Trial Outcomes & Findings for Safety and Tolerability Study of MEDI0382 in Japanese Preobese or Obese Subjects With Type 2 Diabetes (NCT NCT03645421)

Last Updated: 2019-12-23

Results Overview

Twenty four-hour heart rate was determined using an ambulatory blood pressure monitoring (ABPM) device, and the mean change from baseline in the 24-hour heart rate is presented for Days 20 and 48.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

61 participants

Primary outcome timeframe

Baseline (Day -1) and Days 20 and 48.

Results posted on

2019-12-23

Participant Flow

Preobese/obese Japanese adults with Type 2 diabetes mellitus (T2DM) were recruited to this Phase IIa randomised, parallel-group, placebo-controlled, double-blind, study at 5 centres in Japan. The first patient started in August 2018 and the last patient completed in January 2019.

Patients with an early stage of T2DM who had inadequate blood glucose control, defined as glycated haemoglobin (HbA1c) between 7.0% and 10.5%, and who were treated with diet and exercise were enrolled. A body mass index of 24 to 40 kg/m2 was also a requirement. Patients with acutely decompensated blood glucose control were excluded.

Participant milestones

Participant milestones
Measure	Placebo Patients were randomised to receive MEDI0382 matched placebo for 48 days.	MEDI0382 100 mcg Patients were randomised to receive 100 micrograms (mcg) MEDI0382 per day by subcutaneous (SC) injection, titrated as follows: 50 mcg/day for 5 days and then 100 mcg/day for 43 days.	MEDI0382 200 mcg Patients were randomised to receive 200 mcg MEDI0382 per day by SC injection, titrated as follows: 50 mcg/day for 5 days, 100 mcg/day for 7 days and then 200 mcg/day for 36 days.	MEDI0382 300 mcg Patients were randomised to receive 300 mcg MEDI0382 per day by SC injection, titrated as follows: 50 mcg/day for 5 days, 100 mcg/day for 7 days, 200 mcg/day for 7 days and then 300 mcg/day for 29 days.
Overall Study STARTED	16	15	15	15
Overall Study Received Investigational Product (IP)	16	15	15	15
Overall Study COMPLETED	16	15	10	11
Overall Study NOT COMPLETED	0	0	5	4

Reasons for withdrawal

Reasons for withdrawal
Measure	MEDI0382 200 mcg Patients were randomised to receive 200 mcg MEDI0382 per day by SC injection, titrated as follows: 50 mcg/day for 5 days, 100 mcg/day for 7 days and then 200 mcg/day for 36 days.	MEDI0382 300 mcg Patients were randomised to receive 300 mcg MEDI0382 per day by SC injection, titrated as follows: 50 mcg/day for 5 days, 100 mcg/day for 7 days, 200 mcg/day for 7 days and then 300 mcg/day for 29 days.
Overall Study Adverse Event	4	1
Overall Study Withdrawal by patient	0	3
Overall Study Study specific withdrawal criteria	1	0

Baseline Characteristics

Safety and Tolerability Study of MEDI0382 in Japanese Preobese or Obese Subjects With Type 2 Diabetes

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=16 Participants Patients were randomised to receive MEDI0382 matched placebo for 48 days.	MEDI0382 100 mcg n=15 Participants Patients were randomised to receive 100 mcg MEDI0382 per day by SC injection, titrated as follows: 50 mcg/day for 5 days and then 100 mcg/day for 43 days.	MEDI0382 200 mcg n=15 Participants Patients were randomised to receive 200 mcg MEDI0382 per day by SC injection, titrated as follows: 50 mcg/day for 5 days, 100 mcg/day for 7 days and then 200 mcg/day for 36 days.	MEDI0382 300 mcg n=15 Participants Patients were randomised to receive 300 mcg MEDI0382 per day by SC injection, titrated as follows: 50 mcg/day for 5 days, 100 mcg/day for 7 days, 200 mcg/day for 7 days and then 300 mcg/day for 29 days.	Total n=61 Participants Total of all reporting groups
Age, Continuous	60.0 years STANDARD_DEVIATION 8.6 • n=5 Participants	56.7 years STANDARD_DEVIATION 10.7 • n=7 Participants	58.7 years STANDARD_DEVIATION 11.3 • n=5 Participants	57.5 years STANDARD_DEVIATION 9.2 • n=4 Participants	58.2 years STANDARD_DEVIATION 9.8 • n=21 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	7 Participants n=7 Participants	2 Participants n=5 Participants	2 Participants n=4 Participants	14 Participants n=21 Participants
Sex: Female, Male Male	13 Participants n=5 Participants	8 Participants n=7 Participants	13 Participants n=5 Participants	13 Participants n=4 Participants	47 Participants n=21 Participants
Race/Ethnicity, Customized Asian	16 Participants n=5 Participants	15 Participants n=7 Participants	15 Participants n=5 Participants	15 Participants n=4 Participants	61 Participants n=21 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	16 Participants n=5 Participants	15 Participants n=7 Participants	15 Participants n=5 Participants	15 Participants n=4 Participants	61 Participants n=21 Participants

PRIMARY outcome

Timeframe: Baseline (Day -1) and Days 20 and 48.

Population: The Safety Analysis Set included all randomised patients who received at least 1 dose of IP, analysed according to the treatment received. Patients with data available at each timepoint are presented.

