A Study to Evaluate the Efficacy and Safety of MEDI0382 in the Treatment of Overweight and Obese Subjects With Type 2 Diabetes

Sponsor
AstraZeneca (Industry)
Overall Status
Completed
CT.gov ID
NCT03235050
Collaborator
MedImmune LLC (Industry)
834
119
5
22.4
7
0.3

Study Details

Study Description

Brief Summary

This study is designed to evaluate the dose range for MEDI0382 with respect to blood glucose control and weight loss effects, as well as to further explore the safety profile of MEDI0382

Condition or Disease Intervention/Treatment Phase
  • Drug: MEDI0382 low dose
  • Drug: MEDI0382 mid dose
  • Drug: MEDI0382 high dose
  • Drug: Placebo
  • Drug: Liraglutide
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
834 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
Randomised, parallel, double-blind, placebo-controlled study with an open-label active comparator.Randomised, parallel, double-blind, placebo-controlled study with an open-label active comparator.
Masking:
Triple (Participant, Care Provider, Investigator)
Masking Description:
The study will be conducted in a double-blind fashion for MEDI0382 and placebo. The sponsor staff, the subjects, and the Investigators involved in the treatment of subjects or in the clinical evaluation of subjects will not be aware of the treatment received. Liraglutide will be provided in an open-label active comparator arm.
Primary Purpose:
Treatment
Official Title:
A Phase IIb, Randomised, Parallel, Double-Blind Placebo-Controlled and Open-Label Active Comparator Study to Evaluate the Efficacy and Safety of MEDI0382 in the Treatment of Overweight and Obese Subjects With Type 2 Diabetes Mellitus
Actual Study Start Date :
Aug 2, 2017
Actual Primary Completion Date :
May 3, 2018
Actual Study Completion Date :
Jun 14, 2019

Arms and Interventions

Arm Intervention/Treatment
Experimental: MEDI0382 low dose + Metformin

Drug: MEDI0382 low dose Drug: Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)

Drug: MEDI0382 low dose
Pharmaceutical form: solution Route of administration: subcutaneous

Experimental: MEDI0382 mid dose + Metformin

Drug: MEDI0382 mid dose Drug: Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)

Drug: MEDI0382 mid dose
Pharmaceutical form: solution Route of administration: subcutaneous

Experimental: MEDI0382 high dose + Metformin

Drug: MEDI0382 high dose Drug: Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)

Drug: MEDI0382 high dose
Pharmaceutical form: solution Route of administration: subcutaneous

Placebo Comparator: Placebo + Metformin

Drug: Placebo Drug: Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)

Drug: Placebo
Pharmaceutical form: solution Route of administration: subcutaneous

Active Comparator: Liraglutide + Metformin

Drug: Liraglutide Drug: Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)

Drug: Liraglutide
Pharmaceutical form: solution Route of administration: subcutaneous

Outcome Measures

Primary Outcome Measures

  1. Change in HbA1c [From baseline to 14 weeks]

    To assess the effect of 100, 200, 300 μg of cotadutide on HbA1c versus placebo

  2. Percent Change in Body Weight [From baseline to 14 weeks]

    To assess the effect of 100, 200, 300 μg of cotadutide on body weight versus placebo

Secondary Outcome Measures

  1. Change in HbA1c [from baseline to 26 weeks and 54 weeks]

    To assess the effect of 100, 200, 300 μg of cotadutide on HbA1c versus placebo

  2. Percentage of Participants Achieving an HbA1c Target < 7.0% [after 14, 26, and 54 weeks]

    To assess the effect of 100, 200, and 300 μg of cotadutide on percentage of participants achieving an HbA1c target of <7% versus placebo

  3. Percent Change in Body Weight [from baseline to 26 weeks and 54 weeks]

    To assess the effect of 100, 200, and 300 μg of cotadutide on body weight versus placebo

  4. Absolute Change in Body Weight [from baseline to 14 weeks, 26 weeks and 54 weeks]

    To assess the effect of 100, 200, 300 μg of cotadutide on body weight versus placebo

  5. Percent Change in Body Weight Versus Active Comparator [from baseline to 14 weeks, 26 weeks and 54 weeks]

    To assess the effect of 100, 200, and 300 μg of cotadutide on body weight versus liraglutide 1.8 mg once daily

  6. Absolute Change in Body Weight Versus Active Comparator [from baseline to 14 weeks, 26 weeks and 54 weeks]

    To assess the effect of 100, 200, and 300 μg of cotadutide on body weight versus liraglutide 1.8 mg once daily

  7. Percentage of Participants Achieving Weight Loss of ≥5% and ≥10% [after 14 weeks, 26 weeks and 54 weeks]

    To assess the effect of 100, 200, and 300 μg of cotadutide on percentage of subjects achieving weight loss of ≥5% and ≥10% versus placebo

  8. Percentage of Participants Rescued or Discontinued for Lack of Glycaemic Control [at 14 weeks, 26 weeks and 54 weeks]

    To assess the effect of 100, 200, and 300 μg of cotadutide on the requirement for additional blood glucose-lowering therapies versus placebo

  9. Pharmacokinetic (PK) Endpoint: Trough Plasma Concentration (Cmin) [Time points at which outcome measure were assessed for plasma concentration were Weeks 1,2,6,10,14,18,22,26, and 54]

    To characterise the PK profile of 100, 200, and 300 μg of cotadutide

  10. Immunogenicity Endpoint: Overall Antidrug Antibody (ADA) Incidence (Number and Percentage of Positive Partipants) [Baseline through 54-week treatment period and 28-day follow-up]

    To characterise the immunogenicity of 100, 200, and 300 μg of cotadutide

  11. Immunogenicity Endpoint: Median Titer of the Anti-Drug Antibodies (ADA) to MEDI0382 in the Positive Participants [Baseline through 54-week treatment period and 28-day follow-up]

    To characterise the immunogenicity of 100, 200, and 300 μg of cotadutide

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 130 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
  • Provision of informed consent

  • Male and female subjects aged ≥ 18 years at screening

  • Body mass index ≥ 25 kg/m2 at screening

  • HbA1c range of 7.0% to 10.5% (inclusive) at screening

  • Diagnosed with type-2 diabetes mellitus (T2DM) and treated with metformin (stable dose of ≥1500 mg/day or maximal tolerated dose) for at least 2 months prior to screening. Use of another glucose-lowering medication for up to 2 weeks in the 2 months prior to screening is acceptable

  • Women of childbearing potential (WOCBP), not breastfeeding and using appropriate birth control to avoid pregnancy throughout the study and for up to 4 weeks after the last dose of investigational product (IP), with a negative pregnancy test within 72 hours prior to the start of IP

Exclusion Criteria:
  • History of, or any existing condition that, in the opinion of the Investigator, would interfere with evaluation of the IP, put the subject at risk, influence the subject's ability to participate or affect the interpretation of the results of the study and/or any subject unable or unwilling to follow study procedures

  • Any subject who has received another IP as part of a clinical study or a GLP-1 receptor agonist containing preparation within the last 30 days or 5 half lives of the drug (whichever is longer) at the time of screening

  • Severe allergy/hypersensitivity to any of the proposed study treatments or excipients

  • Symptoms of acutely decompensated blood glucose control, a history of type 1 diabetes mellitus or diabetic ketoacidosis, or if the subject has been treated with daily subcutaneous (SC) insulin for a period longer than 2 weeks within 90 days prior to screening

  • Acute or chronic pancreatitis. Subjects with serum triglyceride concentrations above 1000 mg/dL (11 mmol/L) at screening

  • Significant inflammatory bowel disease or other severe disease or surgery affecting the upper Gastrointestinal (GI) tract

  • Significant hepatic disease

  • Impaired renal function defined as estimated glomerular filtration rate (eGFR) ≤30 mL/minute/1.73m2 at screening

  • Severely uncontrolled hypertension

  • Unstable angina pectoris, myocardial infarction (MI), transient ischaemic attack (TIA), or stroke within 3 months prior to screening

