Trial Outcomes & Findings for Safety and Efficacy of Exenatide as Monotherapy and Adjunctive Therapy to Oral Antidiabetic Agents in Adolescents With Type 2 Diabetes (NCT NCT00658021)

Last Updated: 2020-12-01

Results Overview

Change from baseline in HbA1c is reported as adjusted least square (LS) mean values at Week 28. Baseline is defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of study medication. A mixed model with repeated measures (MMRM) analysis was performed, excluding measurements after initiation of rescue medication and study drug discontinuation.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

122 participants

Primary outcome timeframe

Baseline (Day 1) and Week 28

Results posted on

2020-12-01

Participant Flow

This study was conducted in adolescents (aged 10 to 17 years inclusive) with type 2 diabetes who were naïve to antidiabetics, or were receiving metformin, an sulfonylurea (SU) or a combination of metformin and an SU in 7 countries (Brazil, India, South Korea, Mexico, Russia, the United States and South Africa) between 30 May 2008 and 01 April 2020.

The study commenced with a 1-week, single-blind, injectable placebo lead-in period before participants were randomized to 1 of 3 treatment groups: exenatide 5 microgram (mcg) twice daily, exenatide 10 mcg twice daily, or placebo twice daily. A total of 122 participants were randomized in this study.

Participant milestones

Participant milestones
Measure	Exenatide 5 mcg Adolescent participants received exenatide 5 mcg subcutaneous (SC) injection twice daily for 28 weeks. In the Safety Follow-up Period, participants with a height difference of at least 5 millimeter (mm) between Day 1 and Week 28 visits returned for study visits every 6 months for up to 3 years after completion of the treatment period.	Exenatide 10 mcg Adolescent participants received exenatide 5 mcg SC injection twice daily for 4 weeks after randomization. At the end of 4 weeks post-randomization, participants received exenatide 10 mcg SC injection twice daily for next 24 weeks. In the Safety Follow-up Period, participants with a height difference of at least 5 mm between Day 1 and Week 28 visits returned for study visits every 6 months for up to 3 years after completion of the treatment period.	Placebo Adolescent participants received placebo matching with exenatide 5 mcg or 10 mcg SC injection twice daily for 28 weeks. In the Safety Follow-up Period, participants with a height difference of at least 5 mm between Day 1 and Week 28 visits returned for study visits every 6 months for up to 3 years after completion of the treatment period.
28-Week Treatment Period STARTED	42	38	42
28-Week Treatment Period Received Treatment	40	38	42
28-Week Treatment Period COMPLETED	31	25	25
28-Week Treatment Period NOT COMPLETED	11	13	17
Long-term Safety Follow-up Period STARTED	7	5	7
Long-term Safety Follow-up Period COMPLETED	7	2	7
Long-term Safety Follow-up Period NOT COMPLETED	0	3	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Exenatide 5 mcg Adolescent participants received exenatide 5 mcg subcutaneous (SC) injection twice daily for 28 weeks. In the Safety Follow-up Period, participants with a height difference of at least 5 millimeter (mm) between Day 1 and Week 28 visits returned for study visits every 6 months for up to 3 years after completion of the treatment period.	Exenatide 10 mcg Adolescent participants received exenatide 5 mcg SC injection twice daily for 4 weeks after randomization. At the end of 4 weeks post-randomization, participants received exenatide 10 mcg SC injection twice daily for next 24 weeks. In the Safety Follow-up Period, participants with a height difference of at least 5 mm between Day 1 and Week 28 visits returned for study visits every 6 months for up to 3 years after completion of the treatment period.	Placebo Adolescent participants received placebo matching with exenatide 5 mcg or 10 mcg SC injection twice daily for 28 weeks. In the Safety Follow-up Period, participants with a height difference of at least 5 mm between Day 1 and Week 28 visits returned for study visits every 6 months for up to 3 years after completion of the treatment period.
28-Week Treatment Period Adverse Event	3	1	0
28-Week Treatment Period Developed study withdrawal criteria	0	2	0
28-Week Treatment Period Protocol Violation	0	2	1
28-Week Treatment Period Withdrawal by Subject	1	1	3
28-Week Treatment Period Physician Decision	1	2	1
28-Week Treatment Period Withdrawal by parent/guardian	1	1	1
28-Week Treatment Period Loss of glucose control	1	1	10
28-Week Treatment Period Other	2	3	1
28-Week Treatment Period Did not receive treatment	2	0	0
Long-term Safety Follow-up Period Withdrawal by Subject	0	1	0
Long-term Safety Follow-up Period Physician Decision	0	2	0

Baseline Characteristics

Safety and Efficacy of Exenatide as Monotherapy and Adjunctive Therapy to Oral Antidiabetic Agents in Adolescents With Type 2 Diabetes