Twenty four-hour heart rate was determined using an ambulatory blood pressure monitoring (ABPM) device, and the mean change from baseline in the 24-hour heart rate is presented for Days 20 and 48.

Outcome measures

Outcome measures
Measure	Placebo n=16 Participants Patients were randomised to receive MEDI0382 matched placebo for 48 days.	MEDI0382 100 mcg n=15 Participants Patients were randomised to receive 100 mcg MEDI0382 per day by SC injection, titrated as follows: 50 mcg/day for 5 days and then 100 mcg/day for 43 days.	MEDI0382 200 mcg n=15 Participants Patients were randomised to receive 200 mcg MEDI0382 per day by SC injection, titrated as follows: 50 mcg/day for 5 days, 100 mcg/day for 7 days and then 200 mcg/day for 36 days.	MEDI0382 300 mcg n=15 Participants Patients were randomised to receive 300 mcg MEDI0382 per day by SC injection, titrated as follows: 50 mcg/day for 5 days, 100 mcg/day for 7 days, 200 mcg/day for 7 days and then 300 mcg/day for 29 days.
Mean Change From Baseline in 24-Hour Heart Rate at Days 20 and 48 Day 20	-1.86 beats/minute Standard Deviation 7.43	6.65 beats/minute Standard Deviation 7.46	13.50 beats/minute Standard Deviation 5.86	15.80 beats/minute Standard Deviation 7.86
Mean Change From Baseline in 24-Hour Heart Rate at Days 20 and 48 Day 48	-0.25 beats/minute Standard Deviation 7.24	7.87 beats/minute Standard Deviation 8.60	12.81 beats/minute Standard Deviation 4.93	15.22 beats/minute Standard Deviation 5.50

PRIMARY outcome

Timeframe: Baseline (Day -1) and Days 20 and 48.

Twenty four-hour BP was determined using an ABPM device, and the mean change from baseline in the 24-hour systolic BP and 24-hour diastolic BP are presented for Days 20 and 48.

Outcome measures

Outcome measures
Measure	Placebo n=16 Participants Patients were randomised to receive MEDI0382 matched placebo for 48 days.	MEDI0382 100 mcg n=15 Participants Patients were randomised to receive 100 mcg MEDI0382 per day by SC injection, titrated as follows: 50 mcg/day for 5 days and then 100 mcg/day for 43 days.	MEDI0382 200 mcg n=15 Participants Patients were randomised to receive 200 mcg MEDI0382 per day by SC injection, titrated as follows: 50 mcg/day for 5 days, 100 mcg/day for 7 days and then 200 mcg/day for 36 days.	MEDI0382 300 mcg n=15 Participants Patients were randomised to receive 300 mcg MEDI0382 per day by SC injection, titrated as follows: 50 mcg/day for 5 days, 100 mcg/day for 7 days, 200 mcg/day for 7 days and then 300 mcg/day for 29 days.
Mean Change From Baseline in 24-Hour Systolic and Diastolic Blood Pressure (BP) at Days 20 and 48 24-hour Systolic BP: Day 20	2.98 millimetres of mercury Standard Deviation 9.00	-4.09 millimetres of mercury Standard Deviation 8.93	-7.24 millimetres of mercury Standard Deviation 10.54	-2.48 millimetres of mercury Standard Deviation 9.28
Mean Change From Baseline in 24-Hour Systolic and Diastolic Blood Pressure (BP) at Days 20 and 48 24-hour Systolic BP: Day 48	0.08 millimetres of mercury Standard Deviation 14.32	-2.27 millimetres of mercury Standard Deviation 12.42	-5.17 millimetres of mercury Standard Deviation 19.35	-6.97 millimetres of mercury Standard Deviation 7.48
Mean Change From Baseline in 24-Hour Systolic and Diastolic Blood Pressure (BP) at Days 20 and 48 24-hour Diastolic BP: Day 20	0.98 millimetres of mercury Standard Deviation 4.34	-0.62 millimetres of mercury Standard Deviation 3.42	-1.41 millimetres of mercury Standard Deviation 4.56	0.81 millimetres of mercury Standard Deviation 5.58
Mean Change From Baseline in 24-Hour Systolic and Diastolic Blood Pressure (BP) at Days 20 and 48 24-hour Diastolic BP: Day 48	-0.06 millimetres of mercury Standard Deviation 6.82	-0.66 millimetres of mercury Standard Deviation 4.56	-0.27 millimetres of mercury Standard Deviation 9.17	-0.68 millimetres of mercury Standard Deviation 3.88

PRIMARY outcome

Timeframe: Baseline (Day -1) and Day 48: 15 minutes before standardised meal, and then at 15, 30, 45, 60, 90, 120, 180 and 240 minutes (+/-5 minutes) after consumption of the standardised meal.

Population: The Full Analysis Set included all randomised patients who received at least 1 dose of IP, analysed according to their randomised treatment group. MMTs were not conducted on patients who prematurely discontinued IP.

The MMT was conducted following a minimum 8-hour fast. Blood samples for glucose monitoring were taken 15 minutes before the patient consumed a standardised meal, and samples were taken at intervals after the meal, up to 4 hours. The MMT glucose AUC(0-4h) was calculated using a trapezoidal method, and the mean percentage change from baseline at Day 48 was analysed using an analysis of covariance (ANCOVA) model with treatment group as a factor and baseline as a covariate.

