Trial Outcomes & Findings for A Study to Look at the Effect MEDI0382 Has on Blood Sugar in People With Type 2 Diabetes and Kidney Problems and Also to Check That MEDI0382 is Well Tolerated (NCT NCT03550378)
NCT ID: NCT03550378
Last Updated: 2020-04-13
Results Overview
The MMTT involved the consumption of a standardised liquid meal (a nutritional supplement containing the components of fat, carbohydrate, and protein, which make up a standard MMTT) within 15 minutes, and timed serial blood samples obtained for measurement of glucose and parameters related to glucose metabolism through 240 minutes after consumption of the standardized meal (with no additional food intake during this time).
COMPLETED
PHASE2
41 participants
Zero minutes before and 15, 30, 45, 60, 90, 120, 180, and 240 minutes after consumption of the standardised meal on Day -5 (Baseline) and Day 32
2020-04-13
Participant Flow
The study was conducted in the United Kingdom and Germany between 29Jun2018 and 04Feb2019.
A total of 41 participants were randomized to the study.
Participant milestones
| Measure |
Placebo
Participants received subcutaneous dose (SC) of placebo matched to MEDI0382 once daily for 32 days.
|
MEDI0382
Participants received SC dose of MEDI0382 titrated from 50 μg upto 300 μg (50 μg once daily for 4 days, followed by 100 μg daily for 7 days, 200 μg daily for 7 days, and 300 μg daily for 14 days) for 32 days.
|
|---|---|---|
|
Overall Study
STARTED
|
20
|
21
|
|
Overall Study
COMPLETED
|
20
|
20
|
|
Overall Study
NOT COMPLETED
|
0
|
1
|
Reasons for withdrawal
| Measure |
Placebo
Participants received subcutaneous dose (SC) of placebo matched to MEDI0382 once daily for 32 days.
|
MEDI0382
Participants received SC dose of MEDI0382 titrated from 50 μg upto 300 μg (50 μg once daily for 4 days, followed by 100 μg daily for 7 days, 200 μg daily for 7 days, and 300 μg daily for 14 days) for 32 days.
|
|---|---|---|
|
Overall Study
Death
|
0
|
1
|
Baseline Characteristics
A Study to Look at the Effect MEDI0382 Has on Blood Sugar in People With Type 2 Diabetes and Kidney Problems and Also to Check That MEDI0382 is Well Tolerated
Baseline characteristics by cohort
| Measure |
Placebo
n=20 Participants
Participants received subcutaneous dose (SC) of placebo matched to MEDI0382 once daily for 32 days.
|
MEDI0382
n=21 Participants
Participants received SC dose of MEDI0382 titrated from 50 μg upto 300 μg (50 μg once daily for 4 days, followed by 100 μg daily for 7 days, 200 μg daily for 7 days, and 300 μg daily for 14 days) for 32 days.
|
Total
n=41 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
70.9 Years
STANDARD_DEVIATION 4.7 • n=5 Participants
|
71.1 Years
STANDARD_DEVIATION 7.4 • n=7 Participants
|
71.0 Years
STANDARD_DEVIATION 6.1 • n=5 Participants
|
|
Sex: Female, Male
Female
|
11 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
20 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
9 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
21 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
20 Participants
n=5 Participants
|
21 Participants
n=7 Participants
|
41 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
20 Participants
n=5 Participants
|
20 Participants
n=7 Participants
|
40 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Zero minutes before and 15, 30, 45, 60, 90, 120, 180, and 240 minutes after consumption of the standardised meal on Day -5 (Baseline) and Day 32Population: Intent-to-treat (ITT) population included all participants who received any dose of study drug and analyzed according to their randomized treatment group. Here, "N" signifies only the participants with available data were analyzed for the outcome measure.
The MMTT involved the consumption of a standardised liquid meal (a nutritional supplement containing the components of fat, carbohydrate, and protein, which make up a standard MMTT) within 15 minutes, and timed serial blood samples obtained for measurement of glucose and parameters related to glucose metabolism through 240 minutes after consumption of the standardized meal (with no additional food intake during this time).
Outcome measures
| Measure |
Placebo
n=20 Participants
Participants received subcutaneous dose (SC) of placebo matched to MEDI0382 once daily for 32 days.
|
MEDI0382
n=18 Participants
Participants received SC dose of MEDI0382 titrated from 50 μg upto 300 μg (50 μg once daily for 4 days, followed by 100 μg daily for 7 days, 200 μg daily for 7 days, and 300 μg daily for 14 days) for 32 days.
|
|---|---|---|
|
Percent Change From Baseline in Plasma Glucose Area Under the Concentration Time-curve From Time 0 to 4 Hours (AUC0-4 Hrs) as Measured by Mixed-meal Tolerance Test (MMTT) to Day 32
|
3.678 Percent change in plasma glucose
Interval -3.793 to 11.149
|
-26.706 Percent change in plasma glucose
Interval -34.584 to -18.828
|
SECONDARY outcome
Timeframe: Day 1 through Day 60Population: As-treated population included all participants who received any dose of study drug and analyzed according to the treatment they actually received.