  • Severe congestive heart failure

Contacts and Locations

Locations

Site City State Country Postal Code
1 Research Site Birmingham Alabama United States 35205
2 Research Site Chandler Arizona United States 85224
3 Research Site Glendale Arizona United States 85306
4 Research Site Glendale Arizona United States 85308
5 Research Site Mesa Arizona United States 85213
6 Research Site Marietta Georgia United States 30067
7 Research Site Evansville Indiana United States 47715
8 Research Site Baton Rouge Louisiana United States 70808
9 Research Site Metairie Louisiana United States 70006
10 Research Site Elkridge Maryland United States 21075
11 Research Site Bridgeton Missouri United States 63044
12 Research Site Las Vegas Nevada United States 89117
13 Research Site Brooklyn New York United States 11229
14 Research Site Morehead City North Carolina United States 28557
15 Research Site Philadelphia Pennsylvania United States 19104
16 Research Site Greer South Carolina United States 29651
17 Research Site Houston Texas United States 77040
18 Research Site Houston Texas United States 77074
19 Research Site Plano Texas United States 75093
20 Research Site Layton Utah United States 84014
21 Research Site Arlington Virginia United States 22206
22 Research Site Manassas Virginia United States 20110
23 Research Site Botevgrad Bulgaria 2140
24 Research Site Kozloduy Bulgaria
25 Research Site Kyustendil Bulgaria 2500
26 Research Site Lukovit Bulgaria
27 Research Site Petrich Bulgaria 2850
28 Research Site Pleven Bulgaria 5800
29 Research Site Plovdiv Bulgaria 4000
30 Research Site Russe Bulgaria 7002
31 Research Site Sofia Bulgaria 1223
32 Research Site Sofia Bulgaria 1407
33 Research Site Sofia Bulgaria 1606
34 Research Site Sofia Bulgaria 1618
35 Research Site Stara Zagora Bulgaria 6000
36 Research Site Red Deer Alberta Canada T4N 6V7
37 Research Site Sherwood Park Alberta Canada T8L 0N2
38 Research Site Burlington Ontario Canada L7M 4Y1
39 Research Site Etobicoke Ontario Canada M9W 4L6
40 Research Site Guelph Ontario Canada N1H 1B1
41 Research Site London Ontario Canada N5W 6A2
42 Research Site London Ontario Canada N6G 5A9
43 Research Site Newmarket Ontario Canada L3Y 5G8
44 Research Site Sarnia Ontario Canada N7T 4X3
45 Research Site Thornhill Ontario Canada L4J 8L7
46 Research Site Toronto Ontario Canada M4G 3E8
47 Research Site Levis Quebec Canada G6W 0M5
48 Research Site Montreal Quebec Canada H4A 3T2
49 Research Site Montreal Quebec Canada H4N 2W2
50 Research Site Saint-Marc-des-Carrieres Quebec Canada G0A 4B0
51 Research Site Beroun Czechia 266 00
52 Research Site Jilove u Prahy Czechia 254 01
53 Research Site Pardubice Czechia 530 02
54 Research Site Plzen - Severni Predmesti Czechia 301 00
55 Research Site Plzen Czechia 301 66
56 Research Site Praha - Klanovice Czechia 190 14
57 Research Site Praha 10 Czechia 104 00
58 Research Site Praha 4 Czechia 140 00
59 Research Site Praha 4 Czechia 149 00
60 Research Site Praha Czechia 140 59
61 Research Site Uherske Hradiste Czechia 686 01
62 Research Site Aschaffenburg Germany 63739
63 Research Site Berlin Germany 10437
64 Research Site Berlin Germany 10787
65 Research Site Eschweiler Germany 52249
66 Research Site Essen Germany 45136
67 Research Site Essen Germany 45359
68 Research Site Gelnhausen Germany 63571
69 Research Site Hamburg Germany 21109
70 Research Site Hamburg Germany 22607
71 Research Site Hof Germany 95030
72 Research Site Löhne Germany 32584
73 Research Site Lübeck Germany 23538
74 Research Site Magdeburg Germany 39120
75 Research Site Mannheim Germany 68163
76 Research Site Munster Germany 48145
77 Research Site Oldenburg Germany 23758
78 Research Site Pirna Germany 01796
79 Research Site Rhaunen Germany 55624
80 Research Site Villingen-Schwenningen Germany 78048
81 Research Site Guadalajara Mexico 44670
82 Research Site Monterrey Mexico 66465
83 Research Site México Mexico 03300
84 Research Site México Mexico 11650
85 Research Site Veracruz Mexico 91900
86 Research Site Veracruz Mexico 91910
87 Research Site Chelyabinsk Russian Federation 454091
88 Research Site Ekaterinburg Russian Federation 620039
89 Research Site Izhevsk Russian Federation 426035
90 Research Site Kemerovo Russian Federation 650066
91 Research Site Moscow Russian Federation 119034
92 Research Site Moscow Russian Federation 119435
93 Research Site Moscow Russian Federation 125367
94 Research Site Novosibirsk Russian Federation 630051
95 Research Site Perm Russian Federation 614000
96 Research Site Perm Russian Federation 614068
97 Research Site Saint Petersburg Russian Federation 196601
98 Research Site Saint-Petersburg Russian Federation 199226
99 Research Site St. Petersburg Russian Federation 196084
100 Research Site St.Petersburg Russian Federation 198013
101 Research Site Vladikavkaz Russian Federation 362007
102 Research Site Volgograd Russian Federation 400131
103 Research Site Banska Bystrica Slovakia 974 01
104 Research Site Bratislava Slovakia 831 01
105 Research Site Dolny Kubin Slovakia 026 01
106 Research Site Levice Slovakia 934 01
107 Research Site Lucenec Slovakia 984 01
108 Research Site Malacky Slovakia 901 01
109 Research Site Namestovo Slovakia 029 01
110 Research Site Nitra Slovakia 949 11
111 Research Site Nove Mesto nad Vahom Slovakia 915 01
112 Research Site Prievidza Slovakia 971 01
113 Research Site Rimavska Sobota Slovakia 979 01
114 Research Site Roznava Slovakia 048 01
115 Research Site Sabinov Slovakia 083 01
116 Research Site Trebisov Slovakia 075 01
117 Research Site Trencin Slovakia 911 01
118 Research Site Trnava Slovakia 917 01
119 Research Site Zilina Slovakia 010 01

Sponsors and Collaborators

  • AstraZeneca
  • MedImmune LLC

Investigators

None specified.

Study Documents (Full-Text)

More Information

Additional Information:

Publications

None provided.
Responsible Party:
AstraZeneca
ClinicalTrials.gov Identifier:
NCT03235050
Other Study ID Numbers:
  • D5670C00004
First Posted:
Aug 1, 2017
Last Update Posted:
Aug 17, 2020
Last Verified:
Jul 1, 2020
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail
Arm/Group Title Placebo Liraglutide MEDI0382 100 mcg MEDI0382 200 mcg MEDI0382 300 mcg
Arm/Group Description Placebo / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose) Liraglutide + Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose) MEDI0382(cotadutide) low dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose) MEDI0382(cotadutide) mid dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose) MEDI0382(cotadutide) high dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)
Period Title: Overall Study
STARTED 112 110 100 256 256
COMPLETED 108 105 96 242 245
NOT COMPLETED 4 5 4 14 11

Baseline Characteristics

Arm/Group Title Placebo Liraglutide MEDI0382 100 mcg MEDI0382 200 mcg MEDI0382 300 mcg Total
Arm/Group Description Placebo / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose) Liraglutide + Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose) MEDI0382 low dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose) MEDI0382 mid dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose) MEDI0382 high dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose) Total of all reporting groups
Overall Participants 112 110 100 256 256 834
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]
57.3
(9.5)
55.5
(9.8)
57.6
(9.9)
57.3
(9.9)
56.3
(10.2)
56.8
(9.9)
Sex: Female, Male (Count of Participants)
Female
55
49.1%
60
54.5%
57
57%
147
57.4%
129
50.4%
448
53.7%
Male
57
50.9%
50
45.5%
43
43%
109
42.6%
127
49.6%
386
46.3%
Race/Ethnicity, Customized (Count of Participants)
American Indian or Alaska Native
3
2.7%
3
2.7%
0
0%
5
2%
0
0%
11
1.3%
Asian
1
0.9%
1
0.9%
0
0%
3
1.2%
1
0.4%
6
0.7%
Black or African American
0
0%
3
2.7%
1
1%
3
1.2%
3
1.2%
10
1.2%
White
107
95.5%
103
93.6%
99
99%
245
95.7%
252
98.4%
806
96.6%
Other
1
0.9%
0
0%
0
0%
0
0%
0
0%
1
0.1%

Outcome Measures

1. Primary Outcome
Title Change in HbA1c
Description To assess the effect of 100, 200, 300 μg of cotadutide on HbA1c versus placebo
Time Frame From baseline to 14 weeks

