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NCT03645421

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

Completed Phase 2 Results posted Last updated 23 December 2019
What this trial tests

Phase 2 trial testing MEDI0382 100 μg in Type 2 Diabetes in 61 participants. Completed in 17 January 2019.

Timeline
10 August 2018
Primary endpoint
17 January 2019
17 January 2019

Quick facts

Lead sponsorAstraZeneca
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingdouble
Primary purposetreatment
Enrollment61
Start date10 August 2018
Primary completion17 January 2019
Estimated completion17 January 2019
Sites5 locations across Japan

Drugs / interventions tested

Conditions studied

Sponsor

AstraZeneca — full company profile →

Who can join

Adults 20 to 120, any sex, with Type 2 Diabetes. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Mean Change From Baseline in 24-Hour Heart Rate at Days 20 and 48 Primary · Baseline (Day -1) and Days 20 and 48.

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.

Day 20
GroupValue95% CI
Placebo-1.86± 7.43
MEDI0382 100 mcg6.65± 7.46
MEDI0382 200 mcg13.50± 5.86
MEDI0382 300 mcg15.80± 7.86
Day 48
GroupValue95% CI
Placebo-0.25± 7.24
MEDI0382 100 mcg7.87± 8.60
MEDI0382 200 mcg12.81± 4.93
MEDI0382 300 mcg15.22± 5.50
Mean Change From Baseline in 24-Hour Systolic and Diastolic Blood Pressure (BP) at Days 20 and 48 Primary · 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.

24-hour Systolic BP: Day 20
GroupValue95% CI
Placebo2.98± 9.00
MEDI0382 100 mcg-4.09± 8.93
MEDI0382 200 mcg-7.24± 10.54
MEDI0382 300 mcg-2.48± 9.28
24-hour Systolic BP: Day 48
GroupValue95% CI
Placebo0.08± 14.32
MEDI0382 100 mcg-2.27± 12.42
MEDI0382 200 mcg-5.17± 19.35
MEDI0382 300 mcg-6.97± 7.48
24-hour Diastolic BP: Day 20
GroupValue95% CI
Placebo0.98± 4.34
MEDI0382 100 mcg-0.62± 3.42
MEDI0382 200 mcg-1.41± 4.56
MEDI0382 300 mcg0.81± 5.58
24-hour Diastolic BP: Day 48
GroupValue95% CI
Placebo-0.06± 6.82
MEDI0382 100 mcg-0.66± 4.56
MEDI0382 200 mcg-0.27± 9.17
MEDI0382 300 mcg-0.68± 3.88
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 Primary · 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.

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.

GroupValue95% CI
Placebo2.45-3.37 – 8.26
MEDI0382 100 mcg-39.66-45.67 – -33.66
MEDI0382 200 mcg-31.16-38.61 – -23.71
MEDI0382 300 mcg-37.86-44.95 – -30.76
Mean Percentage Change From Baseline in Body Weight at Day 48 Primary · Baseline (Day -1) and Day 48.

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 \[LOCF\]).

GroupValue95% CI
Placebo-0.82-2.06 – 0.43
MEDI0382 100 mcg-2.12-3.40 – -0.84
MEDI0382 200 mcg-3.34-4.68 – -2.01
MEDI0382 300 mcg-3.34-4.61 – -2.06
Mean Change From Baseline in Heart Rate Measured by Electrocardiogram (ECG) at Day 48. Primary · 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.

Day 1: 6 hours postdose
GroupValue95% CI
Placebo1.77± 7.20
MEDI0382 100 mcg4.24± 5.00
MEDI0382 200 mcg2.18± 8.62
MEDI0382 300 mcg6.27± 7.91
Day 6: predose
GroupValue95% CI
Placebo-2.85± 4.93
MEDI0382 100 mcg1.84± 8.56
MEDI0382 200 mcg7.69± 7.11
MEDI0382 300 mcg10.79± 5.87
Day 6: 6 hours postdose
GroupValue95% CI
Placebo0.02± 8.79
MEDI0382 100 mcg4.62± 9.11
MEDI0382 200 mcg8.88± 6.06
MEDI0382 300 mcg10.67± 7.59
Day 13: predose
GroupValue95% CI
Placebo-2.63± 5.58
MEDI0382 100 mcg6.91± 8.83
MEDI0382 200 mcg8.93± 6.84
MEDI0382 300 mcg11.74± 7.92
Day 13: 6 hours postdose
GroupValue95% CI
Placebo2.19± 9.13
MEDI0382 100 mcg6.40± 11.41
MEDI0382 200 mcg16.62± 7.14
MEDI0382 300 mcg13.31± 9.45
Day 20: predose
GroupValue95% CI
Placebo-1.85± 7.52
MEDI0382 100 mcg6.24± 8.02
MEDI0382 200 mcg11.97± 8.12
MEDI0382 300 mcg13.03± 8.65
Day 20: 6 hours postdose
GroupValue95% CI
Placebo0.29± 9.15
MEDI0382 100 mcg5.09± 9.37
MEDI0382 200 mcg16.79± 6.21
MEDI0382 300 mcg16.94± 8.86
Day 48: predose
GroupValue95% CI
Placebo-1.06± 10.06
MEDI0382 100 mcg7.20± 5.88
MEDI0382 200 mcg10.20± 9.70
MEDI0382 300 mcg17.06± 6.12
Number of Patients Who Experienced Adverse Events (AEs) Primary · Day 1 up to 14 days after the last dose of IP (approximately 9 weeks).