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Exenatide 5 mcg n=42 Participants Adolescent participants received exenatide 5 mcg SC injection twice daily for 28 weeks. In the Safety Follow-up Period, participants with a height difference of at least 5 mm between Day 1 and Week 28 visits returned for study visits every 6 months for up to 3 years after completion of the treatment period.	Exenatide 10 mcg n=38 Participants Adolescent participants received exenatide 5 mcg SC injection twice daily for 4 weeks after randomization. At the end of 4 weeks post-randomization, participants received exenatide 10 mcg SC injection twice daily for next 24 weeks. In the Safety Follow-up Period, participants with a height difference of at least 5 mm between Day 1 and Week 28 visits returned for study visits every 6 months for up to 3 years after completion of the treatment period.	Placebo n=42 Participants Adolescent participants received placebo matching with exenatide 5 mcg or 10 mcg SC injection twice daily for 28 weeks. In the Safety Follow-up Period, participants with a height difference of at least 5 mm between Day 1 and Week 28 visits returned for study visits every 6 months for up to 3 years after completion of the treatment period.	Total n=122 Participants Total of all reporting groups
Age, Continuous	13.7 years STANDARD_DEVIATION 1.94 • n=5 Participants	14.0 years STANDARD_DEVIATION 1.95 • n=7 Participants	14.4 years STANDARD_DEVIATION 1.82 • n=5 Participants	14.0 years STANDARD_DEVIATION 1.91 • n=4 Participants
Sex: Female, Male Female	31 Participants n=5 Participants	22 Participants n=7 Participants	29 Participants n=5 Participants	82 Participants n=4 Participants
Sex: Female, Male Male	11 Participants n=5 Participants	16 Participants n=7 Participants	13 Participants n=5 Participants	40 Participants n=4 Participants
Race/Ethnicity, Customized White	7 Participants n=5 Participants	5 Participants n=7 Participants	13 Participants n=5 Participants	25 Participants n=4 Participants
Race/Ethnicity, Customized Black or African American	14 Participants n=5 Participants	8 Participants n=7 Participants	7 Participants n=5 Participants	29 Participants n=4 Participants
Race/Ethnicity, Customized Asian	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants	10 Participants n=4 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race/Ethnicity, Customized Hispanic	18 Participants n=5 Participants	22 Participants n=7 Participants	17 Participants n=5 Participants	57 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline (Day 1) and Week 28

Population: The Evaluable Analysis Set included all randomized participants who received at least 1 dose of randomized study medication and had a baseline and at least 1 post-baseline HbA1c assessment. For analysis of efficacy, a decision was made with agreement by the European Medicines Agency and the Food and Drug Administration to pool participants from both exenatide groups (Total EBID) and compare this pooled group with placebo.

Outcome measures

Outcome measures
Measure	Total Exenatide Twice Daily (EBID) n=78 Participants Efficacy data from participants from both exenatide groups (Total EBID) was pooled for comparison with placebo. Adolescent participants received exenatide 5 mcg SC injection twice daily for 28 weeks; or Adolescent participants received exenatide 5 mcg SC injection twice daily for 4 weeks after randomization. At the end of 4 weeks post-randomization, participants received exenatide 10 mcg SC injection twice daily for next 24 weeks.	Placebo n=42 Participants Adolescent participants received placebo matching with exenatide 5 mcg or 10 mcg SC injection twice daily for 28 weeks. In the Safety Follow-up Period, participants with a height difference of at least 5 mm between Day 1 and Week 28 visits returned for study visits every 6 months for up to 3 years after completion of the treatment period.	Placebo Adolescent participants received placebo matching with exenatide 5 mcg or 10 mcg SC injection twice daily for 28 weeks. In the Safety Follow-up Period, participants with a height difference of at least 5 mm between Day 1 and Week 28 visits returned for study visits every 6 months for up to 3 years after completion of the treatment period.
Adjusted Change From Baseline in Glycated Hemoglobin A1c (HbA1c) at Week 28	0.11 percentage (%HbA1c) Standard Error 0.215	0.38 percentage (%HbA1c) Standard Error 0.293	—

PRIMARY outcome

Timeframe: From 1 day after the Week 28/ED visit to 3 years after Week 28/ED visit.

Population: The Safety Follow-up Analysis Set included all participants who had at least 1 safety follow-up period assessment visit.

Post-treatment adverse events (AEs) were defined as AEs that started or worsened during the off-treatment period (Safety Follow-up Period), which was defined as the day after the Week 28/early discontinuation (ED) visit to the date of completion of the Safety Follow-up Period. The AESIs recorded were as follows: hematological malignancies, thyroid neoplasms, pancreas neoplasms, aplastic anemia, pancreatitis, pregnancy and pregnancy outcomes (including congenital anomalies).

Outcome measures

Outcome measures
Measure	Total Exenatide Twice Daily (EBID) n=7 Participants Efficacy data from participants from both exenatide groups (Total EBID) was pooled for comparison with placebo. Adolescent participants received exenatide 5 mcg SC injection twice daily for 28 weeks; or Adolescent participants received exenatide 5 mcg SC injection twice daily for 4 weeks after randomization. At the end of 4 weeks post-randomization, participants received exenatide 10 mcg SC injection twice daily for next 24 weeks.	Placebo n=5 Participants Adolescent participants received placebo matching with exenatide 5 mcg or 10 mcg SC injection twice daily for 28 weeks. In the Safety Follow-up Period, participants with a height difference of at least 5 mm between Day 1 and Week 28 visits returned for study visits every 6 months for up to 3 years after completion of the treatment period.	Placebo n=7 Participants Adolescent participants received placebo matching with exenatide 5 mcg or 10 mcg SC injection twice daily for 28 weeks. In the Safety Follow-up Period, participants with a height difference of at least 5 mm between Day 1 and Week 28 visits returned for study visits every 6 months for up to 3 years after completion of the treatment period.
Number of Participants With Post-Treatment Adverse Events of Special Interest (AESI) During Safety Follow-up Period	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Weeks 0, 4, 12, 20 and 28

The percentage of participants achieving HbA1c goals of \< 7%, \<= 6.5%, and \< 6.5% through Week 28 were compared between treatments using the Cochran-Mantel-Haenszel (CMH) procedure, in which screening HbA1c strata and background diabetes therapy strata served as the stratification factors. The CMH analysis excluded measurements after initiation of rescue medication and study drug discontinuation with missing data treated as non-responder.