An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug.
Outcome measures
| Measure |
Placebo
n=20 Participants
Participants received subcutaneous dose (SC) of placebo matched to MEDI0382 once daily for 32 days.
|
MEDI0382
n=21 Participants
Participants received SC dose of MEDI0382 titrated from 50 μg upto 300 μg (50 μg once daily for 4 days, followed by 100 μg daily for 7 days, 200 μg daily for 7 days, and 300 μg daily for 14 days) for 32 days.
|
|---|---|---|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
TEAEs
|
13 Participants
|
20 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
TESAEs
|
2 Participants
|
2 Participants
|
SECONDARY outcome
Timeframe: Day 1 through Day 60Population: As-treated population included all participants who received any dose of study drug and analyzed according to the treatment they actually received.
Number of participants with abnormal vital signs reported as TEAEs is reported. Vital sign measurements were obtained after the participant had rested in the supine position for at least 10 minutes at the recording time. Abnormal vital signs is defined as any abnormal finding in the vital sign parameters (blood pressure, pulse rate, body temperature, and respiratory rate).
Outcome measures
| Measure |
Placebo
n=20 Participants
Participants received subcutaneous dose (SC) of placebo matched to MEDI0382 once daily for 32 days.
|
MEDI0382
n=21 Participants
Participants received SC dose of MEDI0382 titrated from 50 μg upto 300 μg (50 μg once daily for 4 days, followed by 100 μg daily for 7 days, 200 μg daily for 7 days, and 300 μg daily for 14 days) for 32 days.
|
|---|---|---|
|
Number of Participants With Abnormal Vital Signs Reported as TEAEs
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Baseline (Day 1) through Day 32Population: As-treated population included all participants who received any dose of study drug and analyzed according to the treatment they actually received. Participants with difference (standing-supine) in DBP or SBP on Day 1 and the participants with difference (standing-supine) in DBP or SBP on Day 32 were analyzed.
The change difference is the change from Day 1 to Day 32 in the difference between systolic blood pressure (SBP) or diastolic blood pressure (DBP) values in standing and supine positions. For this outcome measure, participants with difference (standing-supine) in DBP or SBP on Day 1 and Day 32 were analyzed. For few participants either DBP or SBP was recorded eg, standing DBP was not recorded on Day 1 for 2 participants in Placebo arm and 1 participant in MEDI0382 arm; standing SBP was not recorded on Day 32 for a participant in the Placebo arm.
Outcome measures
| Measure |
Placebo
n=20 Participants
Participants received subcutaneous dose (SC) of placebo matched to MEDI0382 once daily for 32 days.
|
MEDI0382
n=21 Participants
Participants received SC dose of MEDI0382 titrated from 50 μg upto 300 μg (50 μg once daily for 4 days, followed by 100 μg daily for 7 days, 200 μg daily for 7 days, and 300 μg daily for 14 days) for 32 days.
|
|---|---|---|
|
Change From Baseline in Postural Blood Pressure
Systolic Blood Pressure
|
0.1 mmHg
Standard Deviation 9.3
|
8.9 mmHg
Standard Deviation 14.2
|
|
Change From Baseline in Postural Blood Pressure
Diastolic Blood Pressure
|
1.8 mmHg
Standard Deviation 6.3
|
0.8 mmHg
Standard Deviation 5.2
|
SECONDARY outcome
Timeframe: Day 1 through Day 60Population: As-treated population included all participants who received any dose of study drug and analyzed according to the treatment they actually received.
Number of participants with abnormal ECGs reported as TEAEs is reported. Abnormal ECGs is defined as any abnormal findings in heart rate, RR interval, PR interval, QRS, axis, ST-T morphology, and QT intervals from the primary lead of the digital 12-lead ECG.
Outcome measures
| Measure |
Placebo
n=20 Participants
Participants received subcutaneous dose (SC) of placebo matched to MEDI0382 once daily for 32 days.
|
MEDI0382
n=21 Participants
Participants received SC dose of MEDI0382 titrated from 50 μg upto 300 μg (50 μg once daily for 4 days, followed by 100 μg daily for 7 days, 200 μg daily for 7 days, and 300 μg daily for 14 days) for 32 days.
|
|---|---|---|
|
Number of Participants With Abnormal Electrocardiograms (ECGs) Reported as TEAEs
Bradyarrhythmia
|
1 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Electrocardiograms (ECGs) Reported as TEAEs
Bundle branch block left
|
1 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Electrocardiograms (ECGs) Reported as TEAEs
Bundle branch block right
|
0 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: Day 1 through Day 60Population: As-treated population included all participants who received any dose of study drug and analyzed according to the treatment they actually received.