Outcome measures

Outcome measures
Measure	Placebo n=16 Participants Patients were randomised to receive MEDI0382 matched placebo for 48 days.	MEDI0382 100 mcg n=15 Participants Patients were randomised to receive 100 mcg MEDI0382 per day by SC injection, titrated as follows: 50 mcg/day for 5 days and then 100 mcg/day for 43 days.	MEDI0382 200 mcg n=15 Participants Patients were randomised to receive 200 mcg MEDI0382 per day by SC injection, titrated as follows: 50 mcg/day for 5 days, 100 mcg/day for 7 days and then 200 mcg/day for 36 days.	MEDI0382 300 mcg n=15 Participants Patients were randomised to receive 300 mcg MEDI0382 per day by SC injection, titrated as follows: 50 mcg/day for 5 days, 100 mcg/day for 7 days, 200 mcg/day for 7 days and then 300 mcg/day for 29 days.
Mean Percentage Change From Baseline in Glucose Area Under the Plasma Concentration Curve (AUC[0-4h]) as Measured by a Standardised Mixed-Meal Test (MMT) at Day 48	2.45 Percentage change Interval -3.37 to 8.26	-39.66 Percentage change Interval -45.67 to -33.66	-31.16 Percentage change Interval -38.61 to -23.71	-37.86 Percentage change Interval -44.95 to -30.76

PRIMARY outcome

Timeframe: Baseline (Day -1) and Day 48.

Population: The Full Analysis Set included all randomised patients who received at least 1 dose of IP, analysed according to their randomised treatment group. Patients with data available are presented.

The mean percentage change from baseline in body weight at Day 48 was analysed using an ANCOVA model with treatment group as a factor and baseline as a covariate. For patients who prematurely discontinued IP, the last on-treatment measurement, regardless of rescue medication, was used (last observation carried forward \[LOCF\]).

Outcome measures

Outcome measures
Measure	Placebo n=16 Participants Patients were randomised to receive MEDI0382 matched placebo for 48 days.	MEDI0382 100 mcg n=15 Participants Patients were randomised to receive 100 mcg MEDI0382 per day by SC injection, titrated as follows: 50 mcg/day for 5 days and then 100 mcg/day for 43 days.	MEDI0382 200 mcg n=15 Participants Patients were randomised to receive 200 mcg MEDI0382 per day by SC injection, titrated as follows: 50 mcg/day for 5 days, 100 mcg/day for 7 days and then 200 mcg/day for 36 days.	MEDI0382 300 mcg n=15 Participants Patients were randomised to receive 300 mcg MEDI0382 per day by SC injection, titrated as follows: 50 mcg/day for 5 days, 100 mcg/day for 7 days, 200 mcg/day for 7 days and then 300 mcg/day for 29 days.
Mean Percentage Change From Baseline in Body Weight at Day 48	-0.82 Percentage change Interval -2.06 to 0.43	-2.12 Percentage change Interval -3.4 to -0.84	-3.34 Percentage change Interval -4.68 to -2.01	-3.34 Percentage change Interval -4.61 to -2.06

PRIMARY outcome

Timeframe: Baseline (Day -1) and Days 1, 6, 13, 20 and 48: predose and 6 hours (+/-15 minutes) postdose.

Digital ECGs were taken at baseline and predose and postdose on Days 1, 6, 13, 20 and 48. The mean change from baseline is presented.

Outcome measures

Outcome measures
Measure	Placebo n=16 Participants Patients were randomised to receive MEDI0382 matched placebo for 48 days.	MEDI0382 100 mcg n=15 Participants Patients were randomised to receive 100 mcg MEDI0382 per day by SC injection, titrated as follows: 50 mcg/day for 5 days and then 100 mcg/day for 43 days.	MEDI0382 200 mcg n=15 Participants Patients were randomised to receive 200 mcg MEDI0382 per day by SC injection, titrated as follows: 50 mcg/day for 5 days, 100 mcg/day for 7 days and then 200 mcg/day for 36 days.	MEDI0382 300 mcg n=15 Participants Patients were randomised to receive 300 mcg MEDI0382 per day by SC injection, titrated as follows: 50 mcg/day for 5 days, 100 mcg/day for 7 days, 200 mcg/day for 7 days and then 300 mcg/day for 29 days.
Mean Change From Baseline in Heart Rate Measured by Electrocardiogram (ECG) at Day 48. Day 1: 6 hours postdose	1.77 beats/minute Standard Deviation 7.20	4.24 beats/minute Standard Deviation 5.00	2.18 beats/minute Standard Deviation 8.62	6.27 beats/minute Standard Deviation 7.91
Mean Change From Baseline in Heart Rate Measured by Electrocardiogram (ECG) at Day 48. Day 20: predose	-1.85 beats/minute Standard Deviation 7.52	6.24 beats/minute Standard Deviation 8.02	11.97 beats/minute Standard Deviation 8.12	13.03 beats/minute Standard Deviation 8.65
Mean Change From Baseline in Heart Rate Measured by Electrocardiogram (ECG) at Day 48. Day 20: 6 hours postdose	0.29 beats/minute Standard Deviation 9.15	5.09 beats/minute Standard Deviation 9.37	16.79 beats/minute Standard Deviation 6.21	16.94 beats/minute Standard Deviation 8.86
Mean Change From Baseline in Heart Rate Measured by Electrocardiogram (ECG) at Day 48. Day 6: predose	-2.85 beats/minute Standard Deviation 4.93	1.84 beats/minute Standard Deviation 8.56	7.69 beats/minute Standard Deviation 7.11	10.79 beats/minute Standard Deviation 5.87
Mean Change From Baseline in Heart Rate Measured by Electrocardiogram (ECG) at Day 48. Day 6: 6 hours postdose	0.02 beats/minute Standard Deviation 8.79	4.62 beats/minute Standard Deviation 9.11	8.88 beats/minute Standard Deviation 6.06	10.67 beats/minute Standard Deviation 7.59
Mean Change From Baseline in Heart Rate Measured by Electrocardiogram (ECG) at Day 48. Day 13: predose	-2.63 beats/minute Standard Deviation 5.58	6.91 beats/minute Standard Deviation 8.83	8.93 beats/minute Standard Deviation 6.84	11.74 beats/minute Standard Deviation 7.92
Mean Change From Baseline in Heart Rate Measured by Electrocardiogram (ECG) at Day 48. Day 13: 6 hours postdose	2.19 beats/minute Standard Deviation 9.13	6.40 beats/minute Standard Deviation 11.41	16.62 beats/minute Standard Deviation 7.14	13.31 beats/minute Standard Deviation 9.45
Mean Change From Baseline in Heart Rate Measured by Electrocardiogram (ECG) at Day 48. Day 48: predose	-1.06 beats/minute Standard Deviation 10.06	7.20 beats/minute Standard Deviation 5.88	10.20 beats/minute Standard Deviation 9.70	17.06 beats/minute Standard Deviation 6.12
Mean Change From Baseline in Heart Rate Measured by Electrocardiogram (ECG) at Day 48. Day 48: 6 hours postdose	-6.25 beats/minute Standard Deviation 10.34	1.16 beats/minute Standard Deviation 10.21	15.43 beats/minute Standard Deviation 12.15	12.70 beats/minute Standard Deviation 5.95