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.

Any AE
GroupValue95% CI
Placebo6
MEDI0382 100 mcg6
MEDI0382 200 mcg11
MEDI0382 300 mcg9
Any SAE
GroupValue95% CI
Placebo0
MEDI0382 100 mcg0
MEDI0382 200 mcg0
MEDI0382 300 mcg0
Any AE leading to discontinuation of IP
GroupValue95% CI
Placebo0
MEDI0382 100 mcg0
MEDI0382 200 mcg4
MEDI0382 300 mcg1
Mean Change From Baseline in HbA1c at Day 48 Secondary · 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).

GroupValue95% CI
Placebo-0.14-0.41 – 0.12
MEDI0382 100 mcg-1.23-1.51 – -0.96
MEDI0382 200 mcg-1.24-1.53 – -0.96
MEDI0382 300 mcg-0.90-1.18 – -0.63
Mean Change From Baseline in Fasting Plasma Glucose at Day 48 Secondary · 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).

GroupValue95% CI
Placebo-0.40-12.60 – 11.80
MEDI0382 100 mcg-57.10-69.77 – -44.42
MEDI0382 200 mcg-60.98-76.82 – -45.15
MEDI0382 300 mcg-55.47-70.28 – -40.66
Mean Change From Baseline in Fructosamine at Day 48 Secondary · 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).

GroupValue95% CI
Placebo-0.012-0.029 – 0.004
MEDI0382 100 mcg-0.083-0.100 – -0.066
MEDI0382 200 mcg-0.066-0.083 – -0.048
MEDI0382 300 mcg-0.061-0.079 – -0.044
Mean Change From Baseline in the Percentage of Time in Hyperglycaemia Over 24 Hours at Days 5, 12, 19 and 47 Secondary · 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.

Day 5
GroupValue95% CI
Placebo-3.23± 12.59
MEDI0382 100 mcg-48.35± 21.27
MEDI0382 200 mcg-33.71± 24.67
MEDI0382 300 mcg-51.33± 30.04
Day 12
GroupValue95% CI
Placebo-11.72± 28.58
MEDI0382 100 mcg-57.74± 24.59
MEDI0382 200 mcg-53.36± 21.59
MEDI0382 300 mcg-55.78± 25.19
Day 19
GroupValue95% CI
Placebo-12.08± 17.61
MEDI0382 100 mcg-59.57± 16.98
MEDI0382 200 mcg-43.85± 28.96
MEDI0382 300 mcg-60.68± 24.93
Day 47
GroupValue95% CI
Placebo-6.15± 22.80
MEDI0382 100 mcg-47.99± 20.63
MEDI0382 200 mcg-48.96± 20.28
MEDI0382 300 mcg-57.59± 21.86
Mean Change From Baseline in the Percentage of Time in Hypoglycaemia Over 24 Hours at Days 5, 12, 19 and 47 Secondary · 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.