Number of participants with abnormal clinical laboratory parameters reported as TEAEs is reported. Abnormal clinical laboratory parameters defined as any abnormal finding during analysis of serum chemistry, hematology, and urine.
Outcome measures
| Measure |
Placebo
n=20 Participants
Participants received subcutaneous dose (SC) of placebo matched to MEDI0382 once daily for 32 days.
|
MEDI0382
n=21 Participants
Participants received SC dose of MEDI0382 titrated from 50 μg upto 300 μg (50 μg once daily for 4 days, followed by 100 μg daily for 7 days, 200 μg daily for 7 days, and 300 μg daily for 14 days) for 32 days.
|
|---|---|---|
|
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs
Hypoglycaemia
|
1 Participants
|
3 Participants
|
|
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs
Alanine aminotransferase increased
|
1 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs
Aspartate aminotransferase increased
|
1 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs
Glomerular filtration rate decreased
|
0 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: Day 1 through Day 60Population: As-treated population included all participants who received any dose of study drug and analyzed according to the treatment they actually received.
An adverse event of special interest (AESI) was one of scientific and medical interest specific to understanding of the study drug and may require close monitoring and rapid communication by the investigator to the sponsor.
Outcome measures
| Measure |
Placebo
n=20 Participants
Participants received subcutaneous dose (SC) of placebo matched to MEDI0382 once daily for 32 days.
|
MEDI0382
n=21 Participants
Participants received SC dose of MEDI0382 titrated from 50 μg upto 300 μg (50 μg once daily for 4 days, followed by 100 μg daily for 7 days, 200 μg daily for 7 days, and 300 μg daily for 14 days) for 32 days.
|
|---|---|---|
|
Number of Participants With Treatment-emergent Adverse Events of Special Interest (TEAESIs)
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Day -5 (Baseline) and on Days 5, 12, 19, and 32Population: As-treated population included all participants who received any dose of study drug and analyzed according to the treatment they actually received. Here, "n" signifies only the participants with available data were analyzed for the specified time points.
Change from baseline in mean 24-hrs pulse rate to the end of each dosing levels: Day 5 for 50 μg; Day 12 for 100 μg, Day 19 for 200 μg, and Day 32 for 300 μg.
Outcome measures
| Measure |
Placebo
n=20 Participants
Participants received subcutaneous dose (SC) of placebo matched to MEDI0382 once daily for 32 days.
|
MEDI0382
n=21 Participants
Participants received SC dose of MEDI0382 titrated from 50 μg upto 300 μg (50 μg once daily for 4 days, followed by 100 μg daily for 7 days, 200 μg daily for 7 days, and 300 μg daily for 14 days) for 32 days.
|
|---|---|---|
|
Change From Baseline in Mean 24-hrs Pulse Rate to the End of Each Dosing Level
Day 19
|
1.32 Beats/min
Standard Deviation 5.28
|
12.72 Beats/min
Standard Deviation 8.93
|
|
Change From Baseline in Mean 24-hrs Pulse Rate to the End of Each Dosing Level
Day 32
|
-0.92 Beats/min
Standard Deviation 4.51
|
11.85 Beats/min
Standard Deviation 8.82
|
|
Change From Baseline in Mean 24-hrs Pulse Rate to the End of Each Dosing Level
Day 5
|
-0.73 Beats/min
Standard Deviation 4.13
|
6.40 Beats/min
Standard Deviation 5.53
|
|
Change From Baseline in Mean 24-hrs Pulse Rate to the End of Each Dosing Level
Day 12
|
1.04 Beats/min
Standard Deviation 5.07
|
9.01 Beats/min
Standard Deviation 7.73
|
SECONDARY outcome
Timeframe: Day -5 (Baseline) and on Days 5, 12, 19, and 32Population: As-treated population included all participants who received any dose of study drug and analyzed according to the treatment they actually received. Here, "n" signifies only the participants with available data were analyzed for the specified time points.
Change from baseline in mean 24-hrs systolic and diastolic blood pressure to the end of each dosing levels: Day 5 for 50 μg, Day 12 for 100 μg, Day 19 for 200 μg, and Day 32 for 300 μg.
Outcome measures
| Measure |
Placebo
n=20 Participants
Participants received subcutaneous dose (SC) of placebo matched to MEDI0382 once daily for 32 days.
|
MEDI0382
n=21 Participants
Participants received SC dose of MEDI0382 titrated from 50 μg upto 300 μg (50 μg once daily for 4 days, followed by 100 μg daily for 7 days, 200 μg daily for 7 days, and 300 μg daily for 14 days) for 32 days.