PRIMARY outcome

Timeframe: Day 1 up to 14 days after the last dose of IP (approximately 9 weeks).

Population: The Safety Analysis Set included all randomised patients who received at least 1 dose of IP, analysed according to the treatment received.

AEs were collected from Day 1 of treatment up to 14 days after the last dose of IP. Serious AEs (SAEs) were collected from signing of informed consent. The numbers of patients who experienced any AE, any SAE (including events with an outcome of death), and any AE leading to discontinuation of IP are presented.

Outcome measures

Outcome measures
Measure	Placebo n=16 Participants Patients were randomised to receive MEDI0382 matched placebo for 48 days.	MEDI0382 100 mcg n=15 Participants Patients were randomised to receive 100 mcg MEDI0382 per day by SC injection, titrated as follows: 50 mcg/day for 5 days and then 100 mcg/day for 43 days.	MEDI0382 200 mcg n=15 Participants Patients were randomised to receive 200 mcg MEDI0382 per day by SC injection, titrated as follows: 50 mcg/day for 5 days, 100 mcg/day for 7 days and then 200 mcg/day for 36 days.	MEDI0382 300 mcg n=15 Participants Patients were randomised to receive 300 mcg MEDI0382 per day by SC injection, titrated as follows: 50 mcg/day for 5 days, 100 mcg/day for 7 days, 200 mcg/day for 7 days and then 300 mcg/day for 29 days.
Number of Patients Who Experienced Adverse Events (AEs) Any AE	6 Participants	6 Participants	11 Participants	9 Participants
Number of Patients Who Experienced Adverse Events (AEs) Any SAE	0 Participants	0 Participants	0 Participants	0 Participants
Number of Patients Who Experienced Adverse Events (AEs) Any AE leading to discontinuation of IP	0 Participants	0 Participants	4 Participants	1 Participants

SECONDARY outcome

Timeframe: Baseline (Day -1) and Day 48 (predose).

The mean change from baseline in HbA1c at Day 48 was analysed using an ANCOVA model with treatment group as a factor and baseline as a covariate. For patients who prematurely discontinued IP, or for patients who did not have a measurement taken on Day 48, the last post-baseline measurement, regardless of rescue medication, was used (LOCF).

Outcome measures

Outcome measures
Measure	Placebo n=16 Participants Patients were randomised to receive MEDI0382 matched placebo for 48 days.	MEDI0382 100 mcg n=15 Participants Patients were randomised to receive 100 mcg MEDI0382 per day by SC injection, titrated as follows: 50 mcg/day for 5 days and then 100 mcg/day for 43 days.	MEDI0382 200 mcg n=15 Participants Patients were randomised to receive 200 mcg MEDI0382 per day by SC injection, titrated as follows: 50 mcg/day for 5 days, 100 mcg/day for 7 days and then 200 mcg/day for 36 days.	MEDI0382 300 mcg n=15 Participants Patients were randomised to receive 300 mcg MEDI0382 per day by SC injection, titrated as follows: 50 mcg/day for 5 days, 100 mcg/day for 7 days, 200 mcg/day for 7 days and then 300 mcg/day for 29 days.
Mean Change From Baseline in HbA1c at Day 48	-0.14 Percent glycated haemoglobin Interval -0.41 to 0.12	-1.23 Percent glycated haemoglobin Interval -1.51 to -0.96	-1.24 Percent glycated haemoglobin Interval -1.53 to -0.96	-0.90 Percent glycated haemoglobin Interval -1.18 to -0.63

SECONDARY outcome

Timeframe: Baseline (Day -1) and Day 48 (predose).