Outcome measures

Outcome measures
Measure	Total Exenatide Twice Daily (EBID) n=78 Participants Efficacy data from participants from both exenatide groups (Total EBID) was pooled for comparison with placebo. Adolescent participants received exenatide 5 mcg SC injection twice daily for 28 weeks; or Adolescent participants received exenatide 5 mcg SC injection twice daily for 4 weeks after randomization. At the end of 4 weeks post-randomization, participants received exenatide 10 mcg SC injection twice daily for next 24 weeks.	Placebo n=42 Participants Adolescent participants received placebo matching with exenatide 5 mcg or 10 mcg SC injection twice daily for 28 weeks. In the Safety Follow-up Period, participants with a height difference of at least 5 mm between Day 1 and Week 28 visits returned for study visits every 6 months for up to 3 years after completion of the treatment period.	Placebo Adolescent participants received placebo matching with exenatide 5 mcg or 10 mcg SC injection twice daily for 28 weeks. In the Safety Follow-up Period, participants with a height difference of at least 5 mm between Day 1 and Week 28 visits returned for study visits every 6 months for up to 3 years after completion of the treatment period.
Percentage of Participants Achieving HbA1c Goals of < 7%, <= 6.5%, and < 6.5% Through Week 28 HbA1c < 7%: Week 0	37.2 percentage of participants Interval 26.5 to 47.9	38.1 percentage of participants Interval 23.4 to 52.8	—
Percentage of Participants Achieving HbA1c Goals of < 7%, <= 6.5%, and < 6.5% Through Week 28 HbA1c < 7%: Week 4	44.9 percentage of participants Interval 33.8 to 55.9	42.9 percentage of participants Interval 27.9 to 57.8	—
Percentage of Participants Achieving HbA1c Goals of < 7%, <= 6.5%, and < 6.5% Through Week 28 HbA1c < 7%: Week 20	35.9 percentage of participants Interval 25.3 to 46.5	35.7 percentage of participants Interval 21.2 to 50.2	—
Percentage of Participants Achieving HbA1c Goals of < 7%, <= 6.5%, and < 6.5% Through Week 28 HbA1c < 7%: Week 28	33.3 percentage of participants Interval 22.9 to 43.8	28.6 percentage of participants Interval 14.9 to 42.2	—
Percentage of Participants Achieving HbA1c Goals of < 7%, <= 6.5%, and < 6.5% Through Week 28 HbA1c <=6.5%: Week 0	17.9 percentage of participants Interval 9.4 to 26.5	16.7 percentage of participants Interval 5.4 to 27.9	—
Percentage of Participants Achieving HbA1c Goals of < 7%, <= 6.5%, and < 6.5% Through Week 28 HbA1c <=6.5%: Week 4	29.5 percentage of participants Interval 19.4 to 39.6	23.8 percentage of participants Interval 10.9 to 36.7	—
Percentage of Participants Achieving HbA1c Goals of < 7%, <= 6.5%, and < 6.5% Through Week 28 HbA1c <=6.5%: Week 12	33.3 percentage of participants Interval 22.9 to 43.8	23.8 percentage of participants Interval 10.9 to 36.7	—
Percentage of Participants Achieving HbA1c Goals of < 7%, <= 6.5%, and < 6.5% Through Week 28 HbA1c <=6.5%: Week 20	24.4 percentage of participants Interval 14.8 to 33.9	19.0 percentage of participants Interval 7.2 to 30.9	—
Percentage of Participants Achieving HbA1c Goals of < 7%, <= 6.5%, and < 6.5% Through Week 28 HbA1c <=6.5%: Week 28	23.1 percentage of participants Interval 13.7 to 32.4	19.0 percentage of participants Interval 7.2 to 30.9	—
Percentage of Participants Achieving HbA1c Goals of < 7%, <= 6.5%, and < 6.5% Through Week 28 HbA1c <6.5%: Week 0	15.4 percentage of participants Interval 7.4 to 23.4	7.1 percentage of participants Interval 0.0 to 14.9	—
Percentage of Participants Achieving HbA1c Goals of < 7%, <= 6.5%, and < 6.5% Through Week 28 HbA1c <6.5%: Week 20	21.8 percentage of participants Interval 12.6 to 31.0	19.0 percentage of participants Interval 7.2 to 30.9	—
Percentage of Participants Achieving HbA1c Goals of < 7%, <= 6.5%, and < 6.5% Through Week 28 HbA1c <6.5%: Week 28	23.1 percentage of participants Interval 13.7 to 32.4	14.3 percentage of participants Interval 3.7 to 24.9	—
Percentage of Participants Achieving HbA1c Goals of < 7%, <= 6.5%, and < 6.5% Through Week 28 HbA1c < 7%: Week 12	43.6 percentage of participants Interval 32.6 to 54.6	33.3 percentage of participants Interval 19.1 to 47.6	—
Percentage of Participants Achieving HbA1c Goals of < 7%, <= 6.5%, and < 6.5% Through Week 28 HbA1c <6.5%: Week 4	26.9 percentage of participants Interval 17.1 to 36.8	21.4 percentage of participants Interval 9.0 to 33.8	—
Percentage of Participants Achieving HbA1c Goals of < 7%, <= 6.5%, and < 6.5% Through Week 28 HbA1c <6.5%: Week 12	30.8 percentage of participants Interval 20.5 to 41.0	19.0 percentage of participants Interval 7.2 to 30.9	—