|
|---|---|---|
|
Change From Baseline in Mean 24-hrs Systolic and Diastolic Blood Pressure to the End of Each Dosing Level
Day 12: Systolic Blood Pressure
|
-2.67 mmHg
Standard Deviation 12.30
|
-4.34 mmHg
Standard Deviation 11.46
|
|
Change From Baseline in Mean 24-hrs Systolic and Diastolic Blood Pressure to the End of Each Dosing Level
Day 32: Diastolic Blood Pressure
|
1.84 mmHg
Standard Deviation 1.79
|
2.54 mmHg
Standard Deviation 5.34
|
|
Change From Baseline in Mean 24-hrs Systolic and Diastolic Blood Pressure to the End of Each Dosing Level
Day 19: Diastolic Blood Pressure
|
-0.44 mmHg
Standard Deviation 3.85
|
0.76 mmHg
Standard Deviation 3.75
|
|
Change From Baseline in Mean 24-hrs Systolic and Diastolic Blood Pressure to the End of Each Dosing Level
Day 5: Systolic Blood Pressure
|
-3.11 mmHg
Standard Deviation 9.97
|
-1.69 mmHg
Standard Deviation 9.06
|
|
Change From Baseline in Mean 24-hrs Systolic and Diastolic Blood Pressure to the End of Each Dosing Level
Day 19: Systolic Blood Pressure
|
-3.56 mmHg
Standard Deviation 10.15
|
-4.72 mmHg
Standard Deviation 11.65
|
|
Change From Baseline in Mean 24-hrs Systolic and Diastolic Blood Pressure to the End of Each Dosing Level
Day 32: Systolic Blood Pressure
|
2.21 mmHg
Standard Deviation 7.24
|
-1.15 mmHg
Standard Deviation 18.43
|
|
Change From Baseline in Mean 24-hrs Systolic and Diastolic Blood Pressure to the End of Each Dosing Level
Day 5: Diastolic Blood Pressure
|
-0.07 mmHg
Standard Deviation 3.19
|
1.15 mmHg
Standard Deviation 3.64
|
|
Change From Baseline in Mean 24-hrs Systolic and Diastolic Blood Pressure to the End of Each Dosing Level
Day 12: Diastolic Blood Pressure
|
-0.55 mmHg
Standard Deviation 5.17
|
1.28 mmHg
Standard Deviation 5.22
|
SECONDARY outcome
Timeframe: Day 1 (Baseline) and Day 32Population: Intent-to-treat (ITT) population included all participants who received any dose of study drug and analyzed according to their randomized treatment group. Here, "N" signifies only the participants with available data were analyzed for the outcome measure.
Change from baseline in haemoglobin A1c (HbA1c) is reported.
Outcome measures
| Measure |
Placebo
n=20 Participants
Participants received subcutaneous dose (SC) of placebo matched to MEDI0382 once daily for 32 days.
|
MEDI0382
n=19 Participants
Participants received SC dose of MEDI0382 titrated from 50 μg upto 300 μg (50 μg once daily for 4 days, followed by 100 μg daily for 7 days, 200 μg daily for 7 days, and 300 μg daily for 14 days) for 32 days.
|
|---|---|---|
|
Change From Baseline in Haemoglobin A1c (HbA1c) to Day 32
|
0.01 Percent
Interval -0.15 to 0.17
|
-0.65 Percent
Interval -0.82 to -0.49
|
SECONDARY outcome
Timeframe: Day 1 (Baseline) and Day 32Population: An ITT population included all participants who received any dose of study drug and analyzed according to their randomized treatment group. Here, "N" signifies only the participants with available data were analyzed for the outcome measure.
Change from baseline in fasting glucose is reported.
Outcome measures
| Measure |
Placebo
n=20 Participants
Participants received subcutaneous dose (SC) of placebo matched to MEDI0382 once daily for 32 days.
|
MEDI0382
n=19 Participants
Participants received SC dose of MEDI0382 titrated from 50 μg upto 300 μg (50 μg once daily for 4 days, followed by 100 μg daily for 7 days, 200 μg daily for 7 days, and 300 μg daily for 14 days) for 32 days.
|
|---|---|---|
|
Change From Baseline in Fasting Glucose to Day 32
|
0.60 mg/dL
Interval -12.89 to 14.08
|
-19.55 mg/dL
Interval -33.39 to -5.71
|
SECONDARY outcome
Timeframe: Baseline (Days -8 to -2), Days 5 to 11, Days 12 to 18, Days 19 to 25, and Days 26 to 32 (final week of treatment)Population: An ITT population included all participants who received any dose of study drug and analyzed according to their randomized treatment group. Here, "n" signifies only the participants with available data were analyzed for the specified time points.
Change from baseline in percentage of time spent within a target glucose range over a 7-day period to the final week of treatment is reported. Target glucose range was considered as 70 mg/dL (3.9 mmol/L) to 180 mg/dL (10 mmol/L).