The mean change from baseline in fasting plasma glucose at Day 48 was analysed using an ANCOVA model with treatment group as a factor and baseline as a covariate. For patients who prematurely discontinued IP, or for patients who did not have a measurement taken on Day 48, the last post-baseline measurement, regardless of rescue medication, was used (LOCF).

Outcome measures

Outcome measures
Measure	Placebo n=16 Participants Patients were randomised to receive MEDI0382 matched placebo for 48 days.	MEDI0382 100 mcg n=15 Participants Patients were randomised to receive 100 mcg MEDI0382 per day by SC injection, titrated as follows: 50 mcg/day for 5 days and then 100 mcg/day for 43 days.	MEDI0382 200 mcg n=15 Participants Patients were randomised to receive 200 mcg MEDI0382 per day by SC injection, titrated as follows: 50 mcg/day for 5 days, 100 mcg/day for 7 days and then 200 mcg/day for 36 days.	MEDI0382 300 mcg n=15 Participants Patients were randomised to receive 300 mcg MEDI0382 per day by SC injection, titrated as follows: 50 mcg/day for 5 days, 100 mcg/day for 7 days, 200 mcg/day for 7 days and then 300 mcg/day for 29 days.
Mean Change From Baseline in Fasting Plasma Glucose at Day 48	-0.40 milligrams per decilitre (mg/dL) Interval -12.6 to 11.8	-57.10 milligrams per decilitre (mg/dL) Interval -69.77 to -44.42	-60.98 milligrams per decilitre (mg/dL) Interval -76.82 to -45.15	-55.47 milligrams per decilitre (mg/dL) Interval -70.28 to -40.66

SECONDARY outcome

Timeframe: Baseline (Day -1) and Day 48 (predose).

The mean change from baseline in fructosamine at Day 48 was analysed using an ANCOVA model with treatment group as a factor and baseline as a covariate. For patients who prematurely discontinued IP, the last on-treatment measurement, regardless of rescue medication, was used (LOCF).

Outcome measures

Outcome measures
Measure	Placebo n=16 Participants Patients were randomised to receive MEDI0382 matched placebo for 48 days.	MEDI0382 100 mcg n=15 Participants Patients were randomised to receive 100 mcg MEDI0382 per day by SC injection, titrated as follows: 50 mcg/day for 5 days and then 100 mcg/day for 43 days.	MEDI0382 200 mcg n=15 Participants Patients were randomised to receive 200 mcg MEDI0382 per day by SC injection, titrated as follows: 50 mcg/day for 5 days, 100 mcg/day for 7 days and then 200 mcg/day for 36 days.	MEDI0382 300 mcg n=15 Participants Patients were randomised to receive 300 mcg MEDI0382 per day by SC injection, titrated as follows: 50 mcg/day for 5 days, 100 mcg/day for 7 days, 200 mcg/day for 7 days and then 300 mcg/day for 29 days.
Mean Change From Baseline in Fructosamine at Day 48	-0.012 millimoles per litre (mmol/L) Interval -0.029 to 0.004	-0.083 millimoles per litre (mmol/L) Interval -0.1 to -0.066	-0.066 millimoles per litre (mmol/L) Interval -0.083 to -0.048	-0.061 millimoles per litre (mmol/L) Interval -0.079 to -0.044

SECONDARY outcome

Timeframe: Baseline (Day -8 to -2) and Days 5, 12, 19 and 47.

Hyperglycaemia was defined as blood glucose \>7.8 mmol/L or \>140 mg/dL. Continuous glucose monitoring used a device fitted to the upper arm by trained study site staff to measure and record interstitial glucose levels every 15 minutes. Analysis was based on 24-hour readings defined as the first available time point with a valid continuous glucose monitoring glucose reading. The change in the percentage time in hyperglycaemia from the last day of baseline continuous glucose monitoring over 24 hours to the end of dosing at each dose level for the indicated timepoints is presented.

Outcome measures

Outcome measures
Measure	Placebo n=16 Participants Patients were randomised to receive MEDI0382 matched placebo for 48 days.	MEDI0382 100 mcg n=15 Participants Patients were randomised to receive 100 mcg MEDI0382 per day by SC injection, titrated as follows: 50 mcg/day for 5 days and then 100 mcg/day for 43 days.	MEDI0382 200 mcg n=15 Participants Patients were randomised to receive 200 mcg MEDI0382 per day by SC injection, titrated as follows: 50 mcg/day for 5 days, 100 mcg/day for 7 days and then 200 mcg/day for 36 days.	MEDI0382 300 mcg n=15 Participants Patients were randomised to receive 300 mcg MEDI0382 per day by SC injection, titrated as follows: 50 mcg/day for 5 days, 100 mcg/day for 7 days, 200 mcg/day for 7 days and then 300 mcg/day for 29 days.
Mean Change From Baseline in the Percentage of Time in Hyperglycaemia Over 24 Hours at Days 5, 12, 19 and 47 Day 5	-3.23 Percentage of time Standard Deviation 12.59	-48.35 Percentage of time Standard Deviation 21.27	-33.71 Percentage of time Standard Deviation 24.67	-51.33 Percentage of time Standard Deviation 30.04
Mean Change From Baseline in the Percentage of Time in Hyperglycaemia Over 24 Hours at Days 5, 12, 19 and 47 Day 19	-12.08 Percentage of time Standard Deviation 17.61	-59.57 Percentage of time Standard Deviation 16.98	-43.85 Percentage of time Standard Deviation 28.96	-60.68 Percentage of time Standard Deviation 24.93
Mean Change From Baseline in the Percentage of Time in Hyperglycaemia Over 24 Hours at Days 5, 12, 19 and 47 Day 47	-6.15 Percentage of time Standard Deviation 22.80	-47.99 Percentage of time Standard Deviation 20.63	-48.96 Percentage of time Standard Deviation 20.28	-57.59 Percentage of time Standard Deviation 21.86
Mean Change From Baseline in the Percentage of Time in Hyperglycaemia Over 24 Hours at Days 5, 12, 19 and 47 Day 12	-11.72 Percentage of time Standard Deviation 28.58	-57.74 Percentage of time Standard Deviation 24.59	-53.36 Percentage of time Standard Deviation 21.59	-55.78 Percentage of time Standard Deviation 25.19