SECONDARY outcome

Timeframe: Baseline (Day 1) up to Week 28

Population: The Full Analysis Set included all randomized participants who received at least 1 dose of randomized study medication. For analysis of efficacy, a decision was made with agreement by the European Medicines Agency and the Food and Drug Administration to pool participants from both exenatide groups (Total EBID) and compare this pooled group with placebo.

Change from baseline in body weight is reported as adjusted LS mean values at Weeks 4, 12, 20 and 28. Baseline is defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of study medication. A MMRM analysis was performed, excluding measurements after initiation of rescue medication and study drug discontinuation.

Outcome measures

Outcome measures
Measure	Total Exenatide Twice Daily (EBID) n=78 Participants Efficacy data from participants from both exenatide groups (Total EBID) was pooled for comparison with placebo. Adolescent participants received exenatide 5 mcg SC injection twice daily for 28 weeks; or Adolescent participants received exenatide 5 mcg SC injection twice daily for 4 weeks after randomization. At the end of 4 weeks post-randomization, participants received exenatide 10 mcg SC injection twice daily for next 24 weeks.	Placebo n=42 Participants Adolescent participants received placebo matching with exenatide 5 mcg or 10 mcg SC injection twice daily for 28 weeks. In the Safety Follow-up Period, participants with a height difference of at least 5 mm between Day 1 and Week 28 visits returned for study visits every 6 months for up to 3 years after completion of the treatment period.	Placebo Adolescent participants received placebo matching with exenatide 5 mcg or 10 mcg SC injection twice daily for 28 weeks. In the Safety Follow-up Period, participants with a height difference of at least 5 mm between Day 1 and Week 28 visits returned for study visits every 6 months for up to 3 years after completion of the treatment period.
Adjusted Change From Baseline in Body Weight Through Week 28 Week 4	-0.89 kilogram Standard Error 0.196	0.04 kilogram Standard Error 0.260	—
Adjusted Change From Baseline in Body Weight Through Week 28 Week 12	-1.09 kilogram Standard Error 0.401	-0.42 kilogram Standard Error 0.534	—
Adjusted Change From Baseline in Body Weight Through Week 28 Week 20	-0.71 kilogram Standard Error 0.559	-0.33 kilogram Standard Error 0.755	—
Adjusted Change From Baseline in Body Weight Through Week 28 Week 28	-0.81 kilogram Standard Error 0.632	-0.36 kilogram Standard Error 0.857	—

SECONDARY outcome

Timeframe: Baseline (Day 1) and Week 28

Change from baseline in FSG is reported as adjusted LS mean values at Week 28. Baseline is defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of study medication. An analysis of covariance (ANCOVA) analysis was performed, excluding measurements after initiation of rescue medication and study drug discontinuation.

Outcome measures

Outcome measures
Measure	Total Exenatide Twice Daily (EBID) n=78 Participants Efficacy data from participants from both exenatide groups (Total EBID) was pooled for comparison with placebo. Adolescent participants received exenatide 5 mcg SC injection twice daily for 28 weeks; or Adolescent participants received exenatide 5 mcg SC injection twice daily for 4 weeks after randomization. At the end of 4 weeks post-randomization, participants received exenatide 10 mcg SC injection twice daily for next 24 weeks.	Placebo n=42 Participants Adolescent participants received placebo matching with exenatide 5 mcg or 10 mcg SC injection twice daily for 28 weeks. In the Safety Follow-up Period, participants with a height difference of at least 5 mm between Day 1 and Week 28 visits returned for study visits every 6 months for up to 3 years after completion of the treatment period.	Placebo Adolescent participants received placebo matching with exenatide 5 mcg or 10 mcg SC injection twice daily for 28 weeks. In the Safety Follow-up Period, participants with a height difference of at least 5 mm between Day 1 and Week 28 visits returned for study visits every 6 months for up to 3 years after completion of the treatment period.
Adjusted Change From Baseline in Fasting Serum Glucose (FSG) at Week 28	0.791 millimoles per liter (mmol/L) Standard Error 0.4010	1.072 millimoles per liter (mmol/L) Standard Error 0.5466	—

SECONDARY outcome

Timeframe: Pre-meal and 2 hours post-meal on Baseline (Day 1) and Week 28

Change from baseline in SMBG measurements are reported as adjusted LS mean values at Week 28. SMBG measurements were taken before (pre-prandial) and 2 hours after (post-prandial) the 2 main meals of the day on 3 separate days during the week before baseline (Day 1) and Week 28. Post-prandial excursions were calculated as the difference between the pre-prandial and post-prandial blood glucose concentrations (post-prandial - pre-prandial) and averaged (mean) over the 2 main meals over the 3 separate days in each period. Baseline is defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of study medication. An ANCOVA analysis was performed, excluding measurements after initiation of rescue medication and study drug discontinuation.