Outcome measures
| Measure |
Placebo
n=20 Participants
Participants received subcutaneous dose (SC) of placebo matched to MEDI0382 once daily for 32 days.
|
MEDI0382
n=21 Participants
Participants received SC dose of MEDI0382 titrated from 50 μg upto 300 μg (50 μg once daily for 4 days, followed by 100 μg daily for 7 days, 200 μg daily for 7 days, and 300 μg daily for 14 days) for 32 days.
|
|---|---|---|
|
Change From Baseline in Percentage of Time Spent Within a Target Glucose Range Over a 7-day Period to the Final Week of Treatment
Days 12 - 18
|
-5.34 Percentage of time
Interval -12.77 to 2.1
|
15.62 Percentage of time
Interval 8.39 to 22.86
|
|
Change From Baseline in Percentage of Time Spent Within a Target Glucose Range Over a 7-day Period to the Final Week of Treatment
Days 19 - 25
|
-16.05 Percentage of time
Interval -25.02 to -7.08
|
19.18 Percentage of time
Interval 10.21 to 28.15
|
|
Change From Baseline in Percentage of Time Spent Within a Target Glucose Range Over a 7-day Period to the Final Week of Treatment
Days 5 - 11
|
-10.49 Percentage of time
Interval -20.77 to -0.2
|
12.25 Percentage of time
Interval 2.52 to 21.98
|
|
Change From Baseline in Percentage of Time Spent Within a Target Glucose Range Over a 7-day Period to the Final Week of Treatment
Days 26 - 32
|
-21.23 Percentage of time
Interval -33.13 to -9.32
|
14.79 Percentage of time
Interval 2.54 to 27.04
|
SECONDARY outcome
Timeframe: Day 1 (Baseline) and Day 33Population: An ITT population included all participants who received any dose of study drug and analyzed according to their randomized treatment group. Here, "N" signifies only the participants with available data were analyzed for the outcome measure.
Percent change from baseline in body weight is reported.
Outcome measures
| Measure |
Placebo
n=20 Participants
Participants received subcutaneous dose (SC) of placebo matched to MEDI0382 once daily for 32 days.
|
MEDI0382
n=19 Participants
Participants received SC dose of MEDI0382 titrated from 50 μg upto 300 μg (50 μg once daily for 4 days, followed by 100 μg daily for 7 days, 200 μg daily for 7 days, and 300 μg daily for 14 days) for 32 days.
|
|---|---|---|
|
Percent Change Frome Baseline in Body Weight to Day 33
|
-0.21 Percent change in body weight
Interval -1.05 to 0.62
|
-3.69 Percent change in body weight
Interval -4.55 to -2.83
|
SECONDARY outcome
Timeframe: Day 1 (Baseline) and Day 33Population: An ITT population included all participants who received any dose of study drug and analyzed according to their randomized treatment group. Here, "N" signifies only the participants with available data were analyzed for the outcome measure.
Change from baseline in absolute body weight is reported.
Outcome measures
| Measure |
Placebo
n=20 Participants
Participants received subcutaneous dose (SC) of placebo matched to MEDI0382 once daily for 32 days.
|
MEDI0382
n=19 Participants
Participants received SC dose of MEDI0382 titrated from 50 μg upto 300 μg (50 μg once daily for 4 days, followed by 100 μg daily for 7 days, 200 μg daily for 7 days, and 300 μg daily for 14 days) for 32 days.
|
|---|---|---|
|
Change From Baseline in Absolute Body Weight to Day 33
|
-0.15 Kg
Standard Deviation 1.84
|
-3.39 Kg
Standard Deviation 2.16
|
SECONDARY outcome
Timeframe: Predose and at 0.5, 1, 2, 4, 6, 8, and 24 hrs postdose on Day 32Population: Pharmacokinetic (PK) population included all participants who received at least 1 dose of study drug and had at least one PK sample collected with a value above the lower limit of quantitation.
Area under the plasma concentration time curve over a dosing duration (AUCτ) of MEDI0382 at 300 μg is reported.
Outcome measures
| Measure |
Placebo
n=16 Participants
Participants received subcutaneous dose (SC) of placebo matched to MEDI0382 once daily for 32 days.
|
MEDI0382
Participants received SC dose of MEDI0382 titrated from 50 μg upto 300 μg (50 μg once daily for 4 days, followed by 100 μg daily for 7 days, 200 μg daily for 7 days, and 300 μg daily for 14 days) for 32 days.
|
|---|---|---|
|
Area Under the Plasma Concentration Time Curve Over a Dosing Duration (AUCτ) of MEDI0382 at 300 μg
|
285.93 ng.hr/mL
Interval 124.08 to 669.17
|
—
|
SECONDARY outcome
Timeframe: Predose and at 0.5, 1, 2, 4, 6, 8, and 24 hrs postdose on Day 32Population: The PK population included all participants who received at least 1 dose of study drug and had at least one PK sample collected with a value above the lower limit of quantitation.
Maximum observed serum concentration (Cmax) of MEDI0382 at 300 μg is reported.
