples were obtained at baseline (Day 1 or if unavailable, last measurement prior to first study drug dose), Weeks 6, 12, 20, and at study termination (Week 24) or early termination. Number of laboratory values of potential clinical importance presented for Weeks 6 - Week 24 or early termination.

Outcome measures

Outcome measures
Measure	2 mg Exenatide Weekly n=30 Participants 2 milligrams (mg) exenatide microspheres in aqueous diluent were administered once a week as a subcutaneous injection (SC) over 20 weeks.	5 mg Exenatide Monthly n=30 Participants 5 mg exenatide microspheres in Miglyol 812 were administered once a month SC over 20 weeks. Miglyol is a clear oil mixture of medium chain triglycerides.	8 mg Exenatide Monthly n=30 Participants 8 mg exenatide microspheres in Miglyol 812 were administered once a month SC over 20 weeks. Miglyol is a clear oil mixture of medium chain triglycerides. .	11 mg Exenatide Monthly n=30 Participants 11 mg exenatide microspheres in Miglyol 812 were administered once a month SC over 20 weeks. Miglyol is a clear oil mixture of medium chain triglycerides.
Number of Hematology Laboratory Values of Potential Clinical Importance Observed During Treatment Period - ITT Population Week 6 Hematocrit (n=30,30,30,30)	0 laboratory values	1 laboratory values	0 laboratory values	0 laboratory values
Number of Hematology Laboratory Values of Potential Clinical Importance Observed During Treatment Period - ITT Population Hematocrit at study termination (n=30,27,29,28)	0 laboratory values	1 laboratory values	0 laboratory values	0 laboratory values
Number of Hematology Laboratory Values of Potential Clinical Importance Observed During Treatment Period - ITT Population Week 12 Platelets (n=30, 29, 30, 28)	0 laboratory values	1 laboratory values	0 laboratory values	0 laboratory values

SECONDARY outcome

Timeframe: Day 1 to Study Termination (Week24) or early termination

Population: All participants who were randomized and received at least one dose of study drug were analyzed in the intent to treat (ITT) population. n= all participants who received at least one dose of study drug and had available laboratory measurements.

Potential clinical importance (PCI): triacylglycerol lipase high values were \> 3\* upper limit of normal (ULN); creatinine high values in males \>1.6 mg/dL, females \>1.4 mg/dL; gamma glutamyl transferase (GGT) high value \>3\* ULN; bilirubin high value \> 2 mg/dL; Urate high values \> 10 (males), \>8 (females) mg/dL; potassium low value \< 3 milliequivalents per liter (mEq/L), high value \>5.5 mEq/L; calcium low value \< 8 mg/dL and high value \> 11 mg/dL. Laboratory samples were obtained at baseline (Day 1 or if unavailable, last measurement prior to first study drug dose), Weeks 6, 12, 20, and at study termination (Week 24) or early termination. Number of laboratory values of potential clinical importance (values could be either low or high) are presented for Weeks 6 - Week 24 or early termination. Note: those tests with no values meeting the PCI criteria, ie, 0 values observed across all treatment arms, are not presented.