Outcome measures

Outcome measures
Measure	Total Exenatide Twice Daily (EBID) n=78 Participants Efficacy data from participants from both exenatide groups (Total EBID) was pooled for comparison with placebo. Adolescent participants received exenatide 5 mcg SC injection twice daily for 28 weeks; or Adolescent participants received exenatide 5 mcg SC injection twice daily for 4 weeks after randomization. At the end of 4 weeks post-randomization, participants received exenatide 10 mcg SC injection twice daily for next 24 weeks.	Placebo n=42 Participants Adolescent participants received placebo matching with exenatide 5 mcg or 10 mcg SC injection twice daily for 28 weeks. In the Safety Follow-up Period, participants with a height difference of at least 5 mm between Day 1 and Week 28 visits returned for study visits every 6 months for up to 3 years after completion of the treatment period.	Placebo Adolescent participants received placebo matching with exenatide 5 mcg or 10 mcg SC injection twice daily for 28 weeks. In the Safety Follow-up Period, participants with a height difference of at least 5 mm between Day 1 and Week 28 visits returned for study visits every 6 months for up to 3 years after completion of the treatment period.
Adjusted Change From Baseline in Self-Monitored Blood Glucose (SMBG) at Week 28 Pre-meal SMBG	-0.699 mmol/L Standard Error 0.2709	-0.888 mmol/L Standard Error 0.4511	—
Adjusted Change From Baseline in Self-Monitored Blood Glucose (SMBG) at Week 28 Post-meal SMBG	-1.029 mmol/L Standard Error 0.2722	-1.542 mmol/L Standard Error 0.4503	—
Adjusted Change From Baseline in Self-Monitored Blood Glucose (SMBG) at Week 28 Post-prandial excursion SMBG	-0.181 mmol/L Standard Error 0.2107	-0.391 mmol/L Standard Error 0.3418	—
Adjusted Change From Baseline in Self-Monitored Blood Glucose (SMBG) at Week 28 Overall SMBG	-0.877 mmol/L Standard Error 0.2468	-1.193 mmol/L Standard Error 0.4117	—

SECONDARY outcome

Timeframe: Baseline (Day 1) and Week 28

Change from baseline in fasting serum insulin is reported as adjusted LS mean values at Week 28. Baseline is defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of study medication. An ANCOVA analysis was performed, excluding measurements after initiation of rescue medication and study drug discontinuation.

Outcome measures

Outcome measures
Measure	Total Exenatide Twice Daily (EBID) n=78 Participants Efficacy data from participants from both exenatide groups (Total EBID) was pooled for comparison with placebo. Adolescent participants received exenatide 5 mcg SC injection twice daily for 28 weeks; or Adolescent participants received exenatide 5 mcg SC injection twice daily for 4 weeks after randomization. At the end of 4 weeks post-randomization, participants received exenatide 10 mcg SC injection twice daily for next 24 weeks.	Placebo n=42 Participants Adolescent participants received placebo matching with exenatide 5 mcg or 10 mcg SC injection twice daily for 28 weeks. In the Safety Follow-up Period, participants with a height difference of at least 5 mm between Day 1 and Week 28 visits returned for study visits every 6 months for up to 3 years after completion of the treatment period.	Placebo Adolescent participants received placebo matching with exenatide 5 mcg or 10 mcg SC injection twice daily for 28 weeks. In the Safety Follow-up Period, participants with a height difference of at least 5 mm between Day 1 and Week 28 visits returned for study visits every 6 months for up to 3 years after completion of the treatment period.
Adjusted Change From Baseline in Fasting Serum Insulin at Week 28	1.67 picomoles per liter Standard Error 25.323	12.49 picomoles per liter Standard Error 34.825	—

SECONDARY outcome

Timeframe: Baseline (Day 1) and Week 28

Change from baseline in HOMA-B and HOMA-S are reported as adjusted LS mean values at Week 28. Baseline is defined as the last non-missing assessment (scheduled or unscheduled) on or prior to the first dose of study medication. An ANCOVA analysis was performed, excluding measurements after initiation of rescue medication and study drug discontinuation.