Outcome Measure Data

Analysis Population Description
ITT population
Arm/Group Title Placebo MEDI0382 100 mcg MEDI0382 200 mcg MEDI0382 300 mcg
Arm/Group Description Placebo / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose) MEDI0382 low dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose) MEDI0382 mid dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose) MEDI0382 high dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)
Measure Participants 112 100 256 256
Least Squares Mean (95% Confidence Interval) [percentage]
-0.18
-1.01
-1.22
-1.09
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, MEDI0382 100 mcg
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.83
Confidence Interval (2-Sided) 95%
-1.06 to -0.59
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, MEDI0382 200 mcg
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -1.04
Confidence Interval (2-Sided) 95%
-1.23 to -0.85
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, MEDI0382 300 mcg
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.91
Confidence Interval (2-Sided) 95%
-1.11 to -0.72
Parameter Dispersion Type:
Value:
Estimation Comments
2. Primary Outcome
Title Percent Change in Body Weight
Description To assess the effect of 100, 200, 300 μg of cotadutide on body weight versus placebo
Time Frame From baseline to 14 weeks

Outcome Measure Data

Analysis Population Description
ITT population
Arm/Group Title Placebo MEDI0382 100 mcg MEDI0382 200 mcg MEDI0382 300 mcg
Arm/Group Description Placebo / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose) MEDI0382 low dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose) MEDI0382 mid dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose) MEDI0382 high dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)
Measure Participants 112 100 256 256
Least Squares Mean (95% Confidence Interval) [percentage]
-0.70
-2.70
-3.47
-4.33
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, MEDI0382 100 mcg
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -2.00
Confidence Interval (2-Sided) 95%
-3.08 to -0.91
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, MEDI0382 200 mcg
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -2.76
Confidence Interval (2-Sided) 95%
-3.65 to -1.87
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, MEDI0382 300 mcg
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -3.62
Confidence Interval (2-Sided) 95%
-4.51 to -2.73
Parameter Dispersion Type:
Value:
Estimation Comments
3. Secondary Outcome
Title Change in HbA1c
Description To assess the effect of 100, 200, 300 μg of cotadutide on HbA1c versus placebo
Time Frame from baseline to 26 weeks and 54 weeks

Outcome Measure Data

Analysis Population Description
ITT population
Arm/Group Title Placebo MEDI0382 100 mcg MEDI0382 200 mcg MEDI0382 300 mcg
Arm/Group Description Placebo / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose) MEDI0382 low dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose) MEDI0382 mid dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose) MEDI0382 high dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)
Measure Participants 112 100 256 256
from baseline to 26 weeks
-0.40
-1.06
-1.22
-1.12
from baseline to 54 weeks
-0.44
-0.96
-1.06
-1.01
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, MEDI0382 100 mcg
Comments Week 26
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.66
Confidence Interval (2-Sided) 95%
-0.92 to -0.40
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, MEDI0382 200 mcg
Comments Week 26
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.81
Confidence Interval (2-Sided) 95%
-1.03 to -0.60
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, MEDI0382 300 mcg
Comments Week 26
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.72
Confidence Interval (2-Sided) 95%
-0.94 to -0.51
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, MEDI0382 100 mcg
Comments Week 54
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.52
Confidence Interval (2-Sided) 95%
-0.80 to -0.24
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, MEDI0382 200 mcg
Comments Week 54
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.63
Confidence Interval (2-Sided) 95%
-0.86 to -0.39
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, MEDI0382 300 mcg
Comments Week 54
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.57
Confidence Interval (2-Sided) 95%
-0.80 to -0.34
Parameter Dispersion Type:
Value:
Estimation Comments
4. Secondary Outcome
Title Percentage of Participants Achieving an HbA1c Target < 7.0%
Description To assess the effect of 100, 200, and 300 μg of cotadutide on percentage of participants achieving an HbA1c target of <7% versus placebo
Time Frame after 14, 26, and 54 weeks

Outcome Measure Data

Analysis Population Description
Intent-to-Treat (ITT) population
Arm/Group Title Placebo MEDI0382 100 mcg MEDI0382 200 mcg MEDI0382 300 mcg
Arm/Group Description Placebo / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose) MEDI0382 low dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose) MEDI0382 mid dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose) MEDI0382 high dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)
Measure Participants 112 100 256 256
after 14 weeks
19
17%
50
45.5%
143
143%
143
55.9%
after 26 weeks
25
22.3%
48
43.6%
139
139%
143
55.9%
after 54 weeks
23
20.5%
52
47.3%
125
125%
128
50%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, MEDI0382 100 mcg
Comments Week 14
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments
Method Regression, Logistic
Comments
Method of Estimation Estimation Parameter Odds Ratio, log
Estimated Value 6.67
Confidence Interval (2-Sided) 92%
3.34 to 13.30
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, MEDI0382 200 mcg
Comments Week 14
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments
Method Regression, Logistic
Comments
Method of Estimation Estimation Parameter Odds Ratio, log
Estimated Value 9.95
Confidence Interval (2-Sided) 95%
5.39 to 18.36
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, MEDI0382 300 mcg
Comments Week 14
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments
Method Regression, Logistic
Comments
Method of Estimation Estimation Parameter Odds Ratio, log
Estimated Value 8.52
Confidence Interval (2-Sided) 95%
4.65 to 15.61
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, MEDI0382 100 mcg
Comments Week 26
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments
Method Regression, Logistic
Comments
Method of Estimation Estimation Parameter Odds Ratio, log
Estimated Value 3.74
Confidence Interval (2-Sided) 95%
1.98 to 7.03
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, MEDI0382 200 mcg
Comments Week 26
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments
Method Regression, Logistic
Comments
Method of Estimation Estimation Parameter Odds Ratio, log
Estimated Value 5.40
Confidence Interval (2-Sided) 95%
3.13 to 9.34
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, MEDI0382 300 mcg
Comments Week 26
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments
Method Regression, Logistic
Comments
Method of Estimation Estimation Parameter Odds Ratio, log
Estimated Value 5.20
Confidence Interval (2-Sided) 95%
3.02 to 8.97
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo, MEDI0382 100 mcg
Comments Week 54
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments
Method Regression, Logistic
Comments
Method of Estimation Estimation Parameter Odds Ratio, log
Estimated Value 4.94
Confidence Interval (2-Sided) 95%
2.61 to 9.36
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo, MEDI0382 200 mcg
Comments Week 54
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments
Method Regression, Logistic
Comments
Method of Estimation Estimation Parameter Odds Ratio, log
Estimated Value 4.55
Confidence Interval (2-Sided) 95%
2.62 to 7.89
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Placebo, MEDI0382 300 mcg
Comments Week 54
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments
Method Regression, Logistic
Comments
Method of Estimation Estimation Parameter Odds Ratio, log
Estimated Value 4.34
Confidence Interval (2-Sided) 95%
2.51 to 7.51
Parameter Dispersion Type:
Value:
Estimation Comments
5. Secondary Outcome
Title Percent Change in Body Weight
Description To assess the effect of 100, 200, and 300 μg of cotadutide on body weight versus placebo
Time Frame from baseline to 26 weeks and 54 weeks

Outcome Measure Data

Analysis Population Description
ITT population
Arm/Group Title Placebo MEDI0382 100 mcg MEDI0382 200 mcg MEDI0382 300 mcg
Arm/Group Description Placebo / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose) MEDI0382 low dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose) MEDI0382 mid dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose) MEDI0382 high dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)
Measure Participants 112 100 256 256
from baseline to 26 weeks
-1.14
-3.23
-3.94
-4.60
from baseline to 54 weeks
-0.84
-3.27
-3.08
-4.16
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, MEDI0382 100 mcg
Comments Week 26
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -2.09
Confidence Interval (2-Sided) 95%
-3.32 to -0.85
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, MEDI0382 200 mcg
Comments Week 26
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -2.80
Confidence Interval (2-Sided) 95%
-3.82 to -1.79
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, MEDI0382 300 mcg
Comments Week 26
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -3.46
Confidence Interval (2-Sided) 95%
-4.48 to -2.44
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, MEDI0382 100 mcg
Comments Week 54
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -2.43
Confidence Interval (2-Sided) 95%
-3.86 to -1.00
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, MEDI0382 200 mcg
Comments Week 54
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -2.24
Confidence Interval (2-Sided) 95%
-3.41 to -1.06
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, MEDI0382 300 mcg
Comments Week 54
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -3.32
Confidence Interval (2-Sided) 95%
-4.49 to -2.14
Parameter Dispersion Type:
Value:
Estimation Comments
6. Secondary Outcome
Title Absolute Change in Body Weight
Description To assess the effect of 100, 200, 300 μg of cotadutide on body weight versus placebo
Time Frame from baseline to 14 weeks, 26 weeks and 54 weeks