Outcome measures
| Measure |
Placebo
n=18 Participants
Participants received subcutaneous dose (SC) of placebo matched to MEDI0382 once daily for 32 days.
|
MEDI0382
Participants received SC dose of MEDI0382 titrated from 50 μg upto 300 μg (50 μg once daily for 4 days, followed by 100 μg daily for 7 days, 200 μg daily for 7 days, and 300 μg daily for 14 days) for 32 days.
|
|---|---|---|
|
Maximum Observed Serum Concentration (Cmax) of MEDI0382 at 300 μg
|
16.93 ng/mL
Interval 5.17 to 35.4
|
—
|
SECONDARY outcome
Timeframe: Predose and at 0.5, 1, 2, 4, 6, 8, and 24 hrs postdose on Day 32Population: The PK population included all participants who received at least 1 dose of study drug and had at least one PK sample collected with a value above the lower limit of quantitation.
Time to observed maximum serum concentration (Tmax) of MEDI0382 at 300 μg is reported.
Outcome measures
| Measure |
Placebo
n=18 Participants
Participants received subcutaneous dose (SC) of placebo matched to MEDI0382 once daily for 32 days.
|
MEDI0382
Participants received SC dose of MEDI0382 titrated from 50 μg upto 300 μg (50 μg once daily for 4 days, followed by 100 μg daily for 7 days, 200 μg daily for 7 days, and 300 μg daily for 14 days) for 32 days.
|
|---|---|---|
|
Time to Observed Maximum Serum Concentration (Tmax) of MEDI0382 at 300 μg
|
5.6 Hours
Interval 4.0 to 24.0
|
—
|
SECONDARY outcome
Timeframe: Days 1, 5, 12, and 19: Predose; and Day 32: Predose and at 0.5, 1, 2, 4, 6, 8, and 24 hrs postdose (Day 33)Population: The PK population included all participants who received at least 1 dose of study drug and had at least one PK sample collected with a value above the lower limit of quantitation. Here, "n" signifies only the participants with available data were analyzed for the specified time points.
Trough concentration is the lowest concentration reached by a drug before the next dose is administered. Trough plasma concentration of MEDI0382 is reported.
Outcome measures
| Measure |
Placebo
n=21 Participants
Participants received subcutaneous dose (SC) of placebo matched to MEDI0382 once daily for 32 days.
|
MEDI0382
Participants received SC dose of MEDI0382 titrated from 50 μg upto 300 μg (50 μg once daily for 4 days, followed by 100 μg daily for 7 days, 200 μg daily for 7 days, and 300 μg daily for 14 days) for 32 days.
|
|---|---|---|
|
Trough Plasma Concentration (Ctrough) of MEDI0382
Day 33
|
5.96 ng/mL
Interval 2.43 to 19.2
|
—
|
|
Trough Plasma Concentration (Ctrough) of MEDI0382
Day 5
|
1.44 ng/mL
Interval 0.48 to 2.58
|
—
|
|
Trough Plasma Concentration (Ctrough) of MEDI0382
Day 12
|
2.03 ng/mL
Interval 0.63 to 3.75
|
—
|
|
Trough Plasma Concentration (Ctrough) of MEDI0382
Day 19
|
3.68 ng/mL
Interval 0.59 to 8.86
|
—
|
|
Trough Plasma Concentration (Ctrough) of MEDI0382
Day 32
|
5.86 ng/mL
Interval 1.3 to 19.4
|
—
|
SECONDARY outcome
Timeframe: Pre-dose on Days 1, 12, and 32 and on Day 60Population: As-treated population included all participants who received any dose of study drug and analyzed according to the treatment they actually received.
Number of participants with positive Anti-drug antibodies (ADA) Titre to MEDI0382 is reported.
Outcome measures
| Measure |
Placebo
n=20 Participants
Participants received subcutaneous dose (SC) of placebo matched to MEDI0382 once daily for 32 days.
|
MEDI0382
n=21 Participants
Participants received SC dose of MEDI0382 titrated from 50 μg upto 300 μg (50 μg once daily for 4 days, followed by 100 μg daily for 7 days, 200 μg daily for 7 days, and 300 μg daily for 14 days) for 32 days.
|
|---|---|---|
|
Number of Participants With Positive Anti-drug Antibodies (ADA) Titre to MEDI0382
Positive at baseline
|
0 Participants
|
0 Participants
|
|
Number of Participants With Positive Anti-drug Antibodies (ADA) Titre to MEDI0382
Positive at baseline; not detected post-baseline
|
0 Participants
|
0 Participants
|
|
Number of Participants With Positive Anti-drug Antibodies (ADA) Titre to MEDI0382
Positive post-baseline
|
0 Participants
|
2 Participants
|
|
Number of Participants With Positive Anti-drug Antibodies (ADA) Titre to MEDI0382
Positive at baseline and post-baseline
|
0 Participants
|
0 Participants
|
|
Number of Participants With Positive Anti-drug Antibodies (ADA) Titre to MEDI0382
Not detected at baseline; positive post-baseline
|
0 Participants
|
2 Participants
|
Adverse Events
Placebo
MEDI0382
Serious adverse events
| Measure |
Placebo
n=20 participants at risk
Participants received subcutaneous dose (SC) of placebo matched to MEDI0382 once daily for 32 days.