Outcome measures

Outcome measures
Measure	Total Exenatide Twice Daily (EBID) n=78 Participants Efficacy data from participants from both exenatide groups (Total EBID) was pooled for comparison with placebo. Adolescent participants received exenatide 5 mcg SC injection twice daily for 28 weeks; or Adolescent participants received exenatide 5 mcg SC injection twice daily for 4 weeks after randomization. At the end of 4 weeks post-randomization, participants received exenatide 10 mcg SC injection twice daily for next 24 weeks.	Placebo n=42 Participants Adolescent participants received placebo matching with exenatide 5 mcg or 10 mcg SC injection twice daily for 28 weeks. In the Safety Follow-up Period, participants with a height difference of at least 5 mm between Day 1 and Week 28 visits returned for study visits every 6 months for up to 3 years after completion of the treatment period.	Placebo Adolescent participants received placebo matching with exenatide 5 mcg or 10 mcg SC injection twice daily for 28 weeks. In the Safety Follow-up Period, participants with a height difference of at least 5 mm between Day 1 and Week 28 visits returned for study visits every 6 months for up to 3 years after completion of the treatment period.
Adjusted Change From Baseline in Homeostasis Model Assessments - Beta-Cell Function (HOMA-B) and Insulin Sensitivity (HOMA-S) at Week 28 HOMA-S	-3.18 percentage (%HOMA-B and %HOMA-S) Standard Error 2.172	-2.90 percentage (%HOMA-B and %HOMA-S) Standard Error 3.117	—
Adjusted Change From Baseline in Homeostasis Model Assessments - Beta-Cell Function (HOMA-B) and Insulin Sensitivity (HOMA-S) at Week 28 HOMA-B	-25.93 percentage (%HOMA-B and %HOMA-S) Standard Error 10.404	-22.10 percentage (%HOMA-B and %HOMA-S) Standard Error 14.885	—

SECONDARY outcome

Timeframe: Weeks 2, 4, 8, 12, 16, 20, 24 and 28

Participants were discontinued from the study due to failure to maintain glycemic control if either discontinuation reason on summary case report form was "Loss of glucose control" or AE with lower level Medical Dictionary for Regulatory Activities (MedDRA) term "Loss of control of blood sugar" or "Hyperglycaemia" leading to study drug discontinuation, using MedDRA Version 23.0.

Outcome measures

Outcome measures
Measure	Total Exenatide Twice Daily (EBID) n=78 Participants Efficacy data from participants from both exenatide groups (Total EBID) was pooled for comparison with placebo. Adolescent participants received exenatide 5 mcg SC injection twice daily for 28 weeks; or Adolescent participants received exenatide 5 mcg SC injection twice daily for 4 weeks after randomization. At the end of 4 weeks post-randomization, participants received exenatide 10 mcg SC injection twice daily for next 24 weeks.	Placebo n=42 Participants Adolescent participants received placebo matching with exenatide 5 mcg or 10 mcg SC injection twice daily for 28 weeks. In the Safety Follow-up Period, participants with a height difference of at least 5 mm between Day 1 and Week 28 visits returned for study visits every 6 months for up to 3 years after completion of the treatment period.	Placebo Adolescent participants received placebo matching with exenatide 5 mcg or 10 mcg SC injection twice daily for 28 weeks. In the Safety Follow-up Period, participants with a height difference of at least 5 mm between Day 1 and Week 28 visits returned for study visits every 6 months for up to 3 years after completion of the treatment period.
Percentage of Participants Discontinuing the Study Due to Failure to Maintain Glycemic Control Through Week 28 Week 2	0 percentage of participants	0 percentage of participants	—
Percentage of Participants Discontinuing the Study Due to Failure to Maintain Glycemic Control Through Week 28 Week 12	1.4 percentage of participants	5.0 percentage of participants	—
Percentage of Participants Discontinuing the Study Due to Failure to Maintain Glycemic Control Through Week 28 Week 16	1.4 percentage of participants	0 percentage of participants	—
Percentage of Participants Discontinuing the Study Due to Failure to Maintain Glycemic Control Through Week 28 Week 20	0 percentage of participants	14.7 percentage of participants	—
Percentage of Participants Discontinuing the Study Due to Failure to Maintain Glycemic Control Through Week 28 Week 24	0 percentage of participants	6.9 percentage of participants	—
Percentage of Participants Discontinuing the Study Due to Failure to Maintain Glycemic Control Through Week 28 Week 4	0 percentage of participants	2.4 percentage of participants	—
Percentage of Participants Discontinuing the Study Due to Failure to Maintain Glycemic Control Through Week 28 Week 8	0 percentage of participants	0 percentage of participants	—
Percentage of Participants Discontinuing the Study Due to Failure to Maintain Glycemic Control Through Week 28 Week 28	1.6 percentage of participants	0 percentage of participants	—