SECONDARY outcome

Timeframe: Baseline (Day -8 to -2) and Days 5, 12, 19 and 47.

Hypoglycaemia was defined as blood glucose \<3 mmol/L or \<54 mg/dL. Continuous glucose monitoring used a device fitted to the upper arm by trained study site staff to measure and record interstitial glucose levels every 15 minutes. Analysis was based on 24-hour readings defined as the first available time point with a valid continuous glucose monitoring glucose reading. The change in the percentage time in hypoglycaemia from the last day of baseline continuous glucose monitoring over 24 hours to the end of dosing at each dose level for the timepoints is presented.

Outcome measures

Outcome measures
Measure	Placebo n=16 Participants Patients were randomised to receive MEDI0382 matched placebo for 48 days.	MEDI0382 100 mcg n=15 Participants Patients were randomised to receive 100 mcg MEDI0382 per day by SC injection, titrated as follows: 50 mcg/day for 5 days and then 100 mcg/day for 43 days.	MEDI0382 200 mcg n=15 Participants Patients were randomised to receive 200 mcg MEDI0382 per day by SC injection, titrated as follows: 50 mcg/day for 5 days, 100 mcg/day for 7 days and then 200 mcg/day for 36 days.	MEDI0382 300 mcg n=15 Participants Patients were randomised to receive 300 mcg MEDI0382 per day by SC injection, titrated as follows: 50 mcg/day for 5 days, 100 mcg/day for 7 days, 200 mcg/day for 7 days and then 300 mcg/day for 29 days.
Mean Change From Baseline in the Percentage of Time in Hypoglycaemia Over 24 Hours at Days 5, 12, 19 and 47 Day 5	0.00 Percentage of time Standard Deviation 0.00	0.00 Percentage of time Standard Deviation 0.00	0.00 Percentage of time Standard Deviation 0.00	6.28 Percentage of time Standard Deviation 16.61
Mean Change From Baseline in the Percentage of Time in Hypoglycaemia Over 24 Hours at Days 5, 12, 19 and 47 Day 12	0.00 Percentage of time Standard Deviation 0.00	0.00 Percentage of time Standard Deviation 0.00	0.00 Percentage of time Standard Deviation 0.00	0.00 Percentage of time Standard Deviation 0.00
Mean Change From Baseline in the Percentage of Time in Hypoglycaemia Over 24 Hours at Days 5, 12, 19 and 47 Day 19	0.00 Percentage of time Standard Deviation 0.00	0.00 Percentage of time Standard Deviation 0.00	3.68 Percentage of time Standard Deviation 12.75	0.00 Percentage of time Standard Deviation 0.00
Mean Change From Baseline in the Percentage of Time in Hypoglycaemia Over 24 Hours at Days 5, 12, 19 and 47 Day 47	0.00 Percentage of time Standard Deviation 0.00	0.00 Percentage of time Standard Deviation 0.00	0.00 Percentage of time Standard Deviation 0.00	0.00 Percentage of time Standard Deviation 0.00

SECONDARY outcome

Timeframe: Baseline (Day -8 to -2) and Days 1 to 5, 6 to 12, 13 to 19 and 41 to 47.

Hyperglycaemia was defined as blood glucose \>7.8 mmol/L or \>140 mg/dL. Continuous glucose monitoring used a device fitted to the upper arm by trained study site staff to measure and record interstitial glucose levels every 15 minutes. Analysis was based on 24-hour readings defined as the first available time point with a valid continuous glucose monitoring glucose reading. The change in the percentage time in hyperglycaemia from the last day of baseline continuous glucose monitoring over 5 days for 50 mcg MEDI0382 and 7 days for each of the dose levels (during titration) is presented, up to Day 47, per randomised group.