|
MEDI0382
n=21 participants at risk
Participants received SC dose of MEDI0382 titrated from 50 μg upto 300 μg (50 μg once daily for 4 days, followed by 100 μg daily for 7 days, 200 μg daily for 7 days, and 300 μg daily for 14 days) for 32 days.
|
|---|---|---|
|
Metabolism and nutrition disorders
Diabetic ketoacidosis
|
0.00%
0/20 • Day 1 through Day 60
|
4.8%
1/21 • Number of events 1 • Day 1 through Day 60
|
|
Nervous system disorders
Carotid artery stenosis
|
5.0%
1/20 • Number of events 1 • Day 1 through Day 60
|
0.00%
0/21 • Day 1 through Day 60
|
|
Vascular disorders
Hypertensive crisis
|
0.00%
0/20 • Day 1 through Day 60
|
4.8%
1/21 • Number of events 1 • Day 1 through Day 60
|
|
Nervous system disorders
Syncope
|
5.0%
1/20 • Number of events 2 • Day 1 through Day 60
|
0.00%
0/21 • Day 1 through Day 60
|
Other adverse events
| Measure |
Placebo
n=20 participants at risk
Participants received subcutaneous dose (SC) of placebo matched to MEDI0382 once daily for 32 days.
|
MEDI0382
n=21 participants at risk
Participants received SC dose of MEDI0382 titrated from 50 μg upto 300 μg (50 μg once daily for 4 days, followed by 100 μg daily for 7 days, 200 μg daily for 7 days, and 300 μg daily for 14 days) for 32 days.
|
|---|---|---|
|
Cardiac disorders
Bradyarrhythmia
|
5.0%
1/20 • Number of events 1 • Day 1 through Day 60
|
0.00%
0/21 • Day 1 through Day 60
|
|
Cardiac disorders
Bundle branch block left
|
5.0%
1/20 • Number of events 1 • Day 1 through Day 60
|
0.00%
0/21 • Day 1 through Day 60
|
|
Cardiac disorders
Bundle branch block right
|
0.00%
0/20 • Day 1 through Day 60
|
4.8%
1/21 • Number of events 1 • Day 1 through Day 60
|
|
Ear and labyrinth disorders
Vertigo
|
5.0%
1/20 • Number of events 1 • Day 1 through Day 60
|
0.00%
0/21 • Day 1 through Day 60
|
|
Ear and labyrinth disorders
Vertigo positional
|
0.00%
0/20 • Day 1 through Day 60
|
4.8%
1/21 • Number of events 1 • Day 1 through Day 60
|
|
Gastrointestinal disorders
Abdominal distension
|
0.00%
0/20 • Day 1 through Day 60
|
4.8%
1/21 • Number of events 1 • Day 1 through Day 60
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/20 • Day 1 through Day 60
|
4.8%
1/21 • Number of events 1 • Day 1 through Day 60
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.00%
0/20 • Day 1 through Day 60
|
4.8%
1/21 • Number of events 1 • Day 1 through Day 60
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/20 • Day 1 through Day 60
|
23.8%
5/21 • Number of events 5 • Day 1 through Day 60
|
|
Gastrointestinal disorders
Dyspepsia
|
5.0%
1/20 • Number of events 1 • Day 1 through Day 60
|
23.8%
5/21 • Number of events 6 • Day 1 through Day 60
|
|
Gastrointestinal disorders
Eructation
|
0.00%
0/20 • Day 1 through Day 60
|
4.8%
1/21 • Number of events 1 • Day 1 through Day 60
|
|
Gastrointestinal disorders
Flatulence
|
0.00%
0/20 • Day 1 through Day 60
|
9.5%
2/21 • Number of events 2 • Day 1 through Day 60
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
0.00%
0/20 • Day 1 through Day 60
|
4.8%
1/21 • Number of events 1 • Day 1 through Day 60
|
|
Gastrointestinal disorders
Nausea
|
20.0%
4/20 • Number of events 4 • Day 1 through Day 60
|
42.9%
9/21 • Number of events 19 • Day 1 through Day 60
|
|
Gastrointestinal disorders
Vomiting
|
5.0%
1/20 • Number of events 1 • Day 1 through Day 60
|
28.6%
6/21 • Number of events 18 • Day 1 through Day 60
|
|
General disorders
Complication associated with device
|
0.00%
0/20 • Day 1 through Day 60
|
4.8%
1/21 • Number of events 1 • Day 1 through Day 60
|
|
General disorders
Injection site erythema
|
0.00%
0/20 • Day 1 through Day 60
|
4.8%
1/21 • Number of events 1 • Day 1 through Day 60
|
|
General disorders
Injection site pruritus
|
0.00%
0/20 • Day 1 through Day 60
|
4.8%
1/21 • Number of events 1 • Day 1 through Day 60
|
|
Infections and infestations
Influenza
|
5.0%
1/20 • Number of events 1 • Day 1 through Day 60
|
0.00%