Outcome Measure Data

Analysis Population Description
ITT population
Arm/Group Title Placebo MEDI0382 100 mcg MEDI0382 200 mcg MEDI0382 300 mcg
Arm/Group Description Placebo / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose) MEDI0382 low dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose) MEDI0382 mid dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose) MEDI0382 high dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)
Measure Participants 112 100 256 256
from baseline to 14 weeks
-0.71
-2.66
-3.45
-4.42
from baseline to 26 weeks
-1.20
-3.20
-3.94
-4.75
from baseline to 54 weeks
-0.94
-3.20
-3.09
-4.35
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, MEDI0382 100 mcg
Comments Week 14
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -1.95
Confidence Interval (2-Sided) 95%
-3.03 to -0.87
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, MEDI0382 200 mcg
Comments Week 14
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -2.75
Confidence Interval (2-Sided) 95%
-3.63 to -1.86
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, MEDI0382 300 mcg
Comments Week 14
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -3.71
Confidence Interval (2-Sided) 95%
-4.60 to -2.82
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, MEDI0382 100 mcg
Comments Week 26
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.002
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -2.01
Confidence Interval (2-Sided) 95%
-3.27 to -0.74
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, MEDI0382 200 mcg
Comments Week 26
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -2.74
Confidence Interval (2-Sided) 95%
-3.78 to -1.71
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, MEDI0382 300 mcg
Comments Week 26
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -3.55
Confidence Interval (2-Sided) 95%
-4.59 to -2.52
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo, MEDI0382 100 mcg
Comments Week 54
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.003
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -2.27
Confidence Interval (2-Sided) 95%
-3.74 to -0.79
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo, MEDI0382 200 mcg
Comments Week 54
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -2.16
Confidence Interval (2-Sided) 95%
-3.37 to -0.95
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Placebo, MEDI0382 300 mcg
Comments Week 54
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -3.42
Confidence Interval (2-Sided) 95%
-4.63 to -2.20
Parameter Dispersion Type:
Value:
Estimation Comments
7. Secondary Outcome
Title Percent Change in Body Weight Versus Active Comparator
Description To assess the effect of 100, 200, and 300 μg of cotadutide on body weight versus liraglutide 1.8 mg once daily
Time Frame from baseline to 14 weeks, 26 weeks and 54 weeks

Outcome Measure Data

Analysis Population Description
ITT population
Arm/Group Title Liraglutide MEDI0382 100 mcg MEDI0382 200 mcg MEDI0382 300 mcg
Arm/Group Description Liraglutide / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose) MEDI0382 low dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose) MEDI0382 mid dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose) MEDI0382 high dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)
Measure Participants 110 100 256 256
Percent change at 14 weeks
-3.40
-2.70
-3.47
-4.33
Percent change at 26 weeks
-4.12
-3.23
-3.94
-4.60
Percent change at 54 weeks
-3.20
-3.27
-3.08
-4.16
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, MEDI0382 100 mcg
Comments Percent change at Week 14
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.211
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.70
Confidence Interval (2-Sided) 95%
-0.39 to 1.79
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, MEDI0382 200 mcg
Comments Percent change at Week 14
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.881
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.07
Confidence Interval (2-Sided) 95%
-0.96 to 0.83
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, MEDI0382 300 mcg
Comments Percent change at Week 14
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.042
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.93
Confidence Interval (2-Sided) 95%
-1.82 to -0.04
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, MEDI0382 100 mcg
Comments Percent change at Week 26
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.158
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.90
Confidence Interval (2-Sided) 95%
-0.35 to 2.14
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, MEDI0382 200 mcg
Comments Percent change at Week 26
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.734
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.18
Confidence Interval (2-Sided) 95%
-0.85 to 1.20
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, MEDI0382 300 mcg
Comments Percent change at Week 26
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.357
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.48
Confidence Interval (2-Sided) 95%
-1.51 to 0.54
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo, MEDI0382 100 mcg
Comments Percent change at Week 54
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.921
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.07
Confidence Interval (2-Sided) 95%
-1.51 to 1.37
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo, MEDI0382 200 mcg
Comments Percent change at Week 54
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.847
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.12
Confidence Interval (2-Sided) 95%
-1.07 to 1.30
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Placebo, MEDI0382 300 mcg
Comments Percent change at Week 54
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.112
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.96
Confidence Interval (2-Sided) 95%
-2.15 to 0.22
Parameter Dispersion Type:
Value:
Estimation Comments
8. Secondary Outcome
Title Absolute Change in Body Weight Versus Active Comparator
Description To assess the effect of 100, 200, and 300 μg of cotadutide on body weight versus liraglutide 1.8 mg once daily
Time Frame from baseline to 14 weeks, 26 weeks and 54 weeks

Outcome Measure Data

Analysis Population Description
ITT population
Arm/Group Title Liraglutide MEDI0382 100 mcg MEDI0382 200 mcg MEDI0382 300 mcg
Arm/Group Description Liraglutide / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose) MEDI0382 low dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose) MEDI0382 mid dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose) MEDI0382 high dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)
Measure Participants 110 100 256 256
Absolute change at 14 weeks
-3.25
-2.66
-3.45
-4.42
Absolute change at 26 weeks
-3.90
-3.20
-3.94
-4.75
Absolute change at 54 weeks
-2.94
-3.20
-3.09
-4.35
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, MEDI0382 100 mcg
Comments Absolute change at Week 14
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.284
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.59
Confidence Interval (2-Sided) 95%
-0.49 to 1.68
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, MEDI0382 200 mcg
Comments Absolute change at Week 14
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.658
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.20
Confidence Interval (2-Sided) 95%
-1.09 to 0.69
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, MEDI0382 300 mcg
Comments Absolute change at Week 14
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.010
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -1.17
Confidence Interval (2-Sided) 95%
-2.06 to -0.27
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, MEDI0382 100 mcg
Comments Absolute change at Week 26
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.279
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.70
Confidence Interval (2-Sided) 95%
-0.57 to 1.97
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, MEDI0382 200 mcg
Comments Absolute change at Week 26
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.940
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.04
Confidence Interval (2-Sided) 95%
-1.08 to 1.00
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, MEDI0382 300 mcg
Comments Absolute change at Week 26
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.110
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.85
Confidence Interval (2-Sided) 95%
-1.89 to 0.19
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo, MEDI0382 100 mcg
Comments Absolute change at Week 54
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.730
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.26
Confidence Interval (2-Sided) 95%
-1.74 to 1.22
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo, MEDI0382 200 mcg
Comments Absolute change at Week 54
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.804
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.15
Confidence Interval (2-Sided) 95%
-1.38 to 1.07
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Placebo, MEDI0382 300 mcg
Comments Absolute change at Week 54
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.023
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -1.41
Confidence Interval (2-Sided) 95%
-2.63 to -0.19
Parameter Dispersion Type:
Value:
Estimation Comments
9. Secondary Outcome
Title Percentage of Participants Achieving Weight Loss of ≥5% and ≥10%
Description To assess the effect of 100, 200, and 300 μg of cotadutide on percentage of subjects achieving weight loss of ≥5% and ≥10% versus placebo
Time Frame after 14 weeks, 26 weeks and 54 weeks