Outcome measures

Outcome measures
Measure	2 mg Exenatide Weekly n=30 Participants 2 milligrams (mg) exenatide microspheres in aqueous diluent were administered once a week as a subcutaneous injection (SC) over 20 weeks.	5 mg Exenatide Monthly n=30 Participants 5 mg exenatide microspheres in Miglyol 812 were administered once a month SC over 20 weeks. Miglyol is a clear oil mixture of medium chain triglycerides.	8 mg Exenatide Monthly n=31 Participants 8 mg exenatide microspheres in Miglyol 812 were administered once a month SC over 20 weeks. Miglyol is a clear oil mixture of medium chain triglycerides. .	11 mg Exenatide Monthly n=30 Participants 11 mg exenatide microspheres in Miglyol 812 were administered once a month SC over 20 weeks. Miglyol is a clear oil mixture of medium chain triglycerides.
Number of Chemistry Laboratory Values of Potential Clinical Importance Observed During Treatment Period - ITT Population triacylglycerol lipase Week 12 (n=30,29,29,28)	1 laboratory values	1 laboratory values	0 laboratory values	0 laboratory values
Number of Chemistry Laboratory Values of Potential Clinical Importance Observed During Treatment Period - ITT Population triacylglycerol lipase Week 20 (n=30,27,29,28)	1 laboratory values	0 laboratory values	0 laboratory values	1 laboratory values
Number of Chemistry Laboratory Values of Potential Clinical Importance Observed During Treatment Period - ITT Population Creatinine Week 6 (n=30,30,30,30)	0 laboratory values	1 laboratory values	0 laboratory values	0 laboratory values
Number of Chemistry Laboratory Values of Potential Clinical Importance Observed During Treatment Period - ITT Population Creatinine Week 12 (n=30,29,30,28)	1 laboratory values	0 laboratory values	0 laboratory values	0 laboratory values
Number of Chemistry Laboratory Values of Potential Clinical Importance Observed During Treatment Period - ITT Population Creatinine Week 20 (n=30,26,28,28)	0 laboratory values	1 laboratory values	0 laboratory values	0 laboratory values
Number of Chemistry Laboratory Values of Potential Clinical Importance Observed During Treatment Period - ITT Population Creatinine at study termination (n=30,26,29,28)	0 laboratory values	0 laboratory values	1 laboratory values	0 laboratory values
Number of Chemistry Laboratory Values of Potential Clinical Importance Observed During Treatment Period - ITT Population GGT Week 6 (n=30,30,30,30)	2 laboratory values	0 laboratory values	0 laboratory values	0 laboratory values
Number of Chemistry Laboratory Values of Potential Clinical Importance Observed During Treatment Period - ITT Population GGT Week 20 (n=30,26,28,28)	1 laboratory values	0 laboratory values	1 laboratory values	0 laboratory values
Number of Chemistry Laboratory Values of Potential Clinical Importance Observed During Treatment Period - ITT Population GGT study termination (n=30,26,29,28)	1 laboratory values	0 laboratory values	1 laboratory values	0 laboratory values
Number of Chemistry Laboratory Values of Potential Clinical Importance Observed During Treatment Period - ITT Population Bilirubin Week 6 (n=30,30,30,30)	0 laboratory values	1 laboratory values	0 laboratory values	0 laboratory values
Number of Chemistry Laboratory Values of Potential Clinical Importance Observed During Treatment Period - ITT Population Bilirubin Week 12 (n=30,29,30,28)	0 laboratory values	1 laboratory values	0 laboratory values	0 laboratory values
Number of Chemistry Laboratory Values of Potential Clinical Importance Observed During Treatment Period - ITT Population Urate Week 6 (n=30,30,30,30)	1 laboratory values	1 laboratory values	2 laboratory values	2 laboratory values
Number of Chemistry Laboratory Values of Potential Clinical Importance Observed During Treatment Period - ITT Population Urate Week 12 (n=30,29,30,28)	0 laboratory values	3 laboratory values	1 laboratory values	2 laboratory values
Number of Chemistry Laboratory Values of Potential Clinical Importance Observed During Treatment Period - ITT Population Urate Week 20 (n=30,26,28,28)	0 laboratory values	1 laboratory values	2 laboratory values	2 laboratory values
Number of Chemistry Laboratory Values of Potential Clinical Importance Observed During Treatment Period - ITT Population Urate Study termination (n=30,26,29,28)	1 laboratory values	0 laboratory values	0 laboratory values	0 laboratory values
Number of Chemistry Laboratory Values of Potential Clinical Importance Observed During Treatment Period - ITT Population Potassium Week 6 (n=30,30,30,30)	1 laboratory values	0 laboratory values	0 laboratory values	0 laboratory values
Number of Chemistry Laboratory Values of Potential Clinical Importance Observed During Treatment Period - ITT Population Calcium Week 6 (n=30,30,30,30)	1 laboratory values	0 laboratory values	0 laboratory values	0 laboratory values

Adverse Events

2 mg Exenatide Weekly

Serious events: 0 serious events

Other events: 27 other events

Deaths: 0 deaths

5 mg Exenatide Monthly

Serious events: 2 serious events

Other events: 25 other events

Deaths: 0 deaths

8 mg Exenatide Monthly

Serious events: 0 serious events

Other events: 20 other events

Deaths: 0 deaths

11 mg Exenatide Monthly

Serious events: 0 serious events

Other events: 24 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	2 mg Exenatide Weekly n=30 participants at risk 2 milligrams (mg) exenatide microspheres in aqueous diluent were administered once a week as a subcutaneous injection (SC).	5 mg Exenatide Monthly n=30 participants at risk 5 mg exenatide microspheres in Miglyol 812 were administered once a month SC. Miglyol is a clear oil mixture of medium chain triglycerides.	8 mg Exenatide Monthly n=31 participants at risk 8 mg exenatide microspheres in Miglyol 812 were administered once a month SC. Miglyol is a clear oil mixture of medium chain triglycerides. .	11 mg Exenatide Monthly n=30 participants at risk 11 mg exenatide microspheres in Miglyol 812 were administered once a month SC. Miglyol is a clear oil mixture of medium chain triglycerides.
Cardiac disorders Acute Coronary Syndrome	0.00% 0/30 • Day 1 to Week 24 or early termination Note: Injection site related adverse events were defined as adverse events with 'injection site' phrase in Preferred Term excluding 'injection site nodule'.	3.3% 1/30 • Number of events 1 • Day 1 to Week 24 or early termination Note: Injection site related adverse events were defined as adverse events with 'injection site' phrase in Preferred Term excluding 'injection site nodule'.	0.00% 0/31 • Day 1 to Week 24 or early termination Note: Injection site related adverse events were defined as adverse events with 'injection site' phrase in Preferred Term excluding 'injection site nodule'.	0.00% 0/30 • Day 1 to Week 24 or early termination Note: Injection site related adverse events were defined as adverse events with 'injection site' phrase in Preferred Term excluding 'injection site nodule'.
Cardiac disorders Acute myocardial infarction	0.00% 0/30 • Day 1 to Week 24 or early termination Note: Injection site related adverse events were defined as adverse events with 'injection site' phrase in Preferred Term excluding 'injection site nodule'.	3.3% 1/30 • Number of events 1 • Day 1 to Week 24 or early termination Note: Injection site related adverse events were defined as adverse events with 'injection site' phrase in Preferred Term excluding 'injection site nodule'.	0.00% 0/31 • Day 1 to Week 24 or early termination Note: Injection site related adverse events were defined as adverse events with 'injection site' phrase in Preferred Term excluding 'injection site nodule'.	0.00% 0/30 • Day 1 to Week 24 or early termination Note: Injection site related adverse events were defined as adverse events with 'injection site' phrase in Preferred Term excluding 'injection site nodule'.

Other adverse events

Additional Information

AstraZeneca

Clinical Trial Transparency

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
Publication restrictions are in place

Restriction type: OTHER