Day 5
GroupValue95% CI
Placebo0.00± 0.00
MEDI0382 100 mcg0.00± 0.00
MEDI0382 200 mcg0.00± 0.00
MEDI0382 300 mcg6.28± 16.61
Day 12
GroupValue95% CI
Placebo0.00± 0.00
MEDI0382 100 mcg0.00± 0.00
MEDI0382 200 mcg0.00± 0.00
MEDI0382 300 mcg0.00± 0.00
Day 19
GroupValue95% CI
Placebo0.00± 0.00
MEDI0382 100 mcg0.00± 0.00
MEDI0382 200 mcg3.68± 12.75
MEDI0382 300 mcg0.00± 0.00
Day 47
GroupValue95% CI
Placebo0.00± 0.00
MEDI0382 100 mcg0.00± 0.00
MEDI0382 200 mcg0.00± 0.00
MEDI0382 300 mcg0.00± 0.00
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 Secondary · 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

Days 1 to 5
GroupValue95% CI
Placebo-1.43± 10.26
MEDI0382 100 mcg-42.52± 13.46
MEDI0382 200 mcg-38.68± 18.97
MEDI0382 300 mcg-34.74± 18.24
Days 6 to 12
GroupValue95% CI
Placebo-8.97± 26.12
MEDI0382 100 mcg-48.35± 16.01
MEDI0382 200 mcg-50.81± 18.97
MEDI0382 300 mcg-51.82± 16.73
Days 13 to 19
GroupValue95% CI
Placebo-6.09± 19.10
MEDI0382 100 mcg-53.25± 16.47
MEDI0382 200 mcg-52.33± 20.96
MEDI0382 300 mcg-47.50± 20.67
Days 41 to 47
GroupValue95% CI
Placebo-0.40± 22.70
MEDI0382 100 mcg-42.37± 17.22
MEDI0382 200 mcg-43.44± 18.26
MEDI0382 300 mcg-51.25± 17.12

Adverse events — posted to ClinicalTrials.gov

Time frame: Treatment-emergent AEs were collected from Day 1 of treatment up to 14 days after the last dose of IP (approximately 9 weeks).. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo
Serious: 0/16 (0%)
Deaths: 0/16
MEDI0382 100 mcg
Serious: 0/15 (0%)
Deaths: 0/15
MEDI0382 200 mcg
Serious: 0/15 (0%)
Deaths: 0/15
MEDI0382 300 mcg
Serious: 0/15 (0%)
Deaths: 0/15
Other adverse events (23 terms — click to expand)

ReactionSystemPlaceboMEDI0382 100 mcgMEDI0382 200 mcgMEDI0382 300 mcg
NauseaGastrointestinal disorders
VomitingGastrointestinal disorders
MalaiseGeneral disorders
Decreased appetiteMetabolism and nutrition disorders
NasopharyngitisInfections and infestations
Haemorrhage subcutaneousSkin and subcutaneous tissue disorders
Abdominal distensionGastrointestinal disorders
Abdominal painGastrointestinal disorders
Faeces hardGastrointestinal disorders
Gastrointestinal motility disorderGastrointestinal disorders
Gastrooesophageal reflux diseaseGastrointestinal disorders
Abdominal pain upperGastrointestinal disorders
ConstipationGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
Injection site bruisingGeneral disorders
Injection site erythemaGeneral disorders
Injection site pruritusGeneral disorders
FolliculitisInfections and infestations
TonsillitisInfections and infestations
DizzinessNervous system disorders
UrticariaSkin and subcutaneous tissue disorders
Dry eyeEye disorders
InsomniaPsychiatric disorders

Data from ClinicalTrials.gov NCT03645421 adverse events section.

Sponsor's own description

This is a Phase 2a study designed to assess the safety and tolerability of MEDI0382 titrated up to a dose level of 100, 200 or 300 µg from 50 µg vs Placebo across 48 days in Japanese subjects. The study D5674C00001 can be conducted with a reasonable expectation of safety and tolerability in Japanese T2DM patients. The design of this study has taken into account the known benefits and risks of GLP-1 receptor agonists and glucagon receptor agonists as well as the translatable effects observed in nonclinical studies of MEDI0382.

Publications & conference data

3 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Impact of Cotadutide drug on patients with type 2 diabetes mellitus: a systematic review and meta-analysis.
    Ali MM, Hafez A, Abdelgalil MS, Hasan MT, et al · · 2022 · cited 19× · PMID 35488292 · DOI 10.1186/s12902-022-01031-5
  2. Pharmacotherapy for Non-alcoholic Fatty Liver Disease Associated with Diabetes Mellitus Type 2.
    Koullias ES, Koskinas J. · · 2022 · cited 4× · PMID 36304499 · DOI 10.14218/jcth.2021.00564
  3. Glycemic control, weight-loss effects, and safety of cotadutide in individuals with type 2 diabetes: A systematic review and meta-analysis.
    Kamrul-Hasan ABM, Dutta D, Nagendra L, Basavarajappa SD, et al · · 2025 · PMID 41480597 · DOI 10.4239/wjd.v16.i12.112830

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