Outcome measures

Outcome measures
Measure	Placebo n=16 Participants Patients were randomised to receive MEDI0382 matched placebo for 48 days.	MEDI0382 100 mcg n=15 Participants Patients were randomised to receive 100 mcg MEDI0382 per day by SC injection, titrated as follows: 50 mcg/day for 5 days and then 100 mcg/day for 43 days.	MEDI0382 200 mcg n=15 Participants Patients were randomised to receive 200 mcg MEDI0382 per day by SC injection, titrated as follows: 50 mcg/day for 5 days, 100 mcg/day for 7 days and then 200 mcg/day for 36 days.	MEDI0382 300 mcg n=15 Participants Patients were randomised to receive 300 mcg MEDI0382 per day by SC injection, titrated as follows: 50 mcg/day for 5 days, 100 mcg/day for 7 days, 200 mcg/day for 7 days and then 300 mcg/day for 29 days.
Mean Change From Baseline in the Percentage of Time in Hyperglycaemia Over 5 Days for 50 mcg Dose Level and 7 Days for Other Dose Levels Days 41 to 47	-0.40 Percentage of time Standard Deviation 22.70	-42.37 Percentage of time Standard Deviation 17.22	-43.44 Percentage of time Standard Deviation 18.26	-51.25 Percentage of time Standard Deviation 17.12
Mean Change From Baseline in the Percentage of Time in Hyperglycaemia Over 5 Days for 50 mcg Dose Level and 7 Days for Other Dose Levels Days 13 to 19	-6.09 Percentage of time Standard Deviation 19.10	-53.25 Percentage of time Standard Deviation 16.47	-52.33 Percentage of time Standard Deviation 20.96	-47.50 Percentage of time Standard Deviation 20.67
Mean Change From Baseline in the Percentage of Time in Hyperglycaemia Over 5 Days for 50 mcg Dose Level and 7 Days for Other Dose Levels Days 1 to 5	-1.43 Percentage of time Standard Deviation 10.26	-42.52 Percentage of time Standard Deviation 13.46	-38.68 Percentage of time Standard Deviation 18.97	-34.74 Percentage of time Standard Deviation 18.24
Mean Change From Baseline in the Percentage of Time in Hyperglycaemia Over 5 Days for 50 mcg Dose Level and 7 Days for Other Dose Levels Days 6 to 12	-8.97 Percentage of time Standard Deviation 26.12	-48.35 Percentage of time Standard Deviation 16.01	-50.81 Percentage of time Standard Deviation 18.97	-51.82 Percentage of time Standard Deviation 16.73

SECONDARY outcome

Timeframe: Baseline (Day -8 to -2) and Days 1 to 5, 6 to 12, 13 to 19 and 41 to 47.

Hyp0glycaemia was defined as blood glucose \<3 mmol/L or \<54 mg/dL. Continuous glucose monitoring used a device fitted to the upper arm by trained study site staff to measure and record interstitial glucose levels every 15 minutes. Analysis was based on 24-hour readings defined as the first available time point with a valid continuous glucose monitoring glucose reading. The change in the percentage time in hypoglycaemia from the last day of baseline continuous glucose monitoring over 5 days for 50 mcg MEDI0382 and 7 days for each of the randomised dose levels (during titration) is presented, up to Day 47, per randomised group.

Outcome measures

Outcome measures
Measure	Placebo n=16 Participants Patients were randomised to receive MEDI0382 matched placebo for 48 days.	MEDI0382 100 mcg n=15 Participants Patients were randomised to receive 100 mcg MEDI0382 per day by SC injection, titrated as follows: 50 mcg/day for 5 days and then 100 mcg/day for 43 days.	MEDI0382 200 mcg n=15 Participants Patients were randomised to receive 200 mcg MEDI0382 per day by SC injection, titrated as follows: 50 mcg/day for 5 days, 100 mcg/day for 7 days and then 200 mcg/day for 36 days.	MEDI0382 300 mcg n=15 Participants Patients were randomised to receive 300 mcg MEDI0382 per day by SC injection, titrated as follows: 50 mcg/day for 5 days, 100 mcg/day for 7 days, 200 mcg/day for 7 days and then 300 mcg/day for 29 days.
Mean Change From Baseline in the Percentage of Time in Hypoglycaemia Over 5 Days for 50 mcg Dose Level and 7 Days for Other Dose Levels Days 1 to 5	0.21 Percentage of time Standard Deviation 0.76	0.06 Percentage of time Standard Deviation 0.27	0.25 Percentage of time Standard Deviation 0.55	5.50 Percentage of time Standard Deviation 16.57
Mean Change From Baseline in the Percentage of Time in Hypoglycaemia Over 5 Days for 50 mcg Dose Level and 7 Days for Other Dose Levels Days 6 to 12	0.06 Percentage of time Standard Deviation 0.22	0.90 Percentage of time Standard Deviation 2.24	0.07 Percentage of time Standard Deviation 0.19	0.13 Percentage of time Standard Deviation 0.62
Mean Change From Baseline in the Percentage of Time in Hypoglycaemia Over 5 Days for 50 mcg Dose Level and 7 Days for Other Dose Levels Days 13 to 19	0.10 Percentage of time Standard Deviation 0.30	0.41 Percentage of time Standard Deviation 1.25	2.97 Percentage of time Standard Deviation 5.43	1.09 Percentage of time Standard Deviation 1.58
Mean Change From Baseline in the Percentage of Time in Hypoglycaemia Over 5 Days for 50 mcg Dose Level and 7 Days for Other Dose Levels Days 41 to 47	0.01 Percentage of time Standard Deviation 0.04	-0.02 Percentage of time Standard Deviation 0.05	0.30 Percentage of time Standard Deviation 0.60	2.59 Percentage of time Standard Deviation 7.22

SECONDARY outcome

Timeframe: Blood samples collected predose on Days 1 to 6, 13, 20, 34 and 48.

Population: The PK Analysis Set included all patients who received at least 1 dose of MEDI0382 and had at least 1 post-baseline MEDI0382 PK sample taken that was above the lower limit of quantification. Patients with data available at each timepoint are presented.