Adverse Events

Exenatide 5 mcg

Serious events: 3 serious events

Other events: 26 other events

Deaths: 0 deaths

Exenatide 10 mcg

Serious events: 1 serious events

Other events: 24 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 23 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Exenatide 5 mcg n=41 participants at risk Adolescent participants received exenatide 5 mcg SC injection twice daily for 28 weeks.	Exenatide 10 mcg n=37 participants at risk Adolescent participants received exenatide 5 mcg SC injection twice daily for 4 weeks after randomization. At the end of 4 weeks post-randomization, participants received exenatide 10 mcg SC injection twice daily for next 24 weeks.	Placebo n=42 participants at risk Adolescent participants received placebo matching with exenatide 5 mcg or 10 mcg SC injection twice daily for 28 weeks.
Infections and infestations Cellulitis	2.4% 1/41 • Number of events 1 • Serious AEs: From first dose of study drug (Day 1) up to 30 days after last dose of study drug, approximately 32 weeks. Non-serious AEs: From first dose of study drug (Day 1) up to 1 day after last dose of study drug, approximately 28 weeks. The Safety Analysis Set included all participants who received at least 1 dose of randomized study medication. Treatment-emergent AEs (TEAEs) are reported. A TEAE was defined as an AE starting (or worsening) after the first dose of randomized study medication through the end of treatment + 1 day for non-serious AEs or + 30 days for serious AEs.	0.00% 0/37 • Serious AEs: From first dose of study drug (Day 1) up to 30 days after last dose of study drug, approximately 32 weeks. Non-serious AEs: From first dose of study drug (Day 1) up to 1 day after last dose of study drug, approximately 28 weeks. The Safety Analysis Set included all participants who received at least 1 dose of randomized study medication. Treatment-emergent AEs (TEAEs) are reported. A TEAE was defined as an AE starting (or worsening) after the first dose of randomized study medication through the end of treatment + 1 day for non-serious AEs or + 30 days for serious AEs.	0.00% 0/42 • Serious AEs: From first dose of study drug (Day 1) up to 30 days after last dose of study drug, approximately 32 weeks. Non-serious AEs: From first dose of study drug (Day 1) up to 1 day after last dose of study drug, approximately 28 weeks. The Safety Analysis Set included all participants who received at least 1 dose of randomized study medication. Treatment-emergent AEs (TEAEs) are reported. A TEAE was defined as an AE starting (or worsening) after the first dose of randomized study medication through the end of treatment + 1 day for non-serious AEs or + 30 days for serious AEs.
Infections and infestations Gastroenteritis	2.4% 1/41 • Number of events 1 • Serious AEs: From first dose of study drug (Day 1) up to 30 days after last dose of study drug, approximately 32 weeks. Non-serious AEs: From first dose of study drug (Day 1) up to 1 day after last dose of study drug, approximately 28 weeks. The Safety Analysis Set included all participants who received at least 1 dose of randomized study medication. Treatment-emergent AEs (TEAEs) are reported. A TEAE was defined as an AE starting (or worsening) after the first dose of randomized study medication through the end of treatment + 1 day for non-serious AEs or + 30 days for serious AEs.	0.00% 0/37 • Serious AEs: From first dose of study drug (Day 1) up to 30 days after last dose of study drug, approximately 32 weeks. Non-serious AEs: From first dose of study drug (Day 1) up to 1 day after last dose of study drug, approximately 28 weeks. The Safety Analysis Set included all participants who received at least 1 dose of randomized study medication. Treatment-emergent AEs (TEAEs) are reported. A TEAE was defined as an AE starting (or worsening) after the first dose of randomized study medication through the end of treatment + 1 day for non-serious AEs or + 30 days for serious AEs.	2.4% 1/42 • Number of events 1 • Serious AEs: From first dose of study drug (Day 1) up to 30 days after last dose of study drug, approximately 32 weeks. Non-serious AEs: From first dose of study drug (Day 1) up to 1 day after last dose of study drug, approximately 28 weeks. The Safety Analysis Set included all participants who received at least 1 dose of randomized study medication. Treatment-emergent AEs (TEAEs) are reported. A TEAE was defined as an AE starting (or worsening) after the first dose of randomized study medication through the end of treatment + 1 day for non-serious AEs or + 30 days for serious AEs.
Infections and infestations Gastroenteritis viral	0.00% 0/41 • Serious AEs: From first dose of study drug (Day 1) up to 30 days after last dose of study drug, approximately 32 weeks. Non-serious AEs: From first dose of study drug (Day 1) up to 1 day after last dose of study drug, approximately 28 weeks. The Safety Analysis Set included all participants who received at least 1 dose of randomized study medication. Treatment-emergent AEs (TEAEs) are reported. A TEAE was defined as an AE starting (or worsening) after the first dose of randomized study medication through the end of treatment + 1 day for non-serious AEs or + 30 days for serious AEs.	0.00% 0/37 • Serious AEs: From first dose of study drug (Day 1) up to 30 days after last dose of study drug, approximately 32 weeks. Non-serious AEs: From first dose of study drug (Day 1) up to 1 day after last dose of study drug, approximately 28 weeks. The Safety Analysis Set included all participants who received at least 1 dose of randomized study medication. Treatment-emergent AEs (TEAEs) are reported. A TEAE was defined as an AE starting (or worsening) after the first dose of randomized study medication through the end of treatment + 1 day for non-serious AEs or + 30 days for serious AEs.	2.4% 1/42 • Number of events 1 • Serious AEs: From first dose of study drug (Day 1) up to 30 days after last dose of study drug, approximately 32 weeks. Non-serious AEs: From first dose of study drug (Day 1) up to 1 day after last dose of study drug, approximately 28 weeks. The Safety Analysis Set included all participants who received at least 1 dose of randomized study medication. Treatment-emergent AEs (TEAEs) are reported. A TEAE was defined as an AE starting (or worsening) after the first dose of randomized study medication through the end of treatment + 1 day for non-serious AEs or + 30 days for serious AEs.