Outcome Measure Data

Analysis Population Description
ITT population
Arm/Group Title Placebo MEDI0382 100 mcg MEDI0382 200 mcg MEDI0382 300 mcg
Arm/Group Description Placebo / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose) MEDI0382 low dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose) MEDI0382 mid dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose) MEDI0382 high dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)
Measure Participants 112 100 256 256
Participants with weight loss ≥5% at Wk 14 (LOCF)
3
2.7%
18
16.4%
65
65%
92
35.9%
Participants with weight loss ≥5% at Wk 26 (LOCF)
11
9.8%
28
25.5%
76
76%
110
43%
Participants with weight loss ≥5% at Wk 54 (LOCF)
14
12.5%
34
30.9%
71
71%
98
38.3%
Participants with weight loss ≥10% at Wk 14 (LOCF)
0
0%
6
5.5%
15
15%
20
7.8%
Participants with weight loss ≥10% at Wk 26 (LOCF)
1
0.9%
7
6.4%
28
28%
27
10.5%
Participants with weight loss ≥10% at Wk 54 (LOCF)
2
1.8%
11
10%
21
21%
32
12.5%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, MEDI0382 100 mcg
Comments weight loss >=5% at Week 14
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments
Method Regression, Logistic
Comments
Method of Estimation Estimation Parameter Odds Ratio, log
Estimated Value 8.37
Confidence Interval (2-Sided) 95%
2.38 to 29.43
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, MEDI0382 200 mcg
Comments weight loss >=5% at Week 14
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments
Method Regression, Logistic
Comments
Method of Estimation Estimation Parameter Odds Ratio, log
Estimated Value 12.46
Confidence Interval (2-Sided) 95%
3.82 to 40.64
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, MEDI0382 300 mcg
Comments weight loss >=5% at Week 14
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments
Method Regression, Logistic
Comments
Method of Estimation Estimation Parameter Odds Ratio, log
Estimated Value 21.26
Confidence Interval (2-Sided) 95%
6.55 to 68.97
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, MEDI0382 100 mcg
Comments weight loss >=5% at Week 26
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments
Method Regression, Logistic
Comments
Method of Estimation Estimation Parameter Odds Ratio, log
Estimated Value 3.68
Confidence Interval (2-Sided) 95%
1.72 to 7.89
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, MEDI0382 200 mcg
Comments weight loss >=5% at Week 26
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments
Method Regression, Logistic
Comments
Method of Estimation Estimation Parameter Odds Ratio, log
Estimated Value 3.95
Confidence Interval (2-Sided) 95%
2.00 to 7.78
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, MEDI0382 300 mcg
Comments weight loss >=5% at Week 26
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments
Method Regression, Logistic
Comments
Method of Estimation Estimation Parameter Odds Ratio, log
Estimated Value 7.28
Confidence Interval (2-Sided) 95%
3.72 to 14.24
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo, MEDI0382 100 mcg
Comments weight loss >=5% at Week 54
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments
Method Regression, Logistic
Comments
Method of Estimation Estimation Parameter Odds Ratio, log
Estimated Value 3.71
Confidence Interval (2-Sided) 95%
1.84 to 7.45
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo, MEDI0382 200 mcg
Comments weight loss >=5% at Week 54
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.002
Comments
Method Regression, Logistic
Comments
Method of Estimation Estimation Parameter Odds Ratio, log
Estimated Value 2.73
Confidence Interval (2-Sided) 95%
1.46 to 5.09
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Placebo, MEDI0382 300 mcg
Comments weight loss >=5% at Week 54
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Odds Ratio, log
Estimated Value 4.48
Confidence Interval (2-Sided) 95%
2.42 to 8.30
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Placebo, MEDI0382 100 mcg
Comments weight loss >=10% at Week 26
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.048
Comments
Method Regression, Logistic
Comments
Method of Estimation Estimation Parameter Odds Ratio, log
Estimated Value 8.47
Confidence Interval (2-Sided) 95%
1.02 to 70.17
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Placebo, MEDI0382 200 mcg
Comments weight loss >=10% at Week 26
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.010
Comments
Method Regression, Logistic
Comments
Method of Estimation Estimation Parameter Odds Ratio, log
Estimated Value 13.81
Confidence Interval (2-Sided) 95%
1.85 to 102.91
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Placebo, MEDI0382 300 mcg
Comments weight loss >=10% at Week 26
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.012
Comments
Method Regression, Logistic
Comments
Method of Estimation Estimation Parameter Odds Ratio, log
Estimated Value 13.09
Confidence Interval (2-Sided) 95%
1.75 to 97.68
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Placebo, MEDI0382 100 mcg
Comments weight loss >=10% at Week 54
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.013
Comments
Method Regression, Logistic
Comments
Method of Estimation Estimation Parameter Odds Ratio, log
Estimated Value 6.92
Confidence Interval (2-Sided) 95%
1.49 to 32.07
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Placebo, MEDI0382 200 mcg
Comments weight loss >=10% at Week 54
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.032
Comments
Method Regression, Logistic
Comments
Method of Estimation Estimation Parameter Odds Ratio, log
Estimated Value 4.98
Confidence Interval (2-Sided) 95%
1.15 to 21.60
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Placebo, MEDI0382 300 mcg
Comments weight loss >=10% at Week 54
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.005
Comments
Method Regression, Logistic
Comments
Method of Estimation Estimation Parameter Odds Ratio, log
Estimated Value 7.91
Confidence Interval (2-Sided) 95%
1.86 to 33.64
Parameter Dispersion Type:
Value:
Estimation Comments
10. Secondary Outcome
Title Percentage of Participants Rescued or Discontinued for Lack of Glycaemic Control
Description To assess the effect of 100, 200, and 300 μg of cotadutide on the requirement for additional blood glucose-lowering therapies versus placebo
Time Frame at 14 weeks, 26 weeks and 54 weeks

Outcome Measure Data

Analysis Population Description
ITT population
Arm/Group Title Placebo MEDI0382 100 mcg MEDI0382 200 mcg MEDI0382 300 mcg
Arm/Group Description Placebo / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose) MEDI0382 low dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose) MEDI0382 mid dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose) MEDI0382 high dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)
Measure Participants 112 100 256 256
received rescue medication at 14 wks
11
9.8%
1
0.9%
3
3%
2
0.8%
received rescue medication at 26 wks
20
17.9%
3
2.7%
8
8%
6
2.3%
received rescue medication at 54 wks
34
30.4%
10
9.1%
26
26%
24
9.4%
discontinued study IP at 14 wks
2
1.8%
0
0%
1
1%
0
0%
discontinued study IP at 26 wks
4
3.6%
1
0.9%
2
2%
0
0%
discontinued study IP at 54 wks
4
3.6%
1
0.9%
3
3%
0
0%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, MEDI0382 100 mcg
Comments received rescue medication at 14 wks
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.024
Comments
Method Regression, Logistic
Comments
Method of Estimation Estimation Parameter Odds Ratio, log
Estimated Value 0.09
Confidence Interval (2-Sided) 95%
0.01 to 0.73
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, MEDI0382 200 mcg
Comments received rescue medication at 14 wks
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments
Method Regression, Logistic
Comments
Method of Estimation Estimation Parameter Odds Ratio, log
Estimated Value 0.11
Confidence Interval (2-Sided) 95%
0.03 to 0.40
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, MEDI0382 300 mcg
Comments received rescue medication at 14 wks
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments
Method Regression, Logistic
Comments
Method of Estimation Estimation Parameter Odds Ratio, log
Estimated Value 0.07
Confidence Interval (2-Sided) 95%
0.02 to 0.33
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, MEDI0382 100 mcg
Comments received rescue medication at 26 wks
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.002
Comments
Method Regression, Logistic
Comments
Method of Estimation Estimation Parameter Odds Ratio, log
Estimated Value 0.14
Confidence Interval (2-Sided) 95%
0.04 to 0.48
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, MEDI0382 200 mcg
Comments received rescue medication at 26 wks
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments
Method Regression, Logistic
Comments
Method of Estimation Estimation Parameter Odds Ratio, log
Estimated Value 0.14
Confidence Interval (2-Sided) 95%
0.06 to 0.34
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, MEDI0382 300 mcg
Comments received rescue medication at 26 wks
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments
Method Regression, Logistic
Comments
Method of Estimation Estimation Parameter Odds Ratio, log
Estimated Value 0.11
Confidence Interval (2-Sided) 95%
0.04 to 0.28
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo, MEDI0382 100 mcg
Comments received rescue medication at 54 wks
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments
Method Regression, Logistic
Comments
Method of Estimation Estimation Parameter Odds Ratio, log
Estimated Value 0.24
Confidence Interval (2-Sided) 95%
0.11 to 0.53
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo, MEDI0382 200 mcg
Comments received rescue medication at 54 wks
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments
Method Regression, Logistic
Comments
Method of Estimation Estimation Parameter Odds Ratio, log
Estimated Value 0.24
Confidence Interval (2-Sided) 95%
0.13 to 0.44
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Placebo, MEDI0382 300 mcg
Comments received rescue medication at 54 wks
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments
Method Regression, Logistic
Comments
Method of Estimation Estimation Parameter Odds Ratio, log
Estimated Value 0.22
Confidence Interval (2-Sided) 95%
0.12 to 0.41
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Placebo, MEDI0382 200 mcg
Comments discontinued IP at 14 wks
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.216
Comments
Method Regression, Logistic
Comments
Method of Estimation Estimation Parameter Odds Ratio, log
Estimated Value 0.22
Confidence Interval (2-Sided) 95%
0.02 to 2.43
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Placebo, MEDI0382 100 mcg
Comments discontinued IP at 26 wks
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.253
Comments
Method Regression, Logistic
Comments
Method of Estimation Estimation Parameter Odds Ratio, log
Estimated Value 0.28
Confidence Interval (2-Sided) 95%
0.03 to 2.52
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Placebo, MEDI0382 200 mcg
Comments discontinued IP at 26 wks
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.079
Comments
Method Regression, Logistic
Comments
Method of Estimation Estimation Parameter Odds Ratio, log
Estimated Value 0.21
Confidence Interval (2-Sided) 95%
0.04 to 1.19
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Placebo, MEDI0382 100 mcg
Comments discontinued IP at 54 wks
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.252
Comments
Method Regression, Logistic
Comments
Method of Estimation Estimation Parameter Odds Ratio, log
Estimated Value 0.27
Confidence Interval (2-Sided) 95%
0.03 to 2.50
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Placebo, MEDI0382 200 mcg
Comments discontinued IP at 54 wks
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.143
Comments
Method Regression, Logistic
Comments
Method of Estimation Estimation Parameter Odds Ratio, log
Estimated Value 0.32
Confidence Interval (2-Sided) 95%
0.07 to 1.47
Parameter Dispersion Type:
Value:
Estimation Comments
11. Secondary Outcome
Title Pharmacokinetic (PK) Endpoint: Trough Plasma Concentration (Cmin)
Description To characterise the PK profile of 100, 200, and 300 μg of cotadutide
Time Frame Time points at which outcome measure were assessed for plasma concentration were Weeks 1,2,6,10,14,18,22,26, and 54