0/21 • Day 1 through Day 60
|
|
Infections and infestations
Nasopharyngitis
|
10.0%
2/20 • Number of events 2 • Day 1 through Day 60
|
14.3%
3/21 • Number of events 3 • Day 1 through Day 60
|
|
Infections and infestations
Otitis media
|
0.00%
0/20 • Day 1 through Day 60
|
4.8%
1/21 • Number of events 1 • Day 1 through Day 60
|
|
Infections and infestations
Pyelonephritis
|
5.0%
1/20 • Number of events 1 • Day 1 through Day 60
|
0.00%
0/21 • Day 1 through Day 60
|
|
Infections and infestations
Rhinitis
|
10.0%
2/20 • Number of events 2 • Day 1 through Day 60
|
4.8%
1/21 • Number of events 1 • Day 1 through Day 60
|
|
Infections and infestations
Urinary tract infection
|
5.0%
1/20 • Number of events 1 • Day 1 through Day 60
|
0.00%
0/21 • Day 1 through Day 60
|
|
Injury, poisoning and procedural complications
Face injury
|
0.00%
0/20 • Day 1 through Day 60
|
4.8%
1/21 • Number of events 1 • Day 1 through Day 60
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/20 • Day 1 through Day 60
|
4.8%
1/21 • Number of events 1 • Day 1 through Day 60
|
|
Investigations
Alanine aminotransferase increased
|
5.0%
1/20 • Number of events 1 • Day 1 through Day 60
|
0.00%
0/21 • Day 1 through Day 60
|
|
Investigations
Aspartate aminotransferase increased
|
5.0%
1/20 • Number of events 1 • Day 1 through Day 60
|
0.00%
0/21 • Day 1 through Day 60
|
|
Investigations
Glomerular filtration rate decreased
|
0.00%
0/20 • Day 1 through Day 60
|
4.8%
1/21 • Number of events 1 • Day 1 through Day 60
|
|
Metabolism and nutrition disorders
Decreased appetite
|
0.00%
0/20 • Day 1 through Day 60
|
14.3%
3/21 • Number of events 3 • Day 1 through Day 60
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
5.0%
1/20 • Number of events 1 • Day 1 through Day 60
|
14.3%
3/21 • Number of events 8 • Day 1 through Day 60
|
|
Metabolism and nutrition disorders
Hypoglycaemia unawareness
|
0.00%
0/20 • Day 1 through Day 60
|
4.8%
1/21 • Number of events 1 • Day 1 through Day 60
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
5.0%
1/20 • Number of events 1 • Day 1 through Day 60
|
0.00%
0/21 • Day 1 through Day 60
|
|
Nervous system disorders
Carotid artery stenosis
|
5.0%
1/20 • Number of events 1 • Day 1 through Day 60
|
0.00%
0/21 • Day 1 through Day 60
|
|
Nervous system disorders
Dizziness
|
5.0%
1/20 • Number of events 1 • Day 1 through Day 60
|
9.5%
2/21 • Number of events 2 • Day 1 through Day 60
|
|
Nervous system disorders
Headache
|
10.0%
2/20 • Number of events 3 • Day 1 through Day 60
|
9.5%
2/21 • Number of events 3 • Day 1 through Day 60
|
|
Psychiatric disorders
Nervousness
|
5.0%
1/20 • Number of events 1 • Day 1 through Day 60
|
0.00%
0/21 • Day 1 through Day 60
|
|
Respiratory, thoracic and mediastinal disorders
Sleep apnoea syndrome
|
0.00%
0/20 • Day 1 through Day 60
|
4.8%
1/21 • Number of events 1 • Day 1 through Day 60
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
0.00%
0/20 • Day 1 through Day 60
|
4.8%
1/21 • Number of events 1 • Day 1 through Day 60
|
|
Skin and subcutaneous tissue disorders
Night sweats
|
5.0%
1/20 • Number of events 1 • Day 1 through Day 60
|
0.00%
0/21 • Day 1 through Day 60
|
|
Skin and subcutaneous tissue disorders
Skin fissures
|
0.00%
0/20 • Day 1 through Day 60
|
4.8%
1/21 • Number of events 1 • Day 1 through Day 60
|
|
Skin and subcutaneous tissue disorders
Skin swelling
|
0.00%
0/20 • Day 1 through Day 60
|
4.8%
1/21 • Number of events 1 • Day 1 through Day 60
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee MedImmune has 60 days to review results communications prior to public release and may delete information that compromises on going studies or is considered proprietary. This restriction is not intended to compromise the objective scientific integrity of the manuscript, it being understood that results shall be published regardless of outcome.
- Publication restrictions are in place
Restriction type: OTHER