Infections and infestations Staphylococcal abscess	2.4% 1/41 • Number of events 1 • Serious AEs: From first dose of study drug (Day 1) up to 30 days after last dose of study drug, approximately 32 weeks. Non-serious AEs: From first dose of study drug (Day 1) up to 1 day after last dose of study drug, approximately 28 weeks. The Safety Analysis Set included all participants who received at least 1 dose of randomized study medication. Treatment-emergent AEs (TEAEs) are reported. A TEAE was defined as an AE starting (or worsening) after the first dose of randomized study medication through the end of treatment + 1 day for non-serious AEs or + 30 days for serious AEs.	0.00% 0/37 • Serious AEs: From first dose of study drug (Day 1) up to 30 days after last dose of study drug, approximately 32 weeks. Non-serious AEs: From first dose of study drug (Day 1) up to 1 day after last dose of study drug, approximately 28 weeks. The Safety Analysis Set included all participants who received at least 1 dose of randomized study medication. Treatment-emergent AEs (TEAEs) are reported. A TEAE was defined as an AE starting (or worsening) after the first dose of randomized study medication through the end of treatment + 1 day for non-serious AEs or + 30 days for serious AEs.	0.00% 0/42 • Serious AEs: From first dose of study drug (Day 1) up to 30 days after last dose of study drug, approximately 32 weeks. Non-serious AEs: From first dose of study drug (Day 1) up to 1 day after last dose of study drug, approximately 28 weeks. The Safety Analysis Set included all participants who received at least 1 dose of randomized study medication. Treatment-emergent AEs (TEAEs) are reported. A TEAE was defined as an AE starting (or worsening) after the first dose of randomized study medication through the end of treatment + 1 day for non-serious AEs or + 30 days for serious AEs.
Pregnancy, puerperium and perinatal conditions Pregnancy	0.00% 0/41 • Serious AEs: From first dose of study drug (Day 1) up to 30 days after last dose of study drug, approximately 32 weeks. Non-serious AEs: From first dose of study drug (Day 1) up to 1 day after last dose of study drug, approximately 28 weeks. The Safety Analysis Set included all participants who received at least 1 dose of randomized study medication. Treatment-emergent AEs (TEAEs) are reported. A TEAE was defined as an AE starting (or worsening) after the first dose of randomized study medication through the end of treatment + 1 day for non-serious AEs or + 30 days for serious AEs.	2.7% 1/37 • Number of events 1 • Serious AEs: From first dose of study drug (Day 1) up to 30 days after last dose of study drug, approximately 32 weeks. Non-serious AEs: From first dose of study drug (Day 1) up to 1 day after last dose of study drug, approximately 28 weeks. The Safety Analysis Set included all participants who received at least 1 dose of randomized study medication. Treatment-emergent AEs (TEAEs) are reported. A TEAE was defined as an AE starting (or worsening) after the first dose of randomized study medication through the end of treatment + 1 day for non-serious AEs or + 30 days for serious AEs.	0.00% 0/42 • Serious AEs: From first dose of study drug (Day 1) up to 30 days after last dose of study drug, approximately 32 weeks. Non-serious AEs: From first dose of study drug (Day 1) up to 1 day after last dose of study drug, approximately 28 weeks. The Safety Analysis Set included all participants who received at least 1 dose of randomized study medication. Treatment-emergent AEs (TEAEs) are reported. A TEAE was defined as an AE starting (or worsening) after the first dose of randomized study medication through the end of treatment + 1 day for non-serious AEs or + 30 days for serious AEs.
Psychiatric disorders Intentional self-injury	2.4% 1/41 • Number of events 1 • Serious AEs: From first dose of study drug (Day 1) up to 30 days after last dose of study drug, approximately 32 weeks. Non-serious AEs: From first dose of study drug (Day 1) up to 1 day after last dose of study drug, approximately 28 weeks. The Safety Analysis Set included all participants who received at least 1 dose of randomized study medication. Treatment-emergent AEs (TEAEs) are reported. A TEAE was defined as an AE starting (or worsening) after the first dose of randomized study medication through the end of treatment + 1 day for non-serious AEs or + 30 days for serious AEs.	0.00% 0/37 • Serious AEs: From first dose of study drug (Day 1) up to 30 days after last dose of study drug, approximately 32 weeks. Non-serious AEs: From first dose of study drug (Day 1) up to 1 day after last dose of study drug, approximately 28 weeks. The Safety Analysis Set included all participants who received at least 1 dose of randomized study medication. Treatment-emergent AEs (TEAEs) are reported. A TEAE was defined as an AE starting (or worsening) after the first dose of randomized study medication through the end of treatment + 1 day for non-serious AEs or + 30 days for serious AEs.	0.00% 0/42 • Serious AEs: From first dose of study drug (Day 1) up to 30 days after last dose of study drug, approximately 32 weeks. Non-serious AEs: From first dose of study drug (Day 1) up to 1 day after last dose of study drug, approximately 28 weeks. The Safety Analysis Set included all participants who received at least 1 dose of randomized study medication. Treatment-emergent AEs (TEAEs) are reported. A TEAE was defined as an AE starting (or worsening) after the first dose of randomized study medication through the end of treatment + 1 day for non-serious AEs or + 30 days for serious AEs.

Other adverse events

Additional Information

Global Clinical Lead

AstraZeneca

Phone: 1-877-240-9479

Email: [email protected]

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Principal investigator is a sponsor employee
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