Outcome Measure Data

Analysis Population Description
Per-protocol population
Arm/Group Title Placebo MEDI0382 100 mcg MEDI0382 200 mcg MEDI0382 300 mcg
Arm/Group Description Placebo / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose) MEDI0382 low dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose) MEDI0382 mid dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose) MEDI0382 high dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)
Measure Participants 0 100 256 256
Week 1
2.68
(1.27)
2.76
(1.88)
2.77
(1.84)
Week 2
2.66
(1.61)
5.13
(3.23)
5.18
(3.05)
Week 6
2.75
(1.44)
5.20
(3.57)
7.77
(4.88)
Week 10
3.18
(2.26)
5.74
(4.23)
8.23
(4.31)
Week 14
3.79
(4.05)
6.50
(5.26)
9.71
(7.64)
Week 18
4.58
(5.04)
7.43
(6.43)
10.8
(7.95)
Week 22
4.63
(4.28)
8.07
(7.01)
11.5
(9.77)
Week 26
4.39
(3.33)
8.12
(7.31)
12.9
(12.1)
Week 54
4.58
(3.89)
8.99
(9.22)
13.2
(14.3)
12. Secondary Outcome
Title Immunogenicity Endpoint: Overall Antidrug Antibody (ADA) Incidence (Number and Percentage of Positive Partipants)
Description To characterise the immunogenicity of 100, 200, and 300 μg of cotadutide
Time Frame Baseline through 54-week treatment period and 28-day follow-up

Outcome Measure Data

Analysis Population Description
As-treated population
Arm/Group Title Placebo MEDI0382 100 mcg MEDI0382 200 mcg MEDI0382 300 mcg
Arm/Group Description Placebo / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose) MEDI0382 low dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose) MEDI0382 mid dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose) MEDI0382 high dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)
Measure Participants 112 100 256 256
ADA positive at baseline
1
0.9%
1
0.9%
0
0%
0
0%
ADA incidence
3
2.7%
55
50%
152
152%
155
60.5%
ADA positive post-baseline
3
2.7%
54
49.1%
152
152%
155
60.5%
13. Secondary Outcome
Title Immunogenicity Endpoint: Median Titer of the Anti-Drug Antibodies (ADA) to MEDI0382 in the Positive Participants
Description To characterise the immunogenicity of 100, 200, and 300 μg of cotadutide
Time Frame Baseline through 54-week treatment period and 28-day follow-up

Outcome Measure Data

Analysis Population Description
As-treated population
Arm/Group Title Placebo MEDI0382 100 mcg MEDI0382 200 mcg MEDI0382 300 mcg
Arm/Group Description Placebo / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose) MEDI0382 low dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose) MEDI0382 mid dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose) MEDI0382 high dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)
Measure Participants 112 100 256 256
ADA positive at baseline, median titer
5.0
5.0
0
0
ADA incidence, median of maximum titer
5.0
20.0
20.0
20.0
ADA positive post-baseline, median of max. titer
5.0
20.0
20.0
20.0