To evaluate pharmacokinetics (PK), blood samples were collected predose and Ctrough of MEDI0382 was determined. Results are presented for Days 2, 5, 34 and 48.

Outcome measures

Outcome measures
Measure	Placebo n=15 Participants Patients were randomised to receive MEDI0382 matched placebo for 48 days.	MEDI0382 100 mcg n=15 Participants Patients were randomised to receive 100 mcg MEDI0382 per day by SC injection, titrated as follows: 50 mcg/day for 5 days and then 100 mcg/day for 43 days.	MEDI0382 200 mcg n=15 Participants Patients were randomised to receive 200 mcg MEDI0382 per day by SC injection, titrated as follows: 50 mcg/day for 5 days, 100 mcg/day for 7 days and then 200 mcg/day for 36 days.	MEDI0382 300 mcg Patients were randomised to receive 300 mcg MEDI0382 per day by SC injection, titrated as follows: 50 mcg/day for 5 days, 100 mcg/day for 7 days, 200 mcg/day for 7 days and then 300 mcg/day for 29 days.
Mean Trough Plasma Concentration (Ctrough) of MEDI0382 up to Day 48 Day 48	2.83 nanograms per millilitre Geometric Coefficient of Variation 77.5	7.14 nanograms per millilitre Geometric Coefficient of Variation 23.8	9.12 nanograms per millilitre Geometric Coefficient of Variation 24.7	—
Mean Trough Plasma Concentration (Ctrough) of MEDI0382 up to Day 48 Day 2	1.20 nanograms per millilitre Geometric Coefficient of Variation 41.8	1.22 nanograms per millilitre Geometric Coefficient of Variation 22.9	1.11 nanograms per millilitre Geometric Coefficient of Variation 26.9	—
Mean Trough Plasma Concentration (Ctrough) of MEDI0382 up to Day 48 Day 5	1.47 nanograms per millilitre Geometric Coefficient of Variation 36.8	1.61 nanograms per millilitre Geometric Coefficient of Variation 26.6	1.56 nanograms per millilitre Geometric Coefficient of Variation 25.8	—
Mean Trough Plasma Concentration (Ctrough) of MEDI0382 up to Day 48 Day 34	2.70 nanograms per millilitre Geometric Coefficient of Variation 78.0	5.16 nanograms per millilitre Geometric Coefficient of Variation 81.4	7.18 nanograms per millilitre Geometric Coefficient of Variation 39.8	—

SECONDARY outcome

Timeframe: Samples were collected predose on days 1, 13, 20 and 48, and 7 to 14 days after administration of last dose of IP.

The number of patients who were ADA positive at baseline and/or post-baseline are presented. Persistent positive was defined as positive at ≥2 post-baseline assessments (with ≥16 weeks between first and last positive) or positive at the last post-baseline assessment. Transiently positive was defined as having at least 1 post-baseline ADA positive assessment and not fulfilling the conditions of persistently positive. +ve = positive

Outcome measures

Outcome measures
Measure	Placebo n=15 Participants Patients were randomised to receive MEDI0382 matched placebo for 48 days.	MEDI0382 100 mcg n=15 Participants Patients were randomised to receive 100 mcg MEDI0382 per day by SC injection, titrated as follows: 50 mcg/day for 5 days and then 100 mcg/day for 43 days.	MEDI0382 200 mcg n=15 Participants Patients were randomised to receive 200 mcg MEDI0382 per day by SC injection, titrated as follows: 50 mcg/day for 5 days, 100 mcg/day for 7 days and then 200 mcg/day for 36 days.	MEDI0382 300 mcg Patients were randomised to receive 300 mcg MEDI0382 per day by SC injection, titrated as follows: 50 mcg/day for 5 days, 100 mcg/day for 7 days, 200 mcg/day for 7 days and then 300 mcg/day for 29 days.
Number of Patients With Antidrug Antibody (ADA) Response to MEDI0382 Persistent +ve	2 Participants	4 Participants	2 Participants	—
Number of Patients With Antidrug Antibody (ADA) Response to MEDI0382 ADA +ve at baseline	0 Participants	0 Participants	0 Participants	—
Number of Patients With Antidrug Antibody (ADA) Response to MEDI0382 ADA +ve post-baseline	4 Participants	5 Participants	2 Participants	—
Number of Patients With Antidrug Antibody (ADA) Response to MEDI0382 ADA +ve post-baseline & +ve at baseline	0 Participants	0 Participants	0 Participants	—
Number of Patients With Antidrug Antibody (ADA) Response to MEDI0382 ADA+ve post-baseline & not detected at baseline	4 Participants	5 Participants	2 Participants	—
Number of Patients With Antidrug Antibody (ADA) Response to MEDI0382 Transient +ve	2 Participants	1 Participants	0 Participants	—
Number of Patients With Antidrug Antibody (ADA) Response to MEDI0382 ADA not detected post-baseline & +ve baseline	0 Participants	0 Participants	0 Participants	—

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

MEDI0382 100 mcg

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

MEDI0382 200 mcg

Serious events: 0 serious events

Other events: 11 other events

Deaths: 0 deaths

MEDI0382 300 mcg

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Global Clinical Lead

AstraZeneca

Phone: +13028851180

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee PI needs to provide sponsor with the draft to review no later than 30 days prior to the date of publication of trial results.
Publication restrictions are in place

Restriction type: OTHER