A Study to Evaluate the Efficacy and Safety of MEDI0382 in the Treatment of Overweight and Obese Subjects With Type 2 Diabetes
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 |
---|---|---|
|
Phase 2 |
Study Design
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
- Change in HbA1c [From baseline to 14 weeks]
To assess the effect of 100, 200, 300 μg of cotadutide on HbA1c versus placebo
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
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.- D5670C00004
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
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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)
|
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%
|
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
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 |
information.center@astrazeneca.com |
- D5670C00004