Adverse Events

Time Frame Adverse events were collected from time of first IP dose throughout the 54-week treatment period and including the 28-day follow-up period. Serious AEs were recorded from the time of signature of informed consent.
Adverse Event Reporting Description
Arm/Group Title Placebo Liraglutide MEDI0382 100 mcg MEDI0382 200 mcg MEDI0382 300 mcg
Arm/Group Description Placebo / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose) Liraglutide + Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose) MEDI0382 low dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose) MEDI0382 mid dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose) MEDI0382 high dose / Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)
All Cause Mortality
Placebo Liraglutide MEDI0382 100 mcg MEDI0382 200 mcg MEDI0382 300 mcg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 0/112 (0%) 0/110 (0%) 0/100 (0%) 2/256 (0.8%) 1/256 (0.4%)
Serious Adverse Events
Placebo Liraglutide MEDI0382 100 mcg MEDI0382 200 mcg MEDI0382 300 mcg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 12/112 (10.7%) 8/110 (7.3%) 12/100 (12%) 33/256 (12.9%) 20/256 (7.8%)
Cardiac disorders
Acute myocardial infarction 1/112 (0.9%) 1 0/110 (0%) 0 0/100 (0%) 0 1/256 (0.4%) 1 0/256 (0%) 0
Angina pectoris 0/112 (0%) 0 0/110 (0%) 0 0/100 (0%) 0 2/256 (0.8%) 2 1/256 (0.4%) 1
Angina unstable 0/112 (0%) 0 0/110 (0%) 0 1/100 (1%) 1 2/256 (0.8%) 2 1/256 (0.4%) 1
Aortic valve stenosis 0/112 (0%) 0 1/110 (0.9%) 1 0/100 (0%) 0 0/256 (0%) 0 0/256 (0%) 0
Arteriosclerosis coronary artery 0/112 (0%) 0 0/110 (0%) 0 0/100 (0%) 0 1/256 (0.4%) 1 0/256 (0%) 0
Atrial fibrillation 1/112 (0.9%) 1 0/110 (0%) 0 1/100 (1%) 2 0/256 (0%) 0 1/256 (0.4%) 1
Atrial flutter 1/112 (0.9%) 1 0/110 (0%) 0 0/100 (0%) 0 1/256 (0.4%) 1 0/256 (0%) 0
Atrioventricular block complete 1/112 (0.9%) 1 0/110 (0%) 0 0/100 (0%) 0 0/256 (0%) 0 0/256 (0%) 0
Bradycardia 1/112 (0.9%) 1 0/110 (0%) 0 0/100 (0%) 0 0/256 (0%) 0 0/256 (0%) 0
Cardiac failure chronic 0/112 (0%) 0 0/110 (0%) 0 0/100 (0%) 0 1/256 (0.4%) 1 0/256 (0%) 0
Cardiac failure congestive 0/112 (0%) 0 0/110 (0%) 0 0/100 (0%) 0 1/256 (0.4%) 1 0/256 (0%) 0
Coronary artery disease 0/112 (0%) 0 0/110 (0%) 0 1/100 (1%) 1 1/256 (0.4%) 1 0/256 (0%) 0
Myocardial infarction 0/112 (0%) 0 0/110 (0%) 0 0/100 (0%) 0 1/256 (0.4%) 1 1/256 (0.4%) 1
Myocardial ischaemia 0/112 (0%) 0 0/110 (0%) 0 0/100 (0%) 0 1/256 (0.4%) 1 0/256 (0%) 0
Silent myocardial infarction 0/112 (0%) 0 1/110 (0.9%) 1 0/100 (0%) 0 0/256 (0%) 0 0/256 (0%) 0
Eye disorders
Retinal detachment 1/112 (0.9%) 1 0/110 (0%) 0 0/100 (0%) 0 0/256 (0%) 0 0/256 (0%) 0
Retinal tear 0/112 (0%) 0 1/110 (0.9%) 1 0/100 (0%) 0 0/256 (0%) 0 0/256 (0%) 0
Gastrointestinal disorders
Abdominal pain 1/112 (0.9%) 1 0/110 (0%) 0 0/100 (0%) 0 0/256 (0%) 0 0/256 (0%) 0
Abdominal pain upper 0/112 (0%) 0 0/110 (0%) 0 0/100 (0%) 0 1/256 (0.4%) 1 0/256 (0%) 0
Colitis ulcerative 1/112 (0.9%) 1 0/110 (0%) 0 0/100 (0%) 0 0/256 (0%) 0 0/256 (0%) 0
Enterocutaneous fistula 1/112 (0.9%) 1 0/110 (0%) 0 0/100 (0%) 0 0/256 (0%) 0 0/256 (0%) 0
Gastric polyps 0/112 (0%) 0 0/110 (0%) 0 1/100 (1%) 1 1/256 (0.4%) 1 0/256 (0%) 0
Gastrooesophageal reflux disease 0/112 (0%) 0 0/110 (0%) 0 0/100 (0%) 0 0/256 (0%) 0 1/256 (0.4%) 1
Hiatus hernia 0/112 (0%) 0 0/110 (0%) 0 0/100 (0%) 0 1/256 (0.4%) 1 1/256 (0.4%) 1
Inguinal hernia 0/112 (0%) 0 0/110 (0%) 0 0/100 (0%) 0 0/256 (0%) 0 1/256 (0.4%) 1
Irritable bowel syndrome 0/112 (0%) 0 0/110 (0%) 0 0/100 (0%) 0 0/256 (0%) 0 1/256 (0.4%) 1
Megacolon 1/112 (0.9%) 1 0/110 (0%) 0 0/100 (0%) 0 0/256 (0%) 0 0/256 (0%) 0
Pancreatitis acute 0/112 (0%) 0 0/110 (0%) 0 0/100 (0%) 0 1/256 (0.4%) 1 1/256 (0.4%) 1
Retroperitoneal haematoma 0/112 (0%) 0 1/110 (0.9%) 1 0/100 (0%) 0 0/256 (0%) 0 0/256 (0%) 0
General disorders
Impaired healing 0/112 (0%) 0 0/110 (0%) 0 1/100 (1%) 1 0/256 (0%) 0 0/256 (0%) 0
Hepatobiliary disorders
Cholecystitis acute 0/112 (0%) 0 0/110 (0%) 0 0/100 (0%) 0 1/256 (0.4%) 1 0/256 (0%) 0
Cholelithiasis 0/112 (0%) 0 0/110 (0%) 0 1/100 (1%) 1 2/256 (0.8%) 2 0/256 (0%) 0
Gallbladder polyp 0/112 (0%) 0 0/110 (0%) 0 0/100 (0%) 0 0/256 (0%) 0 1/256 (0.4%) 1
Hepatic cirrhosis 0/112 (0%) 0 0/110 (0%) 0 0/100 (0%) 0 1/256 (0.4%) 1 0/256 (0%) 0
Infections and infestations
Acarodermatitis 0/112 (0%) 0 0/110 (0%) 0 0/100 (0%) 0 1/256 (0.4%) 1 0/256 (0%) 0
Appendicitis 0/112 (0%) 0 0/110 (0%) 0 1/100 (1%) 1 0/256 (0%) 0 0/256 (0%) 0
Bacterial infection 1/112 (0.9%) 1 0/110 (0%) 0 0/100 (0%) 0 0/256 (0%) 0 0/256 (0%) 0
Cellulitis 0/112 (0%) 0 0/110 (0%) 0 0/100 (0%) 0 1/256 (0.4%) 1 0/256 (0%) 0
Chronic sinusitis 0/112 (0%) 0 0/110 (0%) 0 0/100 (0%) 0 1/256 (0.4%) 1 0/256 (0%) 0
Erysipelas 0/112 (0%) 0 0/110 (0%) 0 0/100 (0%) 0 0/256 (0%) 0 1/256 (0.4%) 1
Gastroenteritis 0/112 (0%) 0 0/110 (0%) 0 0/100 (0%) 0 1/256 (0.4%) 1 0/256 (0%) 0
Otitis media acute 0/112 (0%) 0 0/110 (0%) 0 0/100 (0%) 0 1/256 (0.4%) 1 0/256 (0%) 0
Pneumonia 0/112 (0%) 0 1/110 (0.9%) 1 2/100 (2%) 2 0/256 (0%) 0 0/256 (0%) 0
Postoperative wound infection 0/112 (0%) 0 0/110 (0%) 0 0/100 (0%) 0 1/256 (0.4%) 1 0/256 (0%) 0
Pyelonephritis 0/112 (0%) 0 1/110 (0.9%) 1 0/100 (0%) 0 0/256 (0%) 0 0/256 (0%) 0
Pyelonephritis chronic 0/112 (0%) 0 1/110 (0.9%) 1 0/100 (0%) 0 0/256 (0%) 0 0/256 (0%) 0
Skin infection 0/112 (0%) 0 0/110 (0%) 0 0/100 (0%) 0 0/256 (0%) 0 1/256 (0.4%) 1
Urinary tract infection 0/112 (0%) 0 1/110 (0.9%) 1 0/100 (0%) 0 0/256 (0%) 0 0/256 (0%) 0
Injury, poisoning and procedural complications
Anastomotic leak 1/112 (0.9%) 1 0/110 (0%) 0 0/100 (0%) 0 0/256 (0%) 0 0/256 (0%) 0
Arterial bypass occlusion 1/112 (0.9%) 1 0/110 (0%) 0 0/100 (0%) 0 0/256 (0%) 0 0/256 (0%) 0
Concussion 0/112 (0%) 0 0/110 (0%) 0 0/100 (0%) 0 0/256 (0%) 0 1/256 (0.4%) 1
Craniocerebral injury 0/112 (0%) 0 0/110 (0%) 0 1/100 (1%) 1 0/256 (0%) 0 0/256 (0%) 0
Humerus fracture 1/112 (0.9%) 1 0/110 (0%) 0 0/100 (0%) 0 0/256 (0%) 0 1/256 (0.4%) 2
Limb injury 0/112 (0%) 0 0/110 (0%) 0 1/100 (1%) 1 0/256 (0%) 0 1/256 (0.4%) 1
Post procedural fistula 0/112 (0%) 0 0/110 (0%) 0 0/100 (0%) 0 1/256 (0.4%) 1 0/256 (0%) 0
Spinal column injury 0/112 (0%) 0 0/110 (0%) 0 1/100 (1%) 1 0/256 (0%) 0 0/256 (0%) 0
Subcutaneous haematoma 0/112 (0%) 0 0/110 (0%) 0 1/100 (1%) 1 0/256 (0%) 0 0/256 (0%) 0
Tibia fracture 0/112 (0%) 0 0/110 (0%) 0 0/100 (0%) 0 0/256 (0%) 0 1/256 (0.4%) 1
Upper limb fracture 0/112 (0%) 0 0/110 (0%) 0 0/100 (0%) 0 0/256 (0%) 0 1/256 (0.4%) 1
Metabolism and nutrition disorders
Diabetic metabolic decompensation 1/112 (0.9%) 1 0/110 (0%) 0 0/100 (0%) 0 0/256 (0%) 0 0/256 (0%) 0
Musculoskeletal and connective tissue disorders
Arthrofibrosis 0/112 (0%) 0 0/110 (0%) 0 0/100 (0%) 0 1/256 (0.4%) 1 0/256 (0%) 0
Haematoma muscle 0/112 (0%) 0 1/110 (0.9%) 1 0/100 (0%) 0 0/256 (0%) 0 0/256 (0%) 0
Intervertebral disc protrusion 0/112 (0%) 0 0/110 (0%) 0 0/100 (0%) 0 1/256 (0.4%) 1 1/256 (0.4%) 1
Meniscal degeneration 0/112 (0%) 0 0/110 (0%) 0 0/100 (0%) 0 0/256 (0%) 0 1/256 (0.4%) 2
Osteoarthritis 0/112 (0%) 0 0/110 (0%) 0 1/100 (1%) 1 3/256 (1.2%) 3 0/256 (0%) 0
Rotator cuff syndrome 0/112 (0%) 0 0/110 (0%) 0 1/100 (1%) 1 0/256 (0%) 0 0/256 (0%) 0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute leukaemia 1/112 (0.9%) 1 0/110 (0%) 0 0/100 (0%) 0 0/256 (0%) 0 0/256 (0%) 0
Gastrointestinal stromal tumour 0/112 (0%) 0 0/110 (0%) 0 1/100 (1%) 1 0/256 (0%) 0 0/256 (0%) 0
Lymphoma 0/112 (0%) 0 0/110 (0%) 0 0/100 (0%) 0 1/256 (0.4%) 1 0/256 (0%) 0
Pancreatic carcinoma 0/112 (0%) 0 0/110 (0%) 0 0/100 (0%) 0 0/256 (0%) 0 1/256 (0.4%) 1
Prostate cancer metastatic 0/112 (0%) 0 1/110 (0.9%) 1 0/100 (0%) 0 0/256 (0%) 0 0/256 (0%) 0
Tongue neoplasm malignant stage unspecified 0/112 (0%) 0 0/110 (0%) 0 1/100 (1%) 1 0/256 (0%) 0 0/256 (0%) 0
Triple negative breast cancer 0/112 (0%) 0 0/110 (0%) 0 0/100 (0%) 0 0/256 (0%) 0 1/256 (0.4%) 1
Nervous system disorders
Cerebrovascular disorder 0/112 (0%) 0 0/110 (0%) 0 1/100 (1%) 1 0/256 (0%) 0 0/256 (0%) 0
Diabetic neuropathy 0/112 (0%) 0 0/110 (0%) 0 0/100 (0%) 0 1/256 (0.4%) 1 0/256 (0%) 0
Haemorrhagic stroke 0/112 (0%) 0 0/110 (0%) 0 0/100 (0%) 0 1/256 (0.4%) 1 0/256 (0%) 0
Ischaemic stroke 0/112 (0%) 0 0/110 (0%) 0 0/100 (0%) 0 2/256 (0.8%) 2 0/256 (0%) 0
Transient ischaemic attack 1/112 (0.9%) 1 0/110 (0%) 0 0/100 (0%) 0 1/256 (0.4%) 1 0/256 (0%) 0
Vertigo cns origin 0/112 (0%) 0 0/110 (0%) 0 0/100 (0%) 0 0/256 (0%) 0 1/256 (0.4%) 1
Renal and urinary disorders
Chronic kidney disease 0/112 (0%) 0 0/110 (0%) 0 0/100 (0%) 0 1/256 (0.4%) 1 0/256 (0%) 0
Nephrolithiasis 1/112 (0.9%) 1 0/110 (0%) 0 0/100 (0%) 0 0/256 (0%) 0 0/256 (0%) 0
Perinephritis 0/112 (0%) 0 1/110 (0.9%) 1 0/100 (0%) 0 0/256 (0%) 0 0/256 (0%) 0
Prerenal failure 0/112 (0%) 0 0/110 (0%) 0 0/100 (0%) 0 1/256 (0.4%) 1 0/256 (0%) 0
Urinary tract disorder 0/112 (0%) 0 0/110 (0%) 0 0/100 (0%) 0 1/256 (0.4%) 1 0/256 (0%) 0
Reproductive system and breast disorders
Acquired phimosis 1/112 (0.9%) 1 0/110 (0%) 0 0/100 (0%) 0 0/256 (0%) 0 0/256 (0%) 0
Uterine prolapse 0/112 (0%) 0 1/110 (0.9%) 1 0/100 (0%) 0 0/256 (0%) 0 0/256 (0%) 0
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure 0/112 (0%) 0 0/110 (0%) 0 0/100 (0%) 0 1/256 (0.4%) 1 0/256 (0%) 0
Asthma 0/112 (0%) 0 0/110 (0%) 0 0/100 (0%) 0 1/256 (0.4%) 1 0/256 (0%) 0
Dysphonia 0/112 (0%) 0 0/110 (0%) 0 0/100 (0%) 0 1/256 (0.4%) 1 0/256 (0%) 0
Pulmonary oedema 0/112 (0%) 0 0/110 (0%) 0 0/100 (0%) 0 0/256 (0%) 0 1/256 (0.4%) 1
Vocal cord dysfunction 0/112 (0%) 0 0/110 (0%) 0 0/100 (0%) 0 1/256 (0.4%) 1 0/256 (0%) 0
Vascular disorders
Hypertension 0/112 (0%) 0 0/110 (0%) 0 0/100 (0%) 0 1/256 (0.4%) 1 1/256 (0.4%) 1
Hypertensive crisis 0/112 (0%) 0 0/110 (0%) 0 0/100 (0%) 0 2/256 (0.8%) 2 0/256 (0%) 0
Peripheral arterial occlusive disease 0/112 (0%) 0 0/110 (0%) 0 1/100 (1%) 1 0/256 (0%) 0 0/256 (0%) 0
Other (Not Including Serious) Adverse Events
Placebo Liraglutide MEDI0382 100 mcg MEDI0382 200 mcg MEDI0382 300 mcg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 45/112 (40.2%) 36/110 (32.7%) 51/100 (51%) 159/256 (62.1%) 164/256 (64.1%)
Gastrointestinal disorders
Constipation 2/112 (1.8%) 2 2/110 (1.8%) 3 1/100 (1%) 1 10/256 (3.9%) 10 13/256 (5.1%) 14
Diarrhoea 10/112 (8.9%) 10 4/110 (3.6%) 7 13/100 (13%) 15 49/256 (19.1%) 68 28/256 (10.9%) 40
Dyspepsia 2/112 (1.8%) 2 3/110 (2.7%) 3 7/100 (7%) 13 19/256 (7.4%) 26 28/256 (10.9%) 38
Eructation 0/112 (0%) 0 0/110 (0%) 0 2/100 (2%) 2 14/256 (5.5%) 17 12/256 (4.7%) 15
Nausea 12/112 (10.7%) 13 17/110 (15.5%) 21 23/100 (23%) 28 85/256 (33.2%) 115 105/256 (41%) 143
Vomiting 5/112 (4.5%) 6 3/110 (2.7%) 3 10/100 (10%) 12 51/256 (19.9%) 66 43/256 (16.8%) 58
Infections and infestations
Nasopharyngitis 15/112 (13.4%) 19 11/110 (10%) 13 11/100 (11%) 13 22/256 (8.6%) 28 28/256 (10.9%) 44
Respiratory tract infection viral 3/112 (2.7%) 3 1/110 (0.9%) 1 1/100 (1%) 1 13/256 (5.1%) 15 7/256 (2.7%) 8
Urinary tract infection 6/112 (5.4%) 6 2/110 (1.8%) 2 3/100 (3%) 4 13/256 (5.1%) 17 7/256 (2.7%) 9
Metabolism and nutrition disorders
Decreased appetite 1/112 (0.9%) 1 1/110 (0.9%) 1 3/100 (3%) 3 12/256 (4.7%) 12 14/256 (5.5%) 14
Musculoskeletal and connective tissue disorders
Back pain 6/112 (5.4%) 6 2/110 (1.8%) 2 8/100 (8%) 8 9/256 (3.5%) 12 9/256 (3.5%) 9
Nervous system disorders
Dizziness 3/112 (2.7%) 3 0/110 (0%) 0 4/100 (4%) 5 11/256 (4.3%) 12 15/256 (5.9%) 19
Headache 1/112 (0.9%) 1 5/110 (4.5%) 5 3/100 (3%) 4 15/256 (5.9%) 18 19/256 (7.4%) 23

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The Principal Investigator shall provide AstraZeneca with copies of any materials relating to the Study, the Study Documentation, or the Developed Technologies that either Party intends to publish (or submit for publication) or make any presentations relating to, at least 60 days in advance of publication, submission or presentation.

Results Point of Contact

Name/Title AstraZenenca Information Center
Organization AstraZeneca
Phone 1-877-240-9479
Email information.center@astrazeneca.com
Responsible Party:
AstraZeneca
ClinicalTrials.gov Identifier:
NCT03235050
Other Study ID Numbers:
  • D5670C00004
First Posted:
Aug 1, 2017
Last Update Posted:
Aug 17, 2020
Last Verified:
Jul 1, 2020